Progesterone Is Important for Transgender Women’s Therapy—Applying Evidence for the Benefits of Progesterone in Ciswomen

Abstract

Abstract Background Although the 2017 Endocrine Society Guidelines for gender dysphoria stipulated that cross-sex hormone therapy (CHT) achieve gonadal steroid levels equivalent to those of a cisperson of the chosen sex, for transgender women (male-to-female gender dysphoria), current gonadal therapy is usually estradiol. Accumulated evidence indicates that normally ovulatory menstrual cycles are necessary for ciswomen’s current fertility, as well as for later-life bone and cardiovascular health and the prevention of breast and endometrial cancers. Evidence Acquisition Extensive past clinical experience with transgender women’s CHT using estradiol/estrogen combined with progesterone/medroxyprogesterone and pioneering the addition of spironolactone. Comprehensive progesterone physiology research plus a brief review of transgender women’s literature to assess current therapy and clinical outcomes, including morbidity and mortality. Purpose To emphasize that both ovarian hormones, progesterone as well as estradiol, are theoretically and clinically important for optimal transgender women’s CHT. Evidence Synthesis It is important to add progesterone to estradiol and an antiandrogen in transgender women’s CHT. Progesterone may add the following: (i) more rapid feminization, (ii) decreased endogenous testosterone production, (iii) optimal breast maturation to Tanner stages 4/5, (iv) increased bone formation, (v) improved sleep and vasomotor symptom control, and (vi) cardiovascular health benefits. Conclusions Evidence has accrued that normal progesterone (and ovulation), as well as physiological estradiol levels, is necessary during ciswomen’s premenopausal menstrual cycles for current fertility and long-term health; transgender women deserve progesterone therapy and similar potential physiological benefits.