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Injectable estrogens are options for gender-affirming hormone therapy per guidelines, which suggest intramuscular dosages of 5-30 mg every 2 weeks or 2-10 mg weekly with estradiol cypionate or valerate interchangeably. Data among transgender and gender-diverse patients are limited due to local unavailability and concerns around laboratory assay variability and estradiol (E2) level fluctuation. We note a concerning trend where patients are prescribed high-dose injections based on the guidelines leading to serum E2 levels well above the range recommended in the same guidelines. Our review indicates that 5 mg weekly or lower should be prescribed when initiating injectable estrogens to avoid supraphysiologic E2 levels., (Copyright 2024, Mary Ann Liebert, Inc., publishers.)

Objective: Feminizing gender-affirming hormone therapy is the mainstay of treatment for many transgender and gender diverse people. Injectable estradiol preparations are recommended by the World Professional Association for Transgender Health Standards of Care 8 and the Endocrine Society guidelines. Many patients prefer this route of administration, but few studies have rigorously assessed optimal dosing or route., Methods: We performed a scoping review of the available data on estradiol levels achieved with various dosages of estradiol injections in transgender and gender diverse adults on feminizing gender-affirming hormone therapy. We also report on testosterone suppression, route (ie, subcutaneous vs intramuscular), and type of injectable estradiol ester as well as timing of blood draw relative to the most recent dose, where available., Results: The data we reviewed suggest that the current guidelines, which recommend starting doses 2 to 10 mg weekly or 5 to 30 mg every 2 weeks of estradiol cypionate or valerate, are too high and likely lead to patients having supraphysiologic levels across much of their injection cycle., Conclusions: The optimal starting dose for injectable estradiol remains unclear and whether it should differ for cypionate and valerate. Based on the data available, we suggest that clinicians start injectable estradiol cypionate or valerate via subcutaneous or intramuscular injections at a dose ≤5 mg weekly and then titrate accordingly to keep levels within guideline-recommended range. Future studies should assess timing of injections and subsequent levels more precisely across the injection cycle and between esters., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2024 AACE. All rights reserved.)

Background: The effect of gender-affirming testosterone therapy (TT) on breast cancer risk is unclear. This study investigated the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs)., Methods: Of the 444 TMIs who underwent chest-contouring surgeries between 2013 and 2019, breast tissue composition was assessed in 425 TMIs by the pathologists (categories of lobular atrophy and stromal composition) and using our automated deep-learning algorithm (% epithelium, % fibrous stroma, and % fat). Forty-two out of 444 TMIs had mammography prior to surgery and their breast tissue density was read by a radiologist. Mammography digital files, available for 25/42 TMIs, were analyzed using the LIBRA software to obtain percent density, absolute dense area, and absolute non-dense area. Linear regression was used to describe the associations between duration of TT use and breast tissue composition or breast tissue density measures, while adjusting for potential confounders. Analyses stratified by body mass index were also conducted., Results: Longer duration of TT use was associated with increasing degrees of lobular atrophy (p < 0.001) but not fibrous content (p = 0.82). Every 6 months of TT was associated with decreasing amounts of epithelium (exp(β) = 0.97, 95% CI 0.95,0.98, adj p = 0.005) and fibrous stroma (exp(β) = 0.99, 95% CI 0.98,1.00, adj p = 0.05), but not fat (exp(β) = 1.01, 95%CI 0.98,1.05, adj p = 0.39). The effect of TT on breast epithelium was attenuated in overweight/obese TMIs (exp(β) = 0.98, 95% CI 0.95,1.01, adj p = 0.14). When comparing TT users versus non-users, TT users had 28% less epithelium (exp(β) = 0.72, 95% CI 0.58,0.90, adj p = 0.003). There was no association between TT and radiologist's breast density assessment (p = 0.58) or LIBRA measurements (p > 0.05)., Conclusions: TT decreases breast epithelium, but this effect is attenuated in overweight/obese TMIs. TT has the potential to affect the breast cancer risk of TMIs. Further studies are warranted to elucidate the effect of TT on breast density and breast cancer risk., (© 2024. The Author(s).)

