Progesterone (Micronized Progesterone)

Micronized progesterone is the bioidentical form of the hormone the ovaries produce during the second half of the menstrual cycle (the luteal phase). Molecular weight: 314.46 Da. CAS number: 57-83-0. 'Micronized' refers to the manufacturing process that reduces particle size, improving absorption compared to standard progesterone, which is poorly absorbed orally.

The primary clinical role of progesterone in HRT is endometrial protection. Estradiol alone stimulates the uterine lining to grow. Without progesterone to periodically counteract this growth, the lining can develop hyperplasia, which is a precursor to endometrial cancer. Every woman with an intact uterus who takes estradiol needs a progestogen.

But not all progestogens are the same. This is where the E3N study changed everything. Published in Breast Cancer Research and Treatment in 2008 (PMID: 17896176), it followed 80,377 postmenopausal French women for 8 years. Women taking estradiol with micronized progesterone had no increased breast cancer risk. Women taking estradiol with synthetic progestins (like medroxyprogesterone acetate, the progestin used in the WHI) had significantly increased risk. This single dataset shifted modern HRT practice decisively toward bioidentical progesterone.

The PEPI trial (JAMA, 1995, PMID: 7823386) added another important finding: micronized progesterone preserved estrogen's beneficial effects on HDL cholesterol better than medroxyprogesterone acetate. This matters for cardiovascular risk.

Beyond endometrial protection, progesterone has its own therapeutic effects. It's a precursor to allopregnanolone, a neurosteroid that binds to GABA-A receptors in the brain. This is the same receptor family targeted by benzodiazepines and alcohol. The result is a genuine calming and sleep-promoting effect. Most practitioners prescribe micronized progesterone at bedtime specifically because of this drowsiness benefit. Women with menopausal insomnia often notice improved sleep within the first few nights.

Dosing protocols vary by approach. Continuous combined therapy uses 100 mg nightly along with daily estradiol. Cyclic therapy uses 200 mg nightly for 12-14 days per month, allowing a withdrawal bleed. The cyclic approach mimics the natural menstrual cycle more closely, which some practitioners prefer in perimenopausal women.

Vaginal progesterone (100-200 mg as a capsule inserted vaginally) provides higher local uterine tissue concentrations with lower systemic exposure. This can be useful for women who experience drowsiness or mood effects from oral dosing, or who want endometrial protection with minimal systemic progesterone.

Store Prometrium capsules at room temperature (25C). The capsules contain progesterone dissolved in peanut oil, so women with peanut allergies should use compounded progesterone in a different base.