Menstrual Cycle vs. Oral Contraceptives: Effects on Muscle Protein Metabolism After Resistance Exercise (MCOC)

The Effect of Menstrual Cycle Phase and Oral Contraceptive Use on Muscle Protein Metabolism Post-Resistance Training

The muscles of the body are constantly breaking down old proteins and building new ones. These two processes, protein breakdown and protein synthesis, together are known as protein turnover. Protein turnover is essential for maintaining healthy muscle.

Despite its importance, females have historically been underrepresented in protein metabolism research. A long-standing assumption has been that fluctuations in female sex hormones such as estrogen and progesterone, whether across the natural menstrual cycle or in individuals using oral contraceptives (OCs), make metabolism and training responses too variable to study. Because of this, many researchers have excluded female participants for logistical reasons.

Resistance exercise, such as weightlifting, is the most effective way to increase muscle size and strength. Each resistance-training session triggers muscle protein synthesis (MPS), the process by which new muscle proteins are built. Consuming dietary protein or individual amino acids further increases the rate at which new proteins are formed. Over time, higher rates of protein synthesis support muscle growth and the maintenance of other lean tissues in the body.

The purpose of this study is to examine how menstrual cycle phases and OC use influence the synthesis of proteins in both muscle tissue and the rest of the body. Improving scientific understanding in this area will support more effective, evidence-based training and nutrition recommendations for females.

Study Overview

• Status: Recruiting
• Conditions: Menstrual Cycle; Oral Contraceptives; Protein Metabolism; Female Sex Hormones
• Intervention / Treatment: Dietary supplement: Protein Beverage; Dietary supplement: Stable Isotope Tracer [D5]phenylalanine; Dietary supplement: Stable Isotope Tracer [13C]phenylalanine

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Daniel R Moore, PhD; Phone Number: 4169464088; Email: dr.moore@utoronto.ca
• Study Contact Backup: Name: Ines Kortebi, PhD Candidate; Email: ines.kortebi@mail.utoronto.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5S 2C9
      • Recruiting
      • Goldring Center for High Performance Sport
      • Contact: Ines Kortebi, PhD Candidate; Phone Number: 6479392755; Email: ines.kortebi@mail.utoronto.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age: 18-40 years
• BMI between 18.5-29.9 kg/m2 (non-obese)
• Recreationally active (resistance train minimum twice a week)
• Using monophasic or triphasic oral contraceptives for >1 year (for oral contraceptive users)
• Have regular menstrual cycles (21-35 days) for the past 3 months and discontinued any hormonal contraceptive use for at least 6 months (non-oral contraceptive users)
• Must meet a progesterone sufficiency test (non-oral contraceptive users)

Exclusion Criteria:

