The use of clomiphene citrate to induce ovulation in women with fertility problems appears to be associated with an increased risk of uterine cancer, according to a new report in the American Journal of Epidemiology.

Dr. Michelle D. Althuis from the National Cancer Institute, Bethesda, Maryland and colleagues investigated the possible link between ovulation induction using clomiphene citrate and uterine cancer risk in 8,431 women who were evaluated for infertility between 1965 and 1988.

Thirty-nine uterine cancers were identified over the study period. This gave these infertile women a 56-percent higher risk of developing uterine cancer than women 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 adjusting the data for previously established risk factors, clomiphene use remained an independent predictor of uterine cancer.

The risk was further elevated for women who were followed for 20 years or longer. These women had an increased risk that was two and one half times higher than women who never used clomiphene, the researchers note.

The highest increased risk - more than 12-times higher - occurred in women who were obese and had never been pregnancy at study entry.

High estrogen levels have been “definitively linked to uterine cancer,” the authors note in their paper. “It is therefore likely that clomiphene increases uterine cancer risk simply by indirectly increasing estrogen levels during the first half of the menstrual cycle,” the Althuis’ group suggests.

SOURCE: American Journal of Epidemiology, April 1, 2005.