Safety Implications of Off-Label Medication Use in Athletes: A Narrative Review
Abstract
1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Inclusion and Exclusion Criteria
2.3. Data Collection and Analysis
3. Results
Substance Name and Anatomical Therapeutic Chemical Code | Therapeutic Use | Off-Label Use in Sports Training | Previous Described AEs in Off-Label Use |
---|---|---|---|
Erythropoietin B03XA01 |
| Nausea [38,49]; headache [38]; injection site infection [38]; blood clotting [38,50]; high risk of thrombosis [35,38]; myocardial infarction [38]; severe anemia [38]; inhibits apoptosis, which can lead to cancer [38,49]. | |
Human Chorionic Gonadotropin (hCG) G03GA01 |
| Suppression of the function of the hypothalamic–pituitary–adrenal axis [9]; decreasing endogenous testosterone production [51], leading to testicular atrophy [1,9]; erectile dysfunction and gynecomastia [1,9,20]. | |
Human Growth Hormone H01AC01 |
| Abdominal pain [1]; carpal tunnel syndrome [1]; flatulence [1]; facial edema [1]; headache [1,47]; nausea [1]; insulin resistance [20,53] and possible type 2 diabetes [1,20]; cardiac instability [20,53]; hypertension [20,46]; sleep apnea [47]; abnormal bone growth [53] [46,47]; muscle weakness [46]; fluid retention [46]. | |
Insulin A10AB01 |
|
| Hypoglycemia (loss of consciousness, coma, and death) [38,56]; respiratory problems [54,56]; chest pain [56]; dehydration [54,56]. |
Oxandrolone A14AA08 | Liver toxicity [62]; hyperlipidemia [63]; cardiovascular strain, including hypertension and an increased risk of heart attack [64]; suppression of natural testosterone production [62]. | ||
Testosterone G03BA03 |
| Alopecia [1]; hypertension [1,9]; renal retention (fluids) [9]; musculoskeletal [9]; immune [9]; dermatological [1,9]; suppresses the hypothalamic–pituitary–adrenal axis function [9]; decreasing endogenous testosterone production [51]; testicular atrophy [1,9], erectile dysfunction, and gynecomastia [1,9,20]. | |
Thyroid Hormones H03AA01 |
|
| Iatrogenic thyrotoxicosis [1,67]; heart failure [1]; tremors [1]; weakness [1,67]; alopecia [1]; tachycardia [1,68]. |
Substance Name and Anatomical Therapeutic Chemical Code | Therapeutic Use | Off-Label Use in Sports Training | Previous Described AEs in Off-Label Use |
---|---|---|---|
Furosemide (Diuretics) C03CA01 |
| Dehydration [56]; electrolyte imbalance [18,56]; cramps [56]; dizziness [56]; gastric diseases [18,56]; skin irritation [56]; impotence [56,68]. | |
Clenbuterol (β2 agonists) R03AC14 |
| Tremors [71]; gastrointestinal disorders [9]; anxiety [9]; severe hypokalemia [71]; hospitalization due to tachycardia [9,17]; death [17]. | |
Glucocorticoids H02AB |
| Inhibition of the hypothalamic–pituitary–adrenal axis [70]; increased risk of infections; insulin resistance [70]; hypertension and atherosclerosis [73]; osteoporosis [1]. | |
Tamoxifen L02BA01 |
|
| Joint pain [56]; cardiovascular disorder [74]; blood clotting [56]; nausea [56]; blurred vision [56]; pulmonary embolism [74]. |
4. Discussion
4.1. Athletes’ Motivations for Off-Label Drug Use
4.2. Misinformation in Off-Label Use
4.3. Physical, Psychological, and Social Risks of Off-Label Drug Use
4.4. Economic Consequences
4.5. Future Research and Interventions
