Progesterone in Gender Affirming Hormone Therapy Study

Last updated: May 13, 2025
Sponsor: Emory University
Overall Status: Active - Recruiting

Phase

2

Condition

N/A

Treatment

Progesterone

Placebo

Clinical Study ID

NCT06807580
STUDY00006161
  • Ages 18-60
  • Male
  • Accepts Healthy Volunteers

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Participants will be transgender women, who have been on gender-affirming hormonetherapy for at least 6 months before the start of the study.

Exclusion

Exclusion Criteria:

  • Peanut allergy

  • Liver disease (liver enzyme elevations and/or evidence of acute or chronichepatitis). In our lab, the upper limit of normal for aspartate aminotransferase (AST) is 39, and the upper limit of normal for alanine aminotransferase (ALT) is 52.

  • Stage 4/5 chronic kidney disease

  • Congestive heart failure

  • Medical disease or medication use associated with gynecomastia (i.e tumor,hyperthyroidism, chronic kidney disease, cirrhosis, ACE inhibitors, statins,haloperidol, tricyclic antidepressants, atypical antipsychotics)

  • Pre-existing cardiovascular disease

  • Prior or current history of thromboembolism, known clotting disorders, current orrecent anti-thrombotic therapy for venous thromboembolism.

  • History of breast cancer

  • Prior progesterone use

  • Uncontrolled depression and/or suicidal ideation

  • Current hypothyroidism (even if controlled with treatment) Progesterone in GenderAffirming Hormone Therapy 9 Version #4, 10/30/24

  • Current or recent (in the past 6 months) cannabis use

  • Previously identified BRCA 1 or 2 gene mutation or other familial breast cancer.

  • Abnormal mammogram (if indicated - for patients above the age of 50 and on estrogenfor 5 or more years OR positive family history of breast cancer) with results ofBIRADS 3 or higher. Subjects with a BIRADS 0 mammogram must have undergoneadditional imaging demonstrating BIRADS 1 or 2 prior to enrollment.

  • Have had or are planning to undergo breast enhancement or gender affirming topsurgery in the next 6 months

  • Uncontrolled hypertension, defined as systolic blood pressure ≥ 140 mm Hg and/ordiastolic blood pressure ≥ 90 mmHg.

  • Triglycerides ≥ 500 mg/dL.

  • In our lab, the upper limit of normal for aspartate aminotransferase (AST) is 39,and the upper limit of normal for alanine aminotransferase (ALT) is 52.

  • Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2.

  • Estradiol levels outside the stable range (100-200 pg/mL)

  • Heavy smoking, defined as 25+ cigarettes per day

  • Non-English speaking or those with limited English proficiency

Study Design

Total Participants: 40
Treatment Group(s): 2
Primary Treatment: Progesterone
Phase: 2
Study Start date:
May 12, 2025
Estimated Completion Date:
February 28, 2027

Study 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.

Connect with a study center

  • Emory Transgender Clinic

    Atlanta, Georgia 30308
    United States

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.