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Age at Natural Menopause and Total Mortality and Mortality from Ischemic Heart Disease: The Adventist Health Study

https://doi.org/10.1016/S0895-4356(98)00170-XGet rights and content

Abstract

We studied the relationship between age at natural menopause and total mortality as well as mortality from ischemic heart disease in a cohort of 6182 California Seventh-Day Adventist women who reported a natural menopause. During follow-up from 1976 through 1988, there were 1831 deaths. A total of 308 deaths due to ischemic heart disease occurred in women who denied ischemic heart disease at start of follow-up. An early menopause was associated with increased total mortality (P value for linear trend <0.001) and ischemic heart disease mortality (P value for linear trend = 0.03). This relationship could not be explained by possible confounding variables. Our results support the hypothesis that an early natural menopause (35–40 years old) increases the risk of ischemic heart disease. There is, however, also some evidence of increased risk of ischemic heart disease in women with a very late menopause (>55 years), particularly in women who never have used postmenopausal estrogens.

Introduction

Women have a lower risk of ischemic heart disease than men. This difference in risk is particularly evident before menopause and the decade after the menopause. Postmenopausal hormone replacement therapy has rather consistently been associated with reduced risk of ischemic heart disease [1]. Whether age at natural menopause is a risk factor for ischemic heart disease, has, however, been disputed [2].

Recently, two studies 3, 4 have indicated that an early natural menopause may increase the risk of ischemic heart disease. In a Norwegian study, there were more than 2700 cases of fatal myocardial infarction during 29 years of follow-up, but information about possible confounders apart from those related to reproduction was not available [3]. In a Dutch study with 824 deaths, no distinction was made between ischemic heart disease and other cardiovascular deaths, and in the main analysis, between natural and surgical menopause. Also adjustments for dietary habits were not undertaken [4]. Both of these studies did, however, indicate that the effect of age at menopause is modified by attained age.

In 1989, Snowdon et al. [5] found in a 6-year follow-up of Californian Seventh-Day Adventists from 1976 thru 1982 that early natural menopause seems to be associated with increased coronary heart disease mortality. Although there were 242 fatal events of coronary heart disease, the association was not statistically significant. Snowdon and coworkers did not, however, adjust for dietary habits, and the analyses were restricted to women aged 55 and older. In light of the knowledge that has accumulated since the paper was published in 1989, we have reanalyzed the Adventist Health Study data, but with a substantially longer follow-up. Our hypothesis was that age at menopause was inversely related to ischemic heart disease mortality.

Section snippets

Materials and methods

In 1976, California Seventh-Day Adventists aged 25 years and older previously identified by a Census Questionnaire in 1974, were mailed a questionnaire (the Lifestyle Questionnaire) 5, 6. Included in this questionnaire were questions about whether the woman was postmenopausal (“Menstrual periods have completely stopped [or never had menstrual periods]”) and, if she were, why the periods stopped (one alternative being: “Natural change of life”). For our purpose, we identified 6182 women who were

Results

The mean age at menopause in this population was 49.2 years (standard deviation [SD] = 4.5). A total of 345 (5%) of the women reported very early (35–40 years) menopause, and a similar proportion (332 women, 5% of the total) reported very late (56–60 years) menopause.

Table 1 gives the associations between age at natural menopause and total mortality as well as deaths not caused by ischemic heart disease. A total of 1831 deaths were observed during 63,893 person-years. Thus, the total mortality

Discussion

The results from this 13-year follow-up of 6000 postmenopausal women indicate a relatively weak inverse relationship between age at natural menopause and total mortality. Comparing women with early menopause (35–40 years) with those who experience menopause when they were 52–55 years old, the former group has approximately 50% higher total mortality. A somewhat weaker relationship was found for mortality not caused by ischemic heart disease. The data are thus compatible with a hypothesis that

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