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Irwig, M.S.; Fleseriu, M.; Jonklaas, J.; Tritos, N.A.; Yuen, K.C.J.; Correa, R.; Elhomsy, G.; Garla, V.; Jasim, S.; Soe, K.; et al. Off-label use and misuse of testosterone, growth hormone, thyroid hormone, and adrenal supplements: Risks and costs of a growing problem. Endocr. Pr. 2020, 26, 340–353. [Google Scholar] [CrossRef] [PubMed]
- Agency, E.M. Guideline on Good Pharmacovigilance Practices (GVP), Module VI—Management and Reporting of Adverse Reactions to Medicinal Products (Rev 1); European Medicines Agency and Heads of Medicines Agencies London: London, UK, 2014. [Google Scholar]
- Claverie, H. On-Label vs Off-Label Drug Prescribing. IG Living 2016, 2016, 28–31. [Google Scholar]
- Stafford, R.S. Regulating off-label drug use—Rethinking the role of the FDA. N. Engl. J. Med. 2008, 358, 1427–1429. [Google Scholar] [CrossRef] [PubMed]
- Kesselheim, A.S. Off-label drug use and promotion: Balancing public health goals and commercial speech. Am. J. Law. Med. 2011, 37, 225–257. [Google Scholar] [CrossRef] [PubMed]
- Beck, J.M.; Azari, E.D. FDA, off-label use, and informed consent: Debunking myths and misconceptions. Food Drug Law. J. 1998, 53, 71–104. [Google Scholar]
- Silva, A.F. Uso Off-Label de Medicamentos: Um Tema Controverso. Ph.D. Thesis, Universidade do Algarve, Faro, Portugal, 2018. [Google Scholar]
- Clement, C.; Marlowe, D.; Patapis, N.; Festinger, D.; Forman, R. Nonprescription steroids on the internet. Subst. Use Misuse 2012, 47, 329–341. [Google Scholar] [CrossRef]
- Ip, E.J.; Doroudgar, S.; Lau, B.; Barnett, M.J. Anabolic steroid users’ misuse of non-traditional prescription drugs. Res. Soc. Adm. Pharm. 2019, 15, 949–952. [Google Scholar] [CrossRef]
- Vari, C.-E.; HOsz, B.-E.; Miklos, A.; Berbecaru-Iovan, A.; Tero-Vescan, A. Aromatase inhibitors in men-off-label use, misuse, abuse and doping. Farmacia 2016, 64, 813–818. [Google Scholar]
- Ashid, M.; Katariya, D.; Agarwal, P.; Soni, K.; Joshi, A. A brief study on performance enhancing drugs (PED’S). World J. Pharm. Res. 2016, 5, 495–533. [Google Scholar]
- Watson, C.J.; Stone, G.L.; Overbeek, D.L.; Chiba, T.; Burns, M.M. Performance-enhancing drugs and the Olympics. J. Intern. Med. 2022, 291, 181–196. [Google Scholar] [CrossRef]
- Miskulin, I.; Grbic, D.S.; Miskulin, M. Doping attitudes, beliefs, and practices among young, amateur Croatian athletes. Sports 2021, 9, 25. [Google Scholar] [CrossRef] [PubMed]
- Ventura, R.; Matabosch, X.; Segura, J. Bioanalytical techniques in discrimination between therapeutic and abusive use of drugs in sport. Bioanalysis 2016, 8, 965–980. [Google Scholar] [CrossRef] [PubMed]
- Catlin, D.H.; Murray, T.H. Performance-enhancing drugs, fair competition, and Olympic sport. JAMA 1996, 276, 231–237. [Google Scholar] [CrossRef] [PubMed]
- Baker, J.S.; Graham, M.R.; Davies, B. Steroid and prescription medicine abuse in the health and fitness community: A regional study. Eur. J. Intern. Med. 2006, 17, 479–484. [Google Scholar] [CrossRef]
- Milano, G.; Chiappini, S.; Mattioli, F.; Martelli, A.; Schifano, F. β-2 agonists as misusing drugs? Assessment of both clenbuterol-and salbutamol-related European medicines agency pharmacovigilance database reports. Basic. Clin. Pharmacol. Toxicol. 2018, 123, 182–187. [Google Scholar] [CrossRef]
