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 eff ects of single doses of progesterone (intramuscular) in post-menopausal wom en and in women with normal menstrual cycles. Although certain metabolites of progesterone (e.g., allopregnanolone) are known to bind to GABAA recepto rs and produce sedative-like effects in laboratory animals, few studies hav e examined the acute effects of these neurosteroids in humans. Postmenopaus al women (N=10) received progesterone (25, 50, 100 mg im) or placebo at wee kly intervals, and women with normal menstrual cycles (N=8) received proges terone (100 mg im) or placebo once a month during the early follicular phas e. Dependent measures included plasma levels of progesterone and allopregna nolone, self-report measures of mood and subjective effects and psychomotor performance. Plasma concentrations of progesterone and allopregnanolone in creased in a time and dose-dependent manner, with relatively little variabi lity. The concentrations were similar in both groups, although the ratio of allopregnanolone to progesterone was higher in cycling women at certain ti me points. Contrary to expectations, progesterone produced only modest beha vioral or subjective effects. In the cycling women, it produced mild sedati ve-like effects (i.e., decreases in ratings of Vigor and Friendliness). In the post-menopausal women, only the highest dose (100 mg) slightly increase d ratings of feeling "sluggish". These results suggest that progesterone an d 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 level s of allopregnanolone do not have direct effects on mood. (C) 2001 Elsevier Science Ltd. All rights reserved.