Ehrnborg C, Rosén T. Physiological and pharmacological basis for the ergogenic effects of growth hormone in elite sports. Asian J Androl. 2008 May;10(3):373-83.

Ehrnborg C, Ellegård L, Bosaeus I, Bengtsson BA, Rosén T. Supraphysiological growth hormone: less fat, more extracellular fluid but uncertain effects on muscles in healthy, active young adults. Clin Endocrinol (Oxf). 2005 Apr;62(4):449-57.

CAS 2008/A/1565 World Anti-Doping Agency (WADA) v. International Military Sports Council (CISM) & Federico Turrini

Related case:

Swiss Federal Court 4A_10_2009 Federico Turrini vs WADA & CISM
July 8, 2009

• Aquatics (swimming)
• Doping (19-norandrosterone)
• Dies a quo of the time limit for the filing of the appeal
• Presence of a prohibited substance
• Conditions of reduction of the period of ineligibility based on exceptional circumstances
• Determination of the disciplinary sanction

1. It is very important that international sports law rules are equally applied for all parties, no matter if they are athletes or organizations, and that the application also must be foreseeable for those involved. If a party which have not taken part in the proceedings leading to the appealed decision shall have a fair opportunity to file an appeal it must be aware of that decision. In spite of the wording of the applicable rule, according to the applicable procedural rules, international sport law and CAS case law, the time limit for the filing of the appeal should not be counted from the date when the decision has been made, but when the party appealing the decision has been notified of such decision. In any event, it is for the respondent to prove that the decision was communicated more than 21 days prior to the appellant’s statement of appeal.

2. The presence of 19-norandrosterone which is an endogenous anabolic androgenic steroid at a concentration greater than 2 ng/ml in an athlete’s bodily specimen constitutes a doping violation incompatible with an endogenous production of the substance.

3. It is the professional duty of an athlete to consult the rules and to be well aware of all the duties an athlete has to fulfil. In this respect, an athlete must be active to ensure that no prohibited substance enters his/her body. As said in the Commentary to WADC, an athlete cannot rely on advice from his/her personal physician in these matters, especially when the doctor is no expert on sports medicine. The fact that an athlete is a professional is also relevant. If the athlete has not done anything to ensure this, s/he has not established that he bears no significant fault or negligence. There is therefore no ground to reduce the sanction on this basis.

4. It is well established that a two-year suspension for a first time doping offence is legally acceptable. Pursuant to the rules, the period of provisional suspension voluntarily accepted by an athlete shall be credited against the total period of ineligibility to be served. Furthermore, it is required by fairness that the starting date of the period of ineligibility should not constitute a disadvantage for the athlete when the process from the sample collection to the date when the sanction can be imposed has been far too long.

On 15 January 2008 the International Military Sports Council (CISM) decided to impose a suspended sanction of 2 years on the Italian swimmer Frederico Turrini after his sample tested positive for the prohibited substance 19-norandrosterone (Nandrolone).

Here the Athlete denied the intentional, accepted the test result and explained that the postitive test was caused by prescribed eye drops that contained the prohibited substance.

Hereafter in May 2008 the World Anti-Doping Agency (WADA) appealed the CISM decision with the Court of Arbitration for Sport (CAS). WADA requested the Panel to set aside the Appealed Decision and to impose a 2 year period of ineligibility on the Athlete.

Following assessment of the case the Panel concludes that the Athlete committed an anti-doping rule violation and that he failed to establish that he bears No Significant Fault or Negligence.

The Panel deems that the Athlete, in order to fulfil his or her duty according to Art. 2.1. of the WADC, has to be active to ensure that a medication that he or she uses does not contain any compound that is on the Prohibited List. In the present case, the Athlete has not done anything to ensure this.

Therefore the Court of Arbitration for Sport decides on 4 November 2008 that:

(1) The appeal filed by WADA on 30 May 2008 is admissible.

(2) The decision of CISM Discipline Commission dated 15 January 2008 in the matter of Federico Turrini. is set aside.

(3) Federico Turrini is sanctioned by a two (2) years ineligibility, which started on 6 February 2008. The period of voluntary suspension from 3 December 2007 to 5 February 2008 shall be credited against the total period of ineligibility to be served.

(4) All competitive results obtained by Federico Turrini from 19 October 2007 until the date of the present decision shall be disqualified with all of the resulting consequences including forfeiture of any medals, points and prizes.

(5) All other prayers for relief are dismissed.

(6) The award is pronounced without costs except for the Court Office fee of CHF 500,- (five hundred Swiss Francs) paid by Mr Federico Turrini and which is kept by the CAS.

(7) Each party shall bear its own costs.

Dufka F, Galloway G, Baggott M, Mendelson J. The effects of inhaled L-methamphetamine on athletic performance while riding a stationary bike: a randomised placebo-controlled trial. Br J Sports Med. 2009 Oct;43(11):832-5. Epub 2008 Nov 3.

Docherty JR. Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA). Br J Pharmacol. 2008 Jun;154(3):606-22.

Thevis M, Kamber M, Schänzer W. Screening for metabolically stable aryl-propionamide-derived selective androgen receptor modulators for doping control purposes. Rapid Commun Mass Spectrom. 2006;20(5):870-6.

