Effect of Feminizing Hormone Therapy on QTc Interval: A Secondary Analysis of a Randomized Clinical Trial.

This secondary analysis of a randomized clinical trial investigates the effect of spironolactone and cyproterone acetate hormone therapy on the QT interval corrected for heart rate among transgender women and nonbinary or transfeminine individuals.

The Impact of Gender-Affirming Hormone Therapy on Physical Performance.

CONTEXT: The inclusion of transgender people in elite sport has been a topic of debate. This narrative review examines the impact of gender-affirming hormone therapy (GAHT) on physical performance, muscle strength, and markers of endurance. EVIDENCE ACQUISITION: MEDLINE and Embase were searched using terms to define the population (transgender), intervention (GAHT), and physical performance outcomes. EVIDENCE SYNTHESIS: Existing literature comprises cross-sectional or small uncontrolled longitudinal studies of short duration. In nonathletic trans men starting testosterone therapy, within 1 year, muscle mass and strength increased and, by 3 years, physical performance (push-ups, sit-ups, run time) improved to the level of cisgender men. In nonathletic trans women, feminizing hormone therapy increased fat mass by approximately 30% and decreased muscle mass by approximately 5% after 12 months, and steadily declined beyond 3 years. While absolute lean mass remains higher in trans women, relative percentage lean mass and fat mass (and muscle strength corrected for lean mass), hemoglobin, and VO2 peak corrected for weight was no different to cisgender women. After 2 years of GAHT, no advantage was observed for physical performance measured by running time or in trans women. By 4 years, there was no advantage in sit-ups. While push-up performance declined in trans women, a statistical advantage remained relative to cisgender women. CONCLUSION: Limited evidence suggests that physical performance of nonathletic trans people who have undergone GAHT for at least 2 years approaches that of cisgender controls. Further controlled longitudinal research is needed in trans athletes and nonathletes.

Disruption of gender-affirming health care, and COVID-19 illness, testing, and vaccination among trans Australians during the pandemic: a cross-sectional survey.

OBJECTIVES: To assess rates of disruption of gender-affirming health care, of coronavirus disease 2019 (COVID-19) illness, testing, and vaccination, and of discrimination in health care among Australian trans people during the COVID-19 pandemic. DESIGN, SETTING: Online cross-sectional survey (1-31 May 2022); respondents were participants recruited by snowball sampling for TRANSform, an Australian longitudinal survey-based trans health study, 1 May - 30 June 2020. PARTICIPANTS: People aged 16 years or older, currently living in Australia, and with a gender different to their sex recorded at birth. MAIN OUTCOME MEASURES: Proportions of respondents who reported disruptions to gender-affirming health care, COVID-19 illness, testing, and vaccination, and positive and negative experiences during health care. RESULTS: Of 875 people invited, 516 provided valid survey responses (59%). Their median age was 33 years (interquartile range, 26-45 years); 193 identified as women or trans women (37%), 185 as men or trans men (36%), and 138 as non-binary (27%). Of 448 respondents receiving gender-affirming hormone therapy, 230 (49%) reported disruptions to treatment during the pandemic; booked gender-affirming surgery had been cancelled or postponed for 37 of 85 respondents (44%). Trans-related discrimination during health care was reported by a larger proportion of participants than in a pre-pandemic survey (56% v 26%). COVID-19 was reported by 132 respondents (26%), of whom 49 reported health consequences three months or more after the acute illness (37%; estimated Australian rate: 5-10%). Three or more COVID-19 vaccine doses were reported by 448 participants (87%; Australian adult rate: 70%). CONCLUSIONS: High rates of COVID-19 vaccination among the trans people we surveyed may reflect the effectiveness of LGBTIQA+ community-controlled organisation vaccination programs and targeted health promotion. Training health care professionals in inclusive services for trans people could improve access to appropriate health care and reduce discrimination.

Epidemiology of Intensive Care Patients Classified as a Third Sex in Australia and New Zealand.

