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COHORT PROFILE: STUDY OF TRANSITION, OUTCOMES AND GENDER

ForJournal: peerBMJ Open review only Manuscript ID bmjopen-2017-018121

Article Type: Cohort profile

Date Submitted by the Author: 13-Jun-2017

Evaluation http://bmjopen.bmj.com/ Giammattei, Shawn; The Rockway Institute, Alliant International University Lash, Timothy; Emory University, Department of Epidemiology Millman, Andrea; Kaiser Permanente Northern California, Division of Research Robinson, Brandi; Kaiser Permanente Georgia Roblin, Douglas; Georgia State University School of Public Health Silverberg, Michael; Kaiser Permanente Northern California Slovis, Jennifer; Kaiser Permanente Northern California, Division of Research on September 30, 2021 by guest. Protected copyright. Tangpricha, Vin; Emory University School of Medicine; The Atlanta VA Medical Center Tolsma, Dennis; Kaiser Permanente Georgia Valentine, Cadence; Kaiser Permanente Southern California, Research & Evaluation Ward, Kevin; Rollins School of Public Health, Emory University, Winter, Savannah; Kaiser Permanente Georgia Goodman, Michael; Emory University Rollins School of Public Health, Epidemiology

Primary Subject Epidemiology Heading:

Secondary Subject Heading: Patient-centred medicine, Research methods, Sexual health

Keywords: Transgender, cohort, electronic medical records

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

1 2 3 COHORT PROFILE: STUDY OF TRANSITION, OUTCOMES & GENDER 4 Virginia P. Quinn, PhD1 5 2 6 Rebecca Nash, MPH 7 Enid Hunkeler, MA, FAHA3 8 Richard Contreras, MS1 9 Lee Cromwell, MS4 10 Tracy A. Becerra-Culqui, PhD1 11 1 12 Darios Getahun, MD, PhD, MPH 5 13 Shawn Giammattei, PhD 14 Timothy L. Lash, DSc2 15 Andrea Millman,For MA6 peer review only 16 Brandi Robinson, MPH4 17 Douglas Roblin, PhD7 18 6 19 Michael J. Silverberg, PhD 20 Jennifer Slovis, MD8 21 Vin Tangpricha, MD, PhD9,10 22 Dennis Tolsma, MPH4 23 Cadence Valentine1 24 2 25 Kevin Ward, PhD, MPH 4 26 Savannah Winter 27 Michael Goodman, MD, MPH2 28 29 Affiliations 30 1 Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, CA 31 2

32 Rollins School of Public Health, Emory University, Atlanta GA http://bmjopen.bmj.com/ 33 3 Retired, formerly with Division of Research, Kaiser Permanente Northern California, Oakland, 34 CA 35 4 Center for Clinical and Outcomes Research, Kaiser Permanente Georgia, Atlanta, GA 36 5The Rockway Institute, Alliant International University, San Francisco, CA 37 6 38 Division of Research, Kaiser Permanente Northern California, Oakland, CA 7 39 School of Public Health, Georgia State University, Atlanta GA 8

40 The Permanente Medical Group, Kaiser Permanente Northern California, Oakland, CA on September 30, 2021 by guest. Protected copyright. 41 9 Emory University, School of Medicine, 42 10 The Atlanta VA Medical Center, Atlanta GA 43 44 45 Corresponding author 46 Michael Goodman, MD, MPH 47 Department of Epidemiology 48 Emory University School of Public Health 49 50 1518 Clifton Road, NE 51 CNR 3021 52 Atlanta, GA 30322 53 404.727.2734 54 [email protected] 55 56 57 Keywords: transgender, cohort, electronic medical records 58 59 60 1

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1 2 3 ABSTRACT 4 5 6 Purpose: The Study of Transition, Outcomes and Gender (STRONG) was initiated to assess 7 morbidity among transgender people in general and following gender affirming treatments at 8 Kaiser Permanente health plans in Georgia, Northern California, and Southern California. 9 Participants: A step-wise methodology involving computerized searches of electronic medical 10 11 records and free text validation of gender identity and eligibility was used to identify a cohort of 12 6,459 members with first evidence of transgender status (index date) between 2006 and 2014. 13 The cohort included 3,477 (54%) transfeminine (TF), 2,893 (45%) transmasculine (TM), and 89 14 (1%) members whose natal sex and gender identity remained undetermined from the records. 15 The cohort was matchedFor to 127,668peer enrollees review with no transgender only evidence (63,855 women and 16 63,813 men) on year of birth, race/ethnicity, study site, and membership year of the index date. 17 18 Cohort follow up extends through the end of 2016. 19 Findings to date: About 58% of TF and 52% of TM cohort members received hormonal therapy 20 at Kaiser Permanente. Chest surgery was more common among TM participants (12% vs. 21 0.3%). The proportions of transgender participants who underwent genital reconstruction 22 surgeries were similar (4-5%) in the two transgender groups. The most common mental health 23 24 conditions identified were anxiety (1338 of TF, 1323 of TM) and depression (1706 of TF, 1594 25 of TM). Results indicate there are sufficient events in the TF and TM cohorts to further examine 26 cardiovascular events, diabetes, HIV, and most common cancers. 27 Future plans: STRONG is well-positioned to fill existing knowledge gaps through comparisons 28 of transgender participants with reference cohorts as well as analyses of health status before and 29 after gender affirmation. Analyses will include incidence of cardiovascular disease, mental 30 31 health, HIV and diabetes, as well as changes in laboratory-based endpoints (e.g., polycythemia

32 and bone density), overall and in relation to gender affirmation therapy. http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 30, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 2

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1 2 3 4 5 ARTICLE SUMMARY 6 • The Study of Transition, Outcomes and Gender (STRONG) is a cohort of transgender 7 people enrolled in Kaiser Permanente health plans 8 • The cohort includes 3,477 transfeminine and 2,893 transmasculine participants matched 9 to 127,668 enrollees with no evidence of transgender status 10 11 • Cohort was identified between 2006 and 2014 and to-date was followed through the end 12 of 2016 13 • Study strengths include systematic cohort identification without a need for participant 14 opt-in, accurate determination of gender identity, and comprehensive ascertainment of 15 For peer review only 16 hormonal and surgical treatment received at Kaiser Permanente. 17 • The weaknesses of the study include relatively short follow up, dearth of information on 18 gender affirmation received outside of the health plans, and lack of data on outcomes not 19 captured in the medical records 20 21 22 23 24 25 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

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1 2 3 INTRODUCTION 4 5 6 Transgender people are a diverse group of individuals whose biological sex does not 7 8 match their gender identity.1 Typically, sex is assigned at birth based on the external appearance 9 10 2 11 of the genitalia. In contrast, an individual’s gender identity is defined as being a male/man, 12 2 3 13 female/woman, or of a different gender. Many transgender people may not self-identify based 14 15 on binary definitions;For4 however, peer a person whosereview gender identity onlydiffers from a male natal sex 16 17 18 assignment is often referred to as male-to-female or transwoman, and a person whose gender 19 20 identity differs from a female natal sex is often referred to as a female-to-male or transman.5 6 21 22 More recently, the terms transfeminine (TF) and transmasculine (TM) have become preferred as 23 24 7 25 they also apply to individuals who do not identify with binary gender categories. 26 27 Transgender individuals sometimes seek medical gender affirmation, which may involve 28 29 administration of cross-sex hormone therapy (HT) to achieve desired masculinization or 30 31 8 9

32 feminization, and/or surgical change of the genitalia and other sex characteristics. Although http://bmjopen.bmj.com/ 33 34 several organizations have established guidelines for clinical care of transgender patients,9 10 35 36 37 many issues in transgender health and gender affirmation therapy remain unresolved due to lack 38 39 of direct evidence. Consequently, many current practices and standards of care are based on

40 on September 30, 2021 by guest. Protected copyright. 41 expert opinion, case reports, or extrapolation of research findings from other populations. For 42 43 44 example, current recommendations regarding risk of venous thromboembolism in TF patients 45 46 receiving estrogen are based on the observed effects of hormone replacement therapy in post- 47 48 menopausal women.11 12 Similarly, expected health risks in TM are inferred from comorbidities 49 50 13 51 associated with polycystic ovary syndrome. 52 53 Critical knowledge gaps include the effect of HT and surgery on gender dysphoria (the 54 55 feeling of distress when natal sex does not match gender identity14) and other mental health 56 57 58 59 60 4

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1 2 3 issues, hematological side effects of HT, and risk of cardiovascular disease, metabolic or 4 5 15 6 endocrine disorders and cancer following hormonal or surgical gender affirmation. A direct 7 8 evaluation of some of these issues requires longitudinal datasets with large numbers of TM and 9 10 11 TF participants with sufficient follow up and variable history of surgical interventions and cross- 12 16 13 sex HT use. These considerations motivated the design of the longitudinal cohort for “Study of 14 15 Transition, OutcomesFor & Gender peer (STRONG).” review The present paper only provides a summary of the 16 17 18 challenges facing transgender health research, describes the main elements of the STRONG 19 20 study design and data collection, and discusses lessons learned during the implementation of this 21 22 project. The focus of this "cohort profile" communication is on the study methods and the 23 24 25 potential for future analyses, rather than specific hypotheses. 26 27 28 29 METHODOLOGICAL CHALLENGES FACING TRANSGENDER HEALTH STUDIES 30 31

32 The methodological challenges in observational studies of transgender health fall into http://bmjopen.bmj.com/ 33 34 five categories: 1) attaining sufficient sample size and statistical power; 2) systematic and 35 36 37 comprehensive identification of eligible study participants and comparable reference groups; 3) 38 39 determination of natal sex and/or gender identity; 4) assessment of current and past gender

40 on September 30, 2021 by guest. Protected copyright. 41 affirmation treatment; and 5) engagement of patient and physician stakeholders at all stages of 42 43 44 research. 45 46 Transgender people represent a hard-to-reach population, and to date most existing 47 48 cohorts assessing transgender health were assembled in specialized clinics that provide gender 49 50 51 affirmation care. This approach provides good options for detailed treatment data and 52 53 biospecimen collection,17 18 but may exclude individuals who have not sought or who have 54 55 already completed treatment, and makes it difficult to select comparable reference groups. In 56 57 58 59 60 5

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1 2 3 addition, establishing a large clinic-based cohort requires coordination across multiple sites, is 4 5 6 costly, and may still have small numbers resulting in studies of relatively low statistical power. 7 8 Besides clinic-based studies, previous efforts to identify transgender individuals for 9 10 19 11 health research also involved population surveys and reviews of electronic records for relevant 12 20 21 13 International Classification of Diseases (ICD) codes. While surveys offer generalizable 14 15 population estimates,For they maypeer be affected reviewby recall bias and low only response rates and require 16 17 18 large-scale efforts to identify sufficient numbers of transgender people. Reliance on ICD codes 19 20 allows identifying large samples from insurance claims or electronic medical records (EMRs), 21 22 but may exclude eligible study participants who do not have or do not wish to receive a 23 24 22 25 transgender-specific diagnosis. 26 27 A critical aspect of transgender research is accurate identification of gender identity. In 28 29 recent years, the U.S. Department of Health and Human Services issued a directive that EMR 30 31 23

32 systems should enable providers to record gender identity and sexual orientation. This http://bmjopen.bmj.com/ 33 34 directive should improve documentation over time; but in the meantime, determination of TF or 35 36 37 TM status presents a methodological challenge because the available demographic data can 38 39 reflect natal sex or gender identity, without specifying which is which. Assessing TM/TF status

40 on September 30, 2021 by guest. Protected copyright. 41 can be achieved by asking two questions about natal sex and gender identity;24 however, reliance 42 43 44 on self-report requires contact with individual participants and is subject to non-response, which 45 46 increases the risk of selection bias. 47 48 Insurance coverage for gender affirmation therapy has increased over time;25-27 however, 49 50 51 it remains sporadic and incomplete, and many transgender people seek care outside of regular 52 53 health care plans.28 This presents a specific challenge for any study that aims to ascertain 54 55 56 57 58 59 60 6

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1 2 3 hormonal exposures and surgical procedures, particularly for transgender people with no or 4 5 6 inadequate insurance coverage and for persons who initiated gender affirming therapy years ago. 7 8 In a rapidly developing field, such as transgender health, even experienced researchers 9 10 11 may lack specific expertise required to prioritize research questions and select the most relevant 12 13 patient-centered outcome measures. Thus, it is important to involve members of the transgender 14 15 community and Fortheir physicians peer to ensure thatreview the proposed research only questions, study design, and 16 17 29 18 data collection methods are relevant, appropriate and feasible. Conversely, as the research 19 20 methods and interpretation of findings are becoming increasingly complex, researchers should 21 22 communicate with stakeholders directly to convey information relevant to their decision- 23 24 30 25 making. 26 27 In sum, transgender health research faces significant methodological challenges and 28 29 logistical barriers. These challenges and barriers contribute to the lack of knowledge about the 30 31

32 health risks in this population and preclude development of evidence-based recommendations for http://bmjopen.bmj.com/ 33 34 transgender health care.31 35 36 37 38 39 COHORT DESCRIPTION

40 on September 30, 2021 by guest. Protected copyright. 41 Study goals, design, and setting 42 43 44 STRONG was initiated in September 2013 with the primary goal of assessing morbidity 45 46 among transgender individuals overall, among TF/TM subgroups, and both subgroups after 47 48 different types of gender affirming treatment. It was designed as an EMR-based 49 50 51 retrospective/prospective cohort study of transgender members enrolled at three Kaiser 52 53 Permanente (KP) health plans located in Georgia (KPGA), Northern California (KPNC) and 54 55 Southern California (KPSC). These health plans are prepaid integrated care systems and 56 57 58 59 60 7

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1 2 3 currently provide comprehensive health services to approximately 8 million members. 4 5 6 Individuals and their families may enroll through an employer, state or federal programs such as 7 8 Medicaid and Medicare, or directly. The populations of enrollees are socio-demographically 9 10 32 33 11 diverse and broadly representative of the communities in the corresponding areas. 12 13 The three KP organizations are members of several research consortia including the 14 15 Health Care SystemsFor Research peer Network34 andreview the Mental Health only Research Network.35 They 16 17 18 share similarly structured databases organized into "Virtual Data Warehouses" (VDW), with files 19 20 stored behind security firewalls at each site. The files have identical variable names, formats, and 21 22 specifications that allow using centrally generated and/or distributed programs to create 23 24 36 25 harmonized analytic datasets. VDW files are linked by unique individual identifiers, allowing 26 27 researchers to construct historical and prospective cohorts.37 28 29 The study was conducted in partnership with the Emory University, which served as the 30 31

32 coordinating center. All activities described in this manuscript were reviewed and approved by http://bmjopen.bmj.com/ 33 34 the Institutional Review Boards (IRB) of the four institutions. 35 36 37 Cohort ascertainment 38 39 Figure 1 shows the three-step algorithm used to identify transgender cohort members. It

40 on September 30, 2021 by guest. Protected copyright. 41 includes initial EMR search to identify cohort candidates (Step 1); validation of transgender 42 43 44 status (Step 2); and determination of TM/TF status (Step 3). 45 46 Step 1: Initial EMR search 47 48 A SAS program (SAS institute, Cary, North Carolina) was used to search the EMRs of 49 50 51 KPGA, KPNC and KPSC members of all ages enrolled between January 1, 2006 and December 52 53 31, 2014 to identify two types of evidence supporting transgender status: 1) relevant 54 55 International Classification of Diseases Ninth edition (ICD-9) codes; and 2) presence of relevant 56 57 58 59 60 8

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1 2 3 specific keywords in free-text clinical notes (Table 1). The program was developed and pilot- 4 5 6 tested at KPGA, and then distributed to the remaining sites. Cohort ascertainment was 7 8 undertaken before the health plans switched to ICD-10 codes. 9 10 11 The diagnostic ICD-9 codes suggestive of transgender status were selected based on 12 13 consultations with the STRONG Stakeholder Advisory Group and methodologies described in 14 15 earlier studies.21For 38 Transvestic peer fetishism (ICD-9review code 302.3) was only included based on previous 16 17 18 observations that men who initially meet criteria for this diagnostic category may later 19 20 experience persistent gender dysphoria consistent with transgender status.20 21 22 We also used ICD-9 V codes, which allow for supplementary classification of factors 23 24 39 40 25 influencing health status. As V codes may cover several conditions, we used them in 26 27 conjunction with internal KP codes to ensure specificity. For example, a combination of ICD-9 28 29 code V49.89 and KP code 121141596 means "Other conditions influencing health: transgender." 30 31

32 The second method of transgender ascertainment involved using a custom-written http://bmjopen.bmj.com/ 33 34 program that identified the relevant keywords in free-text clinical notes recognizing that both 35 36 37 appropriate and inappropriate terms could be found in the EMR. During pilot testing an 38 39 expanded list of keywords provided by the stakeholders was used; that list was gradually

40 on September 30, 2021 by guest. Protected copyright. 41 shortened after step-wise removal of keywords that did not contribute additional cases. The 42 43 44 resulting list provided a complete cohort ascertainment with the shortest program running time. 45 46 Step 2: Cohort validation 47 48 A separate program extracted short strings of text that included 100 characters before and 49 50 51 50 characters after each keyword of interest. When clinical notes contained relevant keywords 52 53 (with or without an ICD-9 code), transgender status was confirmed through an examination of 54 55 the de-identified text strings by two trained reviewers. Disagreements among reviewers were 56 57 58 59 60 9

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1 2 3 adjudicated by a review committee that included two physician investigators (MG and VT) and 4 5 6 the project manager (RN). Cohort candidates with no keywords, but at least two different 7 8 diagnostic codes or the same code on different dates were considered eligible. Members who had 9 10 11 evidence of disorders of sex development (i.e., abnormalities of chromosomal, gonadal, or 12 41 13 anatomic sex ) and those younger than 3 years of age at the index date were excluded. 14 15 Step 3: DeterminationFor of TF/TM peer status review only 16 17 18 Each eligible study participant was categorized as TF or TM using several methods. We 19 20 used all keyword text strings and ICD-9 codes extracted for Step 1 to identify additional words 21 22 such as "male-to-female," "female-to-male," and gender affirmation V codes (V07.8 +12124952 23 24 25 and V07.8 +12124310). During the validation of transgender status, the reviewers were also 26 27 instructed to categorize each eligible person as "natal male," "natal female," or "unclear." 28 29 For persons whose TF/TM status was unclear after the initial review, and for persons 30 31

32 with ICD-9 codes only, another free-text program was developed to search for keywords http://bmjopen.bmj.com/ 33 34 reflecting natal sex anatomy (e.g., "testes" or "ovaries"), history of specific procedures (e.g., 35 36 37 orchiectomy or hysterectomy) or evidence of hormonal therapy (e.g., estrogen or testosterone). 38 39 The keywords used for assigning TM/TF status are included in Table 2. Text strings containing

40 on September 30, 2021 by guest. Protected copyright. 41 TF- and TM-specific keywords were reviewed and adjudicated as discussed above. 42 43 44 Gender affirmation treatment status 45 46 During the initial STRONG cohort validation (Step 2) and natal sex determination (Step 47 48 3), reviewers were instructed to check a box for "Evidence of treatment" if the text strings 49 50 51 provided an indication of receipt or referral for HT, surgery, or other relevant procedures (e.g., 52 53 electrolysis). Disagreements were adjudicated as described previously. 54 55 56 57 58 59 60 10

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1 2 3 In addition to text string reviews, gender affirmation treatment status was determined by 4 5 6 linkage with cross-sex hormone prescriptions using national drug codes, as well as ICD-9, ICD- 7 8 10, and Current Procedure Terminology codes reflecting surgeries and other interventions 9 10 11 (Supplemental Tables 1-6). TF drugs (e.g., estradiol, spironolactone) in a natal male and TM 12 13 drugs (e.g. testosterone) in a natal female were considered as evidence of HT. 14 15 As the resultFor of these peer steps, cohort membersreview were categorized only based on evidence of HT 16 17 18 and surgical or other gender affirmation procedures. Gender affirmation procedures were 19 20 categorized as: bottom (e.g., vaginoplasty for TF or vaginectomy for TM); top (e.g., breast 21 22 augmentation for TF or mastectomy for TM); interventions to change secondary sex 23 24 25 characteristics (e.g., electrolysis); or not specified (i.e., evidence of surgery in the text only). 26 27 Selection of the reference cohort 28 29 Up to 10 male and 10 female KP enrollees without evidence of transgender status were 30 31

32 matched to each member of the final validated transgender cohort on year of birth, race/ethnicity, http://bmjopen.bmj.com/ 33 34 KP site, and membership year at the index date. Index date was defined as the date of the first 35 36 37 recorded evidence of transgender status in the EMR. For some transgender cohort members, the 38 39 number of reference males or females was less than 10 due to duplicate matches; however, no

40 on September 30, 2021 by guest. Protected copyright. 41 transgender participant had less than 7 referents of either sex. A cluster ID for each matched 42 43 44 group was assigned to allow stratified analyses (e.g., by HT type, or gender affirming surgery). 45 46 Data integration and follow up 47 48 Patient identification numbers for both the transgender and reference cohorts were linked 49 50 51 to multiple data sources to obtain ICD-9 and ICD-10 diagnostic codes for the conditions of 52 53 primary interest (e.g., mental health conditions, cardiovascular diseases and diabetes); disease 54 55 registries to ascertain incident cancers and HIV diagnoses; psychiatric and behavioral health care 56 57 58 59 60 11

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1 2 3 utilization; pharmacy records to track mental health treatment and HT receipt over time; and 4 5 6 dates and results of laboratory tests including bone scans, blood chemistry analyses, hormone 7 8 levels, and blood cell counts (Table 3). Mortality was ascertained from linkages to death 9 10 11 registries. All members of the cohort were assigned a study ID by the programmer at each KP 12 13 site and no personally identifiable information was included in the aggregated analytic file. To 14 15 date, cohort followFor up extends peer through the reviewend of 2016. only 16 17 18 19 20 FINDINGS TO DATE 21 22 Initial review of the EMRs identified 12,457 potential transgender individuals. Of these, 23 24 25 7,272 (58%) were identified through keywords only, 1,132 (9%) through ICD-9 codes only, and 26 27 the remaining 4,053 (33%) had both ICD-9 codes and keywords (Figure 2). Among these 28 29 candidates, 6,459 were confirmed as transgender: 10% from ICD-9 codes alone, 29% from 30 31

32 keywords alone and 61% from both codes and keywords. Based on validation results, the http://bmjopen.bmj.com/ 33 34 positive predictive values for keywords, diagnostic codes, and both were 26%, 54%, and 98%, 35 36 37 respectively. The leading reason for non-eligibility was the use of a keyword (e.g., 38 39 "transgender") referring not to the patient, but to the patient’s relative, or partner. In other

40 on September 30, 2021 by guest. Protected copyright. 41 situations, the keywords of interest were used as part of standard text, such as when listing 42 43 44 indications for hormone use. Natal sex and/or gender identity was successfully determined for 45 46 all but 89 (1.4%) of the transgender cohort members. 47 48 The transgender cohort was matched to 127,668 enrollees with no evidence of 49 50 51 transgender status. Of those 63,855 were women and 63,813 were men. 52 53 Figure 3 displays proportions of transgender enrollees over time at each of the three 54 55 participating sites. In 2006, the prevalence estimates (95% confidence intervals) per 100,000 56 57 58 59 60 12

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1 2 3 enrollees were 3.5 (1.9, 6.3), 5.5 (4.8, 6.4) and 17 (16, 19) in KPGA, KPSC and KPNC, 4 5 6 respectively. By 2014, the corresponding estimates increased to 38 (32, 45) in KPGA, 44 (42, 7 8 46) in KPSC, and 75 (72, 78) in KPNC. The composition of the transgender population has also 9 10 11 changed. Whereas in 2006 the TF:TM ratio among newly identified cohort members was 12 13 approximately 1.7:1, in 2014 the same ratio was 1:1. 14 15 As shownFor in Table 4peer, 59% of all participants review were from onlyKPNC, 38% were from KPSC, 16 17 18 and less than 3% were from KPGA. With respect to race and ethnicity, Blacks and Asians each 19 20 comprised about 8% of the study population, 19% were Hispanics, and 55% were non-Hispanic 21 22 Whites. Compared to TF, TM subjects were younger (76% vs 53% under the age of 36) and 23 24 25 included a greater proportion of subjects who were obese (31% vs 22%). Proportions of 26 27 smokers, insurance status, and area-based measures of education were similar in TM and TF 28 29 study subjects. 30 31

32 Nearly two-thirds of the transgender cohort had some evidence of gender affirming http://bmjopen.bmj.com/ 33 34 treatment (Table 5). Approximately 55% of all transgender cohort members had evidence of HT 35 36 37 received at KP. This proportion was slightly higher (58%) in TF than in TM participants (52%). 38 39 About 23% of the transgender cohort had some evidence of gender affirmation surgery.

40 on September 30, 2021 by guest. Protected copyright. 41 Top surgery receipt at KP was far more common among TM cohort members than among their 42 43 44 TF counterparts (12% vs. 0.3%). Similar proportions of TM and TF cohorts had genital 45 46 surgeries (4-5%) or procedures aimed at altering other secondary sex characteristics (11%). 47 48 Tables 6 and 7 present the number of cases for various health outcomes in the STRONG 49 50 51 population through the end of 2016. These frequencies should not be interpreted as evidence of 52 53 increased or decreased risk because they do not account for person-time of follow up, time 54 55 ordering of the conditions and transgender status, and do not take into consideration exposures to 56 57 58 59 60 13

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1 2 3 cross-sex hormones or surgical procedures. Nevertheless, these data indicate that both TF and 4 5 6 TM cohort members, as well as their corresponding referents, have sufficient numbers of 7 8 cardiovascular events, mental health conditions, HIV, diabetes and several common cancers to 9 10 11 permit meaningful analyses. Additional analyses will include changes in laboratory-based 12 13 endpoints including polycythemia and bone density. These analyses are beyond the scope of this 14 15 communication,For which is focused peer on the study review methods rather thanonly specific findings. The 16 17 18 planned analyses will include comparisons of transgender and reference cohorts as well as 19 20 within-transgender cohort examination of health status before and after surgery and initiation of 21 22 HT. 23 24 25 26 27 STRENGTHS AND LIMITATIONS 28 29 In this communication, we describe STRONG, a health system-based observational study 30 31

32 that was designed to examine the health status of transgender people and to evaluate the possible http://bmjopen.bmj.com/ 33 34 risks and health benefits of various gender affirming treatments. STRONG aimed to overcome 35 36 37 five previously described methodological challenges facing transgender health research. 38 39 Sample size and power considerations

40 on September 30, 2021 by guest. Protected copyright. 41 Adequate sample size can be feasibly achieved with the use of large well-defined 42 43 37 44 populations that offer an adequate sampling frame. In practical terms, at least in the US, this 45 46 can be done by basing the study in large integrated health systems with millions of members and 47 48 comprehensive electronic medical records. The EMR data from the health systems allow 49 50 51 assembling cohorts of hard-to-reach populations and ample options for selection of referent 52 53 groups. The STRONG cohort, which included almost 6,500 transgender people and nearly 54 55 130,000 referents, represents one of the largest studies of its kind available to date. 56 57 58 59 60 14

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1 2 3 Nevertheless, a number of important analyses by different sub-types of gender affirmation 4 5 6 treatment may not be feasible due to sparse stratum-specific data. 7 8 Systematic identification of eligible study participants 9 10 11 We demonstrated that by using a relatively simple algorithm—based on standard codes 12 13 and supplemented with analysis of digitized provider notes—it is possible to comprehensively 14 15 identify transgenderFor enrollees peer of large community review based health plans.only The use of keyword- 16 17 18 containing text strings enhanced cohort ascertainment relative to ICD code-alone based 19 20 approaches. On the other hand, reliance on keywords without text validation would have 21 22 erroneously included a substantial number of persons who are not transgender. A review of 23 24 25 records to confirm transgender status added considerable time and resources. A comprehensive 26 27 identification of all transgender people in the KP population (with and without evidence in the 28 29 medical records) would require contacting more than 8 million members to inquire about their 30 31

32 natal sex and gender identity; this does not appear feasible at this time. http://bmjopen.bmj.com/ 33 34 Determination of natal sex and/or gender identity 35 36 37 Our study definitively ascertained natal sex and/or gender identity for nearly 99% of 38 39 cohort members. We obtained information on TM/TF status from three sources: keyword text

40 on September 30, 2021 by guest. Protected copyright. 41 strings, pharmacy records, and procedure codes. In most instances these sources were in 42 43 44 agreement; however, in some cases the results were discordant. Each disagreement was used as 45 46 an opportunity to check data accuracy and allowed reducing misclassification, which would have 47 48 been substantial if STRONG relied on demographic data in the EMR. For example, among adult 49 50 51 TF study subjects, 41% were documented as "female" and 59% were documented as "male." 52 53 The corresponding proportions of people classified as "female" and "male" among adult TM 54 55 56 57 58 59 60 15

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1 2 3 cohort members were 59% and 40%, respectively with 1% recorded as unknown in the EMR. 4 5 6 By contrast, in 96% of persons under the age of 18, the demographic variable reflected natal sex. 7 8 Assessment of current and past gender affirmation treatment 9 10 11 Although the information on gender affirmation received within the KP system is high 12 13 quality, one of the main limitations of STRONG data is the lack of information on HT and 14 15 surgical treatmentFor received outsidepeer the KP reviewsystem. This restricts only our ability to identify a sub- 16 17 18 category of transgender cohort members with no history of gender affirmation treatment of any 19 20 kind. For this reason, the most definitive analyses are limited to people who initiated therapy at 21 22 KP. These individuals can be identified among those STRONG participants whose EMR 23 24 25 demonstrates a gap between index date and the first prescription for HT. This "HT initiation" 26 27 group represents about 35% of TM and 32% of TF subjects. 28 29 The broadening of coverage for gender affirmation services at KP occurred relatively 30 31

32 recently. As the proportion of transgender people among enrollees has been increasing and http://bmjopen.bmj.com/ 33 34 many patients now initiate and receive gender affirmation therapy exclusively within the system, 35 36 37 it is important to both expand the cohort and extend the follow up of current participants. 38 39 Engagement of patient and physician stakeholders

40 on September 30, 2021 by guest. Protected copyright. 41 A critical feature of STRONG is patient-centeredness. The research team at each 42 43 44 participating site included stakeholders representing the transgender community as well as 45 46 physicians actively involved in transgender health care. The Stakeholder Advisory Group was 47 48 involved in all decisions pertaining to study design, data collection, and interpretation of findings 49 50 51 available to date. For example, the list of keywords used for STRONG cohort ascertainment was 52 53 proposed, pilot tested, and refined in close consultation with the study stakeholders. STRONG 54 55 stakeholders also helped to develop a comprehensive list of hormonal medications and 56 57 58 59 60 16

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1 2 3 procedures used for gender affirmation. During the study implementation, we held monthly 4 5 6 stakeholder calls and had three in-person Stakeholder Advisory Group meetings. The 7 8 publications describing our formative research,22 42-44 the current communication, and the reports 9 10 11 in preparation, all include stakeholders as co-authors. 12 13 14 15 CONCLUSIONSFor peer review only 16 17 45 18 Although the body of literature addressing transgender health issues has been growing, 19 20 most studies focus on substance use, sexual health, sexually transmitted infections, and, to a 21 22 lesser extent, mental health conditions.46 By contrast, limited data are available on general 23 24 25 health status, or the incidence of chronic age-related conditions including cardiovascular disease, 26 27 endocrine disorders and cancer. 28 29 To date, most data on morbidity and mortality in transgender populations come from 30 31 18 47-49

32 clinical centers in Europe. These studies are characterized by detailed clinical data; http://bmjopen.bmj.com/ 33 34 however, they are limited by relatively small sample sizes. 35 36 37 In terms of overall design and size, STRONG is comparable to US-based studies that 38 20 50 39 used the Veterans Health Administration (VHA) data. Unlike our study, however, the VHA

40 on September 30, 2021 by guest. Protected copyright. 41 data did not distinguish between TF and TM subjects and were limited to transgender persons 42 43 44 identified via ICD-9 codes, without keywords. 45 46 We recognize that transgender people enrolled through an integrated health care system 47 48 will yield a cohort of persons with health insurance. Weighing against this concern is the 49 50 51 demonstrated ability to cost-effectively identify a large cohort of transgender subjects and 52 53 referents with high degree of internal validity. The availability of a well-defined underlying 54 55 population with detailed EMR ensures that participation does not require subject opt-in and 56 57 58 59 60 17

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1 2 3 allows selecting a complete cohort (rather than a sample) of eligible subjects. Moreover, as KP 4 5 6 now provides ‘one-stop’ delivery of transgender care, the likelihood of capturing full details of 7 8 gender affirmation treatment is increased. These internal validity advantages weigh heavily as a 9 10 11 counter against concerns about representativeness. 12 13 In summary, STRONG is well positioned to fill existing knowledge gaps and make 14 15 important contributionsFor to thepeer current literature. review Lessons learned only while conducting this project 16 17 18 provide support to future transgender health-related research. The methodology can be 19 20 implemented at other health care institutions with EMRs, particularly in organizations 21 22 participating in the Health Care Systems Research Network (total population of almost 20 23 24 25 million) with little site-specific customization. With extended follow up and expanded cohort 26 27 size, the data will permit additional analyses of rare health endpoints across various categories of 28 29 surgical procedures, and different HT formulations, routes of administration and doses. 30 31

32 http://bmjopen.bmj.com/ 33 34 CONTRIBUTORSHIP STATEMENT 35 36 37 Virginia Quinn and Michael Goodman prepared the original draft of the manuscript. 38 39 Rebecca Nash conducted data analyses and put together tables and figures. Richard Contreras

40 on September 30, 2021 by guest. Protected copyright. 41 and Lee Cromwell were responsible for the preparation and application of data collection 42 43 44 programs and ascertainment of study variables. Enid Hunkeler, Virginia Quinn, Darios Getahun, 45 46 Michael Silverberg, and Dennis Tolsma led study implementation at participating sites and were 47 48 actively involved in study planning and design. Tracy Becerra-Culqui, Andrea Millman and 49 50 51 Brandi Robinson were responsible for the day-to-day project management at each site. Douglas 52 53 Roblin and Timothy Lash provided methodological input on various aspects of study design, 54 55 including identification of sources of bias, and ways of addressing threats to validity. Vin 56 57 58 59 60 18

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1 2 3 Tangpricha and Jennifer Slovis provided input on clinical aspects of the study and were 4 5 6 responsible for adjudication of study eligibility, gender identity, and gender affirmation. Kevin 7 8 Ward developed pilot tested, and supervised the cohort validation and gender identity 9 10 11 ascertainment review protocols and programming. Shawn Giammattei, Cadence Valentine and 12 13 Savannah Winter are members of the Stakeholder Advisory Group who assisted with the 14 15 development of Forinclusion and peer exclusion criteria, review assessment of genderonly identity, and interpretation 16 17 18 of the data. All authors provided critical review of the manuscript for important intellectual 19 20 content; and approved the final version. 21 22 23 24 25 COMPETING INTERESTS 26 27 None of the authors report competing interests 28 29 30 31

32 FUNDING http://bmjopen.bmj.com/ 33 34 This research was supported by the Contract AD-12-11-4532 from the Patient Centered 35 36 37 Outcome Research Institute and by the Grant R21HD076387 from the Eunice Kennedy Shriver 38 39 National Institute of Child Health and Human Development

40 on September 30, 2021 by guest. Protected copyright. 41 42 43 44 DATA SHARING STATEMENT 45 46 Once the initial data analyses are complete we will be open to collaborations with outside 47 48 investigators as permitted by the IRBs of participating sites as well as by local, state, and Federal 49 50 51 laws and regulations. In particular, we will encourage collaborations with researchers whose 52 53 expertise is underrepresented on our research team. To become a collaborator, a researcher will 54 55 be required to submit an application, which will undergo both a scientific and an IRB review. In 56 57 58 59 60 19

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1 2 3 view of the complexity of the database, and interested investigators will be asked to form a 4 5 6 collaborative arrangement with the STRONG investigators rather than simply receive the data 7 8 themselves. 9 10 11 ACKNOWLEDGMENTS 12 13 Kimberly L. Cannavale, MPH and Alexander S. Carruth performed additional validations 14 15 of eligibility andFor ascertainment peer of natal sex review via reviews of medical only record 16 17 18 19 REFERENCES 20 21 22 1. Safer JD, Coleman E, Hembree W. There is reason for optimism: an introduction to the special 23 issue on research needs in transgender health and medicine. Curr Opin Endocrinol 24 Diabetes Obes 2016;23(2):165-7. doi: 10.1097/MED.0000000000000228 25 26 2. Lombardi E. Enhancing transgender health care. Am J Public Health 2001;91(6):869-72. 27 3. Bockting W, Coleman E, De Cuypere G. Care of transsexual persons. N Engl J Med 28 29 2011;364(26):2559-60; author reply 60. doi: 10.1056/NEJMc1104884#SA1 30 4. Bockting W. From construction to context: Gender through the eyes of the transgendered. 31 Siecus Report 1999;28:3-7. 32 http://bmjopen.bmj.com/ 33 5. Giami A, Beaubatie E. Gender identification and sex reassignment surgery in the trans 34 population: a survey study in France. Arch Sex Behav 2014;43(8):1491-501. doi: 35 36 10.1007/s10508-014-0382-3 37 6. Reisner SL, Gamarel KE, Dunham E, et al. Female-to-male transmasculine adult health: a 38 mixed-methods community-based needs assessment. Journal of the American Psychiatric 39 Nurses Association 2013;19(5):293-303. doi: 10.1177/1078390313500693

40 on September 30, 2021 by guest. Protected copyright. 41 7. Reisner SL, Radix A, Deutsch MB. Integrated and gender-affirming transgender clinical care 42 43 and research. J Acquir Immune Defic Syndr 2016;72 Suppl 3:S235-42. doi: 44 10.1097/QAI.0000000000001088 45 8. Knudson G, De Cuypere G, Bockting W. Recommendations for revision of the DSM 46 47 diagnoses of gender identity disorders: Consensus statement of the World Professional 48 Association for Transgender Health. Int J Transgenderism 2010;12(2):115-18. 49 9. Coleman E, Bockting WO, Botzer M, et al. Standards of care for the health of transsexual, 50 51 transgender, and gender-nonconforming people, version 7. Int J Transgenderism 52 2012;13(4):165-232. 53 54 10. Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, et al. Endocrine treatment of 55 transsexual persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol 56 Metab 2009;94(9):3132-54. doi: 10.1210/jc.2009-0345 57 58 59 60 20

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1 2 3 11. The Women’s Health Initiative Study Group. Design of the Women's Health Initiative 4 5 clinical trial and observational study. Control Clin Trials 1998;19(1):61-109. 6 12. Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in 7 postmenopausal women with hysterectomy: the Women's Health Initiative randomized 8 9 controlled trial. JAMA 2004;291(14):1701-12. doi: 10.1001/jama.291.14.1701 10 13. Cattrall FR, Healy DL. Long-term metabolic, cardiovascular and neoplastic risks with 11 12 polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol 2004;18(5):803-12. doi: 13 10.1016/j.bpobgyn.2004.05.005 14 14. Schneider C, Cerwenka S, Nieder TO, et al. Measuring gender dysphoria: A multicenter 15 For peer review only 16 examination and comparison of the Utrecht Gender Dysphoria Scale and the Gender 17 Identity/Gender Dysphoria Questionnaire for adolescents and adults. Arch Sex Behav 18 2016;45(3):551-8. doi: 10.1007/s10508-016-0702-x [published Online First: 2016/02/18] 19 20 15. Feldman J, Brown GR, Deutsch MB, et al. Priorities for transgender medical and healthcare 21 research. Current opinion in endocrinology, diabetes, and obesity 2016;23(2):180-7. doi: 22 10.1097/MED.0000000000000231 23 24 16. Reisner SL, Deutsch MB, Bhasin S, et al. Advancing methods for US transgender health 25 research. Current opinion in endocrinology, diabetes, and obesity 2016;23(2):198-207. 26 doi: 10.1097/MED.0000000000000229 27 28 17. Dekker MJ, Wierckx K, Van Caenegem E, et al. A European Network for the Investigation 29 of Gender Incongruence: Endocrine Part. J Sex Med 2016;13(6):994-9. doi: 30 10.1016/j.jsxm.2016.03.371 [published Online First: 2016/05/11] 31

32 18. Kreukels BP, Haraldsen IR, De Cuypere G, et al. A European network for the investigation http://bmjopen.bmj.com/ 33 of gender incongruence: the ENIGI initiative. Eur Psychiatry 2012;27(6):445-50. doi: 34 10.1016/j.eurpsy.2010.04.009 35 36 19. Meier SC, Pardo ST, Labuski C, et al. Measures of clinical health among female-to-male 37 transgender persons as a function of sexual orientation. Arch Sex Behav 2013;42(3):463- 38 74. doi: 10.1007/s10508-012-0052-2 39

40 20. Blosnich JR, Brown GR, Shipherd Phd JC, et al. Prevalence of gender identity disorder and on September 30, 2021 by guest. Protected copyright. 41 suicide risk among transgender veterans utilizing veterans health administration care. Am 42 J Public Health 2013;103(10):e27-32. doi: 10.2105/AJPH.2013.301507 43 44 21. Brown GR, Jones KT. Racial health disparities in a cohort of 5,135 transgender veterans. J 45 Racial Ethnic Health Disparities 2014;1(4):257-66. 46 47 22. Roblin D, Barzilay J, Tolsma D, et al. A novel method for estimating transgender status 48 using electronic medical records. Ann Epidemiol 2016;26(3):198-203. doi: 49 10.1016/j.annepidem.2016.01.004 50 51 23. Centers for Medicare & Medicaid Services. Medicare and Medicaid Programs; Electronic 52 Health Record Incentive Program—Stage 3 and Modifications to Meaningful Use in 53 2015 through 2017. Rockville, MD Department of Health and Human Services 2015. 54 55 24. Cahill S, Singal R, Grasso C, et al. Do ask, do tell: high levels of acceptability by patients of 56 routine collection of sexual orientation and gender identity data in four diverse American 57 58 59 60 21

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1 2 3 community health centers. PLoS One 2014;9(9):e107104. doi: 4 5 10.1371/journal.pone.0107104 6 25. Deutsch MB. Gender-affirming surgeries in the era of insurance coverage: Developing a 7 framework for ssychosocial support and care Navigation in the perioperative period. J 8 9 Health Care Poor Underserved 2016;27(2):386-91. doi: 10.1353/hpu.2016.0092 10 26. Shipherd JC, Kauth MR, Matza A. Nationwide interdisciplinary e-consultation on 11 12 transgender care in the Veterans Health Administration. Telemed J E Health 13 2016;22(12):1008-12. doi: 10.1089/tmj.2016.0013 14 27. Stevens J, Gomez-Lobo V, Pine-Twaddell E. Insurance coverage of puberty blocker 15 For peer review only 16 therapies for transgender youth. Pediatrics 2015;136(6):1029-31. doi: 17 10.1542/peds.2015-2849 18 28. Tangpricha V, den Heijer M. Oestrogen and anti-androgen therapy for transgender women. 19 20 Lancet Diabetes Endocrinol 2016 doi: 10.1016/S2213-8587(16)30319-9 21 29. Quinn V, Becerra T, Gillespie T, et al. Embedding patients, providers, and community 22 23 stakeholders in research to improve transgender health. J Patient-Centered Res Rev 24 2015;2(2):114-15. 25 30. Gabriel SE, Normand SL. Getting the methods right--the foundation of patient-centered 26 27 outcomes research. N Engl J Med 2012;367(9):787-90. doi: 10.1056/NEJMp1207437 28 31. Institute of Medicine. The Health of Lesbian, Gay, Bisexual, and Transgender People: 29 Building a Foundation for Better Understanding. Washington, DC: The National 30 31 Academies Press 2011.

