When is the right time to stop hormone replacement therapy?
Hormone replacement therapy (HRT) appears to help postmenopausal women avoid osteoporosis, heart disease, and other chronic diseases. But some studies have suggested that HRT may increase a woman's risk of breast cancer. Hence, researchers are trying to determine how long women should take HRT to gain the bone-building and heart-protective effects and minimize the risks. HRT is thought to prevent osteoporosis because of its ability to stimulate increases in bone mineral density (BMD). However, a study recently published in the Archives of Internal Medicine suggests that these increases may taper off after 3 years of treatment. In addition, in this study the rate of bone lost after HRT was stopped was not any faster than among women who never took HRT.
About the study
This study was conducted using data from the Postmenopausal Estrogen/Progestin Interventions (PEPI) randomized controlled trial and the PEPI Safety Follow-up Study (PSFS). In the original PEPI trial, 875 postmenopausal women between the ages of 45 and 64 were randomly assigned to receive either one of four HRT drug combinations or a placebo (inactive) pill. Bone mineral density was tested at the start of the study and again at 12 months and 36 months.
In the PSFS study, researchers tested the bone density of the hip and spine in 495 women from the PEPI study approximately four years after the study had ended.
For this recent analysis, researchers analyzed the data from both studies to determine how bone density changed during and after HRT use.
The PEPI trial confirmed that bone density increased in women who took HRT for 1 year or 3 years. However, bone density did not continue to increase over the following 4 years among women who continued HRT. This suggests that HRT may not provide additional gains in bone mass beyond that gained in the first 3 years of therapy.
In addition, women who stopped HRT began to lose bone mass again. However, the rate of bone loss among women who stopped HRT was not greater than the rate of bone loss among women who never took HRT. This suggests that although women may lose bone mass again after they stop HRT, this reflects bone mass gained while taking HRT. Therefore, they still have more bone mass than women who don't take HRT.
In calculating the effects of HRT and discontinuing HRT on bone density, the researchers accounted for other factors that may affect bone density, such as age, exercise, calcium intake, body mass index, ethnicity, alcohol intake, and smoking.
Although these results are interesting, there are limitations to this study. In the time between the PEPI trial and the PSFS follow-up BMD measurements, the women either continued HRT, stopped HRT, or began HRT for the first time. The women self-reported this information and were not asked to specify exactly when they started or stopped HRT in the four years between the two studies. So their HRT status during the 4 years is not entirely clear. This analysis only included 57% of the 875 women who participated in the PEPI trial.
How does this affect you?
Making the decision about whether to take HRT is a complex issue for postmenopausal women and their doctors. Women must weigh their risk of heart disease and osteoporosis with their risk of breast cancer. This study suggests that beyond 3 years of HRT, increases in bone mass may be negligible. This study also confirms the findings of other studies that bone loss does not occur at a faster rate after HRT than the normal rate of bone loss in untreated postmenopausal women. More research is needed to determine the optimal duration of HRT for achieving adequate bone mass in postmenopausal women.
Although this research sheds some light on the effects of shorter- and longer-term HRT on the risk of osteoporosis, it does not explore its effects on heart disease risk. If you are a postmenopausal women considering HRT, talk with your doctor about balancing your risk of osteoporosis and heart disease against your risk of breast cancer.
MGreendale GA, et al. Bone mass response to discontinuation of long-term hormone replacement therapy.
Archives of Internal Medicine . March 25, 2002;162:665-672.
Last reviewed Mar 26, 2002
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