REPRODUCTION AND DEVELOPMENT REPRODUCTION AND DEVELOPMENT MENOPAUSE MALE HYPOGONADISM UP TO VMS LEFT UNTREATED 80% ACCOUNTS FOR 2.29% OF WOMEN OF MEN IN THEIR 40S USD UNDERGOING $1,365 AND (DIRECT COSTS) AND MENOPAUSE EXPERIENCE 3.75% VASOMOTOR $781 USD OF MEN IN THEIR 60S SYMPTOMS (VMS).1 (INDIRECT COSTS) PER YEAR.2 TOOK ANDROGEN REPLACEMENT THERAPY IN 2011.4 DISORDERS OF SEXUAL DEVELOPMENT TURNER 1:16,000– SYNDROME OCCURS IN ONE 1:18,000 IN 2,500 LIVE- BORN FEMALES.8 CONGENITAL ADRENAL HYPERPLASIA HAS AN BETWEEN 2000 TO 2011 INCIDENCE IN THE US.7 GLOBALLY, TESTOSTERONE KLINEFELTER SALES PER YEAR WENT FROM SYNDROME $165 MILLION USD TO IS THE MOST $2 BILLION USD.5 PCOS FREQUENT MALE CHROMOSOMAL DISORDER, $5.46 WITH A PREVALENCE OF $5,000– BILLION APPROXIMATELY ASSOCIATED COST OF 150 PER 100,000 $10,000 EVALUATION AND CARE LIVE-BORN ANNUAL COST OF TOPICAL OF PCOS IN 2005 (IN USD).3 MALES.9 ANDROGEN (IN USD).6 Source: 1 Woods et al. 2005 and Gold et al. 2006 4 Baillargeon et al. 2013 7 Pearce et al. 2016 2 Sarrel et al. 2013 5 Handelsman. 2013 8 Pinsker et al. 2012 3 Azziz et al. 2005 6 Abbvie. 2017 9 Groth et al. 2013 © 2017 The Endocrine Society. All rights reserved. Endocrine Society 2055 L Street NW, Suite 600 Washington, DC 20036 USA Phone: 202.971.3636 Fax: 202.736.9705 endocrine.org Mission Statement of the Acknowledgements We also acknowledge the Endocrine Society The production of Endocrine Facts contributions of Nikki Deoudes The mission of the Endocrine and Figures would not have been and Eric Vohr. Society is to advance excellence possible without the guidance of: in endocrinology and promote For More Information its essential and integrative role Advisory Panel For more information, updates, and in scientific discovery, medical Robert A. Vigersky, MD (Chair) the online version of this report, visit: practice, and human health. Walter Reed National Military endocrinefacts.org Medical Center About Endocrine Facts Suggested Citation and Figures Ursula B. Kaiser, MD The Endocrine Society requests that Endocrine Facts and Figures is a Brigham and Women’s Hospital this document be cited as follows: compendium of epidemiological The Endocrine Society. Endocrine data and trends related to a Sherita H. Golden, MD, MHS Facts and Figures: Reproduction spectrum of endocrine diseases. Johns Hopkins University and Development. First Edition. The data is organized into nine 2017. chapters covering the breadth Joanna L. Spencer-Segal, MD, PhD of endocrinology: Adrenal, University of Michigan Disclaimer Bone and Mineral, Cancers and This publication summarizes Neoplasias, Cardiovascular and R. Michael Tuttle, MD current scientific information Lipids, Diabetes, Hypothalamic- Memorial Sloan Kettering about epidemiology and trends Pituitary, Obesity, Thyroid, and Cancer Center data related to a spectrum of Reproduction and Development. endocrine diseases. It is not a William F. Young, Jr., MD, MSc practice guideline or systematic All data is sourced from peer- Mayo Clinic review. Except when specified, reviewed publications, with an this publication does not represent additional round of review by a Reproduction and Development the official policy of the Endocrine group of world-renowned experts in Expert Reviewers Society. the field. Additional oversight from Adrian Dobs, MD, MHS the Endocrine Facts and Figures Johns Hopkins University © 2017 The Endocrine Society. Advisory Panel ensured fair and All rights reserved. This is an balanced coverage of data across Alice Chang, MD official publication of The Endocrine the therapeutic areas. Mayo Clinic Society. No part of this publication may be reproduced, translated, The first edition ofEndocrine Facts Michael Irwig, MD modified, enhanced, and/or and Figures emphasizes data on the George Washington University transmitted in any form or by United States. Future updates to the any means without the prior report will include additional data for Nanette Santoro, MD written permission of The other countries. University of Colorado, Denver Endocrine Society. To purchase additional reprints Endocrine Society Staff or obtain permissions, e-mail Lucia D. Tejada, PhD [email protected]. © 2017 The Endocrine Society. All rights reserved. generally moderate to severe2-5. Up to 80% of women who I. OVERVIEW are going through the menopausal transition experience This chapter presents data on endocrine and endocrine- VMS6,7. VMS are one of the chief menopause-associated related reproductive and developmental conditions and issues for which women seek medical treatment in the disorders, including: menopause, male hypogonadism, US8,9. VMS may also be associated with greater bone loss, polycystic ovary syndrome (PCOS), premature ovarian higher bone turnover, and elevated cardiovascular