Issue: November 2010
November 01, 2010
2 min read

HT increased CHD risk in women with metabolic syndrome

Issue: November 2010
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NAMS Annual Meeting

CHICAGO — A new study found that women with metabolic syndrome who use hormone therapy are also at increased risk for coronary heart disease; however, the same heart disease risk does not appear to be present in HT users without metabolic syndrome.

The presence or absence of metabolic syndrome at baseline in the Women’s Health Initiative (WHI) was an “effect modifier,” Robert A. Wild, MD, PhD, said of his study that assessed CHD risk based on baseline metabolic syndrome in the WHI estrogen plus progestin and estrogen alone clinical trials for HT users.

Wild and colleagues studies women with incident CHD, defined as nonfatal myocardial infarction or fatal CHD, during the WHI clinical trials (n=359) as compared with 817 matched control women. Metabolic syndrome was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria, which is at least three of the five following risk factors: increased waist circumference; high blood pressure; abnormal glucose tolerance; decreased HDL; and elevated triglycerides.

When the researchers pooled results of the two WHI HT trials, the found that the odds ratio for CHD in the overall cohort greater with the presence of baseline metabolic syndrome (OR=1.72; 95% CI, 1.20-2.47), comparing HT vs. placebo. They found no increased risk if metabolic syndrome was absent at baseline (OR=0.98; 95% CI, 0.66-1.48).

The results for the two trials analyzed separately were as follows:

  • Estrogen plus progestin trial: metabolic syndrome present (OR=1.73; 95% CI, 1.06-2.82); metabolic syndrome absent (OR=1.20; 95% CI, 0.71-2.03).
  • Estrogen alone trial: metabolic syndrome present (OR=1.62; 95% CI, 0.94-2.80); metabolic syndrome absent (OR=0.72; 95% CI, 0.37-1.41).

The relationship between metabolic syndrome and CHD risk was not confounded by age, according to the researchers.

This finding may inform clinical decision making, they concluded.

“Baseline CHD risk assessment may be helpful to identify women at increased risk for a CHD event on HT,” Wild said. “Checking for metabolic syndrome is feasible and accessible for most clinicians.” – by Katie Kalvaitis


This intriguing analysis by Wild et al adds another layer of complexity to the growing body of work highlighting that the relationships between HT and CHD risk vary among different populations of women. The findings of this study support what one might intuitively expect — that HT was associated with increased CHD risk among women with elevated baseline CHD risk as assessed by presence of metabolic syndrome, but not among those with metabolic syndrome.
This study resonates with previous studies reporting that the CHD risk associated with postmenopausal HT is lower among women at lower baseline CHD risk, such as younger women and women closer to menopause. It would be premature to apply these findings in clinical practice, but these findings will hopefully spark further investigation.
These data provide another piece of evidence that a ‘one size fits all’ approach should not be applied to the findings of the WHI HT clinical trials.

Emily Szmuilowicz, MD

Endocrine Today Editorial Board member

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