Does Estrogen Blunt the Effects of Exercise Training on Glycemic Control

NCT07791394 | Not Yet Recruiting

• 1 other identifier: 46726
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Previous research has found that males and females respond differently to exercise training, particularly with respect to improvements in blood sugar control and immune system health. This is crucial since insulin resistance, which can lead to type 2 diabetes and other health problems, affects millions of Canadians. People with insulin resistance often have higher inflammation. Exercise is known to improve insulin resistance and reduce inflammation, but females seem to benefit less from exercise compared to men. The investigators believe this difference might be due to estrogen, a hormone that helps regulate blood sugar (in non-exercising conditions) and reduce inflammation. Females have higher estrogen levels, which might explain their ability to regulate resting blood sugar control and also immune function at rest. Our research will investigate how estrogen influences the acute and chronic effects of exercise males. The investigators will study how estrogen influence's the body's response to exercise, particularly in terms of reducing inflammation and improving blood sugar levels as well as immune function. Overweight and obese males will undergo 2 weeks of high intensity interval training while taking either an estrogen supplement or placebo. Prior to and following training males will undergo an assessment of maximal fitness (VO2max test) and an oral glucose tolerance test. Prior to and following the acute exercise test blood samples will be taken to determine the acute effects of exercise on immune cell function and inflammation. Prior to and during the oral glucose tolerance test participants will have blood samples taken to determine glucose handling and insulin sensitivity. They will also have a muscle biopsy taken prior to and 1h into the oral glucose tolerance test to determine the effects of estrogen supplementation on insulin signaling, mitochondrial content and function, fat metabolism and fat storage in skeletal muscle.

Conditions

To Determine Whether Estrogen Influences the Effects of Training on Glycemic Control and Insulin Sensitivity

Keywords

exercise training; insulin sensitivity; glycemic control; estrogen

Outcome Measures

Primary Outcomes (1)

• Glucose AUC

  Glucose AUC determined from blood samples taken during a 2h oral glucose tolerance test

  Visit 3 (baseline) and Visit 11 (Day 16)

Secondary Outcomes (15)

• Insulin resistance/sensitivity

  Visit 3 (baseline) and Visit 11 (Day 16)

• Markers of insulin signaling

  Visit 3 (baseline) and Visit 11 (Day 16)

• Membrane bound GLUT4

  Visit 3 (baseline) and Visit 11 (Day 16)

• Peripheral blood mononuclear cells

  Visit 2 (baseline) and Visit 10 (Day 14)

• Plasma cytokines from isolated PBMCs

  Visit 2 (baseline) and Visit 10 (Day 14)

Study Arms (2)

Estrogen

EXPERIMENTAL

1mg/d 17-beta estradiol x 2 day and 2mg/d 17-beta estradiol for 14 days

Other: EXERCISE TRAINING WITH OR WITHOUT MEDICATION

Placebo

PLACEBO COMPARATOR

400mg/d of glucose polymer x 16 days

Other: EXERCISE TRAINING WITH OR WITHOUT MEDICATION

Interventions

EXERCISE TRAINING WITH OR WITHOUT MEDICATION OTHER

2 weeks of high intensity interval training while either taking estrogen or placebo

Estrogen; Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Study participation is limited to biological males who are not currently and have not previously taken any sex hormones
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Biological males (with no previous hormonal supplementation).
• Between the ages of 18-35 years old
• Non-smokers
• Sedentary individuals (i.e., engaging in intentional moderate-to-vigorous physical activity \<2x/week)
• Body mass index 27-32 kg/m2
• Body fat % \> 22%

You may not qualify if:

• Any state that can impact the hormonal milieu (e.g., drug/hormonal supplementation related to health).
• Usage of anti-inflammatory medications, \>1 glucose lowering medications, insulin, platelet inhibitors, anti-coagulant medications or simvastatin, beta-blockers, weight loss medications (Orlistat, Saxenda, Contrave, Ozempic) or any medications known to affect protein metabolism (i.e., corticosteroids).
• Presence of cardiovascular, respiratory, metabolic, autoimmune or renal disease.
• Presence of any condition that makes the participant unable to participate in physical activity as determined using the CSEP Get Active Questionnaire.
• Presence of injury that restricts exercise performance.
• VO2max \> 50th percentile for age.
• Previous (within the last 2 months) or current use of ergogenic aids (i.e. creatine).
• Previous or current use of weight loss medications, including liraglutide, semaglutide, orlistat, ozempic, etc.
• History and/or diagnosis of blood clots or family history of blood clot disorders.
• History of allergies or sensitivities to local anesthetic
• Ophthalmic vascular disease
• Classical migraines
• History of thromboembolic disease
• Consume 15 or more alcoholic drinks/week or 3 drinks per day
• Bleeding disorders

Sponsors & Collaborators

• University of Waterloo: lead

Study Sites (1)

University of Waterloo

Waterloo, Ontario, N2L 3G1, Canada

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Exercise; Dosage Forms

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques

Study Officials

• Michaela Devries, PhD

  University of Waterloo

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vito Pipitone, PhD Candidate

CONTACT

519-888-4567; vito.pipitone@uwaterloo.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 14, 2026
• First Posted: August 27, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: August 27, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)