risk10-12. failure/primary ovarian insufficiency (POF/POI), congenital adrenal hyperplasia (CAH), and Turner syndrome (TS). In Data indicates that most women who have moderate to instances when United States (US)-based data are limited, severe VMS do not receive treatment13. The annual direct we present data from international studies. (inpatient and outpatient visits) and indirect (loss of work productivity [medically related absenteeism and disability]) II. MENOPAUSE costs for women with untreated VMS are approximately 13 2.1 US $1,365; and $781, respectively . PREVALENCE AND INCIDENCE 2.3 Menopause is defined as the time when women have their final menstrual period. Data collected from 3,302 DEMOGRAPHIC DIFFERENCES women in the Study of Women’s Health Across the Nation The age of final menopause (when adjusted for other 1 suggests that the median age when US women will factors) does not vary significantly by race (Table 2) . experience menopause is approximately 52.5 years1. However, duration of total VMS does vary by race/ 2.2 ethnicity, with Japanese and Chinese women having the COST BURDEN OF DISEASE shortest total VMS durations (median, 4.8 and 5.4 years, respectively) and African American women having the Vasomotor symptoms (VMS) are a main feature of the longest total VMS duration (median, 10.1 years). The total menopausal transition and can have a significant effect VMS duration for non-Hispanic white women was 6.5 on a person’s quality of life2-4. VMS primarily include years, and for Hispanic women it was 8.9 years15. night sweats and hot flashes, and these symptoms are Table 1 Baseline costs for vasomotor symptom treatment in 2017 US dollars.* MODERATE TO SEVERE VMS COSTS 90-day supply of clonidine $40 Two physician visits $172 THERAPY INITIATION Two physician visits $172 DRUG ACQUISITION COSTS Norethindrone acetate/ethinyl E2 $465 Conjugated estrogen/medroxyprogesterone $618 BREAKTHROUGH BLEEDING AT 3 MONTHS (OR CONTINUED SPOTTING AT 6 MONTHS) Endometrial biopsy $258 Pathology and laboratory fees $191 TELEPHONE CALL TO PHYSICIAN Spotting at 3 months $21 Source: Utian et al. 200514 Abbreviations: VMS, vasomotor symptoms; E2, estradiol. Notes: *, approximated using and inflation calculator. © 2017 The Endocrine Society. All rights reserved. ENDOCRINE SOCIETY | 1 Table 2 Age of final menstrual period by race. RACE/ETHNICITY ADJUSTED P VALUE UNADJUSTED P VALUE Hispanic 53.10 0.653 50.86 0.0009 African American 52.59 0.653 52.17 0.0009 Chinese 52.86 0.653 52.41 0.0009 Japanese 53.24 0.653 53.14 0.0009 Caucasianb 52.85 0.653 52.88 0.0009 Source: Gold et al. 20131 Notes: Median age (years) at final menstrual period, adjusted and unadjusted for baseline covariates and time-invariant predictors (Multivariate Cox Proportional Hazards Model);b, this was the reference group used for covariate adjustments. 2.4 Table 3 LIFE EXPECTANCY AND MORTALITY Symptoms and signs of androgen deficiency in men. Later age at natural menopause has been associated A. MORE SPECIFIC SYMPTOMS AND SIGNS with numerous positive health outcomes16-18, such as longer survival, greater life expectancy19 and Breast discomfort, gynecomastia reduced rates of: all-cause mortality20, cardiovascular Incomplete or delayed sexual development, eunuchoidism 21,22 19,23-29 30 death , cardiovascular disease (CVD) , stroke , Reduced sexual desire (libido) and activity atherosclerosis31, angina after myocardial infarction32, Inability to father children, low or zero sperm count osteoporosis33, and low bone density and fracture34,35. However, later age at menopause has also been Decreased spontaneous erections associated with higher risk of breast, endometrial, and Hot flushes, sweats 19,36-39 ovarian cancer . Loss of body (axillary and pubic) hair, reduced shaving Very small (especially <5 ml) or shrinking testes III. MALE HYPOGONADISM Height loss, low trauma fracture, low bone mineral density As men age past 30 years, circulating testosterone B. OTHER LESS SPECIFIC SYMPTOMS AND SIGNS (T) declines progressively by 0.4 to 2% per year40- Diminished physical or work performance 42. Symptoms of androgen deficiency may include decreased energy, mood, muscle mass and strength, Decreased energy, motivation, initiative, and self-confidence erectile function, bone density, and libido43. Erectile Poor concentration and memory dysfunction, low libido, and lack of morning erections Feeling sad or blue, depressed mood, dysthymia are the symptoms that are most specific for male hypogonadism44. Increased body fat, BMI Sleep disturbance, increased sleepiness 3.1 Mild anemia (normochromic, normocytic, in the female range) PREVALENCE AND INCIDENCE Reduced muscle bulk and strength One US study on osteoporosis and androgens in a cohort Source: Bhasin et al. 201145