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Context Medroxyprogesterone acetate (MPA) is a widely used progestin in feminizing hormone therapy. However, the side effects and hormonal changes elicited by this drug have never been investigated in the transgender population. Objective We evaluated the incidence of self-reported effects among transwomen using MPA and this drug’s impact on hormonal and metabolic parameters. Design, Setting, and Participants We retrospectively collected data from 290 follow-up visits (FUVs) of transwomen treated at Rhode Island Hospital from January 2011 to July 2018 (mean duration of therapy 3.4 ± 1.7 years). FUVs followed regimens of estradiol (E) and spironolactone, with MPA (n = 102) or without MPA (n = 188). Main Outcome Measures We assessed the incidence of self-reported effects after MPA treatment. We also compared blood levels of E, testosterone, and various laboratory parameters between MPA and non-MPA groups. Results Mean weighted E level was 211 ± 57 pg/mL after MPA treatment and 210 ± 31 pg/mL otherwise; this difference was nonsignificant [t(274) = 0.143, P = 0.886]. Mean weighted testosterone level was 79 ± 18 ng/dL after MPA treatment and 215 ± 29 ng/dL otherwise; testosterone levels were significantly lower in the MPA group [t(122) = 32.4, P &lt; 0.001]. There were minimal changes in other laboratory parameters. Of 39 patients receiving MPA, 26 reported improved breast development and 11 reported decreased facial hair. Five patients experienced mood swings on MPA. Conclusions In our cohort of transwomen, we found minimal side effects, unchanged E levels, and a decline in testosterone associated with MPA, outcomes consistent with feminization. Prospective studies are needed to confirm our findings.

Medroxyprogesterone Acetate in Gender-Affirming Therapy for Transwomen: Results From a Retrospective Study