Low-Dose Hormone Replacement Therapy May Prevent Bone Loss Without Adverse Effects
]]>Osteoporosis]]> is a disease that causes bones to become so weak and brittle that they break easily. It is estimated that eight million women in the U.S. have osteoporosis and one in two women over age 50 will have an osteoporosis-related fracture in their lifetime. Osteoporosis is often referred to as a “silent disease” because the symptoms aren’t always obvious and many people don’t find out they have osteoporosis until one of their bones break.
Studies have shown that hormone replacement therapy (HRT) is effective in preventing and treating osteoporosis in postmenopausal women, but reports of adverse effects from the Women’s Health Initiative (WHI) study have caused many physicians to stop prescribing HRT. The WHI found that, although conventional doses of HRT (estrogen plus progestin) protected against colorectal cancer and fractures, it substantially increased the risk of ]]>breast cancer]]> , ]]>heart disease]]> , ]]>stroke]]> , and blood clots. The study ended early because the researchers determined that the risks of HRT outweighed the benefits.
But, does this mean women should no longer take HRT to prevent or treat osteoporosis? Could lower doses of HRT protect bones without causing adverse effects?
Perhaps, according to a study in the August 27, 2003 issue of the Journal of the American Medical Association . Researchers from the University of Connecticut Health Center looked at the effects of low-dose HRT (about a quarter of the conventional dose) on the bones of healthy postmenopausal women. They found that after three years, the low doses increased bone mineral density (BMD) and prevented bone loss without increasing the risk of adverse effects.
About the Study
This study included 167 healthy postmenopausal women over the age of 65 who were taking no medications known to affect bone growth. The women were randomly assigned to receive either HRT (25 milligrams per day (mg/d) of 17β-estradiol) or a placebo. To protect them from endometrial cancer associated with estrogen therapy, all women who had not had a hysterectomy received progestin for two weeks every six months. In addition, all of the women in the study received 1,300 mg/d of calcium and 1,000 international units per day (IU/d) of vitamin D.
The researchers used ]]>duel-energy x-ray absorptiometry]]> (DEXA) to measure the BMD of each woman’s hip, spine, wrist, and total body every year for three years. They also measured blood markers for bone turnover (chemicals that indicate bone loss) at the beginning of the study, after three months, and during the first and third years. The women had a ]]>mammogram]]> once a year during the study. For the women taking progestin, endometrial thickness—which can indicate risk for endometrial cancer—was measured every six months before the progestin was administered. The researchers kept track of mammogram results, breast cancers, endometrial thickness, fractures, and reports of headaches, bloating, fluid retention, and breast tenderness for the three years of the study.
After three years, the women taking HRT had significantly greater increases in BMD of the hip, spine, wrist, and total body compared to women taking a placebo, regardless of whether they were taking progestin or not. When compared to the women taking a placebo, the women on HRT also had decreased markers for bone turnover.
During the three years of the study, there was no significant difference in the number of abnormal mammogram results between the two groups and there were no reports of breast cancer. The endometrial thickness increased slightly in both groups, but there was no significant difference between the groups except at year two, when the HRT group had an average endometrial thickness of 4.6 millimeters (mm), while the placebo group’s average thickness was 3.6 mm. There were eight fractures reported during the course of the study and the number of fractures was higher in the placebo group than the HRT group. Furthermore, there was no difference in headaches, bloating, fluid retention, or breast tenderness between the groups, except that more headaches were reported in the placebo group at three years.
How Does This Affect You?
This study suggests that low doses of HRT may help prevent osteoporosis without increasing the risk for the adverse effects usually associated with HRT. This study was the first long-term randomized placebo-controlled study to examine the effects of low-dose HRT.
Low levels of estrogen, which occur in postmenopausal women, increase the risk of bone loss and fracture. Conventional doses of HRT were designed to bring estrogen levels back to what they were before menopause. The current study supports findings from other studies that suggest lower doses of HRT can protect bones, while conventional doses may increase adverse effects with minimal additional benefit to bones.
In this study, low doses of estrogen resulted in BMD improvements comparable to those seen with medications designed to treat osteoporosis. This study, however, only lasted for three years and cannot conclude whether the low-dose HRT would increase the risk for long-term adverse effects—fractures, breast cancer, heart disease, stroke, and blood clots. This is an important limitation, given the results of the WHI study.
If you are concerned about your bone health, schedule a visit with your physician. In addition to HRT, there are a number of medications and lifestyle modifications that can help protect your bones as you age.
National Institute on Aging
National Osteoporosis Foundation
National Institutes of Health Osteoporosis and Related Bone Diseases Resource Center website. Available at:
Accessed August 26, 2003.
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;288:321-333.
Prestwood KM, Kenny AM, Kleppinger A, Kulldorff M. Ultralow-dose micronized 17β-estradiol and bone density and bone metabolism in older women. JAMA . 2003;290(8):1042-48.
Last reviewed August 29, 2003 by ]]>Richard Glickman-Simon, MD]]>
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