CLINICAL STUDY: ATHEROSCLEROSIS
Hypoestrogenemia of hypothalamic origin and coronary artery disease in premenopausal women: a report from the NHLBI-sponsored WISE study
C. Noel Bairey Merz, MD, FACC*,*,
B. Delia Johnson, PhD ,
Barry L. Sharaf, MD, FACC ,
Vera Bittner, MD, FACC ,
Sarah L. Berga, MD||,
Glenn D. Braunstein, MD*,
T. Keta Hodgson, RN*,
Karen A. Matthews, PhD,
Carl J. Pepine, MD, FACC¶,
Steven E. Reis, MD, FACC#,
Nathaniel Reichek, MD, FACC**,
William J. Rogers, MD, FACC,
Gerald M. Pohost, MD, FACC,
Sheryl F. Kelsey, PhD,
George Sopko, MD WISE Study Group
* Division of Cardiology, Department of Medicine, Cedars-Sinai Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Division of Cardiology, Rhode Island Hospital, Providence, Rhode Island, USA
Division of Cardiology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
|| Division of Reproductive Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
¶ Division of Cardiology, Department of Medicine, University of Florida, Gainesville, Florida, USA
# Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
** Division of Cardiology, Department of Medicine, Allegheny University of the Health Sciences, Pittsburgh, Pennsylvania, USA
National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, USA
Manuscript received April 25, 2002;
revised manuscript received September 23, 2002,
accepted October 10, 2002.
* Reprint requests and correspondence: Dr. C. Noel Bairey Merz, c/o WISE Coordinating Center, University of Pittsburgh, 127 Parran Hall, Graduate School of Public Health, 130 DeSoto Street, Pittsburgh, Pennsylvania 15261, USA.
merz{at}cshs.org
OBJECTIVES: 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.
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Abbreviations and Acronyms
| | ATP | | adenosine triphosphate | | CAD | | coronary artery disease | | CRH | | corticotrophin-releasing hormone | | FSH | | follicle stimulating hormone | | LH | | luteinizing hormone | | NHLBI | | National Heart, Lung, and Blood Institute | | WISE | | Women’s Ischemia Syndrome Evaluation |
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