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Hormone Replacement Therapy and Osteoporosis

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Hormone Replacement Therapy and Osteoporosis This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied. AHRQ is the lead Federal agency charged with supporting research designed to improve the quality of health care, reduce its cost, address patient safety and medical errors, and broaden access to essential services. AHRQ sponsors and conducts research that provides evidence-based information on health care outcomes; quality; and cost, use, and access. The information helps health care decisionmakers— patients and clinicians, health system leaders, and policymakers—make more informed decisions and improve the quality of health care services. Systematic Evidence Review Number 12 Hormone Replacement Therapy and Osteoporosis Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 2101 East Jefferson Street Rockville, MD 20852 http://www.ahrq.gov Contract No. 290-97-0018 Task Order No. 2 Technical Support of the U.S. Preventive Services Task Force Prepared by: Oregon Health Sciences University Evidence-based Practice Center, Portland, Oregon Heidi D. Nelson, MD, MPH August 2002 Preface The Agency for Healthcare Research and Quality (AHRQ) sponsors the development of Systematic Evidence Reviews (SERs) through its Evidence-based Practice Program. With guidance from the third U.S. Preventive Services Task Force∗ (USPSTF) and input from Federal partners and primary care specialty societies, two Evidence-based Practice Centers—one at the Oregon Health Sciences University and the other at Research Triangle Institute-University of North Carolina—systematically review the evidence of the effectiveness of a wide range of clinical preventive services, including screening, counseling, immunizations, and chemoprevention, in the primary care setting. The SERs—comprehensive reviews of the scientific evidence on the effectiveness of particular clinical preventive services—serve as the foundation for the recommendations of the third USPSTF, which provide age- and risk-factor- specific recommendations for the delivery of these services in the primary care setting. Details of the process of identifying and evaluating relevant scientific evidence are described in the “Methods” section of each SER. The SERs document the evidence regarding the benefits, limitations, and cost-effectiveness of a broad range of clinical preventive services and will help to further awareness, delivery, and coverage of preventive care as an integral part of quality primary health care. AHRQ also disseminates the SERs on the AHRQ Web site (http://www.ahrq.gov/uspstfix.htm) and disseminates summaries of the evidence (summaries of the SERs) and recommendations of the third USPSTF in print and on the Web. These are available through the AHRQ Web site (http://www.ahrgq.gov/uspstfix.htm), through the National Guideline Clearinghouse (http://www.ncg.gov), and in print through the AHRQ Publications Clearinghouse (1-800-358-9295). We welcome written comments on this SER. Comments may be sent to: Director, Center for Practice and Technology Assessment, Agency for Healthcare Research and Quality, 6010 Executive Blvd., Suite 300, Rockville, MD 20852. Carolyn M. Clancy, M.D. Acting Director Robert Graham, M.D. Agency for Healthcare Research and Quality Director, Center for Practice and Technology Assessment Agency for Healthcare Research and Quality ∗ The USPSTF is an independent panel of experts in primary care and prevention first convened by the U.S. Public Health Service in 1984. The USPSTF systematically reviews the evidence on the effectiveness of providing clinical preventive services--including screening, counseling, immunization, and chemoprevention--in the primary care setting. AHRQ convened the third USPSTF in November 1998 to update existing Task Force recommendations and to address new topics. iii The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services of a particular drug, device, test, treatment, or other clinical service. iv Structured Abstract Context: Hormone replacement therapy (HRT) is widely used to prevent osteoporosis and fractures. Objective: To systematically review and evaluate studies of the use of estrogen and selective estrogen receptor modulators (SERMs) to prevent bone loss and fractures in healthy postmenopausal women. Data Sources: Studies with English language abstracts identified in MEDLINE, HealthSTAR, and Cochrane Library databases from 1994 to May 2001. Reference lists of key articles and meta-analyses were also reviewed. Study Selection: Only randomized controlled trials and cohort studies were included. Data Extraction: Studies meeting inclusion criteria were formally abstracted and quality was rated using criteria developed by the U.S. Preventive Services Task Force (USPSTF). Data Synthesis: For bone density outcomes, randomized controlled trials consistently indicated improved bone density with estrogen use. These findings were similar between prevention and treatment trials, opposed and unopposed regimens, oral and transdermal forms of estrogen, and types of progestins. For fracture outcomes, 5 randomized controlled trials of estrogen were identified and none met criteria to be ranked as a good- quality study. A primary prevention trial indicated a significant decrease in risk of nonvertebral fractures in 1 of 2 estrogen arms. None of the other trials indicated a significant risk reduction with estrogen, but all had important methodologic limitations. A recent meta-analysis of 22 trials of estrogen, many with unpublished data, reported an overall 27% reduction in nonvertebral fractures (relative risk [RR], 0.73; confidence v interval [CI], 0.56-0.94). Six good-quality cohort studies were identified, and 3 of 4 studies reported 20% to 35% reductions in adjusted relative risks for hip fractures among ever users. In randomized controlled trials, raloxifene increased bone density at lumbar spine, hip, and wrist sites, and tamoxifen modestly increased bone density at the hip and spine, although results were inconsistent between studies. The largest trial of raloxifene reported a protective effect for vertebral fractures (RR, 0.59; 95% CI, 0.05-0.70), but not for nonvertebral fractures. A large trial of tamoxifen indicated no statistically significant fracture benefit. Conclusions. The results of these studies support a benefit for estrogen in improving bone density and protecting against fractures, although the evidence for fractures is based on one arm of one randomized controlled trial and good-quality cohort studies. Trials indicate that raloxifene increases bone density and protects against vertebral fractures. vi Contents Systematic Evidence Review Chapter 1. Introduction .......................................................................................................1 Burden of Suffering/Epidemiology............................................................................2 Healthcare Interventions ............................................................................................3 Prior Recommendations.............................................................................................4 Analytic Framework and Key Questions...................................................................4 Chapter 2. Methods.............................................................................................................5 Literature Search Strategy..........................................................................................5 Inclusion/Exclusion Criteria ......................................................................................5 Literature Synthesis ...................................................................................................7 Chapter 3. Results ...............................................................................................................8 Arrow 1. Does hormone replacement therapy improve or stabalize bone density? ......................................................................................................8 Summary........................................................................................................10 Arrow 2. Does hormone replacement therapy prevent osteoporatic fractures?......10 Randomized controlled trials .........................................................................11 Cohort studies ................................................................................................13 Summary........................................................................................................15 Arrow 1. Does postmenopausal use of SERMs improve or stabalize bone density? ....................................................................................................15 Summary........................................................................................................17 Arrow 2. Does postmenopausal use of SERMs prevent osteoporatic fractures?..................................................................................................17 Summary........................................................................................................19 Chapter 4. Discussion .......................................................................................................20
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