Musculoskeletal Manifestations of Perimenopause: A Systematic Review and Meta-Analysis of 93,021 Women

Abstract

Background:

The prevalence and characterization of specific types of musculoskeletal (MSK) conditions associated with menopausal transition remains unclear and is often underreported. Our objectives were twofold: (1) to systematically review, and conduct meta-analysis whenever appropriate, to compare the prevalence of MSK symptoms across the different stages of menopause and (2) to characterize the specific MSK conditions associated with transition to menopause.

Methods:

We searched Medline, EMBASE, CENTRAL, and PubMed from inception to May 2024. Articles were eligible for inclusion if they included perimenopausal women and reported any primary data on MSK symptoms or pathology. The outcomes we aimed to find included muscle and joint pain, back pain, and the prevalence of various MSK conditions. A pairwise meta-analysis was performed using a DerSimonian-Laird random-effects model for all comparative data, and subgroup analyses were used to explore heterogeneity.

Results:

After screening 5,556 relevant records, 37 observational studies across 22 countries enrolling 93,021 women were included in the quantitative analysis. Four in 10 women experienced muscle or joint pain during the premenopausal phase (40% [95% confidence interval {CI}: 32%-49%]). Whereas over half of perimenopausal women (57% [95% CI: 48%-65%]) and postmenopausal women (59% [95% CI: 50%-67%]) experienced muscle or joint pain, representing a 1.35-fold increased risk (risk ratio [RR] 1.35, 95% CI: 1.25-1.46, p < 0.001, I² = 88.6%; absolute risk difference 130 more per 1,000 [95% CI: 93-171]) and a 1.40-fold increased risk (RR 1.40, 95% CI: 1.28-1.53, p < 0.001, I² = 95.0%; absolute risk difference 148 more per 1,000 [95% CI: 104-197]) on pairwise comparison with premenopausal women, respectively. Geographic study location nor measurement scale explained the considerable heterogeneity in the pooled analyses. There was underreporting of specific MSK conditions beyond the generic descriptors of muscle and/or joint pain.

Conclusion:

Women transitioning to menopause appear to be at increased risk of developing muscle or joint pain. However, as these findings are based on observational studies, specific causes of MSK pain are underreported, and there is significant heterogeneity. Further high-quality research is needed to confirm and clarify this association.

Level of Evidence:

Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Background

Musculoskeletal (MSK) conditions leading to debilitating pain are highly prevalent, affecting a significant proportion of the adult population globally^1-3. Studies have consistently shown that women are at a significantly higher risk of developing MSK pain in comparison with men^2-6. MSK symptoms commonly arise in midlife, and some evidence suggests they may be linked to the menopausal transition and the associated decrease in estrogens^5,7,8. Several animal studies have demonstrated that reduced estrogen levels adversely affect the synovium and joint cartilage^9-11. However, this relationship remains uncertain, as age itself is a competing risk factor in this patient population⁸.

The STRAW criteria provide a standardized framework for reproductive aging, which can be divided into 3 main stages: the premenopause stage, the menopausal transition or perimenopause, and postmenopause. Each stage is further characterized by menstrual cycle patterns and supported by hormonal changes, offering a clinically useful guide for defining the onset and progression of menopause¹². Perimenopausal women appear to experience joint pain and stiffness to a greater extent than premenopausal women^13-15. However, MSK symptoms related to perimenopause are often underrecognized and underreported. For example, well-recognized guidelines for managing menopausal symptoms focus on vasomotor, genitourinary, mood, sleep, and sexual symptoms, but do not address MSK issues^16-18. Furthermore, recently published reviews on menopausal symptoms have not included MSK symptoms, demonstrating the scarcity of focused research in this area^19,20. Many women presenting with MSK pain never receive a clear diagnosis, making it difficult to treat from the perspective of clinicians^8,13.

