Ovulation Inducing Agents and Cancer Risk: Review of Literature

Over the past decades, the use of ovulation inducing drugs has been increasing. A possible causal link between fertility treatments (especially clomiphene citrate and gonadotrophins) and various types of malignancies, including cancers of female reproductive system, thyroid cancer and melanoma, has been postulated. The majority of the available studies on this subject suffers from methodological limitations, including the small number of outcomes, short and incomplete follow-up, and inability to control for potential confounders. Concerning ovarian cancer, while early studies led to the suggestion of an association between ovulation inducing agents and increased risk of malignancies, the majority of data do not support a causal link. An increased risk was recently observed in women giving birth after in vitro fertilization (IVF), but it appeared to be consequential to the infertile status rather than the effect of fertility drugs. More controversial are the results concerning breast cancer with some investigations suggesting an increased risk after exposure to ovulation inducing agents, especially clomiphene citrate, whereas others not supporting this concept. A possible trend towards an increased risk has been reported by some authors for endometrial cancer. Altogether, current data should be thus regarded as a signal for the need of further studies rather than being definitive in them.