Progesterone (micronised) — The Bioidentical Gestagen
Micronised progesterone is a bioidentical form of the endogenous female sex hormone, primarily used in hormone replacement therapy (HRT) to protect the endometrium when estrogen is prescribed. In the context of longevity, it is critical for maintaining hormonal balance during perimenopause and menopause, supporting sleep architecture, bone density, and cardiovascular health without the elevated risks associated with synthetic progestins.
Mechanism of Action
Progesterone exerts its effects by binding to intracellular progesterone receptors (PR-A and PR-B), which act as ligand-activated transcription factors to regulate gene expression. In the endometrium, it counteracts estrogen-induced proliferation, promoting differentiation and secretory changes. Systemically, progesterone modulates GABA-A receptors in the central nervous system through its neuroactive metabolites (e.g., allopregnanolone), producing anxiolytic and sedative effects. It also influences osteoblast activity and exhibits anti-inflammatory properties, distinguishing its physiological profile from synthetic progestins like medroxyprogesterone acetate (MPA), which can negatively impact lipid profiles and vascular function.
Human Trial Evidence
Extensive human evidence supports the use of micronised progesterone in menopausal hormone therapy. The French E3N cohort study demonstrated that unlike synthetic progestins, micronised progesterone combined with estrogen does not significantly increase breast cancer risk. Other clinical trials have shown its efficacy in improving vasomotor symptoms, sleep quality, and providing endometrial protection.
Dosing Protocol
Typically prescribed at 100 mg to 200 mg per day, taken orally at bedtime due to its somnolent effects. It can be administered continuously (100 mg daily) or cyclically (200 mg for 12-14 days per month) depending on the HRT regimen. Prescription required.
Safety & Contraindications
Common adverse effects include drowsiness, dizziness, breast tenderness, and mood fluctuations. It is contraindicated in individuals with undiagnosed vaginal bleeding, severe liver dysfunction, or a history of certain hormone-sensitive cancers. Unlike synthetic progestins, micronised progesterone is generally considered to have a safer cardiovascular and breast tissue profile. Prescription required.