There is limited literature about breast cancer in the transgender population. Very little is known about how gender-affirming hormone therapy affects their breast cancer risk. On the other end, for those diagnosed with breast cancer, there are no clinical guidelines to manage their breast cancer, specifically, how to manage their gender-affirming hormone therapy during breast cancer treatment. Here, we report a 52-year-old transman diagnosed with a grade 2 invasive ductal carcinoma (ER+/PR+/HER2-), and ductal carcinoma in situ (DCIS) of intermediate grade. We discussed his risk factors as well as treatment options., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Finasteride may cause low libido and erectile dysfunction and the product label of finasteride also includes post-marketing reactions of sexual dysfunction that continued after discontinuation of treatment, as well as male infertility and depression. The aim of this study was to evaluate the beliefs and counseling practices among dermatologists regarding adverse effects of finasteride. Anonymous paper surveys were personally distributed to 122 attendees at two annual major dermatology meetings. The participation rate was 82% with 47% women and 77% residents of the United States. 51% of respondents believed that finasteride could cause sexual side effects and 18% believed that it could cause persistent sexual side effects. Fewer than a quarter believed that finasteride could cause depression or lower sperm counts. When initiating finasteride, 69% of respondents counseled at least half of their patients about potential sexual side effects with 52% for persistent sexual side effects and 30% for depression. This study identifies the need for greater awareness of the potential adverse effects of finasteride and identifies opportunities for improvement in counseling practices that reflect finasteride's product labeling., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Although there has been a dramatic increase in visibility and recognition of transgender and gender-diverse populations, remarkably little has been published on prevalence rates of hypertension within these populations. In addition to summarizing the limited data on prevalence rates, this review compares the prevalence rates with those of cisgender populations and explores whether gender-affirming hormone therapy affects blood pressure and hypertension rates. The studies show that hypertension affects a significant proportion of transgender and gender-diverse people and support the practice of routinely monitoring blood pressure in transgender and gender-diverse people, especially after the initiation of gender-affirming hormone therapy. The two largest studies both found that estrogen plus an antiandrogen was associated with a decrease in systolic blood pressure and that testosterone was associated with an increase in systolic blood pressure., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The effects of gender-affirming hormone therapy on lipid profiles among transgender adults have been inconsistent and incompletely characterized., Objective: To longitudinally assess changes to lipid profiles following hormone therapy and to establish prevalence rates of hyperlipidemia/low HDL-cholesterol., Methods: This longitudinal study followed lipid profiles of 366 transgender and gender-diverse adult patients (170 transfeminine and 196 transmasculine; mean age, 28 years) in Washington DC USA. Lipid profiles were measured at baseline and at multiple follow-up clinical visits up to 57 months after the initiation of hormone therapy., Results: Within 2-10 months of starting gender-affirming hormone therapy, mean levels of HDL-cholesterol decreased by 16% in transmasculine individuals and increased by 11% in transfeminine individuals. Over the study, mean triglyceride levels increased by 26-37% in the transmasculine group. Over the study, the prevalence of moderate hypertriglyceridemia (175-499 mg/dL) ranged from 11 to 32% in the transfeminine group and 6-19% in the transmasculine group. Severe hypertriglyceridemia (≥500 mg/dL) was only observed in one individual. On hormone therapy, 24-30% of the transfeminine group had a HDL-cholesterol < 50 mg/dL and 16-24% of the transmasculine group had a HDL-cholesterol < 40 mg/dL. LDL-cholesterol levels ≥160 mg/dL were rare among both groups., Conclusions: In a gender-diverse population on hormone therapy, low HDL-cholesterol and moderate hypertriglyceridemia were relatively common. HDL-cholesterol decreased with testosterone therapy and increased with a combination of oral estrogen and spironolactone. Testosterone use was associated with an increase in triglycerides. Our data support the recommendation to routinely monitor lipid profiles in gender-diverse patients on GAHT., Competing Interests: Declaration of Competing Interest The authors declared no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Background: Transgender healthcare is a rapidly evolving interdisciplinary field. In the last decade, there has been an unprecedented increase in the number and visibility of transgender and gender diverse (TGD) people seeking support and gender-affirming medical treatment in parallel with a significant rise in the scientific literature in this area. The World Professional Association for Transgender Health (WPATH) is an international, multidisciplinary, professional association whose mission is to promote evidence-based care, education, research, public policy, and respect in transgender health. One of the main functions of WPATH is to promote the highest standards of health care for TGD people through the Standards of Care (SOC). The SOC was initially developed in 1979 and the last version (SOC-7) was published in 2012. In view of the increasing scientific evidence, WPATH commissioned a new version of the Standards of Care, the SOC-8. Aim: The overall goal of SOC-8 is to provide health care professionals (HCPs) with clinical guidance to assist TGD people in accessing safe and effective pathways to achieving lasting personal comfort with their gendered selves with the aim of optimizing their overall physical health, psychological well-being, and self-fulfillment. Methods: The SOC-8 is based on the best available science and expert professional consensus in transgender health. International professionals and stakeholders were selected to serve on the SOC-8 committee. Recommendation statements were developed based on data derived from independent systematic literature reviews, where available, background reviews and expert opinions. Grading of recommendations was based on the available evidence supporting interventions, a discussion of risks and harms, as well as the feasibility and acceptability within different contexts and country settings. Results: A total of 18 chapters were developed as part of the SOC-8. They contain recommendations for health care professionals who provide care and treatment for TGD people. Each of the recommendations is followed by explanatory text with relevant references. General areas related to transgender health are covered in the chapters Terminology, Global Applicability, Population Estimates, and Education. The chapters developed for the diverse population of TGD people include Assessment of Adults, Adolescents, Children, Nonbinary, Eunuchs, and Intersex Individuals, and people living in Institutional Environments. Finally, the chapters related to gender-affirming treatment are Hormone Therapy, Surgery and Postoperative Care, Voice and Communication, Primary Care, Reproductive Health, Sexual Health, and Mental Health. Conclusions: The SOC-8 guidelines are intended to be flexible to meet the diverse health care needs of TGD people globally. While adaptable, they offer standards for promoting optimal health care and guidance for the treatment of people experiencing gender incongruence. As in all previous versions of the SOC, the criteria set forth in this document for gender-affirming medical interventions are clinical guidelines; individual health care professionals and programs may modify these in consultation with the TGD person., Competing Interests: Conflict of interests were reviewed as part of the selection process for committee members and at the end of the process before publication. No conflicts of interest were deemed significant or consequential., (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Background: A set of enduring conditions have been reported in the literature involving persistent sexual dysfunction after discontinuation of serotonin reuptake inhibiting antidepressants, 5 alpha-reductase inhibitors and isotretinoin., Objective: To develop diagnostic criteria for post-SSRI sexual dysfunction (PSSD), persistent genital arousal disorder (PGAD) following serotonin reuptake inhibitors, post-finasteride syndrome (PFS) and post-retinoid sexual dysfunction (PRSD)., Methods: The original draft was designed using data from two published case series (Hogan et al., 2014 and Healy et al., 2018), which represent the largest public collections of data on these enduring conditions. It was further developed with the involvement of a multidisciplinary panel of experts., Results: A set of criteria were agreed upon for each of the above conditions. Features of PSSD, PFS and PRSD commonly include decreased genital and orgasmic sensation, decreased sexual desire and erectile dysfunction. Ancillary non-sexual symptoms vary depending on the specific condition but can include emotional blunting and cognitive impairment. PGAD presents with an almost mirror image of unwanted sensations of genital arousal or irritability in the absence of sexual desire. A new term, post-SSRI asexuality, is introduced to describe a dampening of sexual interest and pleasure resulting from a pre-natal or pre-teen exposure to a serotonin reuptake inhibitor., Conclusions: These criteria will help in both clinical and research settings. As with all criteria, they will likely need modification in the light of developments.

Background: Obesity rates and weight changes in adults on gender-affirming hormone therapy are lacking or limited by small sample sizes, duration, and location., Subjects/methods: This longitudinal study followed the body mass index and body weights of 470 transgender and gender-diverse adult patients (247 transfeminine and 223 transmasculine; mean age, 27.8 years) seen at a Federally Qualified Health Center and an academic endocrinology practice, both in Washington DC USA. Body weight and body mass index were recorded at baseline and at multiple follow-up clinical visits up to 57 months after the initiation of gender-affirming hormone therapy. The outcomes of this study were the changes to body weight and obesity rates following hormone therapy., Results: Within 2-4 months of starting gender-affirming hormone therapy, the mean body weight increased in the transmasculine group by 2.35 (1.15-3.55) kg and further increased beyond 34 months. Among the transfeminine group, the mean body weight was stable for the first 21 months of hormone therapy and then began to steadily increase, particularly in those under 30 years old. The prevalence of obesity at baseline was 25% in the transfeminine group and 39% in the transmasculine group. Following the initiation of hormone therapy, rates of obesity ranged from 42 to 52% among the transmasculine group and 21 to 30% among transfeminine group. Following 11-21 months of hormone therapy, weight gain ≥5 kg was seen among 21% of transfeminine individuals and 30% of transmasculine individuals., Conclusions: As compared with transfeminine individuals, transmasculine individuals have greater rates of obesity and weight gain before and during hormone therapy. Body weight and body mass index should be routinely monitored before and after the initiation of gender-affirming hormone therapy. Multidisciplinary weight-reduction interventions should be promoted where appropriate., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

