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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
60
See description of intervention arm.
See description of intervention arm.
See description of intervention arm.
See description of intervention arm.
Energy Metabolism Research Laboratory
Waterloo, Ontario, Canada
RECRUITINGEnergy balance
Energy balance will be calculated as the difference between energy intake and energy expenditure (see below for description of energy intake and energy expenditure).
Time frame: Energy balance will be measured using the data collected surrounding the exercise and no-exercise sessions (6 days total).
Acylated Ghrelin
Appetite-stimulating hormone acylated ghrelin to be measured via commercially available ELISA kits (pg/mL).
Time frame: To be measured pre-exercise, 0 minutes post-exercise, 30 minutes post-exercise, 60 minutes post-exercise, and 120 minutes post-exercise.
Glucagon-like Peptide 1 (GLP-1)
Appetite-inhibiting hormone GLP-1 to be measured via commercially available ELISA kits (pmol/L).
Time frame: To be measured pre-exercise, 0 minutes post-exercise, 30 minutes post-exercise, 60 minutes post-exercise, and 120 minutes post-exercise.
Cholecystokinin (CCK)
Appetite-inhibiting hormone CCK to be measured via commercially available ELISA kits (pg/ml).
Time frame: To be measured pre-exercise, 0 minutes post-exercise, 30 minutes post-exercise, 60 minutes post-exercise, and 120 minutes post-exercise.
Appetite perceptions
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?").
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Food Preferences
For food preferences, a state food preference questionnaire is a survey or questionnaire used to gather information about individuals' food preferences, and dietary habits.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Ad libitum meal energy intake
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 .
Time frame: At the end of each in-lab session (exercise and seated rest; 2 meals total).
Free-living energy intake
Participants will complete a 3 day food record around each in lab session using a mobile application (Keenoa®) monitored by a registered dietician.
Time frame: Day before, day of, and day after each in-lab session (6 days total).
Energy expenditure
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.
Time frame: Day before, day of, and day after each in-lab session (6 days total).
Estradiol
Sex hormone estradiol measured via radioimmunoassay (pg/mL).
Time frame: Pre-exercise only.
Progesterone
Sex hormone progesterone measured via radioimmunoassay (ng/mL).
Time frame: Pre-exercise only.
Testosterone
Sex hormone testosterone measured via radioimmunoassay.
Time frame: Pre-exercise only.
Blood glucose
Will be measured using biochemical assays prior to and following treatment.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Insulin
Will be measured using biochemical assays prior to and following treatment.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
C-Peptide
Will be measured using biochemical assays prior to and following treatment.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Peripheral Blood Mononuclear Cells
Measured by flow cytometry and biochemical assays/arrays both before and after treatment and before and after an acute bout of exercise.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Inflammatory Cytokines
Measured by flow cytometry and biochemical assays/arrays both before and after treatment and before and after an acute bout of exercise.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Brain-derived Neurotrophic Factor (BDNF)
Measured in blood samples via ELISA kits.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Cathepsin B
Measured in blood samples via ELISA kits.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Irisin
Measured in blood samples via ELISA kits.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Klotho
Measured in blood samples via ELISA kits.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Adrenocorticotropic Hormone
Measured in blood samples via immunoassays.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Dickkopf-1 (DKK-1)
Measured in blood samples via immunoassays.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Fibroblast Growth Factor 23 (FGF-23)
Measured in blood samples via immunoassays.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Interleukin 1B (IL-1B)
Measured in blood samples via immunoassays.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Interleukin-6 (IL-6)
Measured in blood samples via immunoassays.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Tumor Necrosis Factor (TNF)
Measured in blood samples via immunoassays.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Osteocalcin
Measured in blood samples via immunoassays.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Osteopontin
Measured in blood samples via immunoassays.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Osteoprotegerin (OPG)
Measured in blood samples via immunoassays.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Parathyroid Hormone (PTH)
Measured in blood samples via immunoassays.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Sclerostin
Measured in blood samples via immunoassays.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
Leptin
Measured in blood samples via immunoassays.
Time frame: Pre-exercise/seated rest as well as 0 minutes, 30 minutes, 60 minutes and 120 minutes following exercise/seated rest.
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