What Is Progesterone?
Bioidentical Micronized Progesterone · Last reviewed by the OPTML clinical team on April 29, 2026
Progesterone is the principal hormone of the luteal phase of the menstrual cycle, produced by the corpus luteum after ovulation. Micronized progesterone (Prometrium, or compounded equivalent) is bioidentical, structurally identical to endogenous ovarian progesterone, and is the form used in modern HRT. It is distinct from synthetic progestins like medroxyprogesterone acetate (Provera, used in the original WHI trial), which are not bioidentical and have a different side-effect and risk profile.
Physiology
Progesterone is produced primarily by the corpus luteum following ovulation, with smaller contributions from the adrenal cortex and (during pregnancy) the placenta. Levels rise sharply in the luteal phase (typically 5-25 ng/mL) and fall to baseline if pregnancy does not occur. Progesterone declines progressively during perimenopause as ovulation becomes irregular, and reaches very low post-menopausal levels.
Progesterone acts on progesterone receptors (PR-A, PR-B) found in the uterus, breast, brain, and other tissues. Centrally, its allopregnanolone metabolite is a positive allosteric modulator of GABAA receptors, explaining the well-documented sedative and anxiolytic effects of oral micronized progesterone.
Forms
| Form | Route | Notes |
|---|---|---|
| Micronized progesterone (Prometrium) | Oral capsule (nightly) | Bioidentical; sedating effect; first-pass metabolism |
| Compounded micronized progesterone | Oral or vaginal | Bioidentical; allows custom dosing |
| Vaginal progesterone | Vaginal gel or insert | Higher uterine concentrations; less sedation |
| Medroxyprogesterone acetate (Provera) | Oral | Synthetic progestin; not bioidentical |
| Norethindrone, levonorgestrel, drospirenone | Oral | Synthetic progestins used in birth control / some HRT |
Indications in HRT
- Endometrial protection in women with a uterus receiving estradiol, without progesterone, unopposed estrogen drives endometrial hyperplasia and increases the risk of endometrial cancer.
- Sleep support, oral micronized progesterone taken at bedtime has well-documented sedative effects via GABAA modulation.
- Mood and anxiety, clinical experience and some trial data suggest benefit, particularly in perimenopause when progesterone fluctuations contribute to mood instability.
- Perimenopausal cycle support, used cyclically (e.g., 12-14 days/month) in women still cycling, or continuously in postmenopause.
Bioidentical Progesterone vs. Synthetic Progestins
The original 2002 WHI trial used medroxyprogesterone acetate (Provera), a synthetic progestin, not bioidentical micronized progesterone. The E3N observational cohort (Fournier et al., Breast Cancer Res Treat, 2008) found that the breast cancer risk associated with HRT was substantially lower when bioidentical micronized progesterone was used compared to synthetic progestins. This distinction is important: most modern HRT prescribing favors bioidentical preparations, and risk-benefit conversations should reference data on the specific formulation rather than treating "progesterone" and "progestins" as interchangeable.
Side Effects and Risks
- Drowsiness or fatigue (often desired at bedtime).
- Dizziness, headache, breast tenderness.
- Mood changes (variable, can improve mood in some, worsen in others).
- Bloating.
- Vaginal preparations may cause local irritation.
Typical Lab Monitoring
- Serum progesterone (to confirm absorption with oral micronized).
- Estradiol (E2), paired with progesterone in HRT.
- FSH, LH (for menopausal-status workup).
- Endometrial assessment (ultrasound or biopsy) if breakthrough bleeding occurs.
Considering progesterone?
$79/mo · Bioidentical micronized · Physician-supervised · Pairs with estradiol.
Talk to a provider →References
- Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat. 2008;107(1):103-111.
- Schumacher M, Mattern C, Ghoumari A, et al. Revisiting the roles of progesterone and allopregnanolone in the nervous system. Prog Neurobiol. 2014;113:6-39.
- The 2022 Hormone Therapy Position Statement of The North American Menopause Society. Menopause. 2022;29(7):767-794.
- Stuenkel CA, Davis SR, Gompel A, et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100(11):3975-4011.