Skeletal Muscle Health in Polycystic Ovary Syndrome: Protective Effect of Hyperandrogenism or Detrimental Effect of Insulin Resistance? A Systematic Review and Meta-Analysis

Women with polycystic ovary syndrome (PCOS) exhibit reduced skeletal muscle insulin-mediated glucose uptake. Altered muscle mass may affect insulin resistance (IR) and inflammation, thereby potentially aggravating reproductive status including ovulatory cyclicity and fertility potential. However, the relationship between PCOS and skeletal muscle mass is elusive given conflicting reports on protective or detrimental influence of PCOS endocrine derangements (hyperandrogenism, IR) on muscle. We evaluated whether muscle mass and function are affected by PCOS in response to a call to elucidate musculoskeletal alterations in the International Evidence-based Guideline for the Assessment and Management of PCOS. Databases of MEDLINE, Web of Science, and Scopus were searched (January 1990 to September 2020) to identify observational studies on skeletal muscle mass (lean tissue mass) and function (strength) in PCOS and control groups. The primary outcome was total lean body mass (LBM) or fat-free mass (FFM). Data were pooled by random-effects models and expressed as weighted mean differences and 95% confidence intervals. Forty-five studies (n = 3,676 [1,854, PCOS; 1,822, controls]) were eligible. Forty-one evaluated lean tissue mass and five strength. PCOS groups had increased total (0.83 [0.08, 1.58] kg; P=0.03; I(2) = 72.0%) yet comparable trunk (0.84 [-0.37, 2.05] kg; P = 0.15; I(2) = 73.0%) LBM/FFM. There were no associations between mean differences of groups in total testosterone (TT) or homeostatic model assessment of IR (HOMA-IR) and total/trunk LBM/FFM (All: P ≥ 0.75) by meta-regressions. However, mean differences of groups in body mass index (BMI) were associated with total (0.65 [0.23, 1.06] kg; P < 0.01; I(2) = 56.9%) and trunk (0.56 [0.11, 1.01] kg; P = 0.02; I(2) = 42.8%) LBM/FFM. Accordingly, PCOS sub-group with overweight/obesity (BMI ≥ 25 kg/m(2)) exhibited greater total LBM/FFM than controls (1.58 [0.82, 2.34] kg; P < 0.01; I(2) = 64.0%) unlike a lean (BMI < 25 kg/m(2)) sub-group (-0.45 [-1.94, 1.05] kg; P = 0.53; I(2) = 69.5%). Some study results were contradictory (i.e., increased appendicular mass or strength in PCOS group or comparable findings between groups) and study methodology varied; thus, inclusion in meta-analyses was not possible. PCOS cohorts have a tendency for increased total and trunk lean tissue mass likely attributed to obesity. However, most critically, whether PCOS influences other lean tissue areas (appendicular), morphology, and function is unclear. Our observations do not support any protective/detrimental influence of hyperandrogenism (TT) or IR (HOMA-IR) on lean mass. Heterogeneity among studies warrants research to address any contributions of lifestyle, healthcare, and biological factors to observed differences for future guideline recommendations to improve PCOS musculoskeletal and reproductive health (www.crd.york.ac.uk/PROSPERO ID, CRD42020203490).