Canadian Task Force on Preventive Health Care

Please note: In 2003, the CTF updated its Grades of Recommendations to include an "I Recommendation" for situations where insufficient evidence exists to allow a recommendation to be made. (Formerly, these situations were captured under a "C Recommendation".) This change is not retroactive, and all "C Recommendations" made prior to 2003 have not been reevaluated in light of the new "I" recommendation grade. For a discussion of these recommendation grades, please link to the 2003 article in the Canadian Medical Association Journal here.

Prevention of Osteoporotic Fractures in Women by Estrogen Replacement Therapy

Prepared by Denice S. Feig, MD, FRCPC, Assistant Professor of Medicine, University of Toronto

Objective
To make recommendations for screening postmenopausal women in Canada to identify those who are at risk for osteoporotic fractures and would benefit from estrogen replacement therapy (ERT).

Burden of Suffering
The most common age-related fractures are those of the distal forearm, vertebrae, and hip. Vertebral fractures are the most common of the osteoporotic fractures. The estimated lifetime risk for a 50 year old woman of sustaining a vertebral fracture is 32%. Hip fractures are associated with more death, morbidity and medical costs than all other osteoporotic fractures combined. The incidence begins to rise after age 50 but rises dramatically after age 70. Mortality rates in the first year following a hip fracture are 12-20% higher than rates in those of similar age and sex who have not sustained a fracture. In the U.S. the cost of acute care attributable to osteoporosis was estimated at U.S. $7-10 billion in 1984.

Options
Screening methods include history and physical examination, single and dual photon absorptiometry, and measures of bone density (quantitative computed tomography, neutron activation analysis, and dual x-ray absorptiometry). The main treatment option was counselling women about the benefits and risks of ERT. Treatment options for ERT include percutaneous estrogen, oral estrogen alone, or oral estrogen combined with progesterone.

Outcomes
Accuracy of tests. ERT-related outcomes include bone mineral loss, fractures, cardiovascular mortality and events, and breast and endometrial cancer.

Evidence
MEDLINE was searched starting in 1987 using the keywords "osteoporosis", "estrogen replacement therapy", "synthetic estrogens", "evaluation studies", "random allocation", "double-blind method", "drug evaluation", "random", "cohort studies", "clinical trial", "menopause", "postmenopausal", and "English". Reference material was consulted and content experts contacted. Only studies of women were included. Study results were synthesized in table or graphic format only.

Values
The 13-member Task Force of experts in family medicine, geriatric medicine, pediatrics, psychiatry and epidemiology used an evidence-based method for evaluating the effectiveness of preventive health care interventions. Recommendations were not based on cost-effectiveness of options. Patient preferences were not discussed.

Background papers providing critical appraisal of the evidence and tentative recommendations prepared by the chapter author were pre-circulated to the members. Evidence for this topic was presented and deliberated upon in 1- to 2-day meetings, 2 to 3 times per year from January 1993 to June 1993. Consensus was reached on final recommendations.

Benefits, Harms, and Costs
The benefits of estrogen replacement therapy must be weighed against its risks. Simple and complex models and procedures for detecting women at risk for fractures have not been successful. No randomized controlled trials have been done to show that screening asymptomatic women can decrease the rate of fractures.

There is good evidence, from RCTs, of that short-term percutaneous estrogen, oral estrogen, or estrogen and progesterone therapy show prevention of or retard bone loss or and even increases in bone mineral density but the studies have not been linked with decreased risk or occurrences of fractures. Case-control studies, cohort studies, and 1 RCT have shown that ERT prevents osteoporotic fractures including hip fractures (point estimates of the relative risk are from 0.65 to 0.79, P < 0.05).Optimal duration of ERT has not been established. One meta-analysis showed that women who had ever used estrogen had a decreased risk for both coronary heart disease (relative risk [RR] 0.65, 95% CI 0.59 to 0.71) and cardiac death (RR 0.63, CI 0.55 to 0.72).

Risks of ERT include increased rates of endometrial and breast cancer. For endometrial cancer, the addition of progesterone decreases the risk of incurred by using estrogen alone: one study showed a decrease in risk for endometrial cancer with an incidence in estrogen users of 359 per 100 000, in estrogen progesterone-users of 56 per 100 000, and in untreated women of 248 per 100 000. One meta-analysis showed that long-term use (after 15 years) of estrogen had an RR for breast cancer of 1.3 (CI 1.2 to 1.6) for all women after 15 years of estrogen use. For studies assessing family history, the RR for breast cancer was 3.4 (CI 2.0 to 6.0) for women with a family history of breast cancer and 1.5 (CI 1.2 to 1.7) for women without a family history. Three other meta-analyses did not show an increased risk for breast cancer after short-term estrogen use. No evidence exists for combination therapy to reduce breast cancer risk.

Recommendations
Recommendation grade [A, B, C, D, E] and level of evidence [I, II-1, II-2, II-3, III] are indicated after each recommendation. Citations in support of individual recommendations are identified in the guideline text.

There is poor evidence to include or exclude, in the PHE of asymptomatic women, initial history taking and physical examination to detect risk factors for osteoporotic fractures [C, II-2]. No evidence exists for using the physical examination and history taking as screening tools for risk for fractures in postmenopausal women [C, II-2].
Fair evidence exists to exclude, from the PHE of asymptomatic women, single and dual photon absorptiometry, quantitative computed tomography, neutron activation analysis, and dual x-ray absorptiometry in the periodic health examination [D, II-2].
Fair evidence exists to include, in the PHE, counselling for all perimenopausal women regarding the benefits and risks of ERT [B, I, II-2].

Validation
This report was externally peer reviewed. This report was externally peer-reviewed. The 1989 U.S. Preventive Services Task Force recommended against routine screening for decreased bone mass in asymptomatic women; it could be considered when the information was to be used in decision-making for ERT. A Consensus Development Conference of the European Foundation of Osteoporosis and Bone Disease, the National Osteoporosis Foundation and the National Institute of Arthritis and Musculoskeletal and Skin Disease of the United States recommended that all women at risk for osteoporosis be considered for estrogen therapy, barring contraindications. They also suggested that bone density measurements could aid in predicting risk.

Sponsors
The Canadian Task Force on Preventive Health Care developed this guideline with funding from Health Canada.

Source Document
Feig D.S. Prevention of osteoporotic fractures in women by estrogen replacement therapy. In: Canadian Task Force on the Periodic Health Examination. Canadian Guide to Clinical Preventive Health Care. Ottawa: Health Canada, 1994; 620-31.