The occurrence of benign brain tumours in transgender individuals during cross-sex hormone treatment.

Benign brain tumours may be hormone sensitive. To induce physical characteristics of the desired gender, transgender individuals often receive cross-sex hormone treatment, sometimes in higher doses than hypogonadal individuals. To date, long-term (side) effects of cross-sex hormone treatment are largely unknown. In the present retrospective chart study we aimed to compare the incidence of common benign brain tumours: meningiomas, pituitary adenomas (non-secretive and secretive), and vestibular schwannomas in transgender individuals receiving cross-sex hormone treatment, with those reported in general Dutch or European populations. This study was performed at the VU University Medical Centre in the Netherlands and consisted of 2555 transwomen (median age at start of cross-sex hormone treatment: 31 years, interquartile range 23-41) and 1373 transmen (median age 23 years, interquartile range 18-31) who were followed for 23 935 and 11 212 person-years, respectively. For each separate brain tumour, standardized incidence ratios with 95% confidence intervals were calculated. In transwomen (male sex assigned at birth, female gender identity), eight meningiomas, one non-secretive pituitary adenoma, nine prolactinomas, and two vestibular schwannomas occurred. The incidence of meningiomas was higher in transwomen than in a general European female population (standardized incidence ratio 4.1, 95% confidence interval 1.9-7.7) and male population (11.9, 5.5-22.7). Similar to meningiomas, prolactinomas occurred more often in transwomen compared to general Dutch females (4.3, 2.1-7.9) and males (26.5, 12.9-48.6). Noteworthy, most transwomen had received orchiectomy but still used the progestogenic anti-androgen cyproterone acetate at time of diagnosis. In transmen (female sex assigned at birth, male gender identity), two cases of somatotrophinomas were observed, which was higher than expected based on the reported incidence rate in a general European population (incidence rate females = incidence rate males; standardized incidence ratio 22.2, 3.7-73.4). Based on our results we conclude that cross-sex hormone treatment is associated with a higher risk of meningiomas and prolactinomas in transwomen, which may be linked to cyproterone acetate usage, and somatotrophinomas in transmen. Because these conditions are quite rare, performing regular screenings for such tumours (e.g. regular prolactin measurements for identifying prolactinomas) seems not necessary.

Endocrine treatment of aging transgender people.

High quality empirical data assessing morbidity and mortality and cancer incidence among transgender people are almost non-existent. Sex hormone treatment of conditions in older non-transgender people might as yet be taken as the best available analogy to hormone administration to aging transgender persons. Testosterone administration to transgender men carries little risk with regard to cardiovascular disease and cancer. A dose adaptation may be needed in men with a high hematocrit or cardiac insufficiency. In transgender men, even after breast ablation, breast cancer may occur in residual mammary tissue. Treatment with estrogens (specifically oral ethinylestradiol) of transgender women, particularly in combination with progestins, carries a significant relative risk of developing cardiovascular disease (almost a twofold incidence compared to the general population). The dose of estrogens may have to be reduced with aging. A change from oral to probably safer transdermal estrogens must be considered. Though rare, tumors of the breasts, prostate, meninges and pituitary have been encountered. Based upon the available expertise, initiation of cross-sex hormone treatment in elderly subjects is without disproportionate risks.

The Amsterdam Cohort of Gender Dysphoria Study (1972-2015): Trends in Prevalence, Treatment, and Regrets.

