Resting energy expenditure (REE) decreases with aging and may decrease in women as a result of the menopause, potentially contributing to weight gain. REE has been observed to fluctuate during the menstrual cycle, suggesting regulation by sex hormones. The aim of the present study was to determine the effects of suppressing estrogen and progesterone on REE. Fourteen premenopausal women, 29 +/- 5 yr old (mean +/- sd), were studied in the midluteal menstrual phase (ML) and after 6 d of GnRH antagonist therapy (GnRHant) administered in the follicular menstrual phase. REE was measured by indirect calorimetry in the morning after a 12-h fast and again during beta-adrenergic blockade to determine sympathetic nervous system (SNS) support of REE. Treatment with GnRHant significantly decreased REE (1405 +/- 42 vs. 1334 +/- 36 kcal/d, mean +/- se, ML vs. GnRHant; P = 0.002). Additionally, SNS blockade tended to alter REE more during ML than during GnRHant (-19 +/- 10 vs. 5 +/- 11 kcal/d; P = 0.14). Suppression of sex hormones to postmenopausal levels by GnRHant reduced REE in young healthy women. These findings suggest that the withdrawal of estrogen and/or progesterone attenuates REE, possibly through a SNS-mediated mechanism.