Sedative and hypnotic effects of oral administration of micronized progesterone may be mediated through its metabolites.

Authors: Arafat ES, Hargrove JT, Maxson WS, Desiderio DM, Wentz AC, Andersen RN.

Publication Year: 1988

Citation: Am J Obstet Gynecol 1988;159(5):1203-9.

This small pilot study evaluated progesterone and its metabolites following administration of oral micronized progesterone in eight postmenopausal women. Progesterone and its metabolites were measured in serum extracts by radioimmunoassay and gas chromatography-mass spectrometry. Evaluation of serial blood samples showed elevated levels of serum progesterone and its metabolites from baseline, reaching a peak between 2 and 6 hours after oral administration. The following compounds: progesterone, 5 beta-pregnan-3 alpha, 5 alpha-pregnan-3 alpha-ol-20-one, 5 beta-pregnan-3 alpha-ol-20-one, 20 beta-diol, and 5 beta-pregnan-3 alpha-ol-11,20-dione, were identified. These compounds have reported anesthetic qualities, which may contribute to the sedative and hypnotic effects seen with oral administration of progesterone. The authors reported that, in one subject, 400 mg of oral micronized progesterone induced a hypnotic state lasting approximately 2 hours