Hormonal Variation in Premenopausal Female Athletes Is Associated With Risk Factors for Shoulder Instability: A Systematic Review

Purpose

To investigate the impact of hormonal variation and the menstrual cycle on risk factors for shoulder instability.

Methods

A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the electronic databases MEDLINE (PubMed), Embase, SportDiscus (Ebsco), and the Cochrane Library. Studies were included if they focused on the impact of the menstrual cycle on the shoulder joint, were published from 2000 to 2024, and were peer-reviewed articles. Results were analyzed and synthesized, and a risk-of-bias analysis and quality assessment were subsequently performed.

Results

Of the 124 studies identified in the initial search, 4 met the inclusion criteria and were included in this review. In total, 129 female patients were included, and the mean patient age was 23.3 years (range, 18.1-25.4 years). For every 1-pg/mL increase in serum relaxin levels, patients were 2.18 times more likely to present with acute shoulder instability. Proprioception, specifically in detecting changes in external rotation and flexion angles through the shoulder joint positioning test, was significantly lower in the luteal phase than in the ovulatory phase of the menstrual cycle. Finally, strength in abduction, internal rotation, and external rotation was higher in the ovulatory phase of the menstrual cycle than in the follicular or luteal phases.

Conclusions

In this study, we found that physiological limitations in strength and proprioception occur during the luteal phase of the menstrual cycle. We also observed a relationship between increasing serum relaxin levels and shoulder instability.

Level of Evidence

Level III, systematic review of Level II and III studies.

Sex differences in injury patterns between male and female patients have been examined in detail. In 2019, Matzkin et al. showed that female athletes are more likely to experience atraumatic shoulder instability compared to traumatic shoulder instability, which may be a result of differences in anatomy, as females have increased shoulder range of motion and greater ligamentous laxity compared to males. In 2020, Vaswani et al. found that female athletes had a higher rate of revision surgery after arthroscopic shoulder stabilization and a lower likelihood of return to play. The authors suggested considering these sex-based differences when creating personalized surgical plans for patients with the goal of minimizing negative outcomes. In a study examining patient experiences following shoulder surgery for shoulder instability, Wright et al. revealed that female athletes have poorer outcomes and experience greater functional deficits, such as impingement and persistent instability. Furthermore, the authors found that shoulder injuries and instability experienced by female athletes are likely to be caused by overuse and capsular pathology, while recurrent shoulder instability in male athletes is more likely to be caused by glenoid bone loss and labral pathology.

There is a paucity of literature examining the role of hormonal fluctuation during the menstrual cycle on the risk of shoulder instability. Hormones such as relaxin, progesterone, and estrogen are closely related as they fluctuate during different stages of the menstrual cycle and have been found to impact ligamentous laxity. In 2019, Tanaka et al. investigated the relationship between estrogen and repair of the supraspinatus tendon by evaluating metrics, such as load to failure, stiffness, ultimate stress, and amount of chondroid tissue in rats that underwent ovariectomies. The authors found that collagen organization and the amount of choroid tissue were greater in the control group compared to rats that underwent ovariectomy, suggesting that the estrogen-deficient rats did not have the same quality of tendon-to-bone healing. Dragoo et al. examined the impact of relaxin on the strength of the anterior cruciate ligament in female guinea pigs and found that animals administered estrogen and relaxin had significantly weaker anterior cruciate ligaments than controls.

Increased estrogen and relaxin levels are risk factors for ligamentous injuries in females, while progesterone serves as an estrogen antagonist. These 3 hormones have been found to fluctuate together to cause variance in ligamentous laxity in female athletes. In a review examining the relationship between the menstrual cycle and orthopaedic injuries, Raj et al. found that the greatest risk of injury in female athletes occurs during the follicular phase. While estrogen levels are low during the follicular phase, the levels remain higher than progesterone. Estrogen decreases collagen synthesis, thereby increasing the risk of injury until the luteal phase, during which progesterone levels rise gradually to rebuild the endometrium after menstruation.

The purpose of this study was to investigate the impact of hormonal variation and the menstrual cycle on risk factors for shoulder instability. It was hypothesized that estrogen fluctuation during the follicular phase and greater relaxin levels would coincide with greater injury and instability risks.

Methods

Search Strategy and Selection

This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and prospectively registered on PROSPERO. A medical librarian (J.P.) with training in systematic review methodology searched MEDLINE (PubMed), Embase, SportDiscus (Ebsco), and the Cochrane Library for studies published from 2000 to 2024. Subject terms, keywords, and synonyms for the following concepts were used: shoulder, shoulder joint, and menstrual cycle/reproductive cycle.

