Skip to main content
OpenTrials
Not yet recruiting

NCT Number: NCT07791394

Does Estrogen Blunt the Effects of Exercise Training on Glycemic Control

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.

Not yet recruiting

Trial opening soon.

Get Notified

Key information

Age range

18 year–35 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

University of Waterloo

Waterloo, Ontario, N2L 3G1, Canada

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

  • 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
  • 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

Treatment and study plan

EXERCISE TRAINING WITH OR WITHOUT MEDICATION

Other

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

Primary outcomes

  1. 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

Secondary outcomes

  1. 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)

  2. 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

  3. 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)

  4. Peripheral blood mononuclear cells

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

    determination of immune cell response to acute exercise

  5. 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

  6. Mitochondrial content

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

    determined using electron microscopy

  7. Mitochondrial respiration

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

    skeletal muscle mitochondrial respiration determined using high-resolution respirometry

  8. intramyocellular lipid (IMCL) content

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

    total and subcellular location-specific content and storage characteristics

  9. aerobic fitness (VO2max)

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

    VO2max determined during a graded exercise test

  10. Sex hormone concentrations

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

    Serum estradiol measured using commercially available kits

  11. Serum hormone concentrations

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

    Serum progesterone measured using commercially available kits

  12. Sex hormone concentrations

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

    Serum testosterone measured using commercially available kits

  13. 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.

  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.

  15. 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.

Interested in participating?

Not yet recruiting

Trial opening soon.

Get Notified

Sponsors and collaborators

Lead sponsor

University of Waterloo

Other

Registry information

Official study title

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

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Aug 27, 2026
Registry last updated
Aug 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.