Pharmacodynamics of selective androgen receptor modulators / Donghua Yin, Wenqing Gao, Jeffrey D. Kearbey, Huiping Xu, Kiwon Chung, Yali He, Craig A. Marhefka, Karen A. Veverka, Duane D. Miller, James T. Dalton. - (Journal of Pharmacology and Experimental Therapeutics 304 (2003) 3 (March), p. 1334-1340)

• PMID: 12604714
• DOI: 10.1124/jpet.102.040840

Abstract

The present study aimed to identify selective androgen receptor modulators (SARMs) with in vivo pharmacological activity. We examined the in vitro and in vivo pharmacological activity of four chiral, nonsteroidal SARMs synthesized in our laboratories. In the in vitro assays, these compounds demonstrated moderate to high androgen receptor (AR) binding affinity, with K(i) values ranging from 4 to 37 nM, and three of the compounds efficaciously stimulated AR-mediated reporter gene expression. The compounds were then administered subcutaneously to castrated rats to appraise their in vivo pharmacological activity. Androgenic activity was evaluated by the ability of these compounds to maintain the weights of prostate and seminal vesicle, whereas levator ani muscle weight was used as a measure of anabolic activity. The maximal response (E(max)) and dose for half-maximal effect (ED(50)) were determined for each compound and compared with that observed for testosterone propionate (TP). Compounds S-1 and S-4 demonstrated in vivo androgenic and anabolic activity, whereas compounds S-2 and S-3 did not. The activities of S-1 and S-4 were tissue-selective in that both compounds stimulated the anabolic organs more than the androgenic organs. These two compounds were less potent and efficacious than TP in androgenic activity, but their anabolic activity was similar to or greater than that of TP. Neither S-1 nor S-4 caused significant luteinizing hormone or follicle stimulating hormone suppression at doses near the ED(50) value. Thus, compounds S-1 and S-4 were identified as SARMs with potent and tissue-selective in vivo pharmacological activity, and represent the first members of a new class of SARMs with selective anabolic effects.

The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women : results of a double-blind, placebo-controlled phase II trial / James T. Dalton, Kester G. Barnette, Casey E. Bohl, Michael L. Hancock, Domingo Rodriguez, Shontelle T. Dodson, Ronald A. Morton, Mitchell S. Steiner. - (Journal of Cachexia, Sarcopenia and Muscle 2 (2011) 3 (September), p. 153-161)

• PMID: 22031847
• PMCID: PMC3177038
• DOI: 10.1007/s13539-011-0034-6

Abstract

BACKGROUND: Cachexia, also known as muscle wasting, is a complex metabolic condition characterized by loss of skeletal muscle and a decline in physical function. Muscle wasting is associated with cancer, sarcopenia, chronic obstructive pulmonary disease, end-stage renal disease, and other chronic conditions and results in significant morbidity and mortality. GTx-024 (enobosarm) is a nonsteroidal selective androgen receptor modulator (SARM) that has tissue-selective anabolic effects in muscle and bone, while sparing other androgenic tissue related to hair growth in women and prostate effects in men. GTx-024 has demonstrated promising pharmacologic effects in preclinical studies and favorable safety and pharmacokinetic profiles in phase I investigation. METHODS: A 12-week double-blind, placebo-controlled phase II clinical trial was conducted to evaluate GTx-024 in 120 healthy elderly men (>60 years of age) and postmenopausal women. The primary endpoint was total lean body mass assessed by dual energy X-ray absorptiometry, and secondary endpoints included physical function, body weight, insulin resistance, and safety. RESULTS: GTx-024 treatment resulted in dose-dependent increases in total lean body mass that were statistically significant (P < 0.001, 3 mg vs. placebo) and clinically meaningful. There were also significant improvements in physical function (P = 0.013, 3 mg vs. placebo) and insulin resistance (P = 0.013, 3 mg vs. placebo). The incidence of adverse events was similar between treatment groups. CONCLUSION: GTx-024 showed a dose-dependent improvement in total lean body mass and physical function and was well tolerated. GTx-024 may be useful in the prevention and/or treatment of muscle wasting associated with cancer and other chronic diseases.

Importance of hemoglobin concentration to exercise : acute manipulations / José A.L. Calbet, Carsten Lundby, Maria Koskolou, Robert Boushel. - (Respiratory Physiology & Neurobiology 151 (2006) 2-3 (28 April); p. 132-140)

• PMID: 16516566
• DOI: 10.1016/j.resp.2006.01.014

Abstract

An acute reduction of blood hemoglobin concentration ([Hb]), even when the circulating blood volume is maintained, results in lower (.)V(O(2)(max) and endurance performance, due to the reduction of the oxygen carrying capacity of blood. Conversely, an increase of [Hb] is associated with enhanced (.)V(O(2)(max) and endurance capacity, that is also proportional to the increase in the oxygen carrying capacity of blood. The effects on endurance capacity appear more pronounced and prolonged than on (.)V(O(2)(max). During submaximal exercise, there is a tight coupling between O(2) demand and O(2) delivery, such that if [Hb] is acutely decreased muscle blood flow is increased proportionally and vice versa. During maximal exercise with either a small or a large muscle mass, neither peak cardiac output nor peak leg blood flow are affected by reduced [Hb]. An acute increase of [Hb] has no effect on maximal exercise capacity or (.)V(O(2)(max) during exercise in acute hypoxia. Likewise, reducing [Hb] in altitude-acclimatized humans to pre-acclimatization values has no effect on (.)V(O(2)(max) during exercise in hypoxia.

Impact of alterations in total hemoglobin mass on VO 2max / Walter Schmidt, Nicole Prommer. - (Exercise and Sport Sciences Reviews 38 (2010) 2 (April); p. 68-75)

• PMID: 20335738
• DOI: 10.1097/JES.0b013e3181d4957a

Abstract

Training and hypoxia-associated changes in maximal oxygen uptake are mediated by different blood adaptations. Training increases blood volume because of plasma and red cell volume expansion, resulting in increased cardiac output, whereas hypoxia increases only red cell volume, leading to increased hemoglobin concentration and oxygen transport capacity. Blood doping mimics the altitude effects, however, by far exceeding its magnitude.