• Mid-luteal progesterone levels <16umol
• Chronic disease diagnosis (cardiovascular, thyroid, diabetes)
• Current or recent remission of cancer
• Regular use of non-steroidal anti-inflammatory drugs (NSAIDs; except low-dose aspirin), anticoagulants
• Use of prescription drugs that would impact muscle protein synthesis, e.g. Statins, Lithium, ADHD medication.
• Insertion of intrauterine device (IUD) - exception: copper
• Use of emergency contraception in the last 3 months (e.g. Plan B)
• Severe food allergies (e.g. soy, nuts)
• Smoking, use of performance enhancing drugs (growth hormones, testosterone)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Mid-Luteal Phase; 5-9 days post-ovulation	Dietary supplement: Protein Beverage; Participants will consume 16 half-hourly (8 hours) isoenergetic, isonitrogenous beverages containing 1.2 g/kg/d protein.; Dietary supplement: Stable Isotope Tracer [D5]phenylalanine; Protein beverages will be enriched with the stable isotope [D5]phenylalanine. The use of [D5]phenylalanine will allow for determination of muscle protein synthesis.; Dietary supplement: Stable Isotope Tracer [13C]phenylalanine; Protein beverages will be enriched with the stable isotope tracer [13C]phenylalanine. The use of [13C]phenylalanine will allow for the determination of the fate of amino acids in the body (incorporation into body protein or oxidation) which can be used to determine protein requirements.
Other: Early Follicular Phase; Days 2-6 post-menses onset	Dietary supplement: Protein Beverage; Participants will consume 16 half-hourly (8 hours) isoenergetic, isonitrogenous beverages containing 1.2 g/kg/d protein.; Dietary supplement: Stable Isotope Tracer [D5]phenylalanine; Protein beverages will be enriched with the stable isotope [D5]phenylalanine. The use of [D5]phenylalanine will allow for determination of muscle protein synthesis.; Dietary supplement: Stable Isotope Tracer [13C]phenylalanine; Protein beverages will be enriched with the stable isotope tracer [13C]phenylalanine. The use of [13C]phenylalanine will allow for the determination of the fate of amino acids in the body (incorporation into body protein or oxidation) which can be used to determine protein requirements.
Other: Active Pill Phase; Days 10-20 of active pill	Dietary supplement: Protein Beverage; Participants will consume 16 half-hourly (8 hours) isoenergetic, isonitrogenous beverages containing 1.2 g/kg/d protein.; Dietary supplement: Stable Isotope Tracer [D5]phenylalanine; Protein beverages will be enriched with the stable isotope [D5]phenylalanine. The use of [D5]phenylalanine will allow for determination of muscle protein synthesis.; Dietary supplement: Stable Isotope Tracer [13C]phenylalanine; Protein beverages will be enriched with the stable isotope tracer [13C]phenylalanine. The use of [13C]phenylalanine will allow for the determination of the fate of amino acids in the body (incorporation into body protein or oxidation) which can be used to determine protein requirements.
Other: Placebo Pill Phase; At least 48h after last active pill is taken	Dietary supplement: Protein Beverage; Participants will consume 16 half-hourly (8 hours) isoenergetic, isonitrogenous beverages containing 1.2 g/kg/d protein.; Dietary supplement: Stable Isotope Tracer [D5]phenylalanine; Protein beverages will be enriched with the stable isotope [D5]phenylalanine. The use of [D5]phenylalanine will allow for determination of muscle protein synthesis.; Dietary supplement: Stable Isotope Tracer [13C]phenylalanine; Protein beverages will be enriched with the stable isotope tracer [13C]phenylalanine. The use of [13C]phenylalanine will allow for the determination of the fate of amino acids in the body (incorporation into body protein or oxidation) which can be used to determine protein requirements.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle Protein Synthesis (MPS)	Muscle protein synthesis (MPS) will be assessed during an 8-hour post-exercise and feeding period using a stable isotope tracer, L-[ring-D5]phenylalanine ([D5]Phe). The incorporation of the [D5]Phe tracer into myofibrillar muscle proteins, collected from muscle biopsies (pre-exercise and post-8h feeding), will be analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the fractional synthesis rate (FSR) of muscle proteins. This will help us understand how menstrual cycle phases and oral contraceptive use influence MPS, providing insight into optimizing protein intake and training adaptations in female athletes.	8 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Whole Body Protein Synthesis (WBPS)	Whole body protein synthesis (WBPS) will be measured over a 4-hour period using the Indicator Amino Acid Oxidation (IAAO) methodology. Participants will consume a stable isotope tracer, L-[1-13C]phenylalanine ([13C]Phe), and breath samples will be collected every 30 minutes during the final 4 hours of the metabolic trial. The enrichment of 13CO₂ in breath samples will be analyzed to determine phenylalanine oxidation rates, providing an estimate of whole-body protein turnover and dietary protein utilization. This will allow us to assess whether hormonal fluctuations influence protein metabolism and nutritional requirements in female athletes.	4 hours

Collaborators and Investigators

• Sponsor: University of Toronto

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: August 20, 2025
• First Submitted That Met QC Criteria: November 28, 2025
• First Posted (Actual): December 2, 2025

Study Record Updates

• Last Update Posted (Actual): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 28, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Menstrual Cycle; Oral Contraceptives; Resistance Exercise; Indicator Amino Acid Oxidation; Protein Metabolism; Weightlifting; Female Sex Hormones; Stable Isotope Tracer
• Other Study ID Numbers: MCOC - REB00048059

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No