Exercise reinforcement, stress, and β-endorphins: an initial examination of exercise in anabolic-androgenic steroid dependence

19 Mar 2014

Exercise reinforcement, stress, and β-endorphins: an initial examination of exercise in anabolic-androgenic steroid dependence / Tom Hildebrandt, Sydney Shope, Eleanna Varangis, Diane Klein, Donald W. Pfaff, Rachel Yehuda. - (Drug and Alcohol Dependence 139 (2014) 1 June; p. 86-92)

  • PMID: 24690349
  • PMCID: PMC4039319
  • DOI: 10.1016/j.drugalcdep.2014.03.008


Abstract

Background: Anabolic-androgenic steroids (AASs) are abused primarily in the context of intense exercise and for the purposes of increasing muscle mass as opposed to drug-induced euphoria. AASs also modulate the HPA axis and may increase the reinforcing value of exercise through changes to stress hormone and endorphin release. To test this hypothesis, 26 adult males drawn from a larger study on AAS use completed a progressive ratio task designed to examine the reinforcing value of exercise relative to financial reinforcer.

Method: Sixteen experienced and current users (8 on-cycle, 8 off-cycle) and 10 controls matched on quantity×frequency of exercise, age, and education abstained from exercise for 24 h prior to testing and provided 24-h cortisol, plasma cortisol, ACTH, β-endorphin samples, and measures of mood, compulsive exercise, and body image.

Results: Between group differences indicated that on-cycle AAS users had the highest β-endorphin levels, lowest cortisol levels, higher ACTH levels than controls. Conversely, off-cycle AAS users had the highest cortisol and ACTH levels, but the lowest β-endorphin levels. Exercise value was positively correlated with β-endorphin and symptoms of AAS dependence.

Conclusion: The HPA response to AASs may explain why AASs are reinforcing in humans and exercise may play a key role in the development of AAS dependence.

Pharmacokinetics of dehydroepiandrosterone and its metabolites after long-term daily oral administration to healthy young men

1 Mar 2004

Pharmacokinetics of dehydroepiandrosterone and its metabolites after long-term daily oral administration to healthy young men / Brian D. Acacio, Frank Z. Stanczyk, Patrick Mullin, Payam Saadat, Neda Jafarian, Rebecca Z. Sokol. - (Fertility and Sterility 81 (2004) 3 (1 March) p. 595-604)

  • PMID: 15037408
  • DOI: 10.1016/j.fertnstert.2003.07.035


Abstract

Objective: To determine the effects of dehydroepiandrosterone (DHEA) supplementation on the pharmacokinetics of DHEA and its metabolites and the reproductive axis of healthy young men.

Design: A prospective, randomized, double-blind, placebo-controlled pharmacokinetic study.

Setting: General Clinical Research Center and laboratories at the Keck School of Medicine of the University of Southern California, Los Angeles, California.

Patient(s): Fourteen healthy men, ages 18-42 years.

Intervention(s): Daily oral administration of placebo (n = 5), 50 mg DHEA (n = 4), or 200 mg DHEA (n = 5) for 6 months. Blood samples were collected at frequent intervals on day 1 and at months 3 and 6 of treatment.

Main outcome measure(s): Quantification of DHEA, DHEA sulfate (DHEAS), androstenedione, T, E(2), dihydrotestosterone (DHT), and 5alpha-androstane-3alpha-17beta-diol glucuronide (ADG). Physical examination, semen analysis, serum LH, FSH, prostate-specific antigen, and general chemistries were carried out.

Result(s): Baseline DHEA, DHEAS, and ADG levels increased significantly from day 1 to months 3 and 6 in the DHEA treatment groups but not in the placebo group. No significant changes were observed in pharmacokinetic values. Clinical parameters were not affected.

Conclusion(s): DHEA, DHEAS, and ADG increased significantly during 6 months of daily DHEA supplementation. Although the pharmacokinetics of DHEA and its metabolites are not altered, sustained baseline elevation of ADG, a distal DHT metabolite, raises concerns about the potential negative impact of DHEA supplementation on the prostate gland.