BACKGROUND: Patient sex affects treatment and outcomes in critical illness. Previous studies of sex differences in critical illness compared female and male patients. In this study, we describe the group of patients classified as a third sex admitted to ICUs in Australia and New Zealand. RESEARCH QUESTION: What are the admission characteristics and outcomes of ICU patients classified as belonging to a third sex group compared with patients classified as female or male? STUDY DESIGN AND METHODS: Retrospective observational study of admissions to 200 ICUs, recorded in the Australian and New Zealand Intensive Care Society's Adult Patient Database from 2018 to 2022. We undertook mixed effect logistic regression to compare hospital mortality across the sex groups, adjusted for illness severity, diagnosis, treatment limitation, year, and hospital. RESULTS: We examined 892,161 admissions, of whom 525 (0.06%) were classified as third sex. Patients classified as third sex were represented across all diagnostic categories, jurisdictions, and hospital types. On average, they were younger than the groups classified as female (59.2 ± 20.0 vs 61.3 ± 18.4 years; P = .02) or male (63.2 ± 16.7 years; P < .001), respectively. Patients classified as third sex were more likely to be admitted after orthopedic surgery (10.1% third sex admissions [95% CI, 7.7%-13.0%]; 6.2% female [95% CI, 6.1%-6.3%]; 4.8% male [95% CI, 4.7%-4.9%]) and drug overdose (8.8% third sex admissions [95% CI, 6.5%-11.5%]; 4.2% female [95% CI, 4.1%-4.2%]; 3.1% male [95% CI, 3.0%-3.1%]). There was no difference in the adjusted hospital mortality of patients classified as third sex compared with the other groups. INTERPRETATION: Patients classified as third sex composed a small minority group of adult ICU patients. This group had a different diagnostic case mix but similar outcomes to the groups classified as female or male. Further characterizing a third sex group will require improved processes for recording sex and gender in health records.

Early Access to Testosterone Therapy in Transgender and Gender-Diverse Adults Seeking Masculinization: A Randomized Clinical Trial.

Importance: Testosterone treatment is a necessary component of care for some transgender and gender-diverse individuals. Observational studies have reported associations between commencement of gender-affirming hormone therapy and improvements in gender dysphoria and depression, but there is a lack of data from randomized clinical trials. Objective: To assess the effect of testosterone therapy compared with no treatment on gender dysphoria, depression, and suicidality in transgender and gender-diverse adults seeking masculinization. Design, Setting, and Participants: A 3-month open-label randomized clinical trial was conducted at endocrinology outpatient clinics and primary care clinics specializing in transgender and gender-diverse health in Melbourne, Australia, from November 1, 2021, to July 22, 2022. Participants included transgender and gender-diverse adults aged 18 to 70 years seeking initiation of testosterone therapy. Interventions: Immediate initiation of testosterone commencement (intervention group) or no treatment (standard care waiting list of 3 months before commencement). This design ensured no individuals would be waiting longer than the time to standard care. Main Outcomes and Measures: The primary outcome was gender dysphoria, as measured by the Gender Preoccupation and Stability Questionnaire. Secondary outcomes included the Patient Health Questionnaire-9 (PHQ-9) to assess depression and the Suicidal Ideation Attributes Scale (SIDAS) to assess suicidality. Questionnaires were undertaken at 0 and 3 months. The evaluable cohort was analyzed. Results: Sixty-four transgender and gender-diverse adults (median [IQR] age, 22.5 [20-27] years) were randomized. Compared with standard care, the intervention group had a decrease in gender dysphoria (mean difference, -7.2 points; 95% CI, -8.3 to -6.1 points; P < .001), a clinically significant decrease in depression (ie, change in score of 5 points on PHQ-9; mean difference, -5.6 points; 95% CI, -6.8 to -4.4 points; P < .001), and a significant decrease in suicidality (mean difference in SIDAS score, -6.5 points; 95% CI, -8.2 to -4.8 points; P < .001). Resolution of suicidality assessed by PHQ-9 item 9 occurred in 11 individuals (52%) with immediate testosterone commencement compared with 1 (5%) receiving standard care (P = .002). Seven individuals reported injection site pain/discomfort and 1 individual reported a transient headache 24 hours following intramuscular administration of testosterone undecanoate. No individual developed polycythemia. Conclusions and Relevance: In this open-label randomized clinical trial of testosterone therapy in transgender and gender-diverse adults, immediate testosterone compared with no treatment significantly reduced gender dysphoria, depression, and suicidality in transgender and gender-diverse individuals desiring testosterone therapy. Trial Registration: ANZCTR Identifier: ACTRN1262100016864.