32 32. Koebnick C, Langer-Gould AM, Gould MK, et al. Sociodemographic characteristics of http://bmjopen.bmj.com/ 33 34 members of a large, integrated health care system: comparison with US Census Bureau 35 data. Perm J 2012;16(3):37-41. 36 33. Gordon NP. How does the adult Kaiser Permanente membership in northern California 37 38 compare with the larger community? . Oakland, CA: Kaiser Permanente Division of 39 Research, 2006.

40 on September 30, 2021 by guest. Protected copyright. 41 34. Lieu TA, Hinrichsen VL, Moreira A, et al. Collaborations in population-based health 42 research: the 17th annual HMO Research Network Conference, March 23-25, 2011, 43 Boston, Massachusetts, USA. Clin Med Res 2011;9(3-4):137-40. doi: 44 10.3121/cmr.2011.1025 45 46 35. Simon GE, Stewart C, Beck A, et al. National prevalence of receipt of antidepressant 47 prescriptions by persons without a psychiatric diagnosis. Psychiatric services 48 2014;65(7):944-6. doi: 10.1176/appi.ps.201300371 49 50 36. Go AS, Magid DJ, Wells B, et al. The Cardiovascular Research Network: a new paradigm 51 for cardiovascular quality and outcomes research. Circ Cardiovasc Qual Outcomes 52 2008;1(2):138-47. doi: 10.1161/CIRCOUTCOMES.108.801654 53 54 37. Goodman M, Fletcher RH, Doria-Rose VP, et al. Observational methods to assess the 55 effectiveness of screening colonoscopy in reducing right colon cancer mortality risk: 56 SCOLAR. Journal of comparative effectiveness research 2015;4(6):541-51. doi: 57 10.2217/cer.15.39 58 59 60 22

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1 2 3 38. Brown GR, Jones KT. Incidence of breast cancer in a cohort of 5,135 transgender veterans. 4 5 Breast cancer research and treatment 2015;149(1):191-8. doi: 10.1007/s10549-014- 6 3213-2 [published Online First: 2014/11/28] 7 39. World Health Organisation. International Statistical Classification of Diseases and Related 8 9 Health Problems, 9th Revision. Geneva: WHO, 1978. 10 40. Maguire N. In search of the "V" codes (ICD-9-CM). The Journal of medical practice 11 12 management : MPM 2012;28(1):56-7. 13 41. Hughes IA. Disorders of sex development: a new definition and classification. Best Pract Res 14 Clin Endocrinol Metab 2008;22(1):119-34. doi: 10.1016/j.beem.2007.11.001 15 For peer review only 16 42. Owen-Smith A, Sineath RC, Sanchez T, et al. Perception of Community Tolerance and 17 Prevalence of Depression among Transgender Persons. J Gay Lesbian Ment Healt 2016( 18 in press) 19 20 43. Owen-Smith A, Woodyatt C, Sineath RC, et al. Perceptions of Barriers to and Facilitators of 21 Participation in Health Research among Transgender People Transgender Health 2016(in 22 23 press) 24 44. Sineath RC, Woodyatt C, Sanchez T, et al. Determinants of and Barriers to Hormonal and 25 Surgical Treatment Receipt Among Transgender People. Transgender Health 26 27 2016;1(1):129-36. 28 45. Collin L, Tangpricha V, Goodman M. Worldwide Prevalence of Transgender and Gender 29 Non-Conformity. In: Ettner R, Monstrey S, Coleman E, eds. Principles of Transgender 30 31 Medicine and Surgery New York, NY: Routledge 2016.

32 46. MacCarthy S, Reisner SL, Nunn A, et al. The Time Is Now: Attention Increases to http://bmjopen.bmj.com/ 33 34 Transgender Health in the United States but Scientific Knowledge Gaps Remain. LGBT 35 Health 2015;2(4):287-91. doi: 10.1089/lgbt.2014.0073 36 47. van Kesteren PJ, Asscheman H, Megens JA, et al. Mortality and morbidity in transsexual 37 38 subjects treated with cross-sex hormones. Clin Endocrinol (Oxf) 1997;47(3):337-42. 39 48. Asscheman H, Giltay EJ, Megens JA, et al. A long-term follow-up study of mortality in

40 on September 30, 2021 by guest. Protected copyright. 41 transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol 42 2011;164(4):635-42. doi: 10.1530/eje-10-1038 [published Online First: 2011/01/27] 43 49. Dhejne C, Lichtenstein P, Boman M, et al. Long-term follow-up of transsexual persons 44 45 undergoing sex reassignment surgery: cohort study in Sweden. PloS One 46 2011;6(2):e16885. doi: 10.1371/journal.pone.0016885 47 50. Kauth MR, Shipherd JC, Lindsay J, et al. Access to care for transgender veterans in the 48 49 Veterans Health Administration: 2006-2013. Am J Public Health 2014;104 Suppl 50 4:S532-4. doi: 10.2105/AJPH.2014.302086 51 52 53 54 55 56 57 58 59 60 23

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24 24 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only FIGURES AND TABLES AND FIGURES flow diagram ascertainment transgender cohort 1: STRONG Figure Page 25 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 26 of 84 Transgender Transgender Transsexual Transvestite identity Gender dysphoria Gender reassignment Gender As V codes may cover several conditions they they several conditions may cover codes V As 3940

Other conditions conditions Other Acquired absence of absence Acquired 25 25 – – specified Other – – specified Other http://bmjopen.bmj.com/ – – – – BMJ Open on September 30, 2021 by guest. Protected copyright. influencing health: transgender. health: transgender. influencing +121141596 V45.77 supplementation supplementation 12124310 + V07.8 genital organs: history of sex reassignment of sex reassignment history organs: genital surgery 12124952 + V07.8 V49.89 + 121141596 121141596 + V49.89 supplementation supplementation ICD-9 V-codes* + internal KP codes internal + KP V-codes* ICD-9 Keywords prophylactic measure: male-to-female hormone hormone male-to-female measure: prophylactic prophylactic measure: female-to-male hormone hormone female-to-male measure: prophylactic For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only

* ICD-9 V codes are used for supplementary classification of factors influencing health status. health influencing factors of classification supplementary used for are codes V * ICD-9 302.5 – Trans-sexualism Trans-sexualism – 302.5 unspecified with Trans-sexualism – 302.50 “transsexualism not (a.k.a. sexualhistory specified”) otherwise history asexual with Trans-sexualism – 302.51 homosexual with Trans-sexualism – 302.52 history; heterosexual with Trans-sexualism – 302.53 history in identity disorder Gender – 302.85 or adults adolescents inchildren identity disorder Gender – 302.6 fetishism Transvestic – 302.3 ICD-9 diagnostic codes codes diagnostic ICD-9 have to be used in conjunction with internal KP codes to ensure specificity toensure codes KP internal with in conjunction used be to have Table 1: ICD-9 codes and keywords used to identify potentially eligible STRONG transgender cohort members among KPGA, KPSC, and KPSC, among KPGA, members cohort transgender STRONG eligible potentially andidentify used to codes keywords ICD-9 Table1: members KPNC 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from

26 26 http://bmjopen.bmj.com/ BMJ Open ovary, ovaries, ovarian, cervix, uterus, uterine, vagina, PAP smear, menstrual bleeding, menses bleeding, menstrual PAP smear, vagina, uterine, cervix,ovarian, uterus, ovaries, ovary, vaginectomy, phalloplasty, metoidioplasty, mastectomy, hysterectomy, oophorectomy hysterectomy, mastectomy, metoidioplasty, phalloplasty, vaginectomy, castration, orchiectomy, penectomy, vaginoplasty, breast augmentation, breast enlargement, enlargement, breast augmentation, breast vaginoplasty, orchiectomy, penectomy, castration, therapy silicone, voice collagen, transplant, hair electrolysis, feminization, shave, laryngeal testes, testicular, penis, penile, prostate, prostatic, PSA, scrotum, neovagina, neo-vagina, neo neo-vagina, neovagina, PSA,scrotum, prostatic, penile, prostate, penis, testicular, testes, erection sperm, vagina, android, androderm, androgel, axiron, delatestryl, depo-testosterone, striant, testim striant, testim depo-testosterone, delatestryl, axiron, androgel, androderm, android, estrogen, anti-androgen, progesterone, aldactone, avodart, cenestin, climara, cyprostat, cyprostat, climara, cenestin, aldactone, avodart, progesterone, anti-androgen, estrogen, estradiol, estrace, elestrin, enjuvia, divigel, dutasteride, delestrogen, depo-estradiol, cyproterone, premarin, medroxyprogesterone, lupron, finasteride, flutamide, estrosorb, estrogel, estroderm, premphase, prempro, propecia, proscar, prometrium, provera, spironolactone, prometrium, provera, proscar, propecia, prempro, premphase, on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only Natal sex keywords sex Natal Natal sex keywords sex Natal Procedure keywords Procedure Procedure keywords Procedure Hormonal therapy keywords therapykeywords Hormonal Hormonal therapy keywords therapykeywords Hormonal

Trans-feminine Trans-feminine Trans-masculine Trans-masculine

Table 2: Keywords used for STRONG transgender cohort natal sex assignment assignment sex natal cohort transgender used forSTRONG Keywords Table2: Page 27 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from BMJ Open Page 28 of 84

1 2 3 Table 3: Data available for STRONG transgender cohort 4 5 Data categories and specific elements 6 Demographic and membership characteristics 7 Age, sex, and race/ethnicity 8 Health plan site 9 Area-based SES factors* 10 11 Enrollment/disenrollment intervals 12 Insurance plan type 13 General health indicators 14 Height/weight (BMI)* 15 Smoking status*For peer review only 16 17 Comorbidities 18 Gender affirmation procedures 19 CPT and/or ICD code 20 Date of procedure 21 History of gender affirmation procedures (clinical notes) 22 23 Pharmacy records (hormone therapy, psych medications) 24 Medication prescribed 25 Filled prescription for medication 26 Dose 27 Form 28 Dates of prescription and fill 29 30 Visit-associated diagnoses 31 CVD

32 Diabetes http://bmjopen.bmj.com/ 33 HIV 34 Mental health problems 35 36 Cancer diagnoses 37 Stage 38 Site 39 Histology

40 Date of diagnosis on September 30, 2021 by guest. Protected copyright. 41 42 Laboratory results 43 Laboratory test 44 Value 45 Date 46 Vital status 47 48 Date of death 49 Cause of death 50 *Assessed at index date (date of first evidence of transgender status in EMR) 51 52 53 54 55 56 57 58 59 60 27

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28 28 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only Figure 2: Results of STRONG transgender cohort ascertainment and validation and validation ascertainment cohort transgender of 2: STRONG Results Figure

Page 29 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 30 of 84 KPGA KPSC 29 29 http://bmjopen.bmj.com/ BMJ Open KPNC

Enrollment Year on September 30, 2021 by guest. Protected copyright. Kaiser Permanente Site: Permanente Kaiser For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

90 80 70 60 50 40 30 20 10 Prevalence per 100,000 per Prevalence Figure 3: Prevalence of transgender status by site and year of health plan enrollment enrollment of plan health and year by site status of transgender 3: Prevalence Figure trends linear represent lines Dotted 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 31 of 84 BMJ Open

Table 4: Characteristics of the STRONG transgender cohort 1 2 Participant Overall transgender cohort TF cohort** TM cohort** 3 characteristics n (col %) n (col %) n (col %) 4 Health plan site 5 KPNC 3842 (59) 1949 (56) 1831 (63) 6 7 KPSC 2443 (38) 1433 (41) 983 (34) 8 KPGA 174 (2.7) 95 (2.7) 79 (2.7) 9 Race/ethnicity 10 11 Non-Hispanic White 3534 (55) 1830 (53) 1669 (58) 12 Non-Hispanic Black 510 (7.9) 248 (7.1) 256 (8.8) 13 Asian 516 (8.0) 305 (8.8) 204 (7.1) 14 Hispanic 1232 (19) 710 (20) 503 (17) 15 For peer review only 16 Other/Unknown 667 (10) 384 (11) 261 (9.0) 17 Age* 18 3-17 years 1347 (21) 588 (17) 745 (26) 19 20 18-25 years 1431 (22) 655 (19) 753 (26) 21 26-35 years 1330 (21) 600 (17) 708 (24) 22 36-45 years 940 (15) 578 (17) 347 (12) 23 46-55 years 779 (12) 552 (16) 219 (7.6) 24 25 > 55 years 632 (10) 504 (14) 121 (4.2) 26 Smoking status* 27 Current 1011 (16) 506 (15) 489 (17) 28 29 Former 874 (14) 462 (13) 401 (14) 30 Never 4031 (62) 2197 (63) 1796 (62) 31 Unknown 543 (8.4) 312 (9.0) 207 (7.2) 32 BMI* http://bmjopen.bmj.com/ 33 34 Underweight 150 (2.3) 96 (2.8) 52 (1.8) 35 Normal Weight 2405 (37) 1356 (39) 1026 (35) 36 Overweight 1648 (26) 915 (26) 710 (25) 37 38 Obese 1692 (26) 779 (22) 886 (31) 39 Unknown 564 (8.7) 331 (10) 219 (7.6)

40 Medicaid status* on September 30, 2021 by guest. Protected copyright. 41 Yes 265 (4.1) 138 (4.0) 123 (4.3) 42 43 No 6032 (93) 3253 (94) 2703 (93) 44 Unknown 162 (2.5) 86 (2.5) 67 (2.3) 45 Census-level education status 46 47 < 30% of residents have high school or less 2635 (41) 1406 (40) 1194 (41) 48 30-50% of residents have high school or less 2234 (35) 1218 (35) 980 (34) 49 > 50% have high school or less 1467 (23) 795 (22) 655 (23) 50 Unknown 123 (1.9) 58 (1.7) 64 (2.2) 51 52 Total, n row (%) 6459 (100) 3477 (54) 2893 (45) 53 *Assessed at index date (date of first evidence of transgender status in electronic medical records) 54 **Excludes 89 persons with unknown natal sex 55 56 57 58 59 60 30

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Table 5: Gender affirmation status of the STRONG transgender cohort members 1 2 Overall TF TM 3 Gender affirmation transgender cohort cohort* cohort* 4 evidence and type n (col %) n (col %) n (col %) 5 Evidence of treatment 6 7 Any** 4043 (63) 2143 (62) 1793 (62) 8 None 2416 (37) 1334 (38) 1100 (38) 9 Cross-sex hormone therapy 10 Specific evidence at KP 3546 (55) 2031 (58) 1515 (52) 11 12 Evidence in the text only 187 (2.9) 112 (3.2) 72 (2.5) 13 No evidence 2726 (42) 1334 (38) 1306 (45) 14 Gender affirmation surgery 15 For peer review only 16 Top surgery at KP only 369 (6) 12 (0.3) 357 (12) 17 Orchiectomy at KP with or without top 52 (0.8) 52 (1.5) 0 (0.0) 18 Hysterectomy and/or oophorectomy at KP with or without top 311 (4.8) 0 (0.0) 311 (11) 19 Genital reconstruction at KP with or without other surgery 299 (4.6) 181 (5.2) 118 (4.1) 20 21 Evidence in the text only 432 (6.7) 253 (7.3) 179 (6.2) 22 No evidence 4996 (77) 2979 (86) 1928 (67) 23 Procedures to alter secondary sex characteristics 24 25 Specific evidence at KP 678 (10) 385 (11) 293 (10) 26 Evidence in the text only 58 (0.9) 52 (1.5) 6 (0.2) 27 No evidence 5723 (89) 3040 (87) 2594 (90) 28 29 Total 6459 (100) 3477 (100) 2893 (100) 30 *Excludes 89 persons with unknown natal sex 31 **Includes non-specific history and referral for treatment

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 30, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 31

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Table 6: Frequency of health outcomes in the STRONG trans-feminine (TF) cohort relative to matched 1 2 comparison groups 3 Health TF cohort Reference males Reference females 4 outcomes n (col %)^ n (col %)^ n (col %)^ 5 6 Cardiovascular disease 7 Venous thromboembolism 86 (2.5) 668 (1.9) 676 (2.0) 8 Stroke 88 (2.5) 943 (2.7) 674 (2.0) 9 Myocardial infarction 61 (1.8) 664 (1.9) 320 (0.9) 10 11 Peripheral artery disease 106 (3.0) 879 (2.6) 647 (1.9) 12 Unstable angina 64 (1.8) 656 (1.9) 337 (1.0) 13 Mental health* 14 Anxiety 1338 (38) 4325 (13) 7490 (22) 15 For peer review only 16 Depression 1706 (49) 4727 (14) 8731 (25) 17 Self-inflicted injury** 75 (2.2) 100 (0.3) 204 (0.6) 18 Suicidal ideation 175 (5.0) 157 (0.5) 194 (0.6) 19 20 Substance abuse disorder 524 (15) 2860 (8.3) 1681 (4.9) 21 Cancer primary site 22 Colorectum 10 (0.3) 107 (0.3) 91 (0.3) 23 24 Lung and bronchus 9 (0.3) 59 (0.2) 59 (0.2) 25 Lymphatic and hematopoietic 22 (0.6) 168 (0.5) 106 (0.3) 26 Melanoma 10 (0.3) 227 (0.7) 180 (0.5) 27 Prostate 25 (0.7) 452 (1.3) 0 (0.0) 28 29 Other chronic conditions* 30 HIV*** 186 (5.3) 191 (0.6) 15 (0.0) 31 Diabetes 315 (9.1) 3361 (9.8) 2620 (7.6)

32 http://bmjopen.bmj.com/ 33 Vital status 34 Alive 3374 (97) 33581 (98) 33858 (98) 35 Dead 103 (3.0) 819 (2.4) 552 (1.6) 36 37 Total 3477 (100) 34400 (100) 34410 (100) 38 *Based on at least 2 diagnoses in the EMR 39 **Combined diagnoses of self-inflicted injury, self-inflicted injury/poisoning, and possible

40 self-inflicted injury on September 30, 2021 by guest. Protected copyright. 41 42 ***HIV status ascertained from disease registries in KPNC and KPSC and from 2 or more 43 ICD codes in the EMR in KPGA 44 ^ Percentages do not add to 100% due to overlapping categories 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 32

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Table 7: Frequency of health outcomes in the STRONG trans-masculine (TM) cohort relative to 1 2 comparison groups 3 Health TM cohort Reference males Reference females 4 outcomes n (col %)^ n (col %)^ n (col %)^ 5 6 Cardiovascular disease 7 Venous thromboembolism 45 (1.6) 266 (0.9) 356 (1.2) 8 Stroke 42 (1.5) 360 (1.3) 250 (0.9) 9 Myocardial infarction 17 (0.6) 210 (0.7) 88 (0.3) 10 11 Peripheral artery disease 38 (1.3) 309 (1.1) 242 (0.8) 12 Unstable angina 20 (0.7) 215 (0.8) 123 (0.4) 13 Mental health* 14 Anxiety 1323 (46) 3583 (13) 6090 (21) 15 For peer review only 16 Depression 1594 (55) 3806 (13) 6814 (24) 17 Self-inflicted injury** 121 (4.2) 109 (0.4) 181 (0.6) 18 Suicidal ideation 193 (6.7) 160 (0.6) 186 (0.7) 19 20 Substance abuse disorder 418 (14) 2391 (8.4) 1523 (5.3) 21 Cancer primary site 22 Breast 20 (0.7) – 217 (0.8) 23 24 Cervix 7 (0.2) 0 (0.0) 172 (0.6) 25 Melanoma 8 (0.3) 109 (0.4) 71 (0.2) 26 Other chronic conditions* 27 HIV*** 9 (0.3) 117 (0.4) 10 (0.0) 28 29 Diabetes 152 (5.3) 1329 (4.7) 1213 (4.2) 30 Vital status 31 Alive 2854 (99) 28247 (99) 28376 (99)

32 http://bmjopen.bmj.com/ 33 Dead 39 (1.3) 283 (1.0) 183 (0.6) 34 Total 2893 (100) 28530 (100) 28559 (100) 35 *Based on at least 2 diagnoses in the EMR 36 **Combined diagnoses of self-inflicted injury, self-inflicted injury/poisoning, and 37 38 possible self-inflicted injury 39 *** HIV status ascertained from disease registries in KPNC and KPSC and from 2 or

40 more ICD codes in the EMR in KPGA on September 30, 2021 by guest. Protected copyright. 41 – Counts < 5 are suppressed 42 43 ^ Percentages do not add to 100% due to overlapping categories 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 33

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 42291-168-30 42291-168-30 35356-210-30 35356-210-30 69189-0712-1 69189-0712-1 NDC Codes NDC 60505-2642-1 60505-2642-1 0781-5409-01 41616-485-08 51991-560-01 65841-613-01 67253-191-03 0378-7017-93 16714-571-01 47335-485-08 63672-0005-0 0093-0220-01 68382-224-01 68084-612-11 63629-5321-1 0904-6019-46 69189-0298-1 60429-177-01 60429-226-05 54868-6133-0 0310-0705-10 54868-4503-0 59212-111-10 24987-111-14 0088-1111-14 0025-1001-31 0173-0712-02 54569-6607-0 16729-023-01 16729-023-01

1 1 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only AVODART (dutasteride) capsule, liquid filled (Repackaged) (Repackaged) liquid filled capsule, (dutasteride) AVODART Label BICALUTAMIDE tablet BICALUTAMIDE tablet BICALUTAMIDE tablet, coated film BICALUTAMIDE tablet, coated film BICALUTAMIDE tablet, coated film BICALUTAMIDE tablet, coated film BICALUTAMIDE tablet, coated film BICALUTAMIDE tablet, coated film BICALUTAMIDE tablet, coated film BICALUTAMIDE tablet, coated film BICALUTAMIDE tablet, coated film BICALUTAMIDE [Repackaged] coated film tablet, (bicalutamide) BICALUTAMIDE tablet [Repackaged] BICALUTAMIDE tablet [Repackaged] BICALUTAMIDE tablet [Repackaged] BICALUTAMIDE [Repackaged] tablet, coated film BICALUTAMIDE [Repackaged] tablet, coated film BICALUTAMIDE [Repackaged] tablet, coated film BICALUTAMIDE [Repackaged] tablet, coated film BICALUTAMIDE tablet (bicalutamide) CASODEX [Repackaged] tablet (bicalutamide) CASODEX coatedfilm tablet, spironolactone ALDACTONE- liquid filled capsule, (dutasteride) AVODART (Repackaged) liquid filled capsule, (dutasteride) AVODART (Repackaged) liquid filled capsule, (dutasteride) AVODART BICALUTAMIDE tablet BICALUTAMIDE BICALUTAMIDE tablet BICALUTAMIDE NILANDRON (nilutamide) tablet tablet (nilutamide) NILANDRON tablet (nilutamide) NILANDRON tablet (nilutamide) NILANDRON

SUPPLEMENTAL MATERIALS MATERIALS SUPPLEMENTAL affirmation gender used forTF reflecting codes medications Table1: NDC Supplemental Page 35 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 36 of 84 54868-1432-0 54868-1432-0 50419-491-04 50419-491-04 54868-1729-0 54868-1729-0 0781-4110-15 0781-4110-15 54868-6328-0 54868-6328-0 0037-4801-35 18860-490-02 18860-480-01 0173-0809-13 0173-0809-13 54868-5570-0 54868-5570-0 42023-110-01 54868-5114-0 54868-5114-0 50419-451-01 50419-451-01 42023-134-01 42023-134-01 0574-0870-05 0009-0271-01 0245-0880-30 68025-065-01 54868-6056-0 0591-2292-19 65162-750-03 51991-749-33 0054-0395-13 60505-3877-3 0173-7077-00 0115-1438-08 62112-8068-1 64980-224-03 64380-763-04 0093-5655-56 42291-257-90 63187-657-30 10370-280-09 10370-280-09 0591-3771-19 2 2 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only ELESTRIN (estradiol gel 0.06%) gel, metered metered gel, 0.06%) gel (estradiol ELESTRIN gel (estradiol) ELESTRIN gel (estradiol) ELESTRIN JALYN (dutasteride and tamsulosin hydrochloride) capsule capsule and hydrochloride) tamsulosin (dutasteride JALYN CLIMARA PRO (estradiol and levonorgestrel) patch levonorgestrel) PRO (estradiol and CLIMARA DELESTROGEN- estradiol valerate injection injection estradiol valerate DELESTROGEN- kit VALERATE/DIENOGEST ESTRADIOL AND VALERATE ESTRADIOL CENESTIN - synthetic conjugated estrogens, a tablet, film coated tablet, a coated film estrogens, conjugated synthetic - CENESTIN CLIMARA (estradiol) patch [Repackaged] patch (estradiol) [Repackaged] CLIMARA CLIMARA PRO (estradiol and levonorgestrel) patch [Repackaged] patch[Repackaged] levonorgestrel) PRO (estradiol and CLIMARA ESTRADIOL VALERATE injection injection VALERATE ESTRADIOL solution injection, VALERATE ESTRADIOL injection cypionate) (estradiol DEPO-ESTRADIOL injection [Repackaged] cypionate) (estradiol DEPO-ESTRADIOL gel (estradiol) DIVIGEL gel (estradiol) DIVIGEL gel [Repackaged] (estradiol) DIVIGEL capsule DUTASTERIDE capsule DUTASTERIDE capsule DUTASTERIDE capsule DUTASTERIDE capsule, liquid filled DUTASTERIDE capsule, liquid filled DUTASTERIDE capsule, liquid filled DUTASTERIDE capsule, liquid filled DUTASTERIDE capsule, liquid filled DUTASTERIDE capsule, liquid filled DUTASTERIDE capsule, liquid filled DUTASTERIDE [Repackaged] capsule (dutasteride) DUTASTERIDE capsule [Repackaged] DUTASTERIDE capsule HYDROCHLORIDE TAMSULOSIN AND DUTASTERIDE capsule HYDROCHLORIDE TAMSULOSIN AND DUTASTERIDE capsule and hydrochloride) tamsulosin (dutasteride JALYN AVODART (dutasteride) capsule, liquid filled (Repackaged) (Repackaged) liquid filled capsule, (dutasteride) AVODART

Page 37 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 38 of 84 54868-4242-0 54868-4242-0 69189-0487-1 69189-0487-1 69189-0899-1 10544-069-30 63629-2766-1 63629-4788-1 63629-3755-1 63629-5208-1 55154-6242-0 61919-278-30 61919-198-30 60429-327-01 0179-0123-70 0179-0073-70 0179-1999-01 49999-083-30 43063-446-01 43063-651-30 55289-761-01 55289-603-07 54868-4030-0 68788-9901-1 68788-9416-1 63187-482-30 64205-048-30 21695-613-00 16590-278-30 16590-052-71 62157-007-02 44911-0199-1 50419-455-04 54868-6182-0 51991-474-28 4 4 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only ESTRADIOL tablet [Repackaged] [Repackaged] tablet ESTRADIOL ESTRADIOL tablet [Repackaged] [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL powder (estradiol) PHARMACEUTICAL AX liquid (estradiol,) PHENOLIC ESTROGEN [Repackaged] patch (estradiol) MENOSTAR [Repackaged] tablet, coated film (estradiol) VAGIFEM [Repackaged] release extended estradiol DOT - patch, VIVELLE tablet, film acetate) norethindrone and ACETATE (estradiol / NORETHINDRONE ESTRADIOL coated

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 0603-7606-02 0603-7606-02 0603-7607-02 0603-7607-02 68180-827-09 68180-827-09 0430-0535-14 0430-0535-14 0603-7609-01 0603-7609-01 0430-0530-14 0430-0530-14 0430-0570-14 0430-0570-14 0430-0005-31 0093-5328-28 0093-5328-28 0603-7608-01 0603-7608-01 0603-7610-01 0603-7610-01 52544-236-31 52544-236-31 52544-175-72 52544-175-72 68180-866-11 68180-866-11 68180-864-11 68180-864-11 68180-865-11 68180-865-11 50102-128-01 50102-128-01 54868-6100-0 54868-6100-0 0093-3122-28 0093-3122-28 0430-0420-14 0430-0420-14 0378-7283-53 0378-7283-53 0378-7301-53 54868-4677-0 54868-4677-0 52544-054-31 52544-054-31 68462-656-29 68462-656-29 68462-132-79 0378-7280-53 0430-0539-14 0430-0539-14

5 5 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only GILDESS 1.5/30 (norethindrone acetate and ethinyl estradiol) tablet, film coated coated film tablet, estradiol) and ethinyl acetate (norethindrone 1.5/30 GILDESS coated film tablet, estradiol) ethinyl and acetate (norethindrone 1/20 GILDESS FYAVOLV (norethindrone acetate and ethinyl estradiol) tablet, film coated coated film tablet, estradiol) and ethinyl acetate (norethindrone FYAVOLV tablet estradiol) and ethinyl acetate (norethindrone LO JEVANTIQUE BLISOVI 24 FE (norethindrone acetate and ethinyl estradiol) kit estradiol) ethinyl and acetate (norethindrone 24 FE BLISOVI kit estradiol) and ethinyl acetate (norethindrone 1/20 FE BLISOVI BLISOVI FE 1.5/30 (norethindrone acetate and ethinyl estradiol) kit estradiol) ethinyl and acetate (norethindrone 1.5/30 FE BLISOVI JINTELI (norethindrone acetate and ethinyl estradiol) tablet tablet estradiol) ethinyl and acetate (norethindrone JINTELI GILDESS 24 FE (norethindrone acetate and ethinyl estradiol and ferrous fumarate) fumarate) ferrous and estradiol ethinyl and acetate (norethindrone FE 24 GILDESS GILDESS FE 1.5/30 (norethindrone acetate, ethinyl estradiol and ferrous fumarate) kit fumarate) ferrous and estradiol ethinyl acetate, (norethindrone 1.5/30 FE GILDESS kit fumarate) ferrous and ethinyl estradiol acetate, (norethindrone 1/20 FE GILDESS JUNEL FE 24 (norethindrone acetate and ethinyl estradiol and ferrous fumarate) kit fumarate) ferrous and estradiol ethinyl and acetate 24 (norethindrone FE JUNEL fumarate) ferrous and estradiol ethinyl estradiol, and ethinyl acetate FE (norethindrone LOESTRIN LO kit LOESTRIN 24 FE (norethindrone acetate and ethinyl estradiol, and ferrous fumarate) kit ferrous fumarate) and estradiol, and ethinyl acetate (norethindrone 24 FE LOESTRIN MICROGESTIN 24 FE (norethindrone acetate and ethinyl estradiol and ferrous fumarate) kit fumarate) ferrous and estradiol andacetate ethinyl (norethindrone 24 FE MICROGESTIN kit and ferrousfumarate) estradiol, ethinyl and acetate FE (norethindrone 24 MINASTRIN 52544-167-31 estradiol ) kit ) estradiol estradiol ) kit ) estradiol ESTRADIOL / NORETHINDRONE ACETATE (estradiol and norethindrone acetate) tablet, film acetate) norethindrone and ACETATE (estradiol / NORETHINDRONE ESTRADIOL [Repackaged] coated ESTROSTEP FE (norethindrone acetate and ethinyl estradiol and ferrous fumarate) kit fumarate) ferrous and estradiol and ethinyl acetate (norethindrone FE ESTROSTEP kit fumarate) ferrous and estradiol and ethinyl acetate (norethindrone FE ESTROSTEP TILIA FE (norethindrone acetate and ethinyl estradiol, and ferrous fumarate) kit fumarate) ferrous and estradiol, ethinyl and acetate (norethindrone FE TILIA kit [Repackaged] ferrous fumarate) and estradiol, and ethinyl acetate (norethindrone 24 FE LOESTRIN and '', and '') kit and '', '') and TARINA FE 1/20 (norethindrone acetate and ethinyl estradiol) kit estradiol) and ethinyl acetate 1/20 (norethindrone FE TARINA TILIA FE (norethindrone acetate and ethinyl estradiol) kit kit estradiol) ethinyl and acetate (norethindrone FE TILIA NORETHINDRONE ACETATE AND ETHINYL ESTRADIOL ( norethindrone acetate and ethinyl ethinyl and acetate norethindrone ( ESTRADIOL ETHINYL AND ACETATE NORETHINDRONE NORETHINDRONE ACETATE AND ETHINYL ESTRADIOL ( norethindrone acetate and ethinyl ethinyl and acetate norethindrone ( ESTRADIOL ETHINYL AND ACETATE NORETHINDRONE ('', FERROUSAND FUMARATE ESTRADIOL ETHINYL AND ACETATE NORETHINDRONE NORETHINDRONE ACETATE AND ETHINYL ESTRADIOL tablet tablet ESTRADIOL ETHINYL AND ACETATE NORETHINDRONE tablet ESTRADIOL ETHINYL AND ACETATE NORETHINDRONE tablet ESTRADIOL ETHINYL AND ACETATE NORETHINDRONE

Page 39 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 40 of 84 54868-5326-0 54868-5326-0 54868-6213-0 54868-6213-0 54868-6251-0 54868-6251-0 0555-9027-42 0555-9027-42 0555-9028-58 0555-9028-58 52544-233-28 52544-233-28 16714-405-01 16714-405-01 0378-7277-53 0378-7277-53 68180-838-11 68180-838-11 16714-406-01 16714-406-01 16714-416-01 16714-416-01 0555-9032-70 0555-9032-70 54868-6274-0 54868-6274-0 21695-685-28 21695-685-28 0555-9026-58 0555-9026-58 65162-316-58 65162-316-58 52544-247-28 52544-247-28 50458-251-00 50458-251-00 52544-143-31 52544-143-31 16714-407-01 16714-407-01 16714-408-01 0430-0537-14 0430-0540-50 54868-4744-0 68462-309-29 68462-565-29 68462-719-29 0555-9025-42 0555-9025-42 6 6 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only TRI-LEGEST FE 28 DAY (norethindrone acetate and ethinyl estradiol) kit estradiol) ethinyl and acetate 28 (norethindrone DAY FE TRI-LEGEST JINTELI (norethindrone acetate and ethinyl estradiol) tablet [Repackaged] [Repackaged] tablet estradiol) ethinyl and acetate (norethindrone JINTELI kit [Repackaged] fumarate) ferrous and estradiol, ethinyl and acetate (norethindrone 1/20 FE JUNEL 54868-5935-0 JUNEL 1.5/30 (norethindrone acetate and ethinyl estradiol) tablet [Repackaged] [Repackaged] tablet estradiol) ethinyl and acetate (norethindrone 1.5/30 JUNEL LARIN FE 1.5/30 (norethindrone acetate/ethinyl estradiol and ferrous fumarate) kit fumarate) ferrous and estradiol acetate/ethinyl (norethindrone 1.5/30 FE LARIN TILIA FE (norethindrone acetate and ethinyl estradiol) kit [Repackaged] kit [Repackaged] estradiol) ethinyl and acetate (norethindrone FE TILIA kit estradiol) ethinyl and / TRINESSA (norgestimate MONONESSA MINASTRIN 24 FE (norethindrone acetate and ethinyl estradiol chewable tablets and ferrous fumarate fumarate ferrous chewable and tablets estradiol ethinyl and acetate FE (norethindrone 24 MINASTRIN kit tablets) JUNEL FE 1.5/30 (norethindrone acetate and ethinyl estradiol, and ferrous fumarate) kit [Repackaged] kit [Repackaged] ferrous fumarate) and estradiol, and ethinyl acetate (norethindrone 1.5/30 FE JUNEL 54868-6272-0 kit [Repackaged] ferrous fumarate) and estradiol, and ethinyl acetate (norethindrone 1.5/30 FE JUNEL 42254-242-28 kit and ferrousfumarate) estradiol ethinyl and acetate (norethindrone FE MICROGESTIN [Repackaged] LARIN 1/20 (norethindrone acetate/ethinyl estradiol) kit kit estradiol) acetate/ethinyl (norethindrone 1/20 LARIN kit fumarate) ferrous estradiol and acetate/ethinyl FE (norethindrone 24 LARIN kit fumarate) ferrous and estradiol acetate/ethinyl (norethindrone 1/20 FE LARIN kit estradiol) and ethinyl acetate (norethindrone 24 FE LOMEDIA / kit tablet estradiol) and ethinyl acetate (norethindrone MICROGESTIN kit estradiol) ethinyl and acetate (norethindrone FE TILIA [Repackaged] tablet estradiol) and ethinyl acetate (norethindrone MICROGESTIN kit estradiol) ethinyl and (norgestimate CYCLEN LO TRI ORTHO LO MINASTRIN FE (norethindrone acetate and ethinyl estradiol, ethinyl estradiol and ferrous ferrous and estradiol ethinyl estradiol, ethinyl and acetate (norethindrone MINASTRIN FE LO kit fumarate) kit [Repackaged] estradiol) ethinyl and acetate (norethindrone FE TILIA JUNEL 1.5/30 (norethindrone acetate and ethinyl estradiol) tablet estradiol) ethinyl and acetate (norethindrone 1.5/30 JUNEL kit fumarate) ferrous and estradiol, ethinyl and acetate (norethindrone 1/20 FE JUNEL kit ferrous fumarate) and estradiol, and ethinyl acetate (norethindrone 1.5/30 FE JUNEL kit estradiol) acetate/ethinyl (norethindrone 1.5/30 LARIN JUNEL 1/20 (norethindrone acetate and ethinyl estradiol) tablet tablet estradiol) and ethinyl acetate (norethindrone 1/20 JUNEL NORGESTIMATE AND ETHINYL ESTRADIOL (norgestimate and ethinyl estradiol) kit estradiol) and ethinyl (norgestimate ESTRADIOL ETHINYL AND NORGESTIMATE NORGESTIMATE AND ETHINYL ESTRADIOL ( norgestimate and ethinyl estradiol ) kit ) estradiol and ethinyl norgestimate ( ESTRADIOL ETHINYL AND NORGESTIMATE NORGESTIMATE AND ETHINYL ESTRADIOL kit ESTRADIOL ETHINYL AND NORGESTIMATE NORGESTIMATE AND ETHINYL ESTRADIOL kit ESTRADIOL ETHINYL AND NORGESTIMATE kit ESTRADIOL ETHINYL AND NORGESTIMATE

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 54868-4093-0 54868-4093-0 76413-128-28 76413-128-28 66116-436-28 54868-5028-0 63187-458-28 21695-770-01 21695-407-01 21695-407-01 21695-769-28 21695-769-28 76413-121-28 76413-121-28 0603-7642-01 0603-7642-01 0781-4062-15 0781-4062-15 54868-4730-0 54868-4730-0 0083-2310-08 0083-2310-08 0013-2150-36 63539-021-01 17139-613-50 0555-9018-58 0555-9018-58 68180-837-11 68180-837-11 65862-777-28 57297-837-11 57297-837-11 0781-4060-15 0781-4060-15 16714-363-01 16714-360-01 16714-360-01 50458-191-00 0555-9016-58 54868-5826-0 54868-5826-0 0781-4058-15 69238-1551-6 65862-776-28 51285-063-90 51285-063-90 0093-2140-28 52544-248-28 52544-087-28 63187-054-28 7 7 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only SPRINTEC (norgestimate and ethinyl estradiol) kit [Repackaged] kit [Repackaged] estradiol) ethinyl and (norgestimate SPRINTEC ESTRING (estradiol) ring ring (estradiol) ESTRING ring (estradiol) ESTRING metered (estradiol) gel, ESTROGEL ESTRADERM- estradiol patch, extended release [Repackaged] [Repackaged] release extended patch, estradiol ESTRADERM- ORTHO TRI CYCLEN (norgestimate and ethinyl estradiol) kit [Repackaged] kit [Repackaged] ethinyl estradiol) and (norgestimate CYCLEN TRI ORTHO kit [Repackaged] estradiol) ethinyl and (norgestimate PREVIFEM TRI-SPRINTEC (norgestimate and ethinyl estradiol) kit [Repackaged] [Repackaged] kit estradiol) ethinyl and (norgestimate TRI-SPRINTEC TRI-SPRINTEC (norgestimate and ethinyl estradiol) kit [Repackaged] [Repackaged] kit estradiol) ethinyl and (norgestimate TRI-SPRINTEC [Repackaged] kit estradiol) ethinyl and (norgestimate TRI-SPRINTEC [Repackaged] kit estradiol) ethinyl and (norgestimate TRI-SPRINTEC [Repackaged] kit estradiol) ethinyl and (norgestimate TRI-SPRINTEC kit [Repackaged] estradiol) ethinyl and (norgestimate TRINESSA TRI-MILI (norgestimate and ethinyl estradiol) kit kit estradiol) ethinyl (norgestimate and TRI-MILI kit estradiol) ethinyl and (norgestimate TRI-SPRINTEC TRI-LO-MARZIA ( norgestimate and ethinyl estradiol ) kit kit ) estradiol ethinyl and norgestimate ( TRI-LO-MARZIA TRI-LINYAH (norgestimate and ethinyl estradiol) kit kit estradiol) ethinyl and (norgestimate TRI-LINYAH kit estradiol) and ethinyl (norgestimate ESTARYLLA TRI-LO- TRI-LO-MARZIA ( norgestimate and ethinyl estradiol ) kit kit ) estradiol ethinyl and norgestimate ( TRI-LO-MARZIA SPRINTEC (norgestimate and ethinyl estradiol) kit estradiol) ethinyl and (norgestimate SPRINTEC ORTHO TRI CYCLEN (norgestimate and ethinyl estradiol) kit ethinyl estradiol) and (norgestimate CYCLEN TRI ORTHO kit estradiol) and ethinyl (norgestimate / TRI-PREVIFEM PREVIFEM kit estradiol) ethinyl and (norgestimate TRI-ESTARYLLA ESTARYLLA (norgestimate and ethinyl estradiol) kit kit estradiol) ethinyl and (norgestimate ESTARYLLA kit estradiol) ethinyl and (norgestimate FEMYNOR kit estradiol) and ethinyl (norgestimate MILI estradiol) kit ethinyl (norgestimate and MONO-LINYAH TRINESSA (norgestimate and ethinyl estradiol) kit estradiol) ethinyl and (norgestimate TRINESSA PREFEST- estradiol/norgestimate estradiol/norgestimate PREFEST- TRI-LO-SPRINTEC (norgestimate and ethinyl estradiol) kit estradiol) ethinyl and (norgestimate TRI-LO-SPRINTEC kit estradiol) ethinyl and (norgestimate TRINESSA kit estradiol) ethinyl (norgestimate and LO TRINESSA kit estradiol) ethinyl and (norgestimate MONONESSA kit estradiol) ethinyl and (norgestimate CYCLEN LO TRI ORTHO

