Primary and Preventive Care for Transgender and Non-Binary People

Madeline B. Deutsch, MD, MPH Associate Professor of Clinical Family & Community Medicine Medical Director, UCSF Transgender Care University of California – San Francisco November 2, 2019 Disclosures

. Nothing relevant to disclose

. Will discuss off-label use of FDA approved medications 46 y/o transgender man wants to begin testosterone therapy

. BMI 32 . Hx oligomenorrhea . Taking escitalopram for anxiety . In a monogamous relationship with non-transgender (cisgender) male partner . Has been living full time as a male for 3 years . Interested in chest surgery 35 year old transgender woman wants to begin estrogen therapy

. History of borderline hyperlipidemia according to her prior physician . ½ ppd smoker x 10 years, unwilling to quit . Has been cross-dressing for many years in secret . Married to a heterosexual woman who is not accepting of pt desires, they have a 3 y/o son . Has not yet spoken with coworkers/boss 19 year old person presents seeking primary care

. Name: Chase . Gender ID: Non-binary . Pronouns: They/Them . Birth-assigned sex: Male . Housing: Couch surfing . Income: Occasional sex work, food stamps . Substance abuse: Tobacco 2-3 cig/day, marijuana . Polyamorous, some condomless receptive and insertive sex Tobacco

. Smoking in the setting of any estrogen use is a risk factor for venous thromboembolism (VTE)

. What if unwilling or unable to quit? . Harm reduction approach . Transdermal estradiol (lower VTE risk) . Aspirin 81mg/day . Risk/benefit ratio for gastrointestinal hemorrhage is unknown Pituitary adenoma

. Several cases have been reported in transgender women(19)

. However, Endocrine Society guidelines recommend watchful waiting only in cases of assymptomatic prolactinomas (20)

. Therefore in the absence of visual disturbances, galactorrhea, or headache syndromes, routine monitoring of prolactin not likely of clinical value Migraines

. Migraines have a clear hormonal component

. Patients with hx of complex/severe migraines should begin at low dose and titrate slowly

. Oral or transdermal routes may be preferred to avoid cyclic levels seen with injected estrogen (24)

. Unclear if the known increased risk of stroke in patients using oral contraceptives with a history of aura applies to transgender patients using 17- beta estradiol Use of estrogens in the perioperative period

. No clear evidence that transgender women at average risk of VTE should stop estrogen in the perioperative period . Lowering dose or changing to transdermal route may be advisable (27)

. Studies of risks of perioperative oral contraceptives (ethinyl estradiol) have mixed results and methodological limitations (28)

. Stopping hormones abruptly in the setting of major surgery and gonadectomy can have negative impact Venous thromboembolism – data from menopause literature

. Menopausal studies suggest no increased risk when transdermal estradiol used (29)

. Menopausal data on oral 17-beta estradiol is mixed, with risks as high as 2.5-4x increase (10,29) . With a background rate of 1:1,000 to 1:10,000 in general population, absolute increase is small (4) Venous thromboembolism – data in transgender women

. Studies > 10 years old showing 20 to 40 fold increase involved use of up to 200mcg/day of ethinyl estradiol, and did not control for tobacco use (30,31) . These studies are not applicable to modern 17-beta estradiol regimens used in an average risk, non-smoking population

. No increased risk has been observed in a large retrospective sample of Dutch transgender women using 17-beta estradiol (5) Primary and secondary prevention of VTE

. Insufficient evidence to guide the use of estrogen therapy, anticoagulation, or antiplatelet therapy in transgender women with risk factors or personal history of DVT

. Case series of 11 transgender women with activated protein C resistance using transdermal estradiol without anticoagulation or antiplatelet therapy found no VTE after mean 64 months (32) Coexisting metabolic disorders

. Metabolic syndrome . Obesity . Hyperlipidemia . Impaired glucose tolerance . Polycystic ovarian syndrome (PCOS) Coexisting metabolic disorders

. PCOS is not a contraindication to testosterone therapy . Do maintain higher index of suspicion for hyperlipidemia and diabetes

. Amenorrhea in the presence of testosterone generally indicates endometrial atrophy (18,19) rather than hyperplasia Coexisting metabolic disorders

