Urinary sex hormone excretions in premenopausal women and coronary heart disease risk: a nested case-referent study in the DOM-cohort.

The low incidence of coronary heart disease (CHD) in premenopausal women is partly ascribed to protection by endogenous estrogen production. As a consequence, we hypothesized that premenopausal women with low endogenous estrogen production or high androgen production might be at increased risk for CHD. We studied the relationship between urinary sex hormone excretions and CHD risk by means of a nested case-referent study within a cohort of premenopausal (ages 40-49 yrs) women (n = 11,284). This cohort was formed at a breast cancer screening project in 1982-1986 (The Diagnostisch Onderzoek Mammacarcinoom [DOM] Project). Baseline data included self-administered questionnaires and anthropometric measurements. At the time of screening the women were instructed to collect an overnight urine sample on day 22 of three separate cycles. These urine samples were stored at -20 degrees C. Up to June 1991, 45 subjects were admitted to local hospitals on diagnosis of CHD (29 with myocardial infarction, and 16 with angiographically confirmed coronary disease). Referents were sampled from the cohort, matched for age and year of screening in a 1:3 ratio. In a follow-up study, menopausal state of the subjects was assessed yearly by mailed questionnaires. Urinary excretions of estrone-glucuronide, pregnanediol-glucuronide, and testosterone-glucuronide adjusted by creatinine were similar for cases and referents. Cases had no earlier menopause than referents, although cases had more anovulatory cycles. The occurrence of CHD in middle-aged women is not preceded by a low premenopausal endogenous estrogen production or high androgen production. Anovulatory cycles appear more frequently in women who develop CHD many years later.