Certain reproductive factors may increase future CV risk

Women’s reproductive factors and incident cardiovascular disease in the UK Biobank

Literature - Peters SAE, and Woodward M. - Heart 2018; published online ahead of print

Introduction and Methods

Data on the association between reproductive factors, such as early menarche, early menopause, or a history of miscarriage, and the risk of CVD in women is conflicting [1,2]. In this analysis of the UK Biobank [3], the relationship between reproductive factors and the risk of incident CVD in later life was evaluated, using prospective data from 482,000 women and men.

The UK Biobank, a large prospective, population-based cohort study, recruited more than 500,000 women and men, aged 40-69 years at baseline, between 2006 and 2010. Reproductive factors were self-reported for this analysis and included age at menarche, number of live births, age at first birth, history and number of miscarriage(s) and stillbirth(s), history of, and age at hysterectomy and oophorectomy, menopausal status and, if menopausal, age at natural menopause, as well as number of children for men. The main study endpoints were the incidence of fatal or non-fatal myocardial infarction (MI) or stroke.

Main results

  • Women with early menarche (before the age of 12 years) had a higher risk of CVD compared with women with a later menarche (HR: 1.10; 95%CI: 1.01-1.30).
  • Women and men with children had a higher risk of coronary heart disease (CHD) compared with individuals without children (HR for women: 1.21; 95%CI: 1.05-1.40; HR for men: 1.13; 95%CI: 1.04-1.23).
  • For every year increase in age at first birth, the adjusted HRs were 0.97 (95%CI: 0.96-0.98) for CVD, 0.96 (95%CI: 0.95-0.97) for CHD, and 0.98 (95%CI: 0.97-0.99) for stroke, indicating an inverse relationship between this reproductive factor and CV risk.
  • A history of miscarriage was associated with a higher risk of CHD (HR: 1.14; 95%CI: 1.01-1.29), and a history of stillbirth was associated with a higher risk of CVD and stroke (HR for CVD: 1.22; 95%CI: 1.01-1.46; HR for stroke: 1.44; 95%CI: 1.12-1.85).
  • A history of oophorectomy was not associated with an increased risk of CVD, CHD or stroke, whereas a history of hysterectomy was associated with an increased risk of CVD (HR: 1.12; 95%CI: 1.03-1.22) and CHD (HR: 1.20; 95%CI: 1.07-1.34).
  • Women with an early age at natural menopause had a higher risk of CVD (HR: 1.44; 95%CI: 1.29-1.61), CHD (HR: 1.43; 1.22-1.67) and stroke (HR: 1.50; 95%CI: 1.28-1.75).


An analysis of the UK Biobank showed that several reproductive factors, including early menarche, a history of miscarriage, stillbirth, or hysterectomy, earlier age at first birth, or an early menopause, are associated with an increased risk of CVD in later life. More frequent CV screening of women with these factors might delay or prevent their onset of CVD.

Editorial comment

In her editorial article, Otto [4] briefly points at the fact that it is not clear whether the associations in Peters and Woodward’s work have a background of biological plausibility: ‘For example, the conventional hypothesis that hormonal changes at menopause are the cause of increased CVD risk might not be correct. As the authors note: It has also been suggested that it is not menopause that adversely affects cardiovascular risk but rather that cardiovascular risk factors determine the age at menopause, possibly through direct effects on the endocrine system or by inducing ischaemic damage in the ovaries.”


1. Atsma F, Bartelink ML, Grobbee DE, et al. Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis. Menopause 2006;13:265–79.

2. Canoy D, Beral V, Balkwill A, et al. Age at menarche and risks of coronary heart and other vascular diseases in a large UK cohort. Circulation 2015;131:237–44.

3. Sudlow C, Gallacher J, Allen N, et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med 2015;12:e1001779.

4. Otto CM. Heartbeat: cardiovascular disease risk and reproductive factors in women. Heart 2018;104(13):1045.

Find this article online at Heart

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