title: Premenopausal Circulating Androgens and Risk of Endometrial Cancer: results of a Prospective Study.
abstract: Endometrial cancer risk is increased by estrogens unopposed by progesterone. In premenopausal women, androgen excess is often associated with progesterone insufficiency, suggesting that premenopausal androgen concentrations may be associated with risk. In a case-control study nested within three cohorts, we assessed the relationship between premenopausal androgens and risk of endometrial cancer (161 cases and 303 controls matched on age and date of blood donation). Testosterone, DHEAS, androstenedione, and SHBG were measured in serum or plasma. Free testosterone was calculated from testosterone and SHBG. We observed trends of increasing risk across tertiles of testosterone (ORT3-T1 = 1.59, 95 % CI = 0.96, 2.64, p = 0.08) and free testosterone (ORT3-T1 = 1.76, 95 % CI = 1.01, 3.07, p = 0.047), which were not statistically significant after adjustment for body mass index (BMI). There was no association for DHEAS, androstenedione, or SHBG. There were significant interactions by age at diagnosis (<55 years, n = 51 cases; ≥55 years, n = 110 cases). Among women who were ≥55 years of age (predominantly postmenopausal) at diagnosis, the BMI-adjusted OR was 2.08 (95 % CI = 1.25, 3.44, p = 0.005) for a doubling in testosterone and 1.55 (95 % CI = 1.04, 2.31, p = 0.049) for a doubling in free testosterone. There was no association among women aged <55 years at diagnosis, consistent with the only other prospective study to date. If pre- and post-menopausal concentrations of androgens are correlated, our observation of an association of premenopausal androgens with risk among women aged ≥55 years at diagnosis could be due to the effect on the endometrium of postmenopausal androgen-derived estrogens in the absence of progesterone, which is no longer secreted.
authors.affiliation: Department of Population Health, Division of Epidemiology and Biostatistics, New York University School of Medicine, 650 1st Ave, New York, NY, 10016, USA.
authors.forename: Tess V
authors.initials: TV
authors.lastname: Clendenen
authors.affiliation: Department of Environmental Medicine, Division of Epidemiology and Biostatistics, New York University School of Medicine, New York, NY, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Hertzmark
authors.affiliation: Department of Population Health, Division of Epidemiology and Biostatistics, New York University School of Medicine, 650 1st Ave, New York, NY, 10016, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Koenig
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Lundin
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Sabina
authors.initials: S
authors.lastname: Rinaldi
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Theron
authors.initials: T
authors.lastname: Johnson
authors.affiliation: Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
authors.affiliation: Department of Public Health and Clinical Medicine/Nutritional Research and Department of Biobank Research, Umeå University, Umeå, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.affiliation: Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Idahl
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Annekatrin
authors.initials: A
authors.lastname: Lukanova
authors.affiliation: Department of Population Health, Division of Epidemiology and Biostatistics, New York University School of Medicine, 650 1st Ave, New York, NY, 10016, USA. anne.jacquotte@nyumc.org.|New York University Cancer Institute, New York, NY, USA. anne.jacquotte@nyumc.org.
authors.forename: Anne
authors.initials: A
authors.lastname: Zeleniuch-Jacquotte
mesh_terms: D000328:Adult; D000368:Aged; D000728:Androgens / Q000097:blood*; D015415:Biomarkers; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017697:Premenopause / Q000097:blood*; D011446:Prospective Studies; D012306:Risk
chemical_list: D000728:Androgens; D015415:Biomarkers