Effects of short-term dehydroepiandrosterone supplementation on body composition in young athletes

28 Feb 2010

Effects of short-term dehydroepiandrosterone supplementation on body composition in young athletes / Sergej M. Ostojic, Julio Calleja, Morteza Jourkesh. - (Chinese Journal of Physiology 53 (2010) 1 (28 February); p. 19-25)

  • PMID: 21789881
  • DOI: 10.4077/cjp.2010.amh090


Abstract

Dehydroepiandrosterone (DHEA) is often promoted as a slimming and weight/fat loss agent and ingestion of DHEA may have hypolipidemic and anti-obesity properties. The main aim of this study was to examine the effects of acute DHEA intake on body composition and serum steroid hormones in young athletes. Twenty young (19 to 22 years) male soccer players were allocated into two randomly assigned trials in double-blind design by ingesting 100-mg daily oral DHEA or as placebo (PLA) for 28 days. Body mass was not affected by 4 weeks of DHEA supplementation (P > 0.05). No significant changes in body mass index (BMI), waist-to-hip ratio (WHR) and body fat or total muscle mass for the two groups were detected at the end of the trial (P > 0.05). There was no within- or between-group difference in arm fat index (AFI) and corrected mid-upper-arm muscle area (cAMA) (P > 0.05). Treatment with DHEA resulted in a significant increase of total testosterone, estradiol and DHEA-S levels in treated subjects versus the placebo group (P < 0.05). Results of this study suggest that DHEA supplementation has no beneficial effects on body composition in young competitive athletes.

Neuropsychiatric Effects of Anabolic Steroids in Male Normal Volunteers

2 Jun 1993

Neuropsychiatric Effects of Anabolic Steroids in Male Normal Volunteers / Tung-Ping Su, Michael Pagliaro, Peter J. Schmidt. - (Journal of the American Medical Association 269 (1993) 21 (2 June); p. 2760-2764)

  • PMID: 8492402
  • DOI:10.1001/jama.1993.0350021006003


Abstract

Objective: To evaluate the acute effects of anabolic steroids on mood and behavior in male normal volunteers.

Design: A 2-week, double-blind (subject and rater), fixed-order, placebo-controlled crossover trial of methyltestosterone.

Setting: An inpatient research unit at the National Institutes of Health.

Subjects: A volunteer sample of 20 men who were medication free, free of medical and psychiatric illness, not involved in athletic training, and had no prior history of anabolic steroid use.

Intervention: A sequential trial for 3 days each of the following four drug conditions: placebo baseline, low-dose methyltestosterone (40 mg/d), high-dose methyltestosterone (240 mg/d), and placebo withdrawal.

Main outcome measures: Mood and behavioral ratings were completed during each drug condition and included both subjective and objective measures.

Results: Significant (P < .05) albeit subtle increases in symptom scores were observed during high-dose methyltestosterone administration compared with baseline in positive mood (euphoria, energy, and sexual arousal), negative mood (irritability, mood swings, violent feelings, and hostility), and cognitive impairment (distractibility, forgetfulness, and confusion). An acute manic episode was observed in one of the 20 subjects, representing a 5% incidence, even under these conservative conditions. An additional subject became hypomanic. Baseline characteristics including family psychiatric history or previous drug abuse did not predict symptom changes.

Conclusion: This is the first placebo-controlled prospective study demonstrating the adverse and activating mood and behavioral effects of anabolic steroids.

ADAK 2020 ADAK vs Boniface Mbuvi Muema

5 Nov 2020

In December 2019 the Anti-Doping Agency of Kenya (ADAK) has reported an anti-doping rule violation against the Athlete Boniface Mbuvi Muema after his sample tested positive for the prohibited substance 19-norandrosterone (Nandrolone).

After notification a provisional suspension was ordered. The Athlete filed a statement in his defence and he was heard for the Kenya Sports Disputes Tribunal.

The Athlete accepted the test result and denied the intentional use of the substance. He stated that he only had used a painkiller for his injury and requested for a reduced sanction.

The Panel holds that the Athlete different statement's were not substantiated by any evidence and deems that he failed to establish that the violation was not intentional nor how the substance entered his system.

Therefore the Sports Disputes Tribunal decides on 5 November 2020 to impose a 4 year period of ineligibility on the Athlete starting on the date of the provisional suspension, i.e. on 20 December 2019.

