Detection and effects on serum and urine steroid and LH of repeated GnRH analog (leuprolide) stimulation.
Non-steroidal drugs that increase endogenous testosterone (T) may be used to exploit ergogenic effects of androgens in power sports. While superactive GnRH analog use is suspected, neither screening nor detection tests are developed. This study aimed to determine if (a) stimulation for 5 days by leuprolide (a superactive GnRH analog) of serum and urine steroids and urine LH is reproducible at a 2 week interval, (b) nandrolone decanoate (ND) co-administration masks responses to leuprolide administration, (c) performance of urine measurement of leuprolide and M1, its major metabolite, as a detection test. Healthy men were randomized into a 4 week parallel group, open label clinical study in which all men had daily sc injections of leuprolide (1mg) for 4 days in the 1st and 3rd weeks with hormone-free 2nd and 4th weeks. In the 3rd week, men were randomized to either ND injections or no extra treatment. Serum steroids were determined by liquid chromatography, tandem mass spectrometry (LC-MS), urine steroids by gas chromatography, mass spectrometry (GC-MS), urine leuprolide and M1 by high resolution LC-MS and urine LH by immunoassay. Leuprolide stimulated striking, reproducible increases in serum and urine LH and steroids (serum T, dihydroT (DHT), 3α diol; urine T, epitestosterone (E) and androsterone (A). ND suppressed basal serum T, E2, 3α diol, and urinary E but did not mask or change the magnitude of responses to leuprolide. Urine leuprolide and M1 measurement had 100% sensitivity and specificity in detecting leuprolide administration up to one day after cessation of injections with the detection window between 1 and 3 days after last dose. Screening using urine steroid and LH measurements, optimally by urinary log10(LHxT), correctly classified 82% of urine samples. It is concluded that leuprolide stimulation of endogenous testosterone is reproducible after a 10-day interval, is not masked by ND and is reliably detected by urine leuprolide or M1 measurement for at least 1 day after administration.
Andrology Department, Concord Hospital, Sydney, NSW 2139, Australia; ANZAC Research Institute, University of Sydney, Sydney, NSW 2139, Australia. Electronic address: djh@anzac.edu.au.
David J
DJ
Handelsman
Andrology Department, Concord Hospital, Sydney, NSW 2139, Australia.
Amanda
A
Idan
Australian Sports Drug Testing Laboratory, National Measurement Institute, Sydney, NSW 2139, Australia.
Janelle
J
Grainger
Australian Sports Drug Testing Laboratory, National Measurement Institute, Sydney, NSW 2139, Australia.
Catrin
C
Goebel
Andrology Department, Concord Hospital, Sydney, NSW 2139, Australia.
Leo
L
Turner
Andrology Department, Concord Hospital, Sydney, NSW 2139, Australia; ANZAC Research Institute, University of Sydney, Sydney, NSW 2139, Australia.
Ann J
AJ
Conway
D000328:Adult; D013196:Dihydrotestosterone / Q000097:blood / Q000652:urine; D004300:Doping in Sports; D004958:Estradiol / Q000097:blood / Q000652:urine; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000652:urine; D007986:Luteinizing Hormone / Q000097:blood* / Q000652:urine; D008297:Male; D008875:Middle Aged; D009277:Nandrolone / Q000031:analogs & derivatives / Q000494:pharmacology; D000077603:Nandrolone Decanoate; D058573:Performance-Enhancing Substances / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000652:urine; D013739:Testosterone / Q000097:blood* / Q000652:urine; D055815:Young Adult
D058573:Performance-Enhancing Substances; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D009277:Nandrolone; D007986:Luteinizing Hormone; D016729:Leuprolide; D000077603:Nandrolone Decanoate
Doping; GnRH Analog; Leuprolide; Testosterone