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

NCT07258576 — Not applicable, Recruiting, 20 participants, University of Toronto

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

Registry	NCT07258576, acronym MCOC
Status	Recruiting
Phase	Not applicable
Study type	Interventional; randomized, crossover, masking: none, basic science
Enrollment	20 (Estimated)
Sponsor	University of Toronto (Other)
Conditions	Female Sex Hormones, Menstrual Cycle, Oral Contraceptives, Protein Metabolism
Interventions	Protein Beverage, Stable Isotope Tracer [D5]phenylalanine, Stable Isotope Tracer [13C]phenylalanine (Dietary supplement)
Dates	start 2025-07-20, primary completion 2026-09-01 (estimated), completion 2026-09-01 (estimated), first posted 2025-12-02, last updated 2025-12-02
Locations	1 site in Canada

-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.

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+Arms and interventions

Arm	Type	Interventions	Description
Mid-Luteal Phase	Other	Dietary Supplement: Protein Beverage; Dietary Supplement: Stable Isotope Tracer [D5]phenylalanine; Dietary Supplement: Stable Isotope Tracer [13C]phenylalanine	5-9 days post-ovulation
Early Follicular Phase	Other	Dietary Supplement: Protein Beverage; Dietary Supplement: Stable Isotope Tracer [D5]phenylalanine; Dietary Supplement: Stable Isotope Tracer [13C]phenylalanine	Days 2-6 post-menses onset
Active Pill Phase	Other	Dietary Supplement: Protein Beverage; Dietary Supplement: Stable Isotope Tracer [D5]phenylalanine; Dietary Supplement: Stable Isotope Tracer [13C]phenylalanine	Days 10-20 of active pill
Placebo Pill Phase	Other	Dietary Supplement: Protein Beverage; Dietary Supplement: Stable Isotope Tracer [D5]phenylalanine; Dietary Supplement: Stable Isotope Tracer [13C]phenylalanine	At least 48h after last active pill is taken

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

+Outcome measures

Primary outcomes

Muscle Protein Synthesis (MPS) [8 hours]: 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.

Secondary outcomes

Whole Body Protein Synthesis (WBPS) [4 hours]: 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.

+Eligibility

Sex: Female, ages: 18 Years to 40 Years, accepts healthy volunteers

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)

+Locations (1)

Facility	City	Country	Status
Goldring Center for High Performance Sport	Toronto, Ontario	Canada	Recruiting

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