The perimenopausal transition appears to be a crucial time period when many women first develop MSK pain, and some studies suggest that declining estrogen levels may contribute to inflammation in MSK tissues^21-23. A longitudinal cohort study of 609 women in an urban Chinese community demonstrated that both the prevalence and severity of muscle and joint pain increased as women progressed through menopausal stages²⁴. A prospective investigation from the Seattle Midlife Women's Health Study reported a significant increase in back pain during the menopausal transition, whereas joint pain appeared to increase primarily with age rather than menopause-related factors, further complicating the relationship between age, menopause, and MSK symptoms²⁵. Beyond this, high-quality longitudinal studies are scarce, and research in this area remains limited. The aim of this systematic review and meta-analysis was to compare the prevalence of MSK pain across the different stages of menopause and characterize the associated MSK conditions.

Methods

This systematic review and meta-analysis is reported in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) (Appendices 1-2)²⁶. The study protocol was registered on Prospective Register of Systematic Reviews (PROSPERO) (CRD42024613054). Local ethics review board approval was not required.

Search Strategy

The following databases covering the period from database inception through May 2024 were searched: Medline, EMBASE, CENTRAL, and PubMed. The search strategy was developed in consultation with a research librarian and modified for each database accordingly (complete search strategy available in Appendix 3). The references of studies meeting inclusion criteria as well as previous pertinent systematic reviews were searched manually to ensure that all relevant articles were included.

Eligibility Criteria

Articles were eligible for inclusion if they included perimenopausal women and reported any primary data on MSK symptoms. Perimenopause was defined by the STRAW criteria¹² and classified as premenopausal, perimenopausal, and postmenopausal. Randomized controlled trials, comparative cohort studies, case-control studies, and surveys were all eligible for inclusion. Articles written in all languages were considered for inclusion. Studies were excluded if they did not differentiate the menopausal state in keeping with the STRAW criteria. Women who had undergone surgical menopause were excluded from data analysis to ensure the review focused solely on the natural menopausal transition, as surgical menopause may involve different physiological mechanisms and symptom profiles²⁷.

Outcomes Assessed

The main outcomes we assessed were the prevalence of muscle or joint pain, back pain, and any defined MSK pathology. In studies that differentiated between severity of pain (i.e., mild, moderate, and severe), patients experiencing moderate and severe pain were included in the muscle or joint pain outcome. Questionnaires, including the standardized Menopause Rating Scale, Menopause-Specific Quality-of-Life Questionnaire, Kupperman Menopausal Index, Greene Climacteric Scale, and de novo questionnaires were used to assess pain symptoms. Data on specific MSK conditions were collected when reported.

Data Extraction

Three reviewers independently screened the systematically searched titles and abstracts using a standardized, pilot-tested form on covidence. Discrepancies that occurred at the title and abstract screening phases were included in the full-text screening stage. At the full-text screening stage, discrepancies were resolved by a fourth reviewer. Three reviewers independently and in duplicate conducted data extraction into a data collection form designed a priori and pilot tested on Microsoft Excel. The extracted data included study characteristics (e.g., author, year of publication, and study design), patient demographics (e.g., age, menopausal status, and body mass index), and outcomes (e.g., muscle and joint pain, back pain, and MSK conditions).

Quality Assessment

Three reviewers assessed the quality of these studies independently using the critical appraisal checklist specifically designed for cross-sectional studies from the 2020 Reviewers' Manual published by the Joanna Briggs Institute.