Page 41 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 42 of 84 15310-010-01 15310-010-01 13925-171-01 13925-171-01 50220-001-01 50220-001-01 53746-077-01 53746-077-01 62559-149-01 57520-0860-1 57520-0860-1 43857-0074-1 43857-0150-1 57520-0094-1 43742-0066-1 61570-072-01 54868-5934-0 29336-325-56 99207-190-56 0574-2067-00 64011-215-41 54868-6157-0 0172-4960-58 49884-753-05 0591-2466-18 60429-272-05 69097-112-02 55111-172-01 65977-5025-0 16729-090-01 16729-089-10 45963-600-03 45963-500-02 65862-686-30 65862-149-01 31722-525-01 31722-525-01 31722-526-10 17139-617-20 17139-617-20 8 8 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only MENEST (esterified estrogens) tablet, film coated coated film tablet, estrogens) (esterified MENEST ESTROGEN (folliculinum, oophorinum) liquid liquid oophorinum) (folliculinum, ESTROGEN liquid oophorinum) (folliculinum, ESTROGEN liquid oophorinum) (folliculinum, ESTROGEN liquid oophorinum) (folliculinum, ESTROGEN coated tablet, methyltestosterone) and esterified (estrogens, EEMT tablet [Repackaged] esterified) (estrogens, MENEST ESTRASORB ESTRASORB spray (estradiol) EVAMIST metered spray, (estradiol) EVAMIST [Repackaged] metered spray, (estradiol) EVAMIST capsule FLUTAMIDE capsule FLUTAMIDE capsule FLUTAMIDE capsule FLUTAMIDE tablet FINASTERIDE tablet FINASTERIDE tablet FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE ESTROGEN (folliculinum, oophorinum) liquid liquid oophorinum) (folliculinum, ESTROGEN ESTERIFIED ESTROGENS AND METHYLTESTOSTERONE tablet, film coated coated film tablet, METHYLTESTOSTERONE ESTROGENSAND ESTERIFIED coated film tablet, METHYLTESTOSTERONE ESTROGENSAND ESTERIFIED ESTROGEL (estradiol) gel, metered metered (estradiol) gel, ESTROGEL ESTERIFIED ESTROGENS AND METHYLTESTOSTERONE tablet tablet METHYLTESTOSTERONE ESTROGENSAND ESTERIFIED ESTERIFIED ESTROGENS AND METHYLTESTOSTERONE tablet tablet METHYLTESTOSTERONE ESTROGENSAND ESTERIFIED

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 57237-062-05 57237-062-05 57237-061-30 55111-171-05 76282-412-05 68554-3025-0 68554-3026-0 50742-123-30 63739-495-40 51079-321-01 51079-520-01 0378-5036-01 58517-200-30 16714-522-10 0603-3633-02 47335-715-08 47335-714-08 0093-7355-05 42291-280-50 33261-833-90 43598-303-30 0179-0175-88 68788-9519-3 52125-403-02 54569-6048-0 68084-919-11 68084-399-01 17856-0090-1 69189-0090-1 50268-323-11 63629-5220-1 63629-1585-1 55154-5685-0 58118-7355-0 43598-390-30 9 9 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only FINASTERIDE tablet, film coated tablet, film coated FINASTERIDE FINASTERIDE tablet, film coated tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE [Repackaged] coated film tablet, (finasteride) FINASTERIDE tablet [Repackaged] FINASTERIDE tablet [Repackaged] FINASTERIDE tablet [Repackaged] FINASTERIDE tablet [Repackaged] FINASTERIDE tablet [Repackaged] FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE

Page 43 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 44 of 84 0074-1053-05 0074-1053-05 0074-1052-05 33261-534-05 33261-534-05 60687-105-11 54569-0809-0 54569-0809-0 54569-3806-2 55289-908-30 55289-908-30 43063-438-05 54569-5616-0 54569-5616-0 54868-5257-0 68788-9233-1 52125-640-01 52125-915-01 68645-446-70 68645-446-70 54868-5636-0 68788-9517-1 68788-9249-3 63187-265-30 61786-340-19 61786-329-19 61786-230-19 61786-302-19 61786-302-02 50436-0446-1 0300-3612-24 0074-3641-03 0074-3663-03 0074-3346-03 0074-2108-03 52125-736-01 59762-4537-1 0703-6801-01 0555-0779-02 59762-3740-1 10 10 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE MEDROXYPROGESTERONE ACETATE injection, suspension [Repackaged] [Repackaged] injection, suspension ACETATE MEDROXYPROGESTERONE MEDROXYPROGESTERONE ACETATE injection, suspension [Repackaged] [Repackaged] injection, suspension ACETATE MEDROXYPROGESTERONE [Repackaged] injection, suspension ACETATE MEDROXYPROGESTERONE [Repackaged] injection, suspension ACETATE MEDROXYPROGESTERONE [Repackaged] injection, suspension ACETATE MEDROXYPROGESTERONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE FINASTERIDE tablet, film coated [Repackaged] [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE solution injection, acetate) (leuprolide LUPRON kit acetate) DEPOT (leuprolide LUPRON kit acetate) DEPOT (leuprolide LUPRON kit acetate) DEPOT (leuprolide LUPRON kit acetate) DEPOT-PED (leuprolide LUPRON kit [Repackaged] acetate) DEPOT-PED (leuprolide LUPRON kit acetate) norethindrone and acetate (leuprolide PACK LUPANETA injection, suspension ACETATE MEDROXYPROGESTERONE tablet ACETATE MEDROXYPROGESTERONE tablet ACETATE MEDROXYPROGESTERONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE FINASTERIDE tablet, film coated [Repackaged] [Repackaged] tablet, film coated FINASTERIDE LUPANETA PACK (leuprolide acetate and norethindrone acetate) kit acetate) norethindrone and acetate (leuprolide PACK LUPANETA injection, suspension ACETATE MEDROXYPROGESTERONE

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 54868-3799-0 54868-3799-0 54868-3800-0 54868-3800-0 0046-0749-05 0046-0749-05 49349-287-08 49349-287-08 52125-803-08 52125-803-08 49349-287-02 52125-562-08 64205-077-10 64205-077-10 21695-896-10 66336-603-20 66336-603-20 55289-160-05 55289-816-30 54868-0109-0 68788-9899-1 63629-2612-1 63629-2612-1 55154-0533-0 63629-2613-1 63629-2613-1 63629-2614-1 69189-3741-1 69189-3741-1 10544-001-30 43353-687-60 43353-687-60 55154-0216-0 49999-109-00 49999-109-00 54868-0365-0 54569-0812-0 54569-0811-3 54569-0811-3 35356-249-00 35356-249-00 53808-0770-1 53808-0770-1 69189-1105-1 69189-1105-1 0046-1100-51 0046-1100-51 0046-0872-04 68258-5978-2 68258-5978-2 11 11 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE tablet, coated film (estrogens, conjugated) PREMARIN PREMARIN (conjugated estrogens) injection, powder, lyophilized, for solution lyophilized,for powder, injection, (conjugatedestrogens) PREMARIN cream estrogens) (conjugated VAGINAL PREMARIN [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN PREMARIN (conjugated estrogens) tablet, film coated [Repackaged] [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE coated kit, sugar tablet, acetate) and medroxyprogesterone estrogens (conjugated PREMPHASE kit [Repackaged] acetate) and medroxyprogesterone estrogens (conjugated PREMPHASE coated tablet, sugar acetate) medroxyprogesterone and estrogens PREMPRO(conjugated 0046-1105-11 [Repackaged] MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN coated tablet, sugar acetate) medroxyprogesterone and estrogens PREMPRO(conjugated PREMARIN (conjugated estrogens) tablet, film coated [Repackaged] [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE

Page 45 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 46 of 84 54868-4120-0 54868-4120-0 0006-0072-31 0032-1708-01 69189-1708-1 63629-2770-1 63629-2767-1 54868-4230-0 63629-1603-1 63629-1603-1 55056-0806-2 55056-0806-2 57520-0318-1 43857-0084-1 55056-0406-1 55714-6634-1 57520-0301-1 17478-766-10 42291-690-01 69387-101-01 10888-7135-2 11014-0189-1 0093-5353-01 0591-3964-01 0143-9725-01 0591-3128-79 0517-0750-01 63323-261-10 43857-0120-1 43857-0103-1 43742-0762-1 43742-0158-1 60429-281-01 43063-649-30 62157-217-01 0006-0071-07 12 12 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only PROSCAR- finasteride tablet, film coated coated film tablet, finasteride PROSCAR- capsule (progesterone) PROMETRIUM [Repackaged] capsule (progesterone) PROMETRIUM [Repackaged] capsule (progesterone) PROMETRIUM [Repackaged] capsule (progesterone) PROMETRIUM [Repackaged] capsule (progesterone) PROMETRIUM PROPECIA (finasteride) tablet, film coated [Repackaged] [Repackaged] coated film tablet, (finasteride) PROPECIA PROCHIEVE (progesterone) gel (progesterone) gel PROCHIEVE liquid (progesterone) PROGESTERONE liquid (progesterone,) PROGESTERONE capsule PROGESTERONE capsule PROGESTERONE capsule PROGESTERONE capsule PROGESTERONE capsule PROGESTERONE capsule PROGESTERONE capsule PROGESTERONE injection PROGESTERONE solution injection, PROGESTERONE solution injection, PROGESTERONE solution injection, PROGESTERONE liquid PROGESTERONE liquid PROGESTERONE liquid PROGESTERONE liquid PROGESTERONE [Repackaged] capsule PROGESTERONE [Repackaged] capsule PROGESTERONE powder (progesterone) X coated film tablet, (finasteride) PROPECIA [Repackaged] coated film tablet, (finasteride) PROPECIA [Repackaged] [Repackaged] gel (progesterone) CRINONE NATURAL PROGESTERONE (progesterone) spray spray (progesterone) PROGESTERONE NATURAL spray (progesterone) PROGESTERONE NATURAL

Page 47 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 48 of 84 59762-5014-1 59762-5014-1 68084-946-11 68084-946-11 51079-104-01 51079-104-01 53808-0796-1 53808-0796-1 50436-9973-1 54569-0505-0 33261-764-30 68084-206-01 63629-4094-1 63629-5341-1 55154-5055-0 68151-2776-1 66336-916-30 35356-419-00 55700-305-30 35356-969-30 76237-246-30 51079-103-01 0615-1535-05 0615-8031-05 51655-838-52 55289-507-01 43063-277-30 54868-0700-0 68788-9227-3 63187-634-30 42254-183-30 21695-960-60 52125-418-02 53808-0338-1 50436-5015-0 50436-4477-2 53489-144-01 53489-144-01 0378-0141-01 14 14 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only SPIRONOLACTONE tablet [Repackaged] tablet [Repackaged] SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE tablet HYDROCHLOROTHIAZIDE AND SPIRONOLACTONE tablet HYDROCHLOROTHIAZIDE AND SPIRONOLACTONE tablet, film coated HYDROCHLOROTHIAZIDE AND SPIRONOLACTONE SPIRONOLACTONE tablet [Repackaged] tablet [Repackaged] SPIRONOLACTONE SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE tablet [Repackaged] HYDROCHLOROTHIAZIDE AND SPIRONOLACTONE tablet [Repackaged] HYDROCHLOROTHIAZIDE AND SPIRONOLACTONE

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 68180-866-13 68180-866-13 68788-9899-3 68788-9899-3 68180-865-13 68180-865-13 54868-0699-1 54868-0699-1 68462-656-90 68462-656-90 68462-132-81 68462-132-81 68788-9729-6 68788-9729-6 68788-9519-6 68788-9517-3 68788-9416-3 68788-9249-6 68788-9227-6 68788-9124-6 68554-3026-1 68554-3025-1 68462-719-84 76282-412-10 76282-412-10 69761-025-12 69761-022-12 69761-020-12 69761-018-12 69761-015-12 69761-012-12 69761-010-12 69761-006-12 69387-102-01 69189-0511-5 69097-112-05 68788-9901-3 68462-309-84 68382-224-05 68258-5980-2 15 15 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only SPIRONOLACTONE tablet [Repackaged] tablet [Repackaged] SPIRONOLACTONE FINASTERIDE tablet [Repackaged] FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet ESTRADIOL [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, coated film SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE ESTRADIOL pellet pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL capsule PROGESTERONE tablet [Repackaged] SPIRONOLACTONE tablet FINASTERIDE [Repackaged] tablet ESTRADIOL tablet [Repackaged] ACETATE MEDROXYPROGESTERONE tablet, coated film BICALUTAMIDE coated tablet, sugar acetate) medroxyprogesterone and estrogens PREMPRO(conjugated [Repackaged] kit estradiol) ethinyl and acetate (norethindrone 1.5/30 FE BLISOVI kit estradiol) and ethinyl acetate (norethindrone 1/20 FE BLISOVI SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE tablet [Repackaged] HYDROCHLOROTHIAZIDE AND SPIRONOLACTONE SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE tablet, film coated [Repackaged] [Repackaged] tablet, film coated HYDROCHLOROTHIAZIDE AND SPIRONOLACTONE tablet, film coated FINASTERIDE 54569-0502-0 NORGESTIMATE AND ETHINYL ESTRADIOL kit ESTRADIOL ETHINYL AND NORGESTIMATE tablet ESTRADIOL ETHINYL AND ACETATE NORETHINDRONE NORETHINDRONE ACETATE AND ETHINYL ESTRADIOL tablet tablet ESTRADIOL ETHINYL AND ACETATE NORETHINDRONE NORGESTIMATE AND ETHINYL ESTRADIOL kit ESTRADIOL ETHINYL AND NORGESTIMATE

Page 49 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 50 of 84 68180-827-11 68180-827-11 68180-838-13 68180-838-13 68180-864-13 68180-864-13 65162-316-84 65162-316-84 64205-087-30 64205-087-30 68084-946-21 68084-946-21 64205-048-90 64205-048-90 64011-215-42 63739-544-10 63739-495-41 63629-5321-2 63629-5220-2 63629-5208-2 63629-4788-2 68180-837-13 68180-837-13 68084-919-21 68084-612-21 68084-399-11 68084-206-11 68025-065-07 68025-065-07 67253-191-10 66336-916-60 65977-5025-1 65862-777-85 65862-776-85 65862-686-90 65862-149-05 65841-613-05 65162-750-09 65162-511-06 65162-226-23 64980-224-09 64380-763-05 16 16 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only ESTRADIOL tablet [Repackaged] [Repackaged] tablet ESTRADIOL EVAMIST (estradiol) spray, metered metered spray, (estradiol) EVAMIST tablet [Repackaged] SPIRONOLACTONE tablet, film coated FINASTERIDE tablet [Repackaged] BICALUTAMIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL FYAVOLV (norethindrone acetate and ethinyl estradiol) tablet, film coated coated film tablet, estradiol) and ethinyl acetate (norethindrone FYAVOLV tablet [Repackaged] HYDROCHLOROTHIAZIDE AND SPIRONOLACTONE tablet [Repackaged] BICALUTAMIDE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet, coated film SPIRONOLACTONE gel (estradiol) DIVIGEL gel (estradiol) DIVIGEL tablet, coated film BICALUTAMIDE [Repackaged] tablet, coated film SPIRONOLACTONE tablet FINASTERIDE kit estradiol) ethinyl (norgestimate and TRI-MILI kit estradiol) and ethinyl (norgestimate MILI tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, coated film BICALUTAMIDE capsule DUTASTERIDE tablet SPIRONOLACTONE kit estradiol) and ethinyl acetate (norethindrone 24 FE LOMEDIA tablet ESTRADIOL capsule, liquid filled DUTASTERIDE capsule, liquid filled DUTASTERIDE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE BLISOVI 24 FE (norethindrone acetate and ethinyl estradiol) kit estradiol) ethinyl and acetate (norethindrone 24 FE BLISOVI FINASTERIDE tablet, film coated [Repackaged] [Repackaged] tablet, film coated FINASTERIDE TRI-LO-MARZIA ( norgestimate and ethinyl estradiol ) kit kit ) estradiol ethinyl and norgestimate ( TRI-LO-MARZIA NORGESTIMATE AND ETHINYL ESTRADIOL (norgestimate and ethinyl estradiol) kit estradiol) and ethinyl (norgestimate ESTRADIOL ETHINYL AND NORGESTIMATE

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 55289-160-07 55289-160-07 55289-908-42 55289-908-42 60687-105-21 60687-105-21 63629-2613-2 63629-2613-2 63629-2612-2 55289-761-30 55289-761-30 55289-603-21 55289-507-30 57297-837-13 57297-837-13 57237-062-30 57237-061-90 59746-216-05 59746-216-05 59212-111-14 58118-7355-3 62559-150-01 62559-150-01 63629-1830-2 63629-1830-2 63629-1585-2 63187-657-60 63187-634-60 63187-482-60 62112-8068-2 61570-073-01 60760-981-90 60505-3877-9 60505-2642-3 60429-328-01 60429-282-01 60429-272-18 60429-226-30 60429-177-05 59762-5011-2 59762-4537-2 59762-3740-5 63629-3755-2 63629-3755-2 17 17 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only ESTRADIOL tablet [Repackaged] [Repackaged] tablet ESTRADIOL ESTRADIOL tablet [Repackaged] [Repackaged] tablet ESTRADIOL [Repackaged] tablet, coated film SPIRONOLACTONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE FINASTERIDE tablet, film coated tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE FINASTERIDE tablet, film coated [Repackaged] [Repackaged] tablet, film coated FINASTERIDE kit ) estradiol ethinyl and norgestimate ( TRI-LO-MARZIA SPIRONOLACTONE tablet [Repackaged] tablet [Repackaged] SPIRONOLACTONE capsule, liquid filled DUTASTERIDE FINASTERIDE tablet, film coated [Repackaged] [Repackaged] tablet, film coated FINASTERIDE capsule [Repackaged] DUTASTERIDE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet ESTRADIOL tablet METHYLTESTOSTERONE ESTROGENSAND ESTERIFIED coated film tablet, estrogens) (esterified MENEST tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE capsule, liquid filled DUTASTERIDE tablet BICALUTAMIDE [Repackaged] tablet ESTRADIOL [Repackaged] capsule PROGESTERONE capsule FLUTAMIDE [Repackaged] tablet, coated film BICALUTAMIDE [Repackaged] tablet, coated film BICALUTAMIDE tablet, coated film SPIRONOLACTONE injection, suspension ACETATE MEDROXYPROGESTERONE tablet ACETATE MEDROXYPROGESTERONE tablet, coated film (spironolactone) SPIRONOLACTONE MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE ESTRADIOL tablet [Repackaged] [Repackaged] tablet ESTRADIOL NILANDRON (nilutamide) tablet tablet (nilutamide) NILANDRON

Page 51 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 52 of 84 54868-1432-1 54868-1432-1 54868-0109-1 54868-0109-1 54569-0809-2 54868-0365-2 54868-0365-2 54569-0812-5 55154-0533-4 55154-0533-4 55154-0216-4 55154-0216-4 54868-6163-1 54868-6163-1 54868-0699-2 54868-0699-2 54868-4243-0 54868-4243-0 53746-078-01 53746-078-01 53489-328-02 53489-328-02 54569-6048-1 54569-6048-1 54569-4907-2 54569-0505-1 53808-0592-1 53746-511-05 54868-0700-1 54868-0700-1 54868-4120-1 54868-4120-1 54868-4030-1 54868-5114-1 54868-5114-1 54868-4866-0 54868-4813-0 54868-4230-1 54868-4230-1 55154-6242-4 55154-6242-4 55154-5065-0 55111-172-05 55111-171-18 55056-1601-5 55056-0808-6 54868-5934-1 54868-5636-1 53489-144-05 53489-144-05 18 18 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only SPIRONOLACTONE tablet, film coated tablet, coated film SPIRONOLACTONE tablet HYDROCHLOROTHIAZIDE AND SPIRONOLACTONE MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet ESTRADIOL [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE tablet SPIRONOLACTONE tablet METHYLTESTOSTERONE ESTROGENSAND ESTERIFIED PREMARIN (conjugated estrogens) tablet, film coated [Repackaged] [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN SPIRONOLACTONE tablet, film coated [Repackaged] [Repackaged] tablet, coated film SPIRONOLACTONE tablet [Repackaged] HYDROCHLOROTHIAZIDE AND SPIRONOLACTONE ESTRADIOL tablet [Repackaged] [Repackaged] tablet ESTRADIOL tablet, a coated film estrogens, conjugated synthetic - CENESTIN PREMPRO (conjugated estrogens and medroxyprogesterone acetate) tablet, sugar coated coated tablet, sugar acetate) medroxyprogesterone and estrogens PREMPRO(conjugated [Repackaged] [Repackaged] patch ESTRADIOL [Repackaged] release extended estradiol DOT - patch, VIVELLE PROMETRIUM (progesterone) capsule [Repackaged] capsule (progesterone) PROMETRIUM [Repackaged] coated film tablet, (finasteride) PROPECIA SPIRONOLACTONE tablet, film coated [Repackaged] [Repackaged] tablet, coated film SPIRONOLACTONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN tablet FINASTERIDE tablet, film coated FINASTERIDE (progesterone) gel PROCHIEVE gel (progesterone) CRINONE tablet [Repackaged] b) estrogens, conjugated (synthetic ENJUVIA tablet [Repackaged] esterified) (estrogens, MENEST [Repackaged] tablet, film coated FINASTERIDE (Repackaged) liquid filled capsule, (dutasteride) AVODART ESTRADIOL tablet [Repackaged] [Repackaged] tablet ESTRADIOL

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 52544-249-28 52544-249-28 51285-407-02 51285-407-02 50220-002-01 50220-002-01 52544-248-28 52544-248-28 50102-128-03 50102-128-03 49999-109-30 49999-109-30 50458-251-12 50458-251-12 51079-104-20 51079-104-20 50090-0136-1 50090-0136-1 53489-143-05 53489-143-05 52544-087-41 52544-087-41 51991-749-90 51991-623-28 51079-520-20 51079-321-20 51079-103-17 50742-123-90 50458-191-12 50436-9973-3 50436-0446-3 50419-451-04 50268-726-15 50268-323-15 50268-290-15 49884-753-13 47781-205-04 47335-715-13 47335-714-18 47335-485-18 45963-600-09 45963-500-08 43598-390-90 19 19 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only TARINA FE 1/20 (norethindrone acetate and ethinyl estradiol) kit estradiol) and ethinyl acetate 1/20 (norethindrone FE TARINA tablet [Repackaged] SPIRONOLACTONE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN MONONESSA / TRINESSA (norgestimate and ethinyl estradiol) kit estradiol) ethinyl and / TRINESSA (norgestimate MONONESSA MICROGESTIN (norethindrone acetate and ethinyl estradiol) tablet / kit tablet estradiol) and ethinyl acetate (norethindrone MICROGESTIN SPIRONOLACTONE tablet SPIRONOLACTONE MICROGESTIN 24 FE (norethindrone acetate and ethinyl estradiol and ferrous fumarate) kit fumarate) ferrous and estradiol andacetate ethinyl (norethindrone 24 FE MICROGESTIN kit estradiol) ethinyl (norgestimate and LO TRINESSA 52544-167-41 DUTASTERIDE capsule DUTASTERIDE tablet, film acetate) norethindrone and ACETATE (estradiol / NORETHINDRONE ESTRADIOL coated tablet, coated film b) estrogens, conjugated (synthetic ENJUVIA tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet [Repackaged] HYDROCHLOROTHIAZIDE AND SPIRONOLACTONE tablet, film coated FINASTERIDE kit estradiol) ethinyl and (norgestimate CYCLEN LO TRI ORTHO tablet [Repackaged] SPIRONOLACTONE [Repackaged] tablet, film coated FINASTERIDE patch (estradiol) [Repackaged] CLIMARA tablet [Repackaged] (spironolactone) SPIRONOLACTONE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] (estradiol) tablet ESTRADIOL coated film tablet, METHYLTESTOSTERONE ESTROGENSAND ESTERIFIED (estradiol) patch SYSTEM TRANSDERMAL ESTRADIOL tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, coated film BICALUTAMIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE SPIRONOLACTONE tablet, film coated [Repackaged] [Repackaged] tablet, coated film SPIRONOLACTONE kit ethinyl estradiol) and (norgestimate CYCLEN TRI ORTHO capsule FLUTAMIDE

Page 53 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 54 of 84 16714-416-02 16714-416-02 43063-438-07 43063-438-07 33261-534-10 21695-896-20 43353-688-60 43353-688-60 35356-250-00 42291-168-50 42291-168-50 16714-407-02 16714-407-02 21695-613-30 21695-613-30 18860-480-30 17478-767-10 17139-617-40 16729-090-10 16729-089-15 16729-023-10 16714-571-02 16714-408-02 43598-303-90 43598-303-90 43063-446-30 43063-201-30 43063-072-30 42291-691-01 42291-280-90 42023-135-01 42023-111-01 41616-485-18 35356-969-60 35356-419-30 33261-869-30 33261-667-60 31722-526-30 31722-525-05 31722-525-05 23155-014-01 20 20 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only ESTRADIOL tablet [Repackaged] [Repackaged] tablet ESTRADIOL ELESTRIN (estradiol) gel (estradiol) ELESTRIN capsule PROGESTERONE metered (estradiol) gel, ESTROGEL tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet BICALUTAMIDE tablet, coated film BICALUTAMIDE kit fumarate) ferrous estradiol and acetate/ethinyl FE (norethindrone 24 LARIN kit estradiol) acetate/ethinyl (norethindrone 1/20 LARIN kit estradiol) acetate/ethinyl (norethindrone 1.5/30 LARIN ESTRADIOL tablet [Repackaged] [Repackaged] tablet ESTRADIOL [Repackaged] tablet, coated film SPIRONOLACTONE PREMARIN (conjugated estrogens) tablet, film coated [Repackaged] [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] (estradiol) tablet ESTRADIOL tablet [Repackaged] SPIRONOLACTONE capsule PROGESTERONE [Repackaged] coated film tablet, (finasteride) FINASTERIDE [Repackaged] coated film tablet, (bicalutamide) BICALUTAMIDE injection estradiol valerate DELESTROGEN- tablet BICALUTAMIDE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN [Repackaged] tablet ESTRADIOL tablet [Repackaged] ACETATE MEDROXYPROGESTERONE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet ESTRADIOL tablet [Repackaged] ACETATE MEDROXYPROGESTERONE FINASTERIDE tablet [Repackaged] FINASTERIDE ESTRADIOL VALERATE injection injection VALERATE ESTRADIOL

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 0603-7606-15 0603-7606-15 0603-7607-15 0603-7607-15 0603-7609-17 0603-7609-17 0603-7608-17 0603-7608-17 16714-405-02 16714-405-02 0603-7610-17 0603-7610-17 16714-406-02 16714-406-02 15310-020-01 15310-020-01 13925-172-01 13925-172-01 10544-062-10 10544-062-10 0603-7642-17 0603-7642-17 0781-4110-52 0781-4110-52 16714-360-02 16714-360-02 10888-7136-2 10544-523-90 10544-070-30 0904-5952-06 0781-7129-58 0781-5409-10 0781-1599-05 0703-6801-04 0615-8031-30 0615-1535-31 0591-2292-30 0591-2292-30 0591-0487-05 0574-0872-05 0555-0886-04 0555-0779-04 0603-5763-28 0603-5763-28 0603-3633-16 0591-3965-01 16714-363-02 16714-363-02 0591-3771-30 0591-3771-30 10370-280-11 10370-280-11 21 21 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only ESTERIFIED ESTROGENS AND METHYLTESTOSTERONE tablet, film coated coated film tablet, METHYLTESTOSTERONE ESTROGENSAND ESTERIFIED capsule PROGESTERONE fumarate) ferrous and estradiol ethinyl and acetate (norethindrone FE 24 GILDESS kit fumarate) ferrous and ethinyl estradiol acetate, (norethindrone 1/20 FE GILDESS kit fumarate) ferrous and estradiol ethinyl acetate, (norethindrone 1.5/30 FE GILDESS EEMT (estrogens, esterified and methyltestosterone) tablet, coated coated tablet, methyltestosterone) and esterified (estrogens, EEMT tablet [Repackaged] SPIRONOLACTONE [Repackaged] tablet ESTRADIOL tablet [Repackaged] ACETATE MEDROXYPROGESTERONE capsule HYDROCHLORIDE TAMSULOSIN AND DUTASTERIDE tablet SPIRONOLACTONE release extended patch, ESTRADIOL tablet BICALUTAMIDE kit VALERATE/DIENOGEST ESTRADIOL AND VALERATE ESTRADIOL tablet, coated film SPIRONOLACTONE injection, suspension ACETATE MEDROXYPROGESTERONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE kit estradiol) and ethinyl (norgestimate / TRI-PREVIFEM PREVIFEM coated film tablet, estradiol) ethinyl and acetate (norethindrone 1/20 GILDESS GILDESS 1.5/30 (norethindrone acetate and ethinyl estradiol) tablet, film coated coated film tablet, estradiol) and ethinyl acetate (norethindrone 1.5/30 GILDESS DUTASTERIDE capsule DUTASTERIDE tablet ESTRADIOL solution injection, VALERATE ESTRADIOL tablet ESTRADIOL tablet ACETATE MEDROXYPROGESTERONE SPIRONOLACTONE tablet, film coated tablet, coated film SPIRONOLACTONE tablet, film coated FINASTERIDE capsule PROGESTERONE capsule HYDROCHLORIDE TAMSULOSIN AND DUTASTERIDE MONO-LINYAH (norgestimate and ethinyl estradiol) kit estradiol) kit ethinyl (norgestimate and MONO-LINYAH LARIN FE 1/20 (norethindrone acetate/ethinyl estradiol and ferrous fumarate) kit fumarate) ferrous and estradiol acetate/ethinyl (norethindrone 1/20 FE LARIN LARIN FE 1.5/30 (norethindrone acetate/ethinyl estradiol and ferrous fumarate) kit fumarate) ferrous and estradiol acetate/ethinyl (norethindrone 1.5/30 FE LARIN kit estradiol) ethinyl and (norgestimate TRI-LINYAH

Page 55 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 56 of 84 0430-0535-50 0430-0535-50 0430-0570-45 0430-0570-45 0430-0530-60 0430-0530-60 0378-7277-85 0378-7277-85 0430-3754-95 0430-3754-95 0430-0721-24 0173-0809-59 0173-0712-04 0172-4960-60 0169-1842-82 0378-7280-98 0378-7280-98 0430-0539-50 0430-0539-50 0430-0537-50 0430-0420-60 0378-7301-85 0378-7283-98 0378-5036-05 0378-5036-05 0378-4640-26 0378-3349-99 0378-1452-05 0378-0243-05 0310-0705-30 0300-3612-28 0245-0880-66 0245-0880-66 0228-2672-50 0179-1999-30 0179-0074-70 0378-0141-05 0378-0141-05 22 22 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only ESTRACE (estradiol) tablet (estradiol) ESTRACE kit fumarate) ferrous and estradiol and ethinyl acetate (norethindrone FE ESTROSTEP liquid filled capsule, (dutasteride) AVODART capsule FLUTAMIDE coated film tablet, (Estradiol) Innofem ESTRACE (estradiol) cream cream (estradiol) ESTRACE LOESTRIN 24 FE (norethindrone acetate and ethinyl estradiol, and ferrous fumarate) kit ferrous fumarate) and estradiol, and ethinyl acetate (norethindrone 24 FE LOESTRIN and '', and '') kit and '', '') and LO MINASTRIN FE (norethindrone acetate and ethinyl estradiol, ethinyl estradiol and ferrous ferrous and estradiol ethinyl estradiol, ethinyl and acetate (norethindrone MINASTRIN FE LO kit fumarate) kit and ferrousfumarate) estradiol, ethinyl and acetate FE (norethindrone 24 MINASTRIN fumarate) ferrous and estradiol ethinyl estradiol, and ethinyl acetate FE (norethindrone LOESTRIN LO kit estradiol ) kit ) estradiol kit ) estradiol FINASTERIDE tablet, film coated tablet, film coated FINASTERIDE ESTRADIOL patch patch ESTRADIOL patch ESTRADIOL tablet ESTRADIOL tablet, coated film SPIRONOLACTONE tablet HYDROCHLOROTHIAZIDE AND SPIRONOLACTONE tablet (bicalutamide) CASODEX solution injection, acetate) (leuprolide LUPRON gel (estradiol) DIVIGEL gel (estradiol) DIVIGEL tablet, coated film SPIRONOLACTONE [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL capsule and hydrochloride) tamsulosin (dutasteride JALYN NORETHINDRONE ACETATE AND ETHINYL ESTRADIOL AND FERROUS FUMARATE ('', FERROUSAND FUMARATE ESTRADIOL ETHINYL AND ACETATE NORETHINDRONE NORETHINDRONE ACETATE AND ETHINYL ESTRADIOL ( norethindrone acetate and ethinyl ethinyl and acetate norethindrone ( ESTRADIOL ETHINYL AND ACETATE NORETHINDRONE ethinyl and acetate norethindrone ( ESTRADIOL ETHINYL AND ACETATE NORETHINDRONE tablet ESTRADIOL ETHINYL AND ACETATE NORETHINDRONE kit ) estradiol and ethinyl norgestimate ( ESTRADIOL ETHINYL AND NORGESTIMATE

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 0093-5328-62 0093-5328-62 0074-1052-10 0074-1052-10 0115-1438-10 0115-1438-10 0093-7355-56 0093-5655-98 0093-5354-01 0093-3122-42 0093-2140-62 0093-0220-56 0083-2310-62 0083-2310-62 0074-3641-71 0074-3473-03 0074-2282-03 0054-0395-22 0046-1100-81 0046-0872-21 0037-4802-35 0032-1711-01 0025-1031-31 0009-0050-11 0006-0072-58 0006-0071-31 0025-1041-31 45963-600-11 0006-0071-54 0009-0064-04 0046-1100-91 0074-2440-03 0074-3642-03 0083-2320-08 0083-2320-08 23 23 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only JINTELI (norethindrone acetate and ethinyl estradiol) tablet tablet estradiol) ethinyl and acetate (norethindrone JINTELI FINASTERIDE tablet, film coated tablet, film coated FINASTERIDE capsule, liquid filled DUTASTERIDE capsule PROGESTERONE kit fumarate) ferrous and estradiol ethinyl and acetate 24 (norethindrone FE JUNEL kit estradiol) ethinyl and (norgestimate TRI-LO-SPRINTEC tablet, coated film BICALUTAMIDE release extended patch, (estradiol) estraderm [Repackaged] release extended patch, estradiol ESTRADERM- kit acetate) DEPOT (leuprolide LUPRON kit acetate) DEPOT (leuprolide LUPRON kit acetate) DEPOT-PED (leuprolide LUPRON kit acetate) norethindrone and acetate (leuprolide PACK LUPANETA coated kit, sugar tablet, acetate) and medroxyprogesterone estrogens (conjugated PREMPHASE tablet, coated film (estrogens, conjugated) PREMARIN cream estrogens) (conjugated VAGINAL PREMARIN 0046-1105-51 metered gel, 0.06%) gel (estradiol ELESTRIN capsule (progesterone) PROMETRIUM coatedfilm tablet, spironolactone ALDACTONE- tablet acetate) (medroxyprogesterone PROVERA coated film tablet, finasteride PROSCAR- coated film tablet, (finasteride) PROPECIA coatedfilm tablet, spironolactone ALDACTONE- tablet, film coated FINASTERIDE coated film tablet, (finasteride) PROPECIA tablet acetate) (medroxyprogesterone PROVERA tablet, coated film (estrogens, conjugated) PREMARIN coated kit, sugar tablet, acetate) and medroxyprogesterone estrogens (conjugated PREMPHASE kit acetate) DEPOT-PED (leuprolide LUPRON kit acetate) DEPOT (leuprolide LUPRON 0046-1106-11 release extended patch, (estradiol) estraderm [Repackaged] release extended patch, estradiol ESTRADERM- DUTASTERIDE capsule, liquid filled capsule, liquid filled DUTASTERIDE DUTASTERIDE capsule DUTASTERIDE

Page 57 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 58 of 84 0603-7606-48 0603-7606-48 0603-7607-48 0603-7607-48 0430-0535-95 0430-0535-95 0430-0530-95 0430-0530-95 0430-0570-60 0430-0570-60 0603-7610-49 0603-7610-49 0173-0809-61 0173-0809-61 0179-1999-60 0228-2673-11 0245-0880-89 0245-0880-89 0310-0705-39 0378-0437-01 0378-1454-01 0378-3350-16 0378-4641-16 0378-5036-77 0430-0420-95 0430-0537-95 0430-0537-95 0093-3122-98 0093-3122-98 0093-7355-98 0169-1843-81 0172-4960-70 0173-0712-15 0430-0539-95 0430-0539-95 0430-0722-24 0555-0872-02 0555-0887-02 0591-0488-01 0603-3633-21 0603-5763-30 24 24 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only ESTRADIOL tablet [Repackaged] [Repackaged] tablet ESTRADIOL tablet, coated film SPIRONOLACTONE gel (estradiol) DIVIGEL gel (estradiol) DIVIGEL tablet (bicalutamide) CASODEX tablet, coated film SPIRONOLACTONE tablet ESTRADIOL patch ESTRADIOL patch ESTRADIOL tablet, film coated FINASTERIDE fumarate) ferrous and estradiol ethinyl estradiol, and ethinyl acetate FE (norethindrone LOESTRIN LO kit kit ferrous fumarate) and estradiol, and ethinyl acetate (norethindrone 24 FE LOESTRIN MINASTRIN 24 FE (norethindrone acetate and ethinyl estradiol, and ferrous fumarate) kit and ferrousfumarate) estradiol, ethinyl and acetate FE (norethindrone 24 MINASTRIN LO MINASTRIN FE (norethindrone acetate and ethinyl estradiol, ethinyl estradiol and ferrous ferrous and estradiol ethinyl estradiol, ethinyl and acetate (norethindrone MINASTRIN FE LO kit fumarate) FINASTERIDE tablet, film coated tablet, film coated FINASTERIDE coated film tablet, (Estradiol) Innofem capsule FLUTAMIDE liquid filled capsule, (dutasteride) AVODART capsule and hydrochloride) tamsulosin (dutasteride JALYN JINTELI (norethindrone acetate and ethinyl estradiol) tablet tablet estradiol) ethinyl and acetate (norethindrone JINTELI GILDESS 24 FE (norethindrone acetate and ethinyl estradiol and ferrous fumarate) fumarate) ferrous and estradiol ethinyl and acetate (norethindrone FE 24 GILDESS and '', and '') kit and '', '') and ESTROSTEP FE (norethindrone acetate and ethinyl estradiol and ferrous fumarate) kit fumarate) ferrous and estradiol and ethinyl acetate (norethindrone FE ESTROSTEP tablet (estradiol) ESTRACE tablet ACETATE MEDROXYPROGESTERONE tablet ESTRADIOL tablet ESTRADIOL tablet, film coated FINASTERIDE tablet, coated film SPIRONOLACTONE coated film tablet, estradiol) and ethinyl acetate (norethindrone 1.5/30 GILDESS coated film tablet, estradiol) ethinyl and acetate (norethindrone 1/20 GILDESS NORETHINDRONE ACETATE AND ETHINYL ESTRADIOL AND FERROUS FUMARATE ('', FERROUSAND FUMARATE ESTRADIOL ETHINYL AND ACETATE NORETHINDRONE

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 16714-405-03 16714-405-03 16714-406-03 16714-406-03 16714-416-03 16714-416-03 33261-534-14 33261-534-14 21695-896-30 21695-896-30 35356-251-00 35356-251-00 0603-7663-01 0603-7663-01 23155-014-05 23155-014-05 31722-525-10 31722-525-10 31722-526-90 33261-714-60 33261-895-30 35356-969-90 41616-485-83 42023-112-01 42023-136-01 43063-072-90 43063-201-90 16714-407-03 16714-407-03 16714-408-03 16714-571-03 16729-090-15 17139-617-43 18860-480-60 21695-623-00 16714-360-03 16714-360-03 16714-363-03 0615-1535-39 0615-1535-39 0615-8031-39 0781-1599-10 0781-5409-31 0781-7129-83 0904-5953-06 25 25 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only FINASTERIDE tablet, film coated tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] tablet ESTRADIOL [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN [Repackaged] tablet, coated film SPIRONOLACTONE tablet BICALUTAMIDE injection estradiol valerate DELESTROGEN- injection VALERATE ESTRADIOL tablet [Repackaged] SPIRONOLACTONE [Repackaged] (estradiol) tablet ESTRADIOL ESTRADIOL tablet tablet ESTRADIOL LARIN 1/20 (norethindrone acetate/ethinyl estradiol) kit kit estradiol) acetate/ethinyl (norethindrone 1/20 LARIN kit fumarate) ferrous estradiol and acetate/ethinyl FE (norethindrone 24 LARIN tablet, coated film BICALUTAMIDE tablet, film coated FINASTERIDE metered (estradiol) gel, ESTROGEL gel (estradiol) ELESTRIN [Repackaged] tablet ESTRADIOL tablet [Repackaged] ACETATE MEDROXYPROGESTERONE TRI-LINYAH (norgestimate and ethinyl estradiol) kit kit estradiol) ethinyl and (norgestimate TRI-LINYAH kit fumarate) ferrous and estradiol acetate/ethinyl (norethindrone 1.5/30 FE LARIN LARIN FE 1/20 (norethindrone acetate/ethinyl estradiol and ferrous fumarate) kit fumarate) ferrous and estradiol acetate/ethinyl (norethindrone 1/20 FE LARIN LARIN 1.5/30 (norethindrone acetate/ethinyl estradiol) kit estradiol) acetate/ethinyl (norethindrone 1.5/30 LARIN SPIRONOLACTONE tablet, film coated [Repackaged] [Repackaged] tablet, coated film SPIRONOLACTONE tablet, coated film SPIRONOLACTONE tablet BICALUTAMIDE release extended patch, ESTRADIOL tablet SPIRONOLACTONE estradiol) kit ethinyl (norgestimate and MONO-LINYAH PREVIFEM / TRI-PREVIFEM (norgestimate and ethinyl estradiol) kit estradiol) and ethinyl (norgestimate / TRI-PREVIFEM PREVIFEM SPIRONOLACTONE tablet, film coated [Repackaged] [Repackaged] tablet, coated film SPIRONOLACTONE

