Clomiphene Use May Boost Uterine Cancer Risk

NEW YORK APR 25, 2005 (Reuters Health) - The use of clomiphene citrate to induce ovulation is associated with an increase in the risk of uterine cancer, according to a report in the April 1st issue of the American Journal of Epidemiology.

Dr. Michelle D. Althuis from the National Cancer Institute, Bethesda, Maryland and colleagues investigated the possible link between clomiphene citrate ovulation induction and uterine cancer risk in 8431 women evaluated for infertility between 1965 and 1988.

Thirty-nine uterine cancers were identified over a total of 145,876 woman-years. This gave infertile women a 56% higher risk of developing uterine cancer than those in the general population.

The increased uterine cancer risk was more pronounced (a more than twofold increase) among women who had been exposed to clomiphene. After adjustment for previously established risk factors, clomiphene use remained an independent predictor of uterine cancer.

The risk was further elevated for women followed for 20 or more years (2.5-fold higher than never users of clomiphene), the researchers note. The highest risk elevation (12.52-fold higher) was faced by women who were both obese and nulligravid at study entry.

"High levels of unopposed estrogen have been definitively linked to uterine cancer," the authors conclude. "It is therefore likely that clomiphene increases uterine cancer risk simply by indirectly increasing estrogen levels during the first half of the menstrual cycle."

SOURCE:

• American Journal of Epidemiology 2005;161:607-615.