title: Urinary steroid profile in females - the impact of menstrual cycle and emergency contraceptives.
abstract: Today's doping tests involving longitudinal monitoring of steroid profiles are difficult in women. Women have more complex hormonal fluctuations than men and commonly take drugs such as hormonal contraceptives that are shown to affect biomarkers used in these doping tests. In this study, we followed six women's urinary steroid profile during one menstrual cycle, including both glucuronides and sulfate conjugated fractions. Additionally, we studied what happens to the steroidal module of the Athlete Biological Passport (ABP) after administration of an emergency contraceptive (levonorgestrel, NorLevo®). The study shows that there are large individual variations in all metabolites included in the ABP and that the administration of emergency contraceptives may lead to suspicious steroid profile findings in the ABP. Urinary epitestosterone concentration increased during the menstrual cycle, leading to a decrease in the testosterone/epitestosterone ratio. The ratios followed in the ABP varied widely throughout the menstrual cycle, the coefficient of variation (CV) ranging from 4 to 99%. There was a 3-fold decrease in epitestosterone 24 h post administration of the emergency contraceptive pill and androsterone, etiocholanolone, and 5β- androstan-3α,17β-diol concentrations decreased about 2-fold. When analyzed with the ABP software, one of the six women had an atypical profile after taking the emergency contraceptive. Furthermore, we could not find any alterations in excretion routes (i.e., if the metabolites are excreted as glucuronide or sulfate conjugates) during the menstrual cycle or after administration of emergency contraceptive, indicating no direct effect on phase II enzymes. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet at Karolinska University Hospital, S-141 86, Stockholm, Sweden.
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Mullen
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet at Karolinska University Hospital, S-141 86, Stockholm, Sweden.
authors.forename: John-Olof
authors.initials: JO
authors.lastname: Thörngren
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet at Karolinska University Hospital, S-141 86, Stockholm, Sweden.
authors.forename: Jenny J
authors.initials: JJ
authors.lastname: Schulze
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet at Karolinska University Hospital, S-141 86, Stockholm, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Ericsson
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet at Karolinska University Hospital, S-141 86, Stockholm, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Gårevik
authors.affiliation: Department of Endocrinology, Metabolism and Diabetes, Departments of Medicine and Molecular Medicine and Surgery, Karolinska Institutet at Karolinska University Hospital, S-141 86, Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Lehtihet
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet at Karolinska University Hospital, S-141 86, Stockholm, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Ekström
mesh_terms: D000328:Adult; D045930:Anabolic Agents / Q000652:urine*; D056352:Athletes; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003281:Contraceptives, Postcoital / Q000652:urine*; D004300:Doping in Sports; D004845:Epitestosterone / Q000652:urine; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D020719:Glucuronides / Q000652:urine; D006801:Humans; D008597:Menstrual Cycle / Q000652:urine*; D008875:Middle Aged; D013256:Steroids / Q000652:urine*; D015813:Substance Abuse Detection / Q000379:methods*; D013739:Testosterone / Q000652:urine
chemical_list: D045930:Anabolic Agents; D003281:Contraceptives, Postcoital; D020719:Glucuronides; D013256:Steroids; D013739:Testosterone; D004845:Epitestosterone
keywords: ABP; HRMS; UHPLC; doping tests; emergency contraceptives; females; menstrual cycle; phase II metabolism; urinary steroid profile