Relevance of the selective oestrogen receptor modulators tamoxifen, toremifene and clomiphene in doping field: Endogenous steroids urinary profile after multiple oral doses

The present study was performed to investigate the influence of the intake of selective oestrogen receptor modulators on the urinary endogenous steroids profile. For this purpose the circadian variability of luteinizing hormone, follicle-stimulating hormone, testosterone, 5α-androstan-3α,17β-diol, 5β-androstan-3α,17β-diol, epitestosterone, 4-androstenedione, androsterone and etiocholanolone were measured on eight subjects (four males and four females) by gas chromatography–mass spectrometry and chemiluminescent immunometric assay techniques before and after oral administration of multiple doses of either tamoxifen (80 mg for 2 days) or toremifene (120 mg for 2 days) or clomiphene (100 mg for 2 days). The individual baseline variability of the steroids studied was set up by collecting the urine samples every 3 h, for 3 days prior to the treatment; whereas the evaluation of the effects of the oral administration of multiple doses of selective oestrogen receptor modulators on the steroid urinary profile was assessed by collecting urine samples every three hours for at least five days from the first administration.The results of our measurements showed that, only in male subjects, the relative urinary concentrations of testosterone, epitestosterone and 4-androstenedione were significantly altered generally after the second day of drug administration. While no significant effects were recorded in both sexes on the luteinizing hormone, follicle-stimulating hormone, androsterone, etiocholanolone, 5α-androstan-3α,17β-diol and 5β-androstan-3α,17β-diol urinary levels and on testosterone/epitestosterone, 5α-androstan-3α,17β-diol/5β-androstan-3α,17β-diol and androsterone/etiocholanolone ratios.

► Since 2005, SERMs were in the World Anti-Doping Agency list of prohibited substances and methods.
► The effects of SERMs administration on the sport performance and on the normal circadian fluctuation of the endogenous hormonal parameters are still unknown.
► The purpose of this study was to verify whatever the oral administration of SERMs (clomiphene, toremifene and tamoxifen) leads to significant variations on the endogenous androgenic steroid urinary excretion.
► The results obtained on urine samples show that only in male subjects, the relative urinary concentrations values of testosterone were significantly altered generally after the second day of drug administration.
► The same finding was not observed in women, whose testosterone is derived mainly from extra-gonad sources that are not involved in any homoeostatic feedback regulation.