Estrogen protective against heart disease in premenopausal women

February 04, 2003

Tue, 04 Feb 2003 22:00:00

Los Angeles, CA - Estrogen deficiency due to central disruption of ovarian function may be a risk factor for heart disease in premenopausal women, a new study suggests.

The findings add yet another piece of information to the already very complicated area of estrogen and heart disease, suggesting that estrogen is indeed protective in premenopausal women.

These latest results come from a new analysis of the Women's Ischemia Syndrome Evaluation (WISE) study, published in the February 5 issue of the Journal of the American College of Cardiology. The study, an NHLBI study designed to improve the diagnosis of heart disease in women, recruited women undergoing coronary angiography for suspected ischemia.

The link between low estrogen levels and heart disease was found serendipitously. On first receiving reports that a surprising number of women taking part in the WISE study had low levels of estrogen, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), the researchers were concerned that these women could have pituitary tumors.

When this was ruled out, they further investigated these women and found that among the 95 premenopausal women who were being tested for heart disease, 9 of the 13 women (69%) actually found to have coronary artery disease had low estrogen levels linked to abnormal functioning of their hypothalamus glands. By contrast, this type of low estrogen level occurred in only 24 of 82 (29%) of the women who were found not to have coronary artery disease.

Stress related?

Use of anxiolytic/sedative/hypnotic medication was also found to be an independent predictor of hypoestrogenemia of hypothalamic origin, suggestive of a behavioral link. "This suggests that stress may play a role, and future work is needed to explore the causes and effects of stress in the lives of these women with early heart disease," the researchers note.

In the paper, the authors, led by Dr Noel Bairey Merz (Cedars-Sinai Medical Center, Los Angeles) note that it has only recently been realized that the higher gender-specific coronary mortality observed in women is due to increased death rates among relatively young women. They say that because much CAD prevalence is attributable to older, postmenopausal women, recent interest has focused on this group, and evaluation of CAD in premenopausal women has been overlooked, despite its being the leading killer of women in this age group, outpacing even breast cancer. "Therefore, if this hormone link is confirmed, it could have important public health implications," Bairey Merz adds.

"Our findings demonstrate, for the first time, that hypoestrogenemia of hypothalamic origin is associated with CAD in premenopausal women undergoing coronary angiography for suspected myocardial ischemia. These results support the concept that female protection is lost when ovarian function is disrupted," they comment. They add that the findings are consistent with animal studies, which have shown a link between premenopausal atherosclerosis and central disruption of ovulatory cycling in primates.

Could explain gender differences in heart disease mortality

The current clinical results provide a potential mechanism to explain the greater CAD mortality experienced in relatively younger women when compared with age-matched men with CAD and suggest the possibility of inherent gender-specific pathophysiologic differences, the researchers say.

It has previously been shown that hypoestrogenemia in females is accompanied by coronary artery dysfunction, characterized by a diminution of normal vasodilation in response to a stressor, they note. These results document that premenopausal women with CAD may have hypoestrogenemia and therefore may have more adverse coronary arterial dysfunction, they add.

Bairey Merz said: "There are biologically plausible reasons behind the gender differences in coronary disease. If we can further understand those differences we can do better at treating women and men."

Diabetes also linked to low estrogen levels

The current study also shows a strong independent association between diabetes and hypoestrogenemia of hypothalamic origin. These findings are consistent with previous epidemiologic data, which demonstrate that diabetic premenopausal women have more frequent menstrual irregularities, lower blood estrogen levels, and higher androgen levels than nondiabetic women, factors that probably contribute to the lower fertility rates observed in diabetic premenopausal women.

"Our finding of a diabetes-related estrogen deficiency, if validated in a prospective study, may provide an explanation for the relatively greater coronary risk that diabetes conveys for women than men, which has been observed repeatedly in previous studies, and which remains unexplained," the authors say.

They caution that although the statistical correlation between the low estrogen condition and CAD was very strong, it is still considered a preliminary finding, as the sample size was low and this was not a prospective study. "There are a lot of things that still need to be answered; but these preliminary data suggest that this could be a very important risk factor," Bairey Merz said.

Commenting on the study, Dr Robert Vogel (University of Maryland Hospital) said: "The most interesting observation in this study is that it does tend to suggest that estrogen is quite beneficial before menopause, which of course is the exact opposite of what many trials have shown after menopause."

Related link

[HeartWire > News; Jul 25, 2000]


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