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

Abstract

D e p a r t m e n t o f In t e r n a l M e d ic in e , A c a d e m ic H o s p it a l U t r e c h t , D e p a r t m e n t o f Epid e m io l o g y a n d H e a l t h C a r e , U n iv e r sit y o f U t r e c h t , a n d D e p a r t m e n t o f E n d o c r in o l o g y , A c a d e m ic H o s p it a l U t r e c h t , 3508 GA U t r e c h t , T h e N e t h e r l a n d s ABSTRACT» 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°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, j c lin epid em io l 5013:275-281, 1997-© 1997 Elsevier Science Inc.

Does accelerated reproductive aging underlie premenopausal risk for cardiovascular disease?

“…Other previous studies examining CVD in pre-menopausal women suggest collectively that disruptions in ovarian function are related to an increase in cardiovascular risk; however, such disruptions have been marked by indicators such as anovulation, lower estradiol, and menstrual cycle irregularity and have not included assessments of ovarian reserve in particular. [49][50][51][52][53][54][55] In the current study, the proportion of White women was significantly lower in the low (23%) compared to high (36%) AMH tertile and the proportion of Latina women was significantly greater in the low (29%) compared to mid (22%) and high (19%) AMH tertiles, suggesting there may be a relation between race/ethnicity and AMH. Although most previous studies have included samples comprised of predominately White women, one study comparing AMH declines across race/ethnic groups reported that the average decline in AMH was greater among African-American and Latina women than in White women.…”

Reproducibility over time of measurements of androgens, estrogens and hydroxy estrogens in urine samples from post-menopausal women

“…First-morning voids or overnight collections can be obtained more easily, but may decrease somewhat the reliability of measurements. Most of the studies published on hormone measurements in overnight urine samples or first morning voids use creatinine measurements to adjust for dilution errors [32,33]. Some papers have questioned whether such creatinine adjustments will actually reduce, or rather increase, measurement errors [34][35][36].…”

Polycystic Ovary Syndrome and Cardiovascular Disease

“…The CVD is very low in premenopausal women and there was no evidence about correlation with increased androgens in circulation or urinary excretion with subsequently developed CVD (Gorgels, v d Graaf et al 1997). Furthermore, prospective researches of postmenopausal populations, circulating androgen levels did not correlate with cardiovascular events (Price, Lee et al 1997).…”

“…This may also underlie the association between hyperandrogenemia and impaired vascular function and reported in some studies involving PCOS subjects (Wu and von Eckardstein 2003). Nevertheless, even though insulin resistance per se has been associated with endothelial dysfunction and increased cardiovascular risk, there is no stable proof that hyperandrogenemia is a risk factor for cardiovascular disease in women (Gorgels, v d Graaf et al 1997).…”