Pre-clinical data has shown progesterone metabolites improve sleep parameters through positive allosteric modulation of the GABA-A receptor. We undertook a systematic review and meta-analysis of randomised controlled trials to assess micronised progesterone treatment on sleep outcomes.
Using PRISMA guidelines, we searched MEDLINE, Embase, PsycInfo and the Cochrane Central Register of Controlled Trials for randomised controlled trials of micronised progesterone treatment on sleep outcomes up to March 31, 2020. This study is registered with the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42020165981. A random-effects model was used for quantitative analysis.
Our search strategy retrieved 9 randomised controlled trials comprising 388 participants. One additional unpublished trial was found. Eight trials enrolled post-menopausal women. Compared with placebo, micronised 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 favoured micronised progesterone for sleep onset latency (effect size, 7.10; C.I. 1.30, 12.91) but not total sleep time (effect size, 20.72; C.I -0.16, 41.59) or sleep efficiency (effect size, 1.31; C.I. -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.
Micronised progesterone improves various sleep outcomes in randomised controlled trials, predominantly in studies enrolling post-menopausal women. Further research could evaluate the efficacy of micronised progesterone monotherapy using polysomnography or validated questionnaires in larger cohorts.

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