- Cadwallader, A.B.; De La Torre, X.; Tieri, A.; Botrè, F. The abuse of diuretics as performance-enhancing drugs and masking agents in sport doping: Pharmacology, toxicology and analysis. Br. J. Pharmacol. 2010, 161, 1–6. [Google Scholar] [CrossRef]
- Baker, J.S.; Graham, M.; Davies, B. Gym users and abuse of prescription drugs. J. R. Soc. Med. 2006, 99, 331–332. [Google Scholar] [CrossRef]
- Parkinson, A.B.; Evans, N.A. Anabolic androgenic steroids: A survey of 500 users. Med. Sci. Sport. Exerc. 2006, 38, 644–651. [Google Scholar] [CrossRef]
- Ahmed, J.; Mohac, L.; Mackey, T.; Raimi-Abraham, B. A critical review on the availability of substandard and falsified medicines online: Incidence, challenges and perspectives. J. Med. Access 2022, 6, 239920262210745. [Google Scholar] [CrossRef]
- Fittler, A.; Lankó, E.; Brachmann, B.; Botz, L. Behaviour analysis of patients who purchase medicines on the internet: Can hospital pharmacists facilitate online medication safety? Eur. J. Hosp. Pharm. 2012, 20, 8–12. [Google Scholar] [CrossRef]
- Fink, J.; Schoenfeld, B.J.; Hackney, A.C.; Matsumoto, M.; Maekawa, T.; Nakazato, K.; Horie, S. Anabolic-androgenic steroids: Procurement and administration practices of doping athletes. Phys. Sportsmed. 2019, 47, 10–14. [Google Scholar] [CrossRef] [PubMed]
- Quaglio, G.; Fornasiero, A.; Mezzelani, P.; Moreschini, S.; Lugoboni, F.; Lechi, A. Anabolic steroids: Dependence and complications of chronic use. Intern. Emerg. Med. 2009, 4, 289–296. [Google Scholar] [CrossRef] [PubMed]
- Sansoucy, M.; Naud, J. Using proteins as markers for anabolic steroid abuse: A new perspective in doping control? Chem. Res. Toxicol. 2023, 36, 1168–1173. [Google Scholar] [CrossRef] [PubMed]
- Pomara, C.; Neri, M.; Bello, S.; Fiore, C.; Riezzo, I.; Turillazzi, E. Neurotoxicity by synthetic androgen steroids: Oxidative stress, apoptosis, and neuropathology: A review. Curr. Neuropharmacol. 2015, 13, 132–145. [Google Scholar] [CrossRef]
- George, A. The actions and side effects of anabolic steroids in sport and social abuse. Andrologie 2003, 13, 354–366. [Google Scholar] [CrossRef]
- Van Amsterdam, J.; Opperhuizen, A.; Hartgens, F. Adverse health effects of anabolic–androgenic steroids. Regul. Toxicol. Pharmacol. 2010, 57, 117–123. [Google Scholar] [CrossRef]
- Abasnejad, M.; Mohammadi, A.; Khajehlandi, A. Investigation of the chronic effects of winstrol and oxandrolone anabolic steroids on liver enzymes in male bodybuilding athletes. Jundishapur J. Chronic Dis. Care 2020, 9, e106517. [Google Scholar] [CrossRef]
- Bird, S.; Goebel, C.; Burke, L.; Greaves, R. Doping in sport and exercise: Anabolic, ergogenic, health and clinical issues. Ann. Clin. Biochem. Int. J. Lab. Med. 2015, 53, 196–221. [Google Scholar] [CrossRef]
- Lentillon-Kaestner, V. The development of doping use in high-level cycling: From team-organized doping to advances in the fight against doping. Scand. J. Med. Sci. Sports 2011, 23, 189–197. [Google Scholar] [CrossRef]
- European Parliament and Council. Directive 2011/62/EU of the European Parliament and of the Council of 8 June 2011 amending Directive 2001/83/EC on the Community Code Relating to Medicinal Products for Human Use, as Regards the Prevention of the Entry into the Legal Supply Chain of Falsied Medicinal Products; Official Journal of the European Union: Musdrok, The Netherlands, 2011. [Google Scholar]