Page 59 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 60 of 84 52544-276-21 52544-276-21 54868-4879-0 54868-4879-0 51285-408-02 51285-408-02 43063-438-10 43063-438-10 54868-0109-2 54569-3807-1 54569-3807-1 49999-109-90 49999-109-90 54868-0365-3 54569-0813-1 54569-0813-1 50458-251-15 50458-251-15 54868-4244-0 54868-4244-0 51079-103-19 51079-103-19 51079-321-30 51079-520-30 43063-446-90 43063-446-90 45963-500-30 47335-485-83 47335-714-81 47335-715-18 47781-206-04 50090-0136-3 50268-291-11 50419-452-01 50458-191-15 53489-143-10 53489-328-03 53746-511-10 54569-0505-3 54569-6048-2 54868-0700-5 54868-4030-2 54868-4230-2 54868-5009-0 53489-144-10 53489-144-10 26 26 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only SPIRONOLACTONE tablet, film coated [Repackaged] [Repackaged] tablet, coated film SPIRONOLACTONE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, coated film b) estrogens, conjugated (synthetic ENJUVIA SPIRONOLACTONE tablet SPIRONOLACTONE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] patch ESTRADIOL ESTRADIOL tablet [Repackaged] [Repackaged] tablet ESTRADIOL tablet, film coated FINASTERIDE tablet, coated film BICALUTAMIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE (estradiol) patch SYSTEM TRANSDERMAL ESTRADIOL [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN tablet [Repackaged] SPIRONOLACTONE [Repackaged] (estradiol) tablet ESTRADIOL patch (estradiol) [Repackaged] CLIMARA kit ethinyl estradiol) and (norgestimate CYCLEN TRI ORTHO kit estradiol) ethinyl and (norgestimate CYCLEN LO TRI ORTHO / kit tablet estradiol) and ethinyl acetate (norethindrone MICROGESTIN tablet HYDROCHLOROTHIAZIDE AND SPIRONOLACTONE tablet, coated film SPIRONOLACTONE tablet SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet ESTRADIOL [Repackaged] capsule (progesterone) PROMETRIUM [Repackaged] release extended estradiol DOT - patch, VIVELLE tablet, a coated film estrogens, conjugated synthetic - CENESTIN MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 63629-2613-3 63629-2613-3 63629-2612-3 63629-2612-3 55289-160-10 55289-160-10 55154-0533-6 55154-0533-6 55154-0216-6 55154-0216-6 54868-6164-0 54868-6164-0 63629-3755-3 63629-3755-3 59746-216-10 59746-216-10 59762-3741-1 59762-4538-1 59762-5012-1 60429-177-30 60429-328-05 61570-074-01 63187-482-90 63187-634-90 63187-657-90 63629-1585-3 63629-1830-3 54868-5047-0 54868-5047-0 54868-5636-2 54868-6211-0 55056-0818-2 55056-1601-6 55111-171-30 55111-172-30 55154-5517-0 55154-6242-6 55289-507-90 55289-603-30 55289-761-90 57237-062-90 58118-7355-8 27 27 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only ESTRADIOL tablet [Repackaged] [Repackaged] tablet ESTRADIOL MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE MEDROXYPROGESTERONE ACETATE tablet ACETATE MEDROXYPROGESTERONE injection, suspension ACETATE MEDROXYPROGESTERONE tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film BICALUTAMIDE [Repackaged] tablet ESTRADIOL coated film tablet, estrogens) (esterified MENEST [Repackaged] tablet ESTRADIOL [Repackaged] tablet, coated film SPIRONOLACTONE capsule [Repackaged] DUTASTERIDE [Repackaged] tablet, film coated FINASTERIDE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE SPIRONOLACTONE tablet, film coated [Repackaged] [Repackaged] tablet, coated film SPIRONOLACTONE FINASTERIDE tablet, film coated [Repackaged] [Repackaged] tablet, film coated FINASTERIDE tablet [Repackaged] b) estrogens, conjugated (synthetic ENJUVIA tablet [Repackaged] esterified) (estrogens, MENEST gel (progesterone) CRINONE (progesterone) gel PROCHIEVE tablet, film coated FINASTERIDE tablet FINASTERIDE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN [Repackaged] tablet ESTRADIOL tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL tablet, film coated FINASTERIDE [Repackaged] tablet, film coated FINASTERIDE tablet, coated film (spironolactone) SPIRONOLACTONE PREMPRO (conjugated estrogens and medroxyprogesterone acetate) tablet, sugar coated coated tablet, sugar acetate) medroxyprogesterone and estrogens PREMPRO(conjugated [Repackaged] MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE

Page 61 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 62 of 84 68180-827-13 68180-827-13 64205-087-90 64205-087-90 68084-946-25 68084-946-25 68462-657-29 68462-657-29 68382-224-06 68382-224-06 68554-3025-2 68554-3026-2 68788-9124-9 68788-9227-9 68788-9249-9 68788-9416-6 68788-9517-6 68788-9519-9 68788-9729-9 68788-9901-6 69761-006-30 69761-010-30 69761-012-30 69761-015-30 63629-4788-3 63629-4788-3 63629-5208-3 63739-495-43 63739-545-10 64205-488-30 65162-511-09 65841-613-06 65862-149-30 65862-686-99 65862-776-86 65862-777-86 65977-5025-2 68025-065-30 68025-065-30 68084-207-01 28 28 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only FYAVOLV (norethindrone acetate and ethinyl estradiol) tablet, film coated coated film tablet, estradiol) and ethinyl acetate (norethindrone FYAVOLV tablet, coated film BICALUTAMIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet [Repackaged] SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet ESTRADIOL [Repackaged] tablet, film coated FINASTERIDE tablet [Repackaged] FINASTERIDE tablet [Repackaged] SPIRONOLACTONE [Repackaged] tablet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL ESTRADIOL tablet [Repackaged] [Repackaged] tablet ESTRADIOL tablet, film coated FINASTERIDE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] tablet ESTRADIOL tablet SPIRONOLACTONE tablet, coated film BICALUTAMIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE kit estradiol) and ethinyl (norgestimate MILI kit estradiol) ethinyl (norgestimate and TRI-MILI tablet FINASTERIDE gel (estradiol) DIVIGEL gel (estradiol) DIVIGEL [Repackaged] tablet, coated film SPIRONOLACTONE tablet [Repackaged] HYDROCHLOROTHIAZIDE AND SPIRONOLACTONE ESTRADIOL tablet [Repackaged] [Repackaged] tablet ESTRADIOL NORETHINDRONE ACETATE AND ETHINYL ESTRADIOL tablet tablet ESTRADIOL ETHINYL AND ACETATE NORETHINDRONE

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 16714-405-04 16714-405-04 0603-7663-17 0603-7663-17 16714-360-04 16714-360-04 16714-363-04 69761-018-30 69761-018-30 69761-020-30 69761-022-30 69761-025-30 76282-412-30 0009-0064-06 0046-1101-81 0074-3683-03 0074-3779-03 0083-2320-62 0083-2320-62 0169-1843-82 0179-1999-70 0228-2673-50 0245-0881-30 0245-0881-30 0378-1454-05 0378-2146-01 0378-3350-99 0378-4641-26 0378-5036-93 0555-0872-04 0555-0887-04 0591-0488-05 0603-3633-28 0603-5763-32 0615-5592-39 0781-5409-64 0781-7138-40 29 29 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only TRI-LINYAH (norgestimate and ethinyl estradiol) kit kit estradiol) ethinyl and (norgestimate TRI-LINYAH kit fumarate) ferrous and estradiol acetate/ethinyl (norethindrone 1.5/30 FE LARIN SPIRONOLACTONE tablet, film coated [Repackaged] [Repackaged] tablet, coated film SPIRONOLACTONE ESTRADIOL pellet pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL tablet, film coated FINASTERIDE tablet acetate) (medroxyprogesterone PROVERA tablet, coated film (estrogens, conjugated) PREMARIN coated kit, sugar tablet, acetate) and medroxyprogesterone estrogens (conjugated PREMPHASE kit acetate) DEPOT (leuprolide LUPRON kit acetate) DEPOT-PED (leuprolide LUPRON 0046-1106-51 release extended patch, (estradiol) estraderm [Repackaged] release extended patch, estradiol ESTRADERM- coated film tablet, (Estradiol) Innofem [Repackaged] tablet ESTRADIOL tablet, coated film SPIRONOLACTONE gel (estradiol) DIVIGEL gel (estradiol) DIVIGEL tablet ESTRADIOL tablet, coated film SPIRONOLACTONE patch ESTRADIOL patch ESTRADIOL tablet, film coated FINASTERIDE tablet ACETATE MEDROXYPROGESTERONE tablet ESTRADIOL tablet ESTRADIOL tablet, film coated FINASTERIDE tablet, coated film SPIRONOLACTONE kit estradiol) and ethinyl (norgestimate / TRI-PREVIFEM PREVIFEM tablet BICALUTAMIDE release extended patch, ESTRADIOL estradiol) kit ethinyl (norgestimate and MONO-LINYAH ESTRADIOL pellet pellet ESTRADIOL

Page 63 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 64 of 84 52544-290-21 52544-290-21 16714-406-04 16714-406-04 16714-416-04 16714-416-04 51285-409-02 51285-409-02 54868-0109-3 54868-0109-3 33261-534-30 33261-534-30 43063-438-13 54868-0451-2 54868-0451-2 35356-426-30 35356-426-30 50458-251-20 50458-251-20 47335-485-88 47335-485-88 47335-714-83 47335-715-81 47781-207-04 50090-0136-6 50268-291-15 50419-452-04 50458-191-20 51079-103-20 51079-321-56 51079-520-56 53489-328-05 53489-328-05 53746-511-30 54569-0505-5 54868-0700-6 54868-4031-0 16714-407-04 16714-407-04 16714-408-04 16729-090-16 21695-623-30 23155-015-01 31722-525-30 31722-525-30 41616-485-88 30 30 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only PREMARIN (conjugated estrogens) tablet, film coated [Repackaged] [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN FINASTERIDE tablet, film coated tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE (estradiol) patch SYSTEM TRANSDERMAL ESTRADIOL tablet [Repackaged] SPIRONOLACTONE [Repackaged] (estradiol) tablet ESTRADIOL patch (estradiol) [Repackaged] CLIMARA kit ethinyl estradiol) and (norgestimate CYCLEN TRI ORTHO kit estradiol) ethinyl and (norgestimate CYCLEN LO TRI ORTHO tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, coated film b) estrogens, conjugated (synthetic ENJUVIA / kit tablet estradiol) and ethinyl acetate (norethindrone MICROGESTIN BICALUTAMIDE tablet, film coated tablet, coated film BICALUTAMIDE [Repackaged] tablet, coated film SPIRONOLACTONE SPIRONOLACTONE tablet SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] tablet ESTRADIOL SPIRONOLACTONE tablet, film coated tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE LARIN 1/20 (norethindrone acetate/ethinyl estradiol) kit kit estradiol) acetate/ethinyl (norethindrone 1/20 LARIN kit fumarate) ferrous estradiol and acetate/ethinyl FE (norethindrone 24 LARIN tablet, film coated FINASTERIDE [Repackaged] tablet ESTRADIOL tablet ESTRADIOL tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN tablet BICALUTAMIDE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE LARIN FE 1/20 (norethindrone acetate/ethinyl estradiol and ferrous fumarate) kit fumarate) ferrous and estradiol acetate/ethinyl (norethindrone 1/20 FE LARIN LARIN 1.5/30 (norethindrone acetate/ethinyl estradiol) kit estradiol) acetate/ethinyl (norethindrone 1.5/30 LARIN

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 54868-4879-1 54868-4879-1 63629-2612-4 63629-2612-4 63629-2613-4 55289-160-13 55289-160-13 55154-0217-0 55154-0217-0 54868-6164-1 54868-6164-1 54868-4862-0 54868-4862-0 59746-217-01 59746-217-01 59762-3741-4 59762-4538-2 59762-5013-1 60429-329-01 61570-075-50 63629-1585-4 63629-1830-4 63629-3755-4 63629-4788-4 63629-5208-4 64205-488-90 65162-511-10 65841-613-10 65862-149-90 65862-776-87 65862-777-87 65862-927-30 54868-4250-0 54868-4250-0 54868-5540-0 55289-603-90 54868-6211-1 54868-6211-1 55056-0818-5 55056-1601-8 55111-171-90 55111-172-78 31 31 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only MEDROXYPROGESTERONE ACETATE tablet ACETATE MEDROXYPROGESTERONE injection, suspension ACETATE MEDROXYPROGESTERONE tablet, coated film SPIRONOLACTONE [Repackaged] tablet ESTRADIOL coated film tablet, estrogens) (esterified MENEST [Repackaged] tablet, film coated FINASTERIDE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL [Repackaged] tablet ESTRADIOL tablet SPIRONOLACTONE tablet, coated film BICALUTAMIDE tablet, film coated FINASTERIDE kit estradiol) and ethinyl (norgestimate MILI kit estradiol) ethinyl (norgestimate and TRI-MILI tablet, film coated FINASTERIDE PREMPRO (conjugated estrogens and medroxyprogesterone acetate) tablet, sugar coated coated tablet, sugar acetate) medroxyprogesterone and estrogens PREMPRO(conjugated [Repackaged] [Repackaged] tablet ESTRADIOL VIVELLE DOT - estradiol patch, extended release [Repackaged] [Repackaged] release extended estradiol DOT - patch, VIVELLE tablet, a coated film estrogens, conjugated synthetic - CENESTIN tablet [Repackaged] b) estrogens, conjugated (synthetic ENJUVIA tablet, coated film (spironolactone) SPIRONOLACTONE PROMETRIUM (progesterone) capsule [Repackaged] capsule (progesterone) PROMETRIUM MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE CRINONE (progesterone) gel gel (progesterone) CRINONE (progesterone) gel PROCHIEVE tablet, film coated FINASTERIDE tablet FINASTERIDE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN MENEST (estrogens, esterified) tablet [Repackaged] esterified) (estrogens, MENEST

Page 65 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 66 of 84 68180-828-09 68180-828-09 68084-946-95 68084-946-95 68462-657-90 68462-657-90 65977-5025-3 65977-5025-3 68025-066-01 68025-066-01 68084-207-11 68382-224-10 68554-3025-3 68788-9416-9 68788-9517-9 68788-9901-9 76282-412-90 0009-0286-03 0046-1102-51 0074-9694-03 0169-1844-81 0179-1999-88 0228-2803-11 0245-0881-66 0245-0881-66 0378-1458-01 0378-2146-05 0378-3351-16 0378-4642-16 0555-0873-02 0555-0899-02 0591-0528-01 0603-5764-21 0615-6591-39 0781-7138-58 16729-090-17 31722-525-90 32 32 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only DIVIGEL (estradiol) gel gel (estradiol) DIVIGEL gel (estradiol) DIVIGEL [Repackaged] tablet, coated film SPIRONOLACTONE tablet [Repackaged] HYDROCHLOROTHIAZIDE AND SPIRONOLACTONE tablet, coated film BICALUTAMIDE tablet, film coated FINASTERIDE [Repackaged] tablet ESTRADIOL [Repackaged] tablet, film coated FINASTERIDE [Repackaged] tablet ESTRADIOL tablet, film coated FINASTERIDE tablet acetate) (medroxyprogesterone PROVERA tablet, coated film (estrogens, conjugated) PREMARIN coated kit, sugar tablet, acetate) and medroxyprogesterone estrogens (conjugated PREMPHASE kit acetate) DEPOT-PED (leuprolide LUPRON coated film tablet, (Estradiol) Innofem 0046-1107-11 [Repackaged] tablet ESTRADIOL tablet, coated film SPIRONOLACTONE gel (estradiol) DIVIGEL gel (estradiol) DIVIGEL tablet ESTRADIOL tablet, coated film SPIRONOLACTONE patch ESTRADIOL patch ESTRADIOL tablet ACETATE MEDROXYPROGESTERONE tablet ESTRADIOL tablet ESTRADIOL tablet, coated film SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE release extended patch, ESTRADIOL tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE FINASTERIDE tablet FINASTERIDE FYAVOLV (norethindrone acetate and ethinyl estradiol) tablet, film coated coated film tablet, estradiol) and ethinyl acetate (norethindrone FYAVOLV NORETHINDRONE ACETATE AND ETHINYL ESTRADIOL tablet tablet ESTRADIOL ETHINYL AND ACETATE NORETHINDRONE

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 54868-4879-2 54868-4879-2 51285-410-02 51285-410-02 63629-2612-5 63629-2612-5 33261-609-30 33261-609-30 43063-438-30 55289-160-30 54868-0109-5 54868-0109-5 54868-0451-6 54868-0451-6 55154-0217-4 55154-0217-4 54868-6165-0 54868-6165-0 54868-4920-0 54868-4920-0 65162-511-11 65162-511-11 59746-217-05 59746-217-05 59762-3742-2 59762-4538-9 60429-329-05 63629-1830-5 47335-714-88 47335-714-88 47335-715-83 47781-208-04 50268-292-11 50419-453-01 50458-197-00 51079-103-63 54868-4031-1 54868-4250-1 54868-4477-0 31722-525-90 31722-525-90 54868-6212-0 55056-0818-9 55111-172-79 53489-328-06 53489-328-06 53746-511-60 54569-0505-6 33 33 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only SPIRONOLACTONE tablet SPIRONOLACTONE MEDROXYPROGESTERONE ACETATE tablet ACETATE MEDROXYPROGESTERONE injection, suspension ACETATE MEDROXYPROGESTERONE [Repackaged] tablet ESTRADIOL tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE FINASTERIDE tablet, film coated tablet, film coated FINASTERIDE [Repackaged] release extended estradiol DOT - patch, VIVELLE FINASTERIDE tablet, film coated tablet, film coated FINASTERIDE (estradiol) patch SYSTEM TRANSDERMAL ESTRADIOL [Repackaged] (estradiol) tablet ESTRADIOL patch (estradiol) [Repackaged] CLIMARA kit ethinyl estradiol) and (norgestimate CYCLEN TRI ORTHO [Repackaged] tablet, coated film SPIRONOLACTONE tablet, coated film b) estrogens, conjugated (synthetic ENJUVIA [Repackaged] tablet ESTRADIOL [Repackaged] capsule (progesterone) PROMETRIUM [Repackaged] tablet, coated film SPIRONOLACTONE tablet, a coated film estrogens, conjugated synthetic - CENESTIN PREMARIN (conjugated estrogens) tablet, film coated [Repackaged] [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN MENEST (estrogens, esterified) tablet [Repackaged] esterified) (estrogens, MENEST tablet [Repackaged] ACETATE MEDROXYPROGESTERONE MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE tablet [Repackaged] b) estrogens, conjugated (synthetic ENJUVIA gel (progesterone) CRINONE tablet FINASTERIDE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN tablet, coated film (spironolactone) SPIRONOLACTONE FINASTERIDE tablet, film coated tablet, film coated FINASTERIDE SPIRONOLACTONE tablet, film coated tablet, coated film SPIRONOLACTONE tablet SPIRONOLACTONE [Repackaged] tablet, coated film SPIRONOLACTONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE

Page 67 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 68 of 84 68180-828-11 68180-828-11 43063-438-40 43063-438-40 33261-740-20 33261-740-20 47335-715-88 47335-715-88 47781-209-04 50268-292-15 50419-453-04 50458-197-12 51079-979-01 65841-613-30 65841-613-30 65862-776-88 65862-777-88 65862-927-90 65977-5025-4 68025-066-07 68025-066-07 68084-208-01 68382-224-30 68554-3025-4 65162-511-50 0046-1102-81 0169-1844-82 0179-1999-90 0228-2803-50 0245-0881-89 0245-0881-89 0378-1458-05 0378-3351-99 0378-4642-26 0555-0873-04 0591-0528-05 0603-5764-28 0781-7138-83 34 34 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE FINASTERIDE tablet, film coated tablet, film coated FINASTERIDE (estradiol) patch SYSTEM TRANSDERMAL ESTRADIOL [Repackaged] (estradiol) tablet ESTRADIOL patch (estradiol) [Repackaged] CLIMARA kit ethinyl estradiol) and (norgestimate CYCLEN TRI ORTHO [Repackaged] tablet, coated film SPIRONOLACTONE MILI (norgestimate and ethinyl estradiol) kit estradiol) and ethinyl (norgestimate MILI kit estradiol) ethinyl (norgestimate and TRI-MILI tablet, film coated FINASTERIDE tablet FINASTERIDE gel (estradiol) DIVIGEL gel (estradiol) DIVIGEL [Repackaged] tablet, coated film SPIRONOLACTONE coated film tablet, estradiol) and ethinyl acetate (norethindrone FYAVOLV tablet, coated film BICALUTAMIDE tablet, film coated FINASTERIDE tablet SPIRONOLACTONE tablet, coated film (estrogens, conjugated) PREMARIN coated kit, sugar tablet, acetate) and medroxyprogesterone estrogens (conjugated PREMPHASE coated film tablet, (Estradiol) Innofem [Repackaged] tablet ESTRADIOL 0046-1108-11 tablet, coated film SPIRONOLACTONE gel (estradiol) DIVIGEL gel (estradiol) DIVIGEL tablet ESTRADIOL patch ESTRADIOL patch ESTRADIOL tablet ACETATE MEDROXYPROGESTERONE tablet ESTRADIOL tablet, coated film SPIRONOLACTONE release extended patch, ESTRADIOL tablet [Repackaged] ACETATE MEDROXYPROGESTERONE BICALUTAMIDE tablet, film coated tablet, coated film BICALUTAMIDE

Page 69 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 70 of 84 54868-5415-1 54868-5415-1 43063-438-50 43063-438-50 33261-740-30 33261-740-30 54868-0109-8 54868-0109-7 54868-0109-7 55289-160-42 54868-0453-4 54868-0453-4 55154-0219-8 55154-0219-8 55154-0218-8 55154-0218-8 54868-0453-2 54868-0453-2 59746-218-05 59746-218-05 65162-511-60 68025-067-01 68025-067-01 0046-1103-81 0245-0882-66 0245-0882-66 0378-3352-99 0378-4643-26 0781-7144-58 50419-454-04 50458-197-20 51079-980-01 53489-329-01 53746-514-05 54868-4370-0 54868-5015-0 50419-454-01 50419-454-01 50458-197-15 51079-979-20 53489-328-10 53746-514-01 54868-4031-3 54868-4477-2 36 36 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only PREMARIN (conjugated estrogens) tablet, film coated [Repackaged] [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN SPIRONOLACTONE tablet SPIRONOLACTONE gel (estradiol) DIVIGEL gel (estradiol) DIVIGEL tablet, coated film (estrogens, conjugated) PREMARIN gel (estradiol) DIVIGEL gel (estradiol) DIVIGEL patch ESTRADIOL patch ESTRADIOL release extended patch, ESTRADIOL tablet [Repackaged] ACETATE MEDROXYPROGESTERONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE patch (estradiol) [Repackaged] CLIMARA kit ethinyl estradiol) and (norgestimate CYCLEN TRI ORTHO [Repackaged] tablet, coated film SPIRONOLACTONE tablet, coated film SPIRONOLACTONE tablet SPIRONOLACTONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] tablet, coated film SPIRONOLACTONE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN ESTRADIOL tablet [Repackaged] [Repackaged] tablet ESTRADIOL PREMARIN (conjugated estrogens) tablet, film coated [Repackaged] [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN SPIRONOLACTONE (spironolactone) tablet, film coated tablet, coated film (spironolactone) SPIRONOLACTONE MEDROXYPROGESTERONE ACETATE tablet [Repackaged] tablet [Repackaged] ACETATE MEDROXYPROGESTERONE ORTHO TRI CYCLEN (norgestimate and ethinyl estradiol) kit ethinyl estradiol) and (norgestimate CYCLEN TRI ORTHO [Repackaged] tablet, coated film SPIRONOLACTONE tablet, coated film SPIRONOLACTONE tablet SPIRONOLACTONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN [Repackaged] tablet ESTRADIOL [Repackaged] tablet, coated film SPIRONOLACTONE tablet, a coated film estrogens, conjugated synthetic - CENESTIN CLIMARA (estradiol) patch [Repackaged] patch (estradiol) [Repackaged] CLIMARA

Page 71 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 72 of 84 54868-2985-2 54868-2985-2 54868-2984-3 54868-2984-3 54868-2985-0 54868-2985-1 54868-2985-3 54868-4865-1 54868-4865-1 54868-2702-0 54868-2702-0 54868-2702-1 54868-4865-0 54868-4865-0 65162-514-50 65162-514-50 0781-7167-58 53489-329-10 53746-515-05 0046-1104-91 0046-1104-91 0378-3361-16 0781-7156-58 50419-459-01 53489-329-05 53746-514-60 54868-5015-3 65162-514-10 0378-3361-99 0781-7156-83 50419-459-04 53489-329-06 53746-514-90 54868-5015-4 65162-514-11 0781-7167-40 53489-329-07 53746-515-01 65162-514-60 0781-7167-83 53746-515-10 38 38 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only PREMARIN (conjugated estrogens) tablet, film coated [Repackaged] [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN tablet SPIRONOLACTONE ESTRADIOL patch, extended release release extended patch, ESTRADIOL tablet, coated film SPIRONOLACTONE tablet SPIRONOLACTONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN ESTRADIOL patch patch ESTRADIOL release extended patch, ESTRADIOL patch (estradiol) [Repackaged] CLIMARA tablet, coated film SPIRONOLACTONE tablet SPIRONOLACTONE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] tablet, coated film SPIRONOLACTONE tablet SPIRONOLACTONE patch ESTRADIOL release extended patch, ESTRADIOL patch (estradiol) [Repackaged] CLIMARA tablet, coated film SPIRONOLACTONE tablet SPIRONOLACTONE [Repackaged] coated film tablet, (conjugatedestrogens) PREMARIN tablet [Repackaged] ACETATE MEDROXYPROGESTERONE [Repackaged] tablet, coated film SPIRONOLACTONE tablet SPIRONOLACTONE release extended patch, ESTRADIOL tablet, coated film SPIRONOLACTONE tablet SPIRONOLACTONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE release extended patch, ESTRADIOL tablet SPIRONOLACTONE tablet [Repackaged] ACETATE MEDROXYPROGESTERONE PREMARIN (estrogens, conjugated) tablet, film coated tablet, coated film (estrogens, conjugated) PREMARIN SPIRONOLACTONE tablet SPIRONOLACTONE

Page 73 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 74 of 84

50090-0875-0 50090-0875-0 54569-5595-0 35356-758-30 35356-758-30 54868-4989-0 16590-853-30 50090-1306-0 50090-1306-0 54569-6337-0 54569-6337-0 54569-5339-0 54868-4792-0 21695-112-30 54868-6406-0 54868-6406-0 0187-0902-01 0187-0902-01 67979-501-40 67979-501-40 NDC Code NDC 54569-5301-0 54569-5301-0 54569-1411-0 50090-0746-0 54868-0216-0 52244-030-60 55056-3060-1 66887-001-05 52544-076-60 52544-076-60 0051-8462-01 0051-8425-01 49884-418-48 0002-1975-61 40 40 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only Label DELATESTRYL- testosterone enanthate injection, solution injection, solution enanthate testosterone DELATESTRYL- solution cypionate) injection, (testosterone DEPO-TESTOSTERONE solution cypionate) injection, (testosterone DEPO-TESTOSTERONE solution cypionate) injection, (testosterone DEPO-TESTOSTERONE solution cypionate) injection, (testosterone DEPO-TESTOSTERONE 0009-0085-10 [Repackaged] 0009-0347-02 solution cypionate) injection, (testosterone DEPO-TESTOSTERONE 0009-0520-01 [Repackaged] solution cypionate) injection, (testosterone DEPO-TESTOSTERONE [Repackaged] solution cypionate) injection, (testosterone DEPO-TESTOSTERONE [Repackaged] tablet (testosterone) STRIANT tablet (testosterone) STRIANT gel (testosterone) TESTIM [Repackaged] gel (testosterone) TESTIM [Repackaged] gel (testosterone) TESTIM ANDRODERM - testosterone patch testosterone - ANDRODERM ANDROGEL (testosterone) gel (testosterone) gel ANDROGEL (testosterone) gel ANDROGEL (testosterone) gel ANDROGEL [Repackaged] (testosterone) gel ANDROGEL [Repackaged] (testosterone) gel ANDROGEL [Repackaged] (testosterone) gel ANDROGEL [Repackaged] (testosterone) gel ANDROGEL [Repackaged] (testosterone) gel ANDROGEL solution (testosterone) AXIRON solution [Repackaged] (testosterone) AXIRON [Repackaged] gel (testosterone) TESTIM [Repackaged] gel (testosterone) TESTIM [Repackaged] gel (testosterone) TESTIM ANDROID - methyltestosterone capsule methyltestosterone - ANDROID

Supplemental Table 2: NDC codes for medications used for TM gender affirmation affirmation gender forTM used for codes medications Table2: NDC Supplemental 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 54569-5339-1 54569-5339-1 54868-4810-0 54868-5814-0 0002-1975-90 0002-1975-90 0051-8425-30 0051-8462-12 49884-418-72 52544-077-30 54868-0216-1 0051-8450-01 0051-8462-30 49884-510-63 0051-8450-30 0051-8462-31 49884-510-72 0051-8488-33 0051-8462-33 0051-8488-88 41 41 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only

DEPO-TESTOSTERONE (testosterone cypionate) injection, solution cypionate) injection, (testosterone DEPO-TESTOSTERONE solution cypionate) injection, (testosterone DEPO-TESTOSTERONE solution cypionate) injection, (testosterone DEPO-TESTOSTERONE (testosterone) gel ANDROGEL 0009-0086-01 (testosterone) gel ANDROGEL 0009-0417-01 (testosterone) gel ANDROGEL 0009-0520-10 patch testosterone - ANDRODERM [Repackaged] (testosterone) gel ANDROGEL solution cypionate) injection, (testosterone DEPO-TESTOSTERONE [Repackaged] [Repackaged] (testosterone) gel ANDROGEL solution cypionate) injection, (testosterone DEPO-TESTOSTERONE solution cypionate) injection, (testosterone DEPO-TESTOSTERONE (testosterone) gel ANDROGEL (testosterone) gel ANDROGEL 0009-0086-10 (testosterone) gel ANDROGEL 0009-0417-02 [Repackaged] (testosterone) gel ANDROGEL (testosterone) gel ANDROGEL (testosterone) gel ANDROGEL (testosterone) gel ANDROGEL (testosterone) gel ANDROGEL (testosterone) gel ANDROGEL (testosterone) gel ANDROGEL AXIRON (testosterone) solution (testosterone) AXIRON

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Code 54520 54522 54535 55970 19324 19325 17380 54125 56800 56805 57291 57292 57295 57296 57426 57335 57291 57292 56805 58999 31899 54690 54530

42 42 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only Procedure name Procedure Orchiectomy, simple (including subcapsular), with or without testicular prosthesis, scrotal or inguinal approach inguinal approach or prosthesis, scrotal testicular with without or subcapsular), (including simple Orchiectomy, partial Orchiectomy, orchiectomy) routine that for may use some but evidence only, for tumor testis(supposedly of Removal (same) exploration with testis, of Removal to male female surgery; Intersex implant prosthetic without augmentation; Mammaplasty, implant prosthetic with augmentation; Mammaplasty, minutes 30 each epilation, Electrolysis laser) by removal permanent hair as (when tissue specified subcutaneous and membrane mucous skin, procedure, Unlisted Penis;complete of Amputation introitus of repair Plastic state intersex for Clitoroplasty 17999 graft without vagina; artificial of Construction graft with vagina; artificial of Construction approach vaginal vaginal graft; prosthetic of removal) (including Revision abdominal approach open vaginal graft; prosthetic of removal) (including Revision approach laparoscopic vaginal graft, prosthetic of removal) (including Revision Vaginoplasty Colovaginoplasty Colovaginoplasty Clitoroplasty Labiaplasty chondroplasty thyroid shave/reduction Trachea Laparoscopy, orchiectomy Laparoscopy,

Supplemental Table 3: CPT codes reflecting procedures for TF gender affirmation for TF procedures codes reflecting Table3: CPT Supplemental 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from

Code 58152 58291 58661 58275 58280 58150 58180 58720 58920 58940 55980 19303 19304 58260 58262 58263 58267 58270 58285 58290 58293 58294 54660 56625 57110 55180

43 43 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only Procedure Procedure Salpingo-oophorectomy, complete or partial, unilateral or bilateral or partial,unilateral or complete Salpingo-oophorectomy, bilateral or unilateral ovary, of bisection or (partial) resection Wedge bilateral or partial or unilateral total, Oophorectomy, female tomale surgery; Intersex complete simple, Mastectomy, subcutaneous Mastectomy, ovary(s) of or with removal without tube(s), of removal without or with hysterectomy, abdominal Total Burch) Marshall-Machetti-Krantz, (e.g., colpo-urethrocystopexy with hysterectomy: abdominal Total ovary(s) or tube(s), of without or with removal hysterectomy), (subtotal abdominal hysterectomy Supracervical less; or 250 grams foruterus hysterectomy, Vaginal ovary(s) and/or tube(s), of removal with hysterectomy Vaginal enterocele of repair with ovary(s), and/or tube(s), of removal with hysterectomy Vaginal control) endoscopic without (with or withhysterectomy colpo-urethrocystopexy Vaginal of enterocele repair with hysterectomy Vaginal vaginectomy; withpartial or hysterectomy, total Vaginal enterocele of repair with vaginectomy; withpartial or hysterectomy, total Vaginal operation) type (Schauta radical hysterectomy, Vaginal 250 than grams; foruterus greater hysterectomy, Vaginal ovary(s) and/or tube(s) of removal with 250 than grams; foruterus greater hysterectomy, Vaginal of enterocele repair ovary(s), with and/or tube(s) of removal 250 than grams;with foruterus greater hysterectomy, Vaginal colpo-urethrocystopex with 250 than grams; foruterus greater hysterectomy, Vaginal of enterocele repair 250 than grams;with foruterus greater hysterectomy, Vaginal 58292 Prosthesis Testicular of Insertion complete simple; Vulvectomy, wall vaginal of removal complete Vaginectomy, complicated Scrotoplasty; Laparoscopy, surgical with removal of adnexal structures (partial or total oophorectomy and/or salpingectomy salpingectomy and/or oophorectomy total or (partial adnexal structures of with surgical removal Laparoscopy,

Supplemental Table 4: CPT codes reflecting procedures for TM genderaffirmation forTM procedures codes reflecting Table4: CPT Supplemental Page 77 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 78 of 84

Z90.79 Z87.890 0H0V0JZ 0VT94ZZ 0VT94ZZ 0VT50ZZ 0VT54ZZ 0H0V07Z 0VT90ZZ 0VTS4ZZ 0VTS4ZZ 0VTS0ZZ 0VTS0ZZ 0H0V0ZZ 0VTB0ZZ 0VTB4ZZ 0VTC0ZZ 0VTC4ZZ 0H0V0KZ 0VT5XZZ 0VTSXZZ ICD 10 Codes 10 ICD

85.5 64.3 62.3 62.41 62.42 85.51 85.52 85.53 85.54 85.55 70.61

ICD 9 Codes 9 ICD 44 44 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only Name of Procedure Name Removal of both testes at same operative episode episode operative at testes same both of Removal testis remaining of Removal organ other genital of absence Acquired Approach Testis, Open Right of Resection Endoscopic Approach Testis, Percutaneous Right of Resection Approach Testis, Open of Left Resection Approach Endoscopic Testis, Percutaneous of Left Resection Approach Open Testes, Bilateral of Resection Approach Endoscopic Percutaneous Testes, Bilateral of Resection of sex reassignment history Personal specified otherwise not mammoplasty, Augmentation for augmentation intobreast injection Unilateral augmentation for intobreast injection Bilateral implant breast Unilateral implant breast Bilateral toBreast Graft Fat Approach Open Scrotum, of Resection Approach Endoscopic Percutaneous Scrotum, of Resection External Approach Scrotum, of Resection Approach Open Penis, of Resection Approach Endoscopic Percutaneous Penis, of Resection Approach External Penis, of Resection construction Vaginal Penis of Amputation Approach Tissue Substitute, Open Autologous with Bilateral Breast of Alteration Approach Open Substitute, Synthetic with Bilateral Breast of Alteration Approach Substitute, Open Tissue Nonautologous with Bilateral Breast of Alteration Approach Open Bilateral Breast, of Alteration Unilateral orchiectomy Unilateral

Supplemental Table 5: ICD-9 and ICD-10 codes reflecting procedures for TF gender affirmation gender forTF procedures codes reflecting and ICD-10 Table5: ICD-9 Supplemental 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from

0H0V3JZ 0H0V37Z 0UQJ0ZZ 0H0V3ZZ 0H0VXJZ 0W4M0J0 0H0VX7Z 0H0V3KZ 0UQJXZZ 0W4M070 0H0VXZZ 0UQG0ZZ 0HDSXZZ 0W4M0Z0 0H0VXKZ 0W4M0K0

64.5 85.59 85.95 85.96 45 45 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only Alteration of Bilateral Breast with Autologous Tissue Substitute, Percutaneous Approach Approach Tissue Substitute, Percutaneous Autologous with Bilateral Breast of Alteration Alteration of Bilateral Breast with Synthetic Substitute,Percutaneous Approach Approach Substitute,Percutaneous Synthetic with Bilateral Breast of Alteration Approach Substitute, Percutaneous Tissue Nonautologous with Bilateral Breast of Alteration Approach Percutaneous Bilateral Breast, of Alteration Approach Tissue Substitute, External Autologous with Bilateral Breast of Alteration Approach External Substitute, Synthetic with Bilateral Breast of Alteration Approach Substitute, External Tissue Nonautologous with Bilateral Breast of Alteration Approach External Bilateral Breast, of Alteration approach external hair, of Extraction open approach vagina, Repair Approach Clitoris, Open Repair Approach Clitoris, External Repair approach open substitute, tissue autologous with inmale perineum vagina of Creation approach open substitute, synthetic with inmale perineum vagina of Creation approach open substitute, tissue nonautologous with inmale perineum vagina of Creation open approach inmale perineum, vagina of Creation penis) (on classified elsewhere not sex for transformation, Operations mammoplasty Other expander tissue breast of Insertion tissue expander breast of Removal

Page 79 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 80 of 84

Z90.79 Z90.72 Z90.721 Z90.722 0UT07ZZ 0UT08ZZ 0UT17ZZ 0UT18ZZ 0UT24ZZ 0UT00ZZ 0UT04ZZ 0UT10ZZ 0UT14ZZ 0UT20ZZ 0UT1FZZ 0UT0FZZ ICD 10 Codes 10 ICD

65.63 65.61 65.53 65.09 65.31 65.39 65.41 65.49 65.52 65.54 65.62 65.64 65.01 65.51

ICD 9 Codes 9 ICD 46 46 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only

Other oophorotomy Other oophorectomy unilateral Laparoscopic oophorectomy unilateral Other salpingo-oophorectomy unilateral Laparoscopic salpingo-oophorectomy unilateral Other operative episode same at ovaries both of removal Other ovary remaining of removal Other episode operative same at of removal ovaries both Laparoscopic ovary of removal remaining Laparoscopic episode operative tubes same at and ovaries both of removal Other tube and ovary remaining of removal Other episode operative at tubes same and of removal ovaries both Laparoscopic ovary tube and of removal remaining Laparoscopic organ other genital of absence Acquired ovaries of absence Acquired unilateral ovaries, of absence Acquired bilateral ovaries, of absence Acquired Approach Open Ovary, Right of Resection Endoscopic Approach Percutaneous Ovary, Right of Resection orOpening Artificial Via Natural Ovary, Right of Resection Endoscopic orOpening Artificial Via Natural Ovary, Right of Resection Assistance With Percutaneous orOpening Artificial Via Natural Ovary, Right of Resection Approach Ovary, Open of Left Resection Approach Endoscopic Ovary, Percutaneous of Left Resection Opening or Artificial Natural Ovary, Via of Left Resection Endoscopic Opening or Artificial Natural Ovary, Via of Left Resection With Assistance Percutaneous Opening or Artificial Natural Ovary, Via of Left Resection Approach Open Ovaries, Bilateral of Resection Approach Endoscopic Percutaneous Ovaries, Bilateral of Resection Laparoscopic oophorotomy Laparoscopic Supplemental Table 6: ICD-9 and ICD-10 codes reflecting procedures for TM gender affirmation gender forTM procedures codes reflecting and ICD-10 Table6: ICD-9 Supplemental Name of Procedure Name 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from

Z87.890 0UT27ZZ 0UT28ZZ 0UT2FZZ 0HTT0ZZ 0HTU0ZZ 0HTU0ZZ 0HTV0ZZ 0UTG0ZZ 0UTG4ZZ 0UTG7ZZ 0UTG8ZZ 0HBV0ZZ 0HBV0ZZ 0HBV3ZZ 0HBV7ZZ

