Effect of menstrual cycle and hormonal contraception on musculoskeletal health and performance: A prospective cohort design and cross-sectional comparison

Sarah J. Myers, Rebecca L. Double, Sophie L. Wardle, Kirsty A. M. Waldock, Thomas J. O'Leary, Richard K. Jones, Paul E. Muckelt, Anton Eisenhauer, Jonathan C. Y. Tang, William D. Fraser, Julie Greeves (Lead Author)

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Background: Women of reproductive age experience cyclical variation in the female sex steroid hormones, 17β-oestradiol and progesterone, during the menstrual cycle that are attenuated by some hormonal contraceptives. Oestrogens perform a primary function in sexual development and reproduction, but have non-reproductive effects on bone, muscle, and sinew tissues (i.e., ligaments and tendons), which may influence injury risk and physical performance. Objectives: The purpose of the study is to understand the effect of the menstrual cycle and hormonal contraceptive use on bone and calcium metabolism, and musculoskeletal health and performance. Methods: Five cohorts of physically active women (aged 18-40 years) will be recruited to participate: eumenorrheic, non-hormonal contraceptive users (EUM; n=20), combined oral contraceptive pill users (COCP; n=20); hormonal implant users (n=20); hormonal intra-uterine system users (IUS; n=20); and hormonal injection users (n=20). Participants must have been using the COCP and Implant for at least 1 year and the IUS and Injection for at least 2 years. First void urine samples and fasted blood samples will be collected for biochemical analysis of calcium and bone metabolism, hormones, and metabolic markers. Knee extensor and flexor strength will be measured using an isometric dynamometer, and lower limb tendon and stiffness, tone and elasticity will be measured using a Myoton device. Functional movement will be assessed using a single leg drop to assess frontal plane projection angle and the qualitative assessment of single leg loading. Bone density and macro- and microstructure will be measured using ultrasound, DXA, and HRpQCT. Skeletal material properties will be estimated from Reference Point Indentation, performed on the flat surface of the medial tibia diaphysis. Body composition will be assessed by DXA. The differences in outcome measures between the hormonal contraceptive groups will be analysed in a one-way between group ANCOVA. Within the EUM group, the influence of the menstrual cycle on outcome measures will be assessed using linear mixed effects model. Within the COCP, differences across two time points will be analysed using paired samples t-test. Results: The research was funded in January 2020 and data collection started in January 2022, with a projected data collection completion date of August 2024. The number of participants that have consented at the point of manuscript submission is 66. It is expected that all data analysis will be completed, and results published by the end of 2024. Conclusions: Understanding the effects of the menstrual cycle and hormonal contraception on musculoskeletal health and performance will inform contraceptive choices for physically active women to manage injury risk.
Original languageEnglish
JournalJMIR Research Protocols
Publication statusAccepted/In press - 22 May 2024

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