BACKGROUND: Over the past decade, the number of people referred to gender identity clinics has rapidly increased. This raises several questions, especially concerning the frequency of performing gender-affirming treatments with irreversible effects and regret from such interventions. AIM: To study the current prevalence of gender dysphoria, how frequently gender-affirming treatments are performed, and the number of people experiencing regret of this treatment. METHODS: The medical files of all people who attended our gender identity clinic from 1972 to 2015 were reviewed retrospectively. OUTCOMES: The number of (and change in) people who applied for transgender health care, the percentage of people starting with gender-affirming hormonal treatment (HT), the estimated prevalence of transgender people receiving gender-affirming treatment, the percentage of people who underwent gonadectomy, and the percentage of people who regretted gonadectomy, specified separately for each year. RESULTS: 6,793 people (4,432 birth-assigned male, 2,361 birth-assigned female) visited our gender identity clinic from 1972 through 2015. The number of people assessed per year increased 20-fold from 34 in 1980 to 686 in 2015. The estimated prevalence in the Netherlands in 2015 was 1:3,800 for men (transwomen) and 1:5,200 for women (transmen). The percentage of people who started HT within 5 years after the 1st visit decreased over time, with almost 90% in 1980 to 65% in 2010. The percentage of people who underwent gonadectomy within 5 years after starting HT remained stable over time (74.7% of transwomen and 83.8% of transmen). Only 0.6% of transwomen and 0.3% of transmen who underwent gonadectomy were identified as experiencing regret. CLINICAL IMPLICATIONS: Because the transgender population is growing, a larger availability of transgender health care is needed. Other health care providers should familiarize themselves with transgender health care, because HT can influence diseases and interact with medication. Because not all people apply for the classic treatment approach, special attention should be given to those who choose less common forms of treatment. STRENGTHS AND LIMITATIONS: This study was performed in the largest Dutch gender identity clinic, which treats more than 95% of the transgender population in the Netherlands. Because of the retrospective design, some data could be missing. CONCLUSION: The number of people with gender identity issues seeking professional help increased dramatically in recent decades. The percentage of people who regretted gonadectomy remained small and did not show a tendency to increase. Wiepjes CM, Nota NM, de Blok CJM, et al. The Amsterdam Cohort of Gender Dysphoria Study (1972-2015): Trends in Prevalence, Treatment, and Regrets. J Sex Med 2018;15:582-590.

Sex reassignment of transsexual people from a gynecologist's and urologist's perspective.

Cross-sex hormone treatment of transgender persons is usually uneventful, but hormone-sensitive malignancies of the (reproductive) organs of the natal and new sex (breasts, neovagina) may arise. Sex reassignment surgery impacts on the urodynamics of the reassigned sex. Pathology originating from organ systems of the natal sex may be overlooked in the new sex. In male-to-female transgender individuals, malignant tumors of the breasts and prostate may occur. Neovaginas are constructed with skin or sigmoid. Shortening of the male urethra to female dimensions is usually uneventful. In female-to-male transgender individuals breast cancer may develop, sometimes in residual mammary tissue after reductive mammoplasty. Malignancies of the vagina and ovaries are rare. Testosterone may be aromatized to estrogens, with effects on the endometrium. Lengthening of the female urethra to male dimensions may cause urethral fistulae, urethral strictures, and meatal stenoses. A degree of post-voiding incontinence may occur.

Cross-sex hormone use, functional health and mental well-being among transgender men (Toms) and Transgender Women (Kathoeys) in Thailand.

There exists limited understanding of cross-sex hormone use and mental well-being among transgender women and, particularly, among transgender men. Moreover, most studies of transgender people have taken place in the Global North and often in the context of HIV. This exploratory study compared 60 transgender men (toms) with 60 transgender women (kathoeys) regarding their use of cross-sex hormones, mental well-being and acceptance by their family. Participants also completed a dispositional optimism scale (the Life Orientation Test Revised), the Social Functioning Questionnaire and the Short Form Health Survey 36 assessing their profile of functional health and mental well-being. Cross-sex hormones were used by 35% of toms and 73% of kathoeys and were largely unsupervised by health-related personnel. There were no differences in functional health and mental well-being among toms and kathoeys. However, toms currently using cross-sex hormones scored on average poorer on bodily pain and mental health, compared to non-users. Furthermore, compared to non-users, cross-sex hormone users were about eight times and five times more likely to be associated with poor parental acceptance among toms and kathoeys, respectively. This study was the first to compare cross-sex hormone use, functional health and mental well-being among transgender women and transgender men in Southeast Asia.

Breast cancer development in transsexual subjects receiving cross-sex hormone treatment.

