Luteinizing hormone, its beta-subunit variant, and epithelial ovarian cancer: The gonadotropin hypothesis revisited

The gonadotropin hypothesis postulates that excessive gonadotropin stimulat ion results in increased proliferation and subsequent malignant transformat ion of ovarian epithelium. The authors evaluated this hypothesis by analyzi ng the association between serum levels of wild-type luteinizing hormone (L H) and ovarian cancer risk. They also examined the relation between a varia nt of LH containing two missense point mutations (Trp(8)Arg and lle(15)Thr) in its beta -subunit and ovarian cancer risk. Fifty-eight cases of epithel ial ovarian cancer and 116 controls matched on age, menopausal status, and date of blood donation were included in a case-control study nested within the New York University Women's Health Study, a prospective cohort enrolled between 1985 and 1991 in New York City, Wild-type serum levels and Variant LH status were determined by immunofluorometric assays in which monoclonal antibodies specific for wild-type and variant LH were used. Compared with women in the lowest tertile of wild-type LH, women in the highest tertile h ad a lower risk of ovarian cancer, after adjustment for potential confounde rs (odds ratio = 0.42, 95% confidence interval: 0.09, 2.09). Women heterozy gous for variant LH were not at increased risk (adjusted odds ratio = 0.95, 95% confidence interval: 0.27, 3.34). The results suggest that neither wil d-type LH levels nor variant LH status is associated with increased risk of epithelial ovarian cancer.