OBJECTIVE:

To review and critique the literature regarding ovulation induction and cancer risk.

DESIGN:

Identification of relevant clinical and epidemiological literature through PubMed and other sources.

CONCLUSION(S):

Ovulation and associated hormonal changes have been linked with selected cancers, raising concerns regarding ovulation-inducing agents. Clinical studies have suggested potential links, but more definitive analytic investigations have been difficult to interpret given the small numbers, short follow-up, and imprecise information on drugs or indications for usage. Prospective studies have been limited by inabilities to control for other cancer predictors (including parity), while selective recall has been a concern for retrospective studies. Reports of large increases in ovarian cancer risk associated with fertility medications have not been replicated by more recent investigations. Some findings, based on small numbers, suggest slight increases in risk associated with fertility drugs among nulligravid women or after extended follow-up or for certain tumor subtypes, but further replication is needed. Fewer studies have assessed relationships with other hormonally related cancers, but limited findings support the need for further monitoring of long-term effects for breast and endometrial cancers. Findings regarding other cancers are extremely limited but should be pursued for cancers showing evidence of hormonal influences, including colon cancers and melanomas.