Detailed definition
Allopregnanolone (also called 3α,5α-tetrahydroprogesterone or 3α-hydroxy-5α-pregnan-20-one) is a neurosteroid synthesized from progesterone in two steps: 5α-reductase converts progesterone to 5α-dihydroprogesterone, then 3α-hydroxysteroid dehydrogenase converts that to allopregnanolone. It crosses the blood-brain barrier readily and is also synthesized de novo in the brain. Mechanistically it is a positive allosteric modulator of the GABA-A receptor, increasing the receptor's response to GABA, which is the brain's primary inhibitory neurotransmitter. This is the same receptor family activated by benzodiazepines, ethanol, and barbiturates. Allopregnanolone has been studied in postpartum depression — the FDA-approved drug brexanolone is a synthetic allopregnanolone — and its concentration changes have been implicated in premenstrual mood disorders and perimenopausal mood symptoms.
Why it matters in menopause
When women take oral micronized progesterone (Prometrium) at bedtime, gut and liver metabolism converts a fraction of the dose to allopregnanolone, producing a calming, sleep-promoting effect within 1–2 hours. This is why bedtime oral progesterone is one of the most reliable sleep-restoring tools in menopause care, even before the slower estradiol effects on hot flashes kick in. Vaginal progesterone, by contrast, generates much less allopregnanolone and does not produce the same sleep effect.
Related terms
Sources
External references: Wikipedia.