INTRODUCTION: Transsexual people receive cross-sex hormones as part of their treatment, potentially inducing hormone-sensitive malignancies. AIM: To examine the occurrence of breast cancer in a large cohort of Dutch male and female transsexual persons, also evaluating whether the epidemiology accords with the natal sex or the new sex. MAIN OUTCOME MEASURE: Number of people with breast cancer between 1975 and 2011. METHODS: We researched the occurrence of breast cancer among transsexual persons 18-80 years with an exposure to cross-sex hormones between 5 to >30 years. Our study included 2,307 male-to-female (MtF) transsexual persons undergoing androgen deprivation and estrogen administration (52,370 person-years of exposure), and 795 female-to-male (FtM) subjects receiving testosterone (15,974 total years of exposure). RESULTS: Among MtF individuals one case was encountered, as well as a probable but not proven second case. The estimated rate of 4.1 per 100,000 person-years (95% confidence interval [CI]: 0.8-13.0) was lower than expected if these two cases are regarded as female breast cancer, but within expectations if viewed as male breast cancer. In FtM subjects, who were younger and had shorter exposure to cross-sex hormones compared with the MtF group, one breast cancer case occurred. This translated into a rate of 5.9 per 100,000 person-years (95% CI: 0.5-27.4), again lower than expected for female breast cancer but within expected norms for male breast cancer. CONCLUSIONS: The number of people studied and duration of hormone exposure are limited but it would appear that cross-sex hormone administration does not increase the risk of breast cancer development, in either MtF or FtM transsexual individuals. Breast carcinoma incidences in both groups are comparable to male breast cancers. Cross-sex hormone treatment of transsexual subjects does not seem to be associated with an increased risk of malignant breast development.

Diagnosing and treating testosterone deficiency in different parts of the world: changes between 2006 and 2010.

AIM: An analysis of variations in diagnosing and treating testosterone (T) deficiency between different regions of the world in 2006 was repeated in 2010. METHODS: Physicians were interviewed in Germany, Spain, the United Kingdom, Brazil and Saudi Arabia about (1) reasons to use/not to use T. (2) safety (prostate pathology) and other concerns in the decision not to provide T treatment. (3) the actual usage of T preparations for treatment of erectile dysfunction (ED). RESULTS: More men were treated with T in 2010. ED and lack of libido (2006) but also depression and obesity (2010) were regarded as symptoms of T deficiency. For 70% of physicians, severity of complaints was more significant than the laboratory value of T to prescribe T, more so in Germany (96%) than in Spain and Saudi Arabia. Concerns about prostate disease remained strong and, therefore, 11% of eligible patients did not receive T. PDE-5 inhibitors are more often combined with T in 2010 for ED. CONCLUSION: More appropriate studies and more education of physicians are needed on diagnosing T deficiency, on the role of T in ED and on the evidence-based relative safety of T treatment.

A randomized, double-blind, placebo-controlled trial of testosterone gel on body composition and health-related quality-of-life in men with hypogonadal to low-normal levels of serum testosterone and symptoms of androgen deficiency over 6 months with 12 months open-label follow-up.

INTRODUCTION: The clinical significance of low to low-normal testosterone (T) levels in men remains debated. AIM: To analyze the effects of raising serum T on lean body mass (LBM), fat mass (FM), total body mass, and health-related quality-of-life (HRQoL). METHODS: Randomized, double-blind, placebo-controlled study. Men, aged 50-80 years, with serum total T<15 nmol/L and bioavailable T < 6.68 nmol/L, and a Aging Males' Symptoms (AMS) total score >36, received 6 months treatment with transdermal 1% T gel (5-7.5 mg/day; n =183) or placebo gel (n =179), followed by 12 months open-label with T in all. RESULTS: After 6 months, LBM increased in T- treated patients by 1.28 ± 0.15 kg (mean ± SE) and FM decreased by 1.16 ± 0.16 kg, with minor changes with placebo (LBM +0.02 ± 0.10 kg and FM -0.14 ± 0.12 kg; all p < 0.001, T group vs. placebo). Changes were largely similar across subgroups of age, baseline total testosterone, and baseline BMI. Total HRQoL improved compared with placebo (p < 0.05, T group vs. placebo). CONCLUSIONS: Six months 1% T gel improved body composition and HRQoL in symptomatic men with low to low-normal T, with further improvements over the following 12 months.

Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double-blinded placebo-controlled Moscow study.

OBJECTIVE: Men with the metabolic syndrome (MetS) have low plasma testosterone (T) levels. The aim of this study was to establish whether the normalization of plasma T improves the features of the MetS. DESIGN: A randomized, placebo-controlled, double-blinded, phase III trial of 184 men suffering from both the MetS and hypogonadism. PATIENTS: One hundred and eighty-four men, aged 35-70, with the MetS and hypogonadism (baseline total T level <12·0 nm or calculated free T level <225 pm.), recruited in the outpatient andrology and urology clinic, Research Center for Endocrinology in Moscow, Russia. INTERVENTION: Treatment for 30 weeks with either parenteral T undecanoate (n = 113; TU; 1000 mg IM) or placebo (n = 71), administered at baseline, and after 6 and 18 weeks. One hundred and five (92·9%) men receiving TU and 65 (91·5%) receiving placebo completed the trial. MEASUREMENTS: Body weight, body mass index (BMI), waist circumference (WC), hip circumference, waist-to-hip ratio, insulin, leptin, glucose, cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, C-reactive protein (CRP), interleukin-1-beta (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumour necrosis factor-alpha (TNF-α). RESULTS: There were significant decreases in weight, BMI and WC in the TU vs placebo group. Levels of leptin and insulin also decreased, but there were no changes in serum glucose or lipid profile. Of the inflammatory markers, IL-1ß, TNF-α and CRP decreased, while IL-6 and IL-10 did not change significantly. CONCLUSIONS: Thirty weeks of T administration normalizing plasma T in hypogonadal men with the MetS improved some components of the MetS and a number of inflammatory markers.

Safety of physiological testosterone therapy in women: lessons from female-to-male transsexuals (FMT) treated with pharmacological testosterone therapy.

INTRODUCTION: The safety of long-term physiological doses of testosterone (T) therapy in women with sexual dysfunction is a contentious issue, in part, because of fear of adverse effects, such as breast cancer, vascular disease, and excessive virilization. This unsubstantiated fear has hampered progress in treating women with sexual dysfunction using T therapy in physiological doses to achieve circulating levels in the normal range. AIM: To examine evidence derived from studies in female-to-male transsexuals (FMT) treated with supraphysiological (pharmacological) doses of T for long periods of time with no apparent major adverse effects. METHODS: A comprehensive literature search of relevant articles published between 1980 and 2010 pertaining to the topic of T in FMTs was performed using PubMed. The following key words were used: female-to-male transsexuals; testosterone; virilization; gender re-assignment; and androgen therapy in women. Relevant articles were retrieved, reviewed, and the information was analyzed and evaluated for study methodology and major findings. MAIN OUTCOME MEASURES: Data from peer-reviewed publications were critically analyzed and the information was summarized. RESULTS: The data from the studies reported in the literature to date strongly suggest that treatment of FMTs with supra-physiological doses of T had minimal adverse effects. No increase in mortality, breast cancer, vascular disease, or other major health problems were reported. CONCLUSIONS: No significant serious adverse effects were reported in FMTs treated with pharmacological doses of T. In light of the findings with supraphysiological doses of T, we suggest that treatment with T at doses producing physiological levels in women with sexual dysfunction are expected to produce limited and minimal adverse effects.

Effects of testosterone supplementation on depressive symptoms and sexual dysfunction in hypogonadal men with the metabolic syndrome.