Statistical Analysis

All statistical analyses were performed on STATA version 18 (StataCorp). A restricted maximum likelihood random-effects model was used to generate the pooled proportion of each outcome along with their respective 95% confidence intervals (CI) for noncomparative data. A logit-transformed proportion was estimated as the effect size. A pairwise meta-analysis was performed using a DerSimonian-Laird random-effects model for all comparative data. Pooled effect estimates for binary outcomes were estimated by calculating the risk ratio (RR) along with their respective 95% CIs. Mean and standard deviation (SD) were estimated for studies that only report median and interquartile range using the method described by Wan et al.²⁸. Missing SD data were calculated according to the prognostic method²⁹. Assessment of between-study heterogeneity was performed using the inconsistency (I²) statistic. An I² greater than 40% was considered to represent considerable heterogeneity³⁰. Bias in meta-analyzed outcomes was assessed with funnel plots³¹. A leave-one-out sensitivity analysis was performed. Subgroup analysis was determined a priori and performed for the primary outcome of muscle or joint pain on the basis of (1) pain scale used, (2) geographic location of corresponding author, (3) pain severity, and (4) mean age of study cohort (i.e., greater than or equal to 50 vs. less than 50).

Results

Study Characteristics

Database and registry searches identified 5,556 relevant records. After excluding 24 duplicates, 5,532 independent records were available for screening. Title and abstract screening excluded 5,380 records. After the assessment of 152 full texts for eligibility, there were 37 studies that reported the outcomes of interest that could be included in the quantitative analysis. A PRISMA flow diagram is demonstrated in Figure 1.

Fig. 1.

PRISMA diagram—transparent reporting of systematic reviews and meta-analysis flow diagram outlining the search strategy results from initial search to included studies.

Pooled study characteristics are reported in Table I. Individual study characteristics are reported in Supplemental Tables 1-2. Included studies were published from 1993 to 2024. The majority of studies (35 of 37) were cross-sectional studies, with the other 2 studies being prospective cohort studies. In terms of geographic location of the included studies, 12 studies were from East Asia^15,32-42, 8 studies from South Asia^43-50, 4 studies from West Asia^51-54, 4 studies from Southeast Asia^55-58, 4 studies from Europe^59-62, 3 studies from North America^63-65, and 1 study from both South America⁶⁶ and Africa⁶⁷, totaling 22 different countries (Fig. 2). There were 26,789 patients who were categorized as premenopausal, 24,326 patients who were perimenopausal and 41,906 patients who were postmenopausal.

Fig. 2.

Geographic distribution of number of included patients in data synthesis (North America: n = 3,096; South America: n = 8,373; Europe: n = 12,384; Africa: n = 1,189; West Asia: n = 2,862; South Asia: n = 5,013; Southeast Asia: n = 1,914; East Asia: n = 58,653). *n corresponds to the number of patients.

TABLE I.

Pooled Study Characteristics

Study Characteristic	No. of Studies (n = 37)
Geographic location
East Asia	12 (32.4)
Southeast Asia	4 (10.8)
South Asia	8 (21.6)
West Asia	4 (8.1)
Africa	1 (10.8)
Europe	4 (10.8)
South America	1 (2.7)
North America	3 (8.1)
Study design
Cross sectional	35 (94.6)
Prospective cohort	2 (5.4)
No. of included patients
<1,000	19 (51.4)
1,000-1,999	10 (27.0)
2,000-4,999	4 (10.8)
≥5,000	4 (10.8)
Mean patient age
<50	20 (54.1)
≥50	14 (37.8)
NR	3 (8.1)
Outcomes
Muscle and joint pain	25 (67.6)
Joint pain	11 (29.7)
Muscle pain	1 (2.7)
Back pain	11 (29.7)
Measurement scales
MRS	9 (24.3)
MENQOL	6 (16.2)
Kupperman Index	5 (13.5)
Greene Climacteric Scale	2 (5.4)
De novo questionnaire	15 (40.5)

MENQOL = Menopause-Specific Quality-of-Life Questionnaire, MRS = Menopause Rating Scale, and n = number of studies.

