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 wom en is partly ascribed to protection by endogenous estrogen production. As a consequence, we hypothesized that premenopausal women with low e ndogenous estrogen production or high androgen production might be at increased risk for CHD. We studied the relationship between urinary se x hormone excretions and CHD risk by means of a nested case-referent s tudy within a cohort of premenopausal (ages 40-49 yrs) women (n = 11,2 84). This cohort was formed at a breast cancer screening project in 19 82-1986 (The Diagnostisch Onderzoek Mammacarcinoom [DOM] Project). Bas eline data included self administered;questionnaires and anthropometri c 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 coronar y disease). Referents were sampled from the cohort, matched for age an d year of screening in a 1:3 ratio. In a follow-up study, menopausal s tate of the subjects was assessed yearly by mailed questionnaires. Uri nary 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, althoug h cases had more anovulatory cycles. The occurrence of CHD in middle-a ged women is not preceded by a low premenopausal endogenous estrogen p roduction or high androgen production. Anovulatory cycles appear more frequently in women who develop CHD many years later. (C) 1997 Elsevie r Science Inc.