Anxiolytic metabolites of progesterone: correlation with mood and performance measures following oral progesterone administration to healthy female volunteers.
Level 2 - randomized trial
Individual double-blind randomized controlled trial
PubMed 7904330 · doi:10.1159/000126579
What was done
In a double-blind, placebo-controlled study, 18 healthy female volunteers aged 18–25 received an oral dose of micronized progesterone (1,200 mg). Investigators measured plasma levels of progesterone and its A-ring metabolites, allopregnanolone and pregnanolone, at peak progesterone concentration and evaluated correlations with changes in mood, cognition, and motor performance.
What was found
Plasma progesterone correlated with plasma allopregnanolone (r = 0.85), pregnanolone (r = 0.81), and combined metabolites (r = 0.92). Allopregnanolone significantly correlated with measures of fatigue, confusion, and immediate recall. Subjects reaching high metabolite levels (>= 95.55 nmol/l) showed significant changes in fatigue, delayed verbal recall, and symbol copying, whereas subjects with lower levels reported no negative effects.
Why it matters
These findings suggest that behavioral and cognitive effects following oral progesterone administration may be mediated by its neuroactive metabolites rather than the parent steroid alone.
Limits
The study had a very small sample size (n = 18), tested only young healthy females, evaluated only a single acute high dose, and did not report exact p-values or numerical cognitive scores in the abstract.
Cited by
- supports Oral micronized progesterone undergoes extensive first-pass hepatic metabolism where a significant amount is converted into allopregnanolone, which exerts neural calming and sedative effects.