Differential Endocrine and Metabolic Effects of Testosterone Suppressive Agents in Transgender Women.

Suppression of testosterone secretion and/or action in transgender women using cyproterone acetate (CPA), spironolactone, or gonadotropin-releasing hormone analogues (GA) is achieved through various mechanisms. Our objective was to characterize possible differential effects of these compounds on metabolic and endocrine variables. We conducted a historic cohort study of transgender patients treated in a tertiary referral center. A longitudinal analysis of treatment naïve patients and a cross-sectional analysis of the whole cohort at the last visit was carried out. Among 126 transgender women (75 treatment-naïve), CPA was the predominant androgen suppressive therapy (70%), followed by spironolactone (17.6%), and GA (10.2%). Among those who were treatment-naïve, the increase in serum prolactin levels over baseline was greater at 3 months following CPA initiation (mean change 397 ± 335 mIU/L) than following spironolactone (20.1 ± 87 mIU/L) or GA initiation (64.6 ± 268 mIU/L; P = .0002). Prolactin levels remained higher in the CPA-treated group throughout follow-up, irrespective of estradiol levels, which were similar between the groups. A worse metabolic profile was associated with treatment with CPA than with spironolactone or GA. In the CPA compared to the spironolactone and GA groups, high-density lipoprotein-cholesterol levels were lower (47.1 ± 10.4, 54.4 ± 12.2, and 60.3 ± 13, respectively; P = .0076), while body mass index levels (24.3 ± 5, 21.7 ± 2.3, and 20.7±3.1 kg/m Treatment of transgender women with CPA was associated with hyperprolactinemia and a worse cardiovascular risk profile than treatment with spironolactone or GA. BMI = body mass index; CPA = cyproterone acetate; E2 = estradiol; FSH = follicle-stimulating hormone; GA = gonadotropin-releasing hormone analogues; LH = luteinizing hormone.

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