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International Journal of Endocrinology
Volume 2016, Article ID 8671762, 17 pages
http://dx.doi.org/10.1155/2016/8671762
Review Article

Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

1Unit of Endocrinology, Regina Elena National Cancer Institute, Rome, Italy
2Unit of Endocrinology, Department of Systems’ Medicine, University of Rome Tor Vergata, Section of Reproductive Endocrinology, Fatebenefratelli Hospital “San Giovanni Calibita” Rome, Italy
3Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy
4Department of Gynaecologic Oncology, HPV-Unit, Regina Elena National Cancer Institute, Rome, Italy

Received 13 May 2016; Revised 12 July 2016; Accepted 8 August 2016

Academic Editor: Vittorio Unfer

Copyright © 2016 Rosa Lauretta et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis.