Women with coronary heart disease (CHD) who were randomly assigned to postmenopausal hormone therapy had a 35% lower risk for developing diabetes mellitus than those assigned to placebo, according to an analysis of data from the Heart and Estrogen/progestin Replacement Study (HERS).
Observational studies in the past have found that postmenopausal women taking hormone therapy have lower fasting glucose or hemoglobin A1c levels than women not taking hormones, while only a few of these studies have found a corresponding reduction in incidence of diabetes. To date, there has been no prospective, controlled trial evaluating the effect of postmenopausal hormone therapy on the development of diabetes. To address these unresolved issues, investigators analysed data from HERS, a randomized, double-blind, placebo-controlled trial of 0.625mg conjugated estrogen plus 2.5mg medroxyprogesterone acetate for the prevention of coronary events in postmenopausal women with established CHD.
In the 2,763 women enrolled, fasting serum glucose was measured at baseline, at one year and at the end of trial visit; participants were followed for an average of 4.1 years. Self-report of diabetes or disease complication, initiation of therapy with diabetes medication, or a fasting glucose level of 6.9mmol/L or greater was taken as an indication of diabetes, whereas women with fasting glucose levels between 6.0 and 6.9mmol/L were classified as having impaired fasting glucose.
Analyses found that women with and without diabetes at baseline who were assigned to placebo had significantly worse fasting glucose values compared with women in the hormone therapy group, who experienced no significant change in glucose measurements. A similar pattern was seen among women with impaired fasting glucose. Furthermore, the cumulative incidence of diabetes was 6.2% for women in the hormone therapy group compared with 9.5% for those assigned to placebo (p=0.006). This 35% lower risk for diabetes was primarily attributed to the fact that women in the hormone group maintained lower fasting glucose levels than women in the placebo group. Other characteristics commonly associated with diabetes, such as body mass index, hypertension, dyslipidemia and smoking, were not found to be responsible for the treatment effect.
In the present study, for every 30 women treated for about four years, hormone therapy was found to prevent one case of diabetes. However, all must now be well aware of the increased risks for venous thromboembolic events, stroke and breast cancer with long-term hormone therapy use. Therefore, although hormone therapy is not a viable approach to diabetes prevention in women with heart disease, these data allude to the important metabolic benefits of hormone therapy which warrant further investigation.
- Kanaya AM, Herrington D, Vittinghoff E, et al. Glycemic effects of postmenopausal hormone therapy: The Heart and Estrogen/progestin Replacement Study. Ann Intern Med 2003;138:1-9.