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

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.

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.

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.

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.