ArticleMenopause (New York, N.Y.)2018
Genetic variants associated with earlier age at menopause increase the risk of cardiovascular events in women.
Article in Menopause (New York, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 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
- Lipid Profile in Patients With Primary Ovarian Insufficiency: A Systematic Review and Meta-Analysis.Frontiers in endocrinology · 2022Pooled it
- Menopause and women's cardiovascular health: is it really an obvious relationship?Archives of medical science : AMS · 2023Article
- Age at Natural Menopause and Influencing Factors in Women Attending the Gynecological Outpatient Clinic at a Tertiary Care Hospital.International journal of women's health · 2023Article
- Review of mendelian randomization studies on age at natural menopause.Frontiers in endocrinology · 2023Review
- Women's reproductive traits and ischemic stroke: a two-sample Mendelian randomization study.Annals of clinical and translational neurology · 2023Article
- Does reproductive stage impact cardiovascular disease risk factors? Results from a population-based cohort in Lausanne (CoLaus study).Clinical endocrinology · 2022Article
- Long-term changes in plasma proteomic profiles in premenopausal and postmenopausal Black and White women: the Atherosclerosis Risk in Communities study.Menopause (New York, N.Y.) · 2022Article
- Anti-Müllerian Hormone and Cardiometabolic Disease in Women: A Two-Sample Mendelian Randomization Study.Reviews in cardiovascular medicine · 2022Article
- Genetically Determined Reproductive Aging and Coronary Heart Disease: A Bidirectional 2-sample Mendelian Randomization.The Journal of clinical endocrinology and metabolism · 2022Article
- The relationship between genetic variants associated with primary ovarian insufficiency and lipid profile in women recruited from MASHAD cohort study.BMC women's health · 2022Article
- Shared Genetics Between Age at Menopause, Early Menopause, POI and Other Traits.Frontiers in genetics · 2021Review
- Objectives, design and main findings until 2020 from the Rotterdam Study.European journal of epidemiology · 2020Article
- Age at period cessation and trajectories of cardiovascular risk factors across mid and later life.Heart (British Cardiac Society) · 2020Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveTo better understand the relationship between cardiovascular disease risk and age-at-natural menopause using genetic data.
methodsEarly menopause is associated with cardiovascular disease risk. We constructed a genetic risk score comprising 56 age-at-natural menopause decreasing alleles in men and women from the Framingham Heart Study, the Atherosclerosis Risk in Communities Study, and the Rotterdam Study. If the genetic predisposition to earlier age-at-natural menopause is associated with increased cardiovascular disease risk, it is reasonable to ask whether the risk is shared by men carrying the alleles, despite not experiencing menopause. We estimated the hazard ratio for the score for time to first cardiovascular event. To investigate the possible genetic pleiotropy between age-at-natural menopause and cardiovascular disease, we performed cross-trait linkage disequilibrium score regressions between age-at-natural menopause and cardiovascular disease and risk factors using genome-wide association studies.
resultsTwenty-two thousand five hundred and sixty-eight cardiovascular disease-free participants at baseline were analyzed (9,808 men, 12,760 women). Each additional unit of the genetic propensity to earlier age-at-natural menopause increased the hazard of both cardiovascular disease and cardiac death in women (cardiovascular disease: hazard ratio 1.10 [1.04-1.16], P = 9.7 × 10; cardiac death: 1.12 [1.02-1.24], P = 0.03), whereas no effect was observed for either outcome in men (hazard ratio 0.99 [0.95-1.04], P = 0.71; 1.05 [0.94-1.16], P = 0.34). We found significant negative genetic correlations in women, but not men, between age-at-natural menopause and cardiovascular disease and risk factors.
conclusionGenetic variants associated with earlier age-at-natural menopause are associated with increased cardiovascular disease risk in women, but not men, suggesting sex-specific genetic effects on cardiovascular disease risk.
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Registered trials
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