Background Case reports and the results of a recent case-controlstudy have raised questions about the potential neoplastic effectsof medications used as treatment for infertility.
Methods We examined the risk of ovarian tumors in a cohort of3837 women evaluated for infertility between 1974 and 1985 inSeattle. Computer linkage with a population-based tumor registrywas used to identify women in whom tumors were diagnosed beforeJanuary 1, 1992. Data on infertility testing and treatment wereabstracted from the medical records of women who had ovariancancer and those of a randomly selected comparison group. Therisk of ovarian tumors associated with exposure to ovulation-inducingmedications was assessed through an age-standardized comparisonwith the rate of ovarian tumors in the general population, andCox regression analysis was used to compare the risk of canceramong women who received these medications with the risk amonginfertile women who did not receive them.
Results There were 11 invasive or borderline malignant ovariantumors, as compared with an expected number of 4.4 (standardizedincidence ratio, 2.5; 95 percent confidence interval, 1.3 to4.5). Nine of the women in whom ovarian tumors developed hadtaken clomiphene; the adjusted relative risk among these women,as compared with that among infertile women who had not takenthis drug, was 2.3 (95 percent confidence interval, 0.5 to 11.4).Five of the nine women had taken the drug during 12 or moremonthly cycles. This period of treatment was associated withan increased risk of ovarian tumors among both women with ovarianabnormalities and those without apparent abnormalities (relativerisk, 11.1; 95 percent confidence interval, 1.5 to 82.3), whereastreatment with the drug for less than one year was not associatedwith an increased risk.
Conclusions Prolonged use of clomiphene may increase the riskof a borderline or invasive ovarian tumor.
Source Information
From the Departments of Epidemiology (M.A.R., J.R.D., N.S.W.) and Biostatistics (S.G.S.), School of Public Health and Community Medicine, and the Department of Obstetrics and Gynecology, School of Medicine (D.E.M.), University of Washington; and the Fred Hutchinson Cancer Research Center (M.A.R., J.R.D., N.S.W., S.G.S.) -- all in Seattle.
Address reprint requests to Dr. Rossing at Fred Hutchinson Cancer Research Center, 1124 Columbia St., Seattle, WA 98104.
Risk of Ovarian Cancer after Treatment for Infertility
Del Priore G., Robischon K., Phipps W. R., Kurman R., Wallach E. E., Zacur H. A., Shapiro S., Rossing M. A., Daling J. R., Weiss N. S., Cramer D. W., Hartge P., Nasca P. C., Whittemore A. S.
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N Engl J Med 1995;
332:1300-1302, May 11, 1995.
Correspondence
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