85.2 70.4 85.23 85.31 85.32 85.34 85.36 85.41 85.42 85.43 85.44 85.45 85.46 85.47 85.48 64.43 64.95 64.97 47 47 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only Resection of Bilateral Ovaries, Via Natural or Artificial Opening Opening or Natural Artificial Via Ovaries, Bilateral of Resection Resection of Bilateral Ovaries, Via Natural or Artificial Opening With Percutaneous Assistance Assistance Percutaneous With Opening Endoscopic Opening or Natural Artificial Via Ovaries, Bilateral of Resection Artificial or Natural Via Ovaries, Bilateral of Resection of sex reassignment history Personal specified otherwise not tissue, breast of destruction Excisionor mastectomy Subtotal mammoplasty reduction Unilateral mammoplasty reduction Bilateral mammectomy subcutaneous unilateral Other mammectomy subcutaneous bilateral Other mastectomy simple Unilateral mastectomy simple Bilateral mastectomy simple extended Unilateral mastectomy simple extended Bilateral mastectomy radical Unilateral mastectomy radical Bilateral radical mastectomy extended Unilateral radical mastectomy extended Bilateral Approach Right Open Breast, of Resection Approach Open Breast, of Left Resection Approach Open Bilateral Breast, of Resection Approach Open Vagina, of Resection Approach Endoscopic Percutaneous Vagina, of Resection Opening Artificial or ViaNatural Vagina, of Resection Endoscopic Opening Artificial or ViaNatural Vagina, of Resection vagina excision of total and Obliteration penis of Construction penile prosthesis non-inflatable of replacement or Insertion prosthesis penile inflatable of replacement or Insertion Approach Open Breast, Bilateral Excisionof Approach Percutaneous Breast, Bilateral Excisionof Opening Artificial or Natural Via Breast, Bilateral Excisionof Page 81 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 82 of 84

0UTJ0ZZ 0UT78ZZ 0UT74ZZ 0UT77ZZ 0W4N0J1 0UT70ZZ 0UT90ZZ 0UT94ZZ 0UT97ZZ 0UT98ZZ 0UT7FZZ 0W4N071 0UTJXZZ 0UTC0ZZ 0UTC4ZZ 0UTC7ZZ 0UTC8ZZ 0W4N0Z1 0HBV8ZZ 0UT9FZZ 0W4N0K1 0UTM0ZZ 0HBVXZX 0UTMXZZ

62.7 67.4 64.95 66.51 68.31 68.41 68.39 48 48 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only Excision of Bilateral Breast, Via Natural or Artificial Opening Endoscopic Endoscopic Opening Artificial or Natural Via Breast, Bilateral Excisionof Excision of Bilateral Breast, External Approach, Diagnostic Diagnostic Approach, External Breast, Bilateral Excisionof Approach Open tubes, fallopian bilateral of Resection Approach Endoscopic Percutaneous tubes, fallopian bilateral of Resection Opening Artificial Natural or Via tubes, fallopian bilateral of Resection Endoscopic Opening Artificial Natural or Via tubes, fallopian bilateral of Resection With Percutaneous Opening Artificial Natural or Via tubes, fallopian bilateral of Resection Assistance Endoscopic Open uterus, Approach of Resection Opening Endoscopic Percutaneous uterus, of Resection Opening Artificial or Via Natural uterus, of Resection Endoscopic Opening Artificial or Via Natural uterus, of Resection Endoscopic With Percutaneous Opening Artificial or Via Natural uterus, of Resection Assistance Approach cervix, of Open Resection Opening Endoscopic cervix, of Percutaneous Resection Opening Artificial or Natural cervix, of Via Resection Endoscopic Opening Artificial or Natural cervix, of Via Resection Approach Open clitoris, of Resection Approach External clitoris, of Resection Approach Open vulva, of Resection Approach External vulva, of Resection approach open substitute, tissue autologous with perineum infemale penis of Creation approach open substitute, synthetic with perineum infemale penis of Creation approach open substitute, tissue nonautologous with perineum infemale penis of Creation open approach perineum, infemale penis of Creation Prosthesis Testicular of Insertion prosthesis testicular of Insertion cervix of Amputation operative episode same at tubes fallopian both of Removal hysterectomy supracervical Laparoscopic hysterectomy subtotal abdominal unspecified and Other abdominalhysterectomy total Laparoscopic 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from

0VUS4JZ 0VUS0JZ 0VRC0JZ 0VUS47Z 0VUS07Z 0VUSXJZ 0VUS4KZ 0VUSX7Z 0VUS0KZ 0VUSXKZ

68.9 68.49 68.51 68.59 68.61 68.71 68.79 68.69 49 49 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only Other and unspecified total abdominal hysterecto hysterecto total unspecified abdominal and Other

Laparoscopically assisted vaginal hysterectomy hysterectomy assisted vaginal Laparoscopically hysterectomy vaginal unspecified and Other abdominalhysterectomy radical Laparoscopic hysterectomy radical abdominal unspecified and Other vaginal hysterectomy radical Laparoscopic hysterectomy radical vaginal unspecified and Other hysterectomy unspecified and Other approach substitute, open bilateral synthetic with of testes Replacement Approach Open substitute, tissue autologous with penis Supplement Approach Endoscopic Percutaneous substitute, tissue autologous with penis Supplement Approach External substitute, tissue autologous with penis Supplement Approach Open substitute, synthetic with penis Supplement Approach Endoscopic Percutaneous substitute, synthetic with penis Supplement Approach External substitute, synthetic with penis Supplement Approach Open substitute, tissue nonautologous with penis Supplement Approach Percutaneous substitute, tissue nonautologous with penis Supplement Approach External substitute, tissue nonautologous with penis Supplement Page 83 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from BMJ Open Page 84 of 84

1 STROBE Statement—Checklist of items that should be included in reports of cohort studies 2 Item No Recommendation Where addressed 3 Title and abstract 1 (a) Indicate the study’s design with a commonly used See title and abstract 4 term in the title or the abstract 5 (b) Provide in the abstract an informative and See title and abstract 6 balanced summary of what was done and what was 7 found Introduction 8 9 Background/rationale 2 Explain the scientific background and rationale for the See pages 4-5 & 7 investigation being reported 10 Objectives 3 State specific objectives, including any prespecified This is a “cohort profile” 11 hypotheses manuscript with the focus 12 on study methods and the 13 potential for future 14 analyses, rather than 15 For peer review only specific hypotheses (see 16 page 5) 17 Methods 18 Study design 4 Present key elements of study design early in the See pages 7-8 19 paper 20 Setting 5 Describe the setting, locations, and relevant dates, See pages 7-8 21 including periods of recruitment, exposure, follow-up, 22 and data collection a 23 Participants 6 ( ) Give the eligibility criteria, and the sources and See pages 8-9, and 24 methods of selection of participants. Describe methods Figures 1-2 of follow-up 25 (b) For matched studies, give matching criteria and See page 11 26 number of exposed and unexposed 27 Variables 7 Clearly define all outcomes, exposures, predictors, This is a “cohort profile” 28 potential confounders, and effect modifiers. Give manuscript with the focus 29 diagnostic criteria, if applicable on study methods and the 30 potential for future 31 analyses, rather than

32 specific hypotheses (see http://bmjopen.bmj.com/ 33 page 5). The general list 34 of variables is included in 35 Table 3 The specific 36 analytic variables will 37 depend on the analysis in 38 question, which will be 39 covered in separate publications

40 on September 30, 2021 by guest. Protected copyright. Data sources/ measurement 8* For each variable of interest, give sources of data and See Table 3 41 details of methods of assessment (measurement). 42 Describe comparability of assessment methods if there 43 is more than one group 44 Bias 9 Describe any efforts to address potential sources of See pages 15-16 45 bias 46 Study size 10 Explain how the study size was arrived at See page 12 & Figure 2 47 Quantitative variables 11 Explain how quantitative variables were handled in See item #7 above 48 the analyses. If applicable, describe which groupings 49 were chosen and why 50 Statistical methods 12 (a) Describe all statistical methods, including those See item #7 above 51 used to control for confounding 52 (b) Describe any methods used to examine subgroups See item #7 above 53 and interactions c 54 ( ) Explain how missing data were addressed See item #7 above d 55 ( ) If applicable, explain how loss to follow-up was See item #7 above 56 addressed (e) Describe any sensitivity analyses See item #7 above 57 Results 58 Participants 13* (a) Report numbers of individuals at each stage of See pages 8-9, 12 & 59 study—eg numbers potentially eligible, examined for Figure 2 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml1 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 85 of 84 BMJ Open

1 eligibility, confirmed eligible, included in the study, 2 completing follow-up, and analysed 3 (b) Give reasons for non-participation at each stage See page 12 & Figure 2 4 (c) Consider use of a flow diagram See Figure 2 Descriptive data 14* (a) Give characteristics of study participants (eg See Table 3 5 demographic, clinical, social) and information on 6 exposures and potential confounders 7 (b) Indicate number of participants with missing data See Table 3 8 for each variable of interest 9 (c) Summarise follow-up time (eg, average and total 10 amount) 11 Outcome data 15* Report numbers of outcome events or summary See Tables 6-7 12 measures over time 13 Main results 16 (a) Give unadjusted estimates and, if applicable, This is a “cohort profile” 14 confounder-adjusted estimates and their precision (eg, manuscript with the focus 15 For peer95% confidence review interval). Make clear onlywhich on study methods and the 16 confounders were adjusted for and why they were potential for future 17 included analyses, rather than 18 (b) Report category boundaries when continuous specific hypothesis testing 19 variables were categorized (see page 5). The c overview of planned 20 ( ) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time analyses is provided on 21 period pages 13-14 22 Other analyses 17 Report other analyses done—eg analyses of subgroups 23 and interactions, and sensitivity analyses 24 Discussion 25 Key results 18 Summarise key results with reference to study This is a “cohort profile” 26 objectives manuscript with the focus 27 on study methods and the 28 potential for future 29 analyses, rather than 30 specific results 31 Limitations 19 Discuss limitations of the study, taking into account Pages 14-16 discuss

32 sources of potential bias or imprecision. Discuss both methodological strengths http://bmjopen.bmj.com/ 33 direction and magnitude of any potential bias and limitations of the 34 cohort 35 Interpretation 20 Give a cautious overall interpretation of results This is a “cohort profile” 36 considering objectives, limitations, multiplicity of manuscript with the focus analyses, results from similar studies, and other on study methods and the 37 relevant evidence potential for future 38 analyses, rather than 39 specific results

40 Generalisability 21 Discuss the generalisability (external validity) of the See pages 17-18 on September 30, 2021 by guest. Protected copyright. 41 study results 42 Other information 43 Funding 22 Give the source of funding and the role of the funders See page 19 44 for the present study and, if applicable, for the original 45 study on which the present article is based 46 47 *Give information separately for exposed and unexposed groups. 48 49 50 Note: An Explanation and Elaboration article discusses each checklist item and gives methodological background and 51 published examples of transparent reporting. The STROBE checklist is best used in conjunction with this article (freely 52 available on the Web sites of PLoS Medicine at http://www.plosmedicine.org/, Annals of Internal Medicine at 53 http://www.annals.org/, and Epidemiology at http://www.epidem.com/). Information on the STROBE Initiative is 54 55 available at http://www.strobe-statement.org. 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml2 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from BMJ Open

COHORT PROFILE: STUDY OF TRANSITION, OUTCOMES & GENDER (STRONG) TO ASSESS HEALTH STATUS OF TRANSGENDER PEOPLE

For peer review only Journal: BMJ Open

Manuscript ID bmjopen-2017-018121.R1

Article Type: Cohort profile

Date Submitted by the Author: 11-Sep-2017

Complete List of Authors: Quinn, Virginia; Kaiser Permanente Southern California, Research & Evaluation Nash, Rebecca; Emory University Rollins School of Public Health, Epidemiology Hunkeler, Enid; Retired (formerly with Division of Research, Kaiser Permanente Northern California) Contreras, Richard; Kaiser Permanente Southern California, Research & Evaluation Cromwell, Lee; Kaiser Permanente Georgia Becerra-Culqui, Tracy; Kaiser Permanente Southern California, Research & Evaluation Getahun, Darios; Kaiser Permanente Southern California, Research & http://bmjopen.bmj.com/ Evaluation Giammattei, Shawn; The Rockway Institute, Alliant International University Lash, Timothy; Emory University, Department of Epidemiology Millman, Andrea; Kaiser Permanente Northern California, Division of Research Robinson, Brandi; Kaiser Permanente Georgia Roblin, Douglas; Georgia State University School of Public Health Silverberg, Michael; Kaiser Permanente Northern California

Slovis, Jennifer; Kaiser Permanente Northern California, Division of on September 30, 2021 by guest. Protected copyright. Research Tangpricha, Vin; Emory University School of Medicine; The Atlanta VA Medical Center Tolsma, Dennis; Kaiser Permanente Georgia Valentine, Cadence; Kaiser Permanente Southern California, Research & Evaluation Ward, Kevin; Rollins School of Public Health, Emory University, Winter, Savannah; Kaiser Permanente Georgia Goodman, Michael; Emory University Rollins School of Public Health, Epidemiology

Primary Subject Epidemiology Heading:

Secondary Subject Heading: Patient-centred medicine, Research methods, Sexual health

Keywords: Transgender, cohort, electronic medical records

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

1 2 COHORT PROFILE: STUDY OF TRANSITION, OUTCOMES & GENDER (STRONG) 3 TO ASSESS HEALTH STATUS OF TRANSGENDER PEOPLE 4

5 1 6 Virginia P. Quinn, PhD 2 7 Rebecca Nash, MPH 8 Enid Hunkeler, MA, FAHA3 9 Richard Contreras, MS1 10 Lee Cromwell, MS4 11 1 12 Tracy A. Becerra-Culqui, PhD 1 13 Darios Getahun, MD, PhD, MPH 14 Shawn Giammattei, PhD5 15 Timothy L. Lash,For DSc2 peer review only 16 Andrea Millman, MA6 17 Brandi Robinson, MPH4 18 7 19 Douglas Roblin, PhD 6 20 Michael J. Silverberg, PhD 21 Jennifer Slovis, MD8 22 Vin Tangpricha, MD, PhD9,10 23 Dennis Tolsma, MPH4 24 1 25 Cadence Valentine 2 26 Kevin Ward, PhD, MPH 27 Savannah Winter4 28 Michael Goodman, MD, MPH2 29 30 Affiliations 31 1

32 Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, CA http://bmjopen.bmj.com/ 2 33 Rollins School of Public Health, Emory University, Atlanta GA 34 3 Retired, formerly with Division of Research, Kaiser Permanente Northern California, Oakland, 35 CA 36 4 Center for Clinical and Outcomes Research, Kaiser Permanente Georgia, Atlanta, GA 37 5 38 The Rockway Institute, Alliant International University, San Francisco, CA 6 39 Division of Research, Kaiser Permanente Northern California, Oakland, CA 7

40 School of Public Health, Georgia State University, Atlanta GA on September 30, 2021 by guest. Protected copyright. 41 8 The Permanente Medical Group, Kaiser Permanente Northern California, Oakland, CA 42 9 Emory University, School of Medicine, 43 10 44 The Atlanta VA Medical Center, Atlanta GA 45 46 Corresponding author 47 Michael Goodman, MD, MPH 48 Department of Epidemiology 49 50 Emory University School of Public Health 51 1518 Clifton Road, NE 52 CNR 3021 53 Atlanta, GA 30322 54 404.727.2734 55 [email protected] 56 57 58 Keywords: transgender, cohort, electronic medical records 59 60 1

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1 2 3 ABSTRACT 4 5 6 Purpose: The Study of Transition, Outcomes and Gender (STRONG) was initiated to assess 7 health status of transgender people in general and following gender affirming treatments at 8 Kaiser Permanente health plans in Georgia, Northern California, and Southern California. The 9 objectives of this communication are to describe methods of cohort ascertainment and data 10 11 collection, and to characterize the study population. 12 Participants: A step-wise methodology involving computerized searches of electronic medical 13 records and free text validation of eligibility and gender identity was used to identify a cohort of 14 6,456 members with first evidence of transgender status (index date) between 2006 and 2014. 15 The cohort includedFor 3,475 (54%)peer transfeminine review (TF), 2,892 (45%) only transmasculine (TM), and 89 16 (1%) members whose natal sex and gender identity remained undetermined from the records. 17 18 The cohort was matched to 127,608 enrollees with no transgender evidence (63,825 women and 19 63,783 men) on year of birth, race/ethnicity, study site, and membership year of the index date. 20 Cohort follow up extends through the end of 2016. 21 Findings to date: About 58% of TF and 52% of TM cohort members received hormonal therapy 22 at Kaiser Permanente. Chest surgery was more common among TM participants (12% vs. 23 24 0.3%). The proportions of transgender participants who underwent genital reconstruction 25 surgeries were similar (4-5%) in the two transgender groups. Results indicate there are sufficient 26 numbers of events in the TF and TM cohorts to further examine mental health status, 27 cardiovascular events, diabetes, HIV, and most common cancers. 28 Future plans: STRONG is well-positioned to fill existing knowledge gaps through comparisons 29 of transgender and reference populations and through analyses of health status before and after 30 31 gender affirmation. Analyses will include incidence of cardiovascular disease, mental health,

32 HIV and diabetes, as well as changes in laboratory-based endpoints (e.g., polycythemia and bone http://bmjopen.bmj.com/ 33 density), overall and in relation to gender affirmation therapy. 34 35 36 37 38 39

40 on September 30, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 2

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1 2 3 4 5 ARTICLE SUMMARY 6 • Study strengths include systematic cohort identification without a need for participant 7 opt-in, accurate determination of gender identity, and comprehensive ascertainment of 8 hormonal and surgical treatment received at Kaiser Permanente. 9 • The weaknesses of the study include relatively short follow up, dearth of information on 10 11 gender affirmation received outside of the health plans, and lack of data on outcomes not 12 captured in the medical records 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 30, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 3

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1 2 3 INTRODUCTION 4 5 6 Transgender people are a diverse group of individuals whose biological sex does not 7 8 match their gender identity.1 Typically, sex is assigned at birth based on the external appearance 9 10 2 11 of the genitalia. In contrast, an individual’s gender identity is defined as being a male/man, 12 2 3 13 female/woman, or of a different gender. Many transgender people may not self-identify based 14 15 on binary definitions;For4 however, peer a person whosereview gender identity onlydiffers from a male natal sex 16 17 18 assignment is often referred to as male-to-female or trans woman, and a person whose gender 19 20 identity differs from a female natal sex is often referred to as a female-to-male or trans man.5 6 21 22 More recently, the terms transfeminine (TF) and transmasculine (TM) have become preferred as 23 24 7 25 they also apply to individuals who do not identify with binary gender categories. 26 27 Transgender individuals sometimes seek medical gender affirmation, which may involve 28 29 administration of cross-sex hormone therapy (HT) to achieve desired masculinization or 30 31 8 9

32 feminization, and/or surgical change of the genitalia and other sex characteristics. Although http://bmjopen.bmj.com/ 33 34 several organizations have established guidelines for clinical care of transgender patients,9 10 35 36 37 many issues in transgender health and gender affirmation therapy remain unresolved due to lack 38 11 39 of direct evidence. Consequently, many current practices and standards of care are based on

40 on September 30, 2021 by guest. Protected copyright. 41 expert opinion, case reports, or extrapolation of research findings from other populations. For 42 43 44 example, current recommendations regarding risk of venous thromboembolism in TF patients 45 46 receiving estrogen are based on the observed effects of hormone replacement therapy in post- 47 48 menopausal women.12 13 Similarly, expected health risks in TM are inferred from comorbidities 49 50 14 51 associated with polycystic ovary syndrome. 52 53 Critical knowledge gaps include the effect of HT and surgery on gender dysphoria (the 54 55 feeling of distress when natal sex does not match gender identity15) and other mental health 56 57 58 59 60 4

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1 2 3 issues, hematological side effects of HT, and risk of cardiovascular disease, metabolic or 4 5 16 6 endocrine disorders and cancer following hormonal or surgical gender affirmation. A direct 7 8 evaluation of some of these issues requires longitudinal datasets with large numbers of TM and 9 10 11 TF participants with sufficient follow up and variable history of surgical interventions and cross- 12 17 13 sex HT use. These considerations motivated the design of the longitudinal cohort for “Study of 14 15 Transition, OutcomesFor & Gender peer (STRONG).” review The present paper only provides a summary of the 16 17 18 challenges facing transgender health research, describes the main elements of the STRONG 19 20 study design and data collection, and discusses lessons learned during the implementation of this 21 22 project. In this "cohort profile" communication we offer a detailed documentation of methods 23 24 25 used to assemble, validate and characterize the STRONG cohort and offer an overall description 26 27 of the study population that will provide data for a multitude of subsequent hypothesis-testing 28 29 studies. 30 31

32 http://bmjopen.bmj.com/ 33 34 METHODOLOGICAL CHALLENGES FACING TRANSGENDER HEALTH STUDIES 35 36 37 The methodological challenges in observational studies of transgender health fall into 38 39 five categories: 1) attaining sufficient sample size and statistical power; 2) systematic and

40 on September 30, 2021 by guest. Protected copyright. 41 comprehensive identification of eligible study participants and comparable reference groups; 3) 42 43 44 determination of natal sex and/or gender identity; 4) assessment of current and past gender 45 46 affirmation treatment; and 5) engagement of patient and physician stakeholders at all stages of 47 48 research.17 49 50 51 Transgender people represent a hard-to-reach population, and to date most existing 52 53 cohorts assessing transgender health were assembled in specialized clinics that provide gender 54 55 affirmation care.18 19 This approach provides good options for detailed treatment data and 56 57 58 59 60 5

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1 2 3 biospecimen collection but may exclude individuals who have not sought or who have already 4 5 20 6 completed treatment, and makes it difficult to select comparable reference groups. In addition, 7 8 establishing a large clinic-based cohort requires coordination across multiple sites, is costly, and 9 10 17 11 may still have small numbers resulting in studies of relatively low statistical power. 12 13 Besides clinic-based studies, previous efforts to identify transgender individuals for 14 15 health research alsoFor involved peer population surveys review21 and reviews ofonly electronic records for relevant 16 17 22 23 18 International Classification of Diseases (ICD) codes. While surveys offer generalizable 19 20 population estimates, they may be affected by recall bias and low response rates and require 21 22 large-scale efforts to identify sufficient numbers of transgender people. Reliance on ICD codes 23 24 25 allows identifying large samples from insurance claims or electronic medical records (EMRs), 26 27 but may exclude eligible study participants who do not have or do not wish to receive a 28 29 transgender-specific diagnosis.24 30 31

32 A critical aspect of transgender research is accurate identification of gender identity. In http://bmjopen.bmj.com/ 33 34 recent years, the U.S. Department of Health and Human Services issued a directive that EMR 35 36 25 37 systems should enable providers to record gender identity and sexual orientation. This 38 39 directive should improve documentation over time; but in the meantime, determination of TF or

40 on September 30, 2021 by guest. Protected copyright. 41 TM status presents a methodological challenge because the available demographic data can 42 43 44 reflect natal sex or gender identity, without specifying which is which. Assessing TM/TF status 45 46 can be achieved by asking two questions about natal sex and gender identity;26 however, reliance 47 48 on self-report requires contact with individual participants and is subject to non-response, which 49 50 51 increases the risk of selection bias. 52 53 Insurance coverage for gender affirmation therapy has increased over time;27-29 however, 54 55 it remains sporadic and incomplete, and many transgender people seek care outside of regular 56 57 58 59 60 6

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1 2 3 health care plans.30 This presents a specific challenge for any study that aims to ascertain 4 5 6 hormonal exposures and surgical procedures, particularly for transgender people with no or 7 8 inadequate insurance coverage and for persons who initiated gender affirming therapy years ago. 9 10 11 In a rapidly developing field, such as transgender health, even experienced researchers 12 13 may lack specific expertise required to prioritize research questions and select the most relevant 14 15 patient-centered Foroutcome measures. peer Thus, reviewit is important to involve only members of the transgender 16 17 18 community and their physicians to ensure that the proposed research questions, study design, and 19 20 data collection methods are relevant, appropriate and feasible.31 Conversely, as the research 21 22 methods and interpretation of findings are becoming increasingly complex, researchers should 23 24 25 communicate with stakeholders directly to convey information relevant to their decision- 26 27 making.32 28 29 In sum, transgender health research faces significant methodological challenges and 30 31

32 logistical barriers. These challenges and barriers contribute to the lack of knowledge about the http://bmjopen.bmj.com/ 33 34 health risks in this population and preclude development of evidence-based recommendations for 35 36 11 37 transgender health care. 38 39

40 on September 30, 2021 by guest. Protected copyright. 41 COHORT DESCRIPTION 42 43 44 Study goals, design, and setting 45 46 STRONG was initiated in September 2013 with the primary long-term goal of assessing 47 48 the health status of transgender individuals overall, among TF/TM subgroups, and both 49 50 51 subgroups after different types of gender affirming treatment. It was designed as an EMR-based 52 53 retrospective/prospective cohort study of transgender members enrolled at three Kaiser 54 55 Permanente (KP) health plans located in Georgia (KPGA), Northern California (KPNC) and 56 57 58 59 60 7

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1 2 3 Southern California (KPSC). These health plans are prepaid integrated care systems and 4 5 6 currently provide comprehensive health services to approximately 8 million members. 7 8 Individuals and their families may enroll through an employer, state or federal programs such as 9 10 11 Medicaid and Medicare, or directly. The populations of enrollees are socio-demographically 12 33 34 13 diverse and broadly representative of the communities in the corresponding areas. 14 15 The threeFor KP organizations peer are members review of several research only consortia including the 16 17 35 36 18 Health Care Systems Research Network and the Mental Health Research Network. They 19 20 share similarly structured databases organized into "Virtual Data Warehouses" (VDW), with files 21 22 stored behind security firewalls at each site. The files have identical variable names, formats, and 23 24 25 specifications that allow using centrally generated and/or distributed programs to create 26 27 harmonized analytic datasets.37 VDW files are linked by unique individual identifiers, allowing 28 29 researchers to construct historical and prospective cohorts.38 30 31

32 The study was conducted in partnership with the Emory University, which served as the http://bmjopen.bmj.com/ 33 34 coordinating center. All activities described in this manuscript were reviewed and approved by 35 36 37 the Institutional Review Boards (IRB) of the four institutions. 38 39 The stakeholder involvement was achieved by assembling an project advisory group. To

40 on September 30, 2021 by guest. Protected copyright. 41 recruit the Stakeholder Advisory Group members, investigators at each site were charged with 42 43 44 identifying a leading clinician specializing in transgender care. The physicians were then asked 45 46 to nominate one or two patients to serve as representatives of the transgender community. The 47 48 resulting Stakeholder Advisory Group included 12 members. The stakeholders made a number 49 50 51 of important contributions to the project at various stages of study design, planning and 52 53 implementation, as described below. 54 55 Cohort ascertainment 56 57 58 59 60 8

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1 2 3 Figure 1 shows the three-step algorithm used to identify transgender cohort members. It 4 5 6 includes initial EMR search to identify cohort candidates (Step 1); validation of transgender 7 8 status (Step 2); and determination of TM/TF status (Step 3). 9 10 11 Step 1: Initial EMR search 12 13 A SAS program (SAS institute, Cary, North Carolina) was used to search the EMRs of 14 15 KPGA, KPNC andFor KPSC memberspeer of all agesreview enrolled between only January 1, 2006 and December 16 17 18 31, 2014 to identify two types of evidence supporting transgender status: 1) relevant 19 20 International Classification of Diseases Ninth edition (ICD-9) codes; and 2) presence of relevant 21 22 specific keywords in free-text clinical notes (Table 1). The program was developed and pilot- 23 24 25 tested at KPGA, and then distributed to the remaining sites. Cohort ascertainment was 26 27 undertaken before the health plans switched to ICD-10 codes. 28 29 The diagnostic ICD-9 codes suggestive of transgender status were selected based on 30 31

32 consultations with the STRONG Stakeholder Advisory Group and methodologies described in http://bmjopen.bmj.com/ 33 34 earlier studies.23 39 Transvestic fetishism (ICD-9 code 302.3) was included based on previous 35 36 37 observations that men who initially meet criteria for this diagnostic category may later 38 22 39 experience persistent gender dysphoria consistent with transgender status.

40 on September 30, 2021 by guest. Protected copyright. 41 We also used ICD-9 V codes, which allow for supplementary classification of factors 42 43 40 41 44 influencing health status. As V codes may cover several conditions, we used them in 45 46 conjunction with internal KP codes to ensure specificity. For example, a combination of ICD-9 47 48 code V49.89 and KP code 121141596 means "Other conditions influencing health: transgender." 49 50 51 The second method of transgender ascertainment involved using a custom-written 52 53 program that identified the relevant keywords in free-text clinical notes recognizing that both 54 55 appropriate and inappropriate terms could be found in the EMR. During pilot testing an 56 57 58 59 60 9

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1 2 3 expanded list of keywords provided by the stakeholders was used; that list was gradually 4 5 6 shortened after step-wise removal of keywords that did not contribute additional cases. The 7 8 resulting list provided a complete cohort ascertainment with the shortest program running time. 9 10 11 Step 2: Cohort validation 12 13 A separate program extracted short strings of text that included 100 characters before and 14 15 50 characters afterFor each keyword peer of interest. review When clinical notes only contained relevant keywords 16 17 18 (with or without an ICD-9 code), transgender status was confirmed through an examination of 19 20 the de-identified text strings by two trained reviewers. Disagreements among reviewers were 21 22 adjudicated by a review committee that included two physician investigators (MG and VT) and 23 24 25 the project manager (RN). 26 27 Cohort candidates with no keywords, but at least two different diagnostic codes or the 28 29 same code on different dates were considered eligible. The validity of this approach was 30 31

32 confirmed using unstructured chart review during pilot testing of the study protocol, as described http://bmjopen.bmj.com/ 33 34 previously.24 35 36 37 Members who had evidence of disorders of sex development (i.e., abnormalities of 38 42 39 chromosomal, gonadal, or anatomic sex ) and those younger than 3 years of age at the index

40 on September 30, 2021 by guest. Protected copyright. 41 date were excluded. 42 43 44 Step 3: Determination of TF/TM status 45 46 Each eligible study participant was categorized as TF or TM using several methods. We 47 48 used all keyword text strings and ICD-9 codes extracted for Step 1 to identify additional words 49 50 51 such as "male-to-female," "female-to-male," and gender affirmation V codes (V07.8 +12124952 52 53 and V07.8 +12124310). During the validation of transgender status, the reviewers were also 54 55 instructed to categorize each eligible person as "natal male," "natal female," or "unclear." 56 57 58 59 60 10

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1 2 3 For persons whose TF/TM status was unclear after the initial review, and for persons 4 5 6 with ICD-9 codes only, another free-text program was developed to search for keywords 7 8 reflecting natal sex anatomy (e.g., "testes" or "ovaries"), history of specific procedures (e.g., 9 10 11 orchiectomy or hysterectomy) or evidence of hormonal therapy (e.g., estrogen or testosterone). 12 13 The keywords used for assigning TM/TF status are included in Table 2. Text strings containing 14 15 TF- and TM-specificFor keywords peer were reviewed review and adjudicated asonly discussed above. 16 17 18 Gender affirmation treatment status 19 20 During the initial STRONG cohort validation (Step 2) and natal sex determination (Step 21 22 3), reviewers were instructed to check a box for "Evidence of treatment" if the text strings 23 24 25 provided an indication of receipt or referral for HT, surgery, or other relevant procedures (e.g., 26 27 electrolysis). Disagreements were adjudicated as described previously. 28 29 In addition to text string reviews, gender affirmation treatment status was determined by 30 31

32 linkage with cross-sex hormone prescriptions using national drug codes, as well as ICD-9, ICD- http://bmjopen.bmj.com/ 33 34 10, and Current Procedure Terminology codes reflecting surgeries and other interventions 35 36 37 (Supplemental Tables 1-6). TF drugs (e.g., estradiol, spironolactone) in a natal male and TM 38 39 drugs (e.g. testosterone) in a natal female were considered as evidence of HT.

40 on September 30, 2021 by guest. Protected copyright. 41 As the result of these steps, cohort members were categorized based on evidence of HT 42 43 44 and surgical or other gender affirmation procedures. Gender affirmation procedures were 45 46 categorized as: bottom (e.g., vaginoplasty for TF or vaginectomy for TM); top (e.g., breast 47 48 augmentation for TF or mastectomy for TM); interventions to change secondary sex 49 50 51 characteristics (e.g., electrolysis); or not specified (i.e., evidence of surgery in the text only). 52 53 Selection of the reference cohort 54 55 56 57 58 59 60 11

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1 2 3 Up to 10 male and 10 female KP enrollees without evidence of transgender status were 4 5 6 matched to each member of the final validated transgender cohort on year of birth (within 5-year 7 8 groups for adults, and 2-year groups for children and adolescents), race/ethnicity, KP site, and 9 10 11 membership year at the index date. Index date was defined as the date of the first recorded 12 13 evidence of transgender status in the EMR. For some transgender cohort members, the number 14 15 of reference malesFor or females peer was less than review 10 due to duplicate matches;only however, no 16 17 18 transgender participant had less than 7 referents of either sex. A cluster ID for each matched 19 20 group was assigned to allow stratified analyses (e.g., by HT type, or gender affirming surgery). 21 22 Data integration and follow up 23 24 25 Patient identification numbers for both the transgender and reference cohorts were linked 26 27 to multiple data sources to obtain ICD-9 and ICD-10 diagnostic codes for the conditions of 28 29 primary interest (e.g., mental health conditions, cardiovascular diseases and diabetes); disease 30 31

32 registries to ascertain incident cancers and HIV diagnoses; psychiatric and behavioral health care http://bmjopen.bmj.com/ 33 34 utilization; pharmacy records to track mental health treatment and HT receipt over time; and 35 36 37 dates and results of laboratory tests including bone scans, blood chemistry analyses, hormone 38 39 levels, and blood cell counts (Table 3). Mortality was ascertained from linkages to death

40 on September 30, 2021 by guest. Protected copyright. 41 registries. All members of the cohort were assigned a study ID by the programmer at each KP 42 43 44 site and no personally identifiable information was included in the aggregated analytic file. To 45 46 date, cohort follow up extends through the end of 2016. 47 48 49 50 51 FINDINGS TO DATE 52 53 Initial review of the EMRs identified 12,457 potential transgender individuals. Of these, 54 55 7,272 (58%) were identified through keywords only, 1,132 (9%) through ICD-9 codes only, and 56 57 58 59 60 12

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1 2 3 the remaining 4,053 (33%) had both ICD-9 codes and keywords (Figure 2). Among these 4 5 6 candidates, 6,456 were confirmed as transgender: 10% from ICD-9 codes alone, 29% from 7 8 keywords alone and 61% from both codes and keywords. Based on validation results, the 9 10 11 positive predictive values for keywords, diagnostic codes, and both were 26%, 54%, and 98%, 12 13 respectively. The leading reason for non-eligibility was the use of a keyword (e.g., 14 15 "transgender") referringFor not peerto the patient, butreview to the patient’s relative, only or partner. In other 16 17 18 situations, the keywords of interest were used as part of standard text, such as when listing 19 20 indications for hormone use. Natal sex and/or gender identity was successfully determined for 21 22 all but 89 (1.4%) of the transgender cohort members. 23 24 25 The transgender cohort was matched to 127,608 enrollees with no evidence of 26 27 transgender status. Of those 63,825 were women and 63,783 were men. 28 29 Figure 3 displays proportions of transgender enrollees over time at each of the three 30 31

32 participating sites. In 2006, the prevalence estimates (95% confidence intervals) per 100,000 http://bmjopen.bmj.com/ 33 34 enrollees were 3.5 (1.9, 6.3), 5.5 (4.8, 6.4) and 17 (16, 19) in KPGA, KPSC and KPNC, 35 36 37 respectively. By 2014, the corresponding estimates increased to 38 (32, 45) in KPGA, 44 (42, 38 39 46) in KPSC, and 75 (72, 78) in KPNC. The composition of the transgender population has also

40 on September 30, 2021 by guest. Protected copyright. 41 changed. Whereas in 2006 the TF:TM ratio among newly identified cohort members was 42 43 44 approximately 1.7:1, in 2014 the same ratio was 1:1. 45 46 As shown in Table 4, 59% of all participants were from KPNC, 38% were from KPSC, 47 48 and less than 3% were from KPGA. With respect to race and ethnicity, Blacks and Asians each 49 50 51 comprised about 8% of the study population, 19% were Hispanics, and 55% were non-Hispanic 52 53 Whites. Compared to TF, TM subjects were younger (76% vs 53% under the age of 36) and 54 55 included a greater proportion of subjects who were obese (31% vs 22%). Proportions of 56 57 58 59 60 13

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1 2 3 smokers, insurance status, and area-based measures of education were similar in TM and TF 4 5 6 study subjects. 7 8 Nearly two-thirds of the transgender cohort had some evidence of gender affirming 9 10 11 treatment (Table 5). Approximately 55% of all transgender cohort members had evidence of HT 12 13 received at KP. This proportion was slightly higher (58%) in TF than in TM participants (52%). 14 15 About 23%For of the transgender peer cohort review had some evidence only of gender affirmation surgery. 16 17 18 Top surgery receipt at KP was far more common among TM cohort members than among their 19 20 TF counterparts (12% vs. 0.3%). Similar proportions of TM and TF cohorts had genital 21 22 surgeries (4-5%) or procedures aimed at altering other secondary sex characteristics (11%). 23 24 25 Tables 6 and 7 present the number of cases for various health outcomes in the STRONG 26 27 population through the end of 2016. These frequencies should not be interpreted as evidence of 28 29 increased or decreased risk because they do not account for person-time of follow up, time 30 31

32 ordering of the conditions and transgender status, and do not take into consideration exposures to http://bmjopen.bmj.com/ 33 34 cross-sex hormones or surgical procedures. Nevertheless, these data indicate that both TF and 35 36 37 TM cohort members, as well as their corresponding referents, have sufficient numbers of 38 39 cardiovascular events, mental health conditions, HIV, diabetes and several common cancers to

40 on September 30, 2021 by guest. Protected copyright. 41 permit meaningful analyses. Additional analyses will include changes in laboratory-based 42 43 44 endpoints including polycythemia and bone density. These analyses are beyond the scope of this 45 46 communication, which is focused on the study methods rather than specific findings. The 47 48 planned analyses will include comparisons of transgender and reference cohorts as well as 49 50 51 within-transgender cohort examination of health status before and after surgery and initiation of 52 53 HT. 54 55 56 57 58 59 60 14

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1 2 3 STRENGTHS AND LIMITATIONS 4 5 6 In this communication, we describe STRONG, a health system-based observational study 7 8 that was designed to examine the health status of transgender people and to evaluate the possible 9 10 11 risks and health benefits of various gender affirming treatments. STRONG aimed to overcome 12 13 five previously described methodological challenges facing transgender health research. 14 15 Sample size andFor power considerations peer review only 16 17 18 Adequate sample size can be feasibly achieved with the use of large well-defined 19 20 populations that offer an adequate sampling frame.38 In practical terms, at least in the US, this 21 22 can be done by basing the study in large integrated health systems with millions of members and 23 24 25 comprehensive electronic medical records. The EMR data from the health systems allow 26 27 assembling cohorts of hard-to-reach populations and ample options for selection of referent 28 29 groups. The STRONG cohort, which included almost 6,500 transgender people and nearly 30 31

32 130,000 referents, represents one of the largest studies of its kind available to date. http://bmjopen.bmj.com/ 33 34 Nevertheless, a number of important analyses by different sub-types of gender affirmation 35 36 37 treatment may not be feasible due to sparse stratum-specific data. 38 39 Systematic identification of eligible study participants

40 on September 30, 2021 by guest. Protected copyright. 41 We demonstrated that by using a relatively simple algorithm—based on standard codes 42 43 44 and supplemented with analysis of digitized provider notes—it is possible to comprehensively 45 46 identify transgender enrollees of large community based health plans. The use of keyword- 47 48 containing text strings enhanced cohort ascertainment relative to ICD code-alone based 49 50 51 approaches. On the other hand, reliance on keywords without text validation would have 52 53 erroneously included a substantial number of persons who are not transgender. A review of 54 55 records to confirm transgender status added considerable time and resources: however it is still 56 57 58 59 60 15

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1 2 3 more efficient and more comprehensive than the traditional unstructured chart review. In 4 5 6 conducting cohort validation we reviewed up to three clinical note excerpts on 11,325 people. 7 8 This task was accomplished within 6 months. 9 10 11 A comprehensive identification of all transgender people in the KP population (with and 12 13 without evidence in the medical records) would require contacting more than 8 million members 14 15 to inquire about Fortheir natal sexpeer and gender identity;review this does not only appear feasible at this time. 16 17 18 Determination of natal sex and/or gender identity 19 20 Our study definitively ascertained natal sex and/or gender identity for nearly 99% of 21 22 cohort members. We obtained information on TM/TF status from three sources: keyword text 23 24 25 strings, pharmacy records, and procedure codes. In most instances these sources were in 26 27 agreement; however, in some cases the results were discordant. Each disagreement was used as 28 29 an opportunity to check data accuracy and allowed reducing misclassification, which would have 30 31

32 been substantial if STRONG relied on demographic data in the EMR. For example, among adult http://bmjopen.bmj.com/ 33 34 TF study subjects, 41% were documented as "female" and 59% were documented as "male." 35 36 37 The corresponding proportions of people classified as "female" and "male" among adult TM 38 39 cohort members were 59% and 40%, respectively with 1% recorded as unknown in the EMR.

