Reflex vasodilation and sweating responses to passive heating are attenuated by age but not menopausal status in middle-aged women

Aging is associated with impaired thermoregulatory function, including attenuated skin vasodilation and sweating responses, whereas estrogen enhances heat dissipation. In women, during midlife, menopause-related estrogen declines occur concurrently with biological aging, yet its independent role in thermoregulation before and after the menopause transition remains unclear. The purpose of this study was to compare the thermoregulatory responses to passive whole-body heating between young women and two groups of middle-aged women: late premenopausal and early postmenopausal. Sixteen young women (18-36 yrs) and sixteen middle-aged women (43-59 yrs) were passively heated using a water-perfused suit until core temperature (Tc: telemetry pill) increased by 1°C. Eight of the middle-aged women (age 43-55 yrs) were late premenopausal and eight (age 50-59 yrs) were early postmenopausal (all naïve to hormone therapy). Forearm blood flow (FBF; venous occlusion plethysmography), an index of skin blood flow (SkBF) during passive heat stress, was measured at every 0.1°C increase in Tc, normalized to mean arterial pressure (MAP), and expressed as forearm vascular conductance (FVC). In the middle-aged women, intradermal microdialysis was used in conjunction with laser-Doppler flowmetry to determine cutaneous vascular conductance (CVC = red blood cell flux/MAP) and expressed as a percentage of maximum (%CVCmax; 28 mM sodium nitroprusside and 43°C local heat). The nitric oxide contribution to SkBF was calculated by infusing NG-nitro-l-arginine methyl ester (15mM L-NAME) once a stable Tc of 1.0°C was reached. Additionally, local sweat rate (LSR; ventilated sweat capsule) was continuously measured on the right forearm of all participants. FVC during heating was attenuated in the combined cohort of middle-aged women compared to the young (P< 0.02), but there were no differences due to menopausal status. The change in Tc from baseline (ΔTc) at which LSR began to increase occurred at a significantly higher ΔTc in the middle-aged pre- (0.32 ± 0.29°C, P=0.04) and post-menopausal (0.31 ± 0.30°C, P=0.04) women compared to the young women (0.07 ± 0.12°C). Similarly, the ΔTc at which SkBF began to increase was significantly higher in the pre- (0.11 ± 0.08°C, P=0.002) and post-menopausal (0.16 ± 0.13°C, P=0.003) women compared to the young (0.00 ± 0.09°C), with no effect of menopause status. Linear regression revealed an inverse relation between age and the ΔTc onset of vasodilation (R2=0.39, P=0.0002) and LSR (R2=0.35, P=0.0003). No differences were observed in the contribution of nitric oxide to skin vasodilation at ΔTc = 1°C between the pre- (9±5 %) and post-menopausal women (12 ± 9%). There is an age-related attenuation in cutaneous reflex vasodilation in response to passive whole-body heating coupled with a delayed onset of thermoregulatory effector function. However, these alterations in thermoregulatory function are not further affected by the transition from late premenopause to early postmenopause. Funding: NIH Grants F31 AG096955 (OKL), T32 AG049676 (KGF and WLK), and R01 AG067471 (WLK) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.