This commentary will explore the important clinical question regarding whether the antiandrogen class of 5α-reductase inhibitors should be considered as an effective and safe treatment option for transfeminine and/or transmasculine individuals. The use of finasteride in transfeminine individuals is based upon the theory that the goal of medical treatment is to reduce the concentrations of androgens, including dihydrotestosterone. Nonetheless, it is unclear that finasteride will have any additive clinical benefit once testosterone levels have already been lowered with standard treatment regimens (i.e. estrogen with spironolactone or cyproterone acetate). For transmasculine individuals, 5α-reductase inhibitors may be a potential treatment option for a subset with androgenetic alopecia but may come at the expense of impairing virilization driven by dihydrotestosterone. In the absence of efficacy and safety data on 5α-reductase inhibitors in gender diverse populations, clinicians should discuss this issue with patients who request or are contemplating their use., (© 2020 American Society of Andrology and European Academy of Andrology.)

Male hypogonadism is defined as an abnormally low serum testosterone concentration or sperm count. As men age, often in the context of obesity and other comorbid conditions, serum testosterone levels may decrease. Normalizing serum testosterone levels in male adults with hypogonadism may improve symptoms related to androgen deficiency, but controversies exist regarding the long-term benefits and risks of hormone supplementation in this setting. In 2020, the American College of Physicians published a clinical guideline for the use of testosterone supplementation in adult men based on a systematic review of available evidence. Among their recommendations were that clinicians discuss whether to initiate testosterone treatment in men with age-related low testosterone with sexual dysfunction who want to improve sexual function and not initiate testosterone treatment in men with age-related low testosterone to improve energy, vitality, physical function, or cognition. Here, two clinicians with expertise in this area, one a generalist and the other an endocrinologist, debate the management of a patient with sexual symptoms and a low serum testosterone level. They discuss the diagnosis of male hypogonadism, the indications for testosterone therapy, its potential benefits and risks, how it should be monitored, and how long it should be continued.

[Figure: see text].

Despite the growing number of adult transgender and gender diverse (TGD) patients seeking health services, there are many unknowns regarding how routine screening recommendations should be applied to TGD persons receiving gender-affirming hormone therapy (GAHT). Patients taking GAHT may have disease risks that differ from what is expected based on their sex assigned at birth or affirmed gender identity. We discuss two patient cases, one transgender man and one transgender woman who present for routine medical care, to review several conditions that may be impacted by the hormones utilized in masculinizing and feminizing GAHT and for which screening recommendations are available for TGD adults: cardiovascular risk factors, osteoporosis, breast cancer, cervical cancer, and prostate cancer. We reviewed the TGD-specific screening recommendations from several major medical organizations and programs and found them to be largely based upon expert opinion due to a lack of evidence. The goal of this narrative review is to assist healthcare professionals in counseling and screening their TGD patients when and where appropriate. Not all TGD adults have the ability or need to receive routine medical care from a specialized TGD health clinic; therefore, it is essential for all healthcare professionals involved in routine and gender-affirming care to have knowledge about these conditions and screenings.

A decades-long decline in sperm counts in Western countries has coincided with an increase in obesity rates, prompting study into their association. Few of these studies have incorporated men of color, the sperm health of whom is relatively unknown. The present exploratory study evaluated the association between body mass index (BMI), race, ethnicity, and sperm parameters among a diverse sample of U.S. men attending a Washington, DC physician practice. Semen samples were collected and processed at a single laboratory and sperm concentration, motility, morphology, and count were evaluated according to World Health Organization (WHO) 5th edition criteria. Multivariate models accounted for covariates related to sperm health. The study population ( n = 128) was largely obese (45.3%) or overweight (34.4%), and 36.0% were black or Hispanic. Black men had lower adjusted sperm concentration compared to white men (75.0 million/mL to 107.4 million/mL, p = .01) and were more likely to have oligozoospermia ( p = .01), asthenozoospermia ( p = .004), and low sperm count ( p < .0001). Hispanic men had higher adjusted sperm concentration compared to non-Hispanic men (124.5 million/mL to 62.1 million/mL, p = .007) and were less likely to have teratozoospermia ( p = .001). Obesity and BMI were associated with lower sperm motility and count in crude models only. Given the study's sample size its findings should be interpreted with caution but align with the limited epidemiological literature to date that has evaluated racial and ethnic differences in semen quality. Heightened clinical research attention is needed to ensure men of color are included in representative numbers in studies of urologic and andrologic health.

Over the past few decades, there has been an unprecedented rise in off-label use and misuse of testosterone, growth hormone, thyroid hormone, and adrenal supplements. Testosterone therapy is often promoted to men for the treatment of low energy, lower libido, erectile dysfunction, and other symptoms. Growth hormone is used in attempts to improve athletic performance in athletes and to attenuate aging in older adults. Thyroid hormone and/or thyroid supplements or boosters are taken to treat fatigue, obesity, depression, cognitive impairment, impaired physical performance, and infertility. Adrenal supplements are used to treat common nonspecific symptoms due to "adrenal fatigue," an entity that has not been recognized as a legitimate medical diagnosis. Several factors have contributed to the surge in off-label use and misuse of these hormones and supplements: direct-to-consumer advertising, websites claiming to provide legitimate medical information, and for-profit facilities promoting therapies for men's health and anti-aging. The off-label use and misuse of hormones and supplements in individuals without an established endocrine diagnosis carries known and unknown risks. For example, the risks of growth hormone abuse in athletes and older adults are unknown due to a paucity of studies and because those who abuse this hormone often take supraphysiologic doses in sporadic intervals. In addition to the health risks, off-label use of these hormones and supplements generates billions of dollars of unnecessary costs to patients and to the overall health-care system. It is important that patients honestly disclose to their providers off-label hormone use, as it may affect their health and treatment plan. General medical practitioners and adult endocrinologists should be able to begin a discussion with their patients regarding the unfavorable balance between the risks and benefits associated with off-label use of testosterone, growth hormone, thyroid hormone, and adrenal supplements. Abbreviations: DHEA = dehydroepiandrosterone; FDA = U.S. Food and Drug Administration; GH = growth hormone; IGF-1 = insulin-like growth factor 1; LT3 = L-triiodothyronine; LT4 = levothyroxine; T3 = total triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.

