To Determine Whether Estrogen Influences the Effects of Training on Glycemic Control and Insulin SensitivityNCT07791394
Does Estrogen Blunt the Effects of Exercise Training on Glycemic Control
A study testing EXERCISE TRAINING WITH OR WITHOUT MEDICATION in people with To Determine Whether Estrogen Influences the Effects of Training on Glycemic Control and Insulin Sensitivity, run by University of Waterloo at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- To Determine Whether Estrogen Influences the Effects of Training on Glycemic Control and Insulin Sensitivity
- What is being tested?
- EXERCISE TRAINING WITH OR WITHOUT MEDICATION
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2026to Apr 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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%
Who cannot join
- 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.
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- 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
- Severe peripheral neuropathy
- Muscular dystrophy
- Prior bariatric surgery
- Osteoporosis/osteopenia
- Orthopaedic issues
- Presence of GI disorders (i.e., Colitis, Crohns disease, Celiac disease)
- Presence of liver disease or dysfunction (i.e., diagnosed NAFLD, NASH, cirrhosis, previous liver transplant)
- History of cancer
- Type 1 or 2 diabetes
- Presence of renal disorders (creatinine > 140)
- Uncontrolled hypertension (>140/90 mmHg)
- History of allergies or sensitivities to estradiol or to any ingredient in the formulation or component of the container
- History and/or diagnosis of blood clots or family history of blood clot disorders
- Have an implantable electronic device
- Medical psychiatric history of depression, bipolar, anxiety, suicidal ideation, etc.
- Inherited clotting disorders
- Chest pain or shortness of breath
- Inflammatory disorders (e.g., inflammatory bowel disorder)
- Significant weight loss in the 3-month period prior to the study (10% of total body weight)
- Any kind of major surgery recently
- Bleeding disorders
- Active or history of thromboembolic disease (including confirmed venous thromboembolism)
- Ophthalmic vascular disease
- Classical migraines
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site
University of Waterloo
Waterloo, Ontario, N2L 3G1
Vito Pipitone, PhD Candidate, 519-888-4567, vito.pipitone@uwaterloo.ca
Michaela Devries-Aboud, PhD
About this study
Official title: 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.
- Being tested
- EXERCISE TRAINING WITH OR WITHOUT MEDICATION
- Keywords
- exercise training, insulin sensitivity, glycemic control, estrogen
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EXERCISE TRAINING WITH OR WITHOUT MEDICATIONOther
2 weeks of high intensity interval training while either taking estrogen or placebo
| Study group | Role | What they receive |
|---|---|---|
| Estrogen | Experimental | 1mg/d 17-beta estradiol x 2 day and 2mg/d 17-beta estradiol for 14 days Receives: Other: EXERCISE TRAINING WITH OR WITHOUT MEDICATION |
| Placebo | Placebo comparator | 400mg/d of glucose polymer x 16 days Receives: Other: EXERCISE TRAINING WITH OR WITHOUT MEDICATION |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucose AUC
Glucose AUC determined from blood samples taken during a 2h oral glucose tolerance test
Measured: Visit 3 (baseline) and Visit 11 (Day 16)
Secondary outcomes (15)
Insulin resistance/sensitivity
at rest (HOMA-IR) and during a 2 h oral glucose tolerance test (Matsuda index)
Measured: Visit 3 (baseline) and Visit 11 (Day 16)
Markers of insulin signaling
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
Measured: Visit 3 (baseline) and Visit 11 (Day 16)
Membrane bound GLUT4
GLUT4 content at the membrane in the fasted and insulin stimulated state (determined via immunofluorescence)
Measured: Visit 3 (baseline) and Visit 11 (Day 16)
Peripheral blood mononuclear cells
determination of immune cell response to acute exercise
Measured: Visit 2 (baseline) and Visit 10 (Day 14)
Plasma cytokines from isolated PBMCs
pro- and anti-inflammatory cytokine content will be determine using a cytokine array and commercially available kits
Measured: Visit 2 (baseline) and Visit 10 (Day 14)
Mitochondrial content
determined using electron microscopy
Measured: Visit 3 (baseline) and Visit 11 (Day 16)
Mitochondrial respiration
skeletal muscle mitochondrial respiration determined using high-resolution respirometry
Measured: Visit 3 (baseline) and Visit 11 (Day 16)
intramyocellular lipid (IMCL) content
total and subcellular location-specific content and storage characteristics
Measured: Visit 3 (baseline) and Visit 11 (Day 16)
aerobic fitness (VO2max)
VO2max determined during a graded exercise test
Measured: Visit 2 (baseline) and Visit 10 (Day 14)
Sex hormone concentrations
Serum estradiol measured using commercially available kits
Measured: Visit 3 (baseline) and Visit 11 (Day 16)
Serum hormone concentrations
Serum progesterone measured using commercially available kits
Measured: Visit 3 (baseline) and Visit 11 (Day 16)
Sex hormone concentrations
Serum testosterone measured using commercially available kits
Measured: Visit 3 (baseline) and Visit 11 (day 16)
Serum hormone concentrations
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.
