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

NCT07258576 | Recruiting

• 1 other identifier: MCOC - REB00048059
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Female Sex Hormones; Menstrual Cycle; Oral Contraceptives; Protein Metabolism

Keywords

Protein Metabolism; Female Sex Hormones; Menstrual Cycle; Oral Contraceptives; Resistance Exercise; Weightlifting; Indicator Amino Acid Oxidation; Stable Isotope Tracer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Whole Body Protein Synthesis (WBPS)

  4 hours

Study Arms (4)

Mid-Luteal Phase

OTHER

5-9 days post-ovulation

Dietary Supplement: Protein Beverage; Dietary Supplement: Stable Isotope Tracer [D5]phenylalanine; Dietary Supplement: Stable Isotope Tracer [13C]phenylalanine

Early Follicular Phase

OTHER

Days 2-6 post-menses onset

Dietary Supplement: Protein Beverage; Dietary Supplement: Stable Isotope Tracer [D5]phenylalanine; Dietary Supplement: Stable Isotope Tracer [13C]phenylalanine

Active Pill Phase

OTHER

Days 10-20 of active pill

Dietary Supplement: Protein Beverage; Dietary Supplement: Stable Isotope Tracer [D5]phenylalanine; Dietary Supplement: Stable Isotope Tracer [13C]phenylalanine

Placebo Pill Phase

OTHER

At least 48h after last active pill is taken

Dietary Supplement: Protein Beverage; Dietary Supplement: Stable Isotope Tracer [D5]phenylalanine; Dietary Supplement: Stable Isotope Tracer [13C]phenylalanine

Interventions

Protein Beverage DIETARY_SUPPLEMENT

Participants will consume 16 half-hourly (8 hours) isoenergetic, isonitrogenous beverages containing 1.2 g/kg/d protein.

Active Pill Phase; Early Follicular Phase; Mid-Luteal Phase; Placebo Pill Phase

Stable Isotope Tracer [D5]phenylalanine DIETARY_SUPPLEMENT

Protein beverages will be enriched with the stable isotope \[D5\]phenylalanine. The use of \[D5\]phenylalanine will allow for determination of muscle protein synthesis.

Active Pill Phase; Early Follicular Phase; Mid-Luteal Phase; Placebo Pill Phase

Stable Isotope Tracer [13C]phenylalanine DIETARY_SUPPLEMENT

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.

Active Pill Phase; Early Follicular Phase; Mid-Luteal Phase; Placebo Pill Phase

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Cis-females with regular menses or using oral contraceptives.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Toronto: lead

Study Sites (1)

Goldring Center for High Performance Sport

Toronto, Ontario, M5S 2C9, Canada

RECRUITING

Central Study Contacts

Daniel R Moore, PhD

CONTACT

4169464088; dr.moore@utoronto.ca

Ines Kortebi, PhD Candidate

CONTACT

ines.kortebi@mail.utoronto.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Between-Subject Crossover Design

Study Record Dates

• First Submitted: August 20, 2025
• First Posted: December 2, 2025
• Study Start: July 20, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: December 2, 2025

Record last verified: 2025-11

Locations

CA (1)