Age of natural menopause onset in BRCA1/2 carriers - systematic review and meta-analysis

Germinal pathogenic variants in and genes are associated with high risk of cancers, including breast, ovary, fallopian tubes and primary peritoneal. Non-oncological implications of germline pathogenic variants in and genes, complicating reproductive health are less described. The influence of and on age of natural menopause remains inconclusive and controversial. PubMed database was searched for potentially relevant abstracts. Studies which were not case-control, cohort or cross-sectional studies were subsequently excluded. Reference lists from systematic reviews or meta-analyses, dealing with the topic of menopause and and germinal pathogenic variants, were also checked to identify eligible studies. We also included our original, unpublished data from families, affected by or pathogenic variant, consisted of at least two postmenopausal female siblings with differing variant status. Initial database search retrieved 193 abstracts. We identified 4 eligible studies for meta-analysis. Two studies not reporting dispersion measures and not reporting age of natural menopause in control group were left in summary for illustrational purposes, yet were excluded from meta-analysis. 4 studies and our original, unpublished data, combining data from 1535 germinal and pathogenic variant carriers and 3191 control individuals, did not support the hypothesis of association between germinal pathogenic variants of "breast cancer genes" and premature menopause.