. Psychosocial benefits of testosterone may include positive lifestyle changes which can reduce obesity and glucose and lipid disorders

. These benefits likely outweigh any potential increased metabolic risks Acne

. Approach is similar to that in non-transgender people

. Acne tends to peak in 1st year of therapy, then declines (20)

. Avoiding supraphysiologic levels, and avoiding excessive peaks associated with prolong (2-4 week) dosing intervals may help minimize acne Coronary artery disease screening

. 48 y/o transgender person seeking to begin hormone therapy . Father died at age 59 of heart attack . BMI 29 . They want to know about their cardiac risk . Should they have their cholesterol checked before starting treatment? Coronary artery disease screening Considerations

. Any additional/specific screening recommendations?

. What does the evidence say . Baseline risk, contributions of minority stress . Any added risk from hormone therapy?

. What gender to use when calculating risk?

. Primary prevention?

. Any specific hormone therapy considerations to reduce risk?

Cis Cis Cis Cis Cis Cis

Vaginal Flora in the Neovagina

. Lack of lactobacilli and presence of BV

. No association between symptoms and a particular species STI screening after vaginoplasty?

. Penile inversion technique – skin lined vagina . ? Urethral mucosa used

. Sigmoid colon vaginoplasty . Less common . Mucosa Breast Cancer Breast Cancer – Transgender Women

Mean age @ start of tx 29 +/- 13 yrs Mean follow-up period 21 +/- 9 yrs

Estimated 4.1 cases / 100k person-years (95% CI = 0.8 to 13)

Rates in the cis Dutch population 1.1/100k men and 155/100k women Breast Cancer – Transgender Men

. Estrogen levels persist when on testosterone (aromatase activity) . Role of testosterone in breast cancer pathogenesis . How do you screen someone post-mastectomy? Breast Cancer – Transgender Men

Mean age @ start of tx 23 +/- 7 yrs Mean follow-up period 20 +/- 7 yrs

Estimated 5.9 cases / 100k person-years (95% CI = 0.5 to 27.4)

Rates in the cis Dutch population 1.1/100k men and 155/100k women

? Study Limitations

. Retrospective cohort - this was not a screened population . Outcome of breast cancer was only based on clinical presentation / diagnosis . Did not stratify by mastectomy status . Use of hormones not clear . How were transgender subjects identified?

Female >90% endorsed preference for self-collection over provider collection

47 Cancer Screening Potpourri

. Trans women . Breast CA if > 5 yrs lifetime estrogen AND > 50 y/o . Prostate CA ? (tx for prostate CA is E + anti-andr)

. Trans men . Breast CA as with non-trans women if no surg . Chest wall exam/MRI/UTZ if post-surg? . No evidence of risk of Ovarian/Uterine CA . Trans men require routine cervical screening Cancer & Osteoporosis Potpourri

. Trans women . Breast CA if > 5 yrs lifetime estrogen AND > 50 y/o . Prostate CA ? (tx for prostate CA is E + anti-andr) . Osteoporosis as with non-trans or sooner if prolonged period without hormones < age 50

. Trans men . Breast CA as with non-trans women if no surg . Chest wall exam/MRI/UTZ if post-surg? . No evidence of risk of Ov/Ut CA . Trans men require routine cervical screening . Osteoporosis as with non-trans or sooner if prolonged period without hormones < age 50

Fertility Fertility

. Transgender women . Sperm storage . Surgical sperm extraction . Removes need for orgasm . Invasive procedure

. Transgender men . Oocyte / embryo / tissue preservation Fertility - Options

. Post-hormones . Sperm preservation…. Stop hormones? HCG?

. Impact of T on ovarian structure/function . Cumulative T exposure? . Time since d/c T?

. Role of contraception Pregnancy and Transgender Men

. 41 FTM, mean age 28

. 20% conceived while still amenorrheic

. 11/13 “at risk” wanted to avoid pregnancy . 4 of 11 on T . 3 of 4 w/ amenorrhea

. 3 of 11 not using contraception . 2 of 3 on T . 1 of 2 amenorrheic