5th European Congress on Menopause

Lorraine Dennerstein, AO, MBBS, PhD, FRANZCP, DPM


July 19, 2000

In This Article

Cardiovascular Disease

A number of presentations and 2 lively debates focused on the continuing controversy about the long-term effects of menopause on health and the role of hormone replacement therapy (HRT) in preventing or treating the postulated consequences of loss of ovarian function. Major causes of morbidity and mortality in women include cardiovascular disease (CVD), dementia, and osteoporosis. These have all been linked to menopausal hormonal changes, and large clinical trials of various forms of HRT are currently under way.

Cardiovascular disease remains the most common cause of death among both men and women. There is a well-documented gender difference in CVD, based on epidemiologic data, with men having an earlier incidence of clinically significant atherosclerosis. However, the prevalence of CVD increases more dramatically in older postmenopausal women, potentially attributable to the decline in sex steroids. Observational studies suggest a protective effect of ovarian steroids, with an inverse relationship between menopausal age and risk of CVD and an increased risk of CVD in women with early surgically induced menopause -- an effect not evident in oophorectomized women who have received estrogen replacement.

Long-term observational cohort studies of aging populations have found that ever users of HRT have a reduced risk of CVD of around 50% compared with never users. These observational data were limited by a "healthy user" selection bias in the older North American cohorts. Intervention trials of HRT have found diverse beneficial effects of HRT, including improvement in low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C) and fibrinogen. However, the Heart and Estrogen/progestin Replacement Study (HERS), a secondary-prevention, double-blind, randomized trial, conducted in women with established coronary artery disease, found an initial increase in risk of CVD deaths associated with continuous combined HRT in the first year of the study and a slow reduction in risk over 4-5 years.

A 4-fold increased risk of venous thromboembolism during HRT was confirmed in a Norwegian double-blind trial that enrolled 140 women between 1996 and 1998. Dr. E. Hoibraaten and colleagues,[1] from the Department of Hematology, Ullevaal University Hospital, Oslo, Norway, randomized women with a previous history of venous thromboembolism to either placebo or 2 mg estradiol plus 1 mg norethisterone acetate daily. Eight women in the HRT group and 1 woman in the placebo group experienced thromboembolism. The events on HRT occurred within 220 days after entry into the study, while the placebo-related event occurred at day 413. The study was terminated early.

The general conclusion from the debates and presentations was that in view of the results from the HERS study, and more recently from the Women's Health Initiative, we must await the results of the very large randomized clinical trials now in progress in the United States and Europe. Women should be warned of the increased risk of venous thromboembolism, and those with a past history of this disorder should consider other therapeutic approaches.


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