Role of Menopause in Thermoregulation

NCT06798571 — Phase 4, Recruiting, 24 participants, Penn State University

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The Influence of Estrogen on the Thermoregulatory Responses to Heat Stress in Pre and Postmenopausal Women

Registry	NCT06798571
Status	Recruiting
Phase	Phase 4
Study type	Interventional; randomized, crossover, masking: double, basic science
Enrollment	24 (Estimated)
Sponsor	Penn State University (Other)
Conditions	Menopause, Aging
Interventions	Elagolix Oral Tablet, Estradiol patch, cellulose placebo, placebo patch (Drug, other)
Dates	start 2025-03-01, primary completion 2026-12-01 (estimated), completion 2026-12-01 (estimated), first posted 2025-01-29, last updated 2026-10-02
Locations	1 site in United States

-Summary

The frequency and severity of heat waves has increased in the last decades. Older adults (over 65 years) have impaired responses to heat stress making them at increased risk for adverse events. Previous heat waves report that women over 65 experience worse health outcomes than any other age group and age matched men.

Aging and reproductive hormones, specifically estrogen, independently alter responses to heat stress. However, the combined effects of low estrogen following menopause and aging on the response to heat stress are unknown. In this study, the investigators will identify the role of estrogen in pre and post menopausal women on thermoregulatory responses to heat stress.

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+Detailed description

Premenopausal and postmenopausal women will be recruited and different interventions will be given to each group. To mimic a postmenopausal hormone profile, premenopausal women will be given a GnRH antagonist, which acutely reduces estrogen concentrations. This induces a temporary post-menopausal state without compounding aging effects. Postmenopausal women will be given a transdermal estradiol patch to acutely raise estrogen concentrations. Supplementing estrogen in postmenopausal women allows for the effect of menopausal low estrogen concentration to be removed from the physiological effects of aging.

Subjects sign an informed consent form and undergo a medical screening prior to participation. The screening includes a physical exam, anthropometry, chemical and lipid profiles.

Each subject will complete 6 (3 for each treatment) experimental trials. For each intervention, participants will complete one passive heating experiment first, followed by two active heating experiments.

+Arms and interventions

Arm	Type	Interventions	Description
Premenopausal estrogen suppression	Experimental	Drug: Elagolix Oral Tablet; Other: cellulose placebo	Participants take a cellulose placebo tablet for 4 days prior to baseline testing and continue until experimental visits are complete. Following completion of placebo testing, participants begin taking 400 mg/day Elagolix for 4 days prior to testing and continue until experimental visits are complete.
Postmenopausal estrogen supplementation	Experimental	Drug: Estradiol patch; Other: placebo patch	Participants wear a transdermal estradiol patch or placebo patch for 5 days prior to testing and continue until experimental visits are complete. After 48 hr washout, participants then wear the alternative treatment for 5 days prior to testing until experimental visits are complete.

Elagolix Oral Tablet (Drug), also known as Orilissa: 2 x 200 mg tablet
Estradiol patch (Drug): 0.05 mg/day patch
cellulose placebo (Other): placebo tablet
placebo patch (Other): placebo patch

+Outcome measures

Primary outcomes

Skin Blood Flow [Monitored continuously during both 3 hour passive heating experiments (Visit 1 and Visit 3 approx 3 weeks)]: Skin blood flow response to whole body heating is continuously monitored
Local Sweat Rate [Monitored continuously during both 3 hour passive heating experiments (Visit 1 and Visit 3 approx 3 weeks)]: A small sweat capsule is placed on the forearm for the duration of whole body heating.
Core Temperature [Monitored continuously during all 3 hour experimental visits (6 total average of 3 weeks)]: Changes in body temperature are measured through a telemetry pill swallowed before each experiment.

Secondary outcomes

Body Mass [Baseline and following 3 hr experimental visit (6 total visits for study completion, an average of 3 weeks)]: Body mass is measured on a scale.
Skin Temperature [Calculated continuously for the duration of each 3 hr experimental visit (6 total visits for study completion, an average of 3 weeks)]: Mean skin temperature is calculated from a weighted average of skin temperature from 4 different sites.

+Eligibility

Sex: Female, ages: 42 Years to 64 Years, accepts healthy volunteers

Inclusion Criteria:

* Women ages 42-64

Exclusion Criteria:

* Chron's disease, diverticulitis, or similar gastrointestinal disease
* Abnormal resting exercise electrocardiogram (ECG)
* Tobacco use
* High-risk determined by the Atherosclerotic Cardiovascular Disease (CVD) Risk Factor
* Assessment
* Using hormone therapy
* Using hormonal contraceptives

+Locations (1)

Facility	City	Country	Status
Noll Laboratory	University Park, Pennsylvania	United States	Recruiting

+Investigators

W. Larry Kenney, Ph.D., Principal investigator, The Pennsylvania State University