Raya Geels1, Bente Dijkman1, Lidewij Boogers1, Noor Gieles1, Jason van Heesewijk1, Christel de Blok1, Jos Twisk2, Niels Liberton3, Martin den Heijer1, Koen Dreijerink1
(1) Endocrinology and Metabolism, Amsterdam UMC, Amsterdam, Nederland.
(2) Epidemiology and Data Science, Amsterdam UMC, Amsterdam, Nederland.
(3) Medical Technology, Amsterdam UMC, Amsterdam, Nederland.
Background
Breast development as a result of feminizing gender-affirming hormone therapy (fGAHT) is often limited. The addition of progesterone may increase breast volume, but thus far no prospective randomized trials have been conducted.
Methods
We conducted an open-label, randomized controlled trial in transgender individuals assigned male sex at birth, who had been using fGAHT for at least one year and had undergone vaginoplasty and/or orchiectomy. Participants were randomized to one of six study groups: baseline estradiol dosage (E, control), baseline estradiol plus 200 mg progesterone (EP), baseline estradiol plus 400 mg progesterone (EPP), double baseline estradiol dosage (EE), double baseline estradiol plus 200 mg progesterone (EEP), or double baseline estradiol plus 400 mg progesterone (EEPP). The primary outcome was percentage change in breast volume, measured by 3D imaging at baseline and after 3, 6, and 12 months. Secondary outcomes included safety and satisfaction.
Results
Ninety participants (median age 33 years, IQR 28-48) were randomized. Compared with group E, mean percentage breast volume increase was 13% (95% CI -7 to 33) in EP, 20% (95% CI 0 to 40) in EPP, 6% (95% CI -13 to 24) in EE, 37% (95% CI 18 to 57) in EEP, and 27% (95% CI 8 to 47) in EEPP. One-year progesterone use was safe but caused side effects such as tiredness (44%), breast tenderness (27%), and mood changes (22%). Satisfaction with breast growth improved in all intervention groups.
Conclusion
The addition of progesterone may increase breast volume in transgender individuals, especially when combined with increased estradiol dosage. Progesterone use was safe but caused side effects. These findings support a potential future role for progesterone in fGAHT and highlight the need for research on long-term outcomes.