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e-Article

Association of endogenous pregnenolone, progesterone, and related metabolites with risk of endometrial and ovarian cancers in postmenopausal women: the B~FIT cohort
Document Type
article
Source
Cancer Epidemiology Biomarkers & Prevention. 30(11)
Subject
Biomedical and Clinical Sciences
Health Services and Systems
Health Sciences
Oncology and Carcinogenesis
Reproductive Medicine
Clinical Research
Prevention
Rare Diseases
Ovarian Cancer
Aging
Cancer
Estrogen
Uterine Cancer
Breast Cancer
Aged
Biomarkers
Case-Control Studies
Cohort Studies
Endometrial Neoplasms
Estradiol
Female
Humans
Middle Aged
Ovarian Neoplasms
Postmenopause
Pregnenolone
Progesterone
Prospective Studies
Risk Factors
Medical and Health Sciences
Epidemiology
Biomedical and clinical sciences
Health sciences
Language
Abstract
BackgroundPostmenopausal pregnenolone and/or progesterone levels in relation to endometrial and ovarian cancer risks have been infrequently evaluated. To address this, we utilized a sensitive and reliable assay to quantify prediagnostic levels of seven markers related to endogenous hormone metabolism.MethodsHormones were quantified in baseline serum collected from postmenopausal women in a cohort study nested within the Breast and Bone Follow-up to the Fracture Intervention Trial (B∼FIT). Women using exogenous hormones at baseline (1992-1993) were excluded. Incident endometrial (n = 65) and ovarian (n = 67) cancers were diagnosed during 12 follow-up years and compared with a subcohort of 345 women (no hysterectomy) and 413 women (no oophorectomy), respectively. Cox models with robust variance were used to estimate cancer risk.ResultsCirculating progesterone levels were not associated with endometrial [tertile (T)3 vs. T1 HR (95% confidence interval): 1.87 (0.85-4.11); P trend = 0.17] or ovarian cancer risk [1.16 (0.58-2.33); 0.73]. Increasing levels of the progesterone-to-estradiol ratio were inversely associated with endometrial cancer risk [T3 vs. T1: 0.29 (0.09-0.95); 0.03]. Increasing levels of 17-hydroxypregnenolone were inversely associated with endometrial cancer risk [0.40 (0.18-0.91); 0.03] and positively associated with ovarian cancer risk [3.11 (1.39-6.93); 0.01].ConclusionsUsing sensitive and reliable assays, this study provides novel data that endogenous progesterone levels are not strongly associated with incident endometrial or ovarian cancer risks. 17-hydroxypregnenolone was positively associated with ovarian cancer and inversely associated with endometrial cancer.ImpactWhile our results require replication in large studies, they provide further support of the hormonal etiology of endometrial and ovarian cancers.