Prediagnostic circulating follicle stimulating hormone concentrations and ovarian cancer risk

Abstract

Gonadotropins have been indicted in ovarian carcinogenesis but direct evidence has been limited and inconsistent. The aim of this study was to determine the association between prediagnostic levels of follicle stimulating hormone (FSH) and subsequent development of invasive epithelial ovarian cancer. A nested case-control study was conducted using cases and controls drawn from three cohorts: CLUE I and CLUE II of Washington County, MD, and the Island of Guernsey Study, United Kingdom. In total, 67 incident invasive epithelial ovarian cancer cases were each matched to 1 to 2 controls on age, menopausal status, time since last menstrual period, current hormone use and other relevant factors. FSH concentrations were classified into ranked thirds of low, medium or high based on the distribution among controls. Conditional logistic regression was used to estimate the odds ratio (OR) across increasing thirds of FSH concentrations. Results of the analysis showed that ovarian cancer risk decreased with higher FSH concentrations (p-trend 5 0.005). Compared with the lowest third of FSH concentrations, the OR among those in the middle and highest thirds were 0.45 [95% Confidence Interval (CI): 0.20-1.00] and 0.26 (95% CI: 0.10-0.70), respectively. Associations persisted after excluding cases diagnosed within 5 years of follow-up. In conclusion, a reduction in subsequent risk of invasive epithelial ovarian cancer was observed among women with higher circulating FSH concentrations. These findings contradict the hypothesized role of FSH as a risk factor in ovarian carcinogenesis. ' 2009 UICC Key words: follicle stimulating hormone (FSH); ovarian cancer; gonadotropins; epidemiology; cohort study Exposure of the ovarian surface epithelium to elevated gonadotropin levels has been proposed to play a deleterious role in ovarian carcinogenesis.1 This view is based on the concept that postovulatory inclusion cysts formed from invagination of the ovarian surface epithelium (OSE) are exposed to excessive substromal stimulation by gonadotropins and estrogen in the premenopausal period, resulting in increased cellular proliferation with eventual progression to malignant transformation. The hypothesis is largely based on observations in animal models in which various means of increased production of gonadotropins [follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH)] was associated with ovarian tumor development.1 In humans, epidemiologic evidence in support of this hypothesis includes the decreased risk observed with oral contraceptive use, pregnancy and possibly lactation. All of these factors, which suppress gonadotropin-releasing hormone (GnRH) signaling for synthesis and secretion of both FSH and LH, are in agreement with this hypothesis. 2Only 2 studies of actual prediagnostic circulating concentrations of gonadotropin in relation to ovarian cancer risk have been reported and their results do not, overall, support the ''gonadotropin hypothesis.'' 1,3 A small nested-case-control study of 31 cases (of whom 14 were prem...

Demographic, lifestyle, and other factors in relation to antimüllerian hormone levels in mostly late premenopausal women

“…The aim of that study is to examine associations between AMH concentrations and ovarian and endometrial cancer risks using blood samples and covariate data from nine cohorts including the Columbia, Missouri Serum Bank (USA) (19), the Campaign Against Cancer and Heart Disease (CLUE I/II; USA) (45), the European Prospective Investigation into Cancer and Nutrition (EPIC; Europe) (46), the Guernsey Cohort Study (UK) (47), the New York University Women’s Health Study (NYUWHS; USA) (48), the Nurses’ Health Study and Nurses’ Health Study II (NHS/NHSII;USA) (49), the Hormones and Diet in the Etiology of Breast Cancer (ORDET; Italy) (50), the Northern Sweden Health and Disease Study (NSHDS; Sweden) (51), and the Shanghai Women’s Health Study (SWHS; China) (52). …”

“…Blood samples were collected during visits to the study centers (19, 45–48, 50–52) or by mailing phlebotomy kits to the laboratory via overnight couriers (49) in each of the original cohorts. These blood samples were processed, separated into serum (19, 45–48) or plasma (45, 46, 49–52) using EDTA (51, 52), heparin (45, 49, 50) or multiple anticoagulants (e.g., EDTA, heparin, citrate) (46) at each cohort and archived in freezers at −70°C or colder except in Guernsey where samples were stored at −20°C.…”

“…These blood samples were processed, separated into serum (19, 45–48) or plasma (45, 46, 49–52) using EDTA (51, 52), heparin (45, 49, 50) or multiple anticoagulants (e.g., EDTA, heparin, citrate) (46) at each cohort and archived in freezers at −70°C or colder except in Guernsey where samples were stored at −20°C.…”

“…Plasma (45, 46, 49–52) or serum samples (19, 45–48) stored in each cohort were sent to a single laboratory at the Massachusetts General Hospital (Boston, MA, USA) for AMH assays. Case-control pair samples blinded to case and control status were randomly ordered and assayed together within batches for AMH using a picoAMH Enzyme-Linked Immunosorbent Assay (ELISA) kit (Ansh Catalog no.…”

Steroid Hormones and Ovarian Cancer

“…Similarly, peritoneal fluid aspirates contained elevated levels of FSH and LH in ovarian carcinoma versus benign tumors (Chudecka-Glaz et al, 2004;Halperin et al, 2003). One recent study actually found that in 67 patients with ovarian cancer versus controls, increased circulating levels of FSH were correlated with a reduced prediagnostic risk of EOC, which argues against the excess gonadotropin hypothesis in ovarian carcinogenesis (McSorley et al, 2009). …”