Hot flashes, night sweats, and vaginal dryness—these menopausal symptoms affect the lives of millions of postmenopausal women. In the past, women have taken hormone replacement therapy (HRT) to relieve these symptoms and help prevent osteoporosis. But in 2002, findings from the Women’s Health Initiative (WHI) trial revealed that the risks of HRT may outweigh the benefits.

Women generally take one of two forms of HRT—estrogen alone or a combination of estrogen and progestin. Estrogen alone is recommended for women who have had a hysterectomy . But because estrogen without progestin causes the lining of the uterus to thicken, increasing the risk of endometrial cancer , estrogen-progestin therapy (EPT) is recommended for women who haven’t had a hysterectomy.

The WHI compared the effects of EPT to a placebo in postmenopausal women. While EPT slightly improved hot flashes, night sweats, and sleep, it also had the following effects:

Disease or conditionChange in risk
Heart attacks 29% increase
Breast cancer 26% increase
Strokes 41% increase
Blood clots111% increase
Dementia 105% increase in women over age 65
Hip fractures 33% decrease
Colon cancer 37% decrease

While these changes in risk are certainly cause for concern, their absolute effect on women is actually small. For example, according to the WHI findings, even though there was a 111% increase in the risk of blood clots, only 18 out of 10,000 extra women would develop a blood clot if they took this EPT. Still, on account of these results, the trial was stopped three years early, in July 2002.

Some questions about the risks of EPT still remain. For example, would the benefits of EPT in women at increased risk for fractures outweigh the risks? Does EPT, like estrogen alone, increase the risk of endometrial cancer?

Two studies in the October 1, 2003 issue of the Journal of the American Medical Association reported new findings from the WHI. The first study found that EPT increased bone mineral density (BMD, a marker for bone health) and reduced the risk of fracture in postmenopausal women. When considering the known benefits and risks of EPT, however, there was no net benefit—even for women at the highest risk for fractures. The second study found that EPT increased the risk for endometrial biopsies and abnormal Papanicolaou (Pap) tests .

About the Studies

Both studies looked at WHI data from the 16,608 healthy postmenopausal women with a uterus between the ages 50 and 79. The women were randomly assigned to receive either EPT or a placebo. Researchers followed the women for 5.6 years.

For the fracture and BMD study, the women were classified as at low, moderate, or high risk for fractures, according to their answers on a questionnaire. The women reported hip, spine, and other osteoporotic fractures that occurred during the study. Researchers measured the women’s hip BMD before the study began, and after one and three years.

The researchers kept track of the women who developed heart disease, breast cancer, stroke, blood clots, endometrial cancer, colorectal cancer, or hip fracture, or died from other causes. They used these data to measure the overall balance of risks and benefits associated with taking EPT among the different fracture risk groups.

For the gynecologic cancers study, the women underwent routine Pap tests and pelvic examinations every three years. They were evaluated to determine whether an endometrial biopsy was indicated.

The researchers tracked the rates and results of endometrial biopsies and Pap tests, as well as whether the women developed ovarian or endometrial cancer.

The Findings

The women taking EPT had a 33% reduction in the risk of hip fracture. When researchers looked more closely at these results, they found that EPT reduced the risk of hip fracture by 60% in women who reported a calcium intake of more than 1,200 mg/d. Women with lower calcium intake didn’t have a significant risk reduction. Hip BMD increased significantly more in the EPT group than in the placebo group.

Considering all of the known risks and benefits of EPT, there was no net benefit in any of the fracture risk groups.

Although 20 women in the EPT group and 12 women in the placebo group developed ovarian cancer, this difference was not significant. The EPT group had a small, nonsignificant reduction in endometrial cancer risk. The women taking EPT were five times as likely to have an endometrial biopsy than the women taking a placebo. The EPT group was also slightly more likely to have an abnormal Pap test.

The WHI was a large, randomized, controlled, double-blinded trial, but it did have certain limitations. The women in these studies were healthy, postmenopausal women. The findings may not apply to other populations, such as women with osteoporosis . Also, there were not many cases of gynecologic cancers, so the study had limited power to determine the effects of EPT on these cancers. Finally, this part of the WHI only examined the effects of one EPT formula. Others—patches or creams, for example—may have different effects.

How Does This Affect You?

These results provide even more evidence that EPT is probably not in the best interest of most women. Although the WHI showed that EPT reduces the risk of fractures in postmenopausal women, there was no net benefit for taking EPT, even in women at high risk for fractures. Furthermore, EPT was associated with more biopsies and abnormal Pap tests. Unnecessary procedures and falsely abnormal results are more than just a burden—they can provoke anxiety and substantially increase health care costs.

Even though the results were not significant, the fact that more women in the EPT group developed ovarian cancer raises some concern. More studies are needed to determine if EPT increases the risk for ovarian cancer.

If you have taken EPT, it’s important to keep these findings in perspective. The individual risk of developing these diseases and conditions is still very small. Talk to your doctor if you are taking—or considering taking—EPT. The extent of your menopausal symptoms, your medical history, and your family medical history make the decision about whether or not to take EPT highly individual. Other therapies are available that will help relieve menopausal symptoms and prevent fractures. You and your doctor can weigh your options.