Skip to content

A recent manuscript describes a nested case–control study of incident coronary heart disease (CHD) events during the first 4 years of follow-up in the Women’s Health Initiative hormone therapy trials (estrogen plus progestin therapy, EPT and estrogen therapy, ET) [1]. There were 359 incident cases of CHD during follow-up. After the exclusion of women with cardiovascular disease ([i]n[/i] = 90), diabetes, or hypertension at baseline ([i]n[/i] = 103), 166 CHD cases were matched to 524 controls on age, randomization date, and hysterectomy status. Metabolic syndrome (MetS) classification required at least three of five Adult Treatment Panel III criteria. The main outcome measure was the odds for CHD with hormone therapy use versus placebo by MetS status. MetS modified the risk of CHD events with hormone therapy. In the pooled analysis, risk was increased with hormone therapy versus placebo in women with MetS (odds ratio (OR) 2.26; 95% confidence interval (CI) 1.26–4.07), whereas women without MetS were not found to have an increased risk for a CHD event with hormone therapy (OR 0.97; 95% CI 0.58–1.61; [i]p[/i] for interaction = 0.03). Results of the EPT and ET trials, when examined separately, were similar. The constellation of MetS variables was more predictive of risk from hormone therapy than MetS components assessed individually. When women with diabetes or hypertension were included in the analysis, statistically significant effect modification was not detected. In conclusion, MetS at baseline in women without prior cardiovascular disease, diabetes, or hypertension at baseline identifies women who are more likely to have had adverse coronary outcomes on hormone therapy. CHD risk stratification is recommended before initiating hormone therapy.


  • Amos Pines
    Department of Medicine T, Ichilov Hospital, Tel-Aviv, Israel


  1. Wild RA, Wu C, Curb JD, et al. Coronary heart disease events in the Womens Health Initiative hormone trials: effect modification by metabolic syndrome: A nested case-control study within the Womens Health Initiative randomized clinical trials. Menopause 2012 Oct 25. Epub ahead of print.
  2. Mottillo S, Filion KB, Genest J, et al. The metabolic syndrome and cardiovascular risk: a systematic review and meta-analysis. J Am Coll Cardiol 2010;56:111332.
  3. Rezaianzadeh A, Namayandeh SM, Sadr SM. National Cholesterol Education Program Adult Treatment Panel III versus International Diabetic Federation definition of Metabolic Syndrome, which one is associated with diabetes mellitus and coronary artery disease? Int J Prev Med 2012;3:552-8.
  4. Hunt KJ, Resendez RG, Williams K, Haffner SM, Stern MP. National Cholesterol Education Program versus World Health Organization metabolic syndrome in relation to all-cause and cardiovascular mortality in the San Antonio Heart Study. Circulation 2004;110:125157.
  5. Tenenbaum A, Fisman EZ. ‘The metabolic syndrome… is dead: these reports are an exaggeration. Cardiovasc Diabetol 2011;10:11.
International Menopause Society

Install International Menopause Society - DEV

Install this application on your home screen for quick and easy access when you’re on the go.

Just tap then “Add to Home Screen”