Journal Article

Uterine Cancer after Use of Clomiphene Citrate to Induce Ovulation

Michelle D. Althuis, Kamran S. Moghissi, Carolyn L. Westhoff, Bert Scoccia, Emmet J. Lamb, Jay H. Lubin and Louise A. Brinton

in American Journal of Epidemiology

Published on behalf of Johns Hopkins Bloomberg School of Public Health

Volume 161, issue 7, pages 607-615
Published in print April 2005 | ISSN: 0002-9262
Published online April 2005 | e-ISSN: 1476-6256 | DOI:
Uterine Cancer after Use of Clomiphene Citrate to Induce Ovulation

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Clomiphene citrate, a selective estrogen receptor modulator, increases estradiol levels and consequently may increase risk of cancer of the uterine corpus. The authors conducted a retrospective cohort study of 8,431 US women (145,876 woman-years) evaluated for infertility during 1965–1988. Through 1999, 39 uterine cancers were ascertained by questionnaire or cancer and death registries. Poisson regression estimated adjusted rate ratios. Study results suggest that clomiphene may increase uterine cancer risk (rate ratio (RR) = 1.79, 95% confidence interval (CI): 0.9, 3.4) and present evidence of a dose response (ptrend = 0.07) and latency effect (ptrend = 0.04). Uterine cancer risk increased with clomiphene dose (RR = 1.93, 95% CI: 0.9, 4.0 for >900 mg), menstrual cycles of use (RR = 2.16, 95% CI: 0.9, 5.2 for ≥6 cycles), and time elapsed since initial use (RR = 2.50, 95% CI: 0.9, 7.2 for women followed for ≥20 years). Risk was more strongly associated with clomiphene among nulligravid (RR = 3.49, 95% CI: 1.3, 9.3) and obese (RR = 6.02, 95% CI: 1.2, 30.0) women, with risk substantially elevated among women who were both obese and nulligravid (RR = 12.52, 95% CI: 1.5, 108.0). Clomiphene may increase uterine cancer risk, with higher doses leading to higher risk. Long-term follow-up of infertility cohorts is necessary to clarify the association between clomiphene use and uterine cancer.

Keywords: clomiphene; fertility agents; gonadotropins; infertility; ovulation; uterine neoplasms; CI, confidence interval; RR, rate ratio; SIR, standardized incidence ratio

Journal Article.  4880 words. 

Subjects: Public Health and Epidemiology

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