Muscle and Joint Pain

The prevalence of muscle or joint symptoms was 40% (95% CI: 32%-49%) in premenopausal women, 57% (95% CI: 48%-65%) in perimenopausal women, and 59% (95% CI: 50%-67%) in postmenopausal women (Figs. 3-A, 3-B, and 3-C). Pairwise meta-analysis (N = 28 studies, 43,715 patients) demonstrated a significantly increased risk of muscle or joint pain among perimenopausal compared with premenopausal women (RR 1.35, 95% CI: 1.25-1.46, p < 0.001; absolute risk difference 130 more per 1,000 [95% CI: 93-171]; I² = 88.6%) (Fig. 4). There were no observed subgroup interactions according to measurement scale (p = 0.84), geographic study location (p = 0.06), or pain severity (p = 0.25) (Supplemental Figure 1-3).

Single-arm meta-analysis of proportions of musculoskeletal symptoms in (Fig. 3-A) premenopausal women, (Fig. 3-B) perimenopausal women, and (Fig. 3-C) postmenopausal women.

Fig. 3-A.

Fig. 3-B.

Fig. 3-C.

Fig. 4.

Pairwise meta-analysis comparing the prevalence of muscle or joint pain in premenopausal women with perimenopausal women.

Pairwise meta-analysis (N = 28 studies, 57,696 patients) demonstrated there was a significantly increased risk of muscle or joint pain among postmenopausal compared with premenopausal women (RR 1.40, 95% CI: 1.28-1.53, p < 0.001; absolute risk difference 148 more per 1,000 [95% CI: 104-197]; I² = 95.0%) (Fig. 5). There was no observed subgroup interaction (p = 0.57) according to measurement scale (Supplemental Figure 4). We identified one subgroup interaction by geographic study location (p < 0.001) and severity of pain (Supplemental Figures 5 and 6). The subgroup analysis by mean cohort age (i.e., greater than or equal to 50 vs. less than 50) did not demonstrate a significant interaction between studies with a mean patient age greater than 50 or less than 50 (Supplemental Figure 7-9).

Fig. 5.

Pairwise meta-analysis comparing the prevalence of muscle or joint pain in premenopausal women with postmenopausal women.

Pairwise meta-analysis (N = 35 studies, 66,232 patients) that compared the prevalence of muscle or joint pain between perimenopausal and postmenopausal women demonstrated no difference between the 2 groups (RR 0.97, 95% CI: 0.92-1.01, p = 0.16; absolute risk difference 16 fewer per 1,000 [95% CI: 143 fewer to 5 more]; I² = 85.7%) (Fig. 6). We identified subgroup interactions according to measurement scale (p < 0.001), geographic location, and pain severity (Supplemental Figures 10-12). A summary of all effect estimates for overall analyses and subgroup analyses is reported in Table II.

Fig. 6.

Pairwise meta-analysis comparing the prevalence of muscle or joint pain in perimenopausal women with postmenopausal women.

TABLE II.

Summary of Effect Estimates and Heterogeneity for Each Pairwise Comparison and Subgroup Analysis

