Brown Adipose Tissue Metabolism in Women is Dependent on Ovarian Status

In rodents, loss of estradiol (E₂) reduces brown adipose tissue (BAT) metabolic activity. Whether E₂ impacts BAT activity in women is not known. BAT oxidative metabolism was measured in premenopausal (N=27, 35±9 years, body mass index (BMI) = 26.0±5.3 kg/m²) and postmenopausal (N=25, 51±8 years, BMI = 28.0±5.0 kg/m²) women at room temperature (RT) and during acute cold exposure using [¹¹C]-acetate with positron emission tomography coupled with computed tomography (PET/CT). BAT glucose uptake was also measured during acute cold exposure using 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG). To isolate the effects of ovarian hormones from biological aging, measurements were repeated in a subset of premenopausal women (N=8, 40±4 years, BMI = 28.0±7.2 kg/m²) after 6 months of gonadotropin-releasing hormone agonist (GnRH_AG) therapy to suppress ovarian hormones. At RT, there was no difference in BAT oxidative metabolism between premenopausal (0.56±0.31^.min^-1) and postmenopausal women (0.63±0.28^.min^-1). During cold exposure, BAT oxidative metabolism (1.28±0.85 vs. 0.91±0.63^.min^-1, P=0.03) and net BAT glucose uptake (84.4±82.5 vs. 29.7±31.4 nmol^.g^-1.min^-1, P<0.01) were higher in premenopausal than postmenopausal women. In premenopausal women who underwent GnRH_AG, cold-stimulated BAT oxidative metabolism was reduced to a similar level (from 1.36±0.66^.min^-1 to 0.91±0.41^.min^-1) to that observed in postmenopausal women (0.91±0.63^.min^-1). These results provide the first evidence in humans that reproductive hormones are associated with BAT oxidative metabolism and suggest that BAT may be a target to attenuate age-related reduction in energy expenditure and maintain metabolic health in postmenopausal women.