Circulating Angiopoietin-like 8 protein (ANGPTL8/Betatrophin) in patients with polycystic ovary syndrome: a systematic review and multi effect size meta-analysis.

The association between circulating betatrophin levels and polycystic ovary syndrome (PCOS) is controversial and the studies in the literature are inconsistent. The aim of our study was to systematically review and meta-analyze all available literature comparing circulating betatrophin levels between human PCOS patients and controls. Relevant studies were retrieved by online database and manual searching. A total of 11 studies were included in this meta-analysis. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were obtained by a random-effects meta-analysis. Meta-analysis of correlations was performed for the associations of betatrophin with anthropometric, lipid and hormonal covariates in PCOS patients. The results indicated that the betatrophin levels were significantly elevated in PCOS patients as compared to non-PCOS controls (SMD = 0.73, 95% CI = 0.22-1.24, Z = 2.83, p = .005). A one-study leave-out sensitivity analysis indicated that no single study had a significant influence on the overall outcome, suggesting the robustness of this meta-analysis. Our sub-group analysis indicated that this increase in betatrophin concentrations was regardless of normo-weight or obese body mass index (BMI) and insulin resistance might have an important role. There were significant positive correlations of betatrophin with age, free androgen index and free-testosterone in PCOS patients. In summary, regardless of BMI, the circulatory betatrophin levels are elevated in PCOS patients compared to controls. PCOS patients with higher insulin resistance had substantially higher circulating betatrophin concentrations.