Role of Menopause in Thermoregulation

Phase 4

Recruiting

• Conditions: Menopause; Aging
• Interventions: Drug: Elagolix Oral Tablet; Drug: Estradiol patch; Other: cellulose placebo; Other: placebo patch

• Registration Number: NCT06798571
• Lead Sponsor: Penn State University

Brief 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.

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.

Study Timeline

• Study First Submitted: 2025-01-15
• Study First Submitted QC: 2025-01-22
• Study First Posted: 2025-01-29
• Study Start: 2025-03-01
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-10
• Last Update Posted: 2025-04-15
• Primary Completion: 2026-03-01
• Study Completion: 2026-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Premenopausal estrogen suppression	Elagolix Oral Tablet	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.
Premenopausal estrogen suppression	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	Estradiol 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.
Postmenopausal estrogen supplementation	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Noll Laboratory; 🇺🇸 University Park, Pennsylvania, United States