The goal of this clinical trial is to learn if micronized progesterone (PROMETRIUM®) influences the muscle-building response to resistance exercise in healthy premenopausal women aged 18-30 years. The main questions it aims to answer are: 1. Does progesterone change the rate of muscle protein synthesis after exercise? 2. Does progesterone alter the difference in synthesis between an exercised leg and a rested leg? Researchers will compare micronized progesterone to a placebo to see if progesterone changes the way skeletal muscle adapts to resistance exercise. Participants will: * Take two oral doses of progesterone (400 mg total, 34 and 10 hours before testing) or placebo * Complete a unilateral leg extension exercise session in the lab * Receive an infusion of a stable isotope tracer and provide blood samples * Undergo muscle biopsies from the exercised and rested legs
This is a single-site, randomized, double-blind, placebo-controlled Phase 1 clinical trial designed to evaluate the effects of micronized progesterone on exercise-induced skeletal muscle protein synthesis (MPS) in premenopausal women. Participants will be healthy, naturally menstruating women aged 18-30 years. Each will be randomized to receive either two oral doses of micronized progesterone (400 mg total, administered as 2 × 200 mg capsules, 34 and 10 hours prior to testing) or a matched placebo. During the infusion trial, participants will consume a standardized nutritional drink (\~530 kcal; 22 g protein, 52 g carbohydrate, 26 g fat) and perform unilateral resistance exercise consisting of single-leg extensions (1 warm-up set followed by 4 working sets to volitional failure, 2-minute rest between sets). To assess myofibrillar MPS, participants will undergo a primed continuous infusion of L-\[ring-¹³C₆\]-phenylalanine, with incorporation into muscle proteins determined from serial biopsies collected from both the exercised and rested legs. Blood samples will be obtained throughout the infusion period to measure plasma amino acids and hormone concentrations. The primary endpoint is the treatment (placebo vs. progesterone) × leg (exercised vs. rested) interaction in MPS over the 5-hour post-exercise period. Secondary outcomes include the exercise-induced change in fractional synthetic rate (ΔFSR), plasma hormone responses, and exploratory measures of body composition and strength. This study will provide direct evidence on whether progesterone modifies the acute anabolic response to resistance exercise in reproductive-age women, addressing an important gap in female skeletal muscle physiology.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
20
Two doses of 400 mg total micronized progesterone, administered as 2 × 200 mg capsules \~34 hours and \~10 hours prior to infusion trial, taken with a standardized nutritional drink.
Matched oral placebo capsules administered on the same schedule (\~34 and \~10 hours prior to infusion trial) with a standardized nutritional drink.
Exercise Metabolism Research Laboratory
Hamilton, Ontario, Canada
Myofibrillar muscle protein synthesis (MPS) rate
Incorporation of L-\[ring-¹³C₆\]-phenylalanine into myofibrillar proteins, measured via bilateral muscle biopsies (vastus lateralis, exercised vs. rested legs). The primary endpoint is the treatment (micronized progesterone vs. placebo) × leg (exercised vs. rested) interaction in MPS under fed conditions.
Time frame: 5 hours after standardized feeding and unilateral resistance exercise (infusion period)
Myofibrillar MPS in rested leg (fed condition)
MPS in the rested (non-exercised) leg to assess whether progesterone alters postprandial muscle anabolism in the absence of exercise.
Time frame: 5 hours after standardized feeding
Myofibrillar MPS in rested leg (fasted condition)
MPS calculated from baseline fasted blood/plasma enrichment and pre-meal biopsy to determine whether progesterone alters basal, fasted-state anabolism.
Time frame: -240 to 0 minutes before feeding (fasted infusion period)
Circulating serum progesterone concentrations (pharmacokinetics)
Serial serum progesterone measured to characterize exposure; pharmacokinetic parameters include AUC, Cavg, Cmax, and Tmax.
Time frame: -240 to 300 minutes (fasted and fed infusion periods)
Postprandial amino acid response
Serial serum amino acid concentrations (including essential and branched-chain amino acids) measured for PK parameters (AUC, Cavg, Cmax, Tmax) to contextualize MPS responses.
Time frame: 0 to 300 minutes after standardized feeding
Plasma tracer enrichment verification
Plasma enrichment of L-\[ring-¹³C₆\]-phenylalanine at steady-state timepoints to confirm validity of MPS calculations (target ≥2.0%).
Time frame: Throughout infusion (-240 to 300 minutes)
Baseline menstrual phase and hormonal status
Baseline serum estradiol, LH, and FSH concentrations to verify early follicular phase timing and ensure group comparability.
Time frame: Pre-dose (-240 minutes)
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