Progesterone for Breast Development in Trans Women

Rationale: Trans women (male sex assigned at birth, female gender identity) receive hor-mone therapy in order to induce secondary female sex characteristics. Traditionally, this hormone therapy includes estradiol and anti-androgenic treatment. Research has demon-strated that breast development in trans women is often limited and as a result trans women may choose to undergo breast augmentation surgery. Progesterone is important for breast development in cis women (female sex assigned at birth, female gender identity) during pu-berty. A potential role for progesterone with regard to breast development in trans women has not been investigated in a controlled experimental set up.

Objective: To explore the effects on breast development of addition of progesterone to the treatment with estradiol in trans women after vaginoplasty or orchiectomy. Secondary objec-tives include safety and patient satisfaction, mood, and sleep.

Study design: This is a non-blinded, non-placebo, randomized controlled pilot trial using a factorial design.

Study population: Adult trans women who have undergone hormone treatment for at least one year, who underwent vaginoplasty or orchiectomy, and do not use cyproterone acetate are eligible for this study. People are excluded in case of mental health disabilities that pre-vent participation, insufficient knowledge of the Dutch language, increased thromboembolic risk or after breast augmentation or reduction surgery.

Intervention: Participants will be randomized into six groups of 15 subjects each (A-F). For 12 months, group A will continue to receive the baseline dose of estradiol (control group), group B will receive the baseline dose of estradiol and progesterone 200 mg daily, group C receive the baseline dose of estradiol and progesterone 400 mg daily, group D will receive twice the baseline dose of estradiol, group E will receive twice the baseline dose of estradiol and progesterone 200 mg daily and group F will receive twice the baseline dose of estradiol and progesterone 400 mg daily.

Main study parameters/endpoints: The main study parameters include change in breast size as determined by measurement of breast volume and determination of the bra cup size. Serum progesterone levels, patient satisfaction, mood changes, sleep quality, and adverse events are secondary endpoints.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participation in the study will include 4 visits to the clinic, at baseline (visit 1) and after 3, 6, and 12 months (visits 2,3,4). During visits 1-4, measurement of breast-chest circumference difference and volume measurement will be performed using breast 3D im-aging. Participants will be asked to fill out questionnaires at visits 1-4. At visits 1, 3 and 4, blood samples will be taken. During the study, participants will continue their regular visits to the gender clinic. We estimate that the risks associated with the investigational treatment will be limited. Increased doses of estradiol may lead to breast tenderness, headache or weight gain. The most common side effect of progesterone is headache. Uncommon and rare side effects include breast tenderness, drowsiness, nausea, diarrhea, constipation, jaundice, pruri-tus, and acne. Increased risks of breast cancer, thromboembolic events, coronary artery disease, and ischemic stroke have been reported for progesterone-like compounds, but not for progesterone itself, when used in combination with estradiol.

Exploratory. To explore the effects on breast development of addition of progesterone to the treatment with estradiol in trans women after vaginoplasty or orchiectomy. Secondary objectives include safety and patient satisfaction, mood, and sleep.

6 months, interim analysis; 12 months, final analysis

Addition of progesterone to the treatment with estradiol in trans women after vaginoplasty or orchiectomy