DIFFERENTIAL ENDOCRINE AND METABOLIC EFFECTS OF TESTOSTERONE SUPPRESSIVE AGENTS IN TRANSGENDER WOMEN

Objective: 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. Methods: We conducted a historic cohort study of transgender patients treated in a tertiary referral center. A longitudinal analysis of treatment naive patients and a cross-sectional analysis of the whole cohort at the last visit was carried out. Results: Among 126 transgender women (75 treatment-naive), CPA was the predominant androgen suppressive therapy (70%), followed by spironolactone (17.6%), and GA (10.2%). Among those who were treatment-naive, 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(2); P =.03), and systolic (117 +/- 12.1, 109 +/- 12.2, and 105 +/- 13.3 mm Hg; P =.01) and diastolic (74 +/- 9, 65.6 +/- 5.5, and 65.4 +/- 11 mm Hg; P =.0008) blood pressure levels were higher at the last visit. Conclusion: Treatment of transgender women with CPA was associated with hyperprolactinemia and a worse cardiovascular risk profile than treatment with spironolactone or GA.