Does Estrogen Blunt the Effects of Exercise Training on Glycemic Control

August 25, 2026 updated by: Michaela Devries-Aboud, University of Waterloo

The Impact of 17beta-estradiol Treatment on Insulin Sensitivity, Immune Function, Inflammation and Skeletal Muscle Metabolism Following Exercise Training in Sedentary, Overweight Males

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Canada
    • Ontario
      • Waterloo, Ontario, Canada, N2L 3G1
        • University of Waterloo
        • Contact:
        • Principal Investigator:
          • Michaela Devries-Aboud, PhD
        • Sub-Investigator:
          • Vito Pipitone, PhD Candidate
        • Sub-Investigator:
          • Emma Dare, PhD
        • Sub-Investigator:
          • Madeline Noble, MSc
        • Sub-Investigator:
          • Sean Gartner, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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%

Exclusion Criteria:

  1. Any state that can impact the hormonal milieu (e.g., drug/hormonal supplementation related to health).
  2. 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).
  3. Presence of cardiovascular, respiratory, metabolic, autoimmune or renal disease.
  4. Presence of any condition that makes the participant unable to participate in physical activity as determined using the CSEP Get Active Questionnaire.
  5. Presence of injury that restricts exercise performance.
  6. VO2max > 50th percentile for age.
  7. Previous (within the last 2 months) or current use of ergogenic aids (i.e. creatine).
  8. Previous or current use of weight loss medications, including liraglutide, semaglutide, orlistat, ozempic, etc.
  9. History and/or diagnosis of blood clots or family history of blood clot disorders.
  10. History of allergies or sensitivities to local anesthetic
  11. Ophthalmic vascular disease
  12. Classical migraines
  13. History of thromboembolic disease
  14. Consume 15 or more alcoholic drinks/week or 3 drinks per day
  15. Bleeding disorders
  16. Severe peripheral neuropathy
  17. Muscular dystrophy
  18. Prior bariatric surgery
  19. Osteoporosis/osteopenia
  20. Orthopaedic issues
  21. Presence of GI disorders (i.e., Colitis, Crohns disease, Celiac disease)
  22. Presence of liver disease or dysfunction (i.e., diagnosed NAFLD, NASH, cirrhosis, previous liver transplant)
  23. History of cancer
  24. Type 1 or 2 diabetes
  25. Presence of renal disorders (creatinine > 140)
  26. Uncontrolled hypertension (>140/90 mmHg)
  27. History of allergies or sensitivities to estradiol or to any ingredient in the formulation or component of the container
  28. History and/or diagnosis of blood clots or family history of blood clot disorders
  29. Have an implantable electronic device
  30. Medical psychiatric history of depression, bipolar, anxiety, suicidal ideation, etc.
  31. Inherited clotting disorders
  32. Chest pain or shortness of breath
  33. Inflammatory disorders (e.g., inflammatory bowel disorder)
  34. Significant weight loss in the 3-month period prior to the study (10% of total body weight)
  35. Any kind of major surgery recently
  36. Bleeding disorders
  37. Active or history of thromboembolic disease (including confirmed venous thromboembolism)
  38. Ophthalmic vascular disease
  39. Classical migraines

