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July 16, 2002 — Women who use estrogen-only hormone replacement therapy (HRT) for a long period of time have an increased risk of developing ovarian cancer, according to a study published in the July 17 issue of The Journal of the American Medical Association (JAMA).
James V. Lacey Jr., Ph.D., and colleagues from the National Cancer Institute (NCI) in Bethesda, Md., conducted a follow-up study of 44,241 former participants in the Breast Cancer Detection Demonstration Project (BCDDP), a mammography screening program conducted between 1973 to 1980. The women in the NCI study were all postmenopausal and had an average age of 56.6 years at the beginning of follow-up. Some had undergone hysterectomy, but all had at least one ovary.
According to background information in the article, most previous studies, have found no association between HRT and ovarian cancer, but these studies examined a small sample of patients, collected incomplete information about ovarian cancer risk factors, or did not distinguish between estrogen replacement therapy (ERT) and estrogen-progestin replacement therapy (EPRT).
Between 1979 and 1998, the authors interviewed participants about the type of hormones used (ERT or EPRT), age at first use of hormones, duration of hormone use, form of hormone administration and other possible ovarian cancer risk factors. The researchers asked participants whether they had been diagnosed with ovarian cancer, and then reviewed medical records, death certificates and state cancer registry data to confirm those diagnoses.
Among the 44,241 women who accounted for 589,213 person-years of follow-up, 329 women developed ovarian cancer. The risk of ovarian cancer was increased with ERT use among women with and without hysterectomy, and risk increased proportionately with longer duration of hormone use. Women who used ERT only had a 60 percent greater risk of developing ovarian cancer than women who have never used HRT, whereas women who used ERT for 20 or more years were approximately three times more likely to develop ovarian cancer (although only 16 ovarian cancers occurred in this group). However, women who used an estrogen-progestin combination did not appear to have a significantly increased risk of developing ovarian cancer.
The authors conclude that while this study and other recent reports point to an association between long-term ERT use and ovarian cancer, more research is needed to gauge the risks of EPRT. "Although earlier studies seemed to indicate that there was no association with ERT, this recent emergence of an increased risk in long-term users should remind investigators that it would be premature to conclude that EPRT has no association with ovarian cancer until other large studies specifically assess ovarian cancer risk among persons with short-term or long-term EPRT use."
Editorial: Estrogen Replacement Therapy and Risk of Ovarian Cancer
In an accompanying editorial, Kenneth L. Noller, M.D., of Tufts University and New England Medical Center in Boston, Mass., writes that old attitudes about estrogen replacement therapy (ERT) are being challenged by new findings in studies such as Lacey et al.
"For a short time, estrogen replacement was viewed as the perfect solution for many health problems in postmenopausal women. Estrogens were thought to prevent coronary artery disease and delay the onset of Alzheimer disease," Dr. Noller writes.
Dr. Noller pointed out that previous studies did not discover a connection between HRT and ovarian cancer, but more recent studies, including the report by Lacey et al., indicate that one could exist. "While the data from these observational studies do not establish causality, the association between estrogen use and ovarian cancer should be worrisome enough for clinicians to consider carefully whether to suggest estrogen-only HRT," he said.
"Estrogen replacement therapy certainly is not the panacea it once appeared. Physicians counseling women about HRT must consider the unique needs of each patient and attempt to weigh the benefits and risks on an individual basis," he said.