The age-related decline in fat-free mass is accelerated in women after menopause, implying that ovarian hormone deficiency may have catabolic effects on lean tissue. To address the hypothesis that ovarian hormones regulate protein metabolism, we examined the effect of menopausal status and hormone replacement therapy on protein turnover. Whole body protein breakdown, oxidation and synthesis were measured under postabsorptive conditions using [¹³C]leucine in healthy premenopausal (n=15; 49 ± 1 yr) and postmenopausal (n=18; 53 ± 1 yr) women. In postmenopausal women, whole body protein turnover and plasma albumin synthesis rates were also measured following two months of treatment with oral hormone replacement therapy (HRT; 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate; n=9) or placebo (n=9). No differences in whole body protein breakdown, oxidation or synthesis were found between premenopausal and postmenopausal women. Protein metabolism remained similar between groups after statistical adjustment for differences in adiposity and when sub-groups of women matched for percent body fat were compared. In postmenopausal women, no effect of HRT was found on whole body protein breakdown, synthesis or oxidation. In contrast, our results support a stimulatory effect of HRT on albumin fractional synthesis rate. In conclusion, our results suggest no detrimental effect of ovarian hormone deficiency coincident with the postmenopausal state, and no salutary effect of hormone repletion with HRT, on rates of whole body protein turnover, although oral HRT may increase synthesis rates of albumin.