INTRODUCTION: Low testosterone levels in men are associated with the metabolic syndrome (MetS) as well as with depressive symptoms, low vitality, and sexual dysfunction. AIM: To assess the effects of testosterone administration on these subjective symptoms, which have not extensively been studied in hypogonadal men with the MetS. MAIN OUTCOME MEASURES: The Beck Depression Inventory (BDI-IA), Aging Males' Symptoms (AMS) scale, and International Index of Erectile Function 5-item (IIEF-5) scale at baseline, 18 and 30 weeks were analysed using multilevel analysis. METHODS: In a randomized, placebo-controlled, double-blind, phase III trial (ClinicalTrials.gov identifier: NCT00696748), 184 men suffering from both the MetS and hypogonadism were included. They were treated for 30 weeks with either parenteral testosterone undecanoate (TU; 1,000 mg IM TU, at baseline, and after 6 and 18 weeks; Nebido or placebo injections, 105 (92.9%) men receiving TU and 65 (91.5%) receiving placebo completed the 30-week trial. RESULTS: The 184 men were aged mean 52.1 years old (standard deviation [SD] 9.6; range 35-69), with a mean body mass index of 35.5 kg/m(2) (SD 6.7; range 25.1-54.8), and a mean total testosterone level of 8.0 nmol/L (SD 4.0). There were significant improvements in BDI-IA (mean difference vs. placebo after 30 weeks: -2.5 points; 95% confidence interval [CI]: -0.9; -4.1; P = 0.003), AMS (-7.4 points; 95% CI: -4.3; -10.5; P < 0.001), and IIEF-5 (+3.1 points; 95% CI: +1.8; +4.4; P < 0.001). The effects on the BDI-IA, AMS, and IIEF-5 were strongest in men with baseline total testosterone levels <7.7 mmol/L (i.e., median value). CONCLUSIONS: TU administration may improve depressive symptoms, aging male symptoms and sexual dysfunction in hypogonadal men with the MetS. The beneficial effects of testosterone were most evident in men with the lowest baseline total testosterone levels.

Bone Development in Transgender Adolescents Treated With GnRH Analogues and Subsequent Gender-Affirming Hormones.

CONTEXT: Hormonal interventions in adolescents with gender dysphoria may have adverse effects, such as reduced bone mineral accrual. OBJECTIVE: To describe bone mass development in adolescents with gender dysphoria treated with gonadotropin-releasing hormone analogues (GnRHa), subsequently combined with gender-affirming hormones. DESIGN: Observational prospective study. SUBJECTS: 51 transgirls and 70 transboys receiving GnRHa and 36 transgirls and 42 transboys receiving GnRHa and gender-affirming hormones, subdivided into early- and late-pubertal groups. MAIN OUTCOME MEASURES: Bone mineral apparent density (BMAD), age- and sex-specific BMAD z-scores, and serum bone markers. RESULTS: At the start of GnRHa treatment, mean areal bone mineral density (aBMD) and BMAD values were within the normal range in all groups. In transgirls, the mean z-scores were well below the population mean. During 2 years of GnRHa treatment, BMAD stabilized or showed a small decrease, whereas z-scores decreased in all groups. During 3 years of combined administration of GnRHa and gender-affirming hormones, a significant increase of BMAD was found. Z-scores normalized in transboys but remained below zero in transgirls. In transgirls and early pubertal transboys, all bone markers decreased during GnRHa treatment. CONCLUSIONS: BMAD z-scores decreased during GnRHa treatment and increased during gender-affirming hormone treatment. Transboys had normal z-scores at baseline and at the end of the study. However, transgirls had relatively low z-scores, both at baseline and after 3 years of estrogen treatment. It is currently unclear whether this results in adverse outcomes, such as increased fracture risk, in transgirls as they grow older.

Prostate Cancer Incidence under Androgen Deprivation: Nationwide Cohort Study in Trans Women Receiving Hormone Treatment.

