Detailed definition
Progesterone is a C21 steroid hormone synthesized from pregnenolone in the corpus luteum, adrenal cortex, and during pregnancy in the placenta. It binds the progesterone receptor (PR), which exists in two main isoforms (PR-A and PR-B), and acts as a key counterweight to estrogen in the endometrium. After ovulation, rising progesterone transforms the proliferative endometrium into a secretory state that can support implantation; without conception, progesterone falls and menstruation occurs. Outside the uterus, progesterone has effects on the brain (its neurosteroid metabolite allopregnanolone is a positive allosteric modulator of GABA-A receptors), respiratory drive, smooth muscle tone, and breast tissue. The bioidentical molecule used in modern HRT is "micronized progesterone," in which the active ingredient is reduced to small particles to improve oral absorption. The FDA-approved oral product is Prometrium; a vaginal formulation is also available. Synthetic progesterone-like molecules (medroxyprogesterone acetate, norethindrone, drospirenone, levonorgestrel) are called progestins and are not bioidentical.
Why it matters in menopause
For patients with a uterus, unopposed estrogen substantially increases the risk of endometrial hyperplasia and endometrial cancer, so combination HRT (estrogen plus progesterone or a progestin) is the standard of care. Bioidentical micronized progesterone is preferred over synthetic progestins by many menopause clinicians because of evidence suggesting a more favorable breast cancer profile and because of the sleep-promoting effects mediated by allopregnanolone when taken at bedtime.