Androgen Abuse in Athletes: Detection and Consequences

Department of Medicine, Division of Endocrinology and Metabolism, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.31). 02/2010; 95(4):1533-43. DOI: 10.1210/jc.2009-1579
Source: PubMed

ABSTRACT Doping with anabolic androgenic steroids (AAS) both in sports (especially power sports) and among specific subsets of the population is rampant. With increasing availability of designer androgens, significant efforts are needed by antidoping authorities to develop sensitive methods to detect their use.
The PubMed and Google Scholar search engines were used to identify publications addressing various forms of doping, methods employed in their detection, and adverse effects associated with their use.
The list of drugs prohibited by the World Anti-Doping Agency (WADA) has grown in the last decade. The newer entries into this list include gonadotropins, estrogen antagonists, aromatase inhibitors, androgen precursors, and selective androgen receptor modulators. The use of mass spectrometry has revolutionized the detection of various compounds; however, challenges remain in identifying newer designer androgens because their chemical signature is unknown. Development of high throughput bioassays may be an answer to this problem. It appears that the use of AAS continues to be associated with premature mortality (especially cardiovascular) in addition to suppressed spermatogenesis, gynecomastia, and virilization.
The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. The development of sensitive detection techniques may help discourage (at least to some extent) the abuse of these compounds. Investigations are needed to identify ways to hasten the recovery of the gonadal axis in AAS users and to determine the mechanism of cardiac damage by these compounds.

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    • "Intake of AAS by athletes and others in an attempt to gain strength and improve performance is often associated with toxic effects on the liver, the cardiovascular system and the Abbreviations: AAS, anabolic-androgenic steroids; CNS, central nervous system; AR, androgen receptor; PARP, poly (adenosine diphosphate [ADP]-ribose) polymerase; Hsp, heat shock protein; NGF, nerve growth factor; PC12, pheochromocytoma 12 cells; EB, Ethidium bromide; AO, Acridine orange. male and female reproductive systems (Trifunovic et al., 1995; Basaria, 2010). At the physiological level, there are a wide range of effects of AAS as they possess both anabolic, or muscle-building, and androgenic, or masculinizing, properties (Kanayama et al., 2007). "
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    ABSTRACT: Anabolic-androgenic steroids (AAS) are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle mass. AAS exert well known toxic effects on specific cell and tissue types and organ systems. The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. Among numerous commercially available steroid hormones, very few have been specifically tested for direct neurotoxicity. We evaluated the effects of supraphysiological doses of methandienone and 17-α-methyltestosterone on sympathetic-like neuron cells. Vitality and apoptotic effects were analyzed, and immunofluorescence staining and western blot performed. In this study, we demonstrate that exposure of supraphysiological doses of methandienone and 17-α-methyltestosterone are toxic to the neuron-like differentiated pheochromocytoma cell line PC12, as confirmed by toxicity on neurite networks responding to nerve growth factor and the modulation of the survival and apoptosis-related proteins ERK, caspase-3, poly (ADP-ribose) polymerase and heat-shock protein 90. We observe, in contrast to some previous reports but in accordance with others, expression of the androgen receptor (AR) in neuron-like cells, which when inhibited mitigated the toxic effects of AAS tested, suggesting that the AR could be binding these steroid hormones to induce genomic effects. We also note elevated transcription of neuritin in treated cells, a neurotropic factor likely expressed in an attempt to resist neurotoxicity. Taken together, these results demonstrate that supraphysiological exposure to the AAS methandienone and 17-α-methyltestosterone exert neurotoxic effects by an increase in the activity of the intrinsic apoptotic pathway and alterations in neurite networks.
    Frontiers in Cellular Neuroscience 05/2013; 7:69. DOI:10.3389/fncel.2013.00069 · 4.18 Impact Factor
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    • "As with other species, chronic administration of estrogens results in hyperplasia and squamous metaplasia of the prostate (Heywood and Wadsworth 1980). Use of SERMs and other estrogen-ablative agents by human males (e.g., bodybuilders ) may lead to increased endogenous androgen production (Basaria 2010), possibly mediated by increased gonadal testosterone production secondary to increased LH concentrations (Leder et al. 2004; Taxel et al. 2001). Treatment of adult male bonnet monkeys (Macaca radiata) with Tamoxifen for ninety days had no effect on the serum T concentrations or total sperm count but resulted in a significant reduction in sperm motility and lack of fertility from day 90 to day 260 (Rao et al. 1998). "
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    • "Even if known since years it has gained attention of anti - doping researchers in the last couple of years since an increasing number of professional athletes were convicted of using this substance for doping purposes ( World Anti - Doping Agency , 2010b ) . However , also recreational and junior athletes and even the broad public are attracted by anabolic steroids , especially MD ( Basaria , 2010 ) . Commonly used methods to detect its abuse are based on the identification of different urinary MD metabolites via liquid chro - matography tandem mass spectrometry ( LC – MS / MS ) and gas chromatography ( tandem ) mass spectrometry ( GC – MS ( / MS ) ) anal - ysis ( Schänzer et al . "
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    ABSTRACT: The metabolism of a variety of anabolic steroids frequently misused for doping purposes has been investigated in the last years. This research mainly focused on main and long-term metabolites suitable for detection, but detailed clearance mechanisms have rarely been elucidated. Recent studies on metandienone focused on the identification of 17β-hydroxymethyl-17α-methyl-18-norandrosta-1,4,13-trien-3-one (20βOH-NorMD) as long-term metabolite, however, the metabolic pathway of its generation remained unclear. Metandienone and its Wagner-Meerwein rearrangement product 17,17-dimethyl-18-norandrosta-1,4,13-trien-3-one (NorMD) were hydroxylated by different human cytochrome P450 enzymes (CYPs). Some of their hydroxylation products were chemically synthesized and characterized by mass spectrometry to allow for their trace detection in urine samples. Following oral administration of metandienone or NorMD in one human volunteer each the post administration urines were checked for the presence of those hydroxylated metabolites using GC-MS/MS analysis. The human mitochondrial steroid hydroxylating enzymes CYP11B1 and CYP11B2 were capable to metabolize metandienone leading to the formation of 11β-hydroxymetandienone and 18-hydroxymetandienone. Following Wagner-Meerwein rearrangement, the resulting products could be assigned to 20βOH-NorMD and 11βOH-NorMD. The contribution of CYP11B1 and CYP11B2 in human metabolism of metandienone was confirmed by analysis of post-administration samples of metandienone and NorMD. Combined with the results from a previous study, enzymatic pathways were identified that involve CYP21 and CYP3A4 in the hydroxylation of NorMD, while CYP21, CYP3A4 and CYP11B2 take part in 20βOH-NorMD generation from MD. The current study represents a valuable contribution to the elucidation of clearance mechanisms of anabolic steroids and also indicates that mainly non-liver CYPs seem to be involved in these processes.
    Toxicology Letters 07/2012; 213(3):381-91. DOI:10.1016/j.toxlet.2012.07.020 · 3.36 Impact Factor
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