Hypoestrogenemia of hypothalamic origin and coronary artery disease in premenopausal women: a report from the NHLBI-sponsored WISE study.
OBJECTIVE
We sought to evaluate hypoestrogenemia of hypothalamic origin and its association with angiographic coronary artery disease (CAD) in premenopausal women.


BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Bairey Merz
C Noel
CN
Division of Cardiology, Department of Medicine, Cedars-Sinai Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. merz@cshs.org
Johnson
B Delia
BD
Sharaf
Barry L
BL
Bittner
Vera
V
Berga
Sarah L
SL
Braunstein
Glenn D
GD
Hodgson
T Keta
TK
Matthews
Karen A
KA
Pepine
Carl J
CJ
Reis
Steven E
SE
Reichek
Nathaniel
N
Rogers
William J
WJ
Pohost
Gerald M
GM
Kelsey
Sheryl F
SF
Sopko
George
G
D000328:Adult; D000367:Age Factors; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000209:etiology*; D004967:Estrogens / Q000097:blood*; D005260:Female; D006801:Humans; D007027:Hypothalamic Diseases / Q000097:blood* / Q000150:complications* / Q000000981:diagnostic imaging; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood* / Q000000981:diagnostic imaging / Q000209:etiology*; D009316:National Institutes of Health (U.S.); D011237:Predictive Value of Tests; D017697:Premenopause / Q000097:blood*; D012307:Risk Factors; D012737:Sex Factors; D014481:United States
D004967:Estrogens