ADAK 2019 ADAK vs Beatrice Jepkorir Rutto

5 Nov 2020

In May 2019 the Anti-Doping Agency of Kenya (ADAK) has reported an anti-doping rule violation against the Athlete Beatrice Jepkorir Rutto after her sample, provided in Kenya in April 2019, tested positive for the prohibited substances Heptaminol and Enobosarm. After notification a provisional suspension was ordered

In August 2019 ADAK reported a new anti-doping rule violation against the Athlete after her sample, provided in Rwanda in June 2019, tested positive for Heptaminol and Enobosarm. After notification again a provisional suspension was ordered.

The Athlete filed a statement in her defence and she was heard for the Kenya Sports Disputes Tribunal.

The Athlete denied the intentional use of the substances and denied that she waived her right to test her B sample. She stated that she sufffered from asthmatic symptoms and chest pain and had used prescribed medication. She mentioned her medication on the Doping Control Form and provided medical information about the severe asthmatic attacks she had.

The Panel accepts that the violations were not intentional since the Athlete mentioned her medication on the Doping Control Form when tested in April and in June 2019.

Further the Panel establishes that the Athlete was duly notified in May 2019 about her first anti-doping rule violation and that she was well aware that a provisional suspension was ordered. Nevertheless she participated in the Marathon in Rwanda in June 2019 where she again tested positive. As a result the Athlete committed a second anti-doping rule violation and she also failed to apply for a TUE.

Therefore the Sports Disputed Tribunal decides on 5 November 2020 to impose a 2 year period of ineligibility for the Athlete's First Anti-Doping Rule Violation and a 4 year period for her second anti-doping rule violation. The Tribunal deems that the Athlete has to serve the 2 and 4 year period of ineligibility consecutively.

CAS 2020_A_6978 Andrea Iannone vs FIM | WADA vs FIM and Andrea Iannone

10 Nov 2020

CAS 2020/A/6978 Andrea Iannone v. FIM
CAS 2020/A/7068 WADA v. FIM and Andrea Iannone

On 31 March 2020 the Disciplinary Court of the International Motorcycling Federation (FIM) decided to impose a reduced 18 month period of ineligibility on the Italian motorcycle racer Andrea Iannone after he tested positive for the prohibited substance Drostanolon.

Here the Disciplinary Court accepted that the positive test was the result of contaminated meat he had ingested in Malaysia prior to the 2019 Sepang FIM World Championship MotoGP. 

Hereafter the Athlete, in April 2020, and WADA, in May 2020, appealed the FIM Decision with the Court of Arbitration for Sport (CAS).

Both parties seeked to set aside the FIM Decision of 31 March 2020: the Athlete requested the Panel for a further reduced sanction while WADA requested the Panel for the imposition of a 4 year period of ineligibility. 

The Athlete asserted, supported by expert witnesses, that there are grounds for No Fault or Negligence to impose a further reduced sanction. He argued that the violation was not intentional; the source of the prohibited substance was contaminated meat; he was tested before without issues; he voluntarily underwent a hair test; and he made any possible and reasonable efforts to prevent the contested anti-doping violation.

FIM supported the Athlete’s assertations that the violation was not intentional and that he demonstrated on a balance of probability that the presence of Drostanolone was the result of his consumption of contaminated meat. 

WADA contended that the Athlete failed to establish on the balance of probability that the origin of the prohibited substance was contaminated meat, nor did he demonstrate that there are grounds to reduce the sanction. 

The Panel deems that the Athlete failed to establish neither the precise type of meat he had consumed nor the origin of the meat in question. It finds that the Athlete nor his expert witnesses were able to establish specifically that there was an issue of meat contamination by Drostanolone in Malaysia. 

The Panel concludes that the Athlete has not established on a balance of probabilities that the violation was not intentional and thus it upholds WADA’s Appeal and sets aside the FIM Decision of 31 March 2020.

Therefore the Court of Arbitration for Sport decides on 10 November 2020 that:

1.) The appeal filed by Mr. Iannone on 21 April 2020 against the decision rendered by the International Disciplinary Court of the Fédération Internationale de Motocyclisme dated 31 March 2020 is rejected.

2.) The appeal filed by WADA on 12 May 2020 against the decision rendered by the International Disciplinary Court of the Fédération Internationale de Motocyclisme dated 31 March 2020 is upheld.

3.) The decision rendered by the International Disciplinary Court of the Fédération Internationale de Motocyclisme dated 31 March 2020 is set aside.

