Doping analysis of the 5a-reductase inhibitor finasteride: determination of its influence on urinary steroid profiles & detection of...

Full Title: Doping-control analysis of the 5alpha-reductase inhibitor finasteride: determination of its influence on urinary steroid profiles and detection of its major urinary metabolite
Ther Drug Monit. 2007 Apr;29(2):236-47.
Thevis M, Geyer H, Mareck U, Flenker U, Schanzer W.
From the Center for Preventive Doping Research, Institute of Biochemistry, German Sport University Cologne, Cologne, Germany.
PubMed ID & Record: 17417080

5alpha-Reductase inhibitors such as finasteride are prohibited in sports according to the World Anti-Doping Agency. This class of drugs is used therapeutically to treat benign prostatic hyperplasia, as well as male baldness, by decreasing 5alpha-reductase activity. Accordingly, metabolic pathways of endogenous as well as synthetic steroids are influenced, which complicates the evaluation of steroid profiles in sports drug testing. The possibility of manipulating steroid excretion profiles and, presumably, to mask steroid abuse was investigated in 5 administration studies with use of finasteride at different doses, with and without coadministration of 19-norandrostenedione. The evaluation of urinary steroid profiles demonstrated the intense effect of finasteride on numerous crucial analytical parameters, in particular the production of 5alpha-steroids such as androsterone and 5alpha-androstane-3alpha,17beta-diol, which was significantly reduced. In addition, the excretion of the main metabolite of norandrostenedione, norandrosterone, was significantly suppressed, by up to 84%, in elimination studies. For doping-control analysis the use of 5alpha-reductase inhibitors causes considerable problems because steroid profile parameters, which are commonly considered stable, are highly affected and complicate the detection of steroid abuse. In addition, the suppression of production and renal excretion of 5alpha-steroids such as 19-norandrosterone generated from anabolic agents such as 19-norandrostenedione may lead to false-negative doping-control results, because urine specimens are reported positive only when a threshold level of 2 ng/mL is exceeded. Finally, a method for the determination of the major urinary metabolite of finasteride (carboxy-finasteride) in routine doping-control screening with use of liquid chromatography-tandem mass spectrometry is described, allowing the detection of carboxy-finasteride for up to 94 hours in urine specimens collected after an oral administration of 5 mg of finasteride.

Air doping: an expose on "frog" insufflation in competitive sports

Am J Phys Med Rehabil. 2007 Apr;86(4):301-303
Bach JR, Tewfik G.
Department of Physical Medicine and Rehabilitation, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, New Jersey, USA.
PubMed ID & Record: 17413543
Comment on: Am J Phys Med Rehabil. 2007 Apr;86(4):290-4.

Doping : High-tech cheating in sport

Internist (Berl) ePpub ahead of print 2007 Apr 11 [Article in German]
Striegel H, Simon P.
Abteilung Sportmedizin, Medizinische Universitatsklinik Tubingen, Silcherstrasse 5, 72076, Tubingen, Deutschland
PubMed ID & Record: 17426943

Today, doping is no longer limited to the classical drugs with well known effects and side effects. Older generation anabolic steroids are used mainly in fitness and recreational sports. In contrast, due to doping tests, substances used in competitive sports include peptide hormones, medications not yet approved, and even specially developed drugs, such as designer steroids. Of the peptide hormones, particularly growth hormones (human growth hormone), erythropoietin and generics, insulin, and presumably insulin-like growth factor 1 are used. Substance groups potentially relevant for doping are selective androgen receptor modulators and gene therapy drugs. For most of these, there is no knowledge about side effects in healthy individuals, and no adequate doping tests. Therefore, anti-doping measures cannot rely solely on the continual improvement of doping analyses, but should include increased measures for doping prevention. Not only sports organizations, but also governmental agencies should be involved in developing and implementing these measures.

Do inhaled beta(2)-agonists have an ergogenic potential in non-asthmatic competitive athletes?

Sports Med. 2007;37(2):95-102
Kindermann W.
Institute of Sports and Preventive Medicine, University of Saarland, Saarbrucken, Germany.
PubMed ID & Record: 17241101

The prevalence of asthma is higher in elite athletes than in the general population. The risk of developing asthmatic symptoms is the highest in endurance athletes and swimmers. Asthma seems particularly widespread in winter-sport athletes such as cross-country skiers. Asthmatic athletes commonly use inhaled beta(2)-agonists to prevent and treat asthmatic symptoms. However, beta(2)-agonists are prohibited according to the Prohibited List of the World Anti-Doping Agency. An exception can be made only for the substances formoterol, salbutamol, salmeterol and terbutaline by inhalation, as long as a therapeutic use exemption has been applied for and granted. In this context, the question arises of whether beta(2)-agonists have ergogenic benefits justifying the prohibition of these substances.In 17 of 19 randomised placebo-controlled trials in non-asthmatic competitive athletes, performance-enhancing effects of the inhaled beta(2)-agonists formoterol, salbutamol, salmeterol and terbutaline could not be proved. This is particularly true for endurance performance, anaerobic power and strength performance. In three of four studies, even supratherapeutic doses of salbutamol (800-1200 microg) had no ergogenic effect. In contrast to inhaled beta(2)-agonists, oral administration of salbutamol seems to be able to improve the muscle strength and the endurance performance. There appears to be no justification to prohibit inhaled beta(2)-agonists from the point of view of the ergogenic effects.

