NCT06807580

Progesterone in Gender Affirming Hormone Therapy Study

Effects of Oral Progesterone in Transgender Women on Breast Development, Sleep Quality, Psychological Distress, and Cardiovascular Risk

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Emory University · Academic / Other
• Sex: Male
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

Summary

This study aims to study the effects of Oral Progesterone in Transgender Women. The primary goal is to study the effect of progesterone on psychological distress and secondarily on sleep quality, breast size, quality of life and gender congruence and cardiovascular risk.

Detailed description

The transgender population in the U.S. has grown significantly, highlighting a lack of comprehensive research on the safety and efficacy of gender-affirming hormone therapy (GAHT). For transgender females, GAHT typically includes estrogen and an anti-androgen. Recently, there has been growing interest in adding progesterone, based on anecdotal reports of improved breast development and quality of life. However, progesterone's role in transgender women remains unclear. Studies have linked progesterone (mainly cyproterone acetate) to increased risks of meningiomas, elevated prolactin levels, decreased testosterone, reduced HDL levels, and higher venous thromboembolism (VTE) risk. Cyproterone acetate, often studied in these contexts, is not FDA-approved in the U.S. due to hepatotoxicity, and its use in GAHT is rare. Limited research exists on micronized progesterone, the form most commonly prescribed. A recent study on low-dose micronized progesterone found no significant effects on sleep quality, psychological distress, or breast development. To address research gaps, a new study aims to evaluate higher-dose micronized progesterone's impact on cardiovascular risk, sleep quality, breast development, and psychological distress over a longer period. The hypothesis suggests neutral effects on breast development, sleep, and quality of life, with potential negative to neutral cardiovascular effects. Given the lack of recommendations for or against progesterone in GAHT, further research is critically needed.

Conditions

• Transgender Women

Interventions

Type	Name	Description
DRUG	Placebo	The placebo will be nearly identical in size, color, and shape to micronized progesterone
DRUG	Progesterone	Oral micronized progesterone 200 mg

Timeline

• Start date: 2025-05-12
• Primary completion: 2027-02-01
• Completion: 2027-02-01
• First posted: 2025-02-04
• Last updated: 2025-12-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study