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1 Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York and 2 IARC, Lyon, France
Requests for reprints: Annekatrin Lukanova, Department of Obstetrics and Gynecology, New York University School of Medicine, 550 First Avenue, NBV 9E2, New York, NY 10016. Phone: 212-263-0486; Fax: 212-263-8887. E-mail: annekatrin.lukanova{at}med.nyu.edu
The effect of major epidemiologic risk factors for ovarian cancer has been reviewed in the light of several hormonal hypotheses, including the gonadotropin, androgens, progesterone, estrogens, insulin-like growth factor-I, and insulin hypotheses. The role of inclusion cyst formation and Mullerian epithelium differentiation in the pathology of the disease are also briefly outlined. Although based on limited data, the observed tendency in current evidence suggests possible etiologic roles for elevated androgens and estrogens and decreased progesterone in the pathogenesis of ovarian cancer. A direct effect of gonadotropins cannot be entirely ruled out, but it is plausible that their effect on ovarian cancer risk is mediated by stimulation of ovarian steroidogenesis. Insulin-like growth factor-I also emerges as a hormone that may be directly involved in the pathogenesis of the disease, but thus far only one prospective study has examined this association. Hyperinsulinemia is an unlikely risk factor for ovarian cancer. The observed tendency for an increased risk with androgens from ovarian origin (in premenopausal women), the lack of association with adrenal androgens, and the relatively weak associations observed with obesity, hormonal replacement therapy use, and endogenous hormones after menopause suggest that ovarian synthesis of sex steroids rather than their circulating levels may be etiologically important. More data from prospective studies will be crucial to improve our understanding of the etiologic role of endogenous hormones in the pathogenesis of ovarian cancer. Such data will ultimately provide opportunities for research targeted; at early detection and preventive interventions.
Key Words: ovarian cancer • androgens • estrogens • progesterone • gonadotropins • Gynecologic cancers: ovarian
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