Long-term use of hormone replacement therapy may be associated with increased risk of ovarian cancer

According to a new study published in the Journal of the National Cancer Institute, menopausal women who use long-term hormone replacement therapy (unopposed estrogen or estrogen in combination with progestin) may have up to a 3-fold increased risk of developing ovarian cancer compared with women who do not use hormone replacement therapy.

The authors stated, "These data expand the range of possible risks associated with menopausal hormone therapy." In 2002, concern over the use of hormone replacement therapy peaked when the Women's Health Initiative Study, a randomized, controlled trial published in the Journal of the American Medical Association (JAMA), demonstrated that the use of hormone replacement therapy in menopausal women resulted in a statistically significant increase in the risk of breast cancer, blood clots, stroke, and heart disease.

In this most recent study, the authors evaluated data from 97,638 menopausal women, aged 50 to 71 years, who were enrolled in the National Institutes of Health (NIH)–AARP Diet and Health Study. Study participants had to complete 2 questionnaires between 1995 and 1997 to be included in this analysis. After completion of the questionnaires, participants were tracked using state and national cancer and death registries.

An NIH statement on the management of menopause-related symptoms stated that a large percentage of women will experience some degree of menopause-related symptoms, including vasomotor symptoms (hot flashes and night sweats), vaginal dryness, and sleep disturbances. For these women, hormone replacement therapy is the most consistently effective treatment, and even after the results of the Women's Health Initiative (WHI) Study, many women have opted to start or remain on hormone replacement therapy because they feel the benefits they receive outweigh the risks. The authors similarly noted that "the increased absolute risks [of ovarian cancer] appear to be small" and thus, "other risk-benefit considerations may dominate patients' and clinicians' decision making regarding hormone therapy." The authors did, however, emphasize that "these associations, if real, represent potentially avoidable risk factors for a highly fatal cancer and therefore warrant continued investigation."

SOURCES Lacey JV Jr, Brinton LA, Leitzmann MF, et al. Menopausal hormone therapy and ovarian cancer risk in the National Institutes of Health–AARP Diet and Health Study cohort. J Natl Cancer Inst. 2006;98:1397–1405.

Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288:321–333.

NIH State of the Science Panel. National Institutes of Health State-of-the-Science Conference Statement: Management of Menopause-Related Symptoms. Ann Intern Med. 2005;142:1003–1013.