Effects of acute progesterone administration in healthy postmenopausal women and normally-cycling women

The goal of this study was to investigate the behavioral and subjective effects of single doses of progesterone (intramuscular) in post-menopausal women and in women with normal menstrual cycles. Although certain metabolites of progesterone (e.g., allopregnanolone) are known to bind to GABAA receptors and produce sedative-like effects in laboratory animals, few studies have examined the acute effects of these neurosteroids in humans. Postmenopausal women (N=10) received progesterone (25, 50, 100 mg im) or placebo at weekly intervals, and women with normal menstrual cycles (N=8) received progesterone (100 mg im) or placebo once a month during the early follicular phase. Dependent measures included plasma levels of progesterone and allopregnanolone, self-report measures of mood and subjective effects and psychomotor performance. Plasma concentrations of progesterone and allopregnanolone increased in a time and dose-dependent manner, with relatively little variability. The concentrations were similar in both groups, although the ratio of allopregnanolone to progesterone was higher in cycling women at certain time points. Contrary to expectations, progesterone produced only modest behavioral or subjective effects. In the cycling women, it produced mild sedative-like effects (i.e., decreases in ratings of Vigor and Friendliness). In the post-menopausal women, only the highest dose (100 mg) slightly increased ratings of feeling sluggish. These results suggest that progesterone and its metabolites, at concentrations well beyond those attained during the normal menstrual cycle, produce only marginal sedative-like effects. These findings suggest that brief (i.e., several hours) increases in plasma levels of allopregnanolone do not have direct effects on mood. (C) 2001 Elsevier Science Ltd. All rights reserved.