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Large Study Finds Prolonged Use Estrogen Replacement Therapy Increases Risk of Death from Ovarian Cancer (dateline March 22, 2001)

In a study of more than 200,000 women, researchers from the American Cancer Society found that using estrogen replacement therapy (ERT) for 10 or more years increases the risk of death from ovarian cancer.  While the chances of developing ovarian cancer doubles with prolonged ERT use, the risk still appears to be small—approximately 2% over a lifetime. Therefore, women who take or plan to take ERT for a prolonged period of time should discuss the benefits and risks of the therapy with their physicians.

The study, which is published in the March 21, 2001 issue of the Journal of the American Medical Association, followed 211,581 women from 1982 to 1996. The study was "prospective" since none of the women had a history of cancer, hysterectomy or ovarian surgery at the time of enrollment. During the 14-year follow-up 944 deaths from ovarian cancer were recorded, and the researchers found that using ERT for 10 or more years doubled the risk of developing ovarian cancer (from 1% to 2%). This risk remained for up to 29 years after women stopped using ERT.

Despite these results, lead researcher Carmen Rodriguez, MD and her colleagues are quick to point out that the study did not include data from women who used combination hormone replacement therapy, which is the most common regimen prescribed today. Combination hormone therapy consists of both estrogen and progestin (a synthetic form of the hormone, progesterone). Additional research is needed to determine whether prolonged hormone therapy with progestin also carries this increased ovarian cancer risk.

This latest study creates even more confusion for the 20 million American women who use hormone replacement therapy to help relieve menopausal symptoms (such as hot flashes and vaginal dryness) or treat osteoporosis, a degenerative bone disease. Recently, women have been overwhelmed with reports that HRT may increase the risk for breast cancer, especially when taken for over five years. Further research is needed to confirm these findings.

While Dr. Rodriguez and the researchers are not certain why ERT increases the risk of ovarian cancer, they do know that estrogen causes ovarian cells to produce at faster than normal rates. The more times a cell divides, the higher the chances that it will replicate an abnormal copy, which could result in cancer if the abnormal copy controls cell growth. ERT has also been associated with an increased risk of endometrial cancer (cancer of the uterine lining), but using combination hormone therapy (with progestin) counteracts this risk.

The following chart summarizes the possible benefits and risks of ERT (estrogen without progestin). The benefits and risks may differ when estrogen is combined with progestin. For example, the increased risk of endometrial cancer is not associated with combination hormone therapy.

Possible Benefits of ERT Possible Risks of ERT
  • Relieves menopausal symptoms—hot flashes, vaginal dryness, etc.
  • Prevents and treats osteoporosis
  • May improve mood
  • May protect against heart disease (further research needed)
  • May provide some protective effect/benefit with Alzheimer’s disease and diabetes
  • May increase risk of breast cancer when taken for more than 5 years
  • Increases risk of endometrial cancer—cancer of the uterine lining (risk counteracted if estrogen is combined with progestin)
  • Increases risk of ovarian cancer
  • May be associated with side effects, such as bloating, nausea, etc.

Dr. Rodriguez and her colleagues recommend that all women who use (or are considering) hormone replacement therapy discuss the benefits and risks with their physicians, and come to a decision about the therapy (including regimen and duration of treatment) based on their personal circumstances. For many women, the benefit of relieving menopausal symptoms or treating osteoporosis outweighs the slightly increased risk of cancer.

Additional Resources and References