Effects of progesterone on sleep and cognition in healthy postmenopausal women

Sleeping problems like difficulty falling asleep and awakenings during the night are frequently reported in postmenopausal women. The cessation of ovarian endocrine function leads to a strong decrease in endogenous progesterone secretion. The neuroactive metabolites of progesterone allopregnanolone and pregnanolone in rats and a single oral administration of progesterone in young healthy males prompted benzodiazepine-like effects on sleep- EEG. There is a lack of data about the influences of exogenous administration of progesterone on sleep- EEG in postmenopausal women.

We tested whether replacement therapy with progesterone might be reversing disturbed sleep during menopause. A double blind cross-over design study with 2 treatment intervals of 21 days duration separated by a 2 weeks washout was performed. An oral dose of 300mg micronized progesterone was given each for 21 days. At the beginning and the end of the two intervals a sleep-EEG was recorded after one night of adaptation and cognitive performance (attention, memory, executive function) was assessed. Subjects consisted of 10 healthy postmenopausal women (age: 54–70yrs, mean 60.3, SD 5.7), who were free of any medication and of specific sleep disorder (sleep apnoe, RLS). Progesterone treatment led to a decrease of intermittent time spent awake (p<0.05, placebo=79.7±13.31min, progesterone=53.5±7.36min) and during the first half of the night to an increase of REM–sleep and to less transitions between the sleep stages. Progesterone produced no consistent effect on cognitive performance. The decrease of wakefulness is more distinct compared to previous reports in animal studies and in males and even more pronounced than effects of estrogens on sleep- EEG in postmenopausal women. The increase of REM-sleep was unexpected. As possible mechanism of progesterone a GABA-agonistic effect and the regulation of gene expression via progesterone receptor are discussed. The present study opens the possibility that progesterone might be useful in the treatment of sleep disturbances of postmenopausal women.