Background: In 2011, depression was added to the product labeling of finasteride in the USA. The US Food and Drug Administration's Adverse Event Reporting System database contains at least 36 death cases for finasteride. The aim of this study is to characterize the clinical histories and symptoms reported by a series of 6 suicide victims who took finasteride for treatment of androgenic alopecia., Methods: Medical records and autopsy reports were provided by family members of the cases. Relevant information was extracted according to guidelines for submitting adverse event reports., Results: An important pattern of symptoms was common among all cases who committed suicide in the setting of finasteride use - insomnia and persistent sexual dysfunction after medication discontinuation. Insomnia and fatigue/tiredness were some of the most debilitating symptoms. Apart from 1 case who had hyperlipidemia, there was no documentation of concomitant medication use with finasteride or any baseline medical or psychiatric diagnoses prior to starting finasteride. The findings of this postmarketing series may not be generalizable to the population of men who committed suicide in the setting of finasteride use due to small sample size and bias. Associations between medication use and symptoms cannot prove causality., Conclusion: Men under the age of 40 who use finasteride for alopecia are at risk for suicide if they develop persistent sexual adverse effects and insomnia. Further research is needed to establish whether finasteride has a causal relationship to suicide., (© 2020 S. Karger AG, Basel.)

Context: There has been a proliferation of clinical practice guidelines in endocrinology and a coincident increased interest in transparency regarding relationships between physicians and industry., Evidence Acquisition: We collected self-reported disclosures and Open Payments data for 169 authors of 26 clinical practice guidelines published between 2010 and 2017 by the Endocrine Society. Conflicts of interest in which pharmaceutical and device companies manufactured drugs or products pertinent to an author's specific clinical practice guideline(s) were deemed relevant. Open Payments data were grouped into research and nonresearch (consultancies, honoraria, travel, food) categories., Evidence Synthesis: We compared the policies of the Endocrine Society regarding seven conflict of interest recommendations issued by the National Academy of Medicine in 2011., Conclusion: Relevant nonresearch financial conflicts of interest were self-reported by 42% of authors of clinical practice guidelines. Open Payments were recorded for 74% (84 of 113) of US authors between 2013 and 2016. Payments to 84 US authors totaled $5.5 million for nonresearch activities and $30.9 million for research. The nonresearch payments were divided into consulting (46%), honoraria (26%), travel (25%), and food (3%). The Endocrine Society partially follows the National Academy of Medicine recommendations to limit conflicts of interest. Readers should be aware of how clinical practice guidelines are developed and the policies of the organizations and journals that publish them. Professional societies and journal editors should strive to ensure that their policies and practices promote objective and unbiased clinical practice guidelines.

This review examines the relationship between exogenous sex steroids and cardiovascular events and surrogate markers in trans (transgender) people. Data from trans populations is compared to data from postmenopausal women and hypogonadal men when appropriate. In an age-adjusted comparison with cisgender people, trans people appear to have an increased risk for myocardial infarction and death due to cardiovascular disease. It is uncertain whether hormone therapy in trans people affects their risk of stroke. In studies that followed trans people on hormone therapy, the rates of myocardial infarction and stroke were consistently higher in trans women than trans men. There is strong evidence that estrogen therapy for trans women increases their risk for venous thromboembolism over 5 fold. Extrapolating from studies of hormone therapy in postmenopausal women, transdermal estrogen likely carries a lower risk for venous thromboembolism than oral estrogen. Regarding red blood cells, testosterone therapy increases hemoglobin in trans men, and lowering testosterone in trans women has the opposite effect. Regarding blood pressure, the effects of hormone therapy on systolic blood pressure in trans women are inconsistent, with most studies showing an increase. In trans men, testosterone therapy consistently increases systolic blood pressure and may increase diastolic blood pressure. For lipids, hormone therapy may increase triglycerides in both trans women and men. In trans men, testosterone therapy also may increase LDL-cholesterol and decrease HDL-cholesterol.

Objective: The decrease in testosterone levels that occurs with aging has become an important clinical issue both due to the growth of the geriatric population and patient interest in testosterone therapy. The decision to assess for testosterone deficiency and the ability to determine whether the benefits exceed the risks require a comprehensive evaluation of the aging patient. This article is part of a series of papers focused on the endocrinology of aging. This review addresses common issues needed for clinical decision making, including how to interpret test results, differential diagnosis, potential impact of testosterone treatment on insulin resistance and cardiovascular disease, and options for therapy., Methods: Papers reviewed were identified through literature searches conducted on PubMed., Results: Assessment of testosterone levels in the geriatric male requires an understanding of the limitations of the assay that is used, the symptoms associated with low testosterone, the impact of comorbid conditions on levels, and risks of therapy. Successful treatment requires setting realistic expectations of the benefits of replacement therapy., Conclusion: While the prevalence of low testosterone concentrations is increased with aging, the common comorbidities such as obesity and diabetes may contribute to changes in testosterone levels. Clinical trial evidence shows modest benefit for treatment of low testosterone in the presence of symptoms. Assessment of the geriatric male should include evaluation of their testosterone level in the context of their functional status and comorbidities., Abbreviations: CDC = Centers for Disease Control and Prevention; CI = confidence interval; CVD = cardiovascular disease; DXA = dual-energy X-ray absorptiometry; EMAS = European Male Aging Study; FDA = U.S. Food and Drug Administration; FHS = Framingham Heart Study; HDL = high-density lipoprotein; HOMA-IR = homeostasis model assessment of insulin resistance; LH = luteinizing hormone; OR = odds ratio; PSA = prostate-specific antigen; SHBG = sex hormone-binding globulin; T2DM = type 2 diabetes mellitus; vBMD = volumetric bone mineral density.

The American Psychological Association defines gender identity as, "A person's deeply-felt, inherent sense of being a boy, a man, or a male; a girl, a woman, or a female; or an alternative gender (e.g., genderqueer, gender nonconforming, gender neutral) that may or may not correspond to a person's sex assigned at birth or to a person's primary or secondary sex characteristics" (American Psychological Association, Am Psychol 70(9):832-864, 2015). Here we review the evidence that gender identity and related socially defined gender constructs are influenced in part by innate factors including genes. Based on the data reviewed, we hypothesize that gender identity is a multifactorial complex trait with a heritable polygenic component. We argue that increasing the awareness of the biological diversity underlying gender identity development is relevant to all domains of social, medical, and neuroscience research and foundational for reducing health disparities and promoting human-rights protections for gender minorities.