CONTEXT: Trans women (male sex assigned at birth, female gender identity) mostly use antiandrogens combined with estrogens and can subsequently undergo vaginoplasty including orchiectomy. Because the prostate remains in situ after this procedure, trans women are still at risk for prostate cancer. OBJECTIVE: To assess the incidence of prostate cancer in trans women using hormone treatment. The incidence of prostate cancer in trans women using hormone treatment. DESIGN: In this nationwide retrospective cohort study, data of participants were linked to the Dutch national pathology database and to Statistics Netherlands to obtain data on prostate cancer diagnosis and mortality. SETTING: Gender identity clinic. PARTICIPANTS: Trans women who visited our clinic between 1972 and 2016 and received hormone treatment were included. MAIN OUTCOME MEASURES: Standardized incidence ratios (SIRs) were calculated using the number of observed prostate cancer cases in our cohort and the number of expected cases based on age-specific incidence numbers from the Netherlands Comprehensive Cancer Organization. RESULTS: The study population consisted of 2281 trans women with a median follow-up time of 14 years (interquartile range 7-24), and a total follow-up time of 37 117 years. Six prostate cancer cases were identified after a median 17 years of hormone treatment. This resulted in a lower prostate cancer risk in trans women than in Dutch reference males (SIR 0.20, 95% confidence interval 0.08-0.42). CONCLUSIONS: Trans women receiving androgen deprivation therapy and estrogens have a substantially lower risk for prostate cancer than the general male population. Our results support the hypothesis that androgen deprivation has a preventive effect on the initiation and development of prostate cancer.

Improvement of the diabetic foot upon testosterone administration to hypogonadal men with peripheral arterial disease. Report of three cases.

BACKGROUND: Lower extremity complications (neuropathy, ulceration, infection, and peripheral arterial disease) are common in diabetes mellitus. There is an inverse relation between plasma testosterone and insulin sensitivity, type 2 diabetes mellitus and HbA1c concentrations. METHODS: We report the beneficial effects of administration of testosterone to three men with a diabetic foot whose serum testosterone was subnormal. RESULTS: Upon normalization of serum testosterone there was an improvement of hyperglycemia, a decrease of leukocytes and of fibrinogen levels, an increase of antithrombin III activity and of tissue oxygen pressure. The wound showed granulation. CONCLUSION: Beneficial effects of administration of testosterone to hypogonadal with a diabetic foot may be due to improved vascularization and to anti-inflammatory action.

Potential side effects of androgen deprivation treatment in sex offenders.

Testosterone is an important hormone involved in sexual arousal, and, indeed, a profound reduction of testosterone levels may be helpful in controlling sexual impulses in sex offenders. Earlier thought of as a sex hormone only, testosterone has been increasingly shown to have manifold actions in the adult male. Normal adult levels of androgens are required for the health of bones, a large number of metabolic functions, mood, erythropoiesis, sebaceous gland activity of the skin, and several other functions. Severe androgen deficiency is associated with pathologies of these biological systems. Androgen deprivation therapy may result in osteoporosis, weight gain with an increased visceral adiposity, impaired glucose tolerance, dyslipidemia, and emotional disturbances. Some of these features combine in the metabolic syndrome that is also frequently associated with the use of psychotropic medication in general. It leads to a moderately increased risk of fractures and diabetes mellitus (by 40%-50%), and a small increased risk of cardiovascular morbidity and depression (by 10%-20%). It should be noted that small proportionate increases in risk may be of modest clinical significance when background risks are very low. Effective and safe management of sex offenders treated with testosterone-deprivation therapy should include careful monitoring of side effects and their prevention and treatment.

Hypertrophic osteoarthropathy: estrogens, prostaglandinE2, prostaglandin A2, and the inflammatory reflex.

It has been claimed that hyperestrogenism occurs in hypertrophic osteoarthropathy (HOA), but not in simple clubbing. However, one of our patients had simple clubbing and hyperestrogenism. We therefore measured estrogens, androgens, sex hormone-binding globulin (SHBG), and gonadotropins in five patients with HOA and in 18 patients with simple clubbing. Of the patients with HOA, 80% had a high urinary estriol concentration. In their serum, 80% had high estrone, 0% high estradiol, and 40% high SHBG. Of the patients with simple clubbing, 89% had a high urinary estriol concentration. In their serum, 76% had high estrone, 6% high estradiol, and 31% high SHBG. In all patients, urinary estriol concentration correlated positively with the degree of clubbing. Serum concentration of androstenedione, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) was mostly normal, but androstenedione concentration correlated positively with the degree of clubbing. Spider angiomas were present in 74%, palmar erythema in 39%, and gynecomastia in 9%. Urinary creatinine concentration was low in 48% and correlated positively with the degree of clubbing. We reject the claim that hyperestrogenism occurs in HOA, but not in simple clubbing. Hyperestrogenism occurs both in HOA and in simple clubbing. Our results also support earlier reports that clubbing and HOA are associated with spider angiomas, palmar erythema, gynecomastia, adrenal cortical hyperfunction, muscle atrophy, and water retention. These results led to a new hypothesis on the pathogenesis of HOA, involving estrogens, prostaglandin E2, prostaglandin A2, and the inflammatory reflex.

