Early Access to Testosterone Therapy in Transgender and Gender-Diverse Adults Seeking Masculinization

Abstract

ImportanceTestosterone 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.ObjectiveTo 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 ParticipantsA 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.InterventionsImmediate 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 MeasuresThe 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.ResultsSixty-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 RelevanceIn 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 RegistrationANZCTR Identifier: ACTRN1262100016864

Implications of hormonal carcinogenesis for transgender and gender-diverse people undergoing gender-affirming hormone therapy: an up-to-date review

“…GAHT frequently serves as an essential, life-saving treatment for TGD individuals. 92 Therefore, in the event of a demonstrated direct correlation between GAHT and increased cancer risk or an interaction between GAHT and cancer care, essential shared decision-making discussions must take place between oncology practitioners and patients, even though such instances are rare in clinical practice. 93 On the other hand, dismissing any clinically relevant association between GAHT and cancer risk would put an end to the phenomenon, rooted in a transphobic society, where TGD individuals frequently perceive their cancer diagnoses as a consequence of their gender identity and hormonal therapy.…”

Limitations and Future Directions in Sex, Sexuality, and Gender Diverse Research in Neurology

“…An example relevant to SSGD individuals includes limited recognition of same-sex marriages, which may impede spousal insurance coverage and lead to adverse health outcomes, or discriminatory laws limiting genderaffirming care that lead to worse health outcomes among SSGD people. [83][84][85] For example, a recent study found a state's passing of anti-transgender rights bills was linked with increased Internet searches pertaining to suicide and depression. 86 There are many relevant social determinants affecting SSGD individuals, and our research should continue to include measurements of these determinants.…”

“…Examples include racial segregation, discriminatory employment, inequitable income and health insurance coverage, and many other factors. An example relevant to SSGD individuals includes limited recognition of same‐sex marriages, which may impede spousal insurance coverage and lead to adverse health outcomes, or discriminatory laws limiting gender‐affirming care that lead to worse health outcomes among SSGD people 83–85 . For example, a recent study found a state's passing of anti‐transgender rights bills was linked with increased Internet searches pertaining to suicide and depression 86 .…”