More Pregnancies, Longer Life?

The Association of Reproductive History With All-Cause and Cardiovascular Mortality in Older Women: The Rancho Bernardo Study

Jacobs MB, Kritz-Silverstein D, Wingard DL, Barrett-Connor E
Fertil Steril. 2012;97:118-124

Background

Cardiovascular and cerebrovascular diseases are among the 3 most common causes of mortality in women.^[1] Numerous risk factors for both conditions are known. Hypertension, diabetes, obesity, dyslipidemia, smoking, and sedentary lifestyle are the most widely accepted risk factors. Hormone use (the oral contraceptive pill or hormone replacement therapy) also is associated with cardiovascular and cerebrovascular disease. These conditions are relatively rare in women of reproductive age, but after menopause the incidence catches up to that in men. It is therefore presumed that ovarian steroids have a protective effect. In fact, estrogen has favorable effects on lipid levels and vascular function and mediates vasodilating effects.

During the reproductive years, a woman can be exposed to hormonal effects other than those associated with regular ovarian activity. Some women use synthetic estrogen/progestin preparations for birth control. Pregnancy is associated with prolonged periods of high dose estrogen/progesterone exposure. Women who need help to conceive may receive multiple cycles of stimulation that alter their hormone production. It is therefore logical to assess the effect of reproductive history on subsequent risk for cardio-vascular and cerebrovascular disease.

Study Summary

This study searched for an association between gravidity/parity and overall mortality from cardiovascular disease (CVD), including coronary heart disease (CHD) and non-coronary heart CVD, in 1294 middle-class women (the Rancho Bernardo cohort). Clinic visits, questionnaires, physical examinations, and laboratory testing were used for data collection. Gravidity/parity was used to divide the cohort into 5 groups (0, 1, 2, 3, 4 or more). The average age of the participants was 70.6 years; both the median gravidity (number of pregnancies) and the median parity (number of live births) were 2. The average age at menopause was 46.5 years, and the average duration of menopause was 23.7 years. During follow-up, 707 of the 1294 women died, with 46.5% of the deaths attributed to CVD (20.5% to CHD and 26% to non-CHD CVD).

Women with higher gravidity/parity were older at menopause, spent fewer years in menopause, had slightly higher body mass index, were less likely to be current users of estrogen therapy, and were more likely to be receiving diabetes medication.

Multivariate analysis controlling for age and other known risk factors found that women with 4 or more pregnancies had lower risks for overall CVD mortality (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.38-0.96) and non-CHD CVD mortality (HR, 0.48; 95% CI, 0.26-0.90) in comparison with nulligravid women. Trend analysis showed reduced risk for overall CVD mortality and non-CHD CVD mortality with increased gravidity.

Viewpoint

Sex steroids affect the cardiovascular system. Estrogen has numerous beneficial as well as some adverse effects related to the risk for CVD and vascular disease. Pregnancy provides a unique hormonal milieu that may have long-term effects on cardiovascular health. Any association has to be studied in relation to other known risk factors.

Several studies have tried to explore the association between gravidity or parity and CVD mortality. Ness and colleagues^[2] reported a slightly increased risk for CVD and CHD among women with 6 or more pregnancies. Palmer and colleagues^[3] found an increased risk for myocardial infarction in women with 5 or more deliveries. This cohort study had different observations. Women with high gravidity (4 or more pregnancies) had lower risk for overall CVD and non-CHD CVD mortality.

Many potential explanations can be offered for the opposing findings. The patient populations were likely dissimilar, the study endpoints (morbidity vs mortality) were not uniform, and the analytic methods differed among the studies. To find an association between reproductive history and CVD mortality, the investigators need to control for other risk factors.

The reasons why people have different family sizes also must be considered. Socioeconomic status influences this decision and CVD risk. Family size and the ability to conceive may be important factors. Women with fewer children may have had infertility issues; some of the conditions leading to infertility are known to be CVD risk factors, such as polycystic ovary syndrome. Women with more children might have had fewer problems with conception, and this could correlate with better general health. Pregnancy could benefit such women through altered hormonal balance that potentially can contribute to risk reduction later in life.

These findings underscore the importance of further study of the effect of sex steroids on cardiovascular health and may help us identify women who are at a higher risk for CVD morbidity and mortality in the later decades of life.

Abstract

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