Progesterone (Bioidentical / Prometrium) — Reproduction
Bioidentical progesterone FDA-approved for luteal support and endometrial protection. Critical component of hormone replacement therapy in women.
Overview
Micronized progesterone (Prometrium) is the bioidentical form of the hormone progesterone, structurally identical to the progesterone produced by the corpus luteum. FDA-approved for secondary amenorrhea and for prevention of endometrial hyperplasia in postmenopausal women receiving estrogen, bioidentical progesterone has become a cornerstone of modern hormone replacement therapy (HRT). Unlike synthetic progestins (medroxyprogesterone acetate/Provera, norethindrone), bioidentical progesterone has a more favorable cardiovascular and breast cancer risk profile. The PEPI trial and observational data suggest that micronized progesterone does not negate estrogen's beneficial effects on lipids (unlike MPA) and may have a lower breast cancer risk than synthetic progestins. Progesterone also has neurosteroid properties — it is metabolized to allopregnanolone, a potent positive allosteric modulator of GABA-A receptors, producing calming, anxiolytic, and sleep-promoting effects. Many women report improved sleep quality on evening oral progesterone. Routes include oral (micronized capsules), vaginal (suppositories, gels — Crinone, Endometrin), and topical (cream). Oral progesterone undergoes extensive first-pass hepatic metabolism producing high allopregnanolone levels (beneficial for sleep) but lower systemic progesterone levels; vaginal administration provides higher local endometrial concentrations with less sedation.
Indications
- FDA-approved: Secondary amenorrhea
- FDA-approved: Prevention of endometrial hyperplasia in postmenopausal women on estrogen
- Off-label: Luteal phase support in fertility treatments (IVF, IUI)
- Off-label: Hormone replacement therapy (menopause)
- Off-label: Premenstrual syndrome (PMS) and PMDD
- Off-label: Sleep support (via allopregnanolone conversion)
Mechanism of Action
Binds nuclear progesterone receptors (PR-A and PR-B), modulating gene transcription in endometrium, breast, brain, and other target tissues
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Micronized Progesterone (Prometrium) | 200 mg | Once daily at bedtime | Standard dose for endometrial protection with estrogen |
| Micronized Progesterone | 200 mg | Days 12-25 of cycle | Cyclic dosing for amenorrhea |
| Progesterone (Endometrin) | 100 mg | 2-3 times daily | Luteal support in IVF |
| Progesterone gel (Crinone 8%) | 90 mg | Once daily | Luteal support and ART |
Evidence Grade
GRADE B
Safety & Contraindications
- Drowsiness and sedation (oral route — due to allopregnanolone; take at bedtime)
- Dizziness, headache, breast tenderness
- Bloating and mood changes in some women
- Allergy: Prometrium capsules contain peanut oil — contraindicated in peanut allergy
- Do not use in known or suspected breast cancer
- Lower VTE risk than synthetic progestins (but not zero risk)
- Oral route has significant first-pass metabolism