The impact of the first three months of the COVID-19 pandemic on the Australian trans community.

Background: Trans and gender diverse individuals (people who identify with a gender different to what was presumed for them at birth) are one of the most medically and socially marginalized groups in our community. The COVID-19 pandemic may compound preexisting depression and thoughts of self-harm or suicide. Aim: We aimed to explore the impact of the COVID-19 pandemic on the Australian trans community. Methods: An online cross-sectional survey was conducted between 1st May 2020 and 30th June 2020, amidst strict Australia-wide social restrictions. Australian trans people aged ≥16 years were eligible to participate. Survey questions explored the impact of the COVID-19 pandemic on living situation, employment, financial situation, and healthcare. Logistic regression to assess negative impacts due to COVID-19 on depression and thoughts of self-harm or suicide (measured by Patient Health Questionnaire-9 (PHQ-9) are presented as odds ratios (95% confidence interval)). Results: Of 1019 participants, 49.6% reported experiencing financial strain, 22% had reduced working hours, and 22.4% were unemployed (three times the national rate). Concerningly, 61.1% experienced clinically significant symptoms of depression (Patient Health Questionnaire-9 score ≥10), considerably higher than pre-COVID rates for the trans community and over twice the national rate. Moreover, 49% reported thoughts of self-harm or suicide (over three times the national rate) which was more likely if a person experienced cancelation or postponement of gender-affirming surgery (OR 1.56 (1.04, 2.35)), financial strain (OR 1.80 (1.36, 2.38)), or felt unsafe or afraid in their household (OR 1.96 (1.23, 3.08)). Discussion: Given rates of clinically significant depression and thoughts of self-harm or suicide are far higher in trans people than the general population, specific strategies to improve mental health in the trans community during the COVID-19 pandemic must be made a priority for policymakers, researchers, and health service providers to prevent suicide.Supplemental data for this article is available online at https://doi.org/10.1080/26895269.2021.1890659.

Implications of gender-affirming endocrine care for sports participation.

Many transgender (trans) individuals utilize gender-affirming hormone therapy (GAHT) to promote changes in secondary sex characteristics to affirm their gender. Participation rates of trans people in sport are exceedingly low, yet given high rates of depression and increased cardiovascular risk, the potential benefits of sports participation are great. In this review, we provide an overview of the evidence surrounding the effects of GAHT on multiple performance-related phenotypes, as well as current limitations. Whilst data is clear that there are differences between males and females, there is a lack of quality evidence assessing the impact of GAHT on athletic performance. Twelve months of GAHT leads to testosterone concentrations that align with reference ranges of the affirmed gender. Feminizing GAHT in trans women increases fat mass and decreases lean mass, with opposite effects observed in trans men with masculinizing GAHT. In trans men, an increase in muscle strength and athletic performance is observed. In trans women, muscle strength is shown to decrease or not change following 12 months of GAHT. Haemoglobin, a measure of oxygen transport, changes to that of the affirmed gender within 6 months of GAHT, with very limited data to suggest possible reductions in maximal oxygen uptake as a result of feminizing GAHT. Current limitations of this field include a lack of long-term studies, adequate group comparisons and adjustment for confounding factors (e.g. height and lean body mass), and small sample sizes. There also remains limited data on endurance, cardiac or respiratory function, with further longitudinal studies on GAHT needed to address current limitations and provide more robust data to inform inclusive and fair sporting programmes, policies and guidelines.