Objective: Increased numbers of transgender and gender-nonconforming people are presenting to physicians in the United States and abroad due to increased public recognition and acceptance and increased access to healthcare facilities. However, there are still gaps in medical knowledge among endocrinologists and other health care professionals. The purpose of these cases is to present several common clinical vignettes of transgender people presenting in an office setting that illustrate some of the key recommendations of the Endocrine Society's revised Endocrine Treatment of Gender Dysphoria/Gender Incongruent Persons guidelines, cosponsored by the American Association of Clinical Endocrinologists., Methods: Cases were developed based on these recently revised guidelines for gender-dysphoric and gender-nonconforming persons., Results: Six cases are presented that illustrate the diagnosis, treatment, and long-term management of trans-gender children and adults based on the revised guidelines for the endocrine care of gender-dysphoric and gender-nonconforming persons. Several key teaching points are presented from the presentation of these cases., Conclusion: Endocrinologists should be familiar with the revised guidelines for gender-dysphoric and gender-nonconforming persons. Important aspects of care are the diagnosis of gender dysphoria, the timing of treatment with gender-affirming hormones, and the long-term monitoring for potential adverse outcomes. Long-term health outcome studies are needed to further help guide care in this unique population., Abbreviations: BMI = body mass index GnRH = gonadotropin-releasing hormone HDL = high-density lipoprotein LDL = low-density lipoprotein.

Purpose: The purpose of this study was to prospectively examine changes in gender-related voice domain of pitch measured by fundamental frequency, function-related domains of vocal quality, range, and habitual pitch level and the self-perceptions of transmasculine people during their first year of testosterone treatment., Method: Seven trans men received 2 voice assessments at baseline and 1 assessment at 3, 6, 9, and 12 months after starting treatment., Results: Vocal quality measures varied between and within participants but were generally within normal limits throughout the year. Mean fundamental frequency (MF0) during reading decreased, although to variable extents and rates. Phonation frequency range shifted down the scale, although it increased in some participants and decreased in others. Considering MF0 and phonation frequency range together in a measure of habitual pitch level revealed that the majority of participants spoke using an MF0 that was low within their range compared with cisgender norms. Although the trans men generally self-reported voice masculinization, it was not correlated with MF0, frequency range, or habitual pitch level at any time point or with MF0 note change from baseline to 1 year of testosterone treatment, but correlations should be interpreted with caution due to the heterogeneous responses of the 7 participants., Conclusion: In trans men, consideration of voice deepening in the context of objective and subjective measures of voice can reveal unique profiles and inform patient care.

Purpose of Review: To explore the medical and surgical clinical dilemmas in the management of trans (transgender) men, a growing population receiving more attention than in the past., Recent Findings: Testosterone therapy is commonly prescribed to trans men for masculinization. Nonetheless, the optimal formulations and doses of testosterone therapy for trans men have not been well established. Testosterone therapy has been associated with increased levels of hemoglobin and triglycerides, as well as diabetes. Periodic monitoring of hemoglobin, cholesterol, and fasting glucose is therefore recommended. As compared to non-transgender women, trans men have lower age-specific rates of breast cancer and cervical cancer which can be attributed, in part, to surgeries such as bilateral mastectomies and hysterectomies. The frequency in which to recommend mammograms and Pap smears (in patients with intact cervices) is uncertain in this population because of a lack of evidence-based data. Many trans men desire and undergo bilateral mastectomies with much fewer undergoing metoidioplasty or phalloplasty., Summary: For trans men, most clinicians target serum testosterone concentrations in the normal male reference range. The frequency of screening for breast and cervical cancer should be individualized based upon anatomy, patient age, age of initiation of testosterone therapy, and other factors.

Testosterone therapy is a cornerstone of medical treatment for transgender men who choose to undergo it. The goal of testosterone therapy is usually to achieve serum testosterone concentrations in the male reference range. Testosterone has several desired effects as well as undesired and unknown effects. The desired effects include increased facial and body hair, increased lean mass and strength, decreased fat mass, deepening of the voice, increased sexual desire, cessation of menstruation, clitoral enlargement, and reductions in gender dysphoria, perceived stress, anxiety, and depression. Achievement of these goals comes with potential undesired effects and risks including acne, alopecia, reduced HDL cholesterol, increased triglycerides, and a possible increase in systolic blood pressure. An additional benefit of testosterone therapy (with or without mastectomy) is a reduced risk of breast cancer. Most of the effects of testosterone start to develop within several months of starting therapy, although facial hair and alopecia continue to develop after 1 year. A major limitation in the study of testosterone therapy for transgender men is a paucity of high-quality data due to a shortage of randomised controlled trials (partly because of ethical issues), few prospective and long-term studies, the use of suboptimum control groups, loss to follow-up, and difficulties in recruitment of representative samples of transgender populations., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

There is sparse prospective data on the effects of testosterone therapy on the voices of transgender men (also referred to as trans men or female-to-male transsexuals). Our aim was to investigate the timing and degree of voice deepening over 12 months among an ethnically diverse sample of transgender men. This was a prospective 12-month study at an academic outpatient endocrinology clinic and speech and voice center. The participants were seven transgender men naïve to testosterone therapy. All patients received two voice assessments at baseline and one assessment at 3, 6, 9, and 12 months while on intramuscular testosterone esters. Serum testosterone and estradiol concentrations were measured at baseline and every 3 months. All seven transgender men reached a cisgender male mean fundamental frequency (MF0) within 6 months of testosterone therapy and four continued to experience a decrease after 6 months. The mean decrease in MF0 after 12 months of testosterone therapy was 6.4 semitones (49 Hz). Several patterns emerged regarding the extent and timing. For example, some participants showed no decrease in MF0 within the first 3 months of testosterone therapy, whereas others showed their greatest decrease in MF0. We concluded that transgender men who start testosterone therapy display different patterns of voice lowering. Clinicians should counsel transgender men that they may or may not experience voice lowering within the first 3 months of testosterone therapy and that the majority of voice deepening will occur within 6-9 months., (© 2016 American Society of Andrology and European Academy of Andrology.)

Objective: Little is known about the attitudes and practice patterns of transgender care by endocrinologists. The objective of this study was to assess the knowledge, practice patterns, access, and competency among a representative sample of endocrinologists in the mid-Atlantic region of the United States., Methods: An anonymous 19-item paper survey was administered to 80 conference attendees that included 61 adult endocrinologists, 13 endocrinology fellows, 2 pediatric endocrinologists, and 4 nurse practitioners/physician assistants., Results: The participation rate was estimated to be ~80%. Sixty-three percent of endocrinology providers were willing to provide transgender care, but the majority of providers had no current transgender patients under their care. Half of providers had read the Endocrine Society's clinical practice guidelines, with a rate of 70% among those under age 40. Nonetheless, only 20% were "very" comfortable in discussing gender identity and/or sexual orientation, and 41% described themselves as "somewhat" or "very" competent to provider transgender care., Conclusion: Endocrinologists and other providers have received more education and training on transgender care within the past decade. Nevertheless, many participants have had little opportunity to care for transgender patients, and they rate their competency to do so as low. Research is needed on how to increase comfort levels regarding gender identity among those who provider care to transgender patients.

