L10: Menstrual cycle phase and protein synthesis

What was the background of the study by Colenso-Semple et al. (2025)?

• Premenopausal women are frequently excluded from exercise physiology research

• The assumption that the menstrual cycle or hormonal contraceptives influence metabolic, performance or muscle-based outcomes has, in part, led to sex bias in research

Describe the physiological rationale of existing research into the effect of menstrual cycle phases on research outcomes

• Oestrogen signalling may be involved in pathways that influence muscular adaptations to exercise

• Ovarian hormones inhibited protein turnover and muscle growth in ovarianised rats

• Ovariectomy impaired the regrowth of atrophied skeletal muscle and oestrogen regulated repair and remodelling of muscle

• Menstrual cycle hormones potentially influence protein catabolism, a process proposed to be enhanced in the luteal phase compared to the follicular phase

• Muscle regeneration could be greater in the follicular phase, when oestrogen is higher and progesterone is lower

• Variations in oestrogen receptor RNA and protein content in muscle occurred across phases of the menstrual cycle, but the significance of this is unknown

What are limitations of the existing research into menstrual cycle phases and research outcomes? (3)

• Very few human studies have investigated the effect of menstrual cycle phases on muscle anabolism

• Small sample sizes, acute measurements and between-groups designs limit wider interpretation of some studies

• The ovariectomy model cannot be generalised to humans and ovarian hormone influences on skeletal muscle across the menstrual cycle in humans is poorly understood

What was the aim and hypothesis of the study by Colenso-Semple et al. (2025)?

• Aim - to investigate muscle protein synthesis and myofibrillar proteolysis in response to resistance exercise in naturally menstruating females

• Hypothesis - muscle protein synthesis will increase in response to resistance exercise in both the late follicular and mid-luteal phases, but to a greater extent in the late follicular phase due to higher oestradiol compared to the mid-luteal phase

What was the study design?

A cross-over design

What ethics approval did the study gain? (2)

• Hamilton integrated research ethics board

• Declaration of Helsinki

What was the eligibility criteria of the study? (5)

• Aged 18-30

• Non-smokers and don’t use tobacco related products

• In good health, determined by a medical screening questionnaire

• Normal menstrual bleed, determined by a menstrual cycle tracking app

• Had not used hormonal contraception in the 6 months prior to the study

What was the exclusion criteria of the study? (4)

• If they had a range of medical conditions expected to impact study outcomes

• Took medication that was known to impact protein metabolism

• Used tobacco or tobacco-related products

• Had been diagnosed with a menstrual cycle disorder or endometriosis

What techniques were used in the study and what did they assess? (8)

• DXA scan - body composition

• Blood analysis - classification of metabolites

• Muscle biopsies

• Analysis of saliva

• Myofibrillar extraction - analysis of amino acids

• Precursor-product method - muscle protein synthesis

• Urine sample - determine creatine concentration and enrichment

• Linear mixed model (statistical analysis)

Describe the main study outcomes (5)

• Changes in hormone concentrations were as expected in line with menstrual cycle phase

• No metabolite changes related to each phase of the menstrual cycle were observed, but notable individualised changes were seen

• Mean myofibrillar fractional synthesis rate was not significantly higher in the follicular phase for both control and exercise legs compared to the luteal phase

• There was a significant effect of exercise, but no significant effect of the menstrual cycle and a non-significant interaction

• Mean whole body muscle protein breakdown was non-significantly higher in the luteal phase than the follicular phase

How did the study findings align with the existing literature? (2)

• They aligned with the results from Miller (2006), who found no influence of menstrual cycle phase on acute resting or post-exercise muscle protein synthesis

• They align with previous studies’ findings on metabolites, where few metabolites were found to be linked to specific phases of the menstrual cycle

What were the main findings of the study? (4)

• There was no significant difference in muscle protein synthesis or whole body muscle protein breakdown between menstrual cycle phases

• There were no trends in metabolites that would indicate a phase-specific pattern

• No evidence to suggest any phase-specific effect on metabolism, muscle anabolic processes, or myofibrillar proteolysis

• No support for the concept that the follicular phase is associated with greater potential for muscle anabolism or that the luteal phase is associated with greater catabolism

What future research direction was given by the study?

The influence of endogenous and exogenous ovarian hormone fluctuations on longitudinal changes in muscle size and strength

What were the limitations of the study? (3)

• Assumed hormonal profile that may or may not be present

• Substantial inter-individual variability in hormone levels

• Substantial inter-individual variability in cycle and phase length