40 on September 30, 2021 by guest. Protected copyright. 41 By contrast, in 96% of persons under the age of 18, the demographic variable reflected natal sex. 42 43 44 A limitation of the current data is the inability to accurately identify persons who reject 45 46 binary gender categories. These individuals are likely to be found among cohort members who 47 48 do not have a transgender specific diagnosis and receive no HT or surgical treatment; however, 49 50 51 at the present time EMR alone are not sufficient for determination of non-binary gender identity. 52 53 This will be possible in the near future after KP introduces new data capture systems with 54 55 56 57 58 59 60 16

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1 2 3 separate fields for natal sex, gender identity, preferred pronouns, organ inventory, and history of 4 5 6 gender affirming procedures. 7 8 Assessment of current and past gender affirmation treatment 9 10 11 Although the information on gender affirmation received within the KP system is high 12 13 quality, one of the main limitations of STRONG data is the lack of information on HT and 14 15 surgical treatmentFor received outsidepeer the KP reviewsystem. This restricts only our ability to identify a sub- 16 17 18 category of transgender cohort members with no history of gender affirmation treatment of any 19 20 kind. For this reason, the most definitive analyses are limited to people who initiated therapy at 21 22 KP. These individuals can be identified among those STRONG participants whose EMR 23 24 25 demonstrates a gap between index date and the first prescription for HT. This "HT initiation" 26 27 group represents about 35% of TM and 32% of TF subjects. 28 29 The broadening of coverage for gender affirmation services at KP occurred relatively 30 31

40 on September 30, 2021 by guest. Protected copyright. 41 A critical feature of STRONG is patient-centeredness. During the study implementation, 42 43 44 we held monthly stakeholder calls and had three in-person Stakeholder Advisory Group 45 46 meetings. These interactions had direct impact on study design and implementation. For 47 48 example, the list of keywords used for STRONG cohort ascertainment was proposed, pilot 49 50 51 tested, and refined in close consultation with the study stakeholders. Following advice from 52 53 stakeholders, we expanded eligibility criteria to include transgender and gender non-conforming 54 55 youth (persons under 18 years of age). This change allowed a number of additional analyses and 56 57 58 59 60 17

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1 2 3 offers important opportunities for future follow up. STRONG stakeholders also helped to 4 5 6 develop a comprehensive list of hormonal medications and procedures used for gender 7 8 affirmation. The publications describing our formative research,24 43-45 the current 9 10 11 communication, and the reports in preparation, all include stakeholders as co-authors. 12 13 14 15 CONCLUSIONSFor peer review only 16 17 46 18 Although the body of literature addressing transgender health issues has been growing, 19 20 most studies focus on substance use, sexual health, sexually transmitted infections, and, to a 21 22 lesser extent, mental health conditions.47 By contrast, limited data are available on general 23 24 25 health status, or the incidence of chronic age-related conditions including cardiovascular disease, 26 27 endocrine disorders and cancer. 28 29 To date, most data on morbidity and mortality in transgender populations come from 30 31 19 48-50

32 clinical centers in Europe. These studies are characterized by detailed clinical data; http://bmjopen.bmj.com/ 33 34 however, they are limited by relatively small sample sizes. 35 36 37 In terms of overall design and size, STRONG is comparable to US-based studies that 38 22 51 39 used the Veterans Health Administration (VHA) data. Unlike our study, however, the VHA

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1 2 3 Tangpricha and Jennifer Slovis provided input on clinical aspects of the study and were 4 5 6 responsible for adjudication of study eligibility, gender identity, and gender affirmation. Kevin 7 8 Ward developed, pilot tested, and supervised the cohort validation and gender identity 9 10 11 ascertainment review protocols and programming. Shawn Giammattei, Cadence Valentine and 12 13 Savannah Winter are members of the Stakeholder Advisory Group who assisted with the 14 15 development of Forinclusion and peer exclusion criteria, review assessment of genderonly identity, and interpretation 16 17 18 of the data. All authors provided critical review of the manuscript for important intellectual 19 20 content; and approved the final version. 21 22 23 24 25 COMPETING INTERESTS 26 27 None of the authors report competing interests 28 29 30 31

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1 2 3 view of the complexity of the database, interested investigators will be asked to form a 4 5 6 collaborative arrangement with the STRONG investigators rather than simply receive the data 7 8 themselves. No additional data are available. 9 10 11 ACKNOWLEDGMENTS 12 13 Kimberly L. Cannavale, MPH and Alexander S. Carruth performed additional validations 14 15 of eligibility andFor ascertainment peer of natal sex review via reviews of medical only records 16 17 18 19 REFERENCES 20 21 22 1. Safer JD, Coleman E, Hembree W. There is reason for optimism: an introduction to the special 23 issue on research needs in transgender health and medicine. Current opinion in 24 endocrinology, diabetes, and obesity 2016;23(2):165-7. doi: 25 10.1097/MED.0000000000000228 26 27 2. Lombardi E. Enhancing transgender health care. Am J Public Health 2001;91(6):869-72. 28 29 3. Bockting W, Coleman E, De Cuypere G. Care of transsexual persons. N Engl J Med 30 31 2011;364(26):2559-60; author reply 60. doi: 10.1056/NEJMc1104884#SA1

32 http://bmjopen.bmj.com/ 33 4. Bockting W. From construction to context: Gender through the eyes of the transgendered. 34 Siecus Report 1999;28:3-7. 35 36 5. Giami A, Beaubatie E. Gender identification and sex reassignment surgery in the trans 37 population: a survey study in France. Arch Sex Behav 2014;43(8):1491-501. doi: 38 10.1007/s10508-014-0382-3 39

40 6. Reisner SL, Gamarel KE, Dunham E, et al. Female-to-male transmasculine adult health: a on September 30, 2021 by guest. Protected copyright. 41 mixed-methods community-based needs assessment. Journal of the American Psychiatric 42 Nurses Association 2013;19(5):293-303. doi: 10.1177/1078390313500693 43 44 7. Reisner SL, Radix A, Deutsch MB. Integrated and gender-affirming transgender clinical care 45 and research. J Acquir Immune Defic Syndr 2016;72 Suppl 3:S235-42. doi: 46 47 10.1097/QAI.0000000000001088 48 49 8. Knudson G, De Cuypere G, Bockting W. Recommendations for revision of the DSM 50 diagnoses of gender identity disorders: Consensus statement of the World Professional 51 Association for Transgender Health. Int J Transgenderism 2010;12(2):115-18. 52 53 9. Coleman E, Bockting WO, Botzer M, et al. Standards of care for the health of transsexual, 54 transgender, and gender-nonconforming people, version 7. Int J Transgenderism 55 2012;13(4):165-232. 56 57 58 59 60 21

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1 2 3 10. Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, et al. Endocrine treatment of 4 5 transsexual persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol 6 Metab 2009;94(9):3132-54. doi: 10.1210/jc.2009-0345 7 8 11. Institute of Medicine. The Health of Lesbian, Gay, Bisexual, and Transgender People: 9 Building a Foundation for Better Understanding. Washington, DC: The National 10 Academies Press 2011. 11 12 12. The Women’s Health Initiative Study Group. Design of the Women's Health Initiative 13 clinical trial and observational study. Control Clin Trials 1998;19(1):61-109. 14 15 13. Anderson GL,For Limacher peer M, Assaf AR, reviewet al. Effects of conjugated only equine estrogen in 16 postmenopausal women with hysterectomy: the Women's Health Initiative randomized 17 18 controlled trial. JAMA 2004;291(14):1701-12. doi: 10.1001/jama.291.14.1701 19 20 14. Cattrall FR, Healy DL. Long-term metabolic, cardiovascular and neoplastic risks with 21 polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol 2004;18(5):803-12. doi: 22 10.1016/j.bpobgyn.2004.05.005 23 24 15. Schneider C, Cerwenka S, Nieder TO, et al. Measuring gender dysphoria: A multicenter 25 examination and comparison of the Utrecht Gender Dysphoria Scale and the Gender 26 Identity/Gender Dysphoria Questionnaire for adolescents and adults. Arch Sex Behav 27 2016;45(3):551-8. doi: 10.1007/s10508-016-0702-x [published Online First: 2016/02/18] 28 29 16. Feldman J, Brown GR, Deutsch MB, et al. Priorities for transgender medical and healthcare 30 31 research. Current opinion in endocrinology, diabetes, and obesity 2016;23(2):180-7. doi:

32 10.1097/MED.0000000000000231 http://bmjopen.bmj.com/ 33 34 17. Reisner SL, Deutsch MB, Bhasin S, et al. Advancing methods for US transgender health 35 research. Current opinion in endocrinology, diabetes, and obesity 2016;23(2):198-207. 36 doi: 10.1097/MED.0000000000000229 37 38 18. Dekker MJ, Wierckx K, Van Caenegem E, et al. A European Network for the Investigation 39 of Gender Incongruence: Endocrine Part. J Sex Med 2016;13(6):994-9. doi:

40 10.1016/j.jsxm.2016.03.371 [published Online First: 2016/05/11] on September 30, 2021 by guest. Protected copyright. 41 42 19. Kreukels BP, Haraldsen IR, De Cuypere G, et al. A European network for the investigation 43 of gender incongruence: the ENIGI initiative. Eur Psychiatry 2012;27(6):445-50. doi: 44 45 10.1016/j.eurpsy.2010.04.009 46 47 20. Reisner SL, Poteat T, Keatley J, et al. Global health burden and needs of transgender 48 populations: a review. Lancet 2016;388(10042):412-36. doi: 10.1016/S0140- 49 6736(16)00684-X 50 51 21. Meier SC, Pardo ST, Labuski C, et al. Measures of clinical health among female-to-male 52 transgender persons as a function of sexual orientation. Arch Sex Behav 2013;42(3):463- 53 74. doi: 10.1007/s10508-012-0052-2 54 55 22. Blosnich JR, Brown GR, Shipherd Phd JC, et al. Prevalence of gender identity disorder and 56 suicide risk among transgender veterans utilizing veterans health administration care. Am 57 58 J Public Health 2013;103(10):e27-32. doi: 10.2105/AJPH.2013.301507 59 60 22

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1 2 3 23. Brown GR, Jones KT. Racial health disparities in a cohort of 5,135 transgender veterans. J 4 5 Racial Ethnic Health Disparities 2014;1(4):257-66. 6 7 24. Roblin D, Barzilay J, Tolsma D, et al. A novel method for estimating transgender status 8 using electronic medical records. Ann Epidemiol 2016;26(3):198-203. doi: 9 10.1016/j.annepidem.2016.01.004 10 11 25. Centers for Medicare & Medicaid Services. Medicare and Medicaid Programs; Electronic 12 Health Record Incentive Program—Stage 3 and Modifications to Meaningful Use in 13 2015 through 2017. Rockville, MD Department of Health and Human Services 2015. 14 15 26. Cahill S, SingalFor R, Grasso peer C, et al. Do ask,review do tell: high levels only of acceptability by patients of 16 routine collection of sexual orientation and gender identity data in four diverse American 17 18 community health centers. PLoS One 2014;9(9):e107104. doi: 19 10.1371/journal.pone.0107104 20 21 27. Deutsch MB. Gender-affirming surgeries in the era of insurance coverage: Developing a 22 framework for ssychosocial support and care Navigation in the perioperative period. J 23 Health Care Poor Underserved 2016;27(2):386-91. doi: 10.1353/hpu.2016.0092 24 25 28. Shipherd JC, Kauth MR, Matza A. Nationwide interdisciplinary e-consultation on 26 transgender care in the Veterans Health Administration. Telemed J E Health 27 2016;22(12):1008-12. doi: 10.1089/tmj.2016.0013 28 29 29. Stevens J, Gomez-Lobo V, Pine-Twaddell E. Insurance coverage of puberty blocker 30 31 therapies for transgender youth. Pediatrics 2015;136(6):1029-31. doi:

32 10.1542/peds.2015-2849 http://bmjopen.bmj.com/ 33 34 30. Tangpricha V, den Heijer M. Oestrogen and anti-androgen therapy for transgender women. 35 Lancet Diabetes Endocrinol 2016 doi: 10.1016/S2213-8587(16)30319-9 36 37 31. Quinn V, Becerra T, Gillespie T, et al. Embedding patients, providers, and community 38 stakeholders in research to improve transgender health. J Patient-Centered Res Rev 39 2015;2(2):114-15.

40 on September 30, 2021 by guest. Protected copyright. 41 32. Gabriel SE, Normand SL. Getting the methods right--the foundation of patient-centered 42 outcomes research. N Engl J Med 2012;367(9):787-90. doi: 10.1056/NEJMp1207437 43 44 33. Koebnick C, Langer-Gould AM, Gould MK, et al. Sociodemographic characteristics of 45 members of a large, integrated health care system: comparison with US Census Bureau 46 47 data. Perm J 2012;16(3):37-41. 48 49 34. Gordon NP. How does the adult Kaiser Permanente membership in northern California 50 compare with the larger community? . Oakland, CA: Kaiser Permanente Division of 51 Research, 2006. 52 53 35. Lieu TA, Hinrichsen VL, Moreira A, et al. Collaborations in population-based health 54 research: the 17th annual HMO Research Network Conference, March 23-25, 2011, 55 Boston, Massachusetts, USA. Clin Med Res 2011;9(3-4):137-40. doi: 56 10.3121/cmr.2011.1025 57 58 59 60 23

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1 2 3 36. Simon GE, Stewart C, Beck A, et al. National prevalence of receipt of antidepressant 4 5 prescriptions by persons without a psychiatric diagnosis. Psychiatric services 6 2014;65(7):944-6. doi: 10.1176/appi.ps.201300371 7 8 37. Go AS, Magid DJ, Wells B, et al. The Cardiovascular Research Network: a new paradigm 9 for cardiovascular quality and outcomes research. Circ Cardiovasc Qual Outcomes 10 2008;1(2):138-47. doi: 10.1161/CIRCOUTCOMES.108.801654 11 12 38. Goodman M, Fletcher RH, Doria-Rose VP, et al. Observational methods to assess the 13 effectiveness of screening colonoscopy in reducing right colon cancer mortality risk: 14 SCOLAR. Journal of comparative effectiveness research 2015;4(6):541-51. doi: 15 For peer review only 16 10.2217/cer.15.39 17 18 39. Brown GR, Jones KT. Incidence of breast cancer in a cohort of 5,135 transgender veterans. 19 Breast cancer research and treatment 2015;149(1):191-8. doi: 10.1007/s10549-014- 20 3213-2 [published Online First: 2014/11/28] 21 22 40. World Health Organisation. International Statistical Classification of Diseases and Related 23 Health Problems, 9th Revision. Geneva: WHO, 1978. 24 25 41. Maguire N. In search of the "V" codes (ICD-9-CM). The Journal of medical practice 26 management : MPM 2012;28(1):56-7. 27 28 42. Hughes IA. Disorders of sex development: a new definition and classification. Best Pract Res 29 Clin Endocrinol Metab 2008;22(1):119-34. doi: 10.1016/j.beem.2007.11.001 30 31 43. Owen-Smith A, Sineath RC, Sanchez T, et al. Perception of Community Tolerance and 32 Prevalence of Depression among Transgender Persons. J Gay Lesbian Ment Healt 2016( http://bmjopen.bmj.com/ 33 34 in press) 35 36 44. Owen-Smith A, Woodyatt C, Sineath RC, et al. Perceptions of Barriers to and Facilitators of 37 Participation in Health Research among Transgender People Transgender Health 2016(in 38 press) 39

40 45. Sineath RC, Woodyatt C, Sanchez T, et al. Determinants of and Barriers to Hormonal and on September 30, 2021 by guest. Protected copyright. 41 Surgical Treatment Receipt Among Transgender People. Transgender Health 42 2016;1(1):129-36. 43 44 46. Collin L, Tangpricha V, Goodman M. Worldwide Prevalence of Transgender and Gender 45 Non-Conformity. In: Ettner R, Monstrey S, Coleman E, eds. Principles of Transgender 46 47 Medicine and Surgery New York, NY: Routledge 2016. 48 49 47. MacCarthy S, Reisner SL, Nunn A, et al. The Time Is Now: Attention Increases to 50 Transgender Health in the United States but Scientific Knowledge Gaps Remain. LGBT 51 Health 2015;2(4):287-91. doi: 10.1089/lgbt.2014.0073 52 53 48. van Kesteren PJ, Asscheman H, Megens JA, et al. Mortality and morbidity in transsexual 54 subjects treated with cross-sex hormones. Clin Endocrinol (Oxf) 1997;47(3):337-42. 55 56 57 58 59 60 24

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1 2 3 49. Asscheman H, Giltay EJ, Megens JA, et al. A long-term follow-up study of mortality in 4 5 transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol 6 2011;164(4):635-42. doi: 10.1530/eje-10-1038 [published Online First: 2011/01/27] 7 8 50. Dhejne C, Lichtenstein P, Boman M, et al. Long-term follow-up of transsexual persons 9 undergoing sex reassignment surgery: cohort study in Sweden. PloS One 10 2011;6(2):e16885. doi: 10.1371/journal.pone.0016885 11 12 51. Kauth MR, Shipherd JC, Lindsay J, et al. Access to care for transgender veterans in the 13 Veterans Health Administration: 2006-2013. Am J Public Health 2014;104 Suppl 14 4:S532-4. doi: 10.2105/AJPH.2014.302086 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 30, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 25

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Transgender Transgender Transsexual Transvestite identity Gender dysphoria Gender reassignment Gender As V codes may cover several conditions they they several conditions may cover codes V As 4041

Other conditions conditions Other Acquired absence of absence Acquired 26 26 – – specified Other – – specified Other http://bmjopen.bmj.com/ – – – – BMJ Open on September 30, 2021 by guest. Protected copyright. influencing health: transgender. health: transgender. influencing +121141596 V45.77 supplementation supplementation 12124310 + V07.8 genital organs: history of sex reassignment of sex reassignment history organs: genital surgery 12124952 + V07.8 V49.89 + 121141596 121141596 + V49.89 supplementation supplementation ICD-9 V-codes* + internal KP codes internal + KP V-codes* ICD-9 Keywords prophylactic measure: male-to-female hormone hormone male-to-female measure: prophylactic prophylactic measure: female-to-male hormone hormone female-to-male measure: prophylactic For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only

TABLES * ICD-9 V codes are used for supplementary classification of factors influencing health status. health influencing factors of classification supplementary used for are codes V * ICD-9 302.5 – Trans-sexualism Trans-sexualism – 302.5 unspecified with Trans-sexualism – 302.50 “transsexualism not (a.k.a. sexualhistory specified”) otherwise history asexual with Trans-sexualism – 302.51 homosexual with Trans-sexualism – 302.52 history; heterosexual with Trans-sexualism – 302.53 history in identity disorder Gender – 302.85 or adults adolescents inchildren identity disorder Gender – 302.6 fetishism Transvestic – 302.3 ICD-9 diagnostic codes codes diagnostic ICD-9 have to be used in conjunction with internal KP codes to ensure specificity toensure codes KP internal with in conjunction used be to have Table 1: ICD-9 codes and keywords used to identify potentially eligible STRONG transgender cohort members among KPGA, KPSC, and KPSC, among KPGA, members cohort transgender STRONG eligible potentially andidentify used to codes keywords ICD-9 Table1: members KPNC Page 27 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 28 of 87

27 27 http://bmjopen.bmj.com/ BMJ Open ovary, ovaries, ovarian, cervix, uterus, uterine, vagina, PAP smear, menstrual bleeding, menses bleeding, menstrual PAP smear, vagina, uterine, cervix,ovarian, uterus, ovaries, ovary, vaginectomy, phalloplasty, metoidioplasty, mastectomy, hysterectomy, oophorectomy hysterectomy, mastectomy, metoidioplasty, phalloplasty, vaginectomy, castration, orchiectomy, penectomy, vaginoplasty, breast augmentation, breast enlargement, enlargement, breast augmentation, breast vaginoplasty, orchiectomy, penectomy, castration, therapy silicone, voice collagen, transplant, hair electrolysis, feminization, shave, laryngeal testes, testicular, penis, penile, prostate, prostatic, PSA, scrotum, neovagina, neo-vagina, neo neo-vagina, neovagina, PSA,scrotum, prostatic, penile, prostate, penis, testicular, testes, erection sperm, vagina, android, androderm, androgel, axiron, delatestryl, depo-testosterone, striant, testim striant, testim depo-testosterone, delatestryl, axiron, androgel, androderm, android, estrogen, anti-androgen, progesterone, aldactone, avodart, cenestin, climara, cyprostat, cyprostat, climara, cenestin, aldactone, avodart, progesterone, anti-androgen, estrogen, estradiol, estrace, elestrin, enjuvia, divigel, dutasteride, delestrogen, depo-estradiol, cyproterone, premarin, medroxyprogesterone, lupron, finasteride, flutamide, estrosorb, estrogel, estroderm, premphase, prempro, propecia, proscar, prometrium, provera, spironolactone, prometrium, provera, proscar, propecia, prempro, premphase, on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only Natal sex keywords sex Natal Natal sex keywords sex Natal Procedure keywords Procedure Procedure keywords Procedure Hormonal therapy keywords therapykeywords Hormonal Hormonal therapy keywords therapykeywords Hormonal

Trans-feminine Trans-feminine Trans-masculine Trans-masculine

Table 2: Keywords used for STRONG transgender cohort natal sex assignment assignment sex natal cohort transgender used forSTRONG Keywords Table2: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 29 of 87 BMJ Open

Table 3: Data available for STRONG transgender cohort 1 2 Data categories and specific elements 3 Demographic and membership characteristics 4 Age, sex, and race/ethnicity 5 Health plan site 6 Area-based SES factors* 7 8 Enrollment/disenrollment intervals 9 Insurance plan type 10 General health indicators 11 Height/weight (BMI)* 12 Smoking status* 13 Comorbidities 14 15 Gender affirmation proceduresFor peer review only 16 CPT and/or ICD code 17 Date of procedure 18 History of gender affirmation procedures (clinical notes) 19 Pharmacy records (hormone therapy, psych medications) 20 21 Medication prescribed 22 Filled prescription for medication 23 Dose 24 Form 25 Dates of prescription and fill 26 27 Visit-associated diagnoses 28 CVD 29 Diabetes 30 HIV 31 Mental health problems

32 http://bmjopen.bmj.com/ 33 Cancer diagnoses 34 Stage 35 Site 36 Histology 37 Date of diagnosis 38 39 Laboratory results Laboratory test

40 on September 30, 2021 by guest. Protected copyright. 41 Value 42 Date 43 Vital status 44 Date of death 45 46 Cause of death 47 *Assessed at index date (date of first evidence of transgender status in EMR) 48 49 50 51 52 53 54 55 56 57 58 59 60 28

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Table 4: Characteristics of the STRONG transgender cohort 1 2 Participant Overall transgender cohort TF cohort** TM cohort** 3 characteristics n (col %) n (col %) n (col %) 4 Health plan site 5 KPNC 3842 (60) 1949 (56) 1831 (63) 6 7 KPSC 2440 (38) 1431 (41) 982 (34) 8 KPGA 174 (2.7) 95 (2.7) 79 (2.7) 9 Race/ethnicity 10 11 Non-Hispanic White 3532 (55) 1828 (53) 1669 (58) 12 Non-Hispanic Black 510 (7.9) 248 (7.1) 256 (8.9) 13 Asian 515 (8.0) 305 (8.8) 203 (7.0) 14 Hispanic 1232 (19) 710 (20) 503 (17) 15 For peer review only 16 Other/Unknown 667 (10) 384 (11) 261 (9.0) 17 Age* 587 (9.1) 337 (10) 229 (7.9) 18 3-17 years 19 20 18-25 years 1347 (21) 588 (17) 745 (26) 21 26-35 years 1431 (22) 655 (19) 753 (26) 22 36-45 years 1329 (21) 600 (17) 707 (24) 23 46-55 years 939 (15) 577 (17) 347 (12) 24 25 > 55 years 779 (12) 552 (16) 219 (7.6) 26 Smoking status* 631 (10) 503 (14) 121 (4.2) 27 Current 28 29 Former 1011 (16) 506 (15) 489 (17) 30 Never 873 (14) 461 (13) 401 (14) 31 Unknown 4029 (62) 2196 (63) 1795 (62) 32 BMI* 543 (8.4) 312 (9.0) 207 (7.2) http://bmjopen.bmj.com/ 33 34 Underweight 35 Normal Weight 150 (2.3) 96 (2.8) 52 (1.8) 36 Overweight 2404 (37) 1356 (39) 1025 (35) 37 38 Obese 1648 (26) 915 (26) 710 (25) 39 Unknown 1690 (26) 777 (22) 886 (31)

40 Medicaid status* 564 (8.7) 331 (10) 219 (7.6) on September 30, 2021 by guest. Protected copyright. 41 Yes 42 43 No 265 (4.1) 138 (4.0) 123 (4.3) 44 Unknown 6029 (93) 3251 (94) 2702 (93) 45 Census-level education status 162 (2.5) 86 (2.5) 67 (2.3) 46 47 < 30% of residents have high school or less 48 30-50% of residents have high school or less 2634 (41) 1405 (40) 1194 (41) 49 > 50% have high school or less 2233 (35) 1218 (35) 979 (34) 50 Unknown 1467 (23) 795 (23) 655 (23) 51 52 Total, n row (%) 6456 (100) 3475 (54) 2892 (45) 53 *Assessed at index date (date of first evidence of transgender status in electronic medical records) 54 **Excludes 89 persons with unknown natal sex 55 56 57 58 59 60 29

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Table 5: Gender affirmation status of the STRONG transgender cohort members 1 2 Overall TF TM 3 Gender affirmation transgender cohort cohort* cohort* 4 evidence and type n (col %) n (col %) n (col %) 5 Evidence of treatment 6 7 Any** 4040 (63) 2244 (65) 1792 (62) 8 None 2416 (37) 1231 (35) 1100 (38) 9 Cross-sex hormone therapy 10 Specific evidence at KP 3544 (55) 2030 (58) 1514 (52) 11 12 Evidence in the text only 187 (2.9) 112 (3.2) 72 (2.5) 13 No evidence 2725 (42) 1333 (38) 1306 (45) 14 Gender affirmation surgery 15 For peer review only 16 Top surgery at KP only 369 (6) 12 (0.3) 357 (12) 17 Orchiectomy at KP with or without top 52 (0.8) 52 (1.5) 0 (0) 18 Hysterectomy and/or oophorectomy at KP with or without top 311 (4.8) 0 (0) 311 (11) 19 Genital reconstruction at KP with or without other surgery 299 (4.6) 181 (5.2) 118 (4.1) 20 21 Evidence in the text only 432 (6.7) 253 (7.3) 179 (6.2) 22 No evidence 4993 (77) 2977 (86) 1927 (67) 23 Procedures to alter secondary sex characteristics 24 25 Specific evidence at KP 678 (11) 385 (11) 293 (10) 26 Evidence in the text only 58 (0.9) 52 (1.5) 6 (0.2) 27 No evidence 5720 (89) 3038 (87) 2593 (90) 28 29 Total 6456 (100) 3475 (100) 2892 (100) 30 *Excludes 89 persons with unknown natal sex 31 **Includes non-specific history and referral for treatment

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Table 6: Frequency of health outcomes in the STRONG transfeminine (TF) cohort relative to matched 1 2 comparison groups 3 Health TF cohort Reference males Reference females 4 outcomes n (col %)^ n (col %)^ n (col %)^ 5 6 Cardiovascular disease 7 Venous thromboembolism 86 (2.5) 670 (1.9) 677 (2.0) 8 Stroke 88 (2.5) 943 (2.7) 674 (2.0) 9 Myocardial infarction 61 (1.8) 664 (1.9) 319 (0.9) 10 11 Peripheral artery disease 106 (3.1) 879 (2.6) 645 (1.9) 12 Unstable angina 64 (1.8) 656 (1.9) 336 (1.0) 13 Mental health* 14 Anxiety 1337 (38) 4323 (13) 7485 (22) 15 For peer review only 16 Depression 1705 (49) 4721 (14) 8726 (25) 17 Self-inflicted injury** 75 (2.2) 100 (0.3) 204 (0.6) 18 Suicidal ideation 175 (5.0) 157 (0.5) 194 (0.6) 19 20 Substance abuse disorder 524 (15) 2860 (8.3) 1680 (4.9) 21 Cancer primary site 22 Colorectum 10 (0.3) 107 (0.3) 91 (0.3) 23 24 Lung and bronchus 9 (0.3) 58 (0.2) 59 (0.2) 25 Lymphatic and hematopoietic 22 (0.6) 168 (0.5) 106 (0.3) 26 Melanoma 10 (0.3) 227 (0.7) 180 (0.5) 27 Prostate 25 (0.7) 451 (1.3) 0 (0.0) 28 29 Other chronic conditions* 30 HIV*** 186 (5.4) 190 (0.6) 15 (0.0) 31 Diabetes 313 (9.0) 3358 (9.8) 2619 (7.6)

32 http://bmjopen.bmj.com/ 33 Vital status 34 Alive 3372 (97) 33562 (98) 33839 (98) 35 Dead 103 (3.0) 818 (2.4) 551 (1.6) 36 37 Total 3475 (100) 34380 (100) 34390 (100) 38 *Based on at least 2 diagnoses in the EMR 39 **Combined diagnoses of self-inflicted injury, self-inflicted injury/poisoning, and possible

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Table 7: Frequency of health outcomes in the STRONG transmasculine (TM) cohort relative to 1 2 comparison groups 3 Health TM cohort Reference males Reference females 4 outcomes n (col %)^ n (col %)^ n (col %)^ 5 6 Cardiovascular disease 7 Venous thromboembolism 45 (1.6) 266 (0.9) 356 (1.2) 8 Stroke 42 (1.5) 360 (1.3) 250 (0.9) 9 Myocardial infarction 17 (0.6) 210 (0.7) 88 (0.3) 10 11 Peripheral artery disease 38 (1.3) 309 (1.1) 242 (0.8) 12 Unstable angina 20 (0.7) 215 (0.8) 123 (0.4) 13 Mental health* 14 Anxiety 1323 (46) 3583 (13) 6089 (21) 15 For peer review only 16 Depression 1594 (55) 3806 (13) 6813 (24) 17 Self-inflicted injury** 121 (4.2) 109 (0.4) 181 (0.6) 18 Suicidal ideation 193 (6.7) 160 (0.6) 186 (0.7) 19 20 Substance abuse disorder 418 (14) 2391 (8.4) 1523 (5.3) 21 Cancer primary site 22 Breast 20 (0.7) 217 (0.8) 23 24 Cervix 7 (0.2) 0 (0.0) 172 (0.6) 25 Melanoma 8 (0.3) 109 (0.4) 71 (0.2) 26 Other chronic conditions* 27 HIV*** 9 (0.3) 117 (0.4) 10 (0.0) 28 29 Diabetes 153 (5.3) 1329 (4.7) 1213 (4.2) 30 Vital status 31 Alive 2853 (99) 28237 (99) 28366 (99)

32 http://bmjopen.bmj.com/ 33 Dead 39 (1.3) 283 (1.0) 183 (0.6) 34 Total 2892 (100) 28520 (100) 28549 (100) 35 *Based on at least 2 diagnoses in the EMR 36 **Combined diagnoses of self-inflicted injury, self-inflicted injury/poisoning, and 37 38 possible self-inflicted injury 39 *** HIV status ascertained from disease registries in KPNC and KPSC and from 2 or

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1 2 FIGURE LEGENDS 3 4 Figure 1: STRONG transgender cohort ascertainment flow diagram 5 6 7 Figure 2: Results of STRONG transgender cohort ascertainment and validation 8 9 10 11 Figure 3: Prevalence of transgender status by site and year of health plan enrollment 12 Dotted lines represent linear trends 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

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40 on September 30, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 33

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 Figure 1: STRONG transgender cohort ascertainment flow diagram 27 28 338x190mm (300 x 300 DPI) 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 Figure 2: Results of STRONG transgender cohort ascertainment and validation 27 28 338x190mm (300 x 300 DPI) 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 Figure 3: Prevalence of transgender status by site and year of health plan enrollment. Dotted lines 27 represent linear trends 28 29 30 338x190mm (300 x 300 DPI) 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 30, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 38 of 87 54569-6607-0 69189-0298-1 54868-6133-0 63629-5321-1 54868-4503-0 63672-0005-0 69189-0712-1 60505-2642-1 68084-612-11 0904-6019-46 42291-168-30 0173-0712-02 60429-177-01 60429-226-05 51991-560-01 65841-613-01 67253-191-03 0378-7017-93 16714-571-01 47335-485-08 0093-0220-01 68382-224-01 0025-1001-31 16729-023-01 0781-5409-01 41616-485-08 NDC Codes 35356-210-30 0310-0705-10 59212-111-10 24987-111-14 0088-1111-14

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Page 39 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 40 of 87 54868-6056-0 54868-4811-0 0781-7129-40 54569-4908-0 54569-4907-0 69189-0886-1 0245-0880-30 68025-065-01 0378-4640-16 0378-3349-16 69761-022-01 69761-012-01 69761-020-01 69761-006-01 69761-018-01 69761-010-01 69761-025-01 69761-015-01 65162-226-21 0555-0886-02 23155-013-01 0378-1452-01 0591-0487-01 50268-290-11 43063-201-01 47781-204-04 33261-667-30 0083-2310-08 0169-1842-81 17089-359-18 3 http://bmjopen.bmj.com/ BMJ Open , film coated , film 51285-406-02 on September 30, 2021 by guest. Protected copyright. (estradiol) patch ns, b) tablet [Repackaged] 54868-6163-0 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml ol) solution/ drops For peer review only ted estrogens, b) tablet blet [Repackaged] blet [Repackaged] ESTRADIOL patch [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL (estradiol) ta ESTRADIOL (estradiol) ta Innofem (Estradiol) tablet, film coated (Estradiol) tablet, film Innofem DIVIGEL (estradiol) gel [Repackaged] GUNA-BETA-ESTRADIOL (estradi ENJUVIA (synthetic conjugated estroge ESTRACE (estradiol) cream ESTRACE (estradiol) tablet gel DIVIGEL (estradiol) gel DIVIGEL (estradiol) (estradiol) patc h, extended release estraderm ESTRADIOL patch ESTRADIOL patch ESTRADIOL patch, extended release 0430-3754-14 0430-0720-24 ENJUVIA (synthetic conjuga ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL tablet ESTRADIOL tablet ESTRADIOL tablet ESTRADIOL tablet ESTRADIOL tablet ESTRADIOL TRANSDERMAL SYSTEM

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 51991-474-28 acetate) tablet, film 4 http://bmjopen.bmj.com/ BMJ Open and norethindrone on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml coated [Repackaged] 54868-6182-0

For peer review only radiol) powder 62157-007-02 radiol,) liquid 44911-0199-1 ESTROGEN PHENOLIC (est MENOSTAR (estradiol) patch [Repackaged] tablet, film VAGIFEM (estradiol) VIVELLE DOT - estradiol patch, extended release [Repackaged] ESTRADIOL / NORETHINDRONE ACETATE (estradiol coated 54868-4242-0 50419-455-04 ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] 69189-0487-1 ESTRADIOL tablet [Repackaged] 69189-0899-1 ESTRADIOL tablet [Repackaged] 10544-069-30 ESTRADIOL tablet [Repackaged] 63629-2766-1 ESTRADIOL tablet [Repackaged] 63629-4788-1 AX PHARMACEUTICAL (est 63629-3755-1 63629-5208-1 55154-6242-0 61919-278-30 61919-198-30 60429-327-01 0179-0123-70 0179-0073-70 0179-1999-01 49999-083-30 43063-446-01 43063-651-30 55289-761-01 55289-603-07 54868-4030-0 68788-9901-1 68788-9416-1 63187-482-30 64205-048-30 21695-613-00 16590-278-30 16590-052-71

Page 41 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 42 of 87 0430-0535-14 52544-175-72 50102-128-01 68180-865-11 52544-236-31 0378-7283-53 0378-7301-53 0430-0539-14 54868-4677-0 0430-0420-14 0093-3122-28 0430-0530-14 68180-864-11 0603-7609-01 0093-5328-28 52544-054-31 68462-132-79 0378-7280-53 68462-656-29 68180-827-09 0603-7607-02 68180-866-11 0603-7606-02 acetate) tablet, film fumarate) kit [Repackaged] fumarate) 54868-6100-0 5 estradiol and ferrous fumarate) ferrous fumarate) kit ferrous fumarate) http://bmjopen.bmj.com/ BMJ Open rrous fumarate) rrous fumarate) 0603-7610-01 ferrous fumarate) kit ferrous fumarate) kit ferrous fumarate) 0430-0570-14 0430-0005-31 ferrous fumarate) kit ferrous fumarate) 0603-7608-01 nd ferrous fumarate) kit nd ferrous fumarate) tablet ferrous fumarate) kit ferrous fumarate) kit ferrous fumarate) kit ferrous fumarate) blet, film coated blet, film tablet, film coated tablet, film OL ( norethindrone acetate and ethinyl OL ( norethindrone acetate and ethinyl et, film coated et, film iol) kit and norethindrone ADIOL AND FERROUS FUMARATE ('', estradiol) ESTRADIOL tablet ESTRADIOL tablet ESTRADIOL tablet on September 30, 2021 by guest. Protected copyright. hinyl estradiol and fe nd ethinyl estradiol) and ethinyl estradiol) kit estradiol) kit and ethinyl and ethinyl estrad and ethinyl estradiol, ferrous ate and ethinyl estradiol, and ate and ethinyl and ethinyl estradiol) kit acetate and ethinyl estradiol and ferrous fumarate) kit ferrous fumarate) and estradiol acetate and ethinyl 52544-167-31 hinyl estradiol) tablet hinyl tate and ethinyl estradiol, a ethinyl estradiol) kit estradiol) kit ethinyl For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml ate and ethinyl estradiol ate and ethinyl estradiol te and ethinyl estradiol) ta and ethinyl estradiol) tabl estradiol) and ethinyl te and ethinyl estradiol For peer review only kit estradiol, and fe rrous fumarate) and ethinyl one acetate and ethinyl one acetate and ethinyl estradiol) TARINA FE 1/20 (norethindr TILIA FE (norethindrone acetate and TILIA FE (norethindrone LOESTRIN 24 FE (norethindrone acetate BLISOVI FE 1/20 (norethindrone acetate BLISOVI 24 FE (norethindrone acetate acetate FYAVOLV (norethindrone GILDESS 1/20 (norethindrone aceta JEVANTIQUE LO (norethindrone acetate a acetate and et JINTELI (norethindrone GILDESS 1.5/30 (norethindr NORETHINDRONE ACETATE AND ETHINYL NORETHINDRONE ACETATE AND ETHINYL acetate TILIA FE (norethindrone BLISOVI FE 1.5/30 (norethindrone acetate BLISOVI FE 1.5/30 (norethindrone NORETHINDRONE ACETATE AND ETHINYL ESTRADI ) kit estradiol NORETHINDRONE ACETATE AND ETHINYL ESTR kit and '') and '', NORETHINDRONE ACETATE AND ETHINYL ESTROSTEP FE (norethindrone acet GILDESS 24 FE (norethindrone acetate and et NORETHINDRONE ACETATE AND ETHINYL ESTRADI ) kit estradiol coated [Repackaged] ESTROSTEP FE (norethindrone acet and acetate, ethinyl estradiol GILDESS FE 1.5/30 (norethindrone ethinyl estradiol and GILDESS FE 1/20 (norethindrone acetate, JUNEL FE 24 (norethindrone aceta LO LOESTRIN FE (norethindrone acetate and ethinyl estradiol, kit LOESTRIN 24 FE (norethindrone ace MICROGESTIN 24 FE (norethindrone MINASTRIN acet 24 FE (norethindrone ESTRADIOL / NORETHINDRONE ACETATE (estradiol

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 54868-5326-0 0378-7277-53 52544-233-28 54868-6274-0 54868-6213-0 68180-838-11 54868-6251-0 16714-407-01 16714-416-01 68462-309-29 68462-565-29 68462-719-29 65162-316-58 50458-251-00 16714-406-01 21695-685-28 0430-0537-14 0430-0540-50 0555-9032-70 54868-4744-0 0555-9026-58 16714-405-01 52544-247-28 0555-9027-42 0555-9028-58 16714-408-01 52544-143-31 0555-9025-42 adiol) kit fumarate) kit [Repackaged] fumarate) 54868-6272-0 kit [Repackaged] fumarate) 42254-242-28 6 fumarate) kit [Repackaged] fumarate) 54868-5935-0 http://bmjopen.bmj.com/ BMJ Open fumarate) kit ferrous fumarate) kit ferrous fumarate) ethinyl estradiol and ferrous and ethinyl estradiol l and ferrous fumarate) kit l and ferrous fumarate) kit tablet [Repackaged] imate and ethinyl estradiol ) kit imate imate and ethinyl estr imate tablet [Repackaged] iol and ferrous fumarate) kit iol and ferrous fumarate) estradiol) on September 30, 2021 by guest. Protected copyright. estradiol and ferrous hinyl estradiol) tablet / kit estradiol and ferrous fumarate) kit estradiol and ferrous fumarate) estradiol) tablet [Repackaged] estradiol) tablet [Repackaged] and ethinyl estradiol) kit and ethinyl estradiol) kit e and ethinyl estradiol chewable tablets and ferrous fumarate ferrous fumarate and tablets estradiol chewable e and ethinyl and ethinyl estradiol, ferrous and ethinyl estradiol, ferrous and ethinyl estradiol, ferrous thinyl estradiol) kit nd ethinyl estradiol) tablet ate and ethinyl estradiol, ethinyl estradiol) kit estradiol) kit ethinyl For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml tate and ethinyl estradiol) etate/ethinyl estrad ferrous fumarate) kit ate and ethinyl estradiol, ferrous fumarate) acetate and ethinyl estradio acetate and ethinyl For peer reviewte and ethinyl estradiol) only ate and ethinyl estradiol) kit [Repackaged] estradiol) kit ate and ethinyl ate and ethinyl estradiol) kit [Repackaged] estradiol) kit ate and ethinyl one acetate and ethinyl ndrone acetate/ethinyl JUNEL 1.5/30 (norethindrone acetate a JUNEL FE 1.5/30 (norethindrone acet ethinyl estradiol) tablet estradiol) acetate and ethinyl JUNEL 1/20 (norethindrone JUNEL FE 1/20 (norethindrone acet LARIN 1.5/30 (norethindrone acetate/e estradiol) kit acetate/ ethinyl LARIN 1/20 (norethindrone LARIN 24 FE (norethindrone acetate/ethinyl LARIN FE 1/20 (norethi estradiol, acetate and ethinyl LO MINASTRIN FE (norethindrone kit fumarate) LOMEDIA 24 FE (norethindr LARIN FE 1.5/30 (norethindrone ac MICROGESTIN (norethindrone acetate and et MINASTRIN acetat 24 FE (norethindrone kit tablets) acetate and TILIA FE (norethindrone TRI-LEGEST FE 28 DAY (norethindrone aceta te and ethinyl estr adiol) kit acetate and ethinyl JINTELI (norethindrone TILIA FE (norethindrone acet TILIA FE (norethindrone MONONESSA / TRINESSA (norgestimate NORGESTIMATE AND ETHINYL ESTRADIOL ( norgest JUNEL 1.5/30 (norethindrone aceta JUNEL FE 1/20 (norethindrone acetate JUNEL FE 1.5/30 (norethindrone acetate JUNEL FE 1.5/30 (norethindrone acetate MICROGESTIN FE (norethindrone [Repackaged] NORGESTIMATE AND ETHINYL ESTRADIOL kit MICROGESTIN (norethindrone ace acet TILIA FE (norethindrone NORGESTIMATE AND ETHINYL ESTRADIOL (norgest NORGESTIMATE AND ETHINYL ESTRADIOL kit ORTHO TRI CYCLEN LO (norgestimate ORTHO TRI CYCLEN LO (norgestimate NORGESTIMATE AND ETHINYL ESTRADIOL kit

