title: Variation in serum biomarkers with sex and female hormonal status: implications for clinical tests.
abstract: Few serum biomarker tests are implemented in clinical practice and recent reports raise concerns about poor reproducibility of biomarker studies. Here, we investigated the potential role of sex and female hormonal status in this widespread irreproducibility. We examined 171 serum proteins and small molecules measured in 1,676 participants from the Netherlands Study of Depression and Anxiety. Concentrations of 96 molecules varied with sex and 66 molecules varied between oral contraceptive pill users, postmenopausal females, and females in the follicular and luteal phases of the menstrual cycle (FDR-adjusted p-value <0.05). Simulations of biomarker studies yielded up to 40% false discoveries when patient and control groups were not matched for sex and up to 41% false discoveries when premenopausal females were not matched for oral contraceptive pill use. High accuracy (over 90%) classification tools were developed to label samples with sex and female hormonal status where this information was not collected.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB2 1QT, United Kingdom.
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Ramsey
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB2 1QT, United Kingdom.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Cooper
authors.affiliation: Department of Psychiatry, VU University Medical Centre and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB2 1QT, United Kingdom.|Department of Neuroscience, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Sabine
authors.initials: S
authors.lastname: Bahn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001008:Anxiety Disorders / Q000097:blood* / Q000175:diagnosis; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D019963:Clinical Chemistry Tests / Q000592:standards; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage*; D003865:Major Depressive Disorder / Q000097:blood* / Q000175:diagnosis; D005189:False Positive Reactions; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D008297:Male; D008597:Menstrual Cycle / Q000097:blood*; D008875:Middle Aged; D009426:Netherlands; D017697:Premenopause / Q000097:blood*; D015203:Reproducibility of Results; D012737:Sex Factors
chemical_list: D015415:Biomarkers; D003278:Contraceptives, Oral, Hormonal; D012739:Gonadal Steroid Hormones