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The Role of Estradiol and Progesterone on Appetite Regulation and Energy Balance

The Role of Estradiol and Progesterone on Appetite Regulation and Energy Balance

Status
Recruiting
Phases
Unknown
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT07620587
Acronym
E2 & P4 in EB
Enrollment
60
Registered
2026-06-02
Start date
2026-06-01
Completion date
2028-08-31
Last updated
2026-06-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Energy Balance, Physiology - Regulation of Appetite and Food Intake

Keywords

ovarian hormones, energy intake, appetite regulation, appetite-regulating hormones, energy balance, regulation of food intake

Brief summary

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.

Detailed description

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.

Interventions

DRUGPlacebo Comparator

See description of intervention arm.

DRUGEstradiol Only

See description of intervention arm.

DRUGProgesterone Only

See description of intervention arm.

DRUGEstradiol and Progesterone Combination

See description of intervention arm.

Sponsors

Wilfrid Laurier University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)

Masking description

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.

Intervention model description

Participants will be randomized into one of four groups where they will receive one of four possible treatments.

Eligibility

Sex/Gender
MALE
Age
18 Years to 30 Years
Healthy volunteers
Yes

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

Design outcomes

Primary

MeasureTime frameDescription
Energy balanceEnergy balance will be measured using the data collected surrounding the exercise and no-exercise sessions (6 days total).Energy balance will be calculated as the difference between energy intake and energy expenditure (see below for description of energy intake and energy expenditure).
Acylated GhrelinTo be measured pre-exercise, 0 minutes post-exercise, 30 minutes post-exercise, 60 minutes post-exercise, and 120 minutes post-exercise.Appetite-stimulating hormone acylated ghrelin to be measured via commercially available ELISA kits (pg/mL).
Glucagon-like Peptide 1 (GLP-1)To be measured pre-exercise, 0 minutes post-exercise, 30 minutes post-exercise, 60 minutes post-exercise, and 120 minutes post-exercise.Appetite-inhibiting hormone GLP-1 to be measured via commercially available ELISA kits (pmol/L).
Cholecystokinin (CCK)To be measured pre-exercise, 0 minutes post-exercise, 30 minutes post-exercise, 60 minutes post-exercise, and 120 minutes post-exercise.Appetite-inhibiting hormone CCK to be measured via commercially available ELISA kits (pg/ml).

Secondary

MeasureTime frameDescription
Appetite perceptionsPre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Subjective appetite perceptions will be assessed using visual analogue scales (VAS) validated for four perceptions: hunger (i.e., "How hungry do you feel?"), satisfaction (i.e., "How satisfied do you feel?"), fullness (i.e., "How full do you feel?"), and prospective food consumption (i.e., "How much do you think you can eat?").
Food PreferencesPre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.For food preferences, a state food preference questionnaire is a survey or questionnaire used to gather information about individuals' food preferences, and dietary habits.
Ad libitum meal energy intakeAt the end of each in-lab session (exercise and seated rest; 2 meals total).A post in-lab session meal will be provided to all participants to determine their ad libitum energy intake for this meal by measuring the food provided before the meal as well as the amount of food not consumed using an analog scale .
Free-living energy intakeDay before, day of, and day after each in-lab session (6 days total).Participants will complete a 3 day food record around each in lab session using a mobile application (Keenoa®) monitored by a registered dietician.
Energy expenditureDay before, day of, and day after each in-lab session (6 days total).Energy expenditure will be measured for the same 3 days of the food records around both in-lab sessions measured using a thigh-worn accelerometer.
EstradiolPre-exercise only.Sex hormone estradiol measured via radioimmunoassay (pg/mL).
ProgesteronePre-exercise only.Sex hormone progesterone measured via radioimmunoassay (ng/mL).
TestosteronePre-exercise only.Sex hormone testosterone measured via radioimmunoassay.
Blood glucosePre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Will be measured using biochemical assays prior to and following treatment.
InsulinPre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Will be measured using biochemical assays prior to and following treatment.
C-PeptidePre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Will be measured using biochemical assays prior to and following treatment.
Peripheral Blood Mononuclear CellsPre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured by flow cytometry and biochemical assays/arrays both before and after treatment and before and after an acute bout of exercise.
Inflammatory CytokinesPre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured by flow cytometry and biochemical assays/arrays both before and after treatment and before and after an acute bout of exercise.
Brain-derived Neurotrophic Factor (BDNF)Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured in blood samples via ELISA kits.
Cathepsin BPre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured in blood samples via ELISA kits.
IrisinPre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured in blood samples via ELISA kits.
KlothoPre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured in blood samples via ELISA kits.
Adrenocorticotropic HormonePre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured in blood samples via immunoassays.
Dickkopf-1 (DKK-1)Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured in blood samples via immunoassays.
Fibroblast Growth Factor 23 (FGF-23)Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured in blood samples via immunoassays.
Interleukin 1B (IL-1B)Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured in blood samples via immunoassays.
Interleukin-6 (IL-6)Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured in blood samples via immunoassays.
Tumor Necrosis Factor (TNF)Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured in blood samples via immunoassays.
OsteocalcinPre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured in blood samples via immunoassays.
OsteopontinPre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured in blood samples via immunoassays.
Osteoprotegerin (OPG)Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured in blood samples via immunoassays.
Parathyroid Hormone (PTH)Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured in blood samples via immunoassays.
SclerostinPre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured in blood samples via immunoassays.
LeptinPre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.Measured in blood samples via immunoassays.

Countries

Canada

Contacts

CONTACTJessica Tucker, MKin, PhD Candidate
tuck5010@mylaurier.ca519-884-1970
PRINCIPAL_INVESTIGATORTom J Hazell, PhD

Wilfrid Laurier University

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Jun 3, 2026