Studies must have been peer-reviewed retrospective or prospective studies to be included in this review (Levels of Evidence I, II, or III). Studies were included if they met the following inclusion criteria: (1) the population was premenopausal female patients, (2) the intervention (hormone levels or physical measurements) pertained to the shoulder, and (3) the study identified which stage of the menstrual cycle outcomes were measured. Studies were excluded if they were case reports, systematic reviews, or expert opinions (Levels of Evidence IV or V).

Two reviewers (R.N.S. and S.E.R.) screened each title and abstract based on the criteria, and eligible studies were then reviewed in full text. A third reviewer (P.T.) resolved any disputes. Two authors (R.N.S. and S.E.R.) independently extracted data using worksheets blinded to each other. Data were reviewed by a third author (P.T.) and discussed with the entire team to identify and resolve any discrepancies. The following data were extracted: study design, number of patients, inclusion/exclusion criteria, mean age, functional measurements of the shoulder joint, and reproductive hormonal levels (relaxin, estrogen, and/or progesterone) during each phase of the menstrual cycle.

Quality Assessment

The 2018 version of the mixed-methods appraisal tool (MMAT) was utilized to assess the methodological quality of the studies included in the review. All studies included met the criteria to be assessed via the MMAT. Five study design types were considered: qualitative, quantitative (randomized, nonrandomized, descriptive), and mixed methods. Each design type was then appraised using 5 criteria, to which the responses were “yes” the criterion is met, “no” the criterion is not met, and “can’t tell,” meaning there is not enough information in the study to judge if the criterion is met or not. There is no summative score for the 2018 version of the MMAT, allowing for better sensitivity of the analysis, validity, and reliability.

Data Analysis

Descriptive statistics included frequencies with percentages for demographic characteristics and injury types. Furthermore, P values of the regressions performed by each study were collected to determine which physiological measures served as the highest risk for shoulder instability. Results were pooled in studies examining the same comparison groups.

Results

Study Identification

The initial search identified 124 relevant studies. The title and abstract review yielded 12 studies, with the full-text review producing 4 studies appropriate for this review. ^,^,^, A total of 129 patients (11.0%-100% of the study population) were included. Mean patient age was 23.3 years (18.1-25.4 years). The average percentage of females ranged from 11.0% to 100.0%. The Quality of Reporting of Meta-analyses flow diagram identifies the studies included and excluded, as well as reasons for exclusions ( Fig 1 ).

Image, AltText currently not available — Fig 1

Study Characteristics

All studies were performed between 2015 and 2020 ( Table 1 ). None of the studies collected demographic data on race and ethnicity. Two case-control studies and two cross-sectional studies were included. Two of these studies examined injured patients, while the remaining 2 studied physiological changes in healthy patients to predict risk factors for injury. Three studies controlled for phases of the menstrual cycle while taking measurements. ^,^, Two studies measured shoulder strength, 1 study measured shoulder impingement syndrome, and 1 study measured shoulder proprioception and instability. ^,^,^, Two studies measured serum relaxin levels, although only 1 controlled for the phase of the menstrual cycle during which the measurement was taken. None of the studies collected data on estrogen and progesterone levels.

Table 1

Selected Study Characteristics

Study	Journal	Year	Level of Evidence	Female, n (%)	Age, Mean ± SD, y	Menstrual Cycle Phases	Shoulder Joint Measurements	Hormone Measurements
Em et al.	Journal of Back and Musculoskeletal Rehabilitation	2015	III	85 (100)	25.2 ± 6.6	Luteal	Shoulder impingement syndrome	Serum relaxin (pg/mL)
Michalski et al.	Polish Annals of Medicine	2020	II	23 (100)	20– 22	Follicular, ovulation, and luteal	Strength	–
Owens et al.	Orthopedics	2016	II	6 (11)	18.4 ± 1.12	Not controlled	–	Serum relaxin (pg/mL)
Forouzandeh Shahraki et al.	Physical Therapy in Sport	2020	III	15 (100)	23.27 ± 1.66	Menses (follicular), ovulation, and luteal	Strength, proprioception, and stability	–

Em et al. evaluated a cohort of 45 female patients diagnosed with joint hypermobility and compared relaxin levels with a control group of 40 female patients matched for age and body mass index (BMI). Michalski et al. studied changes in strength through the menstrual cycle in 23 healthy women between the ages of 20 and 22 years. Owens et al. examined a cohort of 53 patients presenting to a health care provider for shoulder dislocation or subluxation, of whom 6 (11%) were female, and measured relaxin levels without controlling for phase of the menstrual cycle. Forouzandeh Shahraki et al. included 15 healthy collegiate-aged female athletes without a history of upper extremity injury and examined physiological changes over the menstrual cycle.

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