Effect of gender-affirming hormone therapy on hair growth: a systematic review of the literature.

Gender-affirming hormone therapy (GAHT) leads to changes in body composition, secondary sex characteristics and in the distribution and pattern of hair growth. Transgender individuals undergoing GAHT may experience altered hair growth patterns that may be affirming and desirable, or undesirable with a subsequent impact on their quality of life. Given increasing numbers of transgender individuals commencing GAHT worldwide and the clinical relevance of the impact of GAHT on hair growth, we systematically reviewed the existing literature on the impact of GAHT on hair changes and androgenic alopecia (AGA). The majority of studies used grading schemes or subjective measures of hair changes based on patient or investigator's examination. Very few studies used objective quantitative measures of hair parameters but demonstrated statistically significant changes in hair growth length, diameter and density. Feminizing GAHT with estradiol and/or antiandrogens in transgender women may reduce facial and body hair growth and also can improve AGA. Masculinizing GAHT with testosterone in transgender men may increase facial and body hair growth as well as induce or accelerate AGA. The impact of GAHT on hair growth may not align with a transgender person's hair growth goals and specific treatment for AGA and/or hirsutism may be sought. Further research on how GAHT affects hair growth is required.

Gender-Affirming Hormone Therapy for the Trans, Gender Diverse, and Nonbinary Community: Coordinating World Professional Association for Transgender Health and Informed Consent Models of Care.

Purpose: Before commencing gender-affirming hormone therapy, people undergo assessments through the World Professional Association for Transgender Health (WPATH) model (typically with a mental health clinician), or an informed consent (IC) model (without a formal mental health assessment). Despite growing demand, these remain poorly coordinated in Australia. We aimed to compare clients attending WPATH and IC services; compare binary and nonbinary clients; and characterize clients with psychiatric diagnoses or longer assessments. Methods: Cross-sectional audit of clients approved for gender-affirming treatment (March 2017-2019) at a specialist clinic (WPATH model, n=212) or a primary care clinic (IC model, n=265). Sociodemographic, mental health, and clinical data were collected from electronic records, and analyzed with pairwise comparisons and multivariable regression. Results: WPATH model clients had more psychiatric diagnoses (mean 1.4 vs. 1.1, p<0.001) and longer assessments for hormones (median 5 vs. 2 sessions, p<0.001) than IC model clients. More IC model clients than WPATH model clients were nonbinary (27% vs. 15%, p=0.016). Nonbinary clients had more psychiatric diagnoses (mean 1.7 vs. 1.1, p<0.001) and longer IC assessments (median 3 vs. 2 sessions, p<0.001) than binary clients. Total psychiatric diagnoses were associated with nonbinary identities (ß 0.7, p=0.001) and health care cards (ß 0.4, p=0.017); depression diagnoses were associated with regional/remote residence (adjusted odds ratio [aOR] 2.2, p=0.011); and anxiety disorders were associated with nonbinary identities (aOR 2.8, p=0.012) and inversely associated with employment (aOR 0.5, p=0.016). Conclusion: WPATH model clients are more likely to have binary identities, mental health diagnoses, and longer assessments than IC model clients. Better coordination is needed to ensure timely gender-affirming care.

The Effect of Gender-Affirming Hormones on Gender Dysphoria, Quality of Life, and Psychological Functioning in Transgender Individuals: A Systematic Review.