Page 43 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 44 of 87

21695-407-01 54868-5028-0 0013-2150-36 63539-021-01 21695-769-28 0781-4058-15 0555-9018-58 0781-4062-15 16714-360-01 63187-458-28 21695-770-01 76413-128-28 66116-436-28 0083-2310-08 16714-363-01 65862-777-28 0781-4060-15 76413-121-28 57297-837-11 68180-837-11 17139-613-50 0555-9016-58 50458-191-00 65862-776-28 69238-1551-6 0603-7642-01 7 http://bmjopen.bmj.com/ BMJ Open l) kit [Repackaged] 54868-4093-0 kit l) kit ) kit ) kit kit 63187-054-28 kit kit on September 30, 2021 by guest. Protected copyright. kit and ethinyl estradio nyl estradiol) kit nd ethinyl estradiol) kit 54868-4730-0 estradiol) kit [Repackaged] estradiol) kit [Repackaged] estradiol) kit [Repackaged] estradiol) kit [Repackaged] estradiol) kit [Repackaged] estradiol) kit [Repackaged] estradiol) kit [Repackaged] estradiol) kit [Repackaged] estradiol) kit [Repackaged] ethinyl estradiol) tradiol) kit [Repackaged] nyl estradiol) kit tradiol) kit [Repackaged] ethinyl estradiol) kit 0093-2140-28 nd ethinyl estradio nyl estradiol) kit ethinyl estradiol ethinyl estradiol nyl estradiol) l estradiol) kit For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml l estradiol) kit nded release [Repackaged] ethinyl estradiol) kit 52544-087-28 nyl estradiol) kit 54868-5826-0 nyl estradiol) hinyl estradiol) kit 52544-248-28

Forl estradiol) kit peer review only nd ethinyl estradiol) kit [Repackaged] ESTROGEL (estradiol) gel, metered ESTROGEL (estradiol) gel, metered TRINESSA (norgestimate and et TRINESSA (norgestimate and TRINESSA LO (norgestimate and ethi MONONESSA (norgestimate PREFEST- estradiol/norgestimate PREFEST- estradiol/norgestimate and TRI-LO-SPRINTEC (norgestimate 51285-063-90 ORTHO TRI CYCLEN LO (norgestimate a ORTHO TRI CYCLEN LO (norgestimate and ethi TRINESSA (norgestimate and ethinyl estradiol) ESTARYLLA (norgestimate MILI (norgestimate and ethiny MILI (norgestimate and ethi MONO-LINYAH (norgestimate and et hinyl estradiol) kit TRI-ESTARYLLA (norgestimate FEMYNOR (norgestimate and ethiny FEMYNOR (norgestimate a ORTHO TRI CYCLEN (norgestimate TRI-SPRINTEC (norgestimate and ethinyl TRI-SPRINTEC (norgestimate a TRINESSA (norgestimate ESTRADERM- estradiol patch, exte TRI-SPRINTEC (norgestimate and ethinyl TRI-SPRINTEC (norgestimate ESTRING (estradiol) ring ESTRING (estradiol) ring TRI-SPRINTEC (norgestimate and ethinyl TRI-SPRINTEC (norgestimate and ethinyl TRI-SPRINTEC (norgestimate TRI-LINYAH (norgestimate and ethinyl estradiol) TRI-LINYAH (norgestimate TRI-LO- ESTARYLLA (norgestimate and TRI-LO- ESTARYLLA (norgestimate and TRI-LO-MARZIA ( norgestimate and TRI-LO-MARZIA ( norgestimate and ethi TRI-MILI (norgestimate and ethi TRI-SPRINTEC (norgestimate and ethi ORTHO TRI CYCLEN (norgestimate and ethinyl es SPRINTEC (norgestimate and ethinyl TRI-SPRINTEC (norgestimate SPRINTEC (norgestimate and ethiny SPRINTEC (norgestimate PREVIFEM / TRI-PREVIFEM (norgestimate PREVIFEM / TRI-PREVIFEM (norgestimate PREVIFEM (norgestimate and ethinyl es PREVIFEM (norgestimate

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 29336-325-56 99207-190-56 0172-4960-58 49884-753-05 0591-2466-18 60429-272-05 69097-112-02 55111-172-01 65977-5025-0 8 http://bmjopen.bmj.com/ BMJ Open TERONE tablet, film coated TERONE tablet, film coated TERONE tablet, film 13925-171-01 50220-001-01 on September 30, 2021 by guest. Protected copyright. TESTOSTERONE tablet TESTOSTERONE tablet 53746-077-01 62559-149-01 ltestosterone) tablet, coated 15310-010-01 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml tablet, film coated tablet, film 61570-072-01 For peer) tablet [Repackaged] review only 54868-5934-0 oophorinum) liquid oophorinum) liquid oophorinum) liquid oophorinum) liquid oophorinum) liquid oophorinum) 57520-0860-1 43857-0074-1 43857-0150-1 57520-0094-1 43742-0066-1 ESTERIFIED ESTROGENS AND METHYL ESTERIFIED ESTROGENS AND METHYLTESTOS ESTERIFIED ESTROGENS AND METHYLTESTOS ESTROGEN (folliculinum, ESTROGEN (folliculinum, ESTROGEN (folliculinum, ESTROGEN (folliculinum, ESTROGEN (folliculinum, EEMT (estrogens, esterified and methy MENEST (esterified estrogens) MENEST (estrogens, esterified ESTRASORB ESTRASORB EVAMIST (estradiol) spray EVAMIST (estradiol) spray, metered [Repackaged] EVAMIST (estradiol) spray, metered FLUTAMIDE capsule FLUTAMIDE capsule FLUTAMIDE capsule FLUTAMIDE capsule FINASTERIDE tablet FINASTERIDE tablet FINASTERIDE tablet coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film 54868-6157-0 64011-215-41 0574-2067-00 16729-090-01 16729-089-10 45963-600-03 45963-500-02 65862-686-30 65862-149-01 31722-525-01 31722-525-01 31722-526-10 ESTROGEL (estradiol) gel, metered ESTROGEL (estradiol) gel, metered ESTERIFIED ESTROGENS AND METHYL 17139-617-20

Page 45 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 46 of 87 58118-7355-0 54569-6048-0 17856-0090-1 69189-0090-1 63629-5220-1 63629-1585-1 55154-5685-0 68788-9519-3 42291-280-50 68084-919-11 43598-390-30 68084-399-01 50268-323-11 33261-833-90 43598-303-30 0179-0175-88 52125-403-02 9 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only FINASTERIDE tablet, film coated [Repackaged] FINASTERIDE tablet, film coated [Repackaged] FINASTERIDE tablet, film coated [Repackaged] FINASTERIDE tablet, film FINASTERIDE tablet [Repackaged] FINASTERIDE tablet [Repackaged] FINASTERIDE tablet [Repackaged] FINASTERIDE tablet [Repackaged] FINASTERIDE tablet [Repackaged] FINASTERIDE tablet [Repackaged] coated [Repackaged] FINASTERIDE tablet, film coated [Repackaged] FINASTERIDE tablet, film coated [Repackaged] FINASTERIDE tablet, film coated [Repackaged] FINASTERIDE tablet, film coated [Repackaged] FINASTERIDE tablet, film coated [Repackaged] FINASTERIDE tablet, film coated [Repackaged] FINASTERIDE tablet, film coated [Repackaged] FINASTERIDE tablet, film FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated [Repackaged] FINASTERIDE (finasteride) tablet, film 57237-062-05 57237-061-30 55111-171-05 76282-412-05 68554-3025-0 68554-3026-0 50742-123-30 63739-495-40 51079-321-01 51079-520-01 0378-5036-01 58517-200-30 16714-522-10 0603-3633-02 47335-715-08 47335-714-08 0093-7355-05

Page 47 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 48 of 87 68258-5978-2 sugar coated 0046-1105-11 11 http://bmjopen.bmj.com/ BMJ Open acetate) kit, tablet, erone acetate) tablet, sugar coated erone acetate) tablet, 54868-3799-0 sterone acetate) tablet, sugar coated sterone acetate) tablet, ogesterone acetate) kit [Repackaged] 54868-3800-0 on September 30, 2021 by guest. Protected copyright. powder, lyophilized, for solution 0046-0749-05 tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] 69189-3741-1 tablet [Repackaged] 10544-001-30 tablet [Repackaged] 63629-2613-1 tablet [Repackaged] 63629-2614-1 tablet [Repackaged] 63629-2612-1 55154-0533-0 66336-603-20 55289-160-05 55289-816-30 54868-0109-0 68788-9899-1 64205-077-10 21695-896-10 52125-803-08 49349-287-02 52125-562-08 49349-287-08 et, film coated [Repackaged] et, film coated [Repackaged] et, film coated [Repackaged] et, film coated [Repackaged] et, film coated [Repackaged] et, film coated [Repackaged] et, film 55154-0216-0 54868-0365-0 53808-0770-1 54569-0812-0 54569-0811-3 69189-1105-1 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml tablet, film coated tablet, film 0046-1100-51 For peer review d estrogens) cream only 0046-0872-04 PREMPRO (conjugated estrogens and medroxyproge and estrogens PREMPRO (conjugated MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE PREMARIN (conjugated estrogens) injection, PREMARIN (estrogens, conjugated) PREMARIN VAGINAL (conjugate coated [Repackaged] PREMARIN (conjugated estrogens) tablet, film PREMARIN (conjugated estrogens) tabl coated [Repackaged] PREMARIN (conjugated estrogens) tablet, film coated [Repackaged] PREMARIN (conjugated estrogens) tablet, film PREMARIN (conjugated estrogens) tabl PREMARIN (conjugated estrogens) tabl PREMARIN (conjugated estrogens) tabl PREMARIN (conjugated estrogens) tabl PREMARIN (conjugated estrogens) tabl and medroxyprogesterone PREMPHASE (conjugated estrogens and medroxypr PREMPHASE (conjugated estrogens 43353-687-60 [Repackaged] medroxyprogest and estrogens PREMPRO (conjugated 35356-249-00 49999-109-00 MEDROXYPROGESTERONE ACETATE

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 12 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml gesterone) spray gesterone) spray 57520-0318-1 43857-0084-1 For peer review only erone) liquid erone,) liquid 55714-6634-1 57520-0301-1 et, film coated et, film 0006-0072-31 ) tablet, film coated [Repackaged] ) tablet, film coated [Repackaged] ) tablet, film 63629-1603-1 54868-4120-0 one) gel 55056-0806-2 ride) tablet, film coated ride) tablet, film 0006-0071-07 NATURAL PROGESTERONE (pro NATURAL PROGESTERONE (pro PROCHIEVE (progesterone) gel PROGESTERONE (progest PROGESTERONE (progest PROGESTERONE capsule PROGESTERONE capsule PROGESTERONE capsule PROGESTERONE capsule PROGESTERONE capsule PROGESTERONE capsule PROGESTERONE capsule PROGESTERONE injection PROGESTERONE injection, solution PROGESTERONE injection, solution PROGESTERONE injection, solution PROGESTERONE liquid PROGESTERONE liquid PROGESTERONE liquid PROGESTERONE liquid PROGESTERONE capsule [Repackaged] PROGESTERONE capsule [Repackaged] X (progesterone) powder PROPECIA (finaste PROPECIA (finasteride 55056-0406-1 PROPECIA (finasteride PROSCAR- finasteride tabl PROMETRIUM (progesterone) capsule PROMETRIUM (progesterone) capsule [Repackaged] PROMETRIUM (progesterone) capsule [Repackaged] 17478-766-10 PROMETRIUM (progesterone) capsule [Repackaged] 42291-690-01 PROMETRIUM (progesterone) capsule [Repackaged] 69387-101-01 10888-7135-2 11014-0189-1 0591-3128-79 0093-5353-01 0517-0750-01 0591-3964-01 0143-9725-01 63323-261-10 60429-281-01 43857-0120-1 43063-649-30 43857-0103-1 43742-0762-1 43742-0158-1 69189-1708-1 63629-2770-1 63629-2767-1 54868-4230-0 62157-217-01 0032-1708-01 [Repackaged] CRINONE (progester

Page 49 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 50 of 87 50268-726-11 50090-0136-0 69189-0511-1 63629-1830-1 55154-1495-0 68788-9729-3 68788-9124-3 53808-0979-1 59746-216-01 10544-499-90 10544-523-30 63739-544-04 63739-416-10 43063-072-01 21695-766-30 52125-978-02 49349-563-28 52125-603-02 49349-680-02 52125-584-02 49349-563-02 52125-866-02 60760-981-30 59762-5011-1 0378-0243-01 0603-5763-21 0781-1599-01 53489-328-01 0228-2672-11 0904-5951-61 53489-143-01 65162-511-03 53746-511-01 13 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. tablet [Repackaged] For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml acetate) tablet For peer review 0009-0050-02 only film coated film coated film coated film film coated film coated film SPIRONOLACTONE (spironolactone) SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet, film coated SPIRONOLACTONE tablet, film SPIRONOLACTONE tablet, SPIRONOLACTONE tablet, SPIRONOLACTONE tablet, SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet SPIRONOLACTONE tablet, SPIRONOLACTONE tablet, SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE (spironolactone) tablet, film coated SPIRONOLACTONE tablet SPIRONOLACTONE tablet SPIRONOLACTONE tablet PROVERA (medroxyprogesterone PROVERA (medroxyprogesterone SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged]

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 53808-0338-1 54868-0700-0 68788-9227-3 50436-5015-0 50436-4477-2 54569-0505-0 63629-4094-1 63629-5341-1 55154-5055-0 68151-2776-1 55289-507-01 43063-277-30 63187-634-30 42254-183-30 21695-960-60 52125-418-02 51079-103-01 0615-1535-05 0615-8031-05 51655-838-52 33261-764-30 68084-206-01 55700-305-30 35356-969-30 76237-246-30 66336-916-30 35356-419-00 68084-946-11 51079-104-01 59762-5014-1 53489-144-01 0378-0141-01 14 http://bmjopen.bmj.com/ BMJ Open IDE tablet, film coated IDE tablet, film AZIDE tablet [Repackaged] AZIDE tablet [Repackaged] on September 30, 2021 by guest. Protected copyright. OTHIAZIDE tablet OTHIAZIDE tablet OTHIAZIDE tablet For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film SPIRONOLACTONE AND HYDROCHLOR SPIRONOLACTONE AND HYDROCHLOR SPIRONOLACTONE AND HYDROCHLOROTHIAZ SPIRONOLACTONE AND HYDROCHLOROTHI SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film SPIRONOLACTONE AND HYDROCHLOROTHI SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film SPIRONOLACTONE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] coated [Repackaged] SPIRONOLACTONE tablet, film 53808-0796-1 50436-9973-1 SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film

Page 51 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 52 of 87 68788-9227-6 68554-3026-1 68554-3025-1 68382-224-05 68462-719-84 68462-309-84 68180-865-13 68788-9124-6 69761-025-12 69761-022-12 69761-020-12 69761-018-12 69761-015-12 69761-012-12 69761-010-12 69761-006-12 69097-112-05 68258-5980-2 68462-656-90 68462-132-81 68180-866-13 15 http://bmjopen.bmj.com/ BMJ Open iol) kit sterone acetate) tablet, sugar coated sterone acetate) tablet, AZIDE tablet [Repackaged] 54868-0699-1 ESTRADIOL tablet ESTRADIOL tablet on September 30, 2021 by guest. Protected copyright. tablet [Repackaged] 68788-9899-3 and ethinyl estradiol) kit estradiol) kit and ethinyl OROTHIAZIDE tablet, film coated [Repackaged] OROTHIAZIDE tablet, film 54569-0502-0 and ethinyl estrad For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet PROGESTERONE capsule SPIRONOLACTONE tablet [Repackaged] FINASTERIDE tablet ESTRADIOL tablet [Repackaged] MEDROXYPROGESTERONE ACETATE SPIRONOLACTONE tablet [Repackaged] FINASTERIDE tablet [Repackaged] coated [Repackaged] FINASTERIDE tablet, film ESTRADIOL tablet [Repackaged] coated [Repackaged] FINASTERIDE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film SPIRONOLACTONE tablet [Repackaged] coated FINASTERIDE tablet, film 69189-0511-5 69387-102-01 68788-9517-3 68788-9729-6 68788-9901-3 68788-9249-6 68788-9519-6 68788-9416-3 SPIRONOLACTONE AND HYDROCHLOROTHI SPIRONOLACTONE AND HYDROCHL coated FINASTERIDE tablet, film ESTRADIOL pellet 76282-412-10 NORGESTIMATE AND ETHINYL ESTRADIOL kit coated BICALUTAMIDE tablet, film FINASTERIDE tablet, film coated FINASTERIDE tablet, film NORGESTIMATE AND ETHINYL ESTRADIOL kit PREMPRO (conjugated estrogens and medroxyproge and estrogens PREMPRO (conjugated [Repackaged] NORETHINDRONE ACETATE AND ETHINYL NORETHINDRONE ACETATE AND ETHINYL acetate BLISOVI FE 1.5/30 (norethindrone BLISOVI FE 1/20 (norethindrone acetate

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 63629-5321-2 63629-5220-2 68084-612-21 68180-837-13 64980-224-09 64380-763-05 67253-191-10 65841-613-05 68084-206-11 66336-916-60 65162-316-84 68084-919-21 68084-399-11 65862-686-90 65862-149-05 63739-495-41 65862-777-85 68025-065-07 68025-065-07 65977-5025-1 65162-226-23 63629-5208-2 63629-4788-2 68084-946-21 64205-087-30 65862-776-85 63739-544-10 64205-048-90 64011-215-42 68180-827-11 65162-750-09 65162-511-06 iol) kit 68180-838-13 16 http://bmjopen.bmj.com/ BMJ Open kit ate and ethinyl estrad et, film coated et, film kit estradiol) AZIDE tablet [Repackaged] on September 30, 2021 by guest. Protected copyright. kit tablet [Repackaged] and ethinyl estradiol) kit 68180-864-13 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml and ethinyl estradiol) tabl estradiol) and ethinyl nyl estradiol)

For peerl estradiol) kit review only one acetate and ethinyl FINASTERIDE tablet, film coated [Repackaged] FINASTERIDE tablet, film NORGESTIMATE AND ETHINYL ESTRADIOL (norgestim estradiol ) and ethinyl TRI-LO-MARZIA ( norgestimate acetate FYAVOLV (norethindrone SPIRONOLACTONE AND HYDROCHLOROTHI BICALUTAMIDE tablet [Repackaged] BLISOVI 24 FE (norethindrone acetate FINASTERIDE tablet, film coated FINASTERIDE tablet, film MILI (norgestimate and ethiny MILI (norgestimate coated FINASTERIDE tablet, film FINASTERIDE tablet, film coated [Repackaged] FINASTERIDE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film DIVIGEL (estradiol) gel gel DIVIGEL (estradiol) coated BICALUTAMIDE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film FINASTERIDE tablet and ethi TRI-MILI (norgestimate EVAMIST (estradiol) spray, metered EVAMIST (estradiol) spray, metered SPIRONOLACTONE tablet [Repackaged] FINASTERIDE tablet, film coated FINASTERIDE tablet, film BICALUTAMIDE tablet, film coated BICALUTAMIDE tablet, film DUTASTERIDE capsule SPIRONOLACTONE tablet LOMEDIA 24 FE (norethindr ESTRADIOL tablet DUTASTERIDE capsule, liquid filled DUTASTERIDE capsule, liquid filled MEDROXYPROGESTERONE ACETATE ESTRADIOL tablet [Repackaged] BICALUTAMIDE tablet [Repackaged] coated [Repackaged] FINASTERIDE tablet, film ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged]

Page 53 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 54 of 87 62112-8068-2 60505-3877-9 58118-7355-3 60505-2642-3 57297-837-13 60429-226-30 60429-177-05 59762-3740-5 63187-634-60 55289-507-30 57237-062-30 57237-061-90 59762-4537-2 60429-282-01 60429-272-18 61570-073-01 59746-216-05 60687-105-21 55289-160-07 55289-908-42 60760-981-90 63187-482-60 60429-328-01 55289-603-21 55289-761-30 59762-5011-2 62559-150-01 59212-111-14 17 http://bmjopen.bmj.com/ BMJ Open kit on September 30, 2021 by guest. Protected copyright. TESTOSTERONE tablet tablet [Repackaged] tablet [Repackaged] 63629-2613-2 63629-2612-2 tablet [Repackaged] injection, suspension tablet [Repackaged] tablet [Repackaged] For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml ETATE tablet

For coated tablet, film peer review only ESTERIFIED ESTROGENS AND METHYL DUTASTERIDE capsule, liquid filled MEDROXYPROGESTERONE ACETATE SPIRONOLACTONE tablet [Repackaged] coated [Repackaged] FINASTERIDE tablet, film DUTASTERIDE capsule [Repackaged] coated [Repackaged] SPIRONOLACTONE tablet, film ESTRADIOL tablet [Repackaged] MENEST (esterified estrogens) SPIRONOLACTONE tablet [Repackaged] 63629-1585-2 63629-1830-2 63187-657-60 ESTRADIOL tablet [Repackaged] MEDROXYPROGESTERONE ACETATE 63629-3755-2 MEDROXYPROGESTERONE ACETATE coated [Repackaged] BICALUTAMIDE tablet, film DUTASTERIDE capsule, liquid filled BICALUTAMIDE tablet PROGESTERONE capsule [Repackaged] FLUTAMIDE capsule coated [Repackaged] BICALUTAMIDE tablet, film ESTRADIOL tablet [Repackaged] SPIRONOLACTONE tablet, film coated SPIRONOLACTONE tablet, film MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE AC SPIRONOLACTONE (spironolactone) tablet, film coated tablet NILANDRON (nilutamide) coated [Repackaged] FINASTERIDE tablet, film estradiol ) and ethinyl TRI-LO-MARZIA ( norgestimate coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film MEDROXYPROGESTERONE ACETATE ESTRADIOL tablet [Repackaged] MEDROXYPROGESTERONE ACETATE ESTRADIOL tablet [Repackaged]

For) tablet [Repackaged] peer review only film coated film ugated estrogens, a tablet ) tablet, film coated [Repackaged] ) tablet, film one) gel MEDROXYPROGESTERONE ACETATE SPIRONOLACTONE AND HYDROCHLOR MEDROXYPROGESTERONE ACETATE ESTRADIOL tablet [Repackaged] PREMARIN (conjugated estrogens) tabl PREMPRO (conjugated estrogens and medroxyproge and estrogens PREMPRO (conjugated [Repackaged] ESTRADIOL patch [Repackaged] VIVELLE DOT - estradiol patch, extended release [Repackaged] PROMETRIUM (progesterone) capsule [Repackaged] PROPECIA (finasteride coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film SPIRONOLACTONE tablet ESTERIFIED ESTROGENS AND METHYL PREMARIN (conjugated estrogens) tabl SPIRONOLACTONE tablet, ESTRADIOL tablet [Repackaged] conj CENESTIN - synthetic coated [Repackaged] SPIRONOLACTONE tablet, film SPIRONOLACTONE AND HYDROCHLOROTHI coated [Repackaged] FINASTERIDE tablet, film AVODART (dutasteride) capsule, li AVODART (dutasteride) CRINONE (progester ENJUVIA (synthetic conjugated estroge coated [Repackaged] FINASTERIDE tablet, film MEDROXYPROGESTERONE ACETATE PREMARIN (conjugated estrogens) tabl FINASTERIDE tablet coated FINASTERIDE tablet, film MENEST (estrogens, esterified ESTRADIOL tablet [Repackaged] coated [Repackaged] SPIRONOLACTONE tablet, film 55154-6242-4 PROCHIEVE (progesterone) gel

Page 55 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 56 of 87 50436-0446-3 49999-109-30 50419-451-04 47335-485-18 50268-726-15 51079-103-17 50102-128-03 50268-323-15 43598-390-90 50090-0136-1 50436-9973-3 47335-715-13 47335-714-18 50742-123-90 45963-600-09 45963-500-08 50458-251-12 49884-753-13 51991-623-28 50268-290-15 50458-191-12 47781-205-04 50220-002-01 acetate) tablet, film 19 http://bmjopen.bmj.com/ BMJ Open kit and norethindrone l) kit TERONE tablet, film coated TERONE tablet, film estradiol) AZIDE tablet [Repackaged] 51079-104-20 , film coated , film 51285-407-02 on September 30, 2021 by guest. Protected copyright. hinyl estradiol) tablet / kit 52544-249-28 nd ethinyl estradiol) kit 52544-248-28 (estradiol) patch and ethinyl estradiol) kit nd ethinyl estradio acetate and ethinyl estradiol and ferrous fumarate) kit ferrous fumarate) and estradiol acetate and ethinyl 52544-167-41 tablet [Repackaged] For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml ethinyl estradiol) kit For peer review 52544-087-41 only one acetate and ethinyl ted estrogens, b) tablet blet [Repackaged] TARINA FE 1/20 (norethindr ESTERIFIED ESTROGENS AND METHYLTESTOS SPIRONOLACTONE tablet [Repackaged] coated [Repackaged] PREMARIN (conjugated estrogens) tablet, film FLUTAMIDE capsule ESTRADIOL TRANSDERMAL SYSTEM coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film MICROGESTIN 24 FE (norethindrone MICROGESTIN 24 FE (norethindrone and TRINESSA LO (norgestimate DUTASTERIDE capsule ESTRADIOL / NORETHINDRONE ACETATE (estradiol coated [Repackaged] SPIRONOLACTONE tablet, film 51991-749-90 MONONESSA / TRINESSA (norgestimate a MONONESSA / TRINESSA (norgestimate coated ENJUVIA (synthetic conjuga coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film SPIRONOLACTONE AND HYDROCHLOROTHI coated FINASTERIDE tablet, film ORTHO TRI CYCLEN LO (norgestimate a ORTHO TRI CYCLEN (norgestimate SPIRONOLACTONE tablet [Repackaged] CLIMARA (estradiol) patch [Repackaged] SPIRONOLACTONE (spironolactone) coated [Repackaged] FINASTERIDE tablet, film ESTRADIOL (estradiol) ta 51079-520-20 51079-321-20 SPIRONOLACTONE tablet MICROGESTIN (norethindrone acetate and et 53489-143-05 BICALUTAMIDE tablet, film coated BICALUTAMIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film FINASTERIDE tablet, film coated [Repackaged] FINASTERIDE tablet, film FINASTERIDE tablet, film coated [Repackaged] FINASTERIDE tablet, film

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 18860-480-30 35356-250-00 42291-168-50 16714-407-02 16714-416-02 16714-571-02 42291-280-90 35356-419-30 33261-869-30 35356-969-60 31722-526-30 31722-525-05 31722-525-05 16729-090-10 16729-089-15 41616-485-18 16729-023-10 23155-014-01 33261-534-10 21695-896-20 42023-111-01 17139-617-40 17478-767-10 33261-667-60 21695-613-30 16714-408-02 42023-135-01 20 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. estradiol and ferrous fumarate) kit estradiol and ferrous fumarate) tablet [Repackaged] tablet [Repackaged] 43063-438-07 tablet [Repackaged] , film coated [Repackaged] , film thinyl estradiol) kit For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only blet [Repackaged] 43063-201-30 iol valerate injection ESTRADIOL tablet [Repackaged] MEDROXYPROGESTERONE ACETATE FINASTERIDE tablet, film coated FINASTERIDE tablet, film ESTRADIOL (estradiol) ta SPIRONOLACTONE tablet [Repackaged] PROGESTERONE capsule coated [Repackaged] FINASTERIDE (finasteride) tablet, film tablet BICALUTAMIDE (bicalutamide) ESTRADIOL VALERATE injection coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] PREMARIN (conjugated estrogens) tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film 43063-072-30 42291-691-01 FINASTERIDE tablet [Repackaged] FINASTERIDE tablet [Repackaged] coated [Repackaged] PREMARIN (conjugated estrogens) tablet, film ESTRADIOL tablet [Repackaged] MEDROXYPROGESTERONE ACETATE 43353-688-60 43598-303-90 43063-446-30 FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film ESTRADIOL tablet MEDROXYPROGESTERONE ACETATE PROGESTERONE capsule ESTRADIOL tablet [Repackaged] ELESTRIN (estradiol) gel ESTROGEL (estradiol) gel, metered BICALUTAMIDE tablet coated [Repackaged] SPIRONOLACTONE tablet, film DELESTROGEN- estrad FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film BICALUTAMIDE tablet, film coated BICALUTAMIDE tablet, film ethinyl estradiol) kit estradiol) kit acetate/ ethinyl LARIN 1/20 (norethindrone BICALUTAMIDE tablet LARIN 1.5/30 (norethindrone acetate/e LARIN 24 FE (norethindrone acetate/ethinyl

Page 57 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 58 of 87 16714-360-02 0615-8031-30 0615-1535-31 0781-4110-52 10888-7136-2 0603-3633-16 16714-363-02 0781-7129-58 0781-5409-10 0555-0886-04 0591-0487-05 0555-0779-04 0574-0872-05 10544-062-10 15310-020-01 0703-6801-04 10544-523-90 0591-3965-01 0603-7642-17 0603-7609-17 0603-7608-17 10544-070-30 0591-3771-30 10370-280-11 13925-172-01 0603-7607-15 0603-5763-28 0781-1599-05 0591-2292-30 0904-5952-06 0603-7606-15 0603-7610-17 21 http://bmjopen.bmj.com/ BMJ Open fumarate) kit 16714-406-02 rrous fumarate) rrous fumarate) l) kit ferrous fumarate) kit ferrous fumarate) ferrous fumarate) kit ferrous fumarate) blet, film coated blet, film tablet, film coated tablet, film iol and ferrous fumarate) kit iol and ferrous fumarate) 16714-405-02 TERONE tablet, film coated TERONE tablet, film kit on September 30, 2021 by guest. Protected copyright. VALERATE/DIENOGEST kit estradiol and ferrous and ethinyl estradio hinyl estradiol and fe injection, suspension tablet [Repackaged] DROCHLORIDE capsule DROCHLORIDE capsule nyl estradiol) kit ltestosterone) tablet, coated For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml te and ethinyl estradiol) ta etate/ethinyl estrad For peer review only ETATE tablet film coated film film coated film one acetate and ethinyl estradiol) ndrone acetate/ethinyl FINASTERIDE tablet, film coated FINASTERIDE tablet, film PROGESTERONE capsule GILDESS 24 FE (norethindrone acetate and et GILDESS 1.5/30 (norethindr SPIRONOLACTONE tablet, PREVIFEM / TRI-PREVIFEM (norgestimate PREVIFEM / TRI-PREVIFEM (norgestimate ethinyl estradiol and GILDESS FE 1/20 (norethindrone acetate, and acetate, ethinyl estradiol GILDESS FE 1.5/30 (norethindrone GILDESS 1/20 (norethindrone aceta MEDROXYPROGESTERONE AC ESTRADIOL tablet DUTASTERIDE AND TAMSULOSIN HY DUTASTERIDE capsule ESTRADIOL tablet ESTRADIOL VALERATE injection, solution LARIN FE 1/20 (norethi LARIN FE 1.5/30 (norethindrone ac and ethinyl estradiol) TRI-LINYAH (norgestimate MONO-LINYAH (norgestimate and ethi MONO-LINYAH (norgestimate coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film ESTERIFIED ESTROGENS AND METHYLTESTOS PROGESTERONE capsule EEMT (estrogens, esterified and methy SPIRONOLACTONE tablet, MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE ESTRADIOL VALERATE AND DUTASTERIDE AND TAMSULOSIN HY ESTRADIOL patch, extended release SPIRONOLACTONE tablet [Repackaged] ESTRADIOL tablet [Repackaged] SPIRONOLACTONE tablet BICALUTAMIDE tablet

For peer review only le, liquid filled film coated film coated film 0378-0243-05 e) tablet 0310-0705-30 JALYN (dutasteride and tamsulosin ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] FLUTAMIDE capsule coated (Estradiol) tablet, film Innofem AVODART (dutasteride) capsu AVODART (dutasteride) LOESTRIN 24 FE (norethindrone ace LO LOESTRIN FE (norethindrone acetate and ethinyl estradiol, kit acetate and ethinyl estradiol, acetate and ethinyl LO MINASTRIN FE (norethindrone kit fumarate) MINASTRIN acet 24 FE (norethindrone NORETHINDRONE ACETATE AND ETHINYL ESTRADI ) kit estradiol NORETHINDRONE ACETATE AND ETHINYL ESTRADI ) kit estradiol NORETHINDRONE ACETATE AND ETHINYL NORGESTIMATE AND ETHINYL ESTRADIOL ( norgest coated FINASTERIDE tablet, film ESTRADIOL patch ESTRADIOL patch ESTRADIOL tablet SPIRONOLACTONE tablet, SPIRONOLACTONE AND HYDROCHLOR DIVIGEL (estradiol) gel gel DIVIGEL (estradiol) SPIRONOLACTONE tablet, 0378-5036-05 CASODEX (bicalutamid LUPRON (leuprolide acetate) injection, solution NORETHINDRONE ACETATE AND ETHINYL ESTR kit and '') and '', ESTRACE (estradiol) cream ESTRACE (estradiol) tablet ESTROSTEP FE (norethindrone acet 0430-3754-95 0430-0721-24

Page 59 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 60 of 87 0074-3641-71 0074-3473-03 0074-3642-03 0032-1711-01 0074-2282-03 0074-2440-03 0074-1052-10 0025-1031-31 0083-2310-62 45963-600-11 0083-2320-08 0037-4802-35 0025-1041-31 0006-0071-31 0006-0071-54 0009-0050-11 0009-0064-04 0006-0072-58 0046-0872-21 0083-2310-62 0083-2320-08 0054-0395-22 0046-1100-81 0046-1100-91 sugar coated 0046-1105-51 sugar coated 0046-1106-11 23 http://bmjopen.bmj.com/ BMJ Open acetate) kit, tablet, acetate) kit, tablet, ferrous fumarate) kit ferrous fumarate) 0093-5328-62 on September 30, 2021 by guest. Protected copyright. hinyl estradiol) kit 0093-2140-62 hinyl estradiol) tablet hinyl 0093-3122-42 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml tablet, film coated tablet, film tablet, film coated tablet, film nded release [Repackaged] nded release [Repackaged] d estrogens) cream d estrogens) cream et, film coated et, film te and ethinyl estradiol acetate) tablet acetate) tablet e acetate) kit e acetate) kit blet, film coated blet, film e acetate and norethindrone acetate) kit

For peer review %) gel, metered only e acetate) kit e acetate) kit e acetate) kit et, film coated et, film h, extended release ride) tablet, film coated ride) tablet, film ride) tablet, film coated ride) tablet, film DUTASTERIDE capsule, liquid filled coated FINASTERIDE tablet, film DUTASTERIDE capsule, liquid filled PROGESTERONE capsule JUNEL FE 24 (norethindrone aceta 0115-1438-10 0093-5655-98 0093-7355-56 0093-5354-01 JINTELI (norethindrone acetate and et JINTELI (norethindrone and et TRI-LO-SPRINTEC (norgestimate coated BICALUTAMIDE tablet, film (estradiol) patc h, extended release estraderm 0093-0220-56 ESTRADERM- estradiol patch, exte LUPRON DEPOT (leuprolid LUPRON DEPOT (leuprolid LUPRON DEPOT-PED (leuprolid LUPANETA PACK (leuprolid DUTASTERIDE capsule and medroxyprogesterone PREMPHASE (conjugated estrogens PREMARIN (estrogens, conjugated) PREMARIN VAGINAL (conjugate ELESTRIN (estradiol gel 0.06 PROMETRIUM (progesterone) capsule ALDACTONE- spironolactone ta PROSCAR- finasteride tabl PROPECIA (finaste coated FINASTERIDE tablet, film PROVERA (medroxyprogesterone PROVERA (medroxyprogesterone ALDACTONE- spironolactone tabl PROPECIA (finaste PREMARIN (estrogens, conjugated) PROVERA (medroxyprogesterone PROVERA (medroxyprogesterone PREMPHASE (conjugated estrogens and medroxyprogesterone PREMPHASE (conjugated estrogens LUPRON DEPOT-PED (leuprolid LUPRON DEPOT (leuprolid (estradiol) patc estraderm ESTRADERM- estradiol patch, exte

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 0430-0537-95 0430-0539-95 0555-0887-02 0591-0488-01 0172-4960-70 0245-0880-89 0378-1454-01 0378-3350-16 0378-4641-16 0430-0420-95 24 estradiol and ferrous fumarate) ferrous fumarate) kit ferrous fumarate) 0430-0535-95 http://bmjopen.bmj.com/ BMJ Open rrous fumarate) rrous fumarate) 0603-7610-49 ethinyl estradiol and ferrous and ethinyl estradiol ferrous fumarate) kit ferrous fumarate) 0430-0570-60 nd ferrous fumarate) kit nd ferrous fumarate) 0430-0530-95 blet, film coated blet, film 0603-7607-48 tablet, film coated tablet, film 0603-7606-48 ADIOL AND FERROUS FUMARATE ('', on September 30, 2021 by guest. Protected copyright. hinyl estradiol and fe ate and ethinyl estradiol, and ate and ethinyl hinyl estradiol) tablet hinyl 0093-3122-98 tate and ethinyl estradiol, a For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml ate and ethinyl estradiol te and ethinyl estradiol) ta ETATE tablet 0555-0872-02 hydrochloride) capsule 0173-0809-61

le, liquid filled For peer review only 0173-0712-15 film coated film 0603-5763-30 film coated film coated film 0228-2673-11 0378-0437-01 one acetate and ethinyl estradiol) e) tablet 0310-0705-39 ESTRACE (estradiol) tablet MEDROXYPROGESTERONE AC ESTRADIOL tablet GILDESS 1/20 (norethindrone aceta GILDESS 24 FE (norethindrone acetate and et 0430-0722-24 acetate and ethinyl estradiol, acetate and ethinyl LO MINASTRIN FE (norethindrone kit fumarate) NORETHINDRONE ACETATE AND ETHINYL ESTR kit and '') and '', ESTROSTEP FE (norethindrone acet ESTRADIOL tablet coated FINASTERIDE tablet, film SPIRONOLACTONE tablet, GILDESS 1.5/30 (norethindr 0603-3633-21 MINASTRIN acet 24 FE (norethindrone FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated (Estradiol) tablet, film Innofem FLUTAMIDE capsule capsu AVODART (dutasteride) JALYN (dutasteride and tamsulosin ESTRADIOL tablet [Repackaged] SPIRONOLACTONE tablet, DIVIGEL (estradiol) gel gel DIVIGEL (estradiol) CASODEX (bicalutamid SPIRONOLACTONE tablet, ESTRADIOL tablet ESTRADIOL patch ESTRADIOL patch coated FINASTERIDE tablet, film LO LOESTRIN FE (norethindrone acetate and ethinyl estradiol, kit LOESTRIN 24 FE (norethindrone ace 0169-1843-81 0093-7355-98 0179-1999-60 0245-0880-89 0378-5036-77 JINTELI (norethindrone acetate and et JINTELI (norethindrone

Page 61 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 62 of 87 18860-480-60 35356-251-00 16714-407-03 16714-416-03 16714-571-03 16714-360-03 0615-1535-39 0615-8031-39 35356-969-90 33261-895-30 16729-090-15 31722-525-10 31722-525-10 31722-526-90 16714-363-03 16714-406-03 0781-7129-83 0781-5409-31 41616-485-83 23155-014-05 43063-201-90 21695-896-30 33261-534-14 42023-112-01 16714-405-03 17139-617-43 43063-072-90 21695-623-00 33261-714-60 16714-408-03 42023-136-01 0781-1599-10 0904-5953-06 25 http://bmjopen.bmj.com/ BMJ Open fumarate) kit l) kit 0603-7663-01 iol and ferrous fumarate) kit iol and ferrous fumarate) kit on September 30, 2021 by guest. Protected copyright. estradiol and ferrous and ethinyl estradio estradiol and ferrous fumarate) kit estradiol and ferrous fumarate) tablet [Repackaged] tablet [Repackaged] nyl estradiol) kit thinyl estradiol) kit For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml etate/ethinyl estrad For peer review only film coated film blet [Repackaged] iol valerate injection ndrone acetate/ethinyl SPIRONOLACTONE tablet, BICALUTAMIDE tablet ESTRADIOL patch, extended release SPIRONOLACTONE tablet and ethi MONO-LINYAH (norgestimate TRI-LINYAH (norgestimate and ethinyl estradiol) TRI-LINYAH (norgestimate LARIN FE 1/20 (norethi LARIN 1.5/30 (norethindrone acetate/e coated BICALUTAMIDE tablet, film LARIN FE 1.5/30 (norethindrone ac SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film PREVIFEM / TRI-PREVIFEM (norgestimate PREVIFEM / TRI-PREVIFEM (norgestimate FINASTERIDE tablet, film coated FINASTERIDE tablet, film ethinyl estradiol) kit estradiol) kit acetate/ ethinyl LARIN 1/20 (norethindrone LARIN 24 FE (norethindrone acetate/ethinyl ESTROGEL (estradiol) gel, metered ELESTRIN (estradiol) gel MEDROXYPROGESTERONE ACETATE ESTRADIOL tablet [Repackaged] ESTRADIOL tablet coated FINASTERIDE tablet, film SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film BICALUTAMIDE tablet DELESTROGEN- estrad ESTRADIOL VALERATE injection SPIRONOLACTONE tablet [Repackaged] FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film MEDROXYPROGESTERONE ACETATE ESTRADIOL tablet [Repackaged] coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] PREMARIN (conjugated estrogens) tablet, film ESTRADIOL (estradiol) ta