Introduction: Men referred for borderline testosterone levels represent an increasingly common clinical scenario, yet there is little literature on this population., Aim: We hypothesized that men referred for borderline testosterone levels would have higher rates of depression and depressive symptoms than the general population., Methods: Subjects included 200 adult men (mean age of 48 years old) referred for borderline total testosterone levels between 200 and 350 ng/dL (6.9-12 nmol/L). Collected data included demographic information, medical histories, medication use, signs and symptoms of hypogonadism, and assessments of depressive symptoms and/or a known diagnosis of depression or use of an antidepressant., Main Outcome Measures: The main outcome measure was a combination of known depression, current use of an antidepressant, and/or depressive symptoms according to the Patient Health Questionnaire 9 (PHQ-9) with scores ≥10 considered positive., Results: Depression and/or depressive symptoms were present in 56% of the subjects. This rate was significantly higher than rates of 6-23% (PHQ-9 scores ≥10) seen in general populations. Antidepressant use was 25%. The population was notable for high rates of overweight/obesity and physical inactivity. Common symptoms were erectile dysfunction, decreased libido, fewer AM erections, low energy, and sleep disturbances., Conclusions: While sexual and nonspecific symptoms (i.e., fatigue) likely prompted measurements of testosterone in this selected population, clinicians should recognize the high rates of depression and depressive symptoms in men referred for borderline testosterone levels. Clinicians should consider screening for depression/depressive symptoms and overweight and unhealthy lifestyle risk factors in men referred for tertiary care for potential hypogonadism., (© 2015 International Society for Sexual Medicine.)

Purpose of Review: To examine the clinical and basic studies regarding persistent adverse effects associated with 5α reductase inhibitor treatment for androgenetic alopecia., Recent Findings: Recent postmarketing reports and a US Food and Drug Administration analysis have documented uncommon persistent sexual and nonsexual side-effects in a subset of younger men who have taken finasteride 1 mg for androgenic alopecia. While the mechanisms of the sexual side-effects in humans is incompletely understood, one study found lower cerebrospinal fluid concentrations of dihydrotestosterone, progesterone, dihydroprogesterone and allopregnanolone, and higher levels of testosterone, 5α-androstane-3α,17β-diol and pregnenolone. Another study found up-regulation of the androgen receptor in the human foreskin with a mean of 5 years after finasteride discontinuation. Studies of erectile dysfunction in finasteride-treated rats showed fewer autophagosomes in smooth muscle on transmission electron microscopy, increased apoptosis, decreased smooth muscle, increased collagen deposition and decreased endothelial nitric oxide synthase. Finally, 5α reductase inhibitors have also been found to alter semen parameters in healthy men., Summary: Multiple animal studies provide a biological basis for many of the persistent effects seen in humans such as erectile dysfunction, depression and decreased alcohol consumption. Prescribers of 5α reductase inhibitors should discuss the potential risks with their patients seeking treatment for androgenetic alopecia.

Purpose of Review: To examine bone health in relation to testosterone and male hypogonadism., Recent Findings: An emerging area of research pertains to the newly described bone-testis axis. In particular, the peptide hormone osteocalcin, which is made by bone and fat, appears to play a role in testosterone production. Inconsistent weak associations have been noted between vitamin D deficiency or insufficiency and lower testosterone levels. Although a high prevalence of hypogonadism is associated with opioid use, HIV and transfusion-dependent thalassemia, the risk of fracture in these populations is unclear. In fact, one study found that the modest increase in fractures among opioid users was attributed to central nervous system adverse effects of the medications as opposed to chronic hypogonadism. In terms of therapy, many small studies have found that testosterone replacement therapy increases bone mineral density in hypogonadal men, including men with hypopituitarism., Summary: Further research is needed on the cross-talk that occurs in the bone-testis axis. When it comes to managing men with hypogonadism, the benefit of testosterone replacement therapy on prevention of incident fractures is uncertain. Large, long-term randomized controlled trials are needed with fracture as the primary outcome.

Eunuchs are biological males who have undergone voluntary castration for reasons other than male-to-female transsexualism. The term 'eunuch wannabe' refers to individuals who desire, or are planning, voluntary castration. Out of fear of embarrassment or rejection, many eunuch wannabes do not consult medical professionals regarding their desire for voluntary castration. Instead, they commonly resort to self-castration, castration by nonmedical professionals, or self-inflicted testicular damage via injections of toxic substances. Urologists should be aware of the growing popularity of these procedures. In particular, intratesticular injection of toxins is performed so that urologists will remove the damaged testicles.

Introduction: Recent studies have reported persistent sexual and nonsexual adverse effects associated with the 5α-reductase inhibitor finasteride., Aims: The first aim was to review the clinical studies of persistent sexual and nonsexual adverse effects associated with finasteride in younger men who took the medication for treatment of male pattern hair loss. The second aim was to place these findings into context with what is known from basic and clinical studies about the hormones and neurosteroids affected by finasteride., Methods: Relevant published literature on the topic was reviewed. Clinical symptomatology in humans was correlated with findings from rodent models to investigate possible underlying mechanisms., Main Outcome Measures: Persistent sexual and nonsexual adverse effects were summarized., Results: Two clinical studies have described persistent side effects associated with finasteride use in otherwise healthy younger men. The sexual side effects are typically present in multiple domains that include erectile dysfunction, low libido, and decreased orgasms. Erectile dysfunction may be related to low levels of dihydrotestosterone, which has been shown to be an important androgen in both human and animal studies. Nonsexual side effects include depression and decreased alcohol consumption that are linked to the neurosteroid allopregnanolone in both human and animal studies. Three men with persistent side effects associated with finasteride were found to have lower plasma and cerebrospinal fluid levels of several neurosteroids., Conclusions: Persistent adverse effects of finasteride in younger men include erectile dysfunction, low libido, lack of orgasms, depression, and decreased alcohol consumption. One study has found lower levels of several neurosteroids in this population. Out of the various persistent side effects, erectile dysfunction and decreased alcohol consumption have been the most studied in animal models. Further research is needed on who is susceptible to the persistent adverse side effects of finasteride and on the underlying mechanisms of the medication. Irwig MS. Persistent sexual and non-sexual adverse effects of finasteride in younger men. Sex Med Rev 2014;2:24-35., (Copyright © 2014 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: To examine the role of testosterone in skeletal health in men., Recent Findings: Evidence from recent studies shows that the contributing role of testosterone to osteoporosis is modest and likely trumped by other factors such as estradiol levels. A few studies have documented an association between low testosterone levels and lower bone mineral density (BMD), increased prevalence of osteoporosis of the hip and low bone mass-related fractures. Other studies, however, have found that testosterone levels are not independent predictors of bone resorption or formation markers, BMD at the hip or incident fractures. Curiously, hypogonadism does not account for the increased osteoporosis seen in men with Klinefelter Syndrome. Regardless of hypogonadism status, two recent clinical trials have found fewer new morphometric vertebral fractures in men treated with zoledronic acid and increased BMD in men treated with denosumab. Denosumab was also shown to modestly increase bone-metastasis-free survival in men with castration-resistant prostate cancer., Summary: Although male hypogonadism is associated with osteoporosis, estradiol is likely to be the more important hormone for bone health. Although a few large randomized controlled trials have been conducted in men with low bone density (a subset of whom have hypogonadism), more trials are needed, particularly with fractures as the main outcome.