Gender-affirming hormone therapy (GAHT) is an essential part of gender affirmation for many transgender (including people with binary and nonbinary identities) individuals and although controlled studies are unethical, there remains limited evidence on the impact of GAHT on gender dysphoria, quality of life (QoL), and psychological functioning. Some clinicians and policy makers use the lack of evidence to argue against providing gender-affirming care. The aim of this review is to systematically and critically assess the available literature on the influence of GAHT on improving gender- and body-related dysphoria, psychological well-being, and QoL. Using Preferred Reporting Items for Systematic Review and Meta-analysis guidelines, we searched Ovid MEDLINE®, Embase®, and Ovid PsycINFO® from inception to March 6, 2019 to assess the influence of GAHT on (1) gender dysphoria, (2) body uneasiness, (3) body satisfaction, (4) psychological well-being, (5) QoL, (6) interpersonal and global functioning, and (7) self-esteem. Our search strategy found no randomized controlled trials. Ten longitudinal cohort studies, 25 cross-sectional studies, and 3 articles reporting both cross-sectional and longitudinal data were identified. While results are mixed, the majority of studies demonstrate that GAHT reduces gender dysphoria, body dissatisfaction, and uneasiness, subsequently improving psychological well-being and QoL in transgender individuals. However, all current researches are of low to moderate quality comprising longitudinal cohort studies and cross-sectional studies, making it difficult to draw clear conclusions and do not reflect external social factors unaffected by GAHT, which significantly impact on dysphoria, well-being, and QoL.

Pelvic Pain in Transgender People Using Testosterone Therapy.

Purpose: This descriptive study aimed to assess the characteristics of pelvic pain and explore predictive factors for pelvic pain in transgender (trans) individuals using testosterone therapy. Methods: An online cross-sectional survey was open between August 28, 2020, and December 31, 2020, to trans people presumed female at birth, using testosterone for gender affirmation, living in Australia, and >16 years of age. The survey explored characteristics of pelvic pain following initiation of testosterone therapy, type and length of testosterone therapy, menstruation history, and relevant sexual, gynecological, and mental health experiences. Logistic regression was applied to estimate the effect size of possible factors contributing to pain after starting testosterone. Results: Among 486 participants (median age = 27 years), 351 (72.2%)* reported experiencing pelvic pain following initiation of testosterone therapy, described most commonly as in the suprapubic region and as "cramping." Median duration of testosterone therapy was 32 months. Persistent menstruation, current or previous history of post-traumatic stress disorder, and experiences of pain with orgasm were associated with higher odds of pelvic pain after testosterone therapy. No association was observed with genital dryness, intrauterine device use, previous pregnancy, penetrative sexual activities, touching external genitalia, or known diagnoses of endometriosis, vulvodynia, vaginismus, depression, anxiety, or obesity. Conclusions: Pelvic pain is frequently reported in trans people following initiation of testosterone therapy. Given the association with persistent menstruation and orgasm, as well as the known androgen sensitivity of the pelvic floor musculature, further research into pelvic floor muscle dysfunction as a contributor is warranted.

Effects of estradiol on bone in men undergoing androgen deprivation therapy: a randomized placebo-controlled trial.

Objective: In men, many effects of testosterone (T) on the skeleton are thought to be mediated by estradiol (E2), but trial evidence is largely lacking. This study aimed to determine the effects of E2 on bone health in men in the absence of endogenous T. Design: This study is a 6-month randomized, placebo-controlled trial with the hypothesis that E2 would slow the decline of volumetric bone mineral density (vBMD) and bone microstructure, maintain areal bone mineral density (aBMD), and reduce bone remodelling. Methods: 78 participants receiving androgen deprivation therapy for prostate cancer were randomized to 0.9 mg of 0.1% E2 gel daily or matched placebo. The outcome measures were vBMD and microarchitecture at the distal tibia and distal radius by high-resolution peripheral quantitative CT, aBMD at the spine and hip by dual-energy x-ray absorptiometry, and serum bone remodelling markers. Results: For the primary endpoint, total vBMD at the distal tibia, there was no significant difference between groups, mean adjusted difference (MAD) 2.0 mgHA/cm3 (95% CI: -0.8 to 4.8), P = 0.17. Cortical vBMD at the distal radius increased in the E2 group relative to placebo, MAD 14.8 mgHA/cm3 (95% CI: 4.5 to 25.0), P = 0.005. Relative to placebo, E2 increased estimated failure load at tibia, MAD 250 N (95% CI: 36 to 465), P = 0.02, and radius, MAD 193 N (95% CI: 65 to 320), P = 0.003. Relative to placebo, E2 increased aBMD at the lumbar spine, MAD 0.02 g/cm2 (95% CI: 0.01 to 0.03), P = 0.01, and ultra-distal radius, MAD 0.01 g/cm2 (95% CI: 0.00 to 0.02), P = 0.01, and reduced serum bone remodelling markers. Conclusion: Relative to placebo, E2 treatment increases some measures of bone density and bone strength in men and reduces bone remodelling, effects that occur in the absence of endogenous T.

