Home |
Current Issue |
Past Issues |
In the Clinic |
ACP Journal Club |
CME |
Collections |
Audio/Video |
Mobile |
Subscribe |
Tools |
Help |
ACP Online
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
7 January 2003 | Volume 138 Issue 1 | Pages 1-9
Background: 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.
Objective: To evaluate the effect of hormone therapy on fasting glucose level and incident diabetes.
Design: Randomized, double-blind, placebo-controlled trial.
Setting: 20 U.S. clinical centers.
Participants: 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.
Intervention: 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate daily, or placebo.
Measurements: 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 (
Results: 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.
Conclusions: 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.
Editors' Notes
Context
Contribution
Implications
The Editors
Author and Article Information
From University of California, San Francisco, San Francisco, and University of California, San Diego, La Jolla, California; Wake Forest University School of Medicine, Winston-Salem, North Carolina; University of Alabama at Birmingham, Birmingham, Alabama; and University of Pittsburgh, Pittsburgh, Pennsylvania.
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, alkak{at}itsa.ucsf.edu.
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. ARTICLE
Glycemic Effects of Postmenopausal Hormone Therapy: The Heart and Estrogen/progestin Replacement Study: A Randomized, Double-Blind, Placebo-Controlled Trial
126 mg/dL), or initiation of therapy with diabetes medication.
![]()
![]()
Related articles in Annals:
This article has been cited by other articles:
![]() |
M. J. Toth, B. C. Cooper, R. E. Pratley, A. Mari, D. E. Matthews, and P. R. Casson Effect of ovarian suppression with gonadotropin-releasing hormone agonist on glucose disposal and insulin secretion Am J Physiol Endocrinol Metab, June 1, 2008; 294(6): E1035 - E1045. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Rees, J. Stevenson, and on behalf of the British Menopause Society Council Primary prevention of coronary heart disease in women Menopause Int, March 1, 2008; 14(1): 40 - 45. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. E. Van Pelt, R. S. Schwartz, and W. M. Kohrt Insulin Secretion and Clearance after Subacute Estradiol Administration in Postmenopausal Women J. Clin. Endocrinol. Metab., February 1, 2008; 93(2): 484 - 490. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Karim, H. N. Hodis, F. Z. Stanczyk, R. A. Lobo, and W. J. Mack Relationship between Serum Levels of Sex Hormones and Progression of Subclinical Atherosclerosis in Postmenopausal Women J. Clin. Endocrinol. Metab., January 1, 2008; 93(1): 131 - 138. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. M. Boyd, C. Boult, E. Shadmi, B. Leff, R. Brager, L. Dunbar, J. L. Wolff, and S. Wegener Guided Care for Multimorbid Older Adults: Kathleen Walsh Piercy, PhD, Editor Gerontologist, October 1, 2007; 47(5): 697 - 704. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. C. M. Wasko, H. B. Hubert, V. B. Lingala, J. R. Elliott, M. E. Luggen, J. F. Fries, and M. M. Ward Hydroxychloroquine and Risk of Diabetes in Patients With Rheumatoid Arthritis JAMA, July 11, 2007; 298(2): 187 - 193. [Abstract] [Full Text] [PDF] |
||||
![]() |
Authors/Task Force Members, L. Ryden, E. Standl, M. Bartnik, G. V. d. Berghe, J. Betteridge, M.-J. de Boer, F. Cosentino, B. Jonsson, M. Laakso, et al. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: full text: The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD) Eur. Heart J. Suppl., June 1, 2007; 9(suppl_C): C3 - C74. [Full Text] [PDF] |
||||
![]() |
M. E. Wierman and W. M. Kohrt Review Article: Vascular and Metabolic Effects of Sex Steroids: New Insights Into Clinical Trials Reproductive Sciences, May 1, 2007; 14(4): 300 - 314. [Abstract] [PDF] |
||||
![]() |
