Alka M. Kanaya, MD; David Herrington, MD, MHS; Eric Vittinghoff, PhD; Feng Lin, MS; Deborah Grady, MD, MPH; Vera Bittner, MD, MSPH; Jane A. Cauley, DrPH; Elizabeth Barrett-Connor, MD
Acknowledgments: The authors thank members of the HERS Coordinating Center and the Executive Committee for their review and recommended revisions. They also thank Dr. Ira D. Goldfine for recommended revisions.
Grant Support: In part by the Department of Health and Human Services (Faculty Development in General Internal Medicine grant 1D08PE50109-01). The Heart and Estrogen/progestin Replacement Study is funded by Wyeth-Ayerst Research.
Potential Financial Conflicts of Interest:Consultancies: J.A. Cauley; Honoraria: D. Herrington, J.A. Cauley; Grants Received: D. Herrington, D. Grady, V. Bittner, J.A. Cauley, E. Barrett-Connor; Grants Pending: J.A. Cauley; Other: E. Vittinghoff, F. Lin.
Requests for Single Reprints: Alka M. Kanaya, MD, Division of General Internal Medicine, University of California, San Francisco, 1701 Divisadero Street, Suite 536, San Francisco, CA 94143-1732; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Kanaya: Division of General Internal Medicine, University of California, San Francisco, 1701 Divisadero Street, Suite 536, San Francisco, CA 94143-1732.
Dr. Herrington: Wake Forest University School of Medicine, One Medical Center Boulevard, Winston-Salem, NC 27157-1066.
Drs. Vittinghoff and Grady and Ms. Lin: Prevention Sciences Group, 74 New Montgomery Street, Suite 600, San Francisco, CA 94105.
Dr. Bittner: University of Alabama at Birmingham, UAB StationLHRB 310, Birmingham, AL 35294.
Dr. Cauley: University of Pittsburgh, 130 DeSoto Street, A524, Pittsburgh, PA 15261.
Dr. Barrett-Connor: Department of Family and Preventive Medicine, University of California, San Diego, 9500 Gilman Drive, Stein Clinical Research Building, La Jolla, CA 92093-0607.
Author Contributions Conception and design: A.M. Kanaya, D. Grady, E. Barrett-Connor.
Analysis and interpretation of the data: A.M. Kanaya, D. Herrington, E. Vittinghoff, V. Bittner.
Drafting of the article: A.M. Kanaya, E. Vittinghoff.
Critical revision of the article for important intellectual content: A.M. Kanaya, D. Herrington, E. Vittinghoff, D. Grady, V. Bittner, J.A. Cauley, E. Barrett-Connor.
Final approval of the article: A.M. Kanaya, D. Herrington, E. Vittinghoff, F. Lin, D. Grady, V. Bittner, J.A. Cauley, E. Barrett-Connor.
Provision of study materials or patients: D. Herrington, F. Lin, D. Grady, J.A. Cauley, E. Barrett-Connor.
Statistical expertise: E. Vittinghoff.
Obtaining of funding: A.M. Kanaya, D. Grady, E. Barrett-Connor.
Administrative, technical, or logistic support: A.M. Kanaya, D. Grady.
Collection and assembly of data: A.M. Kanaya, D. Grady, J.A. Cauley, E. Barrett-Connor.
Randomized trials of postmenopausal hormone therapy have found differing effects on fasting glucose levels. No trial has evaluated the effect of hormone therapy on diabetes incidence.
To evaluate the effect of hormone therapy on fasting glucose level and incident diabetes.
Randomized, double-blind, placebo-controlled trial.
20 U.S. clinical centers.
2763 postmenopausal women with coronary heart disease who were followed for 4.1 years. At baseline, 734 women had diabetes, 218 women had impaired fasting glucose, and 1811 women were normoglycemic; the 2029 women without diabetes were followed for incident diabetes.
0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate daily, or placebo.
Fasting glucose level was measured at baseline, at year 1, and at the end of the trial. Incident diabetes was defined by self-report of diabetes or disease complication, fasting glucose level of 6.9 mmol/L or greater ( 126 mg/dL), or initiation of therapy with diabetes medication.
Fasting glucose levels increased significantly among women assigned to placebo but did not change among women receiving hormone therapy. The incidence of diabetes was 6.2% in the hormone therapy group and 9.5% in the placebo group (relative hazard, 0.65 [95% CI, 0.48 to 0.89]; P = 0.006). The number needed to treat for benefit to prevent one case of diabetes was 30 (CI, 18 to 103). Changes in weight and waist circumference did not mediate this effect.
In women with coronary disease, hormone therapy reduced the incidence of diabetes by 35%. This observation provides important insights into the metabolic effects of postmenopausal hormones but is insufficient to recommend the use of hormones for secondary prevention of heart disease.
In observational studies, postmenopausal hormone therapy has been associated with lower fasting glucose levels. No prospective, controlled trial has evaluated the effect of postmenopausal hormone therapy on the development of diabetes mellitus.
Among the 2029 women in the Heart and Estrogen/progestin Replacement Study who had coronary disease but no diabetes at baseline, 6.2% of those receiving 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate and 9.5% of those receiving placebo developed diabetes.
Recommendations about combination postmenopausal hormone therapy should consider that for every 30 women treated for 4 years, therapy might prevent one case of diabetes.
Table 1. Baseline Characteristics of Participants by Treatment Group
Table 2. Baseline Characteristics of Participants by Diabetes Status
The flow diagram of the Heart and Estrogen/progestin Replacement Study.
Table 3. Effect of Treatment Assignment on Fasting Serum Glucose Level
Table 4. Criteria for Diagnosis of Diabetes at Year 1 and at the End of the Study
Table 5. Cumulative (4-Year) Incidence of Diabetes from Baseline Classification
Table 6. Risk for Incident Diabetes in the Hormone Therapy Group versus the Placebo Group
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Kanaya AM, Herrington D, Vittinghoff E, Lin F, Grady D, Bittner V, et al. Glycemic Effects of Postmenopausal Hormone Therapy: The Heart and Estrogen/progestin Replacement Study: A Randomized, Double-Blind, Placebo-Controlled Trial. Ann Intern Med. 2003;138:1–9. doi: 10.7326/0003-4819-138-1-200301070-00005
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Published: Ann Intern Med. 2003;138(1):1-9.
Cardiology, Coronary Risk Factors, Diabetes, Endocrine and Metabolism.
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