Compared with women who have never taken hormone therapy, those who currently take it or who have taken it in the past are at increased risk of ovarian cancer, regardless of the duration of use, the formulation, estrogen dose, regimen or route of administration, according to a study in the July 15 issue of JAMA.

Primary prevention of ovarian cancer is challenging because little is known about its cause. Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy (HT), according to background information in the article. Data have been limited on the differing effects of formulations, regimens and routes of administration.

Lina Steinrud Morch, M.Sc., of Rigshospitalet, Copenhagen University, Denmark, and colleagues conducted a study to examine the risk of ovarian cancer associated with hormone therapy use. The study included all Danish women age 50 through 79 years from 1995 through 2005 through linkage to Danish national registers. Prescription data from the National Register of Medicinal Product Statistics provided individually updated information on HT use. The National Cancer Register and Pathology Register provided ovarian cancer incidence data. The analysis included a total of 909,946 women without hormone-sensitive cancer or who had not had both ovaries removed. At the end of follow-up, 63 percent of the women had not been taking HT, 22 percent were previous users of hormones, and 9 percent current users of hormones. Among the current users, 46 percent had used hormones for more than 7 years.

During an average of 8 years of follow-up, 3,068 ovarian cancers were detected. Of these, 2,681 were epithelial tumors. Compared with never users, current users of HT had an overall 38 percent increased risk of ovarian cancer. When restricting the analyses to epithelial ovarian cancer, the relative risk among current HT users was 44 percent higher, with previous HT users having a 15 percent increased risk compared with women who had never used HT. The risk for ovarian cancer and epithelial ovarian cancer did not increase significantly with increasing durations of HT.

The risk of ovarian cancer declined with longer time since last HT use. The risk of ovarian cancer did not differ significantly by formulation, regimen, type of progestin or route of administration.

The absolute risk indicated approximately 1 extra ovarian cancer for roughly 8,300 women taking hormone therapy each year. "If this association is causal, use of hormones has resulted in roughly 140 extra cases of ovarian cancer in Denmark over the mean follow-up of 8 years, i.e., 5 percent of the ovarian cancers in this study. Even though this share seems low, ovarian cancer remains highly fatal, so accordingly this risk warrants consideration when deciding whether to use HT," the authors write.