Prolonged Hormone Replacement Therapy Linked to Increased Ovarian Cancer Risk
Abstract & Commentary
By William B. Ershler, MD, INOVA Fairfax Hospital Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, D.C. Dr. Ershler reports no financial relationship to this field of study.
Synopsis: There have been conflicting reports on the risks of ovarian cancer in users of hormone replacement therapy. In the NIH-AARP Diet and Health Study Cohort, analysis of various aspects of HRT and the development of ovarian cancer in approximately 100,000 women aged 50-71 years was undertaken. Long durations of use of unopposed estrogen and of estrogen plus progestin, especially sequential regimens, were found to be associated with increased ovarian cancer risk.
Source: Lacey JV, 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.
There have been many studies examining the relationship between hormone replacement therapy and ovarian cancer risk, but none have been conclusive in demonstrating increased risk.
The National Institutes of Health-AARP Diet and Health Study was originally conducted in 1995when a questionnaire addressing health related issues was mailed to 3.5 million AARP members. This baseline instrument addressed details of demographics, reproductive history, family history and hormone replacement therapy use including duration and type of treatment. The survey was followed by a second questionnaire (1996 to 1997) that requested more detailed information about the actual hormone replacement therapy.
The study was conducted on 136,409 women aged 50-71 years who completed the second questionnaire. Of these, 97,638 met the criteria for inclusion in the current analysis. Women who used unopposed estrogen for longer than 10 years were found to have a statistically significant increased risk for developing ovarian cancer (RR, 1.89; 95% confidence interval [CI], 1.22-2.95; P = 0.004). This association was slightly attenuated in women with hysterectomy (RR, 1.70; 95% CI, 0.87-3.31; P = 0.06). A similar pattern was found for women with intact uteri who used combination estrogen/progesterone therapy (RR, 1.50; 95% CI, 1.03-2.19; P = 0.04).
Interestingly, risk of ovarian cancer for women with intact uteri was found to be higher for women taking sequential regimens (RR, 1.94; 95% CI, 1.17-3.22; P = 0.01) in contrast those who received continuous regimens (RR, 1.41; 95% CI, 0.90-2.22; P = 0.14). Furthermore, this increase in risk with sequential regimens was apparent even after a shorter duration of treatment (eg, 5 years).
Commentary
Due to its large sample size and detailed questionnaire addressing multiple different patterns of hormone use, this study allows for better determination of hormone replacement risk in post-menopausal women. Based on this analysis, it would appear that short duration with low-dose regimens of hormones may be an option for women with severe symptoms of menopause without significantly increasing risk of developing ovarian cancer.
The finding of increased risk with sequential versus continuous therapy is in line with a large Swedish case-control study published in 2002.1 Sequential regimens typically result in monthly withdrawal bleeding and these are most commonly used by perimenopausal, or early post-menopausal women. The convenience of continuous regimens (including continuous combined regimens) and absence of breakthrough bleeding in most women after the first few months of use are thought to contribute to preferential use among women who are years past menopause.2,3 Because younger women have a lower incidence of ovarian cancer, the more frequent use of the sequential regimen in this age group might have over-emphasized the magnitude of the risk.
Hormonal replacement therapy has declined dramatically since the publication of the Women's Health Initiative in 20034 and it is likely that the increased ovarian cancer risk observed among long-duration users of unopposed estrogens will diminish in scope over the next several years. However, the current study also provides evidence that links use of estrogen plus progestin, especially in sequential regimens to increased ovarian cancer risk. If confirmed, this is a modifiable risk factor that may be explored in strategies to reduce incidence of this often lethal cancer.
References
1. Riman T, et al. Hormone replacement therapy and the risk of invasive epithelial ovarian cancer in Swedish women. J Natl Cancer Inst. 2002;94:497-504.
2. American College of Physicians. Guidelines for counseling post-menopausal women about preventive hormone therapy. American College of Physicians. Ann Intern Med. 1992;117:1038-1041.
3. McNagny SE. Prescribing hormone replacement therapy for menopausal symptoms. Ann Intern Med. 1999;131:605-616.
4. Anderson GL, et al. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial. JAMA. 2003;290:1739-1748.
There have been conflicting reports on the risks of ovarian cancer in users of hormone replacement therapy. In the NIH-AARP Diet and Health Study Cohort, analysis of various aspects of HRT and the development of ovarian cancer in approximately 100,000 women aged 50-71 years was undertaken.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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