No abstract

Antiandrogens are frequently used with estradiol in transgender women seeking feminization. Antiandrogens act by various mechanisms to decrease the production or effects of testosterone, but it is unclear which antiandrogen is most effective at feminization. A systematic review was performed using PRISMA guidelines. We searched online databases (Medline, Embase and PsycINFO) and references of relevant articles for studies of antiandrogens in transgender women aged 16+ years to achieve feminization (namely changes in breast size, body composition, facial or body hair) or changes in serum total testosterone concentration when compared to placebo, estradiol alone or an alternative antiandrogen. Four studies fulfilled eligibility criteria and were included in a narrative review. The addition of cyproterone acetate, leuprolide and medroxyprogesterone acetate may be more effective than spironolactone or estradiol alone at suppressing the serum total testosterone concentration. Body composition changes appear similar in transgender women treated with estradiol and additional cyproterone acetate or leuprolide. No eligible studies adequately evaluated the effects of antiandrogens on breast development or facial and body hair reduction. It remains unclear which antiandrogen is most effective at achieving feminization. Cyproterone acetate, medroxyprogesterone acetate and leuprolide may be more effective than spironolactone at suppressing the serum total testosterone concentration. However, due to spironolactone's antagonism of the androgen receptor, it is unclear whether this results in clinically meaningful differences in feminization. Further research with clinically meaningful endpoints is needed to optimize the use of antiandrogens in transgender women.

To assess the effect of testosterone treatment on bone remodelling and density in dieting obese men, 100 obese men aged 53 years (interquartile range 47–60) with a total testosterone level <12 nmol/L receiving 10 weeks of a very low energy diet (VLED) followed by 46 weeks of weight maintenance were randomly assigned at baseline to 56 weeks of intramuscular testosterone undecanoate (n = 49, cases) or matching placebo (n = 51, controls). Pre-specified outcomes were between-group differences (mean adjusted difference, MAD) in serum c-telopeptide (CTx), N-terminal propeptide of type 1 procollagen (P1NP) and bone mineral density (BMD). At trial end, CTx was significantly reduced in men receiving testosterone compared to placebo, MAD −66 ng/L (95% CI −113, −18), p = 0.018, and this was apparent already after the 10 week VLED phase, MAD −63 ng/L (95% CI −108, −18), p = 0.018. P1NP was marginally increased after VLED, MAD +4.2 ug/L (95% CI −0.01, +8.4), p = 0.05 but lower at study end, MAD −5.6 ug/L (95% CI −10.1, −1.1), p = 0.03. No significant changes in sclerostin, lumbar spine BMD or femoral BMD were seen. We conclude that in obese men with low testosterone levels undergoing weight loss, bone remodelling markers are modulated in a way that may have favourable effects on bone mass.

Salivary cortisol provides additional diagnostic value during the 250 µg ACTH stimulation test in patients with proven or suspected alterations in CBG and potentially those with a borderline 60 min serum cortisol 500-599 nmol/L.

Context Pre-clinical data has shown progesterone metabolites improve sleep parameters through positive allosteric modulation of the GABA-A receptor. We undertook a systematic review and meta-analysis of randomised controlled trials to assess micronised progesterone treatment on sleep outcomes. Evidence Acquisition Using PRISMA guidelines, we searched MEDLINE, Embase, PsycInfo and the Cochrane Central Register of Controlled Trials for randomised controlled trials of micronised progesterone treatment on sleep outcomes up to March 31, 2020. This study is registered with the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42020165981. A random-effects model was used for quantitative analysis. Evidence Synthesis Our search strategy retrieved 9 randomised controlled trials comprising 388 participants. One additional unpublished trial was found. Eight trials enrolled post-menopausal women. Compared with placebo, micronised progesterone improved various sleep parameters as measured by polysomnography, including total sleep time and sleep onset latency, though studies were inconsistent. Meta-analysis of 4 trials favoured micronised progesterone for sleep onset latency (effect size, 7.10; C.I. 1.30, 12.91) but not total sleep time (effect size, 20.72; C.I -0.16, 41.59) or sleep efficiency (effect size, 1.31; C.I. -2.09, 4.70). Self-reported sleep outcomes improved in most trials. Concomitant estradiol administration and improvement in vasomotor symptoms limit conclusions in some studies. Conclusions Micronised progesterone improves various sleep outcomes in randomised controlled trials, predominantly in studies enrolling post-menopausal women. Further research could evaluate the efficacy of micronised progesterone monotherapy using polysomnography or validated questionnaires in larger cohorts.