				Pairwise Meta-Analysis
Outcome	Interaction p value	Subgroup	No. of Studies	RR	95% CI	P	I2
Premenopause vs. perimenopause
Overall MSK symptoms			28	1.35	1.25-1.46	<0.001	88.6
Geographic location subgroup	0.06	East Asia	9	1.37	1.21-1.55	<0.001	93.6
		South America	1	1.23	1.17-1.30	<0.001	-
		Europe	3	1.36	0.94-1.96	0.10	80.8
		North America	3	1.19	1.07-1.33	<0.001	0
		Africa	1	1.35	1.17-1.55	<0.001	-
		South Asia	4	1.72	1.33-2.23	<0.001	86.7
		West Asia	3	0.93	0.45-1.93	0.85	91.4
		Southeast Asia	4	1.47	1.24-1.74	<0.001	18.8
Pain scale subgroup	0.84	MRS	8	1.27	1.08-1.49	<0.001	89.9
		MENQOL	5	1.41	1.15-1.73	<0.001	90.9
		De Novo	9	1.30	1.17-1.45	<0.001	62.3
		Kupperman	4	1.47	1.16-1.88	<0.001	87.1
		Greene	2	1.35	1.13-1.63	<0.001	1.8
Pain severity	0.25	Pain	25	1.34	1.24-1.45	<0.001	89.7
		Moderate-to-severe	3	1.52	1.23-1.89	<0.001	25.0
Premenopause vs. postmenopause
Overall MSK symptoms			28	1.40	1.28-1.53	<0.001	95.0
Geographic location subgroup	<0.001	East Asia	9	1.41	1.17-1.71	<0.001	98.1
		South America	1	1.42	1.36-1.48	<0.001	-
		Europe	3	1.52	1.12-2.06	0.01	76.4
		North America	3	1.15	0.83-1.59	0.40	73.4
		Africa	1	1.26	1.14-1.39	<0.001	-
		South Asia	4	1.68	1.28-2.19	<0.001	89.8
		West Asia	3	1.19	1.12-1.27	<0.001	0.00
		Southeast Asia	4	1.41	1.11-1.78	0.01	70.5
Pain scale subgroup	0.57	MRS	8	1.35	1.21-1.52	<0.001	87.3
		MENQOL	5	1.39	1.13-1.70	<0.001	93.2
		De Novo	9	1.37	1.15-1.64	<0.001	91.7
		Kupperman	4	1.66	1.32-2.07	<0.001	88.8
		Greene	2	1.18	0.70-2.00	0.53	81.2
Pain severity	0.03	Pain	25	1.37	1.24-1.51	<0.001	95.5
		Moderate-to-severe	3	1.73	1.43-2.09	<0.001	0
Perimenopause vs. postmenopause
Overall MSK symptoms			35	0.97	0.92-1.01	0.16	85.7
Geographic location subgroup	<0.001	East Asia	11	0.94	0.87-1.01	0.10	89.0
		South America	1	0.87	0.83-0.90	<0.001	-
		Europe	4	0.94	0.83-1.07	0.34	77.6
		North America	3	1.05	0.79-1.38	0.74	72.3
		Africa	1	1.07	0.94-0.123	0.32	—
		South Asia	7	1.05	0.99-1.12	0.09	43.2
		West Asia	4	0.79	0.62-1.01	0.06	89.6
		Southeast Asia	4	1.05	0.96-1.15	0.25	20.6
Pain scale subgroup	0.03	MRS	9	0.97	0.88-1.08	0.61	90.7
		MENQOL	6	1.01	0.97-1.05	0.77	0.0
		De Novo	13	0.98	0.91-1.05	0.56	83.0
		Kupperman	5	0.83	0.74-0.93	<0.001	73.6
		Greene	2	1.14	0.82-1.59	0.43	60.6
Pain severity	0.03	Pain	31	0.98	0.94-1.03	0.49	86.3
		Moderate-to-severe	4	0.81	0.64-1.01	0.06	73.3

Bolded entries represent statistically significant values (p < 0.05). CI = confidence interval, MENQOL = Menopause-Specific Quality-of-Life Questionnaire, MRS = Menopause Rating Scale, MSK = musculoskeletal, and RR, relative risk.

Back Pain

The overall prevalence of back pain from the pooled data was 42% (95% CI: 26%-60%; 8 studies) in premenopausal women, 57% (95% CI: 44%-69%; 10 studies) in perimenopausal women, and 59% (95% CI: 45%-71%; 10 studies) in postmenopausal women. Pairwise meta-analysis (N = 8 studies, 15,821 patients) demonstrated a 1.15-fold increased risk of back pain in the perimenopausal compared with premenopausal women (RR 1.15, 95% CI: 1.06-1.24, p < 0.001, I² = 59.8%) (Supplemental Figure 13). Pairwise meta-analysis (8 studies, 20,565 patients) demonstrated a 1.2-fold increased risk of back pain among postmenopausal compared with premenopausal women (RR 1.20, 95% CI: 1.11-1.30, p < 0.001, I² = 66.9%) (Supplemental Figure 14).

