The impact of clinical trials on the use of hormone replacement therapy
A population-based study
Received: 01 July 2005 Accepted: 05 July 2005 DOI:
Cite this article as: Kim, N., Gross, C., Curtis, J. et al. J GEN INTERN MED (2005) 20: 1026. doi:10.1111/j.1525-1497.2005.0221.x Abstract The last 5 years of trial data demonstrate the ineffectiveness of hormone replacement therapy (HRT). The impact of these trials on age-specific HRT use, HRT discontinuation, and regional HRT variation has not been evaluated extensively. BACKGROUND: To characterize the relation between HRT trial dissemination and age-specific HRT use, HRT discontinuation, and regional HRT variation before and after the trials’ publication. OBJECTIVE: Using the Medco Health database, we analyzed HRT prescription filling, discontinuation, and regional variation among women ≥55 years from May 1998 to May 2003. DESIGN: Approximately 340,000 women were eligible for Medco benefits each month. Within 3 months of the Women’s Health Initiative (WHI), HRT prescriptions declined from 12.5% to 9.4%, MEASUREMENTS AND MAIN RESULTS: P≤.0001. When stratified by age, a statistically significant decline in HRT post-WHI occurred in all age groups, with the biggest decline among women ≥55 to 64 (18% to 11%, P≤.0001). Among HRT users, we found statistically significant increases in discontinuation in 2002 (67%) compared with 2001 (53%, P<.0001). Prior to the WHI there was substantial regional variation in HRT use, with the West South Central and mid-Atlantic having the highest and lowest proportions, respectively (19% vs 6%, P≤.0001). Despite a relative decline in HRT use of 25% to 42% across all regions, substantial geographic variation remained. Hormone replacement therapy use decreased significantly immediately post-WHI, suggesting that trial results can have a rapid effect on practice. Marked regional variation in HRT use persisted after the WHI, suggesting that local practice patterns exert a strong effect on clinical behavior even after new evidence is available. CONCLUSIONS: Key Words hormone replacement therapy estrogen clinical trials Women’s Health Initiative
The authors have no conflicts of interest to declare.
Dr. Kim’s work was supported by the Robert Wood Johnson Clinical Scholars Program and the Fellowship in Geriatric Medicine and Clinical Epidemiology training grant at the Yale University School of Medicine (T32AG019134). Dr. Gross’s efforts were supported by a Cancer Prevention, Control and Population Sciences Career Development Award (1K07CA-90402) and the Claude D. Pepper Older Americans Independence Center at Yale (P30AG21342).
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. Clinical research to clinical practice—lost in translation? N Engl J Med. 2003;349:868–74.
. Disseminating innovations in health care. JAMA. 2003;289:1969–75.
Col NF, Eckman MH, Karas RH, et al.
Patient-specific decisions about hormone replacement therapy in postmenopausal women. JAMA. 1997;277:1140–7.
Stampfer MJ, Colditz GA, Willett WC, et al.
Postmenopausal estrogen therapy and cardiovascular disease: ten-year follow-up from the Nurses’ Health Study. N Engl J Med. 1991;325:756–62.
Grady D, Gebretsadik T, Kerlikowske K, Ernster V, Petitte D
. Hormone replacement therapy and endometrial cancer risk: a meta-analysis. Obstet Gynecol. 1995;85:304–13.
Stampfer MJ, Colditz GA
. Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prev Med. 1991;20:47–63.
Colditz GA, Willett WC, Stampfer MJ, Rosner B, Speizer FE, Hennekens CH
. Menopause and the risk of coronary heart disease in women. N Engl J Med. 1987;316:1105–10.
Hulley S, Grady D, Bush T, et al.
Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA. 1998;280:605–13.
Viscoli CM, Brass LM, Kernan WN, Sarrel PM, Suissa S, Horwitz RI
. A clinical trial of estrogen-replacement therapy after ischemic stroke. N Engl J Med. 2001;345:1243–9.
Writing Group for the Women’s Health Initiative Investigators
. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288:321–33.
Manson JE, Hsia J, Cushman M, et al.
Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349:523–34.
The Women’s Health Initiative Steering Committee
. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004;291:1701–12.
Austin PC, Mamdani MM, Tu K, Jaakkimainen L
. Prescriptions for estrogen replacement therapy in Ontario before and after publication of the Women’s Health Initiative Study. JAMA. 2003;289:3241–2.
Haas JS, Kaplan CP, Gerstenberger EP, Kerlikowske K
. Changes in the use of postmenopausal hormone therapy after the publication of clinical trial results. Ann Intern Med. 2004;140:184–8.
Hersh AL, Stefanick ML, Stafford RS
. National use of postmenopausal hormone therapy—annual trends and response to recent evidence. JAMA. 2004;291:47–53.
Velde ER, Pearson PL
. The variability of female reproductive ageing. Reprod Update. 2002;8:141–54.
Brunt ME, Murray MD, Hui SL, Kesterson J, Perkins AJ, Tierney WM
. Mass media release of medical research results. An analysis of antihypertensive drug prescribing in the aftermath of the calcium channel blocker scare of March 1995. J Gen Intern Med. 2003;18:84–94.
Anis AH, Carruthers SG, Carter AO, Kierulf J. Variability in prescription drug utilization: issues for research. Can Med Assoc J. 1996;154:635–40.
Feasby TE, Quan H, Ghali WA
. Geographic variation in the rate of carotid endarterectomy in Canada. Stroke. 2001;32:2417–22.
Roumie CL, Grogen EL, Falbe W, Awad J, Speroff T
. A three-part intervention to change the use of hormone replacement therapy in response to new evidence. Ann Intern Med. 2004;141:118–25.
Writing Group for the HERS Research Group
. Cardiovascular disease outcomes during 6.8 years of hormone therapy—Heart and estrogen/progestin replacement study follow-up (HERS II). JAMA. 2002;288:49–57.
Mosca L, Collins P, Herrington DM, et al.
Hormone replacement therapy and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 2001;104:499–503.
Hogan DB, Maxwell CJ, Fun TS, Ebly EM
. Regional variation in the use of medications by older Canadians—a persistent and incompletely understood phenomena. Pharmacoepidemiol Drug Saf. 2003;12:575–82.
Wennberg JE, Barnes BA, Zubkoff M
. Professional uncertainty and the problem of supplier-induced demand. Soc Sci Med. 1982;16:811–24.
U.S. Preventive Services Task Force. Postmenopausal hormone replacement therapy for primary prevention of chronic conditions: recommendations and rationale. Ann Intern Med. 2002;137:834–9.
. Explaining geographic variations: the enthusiasm hypothesis. Med Care. 1993;31(suppl):37–44.
Hirth RA, Tedeschi PJ, Wheeler JRC
. Extent and sources of geographic variation in Medicare end-stage renal disease expenditures. Am J Kidney Dis. 2001;38:824–31.
Sullivan MG. Women overestimate hormones’ risks, benefits. Internal Medicine News; March 1, 2004: 28.
Bozkurt B, Agoston I, Knowlton AA
. Complications of inappropriate use of spironolactone in heart failure: when an old medicine spirals out of new guidelines. J Am College Cardiol. 2003;41:211–4.
Gross CP, Steiner CA, Bass EB, Powe NR
. Relation between prepublication release of clinical trial results and the practice of carotid endarterectomy. JAMA. 2000;284:2886–93.
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