ArticleInternational journal of epidemiology2023
Genetic evidence for causal relationships between age at natural menopause and the risk of ageing-associated adverse health outcomes.
Article in International journal of epidemiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Insights into the relationship between menopausal timing and risk of cardiovascular disease: a systematic review and meta-analysis of Mendelian randomization analyses.Systematic reviews · 2026Pooled it
- Meta-ERS: an exposome-based risk score using non-genetic factors to guide osteoporosis prevention.Journal of translational medicine · 2026Article
- Slowing down the clock on ovarian aging-does the ovary hold the secret to the fountain of youth?GeroScience · 2026Review
- Menopausal status, transition, and age at menopause with accelerated biological aging across multiple organ systems: findings from two cohort studies.BMC medicine · 2025Article
- The causal effects of age at menarche and age at menopause on sepsis: A two-sample Mendelian randomization analysis.PloS one · 2024Article
- Age at Menopause and the Risk of Stroke: Observational and Mendelian Randomization Analysis in 204 244 Postmenopausal Women.Journal of the American Heart Association · 2023Article
- Review of mendelian randomization studies on age at natural menopause.Frontiers in endocrinology · 2023Review
- Genetic causal relationship between age at menarche and benign oesophageal neoplasia identified by a Mendelian randomization study.Frontiers in endocrinology · 2023Article
- Broad clinical manifestations of polygenic risk for coronary artery disease in the Women's Health Initiative.Communications medicine · 2022Article
Corrections and comments
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Authors and funding
9 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundA later age at natural menopause (ANM) has been linked to several ageing-associated traits including an increased risk of breast and endometrial cancer and a decreased risk of lung cancer, osteoporosis and Alzheimer disease. However, ANM is also related to several proxies for overall health that may confound these associations.
methodsWe investigated the causal association of ANM with these clinical outcomes using Mendelian randomization (MR). Participants and outcomes analysed were restricted to post-menopausal females. We conducted a one-sample MR analysis in both the Women's Health Initiative and UK Biobank. We further analysed and integrated several additional data sets of post-menopausal women using a two-sample MR design. We used ≤55 genetic variants previously discovered to be associated with ANM as our instrumental variable.
resultsA 5-year increase in ANM was causally associated with a decreased risk of osteoporosis [odds ratio (OR) = 0.80, 95% CI (0.70-0.92)] and fractures (OR = 0.76, 95% CI, 0.62-0.94) as well as an increased risk of lung cancer (OR = 1.35, 95% CI, 1.06-1.71). Other associations including atherosclerosis-related outcomes were null.
conclusionsOur study confirms that the decline in bone density with menopause causally translates into fractures and osteoporosis. Additionally, this is the first causal epidemiological analysis to our knowledge to find an increased risk of lung cancer with increasing ANM. This finding is consistent with molecular and epidemiological studies suggesting oestrogen-dependent growth of lung tumours.
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