Background Masculinising hormone therapy with testosterone is used to align an individual's physical characteristics with his or her gender identity. Testosterone therapy is typically administered via intramuscular or transdermal routes, and polycythaemia is the most common adverse event. Aims To compare the risk of polycythaemia with different formulations of testosterone therapy in transmasculine individuals. Methods A retrospective cross‐sectional analysis was undertaken of transmasculine individuals at a primary and secondary care clinic in Melbourne, Australia. A total of 180 individuals who were on testosterone therapy for >6 months was included. Groups included those receiving: (i) intramuscular testosterone undecanoate (n = 125); (ii) intramuscular testosterone enantate (n = 31); or (iii) transdermal testosterone (n = 24). Outcome was prevalence of polycythaemia (defined as haematocrit > 0.5). Results Mean age was 28.4 (8.8) years, with a median duration of testosterone therapy of 37.7 (24.2) months; 27% were smokers. There was no difference between groups in serum total testosterone concentration measured. While there was no difference between groups in haematocrit, there was a higher proportion of patients with polycythaemia in those who were on intramuscular testosterone enantate (23.3%) than on transdermal testosterone (0%), P = 0.040. There was no statistically significant difference in polycythaemia between intramuscular testosterone undecanoate (15%) and transdermal testosterone, P = 0.066 nor between intramuscular testosterone enantate and undecanoate, P = 0.275. Conclusions One in four individuals treated with intramuscular testosterone enantate and one in six treated with testosterone undecanoate had polycythaemia. No individual treated with transdermal testosterone had polycythaemia. This highlights the importance of regular monitoring of haematocrit in transmasculine individuals treated with testosterone, and findings may inform treatment choices.

Transgender, including gender diverse and nonbinary, individuals are treated with estradiol with or without antiandrogen to align their physical appearance with their gender identity, improve mental health and quality of life. Consensus guidelines give target ranges for serum estradiol concentration based on premenopausal female reference ranges. However, limited studies have evaluated the relationship between serum estradiol concentrations and clinical outcomes in transgender individuals undergoing feminizing hormone therapy. The available evidence has not found that higher serum estradiol concentrations, together with suppressed testosterone, enhance breast development, or produce more feminine changes to body composition. However, ensuring testosterone suppression appears to be an important factor to maximize these physical changes. Higher serum estradiol concentrations have been associated with higher areal bone mineral density. Although the resultant long-term clinical implications are yet to be determined, this could be a consideration for individuals with low bone mass. The precise serum estradiol concentration that results in adequate feminization without increasing the risk of complications (thromboembolic disease, cholelithiasis) remains unknown. Further prospective trials are required.

Background: Masculinising hormone therapy with testosterone is used to align an individual’s physical characteristics with their gender identity. Standard testosterone doses and formulations recommended for hypogonadal cisgender men are typically administered, although there are currently limited data evaluating the use of 1% testosterone gel in gender-affirming hormone therapy regimens. Objectives: The objective of the study was to assess the prescription patterns and serum total testosterone concentrations achieved with 1% testosterone gel in trans and gender diverse individuals. Materials and Methods: A retrospective cross-sectional analysis was undertaken of trans individuals at a primary and secondary care clinic in Melbourne, Australia. Sixty-seven individuals treated with 1% testosterone gel were included. Primary outcomes were testosterone dose and serum total testosterone concentration achieved. Results: Median age was 25 (22–30) years and median duration of testosterone therapy was 12 (7–40) months. Thirty-five (52%) individuals had a nonbinary gender identity. Initial median testosterone dose was 25 mg (12.5–31.3) daily. Fifty-two (78%) individuals commenced doses <50 mg daily, the recommended starting dose for hypogonadal cisgender men. Median total testosterone concentration achieved was 11.9 nmol/l (7.3–18.6). Polycythaemia (haematocrit >0.5) was documented in eight of 138 (6%) laboratory results in six individuals. Discussion and Conclusions: One percent testosterone gel achieves serum total testosterone concentrations in the cisgender male reference range. A high proportion of individuals had a nonbinary gender identity and most individuals commenced a lower dose than that typically administered to hypogonadal cisgender men, potentially related to slow or ‘partial’ masculinisation goals.