HRT Is Not Recommended to Treat Chronic Conditions

ROCKVILLE, Maryland—An independent advisory board has entered the debate over the safety and efficacy of hormonal replacement therapy (HRT) and recommended against the use of the estrogen/progestin combination in postmenopausal women as a preventive treatment for cardiovascular disease and other chronic conditions. It also concluded that insufficient evidence exists to support a recommendation for or against the use of estrogen alone for preventing chronic conditions in postmenopausal women who have undergone a hysterectomy.

In its assessment, The US Preventive Services Task Force (USPSTF) reported that HRT increases a woman’s risk of developing several hormone-related cancers, while lowering the risk of colorectal cancer. It found fair evidence that HRT increases the risk of cholecystitis.

The panel found good evidence that HRT increases bone mineral density and fair-to-good evidence that it reduces the risk of fractures. It found insufficient evidence for a beneficial effect of HRT on dementia or cognitive dysfunction.

The task force made its recommendation after reviewing the current medical literature on HRT, including the Women’s Health Initiative (WHI) trial that found an increased risk of breast cancer with the use of estrogen and progestin. That arm of the WHI has been canceled.

The literature review was contained in a report prepared by Heidi Nelson, MD, and Linda Humphrey, MD, two researchers at the Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center at the Oregon Health & Science University, Portland. The task force consists of nongovernment experts in primary care who make recommendations for clinical preventive services.

The task force did not address HRT’s role in treating menopausal symptoms. It recommended that women using or considering using hormonal therapy for menopausal symptoms discuss their individual risks with their physician.

"These recommendations reflect the scientific evidence concerning the long-term effects of HRT, but there are no easy answers for women," said USPSTF chairman Alfred Berg, MD, professor and chair of family medicine, University of Washington. "It is, therefore, especially important that women talk to their clinicians to decide what is best for them."

The USPSTF concluded that HRT fails to decrease the incidence of coronary heart disease (CHD) and may even increase a woman’s risk of heart disease. "The effects of HRT on CHD mortality, however, are less certain," the report said. The panel also found fair evidence that HRT increases the risk of stroke and good evidence that it increases the risk of venous thromboembolism.

The task force reported fair to good evidence that HRT, particularly the use of estrogen and progestin in combination, increases the incidence of breast cancer but concluded that its effects on breast cancer mortality are uncertain. "In the aggregate, breast cancer incidence is slightly increased for current or long-term (greater than 5 years) users compared to nonusers," the USPSTF said. "However, there seems to be no effect on or decreased breast cancer mortality in ever- or short-term users. The effects of long-term HRT use on breast cancer mortality in two good-quality cohort studies are conflicting. Whether the combination of estrogen and progestin confers a greater risk than estrogen alone is unknown."

The task force concluded that fair evidence supports observations that HRT reduces the incidence of colorectal cancer. It cited a meta-analysis of 18 observational studies of postmenopausal women showing a 20% reduction in colon cancer and a 19% decrease in rectal cancer in women who had ever used HRT. "The decrease in risk was more apparent when current users were compared with those who had never used HRT," the task force said.

It also noted that the WHI study reported similar colorectal cancer results and that the Heart and Estrogen/Progestin Replacement Study (HERS) found a reduced incidence of colon cancer.

The panel further concluded that unopposed estrogen, but not the combination therapy, increases the risk of endometrial cancer. "Results of a previously published meta-analysis of 29 good-quality observational studies of endometrial cancer reported a relative risk of 2.3 for users of unopposed estrogen compared with nonusers," the USPSTF said. "Risks increased with increasing duration of use. The risk for endometrial cancer remained elevated 5 or more years after discontinuation of unopposed estrogen therapy in these studies."

Studies of women receiving estrogen/progestin offered mixed results. "Cohort studies showed a decreased risk for endometrial cancer compared with nonusers, but case-control studies showed an increase in risk," the panel reported. "Estrogen and progestin did not increase the risk for endometrial cancer in HERS or in the WHI."

As for ovarian cancer, the data are inconsistent. "Results of case-control studies have been mixed, but two good-quality cohort studies reported increased risks for ovarian cancer or ovarian cancer mortality among women who had taken HRT for 10 years," the USPSTF said. A third study found no effect of HRT on ovarian cancer mortality, and one study suggested a higher risk for estrogen-only than for estrogen/progestin therapy. As a result, the panel concluded that there was insufficient evidence to determine the effect of HRT on ovarian cancer.