Prevalence of MSK Conditions in Perimenopausal Women

A single study reported the prevalence of specific MSK conditions in perimenopausal women. This study by Yoon et al. evaluated the causes of perimenopausal arthralgia in the shoulder⁶⁸. The prevalence of adhesive capsulitis, synovitis, rotator cuff disorder, arthritis, and other shoulder pathologies was compared between perimenopausal (n = 197) and premenopausal (n = 113) women. Adhesive capsulitis was the most common diagnosis (35% and 32%, respectively), but there was no significant difference between groups. The second most common diagnosis was shoulder synovitis, and a significantly higher prevalence (25.1%) was observed in the perimenopausal group when compared with premenopausal women (6.2%).

Discussion

Our systematic review of 37 studies and 93,421 women suggests that women experiencing perimenopause have increased risk of muscle and joint pain when compared with premenopausal women. The MSK symptoms identified during perimenopause, however, did not increase significantly in the postmenopausal stage, indicating a potential inflection point at menopause transition. The specific causes or diagnoses associated with MSK symptoms were poorly reported. Common orthopaedic conditions such as osteoarthritis (OA), tendinopathies, synovitis, or bursitis were rarely specified, and their inclusion would have provided more insight into how these symptoms might be better managed.

Our review has several strengths including sample size and rigorous systematic review methodology. Moreover, we comprehensively tried to explain between study heterogeneity. There are also several limitations. Most of the included studies were cross-sectional, making it difficult to infer causality. There is a notable lack of prospective or longitudinal research that could better clarify causal relationships. Nonetheless, the available data provide valuable insights into prevalence. A majority of the pooled data were collected through self-reporting, introducing a risk of misclassification bias regarding menopausal state⁶⁹. Given that data were self-reported and collected across multiple countries, cultural factors are likely to influence how pain is perceived and reported. To address this, we performed a subgroup analysis by geographic location of the study population, which only partially accounted for the between-study heterogeneity. Furthermore, most of the included studies investigated were not designed with MSK symptoms as a key primary outcome measure; rather, they included all types of symptoms. Therefore, underreporting of MSK symptoms and specific causes is a potential risk. Our findings, therefore, may represent an underestimate of the magnitude of the effect. The symptom scales used were not designed to assess MSK pain and lacked details on localization, functional impact, and correlation with clinical or imaging findings. Future prospective studies using more specific tools are needed to clarify the etiology of MSK pain in this population. Finally, lack of reported baseline demographics across studies precluded meta-regression including potential confounding variables, such as age stratified by menopausal status and hormone therapy, which may influence the prevalence of MSK symptoms.

Our results add to the growing body of evidence demonstrating an association between MSK pain and the onset of menopause^9,70,71. A similar review by Lu et al. (n = 14 studies) also demonstrated an increased prevalence of muscle and joint pain in perimenopausal women¹³. Our review included 23 additional (N = 74,423 women) published studies reporting MSK symptoms in perimenopausal women. Lu et al. reported that postmenopausal women were at a higher risk of moderate to severe MSK symptoms than perimenopausal women. Our findings, however, suggest no difference in MSK symptom severity between the perimenopausal and postmenopausal phases with a precise 95% CI [RR 0.97, 95% CI: 0.92-1.01]. In addition, a primary aim of our review was to better characterize the etiology of MSK symptoms in perimenopausal women. Despite MSK symptoms being common in perimenopause, one of the main findings of our review was a glaring lack of reporting on specific MSK conditions.

Altogether, there is evidence suggesting a high prevalence of MSK symptoms in perimenopausal women. The scientific rationale for these symptoms has implicated estrogen deficiency⁸. There have been multiple proposed theories to explain how estrogen deficiency can contribute to these MSK symptoms in this population⁸. Estrogen receptors are found on a range of human immune cells⁷². High estrogen levels produce an anti-inflammatory state^8,73. Similarly, there is some evidence to suggest that low estrogen levels can contribute to a proinflammatory state and could influence the development of OA⁷³.

