Hormone replacement therapy (HRT) is prescribed to relieve symptoms of menopause, such as hot flashes, sleep disturbance, vaginal dryness, and mood swings. It is also prescribed for postmenopausal women to help ward off osteoporosis and heart disease. However, some research suggests that HRT containing only estrogen (called ERT) may increase a woman's risk of uterine and ovarian cancers. Still other research suggests that HRT containing both estrogen and progestin may lower the risk of uterine cancer.

Until now, there has been very little research on how HRT containing both estrogen and progestin affects the risk of ovarian cancer. Research recently published in the Journal of the National Cancer Institute suggests that ERT and one other type of HRT may increase the risk of ovarian cancer.

About the study

Researchers in Sweden studied 655 Swedish women with ovarian cancer (cases) and 3899 Swedish women without ovarian cancer (controls). Participants were between the ages of 50 and 74 and were recruited into the study between October 1, 1993 and December 31, 1995. Cases were women with newly diagnosed ovarian cancer for the first time. Controls were matched to cases in terms of age. Women who had previously undergone surgery to remove their ovaries were excluded from this study.

Participants completed mailed questionnaires about their lifestyle habits, use of HRT, and medical histories—particularly reproductive and gynecologic information. Telephone interviewers called women to clarify their answers or fill in missing details, if necessary. The researchers verified the cancer diagnoses among cases by reviewing the pathology reports in their medical records.

The researchers compared the number of cases who took HRT with the number of controls who took HRT. They also looked specifically at which type of HRT the women had taken:

  • Estrogen only (ERT)
  • Estrogen plus progestin taken sequentially (progestin only on 10 to 15 days per cycle)
  • Estrogen plus progestin taken continuously (progestin on 19 to 28 days per cycle)
  • Low-potency estrogen

The findings

Women who took ERT were about 40% more likely to have developed ovarian cancer than women who never took any form of HRT. And, women who took HRT with sequential progestin were 50% more likely to have developed ovarian cancer when compared with never users of HRT. However, women who took low-potency estrogens or HRT with continuous progestin were at no higher risk of ovarian cancer than never users. In fact, users of sequential progestin HRT were more than 75% more likely than users of continuous progestin HRT to have developed ovarian cancer. The women at highest risk were those who had taken HRT for more than 10 years.

The statistics above seem to suggest that although ERT and sequential progestin HRT may be associated with a higher risk of ovarian cancer, continuous progestin HRT and low-potency estrogens are not. In calculating theses statistics, the researchers accounted for factors that may affect a woman's risk of ovarian cancer, such as age at menopause, number of pregnancies, oral contraceptive use, hysterectomy, and age at first menstrual period.

Although these results are interesting, there are some limitations to this study. First, the researchers relied on the women's recall of the types of HRT they took without verifying the information with their medical records. Second, only newly diagnosed ovarian cancer cases were included, so this study did not include any women with previous ovarian cancer or advanced disease. Third, other factors not accounted for in this study, such as genetic factors, may influence the risk of ovarian cancer.

How does this affect you?

Does this mean that you shouldn't take HRT? Not necessarily. Making the decision about whether to take HRT is a complex issue for postmenopausal women and their doctors. Women must weigh their risk of heart disease and osteoporosis with their risk of breast cancer, and according to this study, possibly ovarian cancer.

This study suggests that HRT with sequential progestin and ERT may increase your risk of ovarian cancer. But it also suggests that HRT with continuous progestin does not increase ovarian cancer risk. However, this is the first study to specifically examine the risks of each type of HRT separately. In fact, the authors of this study do not advocate that doctors change their HRT prescribing practices just yet, because more research is needed to confirm these findings.

If you are a postmenopausal woman considering HRT or currently taking HRT, talk with your health care provider about balancing your risk of osteoporosis and heart disease against your risk of breast and ovarian cancers. Your health care provider can help you assess your risks and understand the possible benefits you might gain from taking HRT.