Progesterone (micronized)

Also known as: micronized progesterone, P4, Prometrium (branded)

Hormone Restoration

In plain English

Progesterone is a natural hormone that, in women taking estrogen, protects the lining of the uterus. It is also used to support sleep and to balance hormone therapy. It is commonly taken as a capsule at bedtime, or as a lozenge or cream. It can cause drowsiness, which is why the oral capsule is usually taken at night.

The science

Micronized (body-identical) progesterone binds progesterone receptors and opposes estrogen-driven endometrial proliferation; oral progesterone also produces sedating neuroactive metabolites (e.g., allopregnanolone) via GABA-A modulation. In estrogen-treated women with a uterus, adequate progestogen prevents endometrial hyperplasia—cyclic micronized progesterone 200 mg for 12 days/month was endometrial-protective in the PEPI trial—and micronized progesterone appears to carry a more favorable breast and cardiovascular profile than some synthetic progestins per NAMS. FDA-approved oral micronized progesterone exists; transdermal progesterone creams achieve low, variable serum levels and are generally not considered reliable for endometrial protection. Compounded troches/creams are not FDA-approved formulations. Main adverse effects are somnolence, dizziness, and mood changes; caution with the peanut-oil vehicle in some capsules.

References

• Writing Group for the PEPI Trial, JAMA 1996
• The NAMS 2022 Hormone Therapy Position Statement, Menopause 2022