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CLINICAL RESEARCH

Heart Disease Risk Determines Menopausal Age Rather Than the Reverse

Helen S. Kok, MD, PhD^_*,,, Kristel M. van Asselt, MD, PhD^_*,,, Yvonne T. van der Schouw, PhD^_*,_*, Ingeborg van der Tweel, PhD, Petra H.M. Peeters, MD, PhD^_*, Peter W.F. Wilson, MD, PhD^||, Peter L. Pearson, MD, PhD and Diederick E. Grobbee, MD, PhD^_*

^_* Julius Center for Health Sciences and Primary Care
Department of Reproductive Medicine
Department of Medical Genetics, University Medical Center
Center for Biostatistics, Utrecht University, Utrecht, the Netherlands
^|| The Framingham Heart Study, Boston-University School of Medicine, Boston, Massachusetts

Manuscript received April 25, 2005; revised manuscript received November 7, 2005, accepted December 21, 2005.

^_* Reprint requests and correspondence: Dr. Yvonne T. van der Schouw, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, HP nr STR 6.131, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands (Email: Y.T.vanderSchouw{at}umcutrecht.nl).

OBJECTIVES: The purpose of this study was to investigate whether a harmful cardiovascular risk profile accelerates menopause.

BACKGROUND: Women with an early menopause are at an increased risk of cardiovascular disease. Although increased cardiovascular risk has been proposed as consequence of menopause, the alternative hypothesis, that increased premenopausal cardiovascular risk promotes early menopause, needs to be examined.

METHODS: We used data from the Framingham Heart Study cohort. This study started in 1948 and has followed up participants biennially since then. Women who were premenopausal at study entry and who reached natural menopause after at least two examination rounds were included in the study (n = 695). Premenopausal age-independent levels of serum total cholesterol, relative weight, blood pressure, and Framingham risk score were determined, as well as premenopausal changes in cholesterol, body weight, and blood pressure.

RESULTS: A higher premenopausal serum total cholesterol level was statistically significantly associated with an earlier age at menopause, as were increases in total serum cholesterol, relative weight, and blood pressure in the premenopausal period. A decrease in total serum cholesterol during premenopause was statistically significantly associated with later age at menopause. Decreasing blood pressure was associated with a later menopausal age, but this association was not statistically significant. A decrease in relative weight was associated with a significant earlier age at menopause. Each 1% higher premenopausal Framingham risk score was associated with a decrease in menopausal age of 1.8 years (95% confidence interval –2.72 to –0.92).

CONCLUSIONS: The findings support the view that heart disease risk determines age at menopause. This offers a novel explanation for the inconsistent findings on cardiovascular disease rate and its relationship to menopausal age and effects of hormone replacement therapy.

Abbreviations and Acronyms   CI = confidence interval   HDL = high-density lipoprotein

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