Reinstatement of serum pregnanolone isomers and progesterone during alcohol detoxification therapy in premenopausal women

Background: Alcohol abuse is associated with menstrual irregularities related to the inhibition of progesterone secretion involved in regulation of the menstrual cycle. Reduced progesterone metabolites, including pregnanolone isomers (PIs), are efficient neuromodulators. The authors attempted to evaluate whether levels of PIs reflect impairment in progesterone biosynthesis in premenopausal women treated for alcohol addiction and whether alcohol detoxification therapy contributes to the restoration of their reproductive functions and psychosomatic stability by influencing steroid biosynthesis. Methods: Serum allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one; P3 alpha 5 alpha), pregnanolone (P3 alpha 5 beta), isopregnanolone (P3 beta 5 alpha), epipregnanolone (P3 beta 5 beta), progesterone, pregnanolone sulfate (PregS), pregnanolone, and estradiol were measured in 20 women during therapy (at start, three days, 14 days, one month, and four months) by gas chromatography-mass spectrometry or radioimmunoassay. The results were evaluated by a linear mixed model for longitudinal data, with stage of the treatment and subject as categorical factors, phase of the menstrual cycle as a time-varying covariate, and age of the subject as a covariate and by regression in individual stages of the menstrual cycle. Results: During detoxification treatment, progesterone increased in the luteal phase. P3 alpha 5 alpha, P3 beta 5 alpha, and P3 beta 5 beta rose in both phases of the menstrual cycle. Discussion: Given the similar mechanism in the effects of alcohol and steroids in activating gamma-aminobutyric acid A receptors, the restoration of progesterone and PIs during therapy could be explained by an adaptation to increasing requests for gamma-aminobutyric acid (A)-receptor activating substances owing to the cessation of alcohol intake or by the regeneration of progesterone formation. In conclusion, the reinstatement of progesterone, P3 alpha 5 alpha, and P3 beta 5 beta serum levels demonstrates the favorable effect of detoxification therapy on both reproductive functions and the psychosomatic stability of premenopausal women treated for alcohol addiction.