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Not yet recruitingNCT07791394Updated Aug 27, 2026

Does Estrogen Blunt the Effects of Exercise Training on Glycemic Control

An interventional study of EXERCISE TRAINING WITH OR WITHOUT MEDICATION in To Determine Whether Estrogen Influences the Effects of Training on Glycemic Control and Insulin Sensitivity, sponsored by University of Waterloo. Not yet recruiting at 1 site in Canada. Open to male participants aged 18 Years to 35 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-27.

Sponsored by University of Waterloo · Not applicable, Interventional, and Basic science

Phase
Not applicable
Study type
Interventional
Enrollment
24
Allocation
Randomized
Ages
18 Years to 35 Years
Sex
Male
01

Study 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.

02

Conditions studied

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

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Keywords

  • exercise training
  • insulin sensitivity
  • glycemic control
  • estrogen
03

Who can participate

Ages eligible
18 Years to 35 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

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

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
04

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
24 participants (estimated)

Study arms

  • 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

  • Placebo comparator
    Placebo

    400mg/d of glucose polymer x 16 days

    Other: EXERCISE TRAINING WITH OR WITHOUT MEDICATION

Interventions

  • OtherEXERCISE TRAINING WITH OR WITHOUT MEDICATION

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

05

What researchers measure

Primary outcomes

  1. Glucose AUC

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

    Time frame: Visit 3 (baseline) and Visit 11 (Day 16)

Secondary outcomes

  1. Insulin resistance/sensitivity

    at rest (HOMA-IR) and during a 2 h oral glucose tolerance test (Matsuda index)

    Time frame: Visit 3 (baseline) and Visit 11 (Day 16)

  2. 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

    Time frame: Visit 3 (baseline) and Visit 11 (Day 16)

  3. Membrane bound GLUT4

    GLUT4 content at the membrane in the fasted and insulin stimulated state (determined via immunofluorescence)

    Time frame: Visit 3 (baseline) and Visit 11 (Day 16)

  4. Peripheral blood mononuclear cells

    determination of immune cell response to acute exercise

    Time frame: Visit 2 (baseline) and Visit 10 (Day 14)

  5. Plasma cytokines from isolated PBMCs

    pro- and anti-inflammatory cytokine content will be determine using a cytokine array and commercially available kits

    Time frame: Visit 2 (baseline) and Visit 10 (Day 14)

  6. Mitochondrial content

    determined using electron microscopy

    Time frame: Visit 3 (baseline) and Visit 11 (Day 16)

  7. Mitochondrial respiration

    skeletal muscle mitochondrial respiration determined using high-resolution respirometry

    Time frame: Visit 3 (baseline) and Visit 11 (Day 16)

  8. intramyocellular lipid (IMCL) content

    total and subcellular location-specific content and storage characteristics

    Time frame: Visit 3 (baseline) and Visit 11 (Day 16)

  9. aerobic fitness (VO2max)

    VO2max determined during a graded exercise test

    Time frame: Visit 2 (baseline) and Visit 10 (Day 14)

  10. Sex hormone concentrations

    Serum estradiol measured using commercially available kits

    Time frame: Visit 3 (baseline) and Visit 11 (Day 16)

  11. Serum hormone concentrations

    Serum progesterone measured using commercially available kits

    Time frame: Visit 3 (baseline) and Visit 11 (Day 16)

  12. Sex hormone concentrations

    Serum testosterone measured using commercially available kits

    Time frame: Visit 3 (baseline) and Visit 11 (day 16)

  13. 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.

    Time frame: Visit 2 (baseline) and visit 10 (day 14)

  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.

    Time frame: Visit 2 (baseline) and visit 10 (Day 14)

  15. 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.

    Time frame: Visit 2 (baseline) and Visit 10 (day 14)

06

Study locations

1 site
  • University of Waterloo
    Waterloo, Ontario N2L 3G1, Canada
    • Vito Pipitone, PhD Candidate · Contact · vito.pipitone@uwaterloo.ca · 519-888-4567
    • Michaela Devries-Aboud, PhD · Principal investigator
    • Vito Pipitone, PhD Candidate · Sub investigator
    • Emma Dare, PhD · Sub investigator
    • Madeline Noble, MSc · Sub investigator
    • Sean Gartner, MD · Sub investigator
07

References and documents

Study documents

  • Protocol and statistical analysis plan · Jul 31, 2025

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT07791394
Lead sponsor
University of Waterloo
Responsible party
Michaela Devries-Aboud (Associate Professor, University of Waterloo) — Principal investigator
First posted
Aug 27, 2026
Start date
Aug 2026 (estimated)
Primary completion
Apr 2027 (estimated)
Completion
Apr 2027 (estimated)
Last update
Aug 27, 2026

Study contacts

Vito Pipitone, PhD Candidate
Contact
vito.pipitone@uwaterloo.ca
519-888-4567
Michaela Devries, PhD
principal investigator · University of Waterloo

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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