Effects of low-dose oral micronised progesterone on sleep, psychological distress, and breast development in transgender individuals undergoing feminising hormone therapy: a prospective controlled study.

Objective: The role of micronised progesterone in hormone regimens for transgender individuals undergoing feminising hormone therapy remains uncertain. We aimed to determine the effect of oral micronised progesterone on sleep quality, psychological distress, and breast development in transgender individuals undergoing feminising hormone therapy. Design: Prospective case-control study. Twenty-three transgender individuals on stable oestradiol treatment newly commencing 100 mg oral progesterone (n = 23) and controls continuing standard care (n = 19) were assessed over 3 months. Methods: Pittsburgh Sleep Quality Index (PSQI), Kessler psychological distress scale (K10), and Tanner stage to assess breast development were assessed at 0 and 3 months. Non-parametric analysis of covariance was used to compare differences between groups. Results: Compared with controls over 3 months, there was no difference in PSQI (P = 0.35), K10 (P = 0.64), or Tanner stage (P = 0.42). There was no significant difference in the proportion of individuals with clinically significant improvement in PSQI (25% vs 22%, P = 0.84). One individual had a significant deterioration in psychological distress that improved following the cessation of progesterone. Conclusions: Low-dose progesterone was not associated with changes in sleep quality, psychological distress, or breast development over 3 months follow-up, though there was significant inter-individual variability. Larger, placebo-controlled trials are required to further evaluate different doses of progesterone in feminising hormone therapy regimens.

Clinical features and prevalence of Klinefelter syndrome in transgender individuals: A systematic review.

OBJECTIVE: Previous studies have suggested a higher prevalence of Klinefelter syndrome amongst transgender individuals. We undertook a systematic review to determine the prevalence of Klinefelter syndrome amongst transgender individuals presumed male at birth and summarize the clinical features and potential treatment implications for individuals with Klinefelter syndrome commencing gender-affirming hormone therapy. DESIGN: Using preferred reporting items for systematic review and meta-analysis guidelines, we searched EMBASE, MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL) up to 31 December 2021. All studies reporting on the prevalence or clinical features of transgender individuals with Klinefelter syndrome were included. This study is registered with the International Prospective Register of Systematic Reviews, number CRD42021227916. RESULTS: Our search strategy retrieved 11 cohort studies comprising 1376 transgender individuals. In all, 14 of 1376 (1.02%) individuals were diagnosed with Klinefelter syndrome. Based on the seven studies in which karyotype was undertaken in all individuals, the prevalence is 9/1013 (0.88%; 95% CI, 0.41%-1.68%). Case reports highlight unique treatment considerations in this population, including azoospermia, venous thromboembolism, and monitoring of breast cancer and bone health. CONCLUSIONS: Compared to the general population, observational studies document a higher prevalence of Klinefelter syndrome amongst transgender individuals, though underdiagnosis in the general population limits conclusions. Routine karyotype in transgender people initiating gender-affirming hormone therapy is not supported unless clinical features of Klinefelter syndrome, such as small testicular volume, or hypergonadotropic hypogonadism are present. Transgender individuals with Klinefelter syndrome need to manage a unique risk profile if they desire feminizing gender-affirming hormone therapy.

Prescription Patterns and Testosterone Concentrations Achieved With AndroForte 5% Testosterone Cream in Transgender and Gender Diverse Individuals.

