Metformin and Gynecologic Cancers

Importance: The obese population in the United States is reaching epic proportions, and obesity is linked to an increased risk for several cancers including gynecologic cancers. Obesity is not only a risk factor but also a marker of poor prognosis. It is crucial to develop novel treatment strategies to target this population. Metformin is a biguanide drug, typically used for diabetes treatment, currently being studied to evaluate its role in the treatment and prevention of gynecologic cancers. Objective: The aim of this study was to review the underlying biologic mechanisms of metformin's antitumorigenic effects. We assessed the epidemiologic and preclinical data that support the use of metformin in patients with endometrial and ovarian cancer. Finally, we reviewed current clinical trials that incorporate metformin as a prevention or treatment strategy for gynecologic cancers. Evidence Acquisition: A thorough search of PubMed for all current literature was performed. All preclinical, clinical, and epidemiologic reviews were evaluated across all cancers, with a focus on gynecologic cancer. Results: The preclinical, epidemiologic, and clinical data evaluated in this review are strongly supportive of the use of metformin for the prevention and treatment of gynecologic cancer. On the basis of these data, centers are currently enrolling for clinical trials using metformin in patients diagnosed with gynecologic malignancies. Conclusions and Relevance: The data supporting the use of metformin in the prevention and treatment of cancers are building, including that of endometrial and ovarian cancer. The association between obesity, insulin resistance, as well as increased risk and poor outcomes in endometrial and ovarian cancer patients makes metformin an attractive agent for the prevention and treatment of these diseases. Target Audience: Obstetricians and gynecologists, family physicians Learning Objectives: After completing this CME activity, physicians should be better able to appraise the underlying biologic mechanisms of metformin's antitumorigenic effects; assess the epidemiologic and preclinical data that affect a woman's risk for developing endometrial cancers, support the use of metformin in patients with endometrial and ovarian cancer, and explore its use in the prevention and treatment of both of these cancers; as well as evaluate clinical trials that incorporate metformin as a prevention or treatment strategy for gynecologic cancers.