Efficacy of Micronized Progesterone for Sleep: A Systematic Review and Meta-analysis of Randomized Controlled Trial Data

Abstract

Abstract Context Preclinical data has shown progesterone metabolites improve sleep parameters through positive allosteric modulation of the γ-aminobutyric acid type A receptor. We undertook a systematic review and meta-analysis of randomized controlled trials to assess micronized progesterone treatment on sleep outcomes. Evidence Acquisition Using preferred reporting items for systematic review and meta-analysis guidelines, we searched MEDLINE, Embase, PsycInfo, and the Cochrane Central Register of Controlled Trials for randomized controlled trials of micronized progesterone treatment on sleep outcomes up to March 31, 2020. This study is registered with the International Prospective Register of Systematic Reviews, number CRD42020165981. A random effects model was used for quantitative analysis. Evidence Synthesis Our search strategy retrieved 9 randomized controlled trials comprising 388 participants. One additional unpublished trial was found. Eight trials enrolled postmenopausal women. Compared with placebo, micronized progesterone improved various sleep parameters as measured by polysomnography, including total sleep time and sleep onset latency, though studies were inconsistent. Meta-analysis of 4 trials favored micronized progesterone for sleep onset latency (effect size, 7.10; confidence interval [CI] 1.30, 12.91) but not total sleep time (effect size, 20.72; CI -0.16, 41.59) or sleep efficiency (effect size, 1.31; CI -2.09, 4.70). Self-reported sleep outcomes improved in most trials. Concomitant estradiol administration and improvement in vasomotor symptoms limit conclusions in some studies. Conclusions Micronized progesterone improves various sleep outcomes in randomized controlled trials, predominantly in studies enrolling postmenopausal women. Further research could evaluate the efficacy of micronized progesterone monotherapy using polysomnography or validated questionnaires in larger cohorts.