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Estrogen
1mg/d 17-beta estradiol x 2 day and 2mg/d 17-beta estradiol for 14 days
Other: EXERCISE TRAINING WITH OR WITHOUT MEDICATION
2 weeks of high intensity interval training while either taking estrogen or placebo
Placebo Comparator: Placebo
400mg/d of glucose polymer x 16 days
Other: EXERCISE TRAINING WITH OR WITHOUT MEDICATION
2 weeks of high intensity interval training while either taking estrogen or placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Glucose AUC
Time Frame: Visit 3 (baseline) and Visit 11 (Day 16)
Glucose AUC determined from blood samples taken during a 2h oral glucose tolerance test
Visit 3 (baseline) and Visit 11 (Day 16)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Insulin resistance/sensitivity
Time Frame: Visit 3 (baseline) and Visit 11 (Day 16)
at rest (HOMA-IR) and during a 2 h oral glucose tolerance test (Matsuda index)
Visit 3 (baseline) and Visit 11 (Day 16)
Markers of insulin signaling
Time Frame: Visit 3 (baseline) and Visit 11 (Day 16)
Western blot of the following markers: AMPKα Thr172 & total AMPKα; phosphorylated Akt Ser437 & total Akt; phosphorylated TBC1D4 Thr642 & total TBC1D4; phosphorylated TBC1D1 Ser237 & total TBC1D; total GLUT4 in human skeletal muscle in the fasted and insulin stimulated state
Visit 3 (baseline) and Visit 11 (Day 16)
Membrane bound GLUT4
Time Frame: Visit 3 (baseline) and Visit 11 (Day 16)
GLUT4 content at the membrane in the fasted and insulin stimulated state (determined via immunofluorescence)
Visit 3 (baseline) and Visit 11 (Day 16)
Peripheral blood mononuclear cells
Time Frame: Visit 2 (baseline) and Visit 10 (Day 14)
determination of immune cell response to acute exercise
Visit 2 (baseline) and Visit 10 (Day 14)
Plasma cytokines from isolated PBMCs
Time Frame: Visit 2 (baseline) and Visit 10 (Day 14)
pro- and anti-inflammatory cytokine content will be determine using a cytokine array and commercially available kits
Visit 2 (baseline) and Visit 10 (Day 14)
Mitochondrial content
Time Frame: Visit 3 (baseline) and Visit 11 (Day 16)
determined using electron microscopy
Visit 3 (baseline) and Visit 11 (Day 16)
Mitochondrial respiration
Time Frame: Visit 3 (baseline) and Visit 11 (Day 16)
skeletal muscle mitochondrial respiration determined using high-resolution respirometry
Visit 3 (baseline) and Visit 11 (Day 16)
intramyocellular lipid (IMCL) content
Time Frame: Visit 3 (baseline) and Visit 11 (Day 16)
total and subcellular location-specific content and storage characteristics
Visit 3 (baseline) and Visit 11 (Day 16)
aerobic fitness (VO2max)
Time Frame: Visit 2 (baseline) and Visit 10 (Day 14)
VO2max determined during a graded exercise test
Visit 2 (baseline) and Visit 10 (Day 14)
Sex hormone concentrations
Time Frame: Visit 3 (baseline) and Visit 11 (Day 16)
Serum estradiol measured using commercially available kits
Visit 3 (baseline) and Visit 11 (Day 16)
Serum hormone concentrations
Time Frame: Visit 3 (baseline) and Visit 11 (Day 16)
Serum progesterone measured using commercially available kits
Visit 3 (baseline) and Visit 11 (Day 16)
Sex hormone concentrations
Time Frame: Visit 3 (baseline) and Visit 11 (day 16)
Serum testosterone measured using commercially available kits
Visit 3 (baseline) and Visit 11 (day 16)
Serum hormone concentrations
Time Frame: Visit 2 (baseline) and visit 10 (day 14)
Serum growth hormone measured using commercially available kits prior to a maximal graded exercise test and immediately (t=0 min), 30 and 60 min after the graded exercise test.
Visit 2 (baseline) and visit 10 (day 14)
Serum hormone concentrations
Time Frame: Visit 2 (baseline) and visit 10 (Day 14)
Serum glucagon measured using commercially available kits prior to a maximal graded exercise test and immediately (t=0 min), 30 and 60 min after the graded exercise test.
Visit 2 (baseline) and visit 10 (Day 14)
Neurotransmitter concentration
Time Frame: Visit 2 (baseline) and Visit 10 (day 14)
Serum epinephrine concentration measured using a commercially available kit prior to a maximal graded exercise test and immediately (t=0 min), 30 and 60 min after the graded exercise test.
Visit 2 (baseline) and Visit 10 (day 14)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Waterloo

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Michaela Devries, PhD, University of Waterloo

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 14, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 25, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 27, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 27, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 25, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 46726

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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