The goal of this study is to determine if estradiol and progesterone are involved in appetite regulation and energy balance. The study aims to complete a 13 day randomized controlled trial (RCT) where oral supplementation of estradiol only, progesterone only, a combination of each, or a placebo in young males will be provided. During the supplementation period, participants will complete two in-lab sessions where they will complete an acute bout of high-intensity interval training or a period of seated rest (completed on separate days by each participant) and have blood samples and perceptions of appetite measured taken over the course of the in-lab sessions. At the end of each session participants will consume an ad-libitum meal and participants will also track free-living energy intake and wear a thigh-worn accelerometer to measure energy expenditure for three days (day before, day of, and day after) each in-lab session.

The purpose of this study is to further elucidate the individual and combined effects of estradiol and progesterone on appetite-regulating hormones, perceptions of appetite, energy intake, and energy expenditure over a 13 day supplementation period using a randomized controlled trial (RCT) model in males who will be supplemented with each hormone. Sixty healthy, recreationally active male participants will be randomized into one of four possible groups: placebo (PLA; 400 milligrams (mg) per day glucose polymer), estradiol only (E; 1 mg per day for 2 days & 2 mg per day of estradiol for 11 days + 300 mg Polycose), progesterone only (P; Prometrium, 100 mg per day), or combined estradiol and progesterone (E+P; 1 mg per day for 2 days & 2 mg per day of estradiol for 11 days + 300 mg Polycose for estradiol and 100 mg per day of Prometrium) for a total of ~15 per group. Participants will be provided enough daily dose of each treatment dependent on randomization for a total of 13 days and will be instructed to take each supplement orally at the same time each day for the entirety of the intervention. Participants will report to the lab on the 7th day, where they will be fed a standardized meal and then complete either an acute bout of high-intensity interval training (HIIT; 1 minute on, 1 minute off at 90% HRmax) or a period of seated rest (CTRL). Participants will return on day 12 to complete either the HIIT or CTRL session in an identical manner (whichever was not completed on day 7). Blood samples to measure appetite-regulating hormones and perceptions of appetite will be completed pre-exercise, 0-, 30-, 60-, and 120-minutes post-HIIT and CTRL. While participants are receiving the 13 day treatment, free-living energy intake will be assessed for a 3 day period (day before, day of and day after both in lab visits (HIIT/CTRL; days 6-8 and days 11-13) using the Keenoa® mobile application, and energy expenditure will be measured via thigh-worn accelerometers for the same 3 day periods. An ad libitum meal will also be provided following the HIIT and CTRL sessions.

We anticipate publishing this RCT in two separate manuscripts. Manuscript #1 will focus on the potential effects on the appetite-regulating hormones (acylated ghrelin, GLP-1, CCK) and perceptions of appetite. Manuscript #2 will focus on potential effects on energy balance from the measures of energy intake (including free-living and ad-libitum meal intake) and energy expenditure.

Inclusion Criteria:

• ages 18-30 years
• deemed healthy using Canadian Society for Exercise Physiology Get Active Questionnaire (CSEP-GAQ)
• non-smoking

Exclusion Criteria:

• failure to meet inclusion criteria

• contraindications to exercise as indicated by the (CSEP-GAQ)

  • hypersensitivity or allergy to estradiol, progesterone, cellulose, or capsule components
  • having been diagnosed with any metabolic disease (ie. diabetes, metabolic syndrome) or current diagnosis of overweight/obesity (BMI > 30.0)
  • personal of family history of stroke or thrombotic (blood clot) disease, blood clot disorder, venous or arterial thromboembolic disease, or any possible blood clotting disease
  • currently taking anticoagulants, antidiabetic medications, cyclosporine, antihypertensives, and CYP3A4 inducers or inhibitors (e.g., rifampin, ketoconazole, St. John's Wort)
  • known liver dysfunction or liver disease
  • history of ophthalmic vascular disease
  • hormone-dependent malignancies or previous diagnosis of cancer
  • recent major surgery (within ~6 months)
  • prolonged use of a cast or presence of immobility deeming inability to exercise, diagnosis of inflammatory disorders (ie. rheumatoid arthritis, celiac disease, inflammatory bowel disease)
  • history of sensitivity to or extreme nausea/vomiting or any gastrointestinal disorder
  • diagnosis of mental health or mood disorder
  • presence of abnormal eating behaviours as assessed by the Food Cravings State Questionnaire and the Three Factor Eating Questionnaire
  • diagnosed or presence of porphyria or classical migraines

Deidentified participant data from this research study will be available to researchers upon review and approval of reasonable requests starting six months after manuscript publication. Proposals should be sent to the corresponding author.

This study will be a double-blind, non-crossover study comprising four arms. The allocation of treatment will be completed by a researcher not involved in data collection. Both the participant and the researchers collecting and analyzing the data will be blinded to the treatment allocation.