Reproductive factors and age at natural menopause: A systematic review and meta-analysis

Objectives: To systematically review the evidence on the association between age at natural menopause (NM) and reproductive factors such as age at menarche, parity and ever use of oral contraceptives. Study design: A literature search was carried out in PubMed, Scielo, Scopus and LILACS databases, without restriction of publication year until July 6, 2017. We excluded clinical trials, case-control studies, case reports and studies using statistical methods other than Cox proportional hazard models to assess the factors associated with age at NM. Cross-sectional studies evaluating women aged <50 years were also excluded. Random-effects models were used to pool the estimates. We registered the systematic review in the International Prospective Register of Systematic Review (PROSPERO) in August 2018, CRD42018099105. Results: We identified 30 articles to include in the meta-analysis. We found that previous ever use of oral contraceptives (OC) (HR = 0.87, CI = 0.82, 0.93), age at menarche ≥13 years (HR = 0.90, CI = 0.84, 0.96), and having at least one live birth (HR = 0.79, CI = 0.74, 0.85) were associated with a later age of NM. Conclusions: Despite differences in results between countries and study design, our findings suggest that previous use of OC, age at menarche ≥13 and having at least one live birth are associated with later menopause. The results suggest that these factors could be markers of later ovarian aging.