Effects of progesterone on sleep and cognition in healthy postmenopausal women

Sleep disturbances are frequently reported in postmenopausal women. The cessation of ovarian endocrine function leads to a strong decrease in endogenous progesterone secretion. A single oral administration of progesterone in young healthy males prompted benzodiazepine-like effects on sleep-EEG. 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 and cognitive performance was assessed. Subjects consisted of 10 healthy postmenopausal women (54–70 yrs). Progesterone treatment led to a decrease of intermittent time spent awake, during the first half of the night to an increase of REM–sleep and to less stage shifts. Progesterone, in sleep influencing dosages, produced no negative effect on cognitive performance. The decrease of wakefulness is more distinct compared to previous reports in animal studies and males and even more pronounced than effects of estrogens in the menopause on sleep-EEG. The increase of REM-sleep was unexpected. Possible mechanism are a GABA-agonistic effect and the regulation of gene expression via progesterone receptor. Progesterone might be useful in the treatment of sleep disturbances of postmenopausal women.