S. H. Golden, A. S. Dobs, D. Vaidya, M. Szklo, S. Gapstur, P. Kopp, K. Liu, and P. Ouyang Endogenous Sex Hormones and Glucose Tolerance Status in Postmenopausal Women J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1289 - 1295. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Miyazaki-Akita, T. Hayashi, Q. F. Ding, H. Shiraishi, T. Nomura, Y. Hattori, and A. Iguchi 17beta-Estradiol Antagonizes the Down-Regulation of Endothelial Nitric-Oxide Synthase and GTP Cyclohydrolase I by High Glucose: Relevance to Postmenopausal Diabetic Cardiovascular Disease J. Pharmacol. Exp. Ther., February 1, 2007; 320(2): 591 - 598. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. W. Mankhey, C. C. Wells, F. Bhatti, and C. Maric 17beta-Estradiol supplementation reduces tubulointerstitial fibrosis by increasing MMP activity in the diabetic kidney Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R769 - R777. [Abstract] [Full Text] [PDF] |
||||
![]() |
Authors/Task Force Members, L. Ryden, E. Standl, M. Bartnik, G. Van den Berghe, J. Betteridge, M.-J. de Boer, F. Cosentino, B. Jonsson, M. Laakso, et al. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary: The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD) Eur. Heart J., January 1, 2007; 28(1): 88 - 136. [Full Text] [PDF] |
||||
![]() |
R. E. van Genugten, K. M. Utzschneider, J. Tong, F. Gerchman, S. Zraika, J. Udayasankar, E. J. Boyko, W. Y. Fujimoto, S. E. Kahn, and and the American Diabetes Association GENNID Study Effects of Sex and Hormone Replacement Therapy Use on the Prevalence of Isolated Impaired Fasting Glucose and Isolated Impaired Glucose Tolerance in Subjects With a Family History of Type 2 Diabetes Diabetes, December 1, 2006; 55(12): 3529 - 3535. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Le May, K. Chu, M. Hu, C. S. Ortega, E. R. Simpson, K. S. Korach, M.-J. Tsai, and F. Mauvais-Jarvis Estrogens protect pancreatic beta-cells from apoptosis and prevent insulin-deficient diabetes mellitus in mice PNAS, June 13, 2006; 103(24): 9232 - 9237. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Gao, G. Bryzgalova, E. Hedman, A. Khan, S. Efendic, J.-A. Gustafsson, and K. Dahlman-Wright Long-Term Administration of Estradiol Decreases Expression of Hepatic Lipogenic Genes and Improves Insulin Sensitivity in ob/ob Mice: A Possible Mechanism Is through Direct Regulation of Signal Transducer and Activator of Transcription 3 Mol. Endocrinol., June 1, 2006; 20(6): 1287 - 1299. [Abstract] [Full Text] [PDF] |
||||
![]() |
D.-J. Kim and E. Barrett-Connor Association of serum proinsulin with hormone replacement therapy in nondiabetic older women: the rancho bernardo study. Diabetes Care, March 1, 2006; 29(3): 618 - 624. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. A. BRINTON Controversies in Dyslipidemias: Atheroprevention in Diabetes and Insulin Resistance Ann. N.Y. Acad. Sci., December 1, 2005; 1055(1): 159 - 178. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. C. Burgener, P. Twigg, and A. Popovich Measuring psychological well-being in cognitively impaired persons Dementia, November 1, 2005; 4(4): 463 - 485. [Abstract] [PDF] |
||||
![]() |
E. Selvin, J. Coresh, S. H. Golden, L. L. Boland, F. L. Brancati, and M. W. Steffes Glycemic Control, Atherosclerosis, and Risk Factors for Cardiovascular Disease in Individuals With Diabetes: The Atherosclerosis Risk in Communities study Diabetes Care, August 1, 2005; 28(8): 1965 - 1973. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. S. Day, W. S. Gozansky, R. E. Van Pelt, R. S. Schwartz, and W. M. Kohrt Sex Hormone Suppression Reduces Resting Energy Expenditure and {beta}-Adrenergic Support of Resting Energy Expenditure J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3312 - 3317. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. K. Sites, G. D. L'Hommedieu, M. J. Toth, M. Brochu, B. C. Cooper, and P. A. Fairhurst The Effect of Hormone Replacement Therapy on Body Composition, Body Fat Distribution, and Insulin Sensitivity in Menopausal Women: A Randomized, Double-Blind, Placebo-Controlled Trial J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2701 - 2707. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. E. Ostberg, M. J. H. Attar, V. Mohamed-Ali, and G. S. Conway Adipokine Dysregulation in Turner Syndrome: Comparison of Circulating Interleukin-6 and Leptin Concentrations with Measures of Adiposity and C-Reactive Protein J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2948 - 2953. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. B. Peterson, S. B. Thacker, P. S. Corso, P. A. Marchbanks, and J. P. Koplan Hormone Therapy: Making Decisions in the Face of Uncertainty Arch Intern Med, November 22, 2004; 164(21): 2308 - 2312. [Full Text] [PDF] |