Justice, fairness, and enhancement

Ann N Y Acad Sci. 2006 Dec;1093:321-38
Savulescu J.
Oxford Uehiro Centre for Practical Ethics, Oxford University, Littlegate House, 87 St. Ebbes St., Oxford OX1 1PT, United Kingdom
PubMed ID & Record: 17312266

This article begins by considering four traditional definitions of enhancement, then proposes a fifth, the Welfarist definition. It then considers fairness-based objections to enhancement, using the example of performance enhancement in sport. In so doing it defines sport and the values proper to it, surveys alternative theories of justice, considers the natural distribution of capabilities and disabilities, and draws a distinction between social, psychological, and biological enhancement. The article advances a new argument that justice requires enhancement.

Anticonvulsants in sports: ethical considerations

Epilepsy Behav. 2007 Mar;10(2):268-71. ePpub 2007 Jan 26
Kaufman KR
Department of Psychiatry, UMDNJ - Robert Wood Johnson Medical School, 125 Paterson Street, Suite 2200, New Brunswick, NJ 08901, USA
PubMed ID & Record: 17258507

OBJECTIVE: Antidoping codes in sport are intended to deter and sanction athletes using performance-enhancing agents while promoting an even playing field for all competitors. Although the World Anti-Doping Code (WADC) permits anticonvulsants in general, harmonization of antidoping permits an international sport federation (IF) to prohibit specific medications within that IF. The anticonvulsants levetiracetam, tiagabine, and lamotrigine may pose ethical dilemmas and could be considered violations of antidoping codes. METHOD: This study is a literature review with analysis. RESULTS: Lamotrigine, with antiglutamatergic and sodium channel properties, is FDA-approved for maintenance treatment of bipolar disorder, in addition to its use in the treatment of major depression, anxiety disorders, and schizophrenia. Tiagabine, a selective GABA reuptake inhibitor, has mood-stabilizing and anxiolytic properties. Levetiracetam, whose unique mechanism involves the modulators beta-carboline and zinc, has anxiolytic and mood-stabilizing properties. Anxiolytics, antidepressants, and antipsychotics are banned in archery; under strict liability, all three anticonvulsants violate WADC/IF for that specific sport and could result in disqualification unless therapeutic use exemptions (TUEs) are obtained. Ethical issues regarding the use of anticonvulsants by athletes and the need to obtain TUEs are addressed. CONCLUSION: The WADC with harmonized IF policies are meant to prevent doping by athletes, but not appropriate medical treatment. When anticonvulsants have other psychotropic properties, ethical issues arise. Athletes should list all medications taken with diagnoses, obtain TUEs as indicated, and contact the appropriate IF or Olympic organization to determine the status of the proposed medication (banned, restricted, nonbanned). Further, clinicians should be knowledgeable regarding these issues when treating athletes.

Current anti-doping policy: a critical appraisal

BMC Med Ethics. 2007 Mar 29;8(1):2
Kayser B, Mauron A, Miah A.
PubMed ID & Record: 17394662

ABSTRACT: BACKGROUND: Current anti-doping in competitive sports is advocated for reasons of fair-play and concern for the athletes health. With the inception of the World Anti Doping Agency (WADA), anti-doping effort has been considerably intensified. Resources invested in anti-doping are rising steeply and increasingly involve public funding. Most of the effort concerns elite athletes with much less impact on amateur sports and the general public. DISCUSSION: We review this recent development of increasingly severe anti-doping control measures and find them based on questionable ethical grounds. The ethical foundation of the war on doping consists of largely unsubstantiated assumptions about fairness in sports and the concept of a level playing field. Moreover, it relies on dubious claims about the protection of an athletes health and the value of the essentialist view that sports achievements reflect natural capacities. In addition, costly anti-doping efforts in elite competitive sports concern only a small fraction of the population. From a public health perspective this is problematic since the high prevalence of uncontrolled, medically unsupervised doping practiced in amateur sports and doping-like behaviour in the general population (substance use for performance enhancement outside sport) exposes greater numbers of people to potential harm. In addition, anti-doping has pushed doping and doping-like behaviour underground, thus fostering dangerous practices such as sharing needles for injection. Finally, we argue that the involvement of the medical profession in doping and anti-doping challenges the principles of non-maleficience and of privacy protection. As such, current anti-doping measures potentially introduce problems of greater impact than are solved, and place physicians working with athletes or in anti-doping settings in an ethically difficult position. In response, we argue on behalf of enhancement practices in sports within a framework of medical supervision. SUMMARY: Current anti-doping strategy is aimed at eradication of doping in elite sports by means of all-out repression, buttressed by a war-like ideology similar to the public discourse sustaining international efforts against illicit drugs. Rather than striving for eradication of doping in sports, which appears to be an unattainable goal, a more pragmatic approach aimed at controlled use and harm reduction may be a viable alternative to cope with doping and doping-like behaviour.