Page 63 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 64 of 87 63629-1585-3 58118-7355-8 55154-5517-0 63629-2612-3 63629-2613-3 60429-177-30 59762-3741-1 55289-507-90 63187-634-90 63629-1830-3 57237-062-90 59762-4538-1 63629-3755-3 54868-5047-0 55111-172-30 55154-6242-6 61570-074-01 63187-657-90 59746-216-10 55289-160-10 55289-603-30 55289-761-90 60429-328-05 63187-482-90 59762-5012-1 27 http://bmjopen.bmj.com/ BMJ Open sterone acetate) tablet, sugar coated sterone acetate) tablet, on September 30, 2021 by guest. Protected copyright. injection, suspension tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] 55154-0533-6 et, film coated [Repackaged] et, film 55154-0216-6 ns, b) tablet [Repackaged] 54868-6164-0 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml ETATE tablet tablet, film coated tablet, film ) tablet [Repackaged] For peer review 54868-6211-0 only one) gel 55056-0818-2 SPIRONOLACTONE (spironolactone) tablet, film coated MEDROXYPROGESTERONE ACETATE FINASTERIDE tablet, film coated FINASTERIDE tablet, film DUTASTERIDE capsule [Repackaged] coated [Repackaged] FINASTERIDE tablet, film SPIRONOLACTONE tablet [Repackaged] MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE ESTRADIOL tablet [Repackaged] [Repackaged] coated [Repackaged] FINASTERIDE tablet, film ENJUVIA (synthetic conjugated estroge MENEST (estrogens, esterified CRINONE (progester PROCHIEVE (progesterone) gel coated FINASTERIDE tablet, film FINASTERIDE tablet PREMARIN (conjugated estrogens) tabl MEDROXYPROGESTERONE ACETATE coated [Repackaged] SPIRONOLACTONE tablet, film ESTRADIOL tablet [Repackaged] MEDROXYPROGESTERONE ACETATE coated [Repackaged] SPIRONOLACTONE tablet, film ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] coated [Repackaged] FINASTERIDE tablet, film 54868-5636-2 MEDROXYPROGESTERONE AC coated SPIRONOLACTONE tablet, film coated [Repackaged] BICALUTAMIDE tablet, film 55056-1601-6 55111-171-30 PREMPRO (conjugated estrogens and medroxyproge and estrogens PREMPRO (conjugated ESTRADIOL tablet [Repackaged] MENEST (esterified estrogens) ESTRADIOL tablet [Repackaged] coated [Repackaged] SPIRONOLACTONE tablet, film

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 68788-9249-9 68788-9517-6 68788-9227-9 68554-3025-2 68554-3026-2 68382-224-06 68788-9519-9 68084-207-01 68788-9124-9 68788-9729-9 65977-5025-2 68025-065-30 68788-9416-6 68788-9901-6 69761-006-30 69761-010-30 69761-012-30 69761-015-30 68084-946-25 68462-657-29 68180-827-13 28 http://bmjopen.bmj.com/ BMJ Open et, film coated et, film AZIDE tablet [Repackaged] ESTRADIOL tablet on September 30, 2021 by guest. Protected copyright. kit 65862-777-86 tablet [Repackaged] 64205-087-90 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml and ethinyl estradiol) tabl estradiol) and ethinyl nyl estradiol)

Forl estradiol) kit peer review only 65862-776-86 FYAVOLV (norethindrone acetate FYAVOLV (norethindrone ESTRADIOL tablet [Repackaged] SPIRONOLACTONE tablet coated BICALUTAMIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film and ethiny MILI (norgestimate and ethi TRI-MILI (norgestimate FINASTERIDE tablet DIVIGEL (estradiol) gel gel DIVIGEL (estradiol) coated [Repackaged] SPIRONOLACTONE tablet, film SPIRONOLACTONE AND HYDROCHLOROTHI coated BICALUTAMIDE tablet, film NORETHINDRONE ACETATE AND ETHINYL 64205-488-30 65841-613-06 65862-149-30 65162-511-09 65862-686-99 68025-065-30 ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] coated FINASTERIDE tablet, film SPIRONOLACTONE tablet [Repackaged] MEDROXYPROGESTERONE ACETATE 63629-4788-3 63739-545-10 63629-5208-3 63739-495-43 FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film SPIRONOLACTONE tablet [Repackaged] coated [Repackaged] SPIRONOLACTONE tablet, film coated [Repackaged] FINASTERIDE tablet, film ESTRADIOL tablet [Repackaged] coated [Repackaged] FINASTERIDE tablet, film FINASTERIDE tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet

Page 65 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 66 of 87 16714-363-04 16714-360-04 0615-5592-39 0603-3633-28 0378-5036-93 0083-2320-62 0245-0881-30 0781-7138-40 0781-5409-64 0555-0887-04 0591-0488-05 0245-0881-30 0378-1454-05 0378-3350-99 0378-4641-26 69761-018-30 69761-020-30 69761-022-30 69761-025-30 0555-0872-04 0603-7663-17 16714-405-04 0179-1999-70 0083-2320-62 0378-2146-01 0603-5763-32 0228-2673-50 0169-1843-82 sugar coated 0046-1106-51 29 http://bmjopen.bmj.com/ BMJ Open l) kit acetate) kit, tablet, iol and ferrous fumarate) kit iol and ferrous fumarate) kit on September 30, 2021 by guest. Protected copyright. and ethinyl estradio nyl estradiol) kit For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml tablet, film coated tablet, film 0046-1101-81 nded release [Repackaged] etate/ethinyl estrad ETATE tablet acetate) tablet 0009-0064-06 Fore acetate) kit peer review only 0074-3779-03 film coated film film coated film film coated film e acetate) kit 0074-3683-03 ESTRADIOL tablet coated FINASTERIDE tablet, film BICALUTAMIDE tablet ESTRADIOL patch, extended release and ethi MONO-LINYAH (norgestimate ESTRADIOL tablet coated [Repackaged] SPIRONOLACTONE tablet, film DIVIGEL (estradiol) gel gel DIVIGEL (estradiol) ESTRADIOL tablet SPIRONOLACTONE tablet, ESTRADIOL patch ESTRADIOL patch coated FINASTERIDE tablet, film MEDROXYPROGESTERONE AC ESTRADIOL pellet ESTRADIOL pellet ESTRADIOL pellet coated FINASTERIDE tablet, film PROVERA (medroxyprogesterone PREMARIN (estrogens, conjugated) and medroxyprogesterone PREMPHASE (conjugated estrogens LUPRON DEPOT (leuprolid LUPRON DEPOT-PED (leuprolid (estradiol) patc h, extended release estraderm ESTRADERM- estradiol patch, exte SPIRONOLACTONE tablet, 76282-412-30 PREVIFEM / TRI-PREVIFEM (norgestimate and ethinyl estradiol) TRI-LINYAH (norgestimate ESTRADIOL pellet Innofem (Estradiol) tablet, film coated (Estradiol) tablet, film Innofem ESTRADIOL tablet [Repackaged] SPIRONOLACTONE tablet, LARIN FE 1.5/30 (norethindrone ac

Page 67 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 68 of 87 63629-1585-4 63629-2612-4 63629-2613-4 65841-613-10 59762-3741-4 63629-1830-4 65862-149-90 65862-927-30 65862-777-87 59762-4538-2 54868-5540-0 55111-172-78 63629-3755-4 63629-4788-4 63629-5208-4 61570-075-50 59746-217-01 65862-776-87 60429-329-01 64205-488-90 59762-5013-1 65162-511-10 31 http://bmjopen.bmj.com/ BMJ Open sterone acetate) tablet, sugar coated sterone acetate) tablet, , film coated , film 54868-4879-1 on September 30, 2021 by guest. Protected copyright. kit tablet [Repackaged] injection, suspension tablet [Repackaged] tablet [Repackaged] 55289-160-13 et, film coated [Repackaged] et, film 55154-0217-0 ns, b) tablet [Repackaged] 54868-6164-1 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml ETATE tablet nyl estradiol) tablet, film coated tablet, film ) tablet [Repackaged] 54868-6211-1

For peer review only l estradiol) kit ugated estrogens, a tablet one) gel 55056-0818-5 PREMPRO (conjugated estrogens and medroxyproge and estrogens PREMPRO (conjugated [Repackaged] ENJUVIA (synthetic conjugated estroge MENEST (estrogens, esterified CRINONE (progester PROCHIEVE (progesterone) gel coated FINASTERIDE tablet, film FINASTERIDE tablet PREMARIN (conjugated estrogens) tabl MEDROXYPROGESTERONE ACETATE ESTRADIOL tablet [Repackaged] SPIRONOLACTONE (spironolactone) tablet, film coated MEDROXYPROGESTERONE AC MEDROXYPROGESTERONE ACETATE coated SPIRONOLACTONE tablet, film ESTRADIOL tablet [Repackaged] MENEST (esterified estrogens) coated [Repackaged] FINASTERIDE tablet, film SPIRONOLACTONE tablet [Repackaged] MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] ESTRADIOL tablet [Repackaged] SPIRONOLACTONE tablet coated BICALUTAMIDE tablet, film coated FINASTERIDE tablet, film 55056-1601-8 and ethiny MILI (norgestimate 55111-171-90 coated FINASTERIDE tablet, film 55289-603-90 PROMETRIUM (progesterone) capsule [Repackaged] VIVELLE DOT - estradiol patch, extended release [Repackaged] conj CENESTIN - synthetic 54868-4862-0 54868-4250-0 TRI-MILI (norgestimate and ethi TRI-MILI (norgestimate

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 68788-9517-9 68554-3025-3 68382-224-10 0074-9694-03 0615-6591-39 68084-207-11 16729-090-17 31722-525-90 76282-412-90 0245-0881-66 0781-7138-58 0378-3351-16 0378-4642-16 65977-5025-3 68025-066-01 0245-0881-66 0378-1458-01 0555-0899-02 0591-0528-01 68788-9416-9 68788-9901-9 68084-946-95 0555-0873-02 0009-0286-03 0179-1999-88 68462-657-90 68180-828-09 0228-2803-11 0378-2146-05 0603-5764-21 0046-1102-51 0169-1844-81 sugar coated 0046-1107-11 32 http://bmjopen.bmj.com/ BMJ Open acetate) kit, tablet, et, film coated et, film AZIDE tablet [Repackaged] ESTRADIOL tablet on September 30, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml tablet, film coated tablet, film cetate) tablet ETATE tablet and ethinyl estradiol) tabl estradiol) and ethinyl For peer e acetate) kit review only film coated film coated film film coated film ESTRADIOL patch ESTRADIOL patch MEDROXYPROGESTERONE AC coated [Repackaged] SPIRONOLACTONE tablet, film ESTRADIOL patch, extended release FINASTERIDE tablet, film coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film FYAVOLV (norethindrone acetate FYAVOLV (norethindrone DIVIGEL (estradiol) gel gel DIVIGEL (estradiol) coated [Repackaged] SPIRONOLACTONE tablet, film SPIRONOLACTONE AND HYDROCHLOROTHI coated BICALUTAMIDE tablet, film NORETHINDRONE ACETATE AND ETHINYL DIVIGEL (estradiol) gel gel DIVIGEL (estradiol) ESTRADIOL tablet SPIRONOLACTONE tablet, 68025-066-01 ESTRADIOL tablet ESTRADIOL tablet SPIRONOLACTONE tablet, FINASTERIDE tablet SPIRONOLACTONE tablet, FINASTERIDE tablet, film coated FINASTERIDE tablet, film ESTRADIOL tablet [Repackaged] coated [Repackaged] FINASTERIDE tablet, film ESTRADIOL tablet [Repackaged] coated FINASTERIDE tablet, film a PROVERA (medroxyprogesterone PREMARIN (estrogens, conjugated) PREMPHASE (conjugated estrogens and medroxyprogesterone PREMPHASE (conjugated estrogens LUPRON DEPOT-PED (leuprolid coated (Estradiol) tablet, film Innofem ESTRADIOL tablet [Repackaged]

Page 69 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 70 of 87 54868-4920-0 54868-6212-0 54868-4477-0 54569-0505-6 54868-4250-1 63629-2612-5 54868-0109-5 55056-0818-9 55154-0217-4 54868-0451-6 59762-3742-2 51079-103-63 63629-1830-5 59762-4538-9 55111-172-79 54868-4031-1 54868-6165-0 59746-217-05 55289-160-30 54868-4879-2 60429-329-05 51285-410-02 53489-328-06 65162-511-11 53746-511-60 33 http://bmjopen.bmj.com/ BMJ Open l) kit 50458-197-00 , film coated , film , film coated , film on September 30, 2021 by guest. Protected copyright. tablet [Repackaged] injection, suspension tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] 33261-609-30 43063-438-30 (estradiol) patch 47781-208-04 et, film coated [Repackaged] et, film et, film coated [Repackaged] et, film ns, b) tablet [Repackaged] nd ethinyl estradio For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml ETATE tablet

For peer review) tablet [Repackaged] only film coated film ted estrogens, b) tablet ugated estrogens, a tablet blet [Repackaged] 50268-292-11 one) gel MEDROXYPROGESTERONE ACETATE SPIRONOLACTONE (spironolactone) tablet, film coated MEDROXYPROGESTERONE AC MEDROXYPROGESTERONE ACETATE ESTRADIOL tablet [Repackaged] SPIRONOLACTONE tablet [Repackaged] MEDROXYPROGESTERONE ACETATE SPIRONOLACTONE tablet PREMARIN (conjugated estrogens) tabl CRINONE (progester FINASTERIDE tablet ESTRADIOL tablet [Repackaged] PROMETRIUM (progesterone) capsule [Repackaged] coated [Repackaged] SPIRONOLACTONE tablet, film VIVELLE DOT - estradiol patch, extended release [Repackaged] ENJUVIA (synthetic conjugated estroge MENEST (estrogens, esterified SPIRONOLACTONE tablet, SPIRONOLACTONE tablet coated [Repackaged] SPIRONOLACTONE tablet, film MEDROXYPROGESTERONE ACETATE PREMARIN (conjugated estrogens) tabl MEDROXYPROGESTERONE ACETATE coated FINASTERIDE tablet, film coated FINASTERIDE tablet, film ESTRADIOL TRANSDERMAL SYSTEM ESTRADIOL (estradiol) ta CLIMARA (estradiol) patch [Repackaged] a ORTHO TRI CYCLEN (norgestimate 47335-714-88 47335-715-83 50419-453-01 FINASTERIDE tablet, film coated FINASTERIDE tablet, film MEDROXYPROGESTERONE ACETATE 31722-525-90 SPIRONOLACTONE tablet, film coated [Repackaged] SPIRONOLACTONE tablet, film ENJUVIA (synthetic conjuga conj CENESTIN - synthetic

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 68554-3025-4 50419-453-04 68382-224-30 51079-979-01 68084-208-01 47335-715-88 0245-0881-89 0781-7138-83 0555-0873-04 0245-0881-89 0378-1458-05 0378-3351-99 0378-4642-26 0591-0528-05 65977-5025-4 68025-066-07 50268-292-15 33261-740-20 43063-438-40 50458-197-12 47781-209-04 0179-1999-90 68180-828-11 65162-511-50 0228-2803-50 0603-5764-28 0046-1102-81 0169-1844-82 sugar coated 0046-1108-11 34 http://bmjopen.bmj.com/ BMJ Open acetate) kit, tablet, et, film coated et, film l) kit on September 30, 2021 by guest. Protected copyright. kit 65862-777-88 tablet [Repackaged] tablet [Repackaged] (estradiol) patch nd ethinyl estradio ATE tablet For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml tablet, film coated tablet, film and ethinyl estradiol) tabl estradiol) and ethinyl nyl estradiol)

l estradiol) kit For peer review 65862-776-88 only film coated film film coated film blet [Repackaged] ORTHO TRI CYCLEN (norgestimate a ORTHO TRI CYCLEN (norgestimate ESTRADIOL patch, extended release CLIMARA (estradiol) patch [Repackaged] coated [Repackaged] SPIRONOLACTONE tablet, film MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE coated FINASTERIDE tablet, film ESTRADIOL TRANSDERMAL SYSTEM ESTRADIOL (estradiol) ta DIVIGEL (estradiol) gel gel DIVIGEL (estradiol) ESTRADIOL tablet ESTRADIOL patch ESTRADIOL patch MEDROXYPROGESTERONE ACET ESTRADIOL tablet SPIRONOLACTONE tablet, BICALUTAMIDE tablet, film coated BICALUTAMIDE tablet, film SPIRONOLACTONE tablet, SPIRONOLACTONE tablet PREMARIN (estrogens, conjugated) FINASTERIDE tablet, film coated FINASTERIDE tablet, film TRI-MILI (norgestimate and ethi TRI-MILI (norgestimate coated FINASTERIDE tablet, film FINASTERIDE tablet DIVIGEL (estradiol) gel gel DIVIGEL (estradiol) coated [Repackaged] SPIRONOLACTONE tablet, film acetate FYAVOLV (norethindrone and medroxyprogesterone PREMPHASE (conjugated estrogens coated (Estradiol) tablet, film Innofem ESTRADIOL tablet [Repackaged] 65862-927-90 68025-066-07 BICALUTAMIDE tablet, film coated BICALUTAMIDE tablet, film and ethiny MILI (norgestimate 65841-613-30

Page 71 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 72 of 87 54868-6212-1 54868-4477-1 63629-2612-6 68382-224-77 55154-0217-6 59762-3742-8 68084-208-11 65862-927-99 0245-0882-30 68025-066-30 0781-7144-40 68025-066-30 0245-0882-30 0378-1458-77 0378-3352-16 0378-4643-16 55111-172-90 54868-6165-1 59746-218-01 33261-740-28 43063-438-42 55289-160-40 65862-776-92 65862-777-92 54868-5415-0 68180-828-13 0228-2803-96 0046-1102-91 sugar coated 0046-2575-12 35 http://bmjopen.bmj.com/ BMJ Open acetate) kit, tablet, et, film coated et, film , film coated , film on September 30, 2021 by guest. Protected copyright. tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] 54868-0109-6 et, film coated [Repackaged] et, film et, film coated [Repackaged] et, film 54868-0453-0 ns, b) tablet [Repackaged] For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml tablet, film coated tablet, film ETATE tablet l estradiol) kit and ethinyl estradiol) tabl estradiol) and ethinyl ) tablet [Repackaged]

For peerl estradiol) kit review only film coated film film coated film 53489-328-07 ugated estrogens, a tablet FINASTERIDE tablet, film coated FINASTERIDE tablet, film DIVIGEL (estradiol) gel DIVIGEL (estradiol) coated [Repackaged] SPIRONOLACTONE tablet, film acetate FYAVOLV (norethindrone coated BICALUTAMIDE tablet, film PREMARIN (estrogens, conjugated) PREMPHASE (conjugated estrogens and medroxyprogesterone PREMPHASE (conjugated estrogens SPIRONOLACTONE tablet, DIVIGEL (estradiol) gel gel DIVIGEL (estradiol) ESTRADIOL tablet ESTRADIOL patch ESTRADIOL patch ESTRADIOL patch, extended release MEDROXYPROGESTERONE ACETATE MEDROXYPROGESTERONE ACETATE TRI-MILI (norgestimate and ethiny TRI-MILI (norgestimate MEDROXYPROGESTERONE ACETATE SPIRONOLACTONE (spironolactone) tablet, film coated MEDROXYPROGESTERONE AC MEDROXYPROGESTERONE ACETATE and ethiny MILI (norgestimate DIVIGEL (estradiol) gel PREMARIN (conjugated estrogens) tabl FINASTERIDE tablet SPIRONOLACTONE tablet MEDROXYPROGESTERONE ACETATE PREMARIN (conjugated estrogens) tabl ESTRADIOL tablet [Repackaged] coated [Repackaged] SPIRONOLACTONE tablet, film conj CENESTIN - synthetic ENJUVIA (synthetic conjugated estroge MENEST (estrogens, esterified 53746-511-90 54868-4031-2 SPIRONOLACTONE tablet,

Page 73 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 74 of 87 54868-5015-2 54868-5015-1 50419-456-04 54868-2984-2 54868-2984-0 54868-0453-6 54868-0453-5 51079-980-20 68025-067-30 0781-7156-40 54868-4370-2 54868-4370-1 68025-067-30 0378-3360-99 0378-4644-26 68025-067-07 0245-0882-89 0378-3360-16 0378-4644-16 53489-329-03 53489-329-02 0046-1104-81 53746-514-30 65162-514-09 65162-514-06 53746-514-10 37 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] tablet [Repackaged] 55289-160-50 43063-438-90 et, film coated [Repackaged] et, film et, film coated [Repackaged] et, film For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml tablet, film coated tablet, film tablet, film coated tablet, film 0046-1104-51 For peer review only film coated film film coated film MEDROXYPROGESTERONE ACETATE ESTRADIOL tablet [Repackaged] coated [Repackaged] SPIRONOLACTONE tablet, film PREMARIN (conjugated estrogens) tabl SPIRONOLACTONE tablet, SPIRONOLACTONE tablet SPIRONOLACTONE tablet MEDROXYPROGESTERONE ACETATE ESTRADIOL tablet [Repackaged] coated [Repackaged] SPIRONOLACTONE tablet, film SPIRONOLACTONE tablet DIVIGEL (estradiol) gel gel DIVIGEL (estradiol) PREMARIN (estrogens, conjugated) ESTRADIOL patch ESTRADIOL patch ESTRADIOL patch, extended release SPIRONOLACTONE tablet PREMARIN (conjugated estrogens) tabl CLIMARA (estradiol) patch [Repackaged] SPIRONOLACTONE tablet DIVIGEL (estradiol) gel gel DIVIGEL (estradiol) PREMARIN (estrogens, conjugated) DIVIGEL (estradiol) gel gel DIVIGEL (estradiol) ESTRADIOL patch ESTRADIOL patch ESTRADIOL patch, extended release MEDROXYPROGESTERONE ACETATE CLIMARA (estradiol) patch [Repackaged] coated [Repackaged] SPIRONOLACTONE tablet, film SPIRONOLACTONE tablet, 65162-514-03 68025-067-07 0781-7144-83 0245-0882-89 50419-456-01 MEDROXYPROGESTERONE ACETATE

Page 75 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 76 of 87 39 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. et, film coated [Repackaged] et, film coated [Repackaged] et, film coated [Repackaged] et, film 54868-4865-2 54868-4865-3 54868-4865-4 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only SPIRONOLACTONE tablet SPIRONOLACTONE tablet PREMARIN (conjugated estrogens) tabl SPIRONOLACTONE tablet SPIRONOLACTONE tablet PREMARIN (conjugated estrogens) tabl SPIRONOLACTONE tablet SPIRONOLACTONE tablet SPIRONOLACTONE tablet SPIRONOLACTONE tablet SPIRONOLACTONE tablet SPIRONOLACTONE tablet 65162-515-03 53746-515-30 65162-515-06 53746-515-60 65162-515-09 53746-515-90 65162-515-10 65162-515-11 65162-515-50 65162-515-60 PREMARIN (conjugated estrogens) tabl

40 http://bmjopen.bmj.com/ BMJ Open solution solution solution 0009-0085-10 0009-0347-02 0009-0520-01 solution 67979-501-40 on September 30, 2021 by guest. Protected copyright. tions used for TM gender affirmation onate) injection, onate) injection, onate) injection, For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml thate injection, For peer review only gel [Repackaged] gel [Repackaged] gel [Repackaged] gel [Repackaged] gel [Repackaged] 50090-1306-0 54569-6337-0 54569-5339-0 54868-4792-0 21695-112-30 terone capsule 0187-0902-01 rone patch 52544-076-60 one) gel one) gel one) gel 0051-8462-01 0051-8425-01 49884-418-48 DEPO-TESTOSTERONE (testosterone cypi DEPO-TESTOSTERONE (testosterone cypi DEPO-TESTOSTERONE (testosterone cypi solution injection, DEPO-TESTOSTERONE (testosterone cypionate) [Repackaged] 54569-5301-0 solution injection, DEPO-TESTOSTERONE (testosterone cypionate) [Repackaged] 54569-1411-0 solution injection, DEPO-TESTOSTERONE (testosterone cypionate) [Repackaged] 50090-0746-0 solution injection, DEPO-TESTOSTERONE (testosterone cypionate) [Repackaged] 54868-0216-0 STRIANT (testosterone) tablet STRIANT (testosterone) tablet TESTIM (testosterone) gel TESTIM (testosterone) gel [Repackaged] TESTIM (testosterone) gel [Repackaged] TESTIM (testosterone) gel [Repackaged] TESTIM (testosterone) gel [Repackaged] TESTIM (testosterone) gel [Repackaged] 50090-0875-0 52244-030-60 54569-5595-0 55056-3060-1 35356-758-30 54868-4989-0 66887-001-05 16590-853-30 ANDROGEL (testoster ANDROGEL (testoster ANDROGEL (testoster ANDROGEL (testosterone) ANDROGEL (testosterone) ANDROGEL (testosterone) ANDROGEL (testosterone) ANDROGEL (testosterone) AXIRON (testosterone) solution AXIRON (testosterone) solution [Repackaged] DELATESTRYL- testosterone enan 54868-6406-0 0002-1975-61 ANDROID - methyltestos ANDRODERM - testoste Label NDC Code Label NDC Supplemental Table 2: NDC codes for medica Page 77 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 78 of 87 41 http://bmjopen.bmj.com/ BMJ Open solution solution solution 0009-0086-01 0009-0417-01 0009-0520-10 solution solution 0009-0086-10 0009-0417-02 on September 30, 2021 by guest. Protected copyright. onate) injection, onate) injection, onate) injection, onate) injection, onate) injection, For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only gel [Repackaged] gel [Repackaged] gel [Repackaged] 54569-5339-1 54868-4810-0 54868-5814-0 rone patch 52544-077-30 one) gel one) gel one) gel one) gel one) gel one) gel one) gel one) gel 0051-8425-30 one) gel 0051-8462-12 one) gel 49884-418-72 one) gel one) gel 0051-8450-01 0051-8462-30 49884-510-63 0051-8450-30 0051-8462-31 49884-510-72 0051-8488-33 0051-8462-33 0051-8488-88 AXIRON (testosterone) solution DEPO-TESTOSTERONE (testosterone cypi 0002-1975-90 DEPO-TESTOSTERONE (testosterone cypi DEPO-TESTOSTERONE (testosterone cypi ANDROGEL (testoster ANDROGEL (testoster ANDROGEL (testoster ANDRODERM - testoste ANDROGEL (testosterone) solution injection, DEPO-TESTOSTERONE (testosterone cypionate) [Repackaged] 54868-0216-1 ANDROGEL (testosterone) DEPO-TESTOSTERONE (testosterone cypi DEPO-TESTOSTERONE (testosterone cypi ANDROGEL (testoster ANDROGEL (testoster ANDROGEL (testoster ANDROGEL (testosterone) ANDROGEL (testoster ANDROGEL (testoster ANDROGEL (testoster ANDROGEL (testoster ANDROGEL (testoster ANDROGEL (testoster

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Code 57295 54530 54520 19324 57296 54535 55970 54690 54522 17380 54125 56800 56805 57291 57292 57335 57291 57292 56805 58999 31899 57426 19325

as permanent hair removal by laser) hair removal as permanent 17999 use for routine orchiectomy) use for routine orchiectomy) 42 http://bmjopen.bmj.com/ BMJ Open open abdominal approach open abdominal t, laparoscopic approach on September 30, 2021 by guest. Protected copyright. and subcutaneous tissue (when specified r), with or without testicular prosthesis, scrotal or inguinal approach r), with or without testicular prosthesis, For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml mor only, but evidence that some may may mor only, but evidence that some

For peer review prosthetic vaginal graft; only of prosthetic vaginal graf of prosthetic vaginal graft; approach thyroid chondroplasty l vagina; without graft exploration (same) exploration (same) Intersex surgery; male to female to female Intersex surgery; male without prosthetic implant augmentation; Mammaplasty, Procedure name Orchiectomy, partial of testis (supposedly for tu Removal testis, with of Removal Laparoscopy, orchiectomy (including subcapsula Orchiectomy, simple Revision (including removal) Mammaplasty, augmentation; with prosthetic implant augmentation; Mammaplasty, Electrolysis epilation, each 30 minutes membrane Unlisted procedure, skin, mucous introitus of Plastic repair state intersex for Clitoroplasty Construction of artificia vagina; with graft Construction of artificial Revision (including removal) Revision (including removal) of Vaginoplasty Colovaginoplasty Colovaginoplasty Clitoroplasty Labiaplasty Trachea shave/reduction Amputation of Penis; complete Amputation Supplemental Table 3: CPT codes reflecting procedures for TF gender affirmation Page 79 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 80 of 87 92 Code 58291 58293 58294 58260 58270 55980 19303 19304 54660 56625 57110 55180 58290 th repair of enterocele 582 tube(s), or ovary(s) 58180 and/or salpingectomy 58661

43 or without removal of ovary(s) 58150 of tube(s) and/or ovary(s), wi l of tube(s) and/or ovary(s) http://bmjopen.bmj.com/ BMJ Open with or without removal of tial or total oophorectomy bilateral 58920 ith repair of enterocele with colpo-urethrocystopex or bilateral 58720 ystopexy (e.g., Marshall-Machetti-Krantz, Burch) ystopexy (e.g., Marshall-Machetti-Krantz, 58152 ilateral or on September 30, 2021 by guest. Protected copyright. d/or ovary(s), with repair of enterocele 58263 opexy (with or without endoscopic control) 58267 ginectomy; with repair of enterocele ginectomy; 58280 ial, unilateral than 250 grams; than 250 grams; without removal of tube(s), with adnexal structures (par For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml of tube(s), and/or ovary(s) 58262 eater than 250 grams; with remova eater than 250 grams; removal eater than 250 grams;with chauta type operation) 58285 l or partial vaginectomy; l or partial vaginectomy; 58275 unilateral or bilateral 58940

For peer review onlyus greater than 250 grams;w erus 250 grams or less; erus 250 grams repair of enterocele repair of enterocele r uterus greater than 250 grams; r uterus greater than 250 grams; Vaginal hysterectomy with removal with removal Vaginal hysterectomy of tube(s), an with removal Vaginal hysterectomy with colpo-urethrocyst Vaginal hysterectomy with Vaginal hysterectomy with tota Vaginal hysterectomy, with total or partial va Vaginal hysterectomy, radical (S Vaginal hysterectomy, for uterus greater Vaginal hysterectomy, for uterus gr Vaginal hysterectomy, for uterus gr Vaginal hysterectomy, fo Vaginal hysterectomy, for uter Vaginal hysterectomy, Vaginal hysterectomy, for ut Vaginal hysterectomy, Wedge (partial) resection or bisection of ovary, un Wedge (partial) resection Oophorectomy, partial or total, to male female surgery; Intersex complete simple, Mastectomy, subcutaneous Mastectomy, with or hysterectomy, Total abdominal with colpo-urethroc hysterectomy: Total abdominal (subtotal hysterectomy), hysterectomy abdominal Supracervical Laparoscopy, surgical with removal of Laparoscopy, surgical with removal or part complete Salpingo-oophorectomy, Procedure Insertion of Testicular Prosthesis Insertion of Testicular Prosthesis complete simple; Vulvectomy, of vaginal wall removal complete Vaginectomy, complicated Scrotoplasty; Supplemental Table 4: CPT codes reflecting procedures for TM gender affirmation 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Z90.79 Z87.890 0H0V0JZ 0VT94ZZ 0H0V07Z 0VT90ZZ 0VT50ZZ 0VT54ZZ 0VTS0ZZ 0VTS4ZZ 0H0V0ZZ 0VTC4ZZ 0VTB4ZZ 0VTB0ZZ 0VTC0ZZ 0H0V0KZ 0VT5XZZ 0VTSXZZ 85.5 64.3 62.3 85.53 62.41 62.42 85.52 70.61 85.54 85.55 85.51

44 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. hetic Substitute, Open Approach Open hetic Substitute, For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml CD-10 codes reflecting procedures for TF gender affirmation aneous Endoscopic Approach eous Endoscopic Approach eous Endoscopic Approach For peert otherwise specified review only with Nonautologous Tissue Substitute, Open Approach Open Tissue Substitute, with Nonautologous with Autologous Tissue Substitute, Open Approach ous Endoscopic Approach t, Open Approach on into breast for augmentation on into breast for augmentation Alteration of Bilateral Breast with Synt Bilateral of Alteration Bilateral Breast Alteration of Breas Bilateral of Alteration Resection of Penis, External Approach Resection of Vaginal construction of Penis Amputation Alteration of Bilateral Breast Personal history of sex reassignment Personal history of sex reassignment no mammoplasty, Augmentation Unilateral injecti Bilateral injection into breast for augmentation implant breast Bilateral to Breast Fat Graft Open Approach Scrotum, Resection of Percutaneous Endoscopic Approach Scrotum, Resection of External Approach Scrotum, Resection of Penis, Open Approach Resection of Penis, Percutane Resection of Unilateral breast implant Unilateral breast implant Resection of Right Testis, Percutan Resection of Left Testis, Open Approach Resection of Left Testis, Percutan Resection of Open Approach Bilateral Testes, Resection of Resection of Bilateral Testes, Percut Bilateral Testes, Resection of Name of Procedure testis of remaining Removal Acquired absence of other genital organ Right Testis, Open Approach Resection of ICD 9 Codes ICD 10 Codes Unilateral orchiectomy orchiectomy Unilateral operative episode of both testes at same Removal Supplemental Table 5: ICD-9 and I Page 81 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 82 of 87 0UQJ0ZZ 0UQJXZZ 0UQG0ZZ 0HDSXZZ 64.5 85.59 , open approach 0W4M0K0 45 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. utologous tissue substitute tologous tissue substitute, open approach 0W4M070 synthetic substitute, open approach 0W4M0J0 elsewhere classified (on penis) For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

th Autologous Tissue Substitute, Percutaneous Approach Percutaneous Approach Tissue Substitute, th Nonautologous th Autologous Tissue Substitute, External Approach External Approach Tissue Substitute, th Nonautologous For 0H0V37Z 0H0V3KZ peer 0H0VX7Z 0H0VXKZ review only Percutaneous Approach 0H0V3ZZ rineum, open approach 0W4M0Z0 Alteration of Bilateral Breast with Synthetic Substitute,Percutaneous Approach Approach Substitute,Percutaneous Breast with Synthetic Bilateral of Alteration Bilateral Breast wi Alteration of Breast, Bilateral of Alteration Alteration of Bilateral Breast wi Approach External Substitute, Breast with Synthetic Bilateral of Alteration Bilateral Breast wi Alteration of Approach Breast, External Bilateral of Alteration Extraction of hair, external approach Repair vagina, open approach Repair Clitoris, Open Approach Repair Clitoris, External Approach perineum with au Creation of vagina in male perineum with Creation of vagina in male 0H0V3JZ perineum with nona Creation of vagina in male pe Creation of vagina in male not sex transformation, Operations for Other mammoplasty Insertion of breast tissue expander 0H0VXJZ of breast tissue expander Removal 0H0VXZZ 85.95 85.96 Alteration of Bilateral Breast wi

46 http://bmjopen.bmj.com/ BMJ Open Percutaneous Assistance 0UT0FZZ ng Endoscopic 0UT08ZZ on September 30, 2021 by guest. Protected copyright. l Opening With Percutaneous Assistance 0UT1FZZ Artificial Openi Artificial Opening Endoscopic 0UT18ZZ and tubes at same operative episode and tubes at same 65.63 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml l or Artificial Opening 0UT07ZZ CD-10 codes reflecting procedures for TM gender affirmation bes at same operative episode bes at same 65.61 ral or Artificial Opening With ral or Artificial Opening With utaneous Endoscopic Approach 0UT24ZZ es at same operative episode es at same 65.53 eous Endoscopic Approach 0UT04ZZ ral or Artificial Opening 0UT17ZZ For peer review only eous Endoscopic Approach 0UT14ZZ at same operative episode 65.51 s, Open Approach 0UT20ZZ ovaries, unilateral bilateral ovaries, Supplemental Table 6: ICD-9 and I Name of Procedure Laparoscopic oophorotomy Other oophorotomy Acquired absence of ovaries Acquired absence of Acquired absence of Right Ovary, Open Approach Resection of Right Ovary, Percutan Resection of Right Ovary, Via Natura Resection of Right Ovary, Via Natural or Resection of Right Ovary, Via Natu Resection of ICD 9 Codes Left Ovary, Open Approach Resection of ICD 10 Codes Left Ovary, Percutan Resection of Left Ovary, Via Natu Resection of Left Ovary, Via Natural or Resection of Left Ovary, Via Natural or Artificia Resection of Ovarie Bilateral Resection of Perc Ovaries, Bilateral Resection of 0UT00ZZ 0UT10ZZ Laparoscopic unilateral oophorectomy Other unilateral oophorectomy Laparoscopic unilateral salpingo-oophorectomy Other unilateral salpingo-oophorectomy of both ovaries Other removal ovary of remaining Other removal of both ovari Laparoscopic removal ovary of remaining Laparoscopic removal of both ovaries and tu Other removal ovary and tube of remaining Other removal of both ovaries Laparoscopic removal ovary and tube of remaining Laparoscopic removal Acquired absence of other genital organ 65.41 65.31 65.49 65.39 65.54 65.52 65.64 65.62 Page 83 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 84 of 87 Z87.890 0UTG0ZZ 0HBV7ZZ 0HBV3ZZ 85.23 64.43 47 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. icial Opening With Percutaneous Assistance icial Opening With 0UT2FZZ l or Artificial Opening Endoscopic 0UT28ZZ For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml ral or Artificial Opening Artificial Opening Endoscopic Artificial Opening 0UTG8ZZ ssue, not otherwise specified 85.2 For peer review only flatable penile prosthesis 64.95 flatable penile prosthesis 64.97 Open Approach 0HBV0ZZ t, Open Approach 0HTV0ZZ Resection of Bilateral Ovaries, Via Natural or Artificial Opening Opening Artificial Via Natural or Ovaries, Bilateral Resection of Via Natura Bilateral Ovaries, Resection of or Artif Via Natural Ovaries, Bilateral Resection of Personal history of sex reassignment Excision or destruction of breast ti Subtotal mastectomy 0UT27ZZ Unilateral reduction mammoplasty Unilateral reduction mammoplasty Bilateral reduction mammoplasty Other unilateral subcutaneous mammectomy Other bilateral subcutaneous mammectomy Unilateral simple mastectomy Bilateral simple mastectomy Unilateral extended simple mastectomy mastectomy Bilateral extended simple Unilateral radical mastectomy Bilateral radical mastectomy Unilateral extended radical mastectomy Bilateral extended radical mastectomy Right Breast, Open Approach Resection of Left Breast, Open Approach Resection of Breas Bilateral Resection of Vagina, Open Approach Resection of 85.34 of non-in Insertion or replacement 85.31 85.36 of in Insertion or replacement 85.32 Breast, Bilateral Excision of Pe rcutaneous Approach Breast, Bilateral Excision of 85.43 85.41 85.44 85.42 85.47 85.45 85.48 85.46 0HTT0ZZ 0HTU0ZZ Resection of Vagina, Percutaneous Endoscopic Approach Approach Vagina, Percutaneous Endoscopic Resection of Opening Artificial Natural or Vagina, Via Resection of Vagina, Via Natural or Resection of Obliteration and total excision of vagina Construction of penis Via Natu Breast, Bilateral Excision of 0UTG4ZZ 0UTG7ZZ 70.4 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from 0UTJ0ZZ 0W4N0J1 0UT77ZZ 0UT74ZZ 0UT90ZZ 0UT98ZZ 0UT97ZZ 0UT94ZZ 0UT78ZZ 0UT70ZZ 0UT7FZZ 0W4N071 0UTJXZZ 0UTC0ZZ 0UTC8ZZ 0UTC4ZZ 0UTC7ZZ 0W4N0Z1 0HBV8ZZ 0UT9FZZ 0W4N0K1 0UTM0ZZ 0HBVXZX 0UTMXZZ 62.7 67.4 64.95 66.51 68.31 68.39 68.41 , open approach 48 http://bmjopen.bmj.com/ BMJ Open ing Endoscopic on September 30, 2021 by guest. Protected copyright. utologous tissue substitute tural or Artificial Open Percutaneous Opening With or Artificial tural synthetic substitute, open approach ial Opening With Percutaneous Endoscopic ial Opening With For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Percutaneous Endoscopic Approach Opening or Artificial Via Natural Artificial Opening Endoscopic Artificial Opening Endoscopic rnal Approach, Diagnostic or Artificial Opening Opening Artificial or l or Artificial Opening Opening Artificial l or

tubes, Open Approach For peer review only ous Endoscopic Opening ous Endoscopic Opening rineum, open approach vical hysterectomy vical hysterectomy Resection of clitoris, Open Approach Resection of clitoris, External Approach Resection of vulva, Open Approach Resection of vulva, External Approach Resection of Creation of penis in female perineum with au tologous tissue substitute, open approach Creation of penis in female pe Insertion of Testicular Prosthesis Insertion of testicular prosthesis of cervix Amputation operative episode of both fallopian tubes at same Removal Laparoscopic supracer hysterectomy Other and unspecified subtotal abdominal hysterectomy Laparoscopic total abdominal Resection of cervix, Via Natural or Resection of Resection of bilateral fallopian fallopian bilateral Resection of Creation of penis in female perineum with Creation of penis in female perineum with nona Resection of bilateral fallopian tubes, Resection of bilateral fallopian tubes, Resection of bilateral fallopian tubes, Via Na Resection of bilateral fallopian tubes, Via Na Resection of Endoscopic Assistance uterus, Open Approach Resection of uterus, Percutane Resection of uterus, Via Natura Resection of uterus, Via Natural or Resection of uterus, Via Natural or Artific Resection of Assistance cervix, Open Approach Resection of cervix, Percutane Resection of cervix, Via Natural Resection of Excision of Bilateral Breast, Via Natural or Artificial Opening Endoscopic Excision of Bilateral Breast, Exte Page 85 of 87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 86 of 87 68.9 68.49 68.51 68.59 68.61 68.69 68.71 68.79 49 http://bmjopen.bmj.com/ BMJ Open on September 30, 2021 by guest. Protected copyright. te, Percutaneous Endoscopic Approach 0VUS47Z ubstitute, Percutaneous Approach ubstitute, 0VUS4KZ e substitute, Open Approach e substitute, 0VUS0KZ ubstitute, External Approach 0VUSX7Z e substitute, Open Approach 0VUS07Z For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml For peer review only l abdominal hysterectomy hysterectomy l abdominal cal vaginal hysterectomy vaginal hysterectomy vaginal hysterectomy abdominal hysterectomy hysterectomy abdominal Supplement penis with nonautologous tissue substitute, External Approach substitute, tissue penis with nonautologous Supplement 0VUSXKZ Other and unspecified total abdominal hysterecto Other and unspecified total abdominal approach open testes with synthetic substitute, of bilateral Replacement penis with autologous tissu Supplement penis with autologous tissue substitu Supplement penis with autologous tissue s Supplement Approach Open substitute, penis with synthetic Supplement Approach Percutaneous Endoscopic substitute, penis with synthetic Supplement External Approach substitute, penis with synthetic Supplement tissu penis with nonautologous Supplement s tissue penis with nonautologous Supplement 0VRC0JZ 0VUS4JZ 0VUS0JZ 0VUSXJZ Laparoscopically assisted Laparoscopically Other and unspecified vaginal hysterectomy Laparoscopic radical radica Other and unspecified Laparoscopic radical vaginal hysterectomy Other and unspecified radi hysterectomy Other and unspecified 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open: first published as 10.1136/bmjopen-2017-018121 on 27 December 2017. Downloaded from Page 87 of 87 BMJ Open