Effects of propyphenazone and other non-steroidal anti-inflammatory agents on the synthetic and endogenous androgenic anabolic steroids urinary excretion and/or instrumental detection

This paper describes the effects of oral administration of non-steroidal anti-inflammatory drugs on the endogenous and synthetic anabolic androgenic steroids urinary excretion as assessed by gas-chromatography mass-spectrometry. Experiments were carried out on 5 male subjects, with pathologies and/or diseases, treated with non-steroidal anti-inflammatory drugs. To set up the individual baseline variability of testosterone and its main metabolites, urine samples were collected for 3 days, every 2 h prior to the administration of the drug(s); whereas the study of the effects of a single dose of each drug, here considered, on the endogenous androgen steroid urinary concentrations, was assessed by collecting urine samples for 2 days, every 2 h. Data obtained after drugs administration were then evaluated taking into account the individual baseline variability. The results showed that, only in the case of propyphenazone administration, the relative urinary concentrations of some testosterone metabolites were significantly altered. More specifically, the urinary levels of dehydroepiandrosterone, 11keto-etiocholanolone, 11β-hydroxyandrosterone, 11β-hydroxyetiocholanolone, androsterone, etiocholanolone and some metabolite ratios decrease significantly, generally between 2 and 10 h after administration of the drug, whereas no effects were observed on urinary calculated concentrations of testosterone, epitestosterone, 5α-androstane-3α,17β-diol, 5β-androstane-3α,17β-diol and testosterone/epitestosterone ratio. The observed effects do not depend on alterations on pharmacokinetics (excretion/metabolism), but on steroid sample preparation steps (hydrolysis and derivatization) inhibition. More specifically the significant decrease of dehydroepiandrosterone and testosterone metabolites urinary levels was due to a reduced yield of the steroid derivatization step for the presence in urine of the main metabolites of propyphenazone, namely hydroxyl-propyphenazone metabolites.