Expert Commentary

HRT and fracture incidence

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Does hormone replacement therapy reduce the incidence of fractures in postmenopausal women with coronary disease?

Past studie:

Observational findings have shown lower fracture rates in postmenopausal women who take hormone replacement therapy (HRT) compared with women who do not. It is estimated that taking HRT for 5 years or more will decrease the probability of vertebral fractures by 50% to 80%, and hip and wrist fractures by 25%.

This study:

About 2,763 postmenopausal women with coronary disease and an intact uterus were enrolled into the Heart Estrogen/progestin Replacement Study (HERS) and monitored every 4 months for about 4 years. The average age of the participants was 66.7±6.7 years, and fewer than 15% had osteoporosis based on bone density. Women were excluded if their coronary event occurred within 6 months prior to the study, serum triglycerides were greater than or equal to 300 mg/dL, or if they had used hormones in the past 3 months. Women who had undergone a hysterectomy or had a history of deep vein thrombosis, pulmonary embolism, breast or endometrial cancer, uncontrolled hypertension, or diabetes could not participate.

Each woman was randomly assigned to take 1 tablet of either a placebo or a combination of 0.625 mg of conjugated equine estrogens and 2.5 mg of medroxyprogesterone acetate. During 10,554 person years of follow-up, 286 women experienced a fracture (138 in the treatment group and 148 in the placebo group). These included 58 wrist fractures (relative risk [RR] 1.01; 95% confidence interval [CI] 0.6 to 1.7), 27 hip fractures (RR 1.09; CI, 0.5 to 2.3), 32 spine fractures (RR 0.69; CI, 0.3 to 1.4), and 192 other fractures (RR 0.91; CI, 0.7 to 1.2). There was no difference in average height loss between the groups.

The researchers concluded that there was no evidence of a reduction in the incidence of fractures or rate of height loss in postmenopausal women without osteoporosis. More studies are needed to clarify the effect HRT has on fracture risk among women with and without osteoporosis.

Find this study:

April 2001 issue of the American Journal of Medicine; abstract online at

Who may be affected by these findings?

Postmenopausal women with and without osteoporosis.

Expert commentary:

This study’s findings support similar data suggesting that no drug therapy—including HRT—has proven effective for fracture prevention in postmenopausal women without osteoporosis. However, the appreciable relationship between changes in lumbar spine bone density and the magnitude of vertebral fracture risk suggest that HRT will have a largely positive effect on vertebral fracture incidence in women with osteoporosis.1 For each standard deviation decline in bone mineral density (BMD) at the lumbar spine, there is a 2.3-fold increase in the risk of vertebral fracture.2

Since evidence for nonvertebral fracture reduction is much more difficult to ascertain, large clinical trials are necessary. Meanwhile, there is an appreciable trend suggesting that HRT reduces nonvertebral fracture risk by 35% to 50% when initiated before age 60.3 Epidemiological studies suggest a 50% reduction in hip fracture with HRT.4 However, confidence intervals from meta-analyses imply that HRT may have little effect. Furthermore, none of the evidence to date considers the risks associated with HRT use.

Observational studies suggest that HRT’s benefits include a reduction in cardiac events, including myocardial infarction and death. However, it has been found to have a negligible effect on the reversal of established cardiovascular disease.

The bottom line:

HRT attenuates the rapid decline in BMD in the estrogen-depleted woman. For this reason, it is an important therapy to consider for the postmenopausal patient. More randomized, controlled trials on HRT and its role in preventing fractures in postmenopausal women with and without osteoporosis, along with long-term effects on other target areas are needed so that physicians and patients can adequately weigh their options.

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