4.) Mr. Iannone is sanctioned with a period of ineligibility of four years commencing on 17 December 2019.

5.) All competitive results obtained by Mr. Iannone within from and including 1 November 2019 through the commencement of his suspension are disqualified, with all resulting consequences, including forfeiture of any medals, points and prizes.

6.) (…)

7.) (…)

8.) (…)

9.) All other or further requests or motions for relief are dismissed.

World Athletics 2019 WA vs Elijah Manangoi

10 Nov 2020

In July 2020 the Athletics Integrity Unit (AIU) of World Athletics has reported an an anti-doping rule violation against the Kenyan Athlete Elijah Managoi for his Whereabouts Filing Failures resulting in 3 Missed Tests within a 12 month period, beginning in July 2019.

After notification the Athlete gave a prompt admission, waived his right for a hearing, accepted a provisional suspension and the sanction proposed by the AIU.

The AIU’s finds in this case that the Athlete's degree of risk is significant. It holds that there is an inherent and increased risk of inaccuracies and delays to filing and updating Whereabouts information in circumstances where an athlete delegates those responsibilities to a third-party.

The Athlete accepted that he simply ‘trusted’ the Delegate to maintain his Whereabouts information and to make updates on his behalf. This was done without any oversight and without the Athlete checking whether the information in his Whereabouts Filing (and any updates made to that information) was accurate. As a result the Athlete failed to exercise any care or investigation in relation to what should have been the perceived significant level of risk in these circumstances.

Therefore the AIU decides on 10 November 2020 to impose a 2 year period of ineligibility on the Athlete starting backdated on the date of third Whereabouts Faulure, i.e. 22 December 2019.

CAS 2019_A_6180 WADA vs USADA & Ryan Hudson - Settlement

23 Oct 2020

CAS 2019_A_6180 WADA vs USADA & Ryan Hudson - Settlement 


Related case:

CAS 2019_A_6180 WADA vs USADA & Ryan Hudson - Preliminary Award
March 10, 2020


Previously in December 2016 the American weightlifter Ryan Hudson was sanctioned with a 4 year period of ineligibility after he tested positive in 2015 for the prohibited substance Stanozolol. 

In July 2017 the United States Anti-Doping Agency (USADA) reported an new anti-doping rule violation against the Athlete after his A and B samples tested positive for the prohibited substance Dehydrochlormethyltestosterone (DHCMT).

USADA deemed on 27 November 2018 that there where grounds for the imposition of a sanction of 4 years for the Athlete’s second anti-doping rule violation instead of the otherwise applicable 8 year period of ineligibility. 

Hereafter in March 2019 the World Anti-Doping Agency (WADA) appealed the USADA Decision with the Court of Arbitration for Sport (CAS).

In this case the Sole Arbitrator on 10 March 2020 already settled preliminairy issues between WADA and USADA and ruled that the Court of Arbitration for Sport has jurisdiction over the present Appeal.

During the proceedings the Parties reached a settlement and requested the CAS Sole Arbitrator to ratify the Settlement Agreement into a Consent Award.

The Parties agreed as follows:

  • The Acceptance of Sanction form signed by the Athlete and USADA on 27 November 2018 shall be set aside;
  • The Athlete is sanctioned with an 8 year period of ineligibility, starting on 27 November 2018; and
  • USADA shall bear the arbitration costs for the CAS Appeal.

The Sole Arbitrator, having reviewed the text of the Settlement Agreement and the evidence on file, finds no reason to object to or to disapprove of the terms of the Settlement Agreement and is satisfied that the agreement constitutes a bona fide
settlement of the dispute of which he was seized.

Therefore the Court of Arbitration for Sport decides on 23 October 2020 that:

1.) The Settlement Agreement submitted to the CAS Court Office by the Parties on 4 June 2020 is hereby ratified by the CAS with the consent of the Parties and its relevant terms
are incorporated into this arbitral A ward.

2.) Each Party is hereby ordered to perform the obligations and duties as per the Settlement Agreement referred to above.

3.) The arbitral procedure CAS 2019/A/6180 World Anti-Doping Agency v. United States Anti-Doping Agency & Ryan Hudson is terminated and deleted from the CAS roll.

4.) In accordance with the Settlement Agreement, the arbitration costs, to be determined and served to the Parties by the CAS Court Office, shall be borne by the United States Anti-Doping Agency.