Objective: We present the case of a male-to-female transsexual person in her 20s requesting hormone therapy in the setting of a history of a deep venous thrombosis and pulmonary embolus and carrying the prothrombin G20210A gene mutation., Methods: We interviewed the patient and reviewed her medical records. We carefully weighed the risks and benefits of hormone therapy and took into account two important ethical principles: beneficence (to act in the patient's best interest) and nonmaleficence (to avoid harm)., Results: Our patient presented to an outside facility with weight loss, generalized weakness, right lower extremity swelling, and chest pain. She was diagnosed with a pulmonary embolus and extensive deep venous thrombus by computed tomography (CT) scan and Doppler ultrasound, respectively. She was found to carry the prothrombin G20210A gene mutation. She was treated with anticoagulation therapy for 12 months, which was restarted prior to beginning therapy with transdermal estrogen., Conclusion: While the exact risk of recurrent deep venous thrombosis and pulmonary embolus in our patient is unknown, we recommended that hormone therapy should only be given in conjunction with anticoagulation. We speculate that this strategy would allow the patient to experience the benefits to her overall well-being with hormone therapy while reducing the risks of venous thrombosis to acceptable levels. Prospective long-term follow-up of this patient is needed to verify the benefits and risk of the intervention chosen.

Background: There is a robust literature in rodents, but not in humans, on the interaction between finasteride and alcohol, particularly as it relates to neurosteroids. Finasteride has been shown to reduce alcohol intake and suppress alcohol preference in male mice. This study examines the role of finasteride in alcohol consumption in humans with male pattern hair loss., Methods: The subjects were 83 otherwise healthy men who developed persistent sexual side effects associated with finasteride, despite the cessation of this medication for at least 3 months. Information from standardized interviews was collected regarding medical histories, sexual function, and alcohol consumption before and after finasteride use., Results: Of the 63 men who consumed at least 1 alcoholic beverage/wk prior to starting finasteride, 41 (65%) noted a decrease in their alcohol consumption after stopping finasteride. This reduction typically began before discontinuing finasteride. Twenty men (32%) reported no change in their alcohol consumption, and 2 men (3%) reported an increase in their alcohol consumption. For the 63 consumers of alcohol, the mean number (± SE) of alcoholic beverages/wk declined from 5.2 ± 0.7 before finasteride to 2.0 ± 0.3 after finasteride (p < 0.0001). A major study limitation is the lack of a comparison group., Conclusions: In former male users of finasteride who developed persistent sexual side effects, 65% noticed a decline in their alcohol consumption as compared to baseline. This finding is consistent with finasteride's ability to modulate alcohol intake in rodents. Further research is needed on the central nervous system effects of finasteride in humans., (Copyright © 2013 by the Research Society on Alcoholism.)

The global obesity epidemic is having a profound impact on the health of populations. From a reproductive standpoint, obesity has been associated with infertility and hypogonadism. We present the case of a 29-year-old male-to-female transsexual with super obesity (body mass index >50) who was found to have profound hypogonadism with total and free testosterone levels in the normal female reference range. There is virtually no literature on the hormonal sequelae of obesity in transsexual people. The patient was prescribed an aromatase inhibitor, letrozole 2.5 mg twice daily for 2 weeks, to determine the role of oestrogen in the hypogonadism. The aromatase inhibitor reduced the serum oestradiol concentration from 125 to 6.9 pm. There were dramatic corresponding rises in total testosterone (2.8 to 10.7 nm), luteinising hormone (4.1 to 20.5 mIU ml(-1) ) and follicle stimulating hormone (1.8 to 15.3 mIU ml(-1) ). This diagnostic test demonstrated the important role of oestrogen in mediating the hypogonadism. After the testing, the patient was started on oestrogen therapy after a careful discussion of the benefits versus risks of oestrogen therapy. We anticipate that similar cases of hypogonadism in male-to-female transsexuals will likely become more common in an era of increased obesity rates., (© 2012 Blackwell Verlag GmbH.)

Introduction: Finasteride has been associated with sexual side effects that may persist despite discontinuation of the medication. In a clinical series, 20% of subjects with male pattern hair loss reported persistent sexual dysfunction for ≥6 years, suggesting the possibility that the dysfunction may be permanent. These subjects also reported a wide range of symptoms including changes in cognition, ejaculate quality, and genital sensation. Other medications have been associated with irreversible neurological effects, such as phenothiazines with tardive dyskinesias., Aim: To prospectively study whether the persistent sexual side effects associated with finasteride resolve or endure over time., Methods: Subjects (N = 54) with persistent sexual side effects associated with finasteride were reassessed after 9-16 months (mean 14 months). All subjects were otherwise healthy young men without any baseline sexual dysfunction, medical conditions, psychiatric conditions, or use of oral prescription medications prior to taking finasteride for male pattern hair loss., Main Outcome Measure: Scores from the Arizona Sexual Experience Scale (ASEX)., Results: The participation rate was 81%. At reassessment persistent sexual side effects continued to be present in 96% of subjects. According to the ASEX scores, 89% of subjects met the definition of sexual dysfunction. Neither the length of finasteride use nor the duration of the sexual side effects correlated to changes in scores of sexual dysfunction., Conclusion: In most men who developed persistent sexual side effects (≥3 months) despite the discontinuation of finasteride, the sexual dysfunction continued for many months or years. Although several rat studies have shown detrimental changes to erectile function caused by 5 alpha reductase inhibitors, the persistent nature of these changes is an area of active research. Prescribers of finasteride and men contemplating its use should be made aware of the potential adverse medication effects., (© 2012 International Society for Sexual Medicine.)