||||
![]() |
J. S. Skyler Effects of Glycemic Control on Diabetes Complications and on the Prevention of Diabetes Clin. Diabetes, October 1, 2004; 22(4): 162 - 166. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. V. Howard, J. Hsia, P. Ouyang, L. Van Voorhees, J. Lindsay, A. Silverman, E. L. Alderman, M. Tripputi, and D. D. Waters Postmenopausal Hormone Therapy Is Associated With Atherosclerosis Progression in Women With Abnormal Glucose Tolerance Circulation, July 13, 2004; 110(2): 201 - 206. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. M. Prisant Preventing Type II Diabetes Mellitus J. Clin. Pharmacol., April 1, 2004; 44(4): 406 - 413. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. T. Chlebowski, J. Wactawski-Wende, C. Ritenbaugh, F. A. Hubbell, J. Ascensao, R. J. Rodabough, C. A. Rosenberg, V. M. Taylor, R. Harris, C. Chen, et al. Estrogen plus Progestin and Colorectal Cancer in Postmenopausal Women N. Engl. J. Med., March 4, 2004; 350(10): 991 - 1004. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Rossi, G. Origliani, and M. G. Modena Transdermal 17-{beta}-Estradiol and Risk of Developing Type 2 Diabetes in a Population of Healthy, Nonobese Postmenopausal Women Diabetes Care, March 1, 2004; 27(3): 645 - 649. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Malik JournalScan Heart, March 1, 2004; 90(3): 353 - 354. [Full Text] [PDF] |
||||
![]() |
J. V.L. Sheffield and E. B. Larson Postmenopausal Hormones and Glycemic Effects Ann Intern Med, December 16, 2003; 139(12): 1043 - 1043. [Full Text] [PDF] |
||||
![]() |
J. P. Girod and D. J. Brotman Postmenopausal Hormones and Glycemic Effects Ann Intern Med, December 16, 2003; 139(12): 1043 - 1043. [Full Text] [PDF] |
||||
![]() |
A. McElduff Postmenopausal Hormones and Glycemic Effects Ann Intern Med, December 16, 2003; 139(12): 1043 - 1044. [Full Text] [PDF] |
||||
![]() |
J. R. Greenfield, K. Samaras, A. B. Jenkins, P. J. Kelly, T. D. Spector, and L. V. Campbell Moderate Alcohol Consumption, Estrogen Replacement Therapy, and Physical Activity Are Associated With Increased Insulin Sensitivity: Is abdominal adiposity the mediator? Diabetes Care, October 1, 2003; 26(10): 2734 - 2740. [Abstract] [Full Text] [PDF] |
||||
![]() |
ADDITIONAL ARTICLES ABSTRACTED IN ACP JOURNAL CLUB Evid. Based Med., September 1, 2003; 8(5): 131 - 131. [Full Text] [PDF] |
||||
![]() |
R. E. Van Pelt, W. S. Gozansky, R. S. Schwartz, and W. M. Kohrt Intravenous estrogens increase insulin clearance and action in postmenopausal women Am J Physiol Endocrinol Metab, August 1, 2003; 285(2): E311 - E317. [Abstract] [Full Text] [PDF] |
||||
![]() |
OTHER ARTICLES NOTED (24 Jan 03 to 18 Apr 03) Evid. Based Nurs., July 1, 2003; 6(3): e1 - 12. [Full Text] [PDF] |
||||
![]() |
N.D. Stojanovic, P. Kwong, D.J. Byrne, A. Arnold, I.A. Jagroop, D. Nair, M. Press, S. Hurel, D.P. Mikhailidis, and G.M. Prelevic The Effects of Transdermal Estradiol Alone or with Cyclical Dydrogesterone on Markers of Cardiovascular Disease Risk in Postmenopausal Women with Type 2 Diabetes: A Pilot Study Angiology, July 1, 2003; 54(4): 391 - 399. [Abstract] [PDF] |
||||
![]() |
G. Koerbel and M. Korytkowski Coronary Heart Disease in Women With Diabetes Diabetes Spectr, July 1, 2003; 16(3): 148 - 153. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. L. Greenspan, N. M. Resnick, and R. A. Parker Combination Therapy With Hormone Replacement and Alendronate for Prevention of Bone Loss in Elderly Women: A Randomized Controlled Trial JAMA, May 21, 2003; 289(19): 2525 - 2533. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Sattar, K. Williams, T. S. Han, C. Gonzalez-Villalpando, M. E.J. Lean, and S. M. Haffner Prospective Relation of C-Reactive Protein With Type 2 Diabetes: Response to Snijder et al. Diabetes Care, May 1, 2003; 26(5): 1657 - 1658. [Full Text] [PDF] |
||||
![]() |
HRT for Diabetes Prevention? Journal Watch (General), January 24, 2003; 2003(124): 4 - 4. [Full Text] |
||||
![]() |
Minerva BMJ, January 18, 2003; 326(7381): 172 - 172. [Full Text] [PDF] |
||||
![]() |
P. W.F. Wilson Lower Diabetes Risk with Hormone Replacement Therapy: An Encore for Estrogen? Ann Intern Med, January 7, 2003; 138(1): 69 - 70. [Full Text] [PDF] |
||||