Long-term treatment of transsexuals with cross-sex hormones: extensive personal experience.

CONTEXT: Transsexuals receive cross-sex hormone treatment. Its short-term use appears reasonably safe. Little is known about its long-term use. This report offers some perspectives. SETTING: The setting was a university hospital serving as the national referral center for The Netherlands (16 million people). PATIENTS: From the start of the gender clinic in 1975 up to 2006, 2236 male-to-female and 876 female-to-male transsexuals have received cross-sex hormone treatment. In principle, subjects are followed up lifelong. INTERVENTIONS: Male-to-female transsexuals receive treatment with the antiandrogen cyproterone acetate 100 mg/d plus estrogens (previously 100 microg ethinyl estradiol, now 2-4 mg oral estradiol valerate/d or 100 microg transdermal estradiol/d). Female-to-male transsexuals receive parenteral testosterone esters 250 mg/2 wk. After 18-36 months, surgical sex reassignment including gonadectomy follows, inducing a profound hypogonadal state. MAIN OUTCOME MEASURES: Outcome measures included morbidity and mortality data and data assessing risks of osteoporosis and cardiovascular disease. RESULTS: Mortality was not higher than in a comparison group. Regarding morbidity, with ethinyl estradiol, there was a 6-8% incidence of venous thrombosis, which is no longer the case with use of other types of estrogens. Continuous use of cross-sex hormones is required to prevent osteoporosis. Androgen deprivation plus an estrogen milieu in male-to-female transsexuals has a larger deleterious effect on cardiovascular risk factors than inducing an androgenic milieu in female-to-male transsexuals, but there is so far no elevated cardiovascular morbidity/mortality. Low numbers of endocrine-related cancers have been observed in male-to-female transsexuals. CONCLUSIONS: Cross-sex hormone treatment of transsexuals seems acceptably safe over the short and medium term, but solid clinical data are lacking.

Prevalence of polycystic ovary syndrome and hyperandrogenemia in female-to-male transsexuals.

INTRODUCTION: It has been postulated that the prevalence of polycystic ovary syndrome (PCOS) in female-to-male transsexuals (FMTs) is higher than normal. AIM: The aim of the study was to investigate the prevalence of PCOS and hyperandrogenemia in FMTs, compared with controls. METHODS: Sixty-one FMTs were evaluated using the Rotterdam 2003 criteria and National Institutes of Health 1990 criteria for the diagnosis of PCOS, compared with 94 controls. MAIN OUTCOME MEASURE(S): Oligoovulation, anovulation, clinical and biochemical signs of hyperandrogenism and polycystic ovaries, and prevalence of PCOS were measured. RESULTS: The prevalence of PCOS was 11.5% in FMTs and 9.6% in controls (not significant) with National Institutes of Health 1990 criteria and 14.8% in FMTs and 12.8% in controls (not significant) with the Rotterdam 2003 criteria. Without adjustments and using multivariate analysis in a logistic regression model with adjustments for age, body mass index, and calculated free testosterone, the odds ratio for the prevalence of PCOS was not found to be significantly increased. However, there was a significantly higher prevalence of biochemical hyperandrogenism in FMTs. Hyperandrogenemia was associated with a moderate increase in the odds ratio for the prevalence of PCOS, at 1.08 and 1.07 (P < 0.001 and P = 0.001), for the two definitions used in this study, respectively. CONCLUSIONS: PCOS was not significantly increased in FMTs in comparison with controls. However, FMTs more frequently had biochemical hyperandrogenism.