Study: Spironolactone with medroxyprogesterone acetate suppresses testosterone in trans women more effectively than spironolactone alone

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

While spironolactone is one of the most commonly used antiandrogens in feminizing hormone therapy, some trans women are still unable to achieve suppression of their testosterone levels into the desired female range with spironolactone. A recent clinical study examined the potentially beneficial effects on trans women’s testosterone levels from adding a medication whose use in feminizing HRT has been hotly debated: the synthetic progestin medroxyprogesterone acetate (MPA).

Jain, Kwan, & Forcier (2019) describe the clinical outcomes recorded at 290 follow-up visits with trans women receiving transition treatment at Rhode Island Hospital, comparing results from 188 visits with patients taking estradiol and spironolactone with 102 visits with those taking estradiol, spironolactone, and MPA. The study included 92 trans women in total, 39 of whom were taking MPA either orally or as a long-acting depot injection. Between the groups, their estradiol levels did not differ, with results from the non-MPA group averaging 210±31 pg/mL and results from the MPA group averaging 211±57 pg/mL.

However, a significant difference was found in their testosterone levels: while the non-MPA group had an average level of 215±29 ng/dL, the MPA group had an average level of 79±18 ng/dL.

Additionally, 67% of those taking MPA reported having better breast development, and 28% described a decrease in their facial hair after taking MPA. 13% of those on MPA experienced mood swings, and one woman stopped taking MPA for this reason, after which her mood swings resolved. No other adverse effects were reported among those on MPA:

Over the 7-year period in which data were collected, there were no incidents of venous thromboembolism (VTE), cardiovascular disease, prolactinoma, galactorrhea, cholelithiasis, breast cancer, or type II diabetes after initiation of MPA. There were no occurrences of hypotension or hyperkalemia that were clinically significant (i.e., necessitating intervention or adjusted regimen). … We found no differences between MPA and non-MPA groups in levels of blood glucose, BUN, creatinine, sodium, potassium, chloride, calcium, albumin, bilirubin, ALP, total protein, ALT, or AST.

Keep in mind that the present findings on achieving testosterone suppression with MPA are distinct from the question of whether progestogenic medications, including either bioidentical progesterone or synthetic progestins, should be included as a routine component of HRT for trans women or are necessary for more thorough physical feminization. That question somehow still remains underresearched after all these decades: UCSF Transgender Care cites anecdotal experiences of progestogens improving breast development, mood, and libido, and reports that they are likely not harmful. Dr. Richard Curtis unhelpfully suggests trans women should instead “just eat more pies” (having gained and lost 40 lbs, I can anecdotally report that this made little difference in breast size). A recent exchange between Prior (2019) and Iwamoto et al. (2019) in the Journal of Clinical Endocrinology & Metabolism succeeded only in revealing that WPATH has commissioned a systematic review of progesterone use before the next Standards of Care are released, which we can only hope will provide some actionable answers.

Instead, the present study seems to add to the accumulating evidence that spironolactone is among the less effective antiandrogens for trans women. Liang et al. (2018) found that among 98 trans women taking estradiol and spironolactone, only the highest quartile for testosterone suppression had testosterone levels in the typical cisgender female range, while Leinung, Feustel, & Joseph (2018) reported that spironolactone “did not aid testosterone suppression and seemed to impair achievement of goal serum 17-β estradiol levels.” Additionally, Angus et al. (2019) compared trans women taking spironolactone to those taking cyproterone acetate, a progestogenic antiandrogen that’s unavailable in the United States, and found that trans women on cyproterone acetate were far more likely to have testosterone levels in the female range. Given that trans women may struggle to achieve testosterone suppression using spironolactone, MPA may serve as another potentially useful option for effective feminization. ■