Evaluation of urinary excretion of androgens conjugated to cysteine in human pregnancy by mass spectrometry

Alterations in the maternal excretion of steroids during pregnancy are not restricted to the production of progesterone and estriol by the fetoplacental unit. Although there is a lack of longitudinal data on urinary androgen concentrations during pregnancy, some studies revealed that modifications in the excretions of androgens might be significant. Recently, several testosterone metabolites excreted as cysteine conjugates have been reported in human urine. We conducted a longitudinal study on androgens conjugated with cysteine and major androgens and estrogens excreted as glucuronides in three pregnant women by mass spectrometric techniques. The urinary concentrations obtained in samples weekly collected during each of the three trimesters and samples collected before pregnancy were compared. Results showed a significant increase in urinary estrogens and norandrosterone and a moderate decrease in the urinary concentrations for most of the androgens. The most significant exception to this behavior was the rise observed for epitestosterone glucuronide when comparing basal levels with the first trimester. Cysteinyl conjugates of testosterone metabolites showed a different behavior. Whereas 4,6-androstanedione remained almost constant through the three trimesters, and Δ6-testosterone decreased as the majority of androgens, the excretion profile of 1,4-androstanedione notably increased, reaching a maximum at the third trimester. Alterations in the steroid profile are used in doping control analysis for the screening of endogenous anabolic androgenic steroid misuse. In this study, the main parameters proposed for doping control have been determined for basal samples and samples collected in the first trimester and they have been compared. In spite of the limited number of cases, significant variations have been found in all pregnancies studied. These alterations have to be taken into consideration if anabolic steroids are included into the Athlete Biological Passport.This article is part of a Special Issue entitled ‘Pregnancy and Steroids’.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A longitudinal study on urinary steroid profile in 3 pregnancies was conducted. ► Novel cysteinyl conjugates of testosterone metabolites were included. ► 1,4-Androstendione and epitestosterone increased parallel to estrogens. ► Δ6-Testosterone decreased as the majority of androgens. ► Some ratios used in doping control are already affected during the first trimester.