Differential Effects of Cyproterone Acetate vs Spironolactone on Serum High-Density Lipoprotein and Prolactin Concentrations in the Hormonal Treatment of Transgender Women

Abstract

Introduction Spironolactone and cyproterone acetate (CPA) are the two main antiandrogen medications used in feminizing hormone therapy in transgender women. Previous studies have suggested that these two agents might have opposite effects on high-density lipoprotein (HDL) level when used in this context, and limited data have suggested CPA increases prolactin more than spironolactone. Aim To compare the effects of spironolactone and CPA on HDL and prolactin serum concentrations in transgender women. Methods A retrospective chart review was conducted at three clinical sites in Toronto, Ontario, Canada. Patients were selected if they (i) identified as a transgender woman, (ii) had newly started spironolactone or CPA with estrogen or restarted spironolactone or CPA after a washout period of at least 6 months, and (iii) had not used other antiandrogens within the previous 6 months. Main Outcome Measures HDL and prolactin concentrations between the two treatment groups at baseline and at 12 months. Results Eighty-two patients were included in the spironolactone group and 31 patients were included in the CPA group. Baseline HDL and prolactin levels were not significantly different between the two groups. At 12 months, HDL increased by 0.10 mmol/L (SD = 0.24) in the spironolactone group but decreased by 0.07 mmol/L (SD = 0.21) in the CPA group (P = .002). The difference remained significant after adjusting for baseline HDL, use of lipid-lowering drugs, and age. The change in prolactin was +3.10 μg/L (SD = 5.70) in the spironolactone group and +11.8 μg/L (SD = 8.63) in the CPA group (P < 0.001). This difference also remained significant after adjusting for baseline prolactin level. Conclusion These data suggest that spironolactone use in transgender women increases HDL levels and that CPA has the opposite effect. CPA also is associated with a larger increase in prolactin. These factors should be considered when choosing between these two antiandrogen agents.

Transgender patients and the role of the coagulation clinician

“…Cyproterone acetate is not available in the United States or Japan. Subtle differences in spironolactone and CPA effects on lipids and prolactin levels may result in the endocrinologist's choosing one over the other for the individual patient . Progestin agents when used alone at higher doses than for contraception, such as for dysfunctional uterine bleeding, are also associated with increased VTE risk but are not frequently used in the transgender population.…”

Health considerations for transgender women and remaining unknowns: a narrative review

“…Defreyne and colleagues 195 revealed that CPA increased prolactin levels in TW but the levels decreased when TW discontinued CPA. Fung and colleagues 117 demonstrated higher prolactin levels in TW receiving CPA than those taking spironolactone. Given these newer data, we recommend checking prolactin only in those patients with signs or symptoms of hyperprolactinaemia before or after starting feminizing GAHT.…”

“…In contrast, other markers suggest a decreased risk compared with reference men and women as well as trans men [e.g. less insulin resistance, 34,39,113,115,118 decreasing/stable blood pressure, 116,118,119 decreasing LDL 34,115,117,118 and smaller waist-to-hip ratio (WHR) 122 ]. Some conflicting results can be explained by the older mean age of TW compared with trans men, geographical location, GAHT regimen, minority stress (e.g.…”

The effect of transgender hormonal treatment on high density lipoprotein cholesterol efflux capacity

“…The addition of the anti-androgen cyproterone acetate (or other agents) to the HT of trans women makes it difficult to isolate effects driven by estrogen, consequent to testosterone suppression or to specific side-effects of the anti-androgen. Indeed, HDL-C concentrations are reduced in trans women treated with cyproterone acetate, whereas they increase with other anti-androgens (e.g., spironolactone or a GnRH-analog) 46,47 . In our study the decreased HDL-CEC in trans women is likely to be attributed to the use of cyproterone acetate; which, aside from the anti-androgen activity also exert progestogen-like effects.…”