How do spironolactone and cyproterone acetate compare for testosterone suppression in trans women?

Disclaimer: I am not a medical professional and this is not medical advice.

Trans women are often understandably curious about which HRT regimens, typically consisting of estrogen and an antiandrogen, are most effective in producing the desired levels of estrogen while suppressing testosterone. Regional differences exist in which antiandrogens are usually prescribed: the synthetic progestin cyproterone acetate (CPA) is widely used in Europe, while this medication is not approved in the United States and spironolactone is usually used instead. Although availability may differ by area, trans women and their providers still deserve quality evidence on which treatments work best for this purpose.

A recent study seeks to address this question by comparing testosterone levels in trans women using CPA and estradiol, spironolactone and estradiol, or estradiol alone. Angus et al. (2019) examined the hormone levels of 80 trans women patients from two clinics in Melbourne, Australia, all of whom had been on HRT for more than 6 months with a median duration of 1.5 years. 88.3% of these women were taking estradiol in oral form, while the rest used transdermal (patch) estrogen. The median doses of these medications were 6mg oral estradiol, 50mg CPA, and 100mg spironolactone. The authors found that the group taking cyproterone acetate achieved significantly lower testosterone levels than the group taking spironolactone:

Additionally, the vast majority of patients taking CPA achieved testosterone levels in the female reference range of less than 2.0 nmol/L, while this was only achieved by a minority of those using spironolactone:

90% of the cyproterone group and 40% of the spironolactone group had total testosterone concentrations <2nmol/L.

Blood levels of estradiol were not significantly different between the three groups, nor were blood pressure or liver function. The authors note that their finding of CPA’s superior efficacy over spironolactone is consistent with the findings of Liang et al. (2018), in which only about a quarter of trans women taking spironolactone and estrogen were able to achieve testosterone suppression to female levels. These results suggest that despite its widespread use in feminizing HRT regimens, spironolactone may not be the most effective medication for suppression of testosterone in trans women. ■