5.) The United States Anti-Doping Agency shall pay to the World Anti-Doping Agency the amount of CHF 9,000 (nine thousand Swiss Francs) as a contribution to the costs and
expenses the latter incurred in connection with the present proceedings. Ryan Hudson shall bear his own costs and expenses incurred in these proceedings.

6.) All other motions or prayers for relief are dismissed.

CAS 2019_A_6180 WADA vs USADA & Ryan Hudson - Preliminary Award

10 Mar 2020

CAS 2019/A/6180 World Anti-Doping Agency (WADA) v. United States Anti-Doping Agency (USADA) and Ryan Hudson - Preliminary Award


Related case:

CAS 2019_A_6180 WADA vs USADA & Ryan Hudson - Settlement
October 23, 2020


Previously in December 2016 the American weightlifter Ryan Hudson was sanctioned with a 4 year period of ineligibility after he tested positive in 2015 for the prohibited substance Stanozolol. 

In July 2017 the United States Anti-Doping Agency (USADA) reported an new anti-doping rule violation against the Athlete after his A and B samples tested positive for the prohibited substance Dehydrochlormethyltestosterone (DHCMT).

Here USADA deemed on 27 November 2018 that there where grounds for the imposition of a sanction of 4 years for the Athlete’s second anti-doping rule violation instead of the otherwise applicable 8 year period of ineligibility. 

Hereafter in March 2019 the World Anti-Doping Agency appealed the USADA Decision with the Court of Arbitration for Sport (CAS).

This Award centres around these preliminairy issues: 

  • whether the CAS has jurisdiction over the appeal;
  • if the CAS does have jurisdiction, what is the scope of the appeal, i.e. does it extend to whether the Athlete committed a second ADRV or is it limited to the sanction for such violation; and
  • whether a "presence" violation is committed (for the purposes of Article 10.7.4.1 of the WADC) on the date of ingestion of a prohibited substance or on the date of the doping control test.

WADA's essential submission is that:

  • The issue of whether the Athlete committed a second ADRV has been already determined;
  • WADA's prayer for relief that the CAS find the Athlete has committed a second ADRV, is a mere formality.

USADA's essential submission is that:

  • It is for WADA to establish that the Athlete committed a second ADRV before any question of sanction can arise;
  • WADA's prayers for relief that the CAS find the Athlete has committed a second ADRV, has made whether he has done so an issue in these proceedings.

Considering the submissions of the parties the Sole Arbitrator holds that there is a specific arbitration agreement in the Appealed Decision entitling WADA to appeal it to the CAS. Moreover, an applicable regulation – the USADA Protocol – properly interpreted, also provides such a right of appeal to WADA. 

The Sole Arbitrator deems that USADA's attempt to change the basis of the agreed sanction i.e. that the DHCMT positive should be treated as a second ADRV - should not be entertained. The fact of the Athlete's second ADRV is the very premise of WADA's appeal and hence outwith its scope. The scope of WADA's appeal is limited to the appropriate sanction for the Athlete's second ADRV; his commission of that second violation is to be treated as res judicata. 

Further the Sole Arbitrator concludes that an ADRV contrary to Article 2.1 WADC (i.e. a "presence" violation) cannot be committed on any date other than the date of the sample on which the prohibited sample is found to be present. 

Therefore the Court of Arbitration for Sport decides on 10 March 2020 in this Preliminary Award that: 

1.) The Court of Arbitration for Sport has jurisdiction over the appeal filed by the World Anti-Doping Agency on 4 March 2019 against the decision rendered by the United States Anti-Doping Agency on 27 November 2018, regarding Ryan Hudson.

2.) The scope of the appeal filed by the World Anti-Doping Agency on 4 March 2019 is limited to the appropriate sanction for Ryan Hudson's second Anti-Doping Rule Violation; his commission of that second violation is to be treated as res judicata.

3.) An Anti-Doping Rule Violation contrary to Article 2.1 (i.e. a "presence" violation) of the World Anti-Doping Code cannot be committed on any date other than the date of the collection of the sample in which the prohibited substance is found to be present.

4.) The substantive proceedings will now go forward in the basis of the above premises 1-3.

5.) The costs of this award will be allocated in the final award.

6.) All other claims or issues will be assessed and determined in the final award.

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