Endocrine Abstracts

Introduction: Transgender women on gender-affirming hormone therapy (GAHT) with estrogens and anti-androgens have low serum androgen levels. These low levels may be associated with clinical symptoms such as depressed mood, reduced sexual desire and tiredness. Whether androgen levels change over the course of anti-androgen use and after gonadectomy, in a context of unchanged estrogen treatment, remains to be elucidated.

Methods: This study is part of the European Network for the Investigation of Gender Incongruence (ENIGI) and aimed to describe androgen profiles in transgender women in the years after initiation of GAHT and after gonadectomy. Transgender women who initiated estrogens and cyproterone acetate (CPA) had regular follow-up at the Ghent University Hospital and the Amsterdam University Medical Center, (Location VUmc) at baseline, three months, twelve months, after two to four years or after gonadectomy. Levels of total testosterone (TT) and androstenedione (A4) were determined using liquid-chromatography tandem mass spectrometry (LC-MS/MS). Sex hormone binding globulin (SHBG) concentrations were obtained using immunoassay. Free testosterone (FT) was calculated according to Vermeulen. In Ghent, dehydroepiandrosterone (DHEA) and dehydroepiandrosteronesulfate (DHEAS) were additionally measured using LC-MS/MS and immunoassay respectively.

Results: In total, 309 transgender women were included. At three months of GAHT, mean TT and FT decreased by 18.4 nmol/L [95% CI -19.24, -17.63] and 0.4 nmol/L [95% CI -0.41, -0.38], respectively compared to baseline and remained stable thereafter. SHBG increased upon initiation of GAHT (mean Δ=19.3 nmol/L [95% CI 13.32, 25.30]) and continued to increase in the first year (mean Δ=6.8 nmol/L [95% CI 2.54, 11.07]), remaining stable afterwards. DHEAS and DHEA decreased by 1.8 umol/l [95% CI -2.17, -1.42] and 6.52 nmol/L [95% CI -9.06, -3.97] respectively after one year of GAHT and did not change afterwards. A4 had decreased by 1.2 nmol/L [95% CI -1.37, -1.00] after three month and remained stable afterwards. No differences in TT, FT, DHEAS, DHEA, A4 between groups were observed between women on anti-androgens and after gonadectomy.

Conclusion: In the first year after initiation of GAHT with estrogen and CPA, levels of TT, FT, DHEAS, DHEA and A4 decrease while remaining stable thereafter. Androgen levels did not change further after gonadectomy. Clinical correlates remain to be elucidated.