Progestogen Use in Gender-Affirming Hormone Therapy: A Systematic Review

Objective: Transgender women take gender-affirming hormone therapy (GAHT) to affirm their gender identity and improve quality of life and well-being. Usually, GAHT in transgender women consists of estrogen plus a testosterone-lowering medication. The use of progestogens in GAHT for transgender women has been a controversial topic due to lack of evidence for benefit and potential for increased harm.

Methods: A systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using 4 databases (PubMed/MEDLINE, Ovid, and Cochrane). Manuscripts were reviewed from January 2000 to March 2022 to identify effects of progestogens in transgender women over the age of 16 years on breast development, cardiovascular disease, bone density, quality of life, and stroke incidence.

Results: Ten articles were deemed eligible based on specific inclusion and exclusion criteria. Studies analyzing users of cyproterone acetate were also included if there was a comparator group. No relevant studies were found assessing stroke incidence in the transgender population using a progestogen compound.

Conclusion: Overall, findings were significant for a decreased high-density lipoprotein level and increased thromboembolism risk in transgender women using progestogens. No conclusive evidence was found regarding improved quality of life or breast development. Further research needs to be conducted assessing the effects of progestogens in transgender women.