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Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis

Atsma, Femke PhD; Bartelink, Marie-Louise E. L. MD, PhD; Grobbee, Diederick E. MD, PhD; van der Schouw, Yvonne T. PhD

doi: 10.1097/01.gme.0000218683.97338.ea
Articles

Objective: Loss of ovarian function and subsequent deficiency of endogenous estrogens is suggested to enhance cardiovascular disease risk and related death after menopause. The aim was to obtain valid estimates of the cardiovascular disease risk associated with postmenopausal status and early menopause.

Design: A literature search of observational studies was performed using PubMed and EMBASE (1966 to May 1, 2004). Eighteen studies on postmenopausal status and age at menopause in relation to cardiovascular disease were selected. Six studies investigated menopausal status, nine studies investigated menopausal age, and three studied both. General variance-based methods were used to pool relative risk estimates and corresponding 95% confidence intervals. Stratification was performed for study design, type of menopause, outcome, and adjustment for age and smoking.

Results: The pooled relative risk estimate for postmenopausal versus premenopausal status and cardiovascular disease was 1.36 (95% CI, 1.15-1.60). In the stratified analysis, the pooled effect was 0.96 (95% CI, 0.77-1.21) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 2.62 (95% CI, 2.05-3.35). For early menopause and cardiovascular disease, with the menopausal age category containing 50 years as a reference, the pooled relative risk estimate was 1.25 (95% CI, 1.15-1.35). In the stratified analysis, the pooled effect was 1.38 (95% CI, 1.21-1.58) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 4.55 (95% CI, 2.56-8.01).

Conclusions: Overall, there was no convincing relationship between postmenopausal status and cardiovascular disease. However, there was a modest effect of early menopause on cardiovascular disease. The effect was more pronounced for women with an artificial menopause than for women with a natural menopause.

Results of 18 studies on postmenopausal status and age at menopause in relation to cardiovascular disease are summarized. Overall, there was no convincing relationship between postmenopausal status and cardiovascular disease, but there was a modest effect of early menopause on cardiovascular disease.

From the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.

Received January 18, 2005; revised and accepted June 20, 2005.

This work was supported by grants from The Netherlands Organisation for Health Research and Development.

Address correspondence to: Yvonne T. van der Schouw, PhD, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands, Room STR 6.131, PO Box 85500, 3508 GA Utrecht, The Netherlands. E-mail: Y.T.vanderSchouw@umcutrecht.nl.

© 2006 by The North American Menopause Society.