Objective: Finasteride, a commonly prescribed medication for male pattern hair loss, has recently been associated with persistent sexual side effects. In addition, depression has recently been added to the product labeling of Propecia (finasteride 1 mg). Finasteride reduces the levels of several neuroactive steroids linked to sexual function and depression. This study assesses depressive symptoms and suicidal thoughts in former users of finasteride who developed persistent sexual side effects despite the discontinuation of finasteride., Method: In 2010-2011, former users of finasteride (n = 61) with persistent sexual side effects for ≥ 3 months were administered standardized interviews that gathered demographic information, medical and psychiatric histories, and information on medication use, sexual function, and alcohol consumption. All former users were otherwise healthy men with no baseline sexual dysfunction, chronic medical conditions, current or past psychiatric conditions, or use of oral prescription medications before or during finasteride use. A control group of men (n = 29), recruited from the community, had male pattern hair loss but had never used finasteride and denied any history of psychiatric conditions or use of psychiatric medications. The primary outcomes were the prevalence of depressive symptoms and the prevalence of suicidal thoughts as determined by the Beck depression inventory II (BDI-II); all subjects self-administered this questionnaire at the time of the interview or up to 10 months later., Results: Rates of depressive symptoms (BDI-II score ≥ 14) were significantly higher in the former finasteride users (75%; 46/61) as compared to the controls (10%; 3/29) (P < .0001). Moderate or severe depressive symptoms (BDI-II score ≥ 20) were present in 64% (39/61) of the finasteride group and 0% of the controls. Suicidal thoughts were present in 44% (27/61) of the former finasteride users and in 3% (1/29) of the controls (P < .0001)., Conclusions: Clinicians and potential users of finasteride should be aware of the potential risk of depressive symptoms and suicidal thoughts. The preliminary findings of this study warrant further research with controlled studies., (© Copyright 2012 Physicians Postgraduate Press, Inc.)

Aims: To test (1) whether a diabetes scorecard can improve glycaemic control, blood pressure control, LDL cholesterol, aspirin usage and exercise; (2) if the scorecard will motivate and/or educate patients to improve their scores for subsequent visits; and (3) whether the scorecard will improve rates of clinical inertia., Methods: Five physicians enrolled 103 patients ≥ 40 years old with uncontrolled Type 2 diabetes [HbA(1c) ≥ 64 mmol/mol (8.0%)] to randomly receive either a diabetes scorecard or not during four clinical visits over a 9-month period. The population was predominantly urban with a disproportionately higher percentage of black people than the general population. Our scorecard assigned points to six clinical variables, with a perfect total score of 100 points corresponding to meeting all targets. The primary outcomes were total scores and HbA(1c) in the scorecard and control groups at 9 months., Results: There were no significant differences between the control and scorecard groups at visits 1 and 4 in total score, HbA(1c) , blood pressure, LDL cholesterol, aspirin usage, exercise or knowledge about diabetic targets. By visit 4 both the control and scorecard groups had statistically significant improvements with their mean total score (9 and 7 points, respectively), HbA(1c) [-9 mmol/mol (-0.8%) and -15 mmol/mol (-1.4%), respectively] and aspirin usage (33% increase and 16% increase, respectively). Rates of clinical inertia were low throughout the study., Conclusions: A diabetes scorecard did not improve glycaemic control, blood pressure control, LDL cholesterol, aspirin usage, exercise or diabetic knowledge in an urban population with uncontrolled Type 2 diabetes., (© 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.)

Introduction: The out-of-pocket cost for an elective orchiectomy, which is often not covered by health insurance, is a significant barrier to male-to-female transsexuals ready to proceed with their physical transition. This and other barriers (lack of access to a surgeon willing to perform the operation, waiting times, and underlying psychological and psychiatric conditions) lead a subset of transsexual women to attempt self-castration. Little information has been published on the financial costs and implications of self-castration to both patients and health care systems., Aim: We compare the financial and psychological costs of elective surgical orchiectomy vs. self-castration in the case of a transsexual woman in her 40s., Methods: We interviewed the patient and her providers and obtained financial information from local reimbursement and billing specialists., Results: After experiencing minor hemorrhage following the self-castration, our patient presented to the emergency department and underwent a bilateral inguinal exploration, ligation and removal of bilateral spermatic cords, and complicated scrotal exploration, debridement, and closure. She was admitted to the psychiatric service for a hospital stay of three days. The total bill was U.S. $14,923, which would compare with U.S. $4,000 for an elective outpatient orchiectomy in the patient's geographical area., Conclusions: From a financial standpoint, an elective orchiectomy could have cost the health care system significantly less than a hospital admission with its associated additional costs. From a patient safety standpoint, elective orchiectomy is preferable to self-castration which carries significant risks such as hemorrhage, disfigurement, infection, urinary fistulae, and nerve damage. Healthcare providers of transsexual women should carefully explore patient attitudes toward self-castration and work toward improving access to elective orchiectomy to reduce the number of self-castrations and costs to the overall health care system. Further research on the financial implications of self-castration from different health care systems and from a series of patients is needed., (© 2012 International Society for Sexual Medicine.)

Introduction: Finasteride has been associated with reversible adverse sexual side effects in multiple randomized, controlled trials for the treatment of male pattern hair loss (MPHL). The Medicines and Healthcare Products Regulatory Agency of the United Kingdom and the Swedish Medical Products Agency have both updated their patient information leaflets to include a statement that "persistence of erectile dysfunction after discontinuation of treatment with Propecia has been reported in post-marketing use.", Aim: We sought to characterize the types and duration of persistent sexual side effects in otherwise healthy men who took finasteride for MPHL., Methods: We conducted standardized interviews with 71 otherwise healthy men aged 21-46 years who reported the new onset of sexual side effects associated with the temporal use of finasteride, in which the symptoms persisted for at least 3 months despite the discontinuation of finasteride., Main Outcome Measures: The types and duration of sexual dysfunction and the changes in perceived sexual frequency and sexual dysfunction score between pre- and post-finasteride use., Results: Subjects reported new-onset persistent sexual dysfunction associated with the use of finasteride: 94% developed low libido, 92% developed erectile dysfunction, 92% developed decreased arousal, and 69% developed problems with orgasm. The mean number of sexual episodes per month dropped and the total sexual dysfunction score increased for before and after finasteride use according to the Arizona Sexual Experience Scale (P<0.0001 for both). The mean duration of finasteride use was 28 months and the mean duration of persistent sexual side effects was 40 months from the time of finasteride cessation to the interview date. Study limitations include a post hoc approach, selection bias, recall bias for before finasteride data, and no serum hormone levels., Conclusion: Physicians treating MPHL should discuss the potential risk of persistent sexual side effects associated with finasteride., (© 2011 International Society for Sexual Medicine.)