Reproductive health in first-degree relatives of patients with polycystic ovary syndrome: a review and meta-analysis.

OBJECTIVE Polycystic ovary syndrome (PCOS) is a highly heritable disease. Emerging evidence elucidated the elevated prevalence of reproductive abnormalities in first-degree relatives (FDRs) of patients with PCOS. METHODS Ten databases were searched in December 2020 (PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, CBM, CNKI, VIP and WanFang and WHO international clinical trials registry platform). This study included cohort, case-control, or cross-sectional studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement was followed. Dichotomous data from each of the eligible studies were combined by Mantel-Haenszel model. Standard mean differences with 95% confidence intervals were assessed. Heterogeneities were assessed using I  2 statistics, and the quality of evidence was evaluated by AHRQ EPC program and GRADE approach. RESULTS Thirty-eight studies were included. The prevalence of PCOS (0.22; 95%CI 0.16 to 0.29), menstrual irregularities (0.28; 95%CI 0.22 to 0.34, P<0.01) and ovary morphological changes were elevated in female PCOS FDRs. Female FDRs also presented with increased levels of luteinizing hormone, total testosterone (SMD, 0.53; 95%CI 0.28 to 0.78, P<0.01), unconjugated testosterone, free androgen index, dehydroepiandrosterone sulfate (DHEAS), and anti-Mullerian hormone levels. Subgroup analyses indicated that some of these changes begun in pubertal girls. Furthermore, fathers of PCOS had higher risk of premature baldness. The DHEAS level was elevated in male FDRs. CONCLUSIONS The findings of this analysis suggested that FDRs of patients with PCOS suffered from reproductive endocrinological dysregulations. Thus, more attention should be focused on this population. (PROSPERO-CRD42020183243).