There are estrogen receptors found in all joint tissues, including articular cartilage, subchondral bone, and synovium⁷⁴. Findings from animal studies suggest that female hormones have an important influence on inflammation-induced cartilage breakdown^10,11. A clinical study by Lou et al. investigated the association between menopause and severity of knee joint cartilage degeneration using magnetic resonance imaging in 860 healthy women and, after removing the effects of age, showed that the severity of cartilage degeneration increased significantly from premenopausal to perimenopausal state and then to postmenopausal state⁷⁵. Women have a significantly higher prevalence of OA in comparison with men and account for more than 60% of OA cases globally^76,77. Radiographic studies of knee cartilage loss show that women experience faster deterioration than men, with the gap becoming more pronounced after the age of 50, potentially implicating the decline in estrogen^9,78-80. However, observational studies have yet to provide conclusive evidence regarding the potential mechanism of estrogen and the development of OA in women^81,82. Although age is an important confounding factor, some authors suggest that arthralgia related to menopausal estrogen changes is often misdiagnosed as age-related OA⁹. Recognizing the effects of declining estradiol on bone and cartilage is important, and many authors have highlighted the need for higher quality studies in this area^9,82,83.

There is also evidence suggesting that sex hormones can influence the properties of soft tissues, such as muscles²¹, tendons²², and ligaments²³. Estrogens maintain energy homeostasis and promote metabolic health throughout the body, and the decline in estrogens during menopause appears to reduce muscle function⁸⁴. This decline can also lead to changes such as decreased collagen production, reduced tendon and ligament elasticity, and overall weakening of connective tissue, which may increase the risk of inflammation, injury, and tendon pathology^85-88. Furthermore, an increasing body of evidence suggests that the loss of estrogen during menopause may contribute to the postclimacteric decline in muscle mass. It is estimated that postmenopausal women lose about 0.6% of muscle mass per year if sarcopenia remains untreated^9,89. Although it is difficult to isolate the exact mechanisms of sex hormones, balanced physiological levels appear to be crucial for regulating inflammation in the body, promoting tendon health, and maintaining physical function^22,87,90.

Owing to the scarcity of studies outlining specific MSK pathologies in perimenopausal women, the evidence regarding any interventions in these patients is also quite limited. The role of Menopausal Hormone Therapy (MHT) in the management of MSK symptoms in women is controversial. A post hoc analysis of the landmark women's health initiative randomized controlled trial demonstrated that estrogen use alone resulted in a modest but sustained reduction in the frequency of joint pain⁹¹. In contrast to these findings, other studies have shown that MHT is associated with a higher risk of knee OA^92,93. There has been little subsequent research investigating MHT in healthy postmenopausal women, and therefore, its effects are not yet fully understood. Recognizing the effects of declining estradiol on the MSK system is essential for physicians to develop treatment plans that address the underlying cause rather than attributing symptoms solely to age-related degeneration⁹.

In summary, our systematic review and meta-analysis identified a potential association between the onset of menopause and the prevalence of muscle and joint symptoms. The risk of developing muscle or joint pain, along with moderate to severe symptoms, appears to increase from premenopause to perimenopause, but were similar between perimenopause and postmenopause, indicating there may be an inflection point at the menopause transition. Because specific diagnoses were not reported, it is difficult to make direct causal inferences or determine the exact contributors to pain in this population, especially given that age is a competing factor. Nonetheless, the findings highlight that MSK pain is a significant concern in perimenopausal women and underscore the urgent need for prospective studies to better characterize and address this issue.

Appendix

Supporting material provided by the authors is posted with the online version of this article as a data supplement at jbjs.org (http://links.lww.com/JBJSOA/B66). This content was not copyedited or verified by JBJS.