Measured: Visit 2 (baseline) and visit 10 (day 14)
Serum hormone concentrations
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.
Measured: Visit 2 (baseline) and visit 10 (Day 14)
Neurotransmitter concentration
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.
Measured: Visit 2 (baseline) and Visit 10 (day 14)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2026
- Study startAug 2026 (estimated)
- Primary completionApr 2027 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for To Determine Whether Estrogen Influences the Effects of Training on Glycemic Control and Insulin SensitivityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Waterloo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michaela Devries-Aboud, University of Waterloo
- Investigators
- Michaela Devries, PhD, Principal investigator, University of Waterloo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07791394
- Sponsor's protocol ID
- 46726
- Status last verified
- Aug 2026
- First submitted
- 14 Aug 2026
- Last updated
- 27 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of 17beta-estradiol Treatment on Insulin Sensitivity, Immune Function, Inflammation and Skeletal Muscle Metabolism Following Exercise Training in Sedentary, Overweight Males
- ClinicalTrials.gov ID
- NCT07791394
- Acronym / sponsor ID
- 46726
- Keywords
- exercise training, insulin sensitivity, glycemic control, estrogen
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- University of WaterlooUniversity, hospital or other
- Study start
- Aug 2026 (estimated)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Apr 2027 (estimated)
- First posted
- 27 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Estrogen | Experimental | Other: EXERCISE TRAINING WITH OR WITHOUT MEDICATION1mg/d 17-beta estradiol x 2 day and 2mg/d 17-beta estradiol for 14 days |
| Placebo | Placebo comparator | Other: EXERCISE TRAINING WITH OR WITHOUT MEDICATION400mg/d of glucose polymer x 16 days |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (39 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EXERCISE TRAINING WITH OR WITHOUT MEDICATION2 weeks of high intensity interval training while either taking estrogen or placebo | Other | Estrogen, Placebo |
Primary outcome
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
15 secondary outcomes
Insulin resistance/sensitivity
Time frame: Visit 3 (baseline) and Visit 11 (Day 16)
Markers of insulin signaling
Time frame: Visit 3 (baseline) and Visit 11 (Day 16)
Membrane bound GLUT4
Time frame: Visit 3 (baseline) and Visit 11 (Day 16)
Peripheral blood mononuclear cells
Time frame: Visit 2 (baseline) and Visit 10 (Day 14)
Plasma cytokines from isolated PBMCs
Time frame: Visit 2 (baseline) and Visit 10 (Day 14)
Mitochondrial content
Time frame: Visit 3 (baseline) and Visit 11 (Day 16)
Mitochondrial respiration
Time frame: Visit 3 (baseline) and Visit 11 (Day 16)
intramyocellular lipid (IMCL) content
Time frame: Visit 3 (baseline) and Visit 11 (Day 16)
aerobic fitness (VO2max)
Time frame: Visit 2 (baseline) and Visit 10 (Day 14)
Sex hormone concentrations
Time frame: Visit 3 (baseline) and Visit 11 (Day 16)
Serum hormone concentrations
Time frame: Visit 3 (baseline) and Visit 11 (Day 16)
Sex hormone concentrations
Time frame: Visit 3 (baseline) and Visit 11 (day 16)
Serum hormone concentrations
Time frame: Visit 2 (baseline) and visit 10 (day 14)
Serum hormone concentrations
Time frame: Visit 2 (baseline) and visit 10 (Day 14)
Neurotransmitter concentration
Time frame: Visit 2 (baseline) and Visit 10 (day 14)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2026.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michaela Devries, PhD principal investigator
University of Waterloo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing EXERCISE TRAINING WITH OR WITHOUT MEDICATION in people with To Determine Whether Estrogen Influences the Effects of Training on Glycemic Control and Insulin Sensitivity, run by University of Waterloo at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vito Pipitone, PhD Candidate (519-888-4567, vito.pipitone@uwaterloo.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glucose AUC (time frame: Visit 3 (baseline) and Visit 11 (Day 16)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2026.