We sought to evaluate hypoestrogenemia of hypothalamic origin and its association
with angiographic coronary artery disease (CAD) in premenopausal women.
Coronary artery disease in premenopausal women appears to have a particularly poor
prognosis. Primate animal data suggest that premenopausal CAD is strongly determined
by psychosocial stress-induced central disruption of ovulatory cycling and resulting
hypoestrogenemia.
We assessed reproductive hormone blood levels and angiographic CAD using core laboratories
in 95 premenopausal women with coronary risk factors who were enrolled in the National
Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation and
were undergoing coronary angiography for evaluation for suspected ischemia.
Premenopausal women with angiographic CAD (n = 13) had significantly lower estradiol,
bioavailable estradiol, and follicle-stimulating hormone (FSH) (all p < 0.05) than
women without angiographic CAD (n = 82), even after controlling for age. Hypoestrogenemia
of hypothalamic origin, defined as estradiol <184 pmol/l (50 pg/ml), FSH <10 IU/l,
and luteinizing hormone <10 IU/l, was significantly more prevalent among the women
with CAD than those without CAD (9/13 [69%] vs. 24/82 [29%], respectively, p = 0.01).
Hypoestrogenemia of hypothalamic origin was the most powerful predictor of angiographic
CAD in a multivariate model (odds ratio [OR] 7.4 [confidence interval (CI) 1.7 to
33.3], p = 0.008). Anxiolytic/sedative/hypnotic and antidepressant medication use
were independent predictors of hypoestrogenemia of hypothalamic origin in a multivariate
model (OR 4.6 [CI 1.3 to 15.7], p = 0.02, OR 0.10 [CI 0.01 to 0.92], p = 0.04, respectively).
Among premenopausal women undergoing coronary angiography for suspected myocardial
ischemia, disruption of ovulatory cycling characterized by hypoestrogenemia of hypothalamic
origin appears to be associated with angiographic CAD.