Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review.

Abstract

Endometrial cancer is a disease of the affluent, developed world, where epidemiological studies have shown that > or =40% of its incidence can be attributed to excess body weight. An additional proportion may be because of lack of physical activity. Alterations in endogenous hormone metabolism may provide the main links between endometrial cancer risk, and excess body weight and physical inactivity. Epidemiological studies have shown increased endometrial cancer risks among pre- and postmenopausal women who have elevated plasma androstenedione and testosterone, and among postmenopausal women who have increased levels of estrone and estradiol. Furthermore, there is evidence that chronic hyperinsulinemia is a risk factor. These relationships can all be interpreted in the light of the "unopposed estrogen" hypothesis, which proposes that endometrial cancer may develop as a result of the mitogenic effects of estrogens, when these are insufficiently counterbalanced by progesterone. In our overall synthesis, we conclude that development of ovarian hyperandrogenism may be a central mechanism relating nutritional lifestyle factors to endometrial cancer risk. In premenopausal women, ovarian hyperandrogenism likely increases risk by inducing chronic anovulation and progesterone deficiency. After the menopause, when progesterone synthesis has ceased altogether, excess weight may continue increasing risk through elevated plasma levels of androgen precursors, increasing estrogen levels through the aromatization of the androgens in adipose tissue. The ovarian androgen excess may be because of an interaction between obesity-related, chronic hyperinsulinemia with genetic factors predisposing to the development of ovarian hyperandrogenism.

• Authors: Rudolf Kaaks, Annekatrin Lukanova, Mindy S Kurzer
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 11 Issue 12 Pg. 1531-43 (Dec 2002) ISSN: 1055-9965 [Print] United States
• PMID: 12496040 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Androgens
• Estrogens
• Gonadal Steroid Hormones
• Insulin
• Sex Hormone-Binding Globulin

Topics

• Age Distribution
• Aged
• Androgens (adverse effects, metabolism)
• Endometrial Neoplasms (epidemiology, etiology)
• Estrogens (analysis, metabolism)
• Female
• Gonadal Steroid Hormones (adverse effects, metabolism)
• Humans
• Insulin (analysis, metabolism)
• Middle Aged
• Obesity (complications)
• Prevalence
• Prognosis
• Risk Assessment
• Risk Factors
• Sex Hormone-Binding Globulin (metabolism)