Thermoregulatory Physiology of Menopausal Hot Flashes

PROJECT SUMMARY / 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.

Grant Number: 1R21AG093284-01
NIH Institute/Center: NIH
Principal Investigator: Fiona Baker