BACKGROUND: Masculinizing hormone therapy with testosterone is used to align an individual's physical characteristics with their gender identity in trans and gender diverse individuals. Standard testosterone doses and formulations recommended for hypogonadal cisgender men are typically administered. 100 mg AndroForte 5% testosterone cream is the recommended starting dose in hypogonadal cisgender men but there are no data evaluating the use of AndroForte 5% testosterone cream in gender-affirming hormone therapy regimens. AIM: To assess the prescription patterns and serum total testosterone concentrations achieved with AndroForte 5% testosterone cream in trans and gender diverse individuals. METHODS: A retrospective analysis was undertaken of trans and gender diverse individuals at a primary and secondary care clinic in Melbourne, Australia. Seventy-two individuals treated with AndroForte 5% testosterone cream to the torso were included. OUTCOMES: Testosterone dose and serum total testosterone concentration. RESULTS: Median age was 26 years (IQR 22-30) and median duration of testosterone therapy was 14 months (7-24). Fifty (69%) individuals had a non-binary gender identity. Initial median testosterone dose was 50 mg (50-100) daily. Thirty-eight (53%) commenced doses <100 mg daily, the recommended starting dose for hypogonadal cisgender men. Median total testosterone concentration achieved from 186 individual laboratory results was 11.9 nmol/L (8.1-16.4). Polycythemia was documented in 5 (7%) individuals. CLINICAL IMPLICATIONS: AndroForte 5% testosterone cream can be used in individuals with a binary and/or non-binary gender identity seeking masculinization. It can be commenced at a lower dose than that administered to hypogonadal cisgender men for individuals seeking slow masculinization goals. STRENGTHS & LIMITATIONS: Limitations include the retrospective study design, lack of clinical end points and lack of standardization of timing of laboratory tests in relation to the last dose. This is the first study to evaluate AndroForte 5% testosterone cream in trans and gender diverse individuals and provides insights into prescription patterns in individuals with a non-binary gender identity. CONCLUSION: AndroForte 5% testosterone cream represents an alternative formulation of testosterone administration for trans and gender diverse individuals seeking masculinization. Nolan BJ, Zwickl S, Locke P, et al. Prescription Patterns and Testosterone Concentrations Achieved With AndroForte 5% Testosterone Cream in Transgender and Gender Diverse Individuals. J Sex Med 2022;19:1049-1054.

Testosterone concentrations and prescription patterns of 1% testosterone gel in transgender and gender diverse individuals.

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.

Effect of estradiol on cognition in men undergoing androgen deprivation therapy: A randomized placebo-controlled trial.

OBJECTIVE: Roles for estradiol in modulating cognition in men remain uncertain. We assessed the isolated effects of estradiol on cognition in men in the absence of testosterone. DESIGN: Randomized trial of transdermal estradiol 0.9 mg daily, or matched placebo, for 6 months, hypothesizing that estradiol would improve verbal learning, verbal memory, and spatial problem solving over time. PATIENTS: Men receiving androgen deprivation therapy (ADT) for prostate cancer. MEASUREMENTS: Cognition was assessed by a tablet-based cognitive battery (Cogstate) at baseline, Month 1, Month 3, and Month 6. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression Scale. RESULTS: Seventy-eight participants were randomized. Baseline mean scores were 21.0 (standard deviation [SD] 4.1) for the International Shopping List test (ISL), assessing verbal learning and memory (higher scores better), and 60.4 (SD 19.5) for the Groton Maze Learning test (GML), assessing spatial problem solving (lower scores better). There was no significant difference in performance over time for the estradiol group versus the placebo group for the ISL, mean adjusted difference (MAD) 0.7 (95% confidence interval [CI] -1.2 to 2.5), p = .36, or the GML, MAD -3.2 (95% CI -12.0 to 5.6), p = 0.53. There was no significant difference between groups over time in performance in any other cognitive domain, or on depression or anxiety scores. CONCLUSIONS: We found no major effects of estradiol on cognition in men with castrate testosterone concentrations. Although the cognitive effects of ADT are debated, this study suggests that any such effects are unlikely to be prevented by the administration of estradiol.