Recently, there has been a realization that premenopausal women tend to have higher rates of coronary death than men. This occurs because women younger than 50 years have more than twice the hospital mortality rate for myocardial infarction when compared with men in the same age group. Despite coronary artery disease (CAD) being the leading killer in premenopausal women, outpacing even breast cancer, this issue has been overlooked when studying CAD in women. Studies in primates have found that premenopausal CAD is strongly determined by central disruption of the menstrual cycle that results in hypoestrogenemia. Bairey Merz and colleagues evaluated the effect of hypoestrogenemia of hypothalamic origin and its association with CAD in premenopausal women.

The study was part of the Women's Ischemia Syndrome Evaluation study that is sponsored by the National Heart, Lung, and Blood Institute. The study was designed to improve diagnostic testing and understanding of ischemic heart disease in women. The participants were women who were undergoing coronary angiography for suspected ischemia. Baseline data collection included physical evaluation, an assessment of coronary risk factors, and lipoprotein measurements. Reproductive hormone assays were performed when the patient entered the study, and a reproductive algorithm established premenopausal status and menstrual phase. Premenopausal status was defined as no current use of hormones, age less than 55 years, follicle-stimulating hormone (FSH) levels less than 15 mIU per mL (15 IU per L) and luteinizing hormone level greater than FSH level, with no history of bilateral oophorectomy. Chronic environmental stress was evaluated by a single question that had a five-point response. Coronary angiographic data also were recorded.

Women with angiography-proven CAD had significantly lower estradiol, bioavailable estradiol, estrone, and FSH levels when compared with women who did not have CAD. Hypothalamic-induced hypoestrogenemia was significantly more common in women with CAD than in patients without this disease. Hypoestrogenemia of hypothalamic origin was the most powerful predictor of CAD. The use of anxiolytic, sedative/hypnotic, or antidepressant medications was independent of hypoestrogenemia of hypothalamic origin.

The authors conclude that hypothalamic-induced hypoestrogenemia appears to be associated with angiographic CAD. In addition, the use of anxiolytic, sedative/hypnotic, or antidepressant medications is a risk factor for developing hypoestrogenemia, which suggests a biobehavioral link. The central disruption of ovarian function may be a risk factor for CAD in premenopausal women.