Role of Estrogen and Progesterone in Obesity Associated Gynecologic Cancers

Abstract

Obesity is an established endometrial cancer risk factor, and may, to a lesser extent, also increase ovarian cancer. Given that the primary source of postmenopausal estrogens is through peripheral conversion of precursors in adipose tissue and that endometrial cancer arises from an imbalance of estrogen to progesterone levels, much attention has focused on these two hormones. Indirect evidence for an important role of these hormones derives from studies of menopausal hormones and oral contraceptives, whose use is, respectively, directly and inversely associated with both endometrial and ovarian cancer risks. Endometrial cancer risks are particularly enhanced if unopposed estrogens are prescribed, especially among thin women. Studies have demonstrated a link between high endogenous estrogen levels and increased endometrial cancer risk, with most metabolites showing evidence of uterotropic activity. Estrogens are less strongly related to ovarian cancer, although may predispose some to non-serous cancers, which are also enhanced among obese women. Difficulties in measuring progesterone levels have hampered our understanding of their effects, although improved assays have recently been developed. To fully understand the role of estrogens and progestogens, additional attention should focus on other hormones (e.g., androgens), insulin, growth factors, and such obesity-related biomarkers as adiponectin. While cervical and vulvar cancers do not show strong relations of risk with obesity, it is possible that hormonal changes associated with obesity may enhance the effects of the human papillomaviruses, important causes of both of these tumors. With obesity rates rapidly increasing, further clarification of the biologic underpinnings of gynecologic cancers are needed to inform future prevention efforts.