Effects of progesterone on gender affirmation outcomes as part of feminizing hormone therapy

The use of progesterone as a component of feminizing gender-affirming hormone therapy (GAHT) is controversial; however, use in transgender women continues owing to anecdotal reports of benefit.

This study aimed to provide quantifiable outcomes data regarding the use of progesterone in transgender women by comparing groups from this population who use feminizing GAHT with and without progesterone.

This retrospective cohort study captured data from transgender female patients seen at the Summa PRIDE Clinic between September 2019 and December 2021. Data were extracted from chart documentation for patients who were prescribed feminizing GAHT, with and without progesterone, for at least 6 months during the study window. Outcomes included satisfaction with breast development, satisfaction with libido, mental health trends, and weight change at 0, 6, and 9 months from initiation of GAHT.

A total of 88 charts were reviewed (59 in the standard group, 29 in the progesterone group). The progesterone group had statistically significant improvements in satisfaction with breast development at 6 months (53.8% vs. 19.6%; P = 0.004) and 9 months (71.4% vs. 20.8%; P = 0.003). The progesterone group had more patients at goal testosterone levels < 55 ng/dL at 6 months (47.6% vs. 33%) and 9 months (50% vs. 24.4%), but these were not statistically different. The progesterone group was also more likely to show improved provider-documented mental health at 6 months (70.6% vs. 28.2%; P = 0.009); however, the difference was not statistically significant at 9 months. There were no differences between groups for weight change and patient satisfaction with libido.

The addition of progesterone to standard feminizing GAHT was associated with greater satisfaction with breast development and improved patient mental health within 6 months compared with standard GAHT regimens alone in this patient population. Progesterone's impact on libido, testosterone suppression, and weight were nonsignificant.