Gender affirmation is multidisciplinary treatment in which endocrinologists play an important role. Gender-dysphoric/gender-incongruent persons seek and/or are referred to endocrinologists to develop the physical characteristics of the affirmed gender. They require a safe and effective hormone regimen that will (1) suppress endogenous sex hormone secretion determined by the person's genetic/gonadal sex and (2) maintain sex hormone levels within the normal range for the person's affirmed gender. Hormone treatment is not recommended for prepubertal gender-dysphoric/gender-incongruent persons. Those clinicians who recommend gender-affirming endocrine treatments-appropriately trained diagnosing clinicians (required), a mental health provider for adolescents (required) and mental health professional for adults (recommended)-should be knowledgeable about the diagnostic criteria and criteria for gender-affirming treatment, have sufficient training and experience in assessing psychopathology, and be willing to participate in the ongoing care throughout the endocrine transition. We recommend treating gender-dysphoric/gender-incongruent adolescents who have entered puberty at Tanner Stage G2/B2 by suppression with gonadotropin-releasing hormone agonists. Clinicians may add gender-affirming hormones after a multidisciplinary team has confirmed the persistence of gender dysphoria/gender incongruence and sufficient mental capacity to give informed consent to this partially irreversible treatment. Most adolescents have this capacity by age 16 years old. We recognize that there may be compelling reasons to initiate sex hormone treatment prior to age 16 years, although there is minimal published experience treating prior to 13.5 to 14 years of age. For the care of peripubertal youths and older adolescents, we recommend that an expert multidisciplinary team comprised of medical professionals and mental health professionals manage this treatment. The treating physician must confirm the criteria for treatment used by the referring mental health practitioner and collaborate with them in decisions about gender-affirming surgery in older adolescents. For adult gender-dysphoric/gender-incongruent persons, the treating clinicians (collectively) should have expertise in transgender-specific diagnostic criteria, mental health, primary care, hormone treatment, and surgery, as needed by the patient. We suggest maintaining physiologic levels of gender-appropriate hormones and monitoring for known risks and complications. When high doses of sex steroids are required to suppress endogenous sex steroids and/or in advanced age, clinicians may consider surgically removing natal gonads along with reducing sex steroid treatment. Clinicians should monitor both transgender males (female to male) and transgender females (male to female) for reproductive organ cancer risk when surgical removal is incomplete. Additionally, clinicians should persistently monitor adverse effects of sex steroids. For gender-affirming surgeries in adults, the treating physi...

Transsexual persons seeking to develop the physical characteristics of the desired gender require a safe, effective hormone regimen that will 1) suppress endogenous hormone secretion determined by the person's genetic/biologic sex and 2) maintain sex hormone levels within the normal range for the person's desired gender. A mental health professional (MHP) must recommend endocrine treatment and participate in ongoing care throughout the endocrine transition and decision for surgical sex reassignment. The endocrinologist must confirm the diagnostic criteria the MHP used to make these recommendations. Because a diagnosis of transsexualism in a prepubertal child cannot be made with certainty, we do not recommend endocrine treatment of prepubertal children. We recommend treating transsexual adolescents (Tanner stage 2) by suppressing puberty with GnRH analogues until age 16 years old, after which cross-sex hormones may be given. We suggest suppressing endogenous sex hormones, maintaining physiologic levels of gender-appropriate sex hormones and monitoring for known risks in adult transsexual persons.

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The new ISA, ISSAM, EAU, EAA and ASA recommendations on the investigation, treatment and monitoring of late-onset hypogonadism in males provide updated evidence-based information for clinicians who diagnose and treat patients with adult onset, age related testosterone deficiency.

Objective: Adverse effects of long-term cross-sex hormone administration to transsexuals are not well documented. We assessed mortality rates in transsexual subjects receiving long-term cross-sex hormones. Design: A cohort study with a median follow-up of 18.5 years at a university gender clinic. Methods: Mortality data and the standardized mortality rate were compared with the general population in 966 male-to-female (MtF) and 365 female-to-male (FtM) transsexuals, who started cross-sex hormones before July 1, 1997. Follow-up was at least 1 year. MtF transsexuals received treatment with different high-dose estrogen regimens and cyproterone acetate 100 mg/day. FtM transsexuals received parenteral/oral testosterone esters or testosterone gel. After surgical sex reassignment, hormonal treatment was continued with lower doses. Results: In the MtF group, total mortality was 51% higher than in the general population, mainly from increased mortality rates due to suicide, acquired immunodeficiency syndrome, cardiovascular disease, drug abuse, and unknown cause. No increase was observed in total cancer mortality, but lung and hematological cancer mortality rates were elevated. Current, but not past ethinyl estradiol use was associated with an independent threefold increased risk of cardiovascular death. In FtM transsexuals, total mortality and cause-specific mortality were not significantly different from those of the general population. Conclusions: The increased mortality in hormone-treated MtF transsexuals was mainly due to nonhormone-related causes, but ethinyl estradiol may increase the risk of cardiovascular death. In the FtM transsexuals, use of testosterone in doses used for hypogonadal men seemed safe.

Transsexuals have the strong feeling, often from childhood onwards, of having been born the wrong sex. The possible psychogenic or biological aetiology of transsexuality has been the subject of debate for many years. Here we show that the volume of the central subdivision of the bed nucleus of the stria terminals (BSTc), a brain area that is essential for sexual behaviour, is larger in men than in women. A female-sized BSTc was found in male-to-female transsexuals. The size of the BSTc was not influenced by sex hormones in adulthood and was independent of sexual orientation. Our study is the first to show a female brain structure in genetically male transsexuals and supports the hypothesis that gender identity develops as a result of an interaction between the developing brain and sex hormones.

Men with the metabolic syndrome (MetS) and type 2 diabetes (T2D) often have low testosterone levels. Elevating low testosterone levels may improve features of the MetS and glycemic control. In a single blind, 52-week randomized clinical trial, the effects of supervised diet and exercise (D&E) with or without transdermal testosterone administration on components of the MetS in hypogonadal men with the MetS and newly diagnosed T2D were assessed. A total of 32 hypogonadal men (total testosterone ,12.0 nmol/L) with newly diagnosed T2D and with the MetS as defined by the Adult Treatment Panel III and the International Diabetes Federation received supervised D&E, but 16 received it in combination with testosterone gel (50 mg) once daily (n 5 16). No glucose-lowering agents were administered prior to or during the study period. Outcome measures were components of the MetS as defined by the Adult Treatment Panel III and the International Diabetes Federation. Serum testosterone, glycosylated hemoglobin (HbA 1c ), fasting plasma glucose, high-density lipoprotein cholesterol, triglyceride concentrations, and the waist circumference improved in both treatment groups after 52 weeks of treatment. Addition of testosterone significantly further improved these measures compared with D&E alone. All D&E plus testosterone patients reached the HbA 1c goal of less than 7.0%; 87.5% of them reached an HbA 1c of less than 6.5%. Based on Adult Treatment Panel III guidelines, 81.3% of the patients randomized to D&E plus testosterone no longer matched the criteria of the MetS, whereas 31.3% of the D&E alone participants did. Additionally, testosterone treatment improved insulin sensitivity, adiponectin, and high-sensitivity C-reactive protein. Addition of testosterone to supervised D&E results in greater therapeutic improvements of glycemic control and reverses the MetS after 52 weeks of treatment in hypogonadal patients with the MetS and newly diagnosed T2D.

SummaryObjective 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 <12AE0 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 (92AE9%) men receiving TU and 65 (91AE5%) 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-1b), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumour necrosis factor-alpha (TNF-a). 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-1b, TNF-a 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.