Progesterone Is Important for Transgender Women's Therapy-Applying Evidence for the Benefits of Progesterone in Ciswomen

J Clin Endocrinol Metab. 2019 Apr 1;104(4):1181-1186. doi: 10.1210/jc.2018-01777.

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.

MeSH terms

  • Administration, Oral
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination / methods
  • Estradiol / administration & dosage*
  • Estradiol / adverse effects
  • Estradiol / physiology
  • Evidence-Based Medicine / methods
  • Female
  • Gender Dysphoria / drug therapy*
  • Gender Dysphoria / physiopathology
  • Hormone Replacement Therapy / methods*
  • Humans
  • Male
  • Menstrual Cycle / drug effects
  • Menstrual Cycle / physiology
  • Ovulation / drug effects
  • Ovulation / physiology
  • Premenopause / drug effects
  • Premenopause / physiology
  • Progesterone / administration & dosage*
  • Progesterone / physiology
  • Pulmonary Embolism / chemically induced
  • Pulmonary Embolism / epidemiology
  • Transdermal Patch / adverse effects
  • Transgender Persons*
  • Venous Thromboembolism / chemically induced
  • Venous Thromboembolism / epidemiology

Substances

  • Progesterone
  • Estradiol