Sex Disparities in Thermoregulatory and Metabolic Responses to Mild Cold Exposure Largely Explained by Differences in Body Mass and Body Surface Area

Abstract Sex-related differences in thermoregulatory responses to cold exposure, such as differences in metabolic heat production and fuel selection, are often attributed to differences in morphology and body composition. Whether these differences persist in response to cold when comparing lean, healthy men and women with equivalent total body mass (BM, heat producing capacity) and body surface areas (BSA, heat loss capacity) remains unknown. In this study, we aimed to compare thermoregulatory and metabolic responses to cold exposure in both men and women, before and after matching for BM (± 0.6 kg) and BSA (± 0.01 m2). Data included in this study were derived from four previously published studies and an additional 13 men and 23 women who recently completed an identical 3h mild cold exposure protocol. Included in the analyses were 45 healthy men and 23 healthy women [27 years (95% CI: 25 to 28) in men vs. 34 years (95% CI: 30 to 38) in women, P = 0.0003], including 7 men and women of the same age [28 years (95% CI: 22 to 34) vs. 29 years (95% CI: 22 to 37), P = 0.78] matched for BM and BSA. Using a combination of indirect calorimetry, electromyography and positron emission tomography with 11C-acetate and 18F-fluorodeoxyglucose, we quantified mean skin temperature, whole-body energy expenditure (EE), shivering intensity, brown adipose tissue (BAT) oxidative metabolism and glucose uptake. The cold-induced decrease in mean skin temperature was greater in women than men [-6.4°C (95% CI: -6.7 to -6.0) vs. -5.4°C (95% CI: -5.8 to -5.1), P = 0.0004], whereas EE was higher in men compared to women both during room temperature and cold exposure, with the cold-induced increase in EE being slightly greater in men than women [3.8 kJ·min-1 (95% CI: 3.2 to 4.5) vs. 2.8 kJ·min-1 (95% CI: 2.0 to 3.7), P = 0.07]. In contrast, shivering intensity (%MVC) was higher in women compared to men [3.0 %MVC (95% CI: 2.1 to 3.8) vs.1.8 %MVC (95% CI: 1.5 to 2.2), P = 0.0069]. Cold exposure also increased BAT oxidative index to a similar magnitude in men and women, increasing ~4-fold in men and ~3-fold in women (effect of sex, P = 0.2067). Both fractional glucose uptake [0.022 min-1 (95%CI: 0.017 to 0.027) in men and 0.021 min-1 (95%CI: 0.013 to 0.030) in women, P = 0.02] and net glucose uptake in BAT [92 nmol.g-1.min-1 (95%CI: 69 to 115) in men and 91 nmol.g-1.min-1 (95%CI: 53 to 129) in women] were not different between the sexes without or with matching for BM and BSA. The sex differences in mean skin temperature, energy expenditure and shivering intensity were all lost once participants were matched for BM and BSA. The present results suggest that much of the sexual dimorphism in thermoregulatory and metabolic responses to mild cold exposure can be explained by differences in BM and BSA.