Hypoestrogenemia of hypothalamic origin and coronary artery disease in premenopausal women: a report from the NHLBI-sponsored WISE study
Key result
Hypothalamic hypoestrogenemia linked to ~7.4-fold higher odds of angiographic CAD in premenopausal women.
- OR 7.4
- 95% CI 1.7 to 33.3
- P=0.008
- n=95
Why the study?
Coronary artery disease in premenopausal women has a poor prognosis and may be linked to psychosocial stress-induced hypoestrogenemia of hypothalamic origin, but this association requires evaluation.
Key Points
- To assess whether hypoestrogenemia of hypothalamic origin is linked to angiographically confirmed coronary artery disease in premenopausal women.
- Evaluated 95 premenopausal women with coronary risk factors undergoing coronary angiography for suspected ischemia in the NHLBI-sponsored WISE study.
- Measured circulating reproductive hormone levels and assessed coronary artery disease using core laboratories.
- Women with angiographic CAD (n = 13) showed significantly lower estradiol, bioavailable estradiol, and FSH levels compared to those without CAD (n = 82; all p < 0.05).
- Hypothalamic hypoestrogenemia occurred in 69% (9/13) of women with CAD versus 29% (24/82) without CAD (p = 0.01), remaining an independent predictor of CAD in multivariate analysis (OR 7.4, 95% CI 1.7–33.3, p = 0.008).
- Use of anxiolytic/sedative/hypnotic medications (OR 4.6, 95% CI 1.3–15.7, p = 0.02) and antidepressants (OR 0.10, 95% CI 0.01–0.92, p = 0.04) independently predicted hypothalamic hypoestrogenemia.
Study Design
Type
Cross-Sectional (n=95)
PICO
P
Population
95 premenopausal women with coronary risk factors undergoing coronary angiography for evaluation of suspected ischemia.
E
Exposure / Comparator
Hypoestrogenemia of hypothalamic origin vs Without hypoestrogenemia of hypothalamic origin
O
Primary Outcome
Angiographic coronary artery disease (CAD) — OR 7.4 (1.7 to 33.3), p=0.008
Main Result
Odds Ratio: 7.4 (95% CI 1.7–33.3)
p-value: p=0.008
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Although coronary artery disease is the leading killer of premenopausal women, taking even more lives than breast cancer does, most studies have focused on heart disease in older women. Our findings demonstrate for the first time that young women with low blood estrogen levels have a significantly greater prevalence of coronary artery disease.”
Implication
Observes hypothalamic hypoestrogenemia correlates with coronary artery disease in premenopausal women, suggesting ovarian cycle disruption influences arterial health.
Abstract
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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Cite This Study
Merz et al. (2003) conducted a cross-sectional in Coronary artery disease (n=95). Hypoestrogenemia of hypothalamic origin vs. Without hypoestrogenemia of hypothalamic origin was evaluated on Angiographic coronary artery disease (CAD) (OR 7.4, 95% CI 1.7 to 33.3, p=0.008). Among premenopausal women undergoing coronary angiography, hypoestrogenemia of hypothalamic origin was a powerful independent predictor of angiographic CAD (OR 7.4; 95% CI 1.7-33.3; p=0.008).