Women who are treated with clomiphene citrate for subfertility should be aware that they are at increased risk of endometrial cancer, largely due to the underlying condition causing subfertility, according to a recent Cochrane review.

Investigators looked at 19 studies involving more than 1.9 million individuals. The trials compared the risk of developing endometrial cancer in women exposed to ovary-stimulating drugs vs either 1) subfertile women not exposed to these drugs or 2) women from the general population. Among the results:

• Overall, exposure to clomiphene citrate—especially at doses greater than 2000 mg and more than 7 cycles—may be linked with an increased risk of developing endometrial cancer later in life.
• Elevated risk may largely be due to underlying risk factors in women who need treatment with clomiphene citrate, such as polycystic ovary syndrome, rather than exposure to the drug itself.