Send to

Choose Destination
Eur J Epidemiol. 2019 Mar;34(3):235-246. doi: 10.1007/s10654-019-00490-w. Epub 2019 Feb 5.

Premenopausal cardiovascular disease and age at natural menopause: a pooled analysis of over 170,000 women.

Author information

School of Public Health, University of Queensland, 288 Herston Road (corner of Herston Rd and Wyndham St), Brisbane, QLD, 4006, Australia.
School of Public Health, University of Queensland, 288 Herston Road (corner of Herston Rd and Wyndham St), Brisbane, QLD, 4006, Australia.
Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Medical Research Council Unit for Lifelong Health and Ageing at UCL, London, UK.
Department of Epidemiology and Public Health, University College London, London, UK.
Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, 3004, Australia.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, 3010, Australia.
Department of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8654, Japan.
Fukushima Medical Center for Children and Women, Fukushima Medical University, Fukushima, 960-1295, Japan.
School of Health Sciences, Gunma University, Maebashi City, Gunma, 371-0044, Japan.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo, Norway.
Genetic Epidemiology Group, Folkhälsan Research Center, Faculty of Medicine, University of Helsinki, 00290, Helsinki, Finland.
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, 9019, Tromsø, Norway.
Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, 0304, Oslo, Norway.


Early menopause is associated with an increased risk of subsequent cardiovascular disease (CVD). Few studies have investigated the converse. We examined whether premenopausal CVD events are associated with early age at menopause. We pooled the individual data of 177,131 women from nine studies. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRR) and 95% confidence intervals (CI) for the associations between age at onset of premenopausal CVD events-including coronary heart disease (CHD) and stroke-and age at natural menopause. Altogether 1561 (0.9%) premenopausal participants reported CVD events (including 1130 CHD and 469 stroke) at a mean age of 41.3 years. Compared with women without any premenopausal CVD events, women who experienced a first CVD event before age 35 years had a twofold risk of menopause before age 45 years (early menopause); adjusted RRR (95% CI) of 1.92 (1.17, 3.14) for any CVD, 1.86 (1.01, 3.43) for CHD and 2.17 (1.43, 3.30) for stroke. Women who experienced a first premenopausal CVD event after age 40 years underwent a natural menopause at the expected age (around 51 years). These associations were robust to adjustment for smoking status, BMI, educational level, race/ethnicity, age at menarche, parity, hypertension and family history of CVD. For premenopausal women, a first CVD event before age 35 years is associated with a doubling of the risk of an early menopause, while a first CVD event occurred after 35 years indicates a normal menopause at around 51 years. Shared genetic and environmental factors (such as smoking), as well as compromised vasculature following CVD events, may contribute to this outcome.


Age at menopause; Cardiovascular disease; Pooled analysis; Premenopausal


Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center