Thermoregulatory Physiology of Menopausal Hot Flashes

/ ABSTRACT Menopausal hot flashes are disruptive, burdensome, interfere with daytime activities and sleep, and are a primary reason that women seek medical attention, however, mechanistic research that advances an understanding of hot flash thermoregulatory physiology is lacking and options for treatment are limited. Hot flashes are characterized by a heat-dissipation response, with increased vasodilation and sweating, making it plausible that cooling could alleviate them. Surprisingly though, there is a paucity of well-controlled, rigorous experiments investigating effects of peripheral skin cooling on objectively-measured hot flashes. Here, we confront this gap with an overarching goal of determining if precisely timed and targeted localized peripheral cooling mitigates menopausal hot flashes. We combine a novel hot flash detection algorithm developed at SRI that can work in real-time to detect impending hot flashes with a novel approach of cooling developed by MPI Heller that can be applied to a thermoregulatory-effective area of the skin (palm of the hand), shown in other populations to be a fast and effective approach to extract heat from the body and improve thermal comfort. This work brings together a multi-disciplined team to advance knowledge about thermal physiology of hot flashes and aligns with the goals of the Trans-NIH Strategic Plan for Women's Health Research, to advance science for the health of women. A total of 30 participants who have a minimum of 4 daily hot flashes, on average, will be monitored for 4 hour sessions on three days under different conditions and instrumented to assess physiological signals relevant for hot flashes, including sternal skin conductance (sweating; gold-standard marker of hot flashes), core (abdominal) and skin temperature (proximal and distal), finger photoplethysmography (PPG) for tracking changes in blood flow, and electrocardiograph for tracking heart rate. For Aim 1, we build on limited historical data in small samples to rigorously investigate effects on menopausal hot flashes of constant ambient cooling (Tambient = 18°C) in symptomatic individuals. In Aim 2, we determine effects on hot flashes of a cold load (10-12°C) applied for 1.5 minutes to a thermoregulatory-effective area of the skin (palm) versus a control location (dorsal neck), with cooling precisely timed when an impending hot flash is detected with our algorithm, in real-time, in symptomatic individuals. Participants will also be monitored on a third day (control, Tambient = 24°C). Our findings, of whether ambient cooling that provides wide-spread cooling to the skin, and/or targeted cooling, reduces hot flash frequency and duration, will inform a future RO1 examining whether personalized thermoregulatory-based interventions are effective at reducing menopausal hot flashes during wakefulness as well as during sleep in free-living individuals. Project Number: 1R21AG093284-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Fiona Baker (+1 co-PI) | Institution: SRI INTERNATIONAL, MENLO PARK, CA | Award Amount: $628,753 | Activity Code: R21 | Study Section: Special Emphasis Panel[ZRG1 EMS-V (59)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11123041