Metabolic effects of testosterone therapy in transgender and gender diverse individuals with polycystic ovary syndrome

BACKGROUND: Polycystic ovary syndrome (PCOS) affects 10% to 13% of individuals assigned female at birth (AFAB), although a greater prevalence is reported in transgender/gender diverse individuals (TGD) (23.8-38.8%). Testosterone therapy (TT) in TGD individuals is linked to worsening cardiovascular risk factors (CVRFs). Whether TT induces more adverse cardiometabolic changes in TGD with PCOS than TGD without PCOS remains uncertain. OBJECTIVE: To compare the effects of TT on CVRF in TGD with and without PCOS. METHODS: We retrospectively reviewed 373 records to identify 62 TGD with PCOS (withestablished guideline criteria) and 132 age-matched TGD without PCOS. Data included longitudinal anthropometric measurements, hormone and metabolic parameters, and CVRF before and after TT. Group comparison of PCOS vs without PCOS before and after TT was conducted via independent t-tests, Mann-Whitney-U, and Chi-square. RESULTS: At baseline, TGD with PCOS had significantly greater body mass index (BMI), obesity prevalence, and, after controlling for BMI, baseline metformin use. There were no significant differences between TGD with and without PCOS when comparing intra-participant changes after TT. Controlling for BMI, TGD with PCOS on TT exhibited significantly greater hyperlipidemia prevalence, alanine transaminase (ALT) levels, and bioavailable testosterone concentrations than TGD without PCOS on TT. CONCLUSION: Greater baseline cardiometabolic risk was largely BMI-related in TGD with PCOS compared to TGD without PCOS. Only hyperlipidemia and elevated ALT were more prevalent during TT after adjusting for BMI. These findings support cardiometabolic monitoring during TT in all TGD individuals without significant increased risk with PCOS history.