Role of Menopause in Thermoregulation

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

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.

Study Overview

• Status: Recruiting
• Conditions: Menopause; Aging
• Intervention / Treatment: Drug: Elagolix Oral Tablet; Other: cellulose placebo; Drug: Estradiol patch; Other: placebo patch

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 Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: W. Larry Kenney, Ph.D.; Phone Number: 814-863-1672; Email: w7k@psu.edu
• Study Contact Backup: Name: Olivia K. Leach, MS; Email: okl5046@psu.edu

Study Locations

• United States
  • Pennsylvania
    • University Park, Pennsylvania, United States, 16802
      • Recruiting
      • Noll Laboratory
      • Contact: W. Larry Kenney, Ph.D.; Phone Number: 814-863-1672; Email: w7k@psu.edu
      • Contact: Olivia Leach, MS; Email: okl5046@psu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Premenopausal estrogen suppression; 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.	Drug: Elagolix Oral Tablet; 2 x 200 mg tablet; Other Names: Orilissa; Other: cellulose placebo; placebo tablet
Experimental: Postmenopausal estrogen supplementation; 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.	Drug: Estradiol patch; 0.05 mg/day patch; Other: placebo patch; placebo patch

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Penn State University
• Investigators: Principal Investigator: W. Larry Kenney, Ph.D., The Pennsylvania State University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: January 15, 2025
• First Submitted That Met QC Criteria: January 22, 2025
• First Posted (Actual): January 29, 2025

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Thermoregulation; Heat Stress
• Additional Relevant MeSH Terms: Wounds and Injuries; Heat Stress Disorders; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Ortho Evra; elagolix
• Other Study ID Numbers: Study 25435

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No