- Neto, J.; Silva, C.; Lima, A.; Caminha, J.; Pinto, D.; Alves, F.; Araújo, J.S.; Daher, E.d.F. Disorder of hypothalamic-pituitary-gonadal axis induced by abusing of anabolic-androgenic steroids for short time: A case report. Andrologia 2018, 50, e13107. [Google Scholar] [CrossRef]
- Hashim, A.; Almukhtar, S. The influence of anabolic-androgenic steroids on males’ hormones among gym-goers in mosul city. In Proceedings of the 1st International Ninevah Conference on Medical Sciences (INCMS 2021), Mosul, Iraq, 5-7 September 2021. [Google Scholar] [CrossRef]
- Rosenzweig, M.Q.; Bender, C.M.; Lucke, J.P.; Yasko, J.M.; Brufsky, A.M. The decision to prematurely terminate a trial ofR-HuEPO due to thrombotic events. J. Pain. Symptom. Manag. 2004, 27, 185–190. [Google Scholar] [CrossRef] [PubMed]
- Ramara, T.; Munayi, S.; Bailasha, N.; Chumba, J. The prevalence of drug abuse as it relates to psychosocial reasons among university athletes in selected competitive sports in kenya. Int. J. Psychol. 2024, 8, 1–18. [Google Scholar] [CrossRef]
- Morente-Sánchez, J.; Zabala, M. Doping in sport: A review of elite athletes’ attitudes, beliefs, and knowledge. Sports Med. 2013, 43, 395–411. [Google Scholar] [CrossRef] [PubMed]
- Birzniece, V. Doping in sport: Effects, harm and misconceptions. Intern. Med. J. 2015, 45, 239–248. [Google Scholar] [CrossRef]
- Palmi, I.; Berretta, P.; Tini, A.; Ricci, G.; Marinelli, S. The unethicality of doping in sports. Clin. Ter. 2019, 170, e100–e101. [Google Scholar]
- Malve, H. Sports pharmacology: A medical pharmacologist’s perspective. J. Pharm. Bioallied Sci. 2018, 10, 126. [Google Scholar] [CrossRef]
- Thomsen, J.J.; Rentsch, R.L.; Robach, P.; Calbet, J.A.; Boushel, R.; Rasmussen, P.; Juel, C.; Lundby, C. Prolonged administration of recombinant human erythropoietin increases submaximal performance more than maximal aerobic capacity. Eur. J. Appl. Physiol. 2007, 101, 481–486. [Google Scholar] [CrossRef]
- Gregor, C.; Cerasoli, E.; Schouten, J.; Ravi, J.; Slootstra, J.; Horgan, A.; Martyna, G.J.; Ryadnov, M.G.; Davis, P.; Crain, J. Antibody recognition of a human chorionic gonadotropin epitope (hcgβ66–80) depends on local structure retained in the free peptide. J. Biol. Chem. 2011, 286, 25016–25026. [Google Scholar] [CrossRef]
- Camperi, J.; Combès, A.; Fournier, T.; Pichon, V.; Delaunay, N. Analysis of the human chorionic gonadotropin protein at the intact level by hilic-ms and comparison with rplc-ms. Anal. Bioanal. Chem. 2020, 412, 4423–4432. [Google Scholar] [CrossRef]
- Chen, Y.; Niu, Y.; Xu, H.; Wang, D.; Jiang, H.; Pokhrel, G.; Wang, T.; Wang, S.-G.; Liu, J.H. Testosterone undecanoate supplementation together with human chorionic gonadotropin does not impair spermatogenesis in males with isolated hypogonadotropic hypogonadism: A retrospective study. Asian J. Androl. 2019, 21, 413–418. [Google Scholar]
- Woldemariam, G.; Butch, A. Immunoextraction–tandem mass spectrometry method for measuring intact human chorionic gonadotropin, free β-subunit, and β-subunit core fragment in urine. Clin. Chem. 2014, 60, 1089–1097. [Google Scholar] [CrossRef] [PubMed]
- Holt, R.I.G.; Ho, K.K.Y. The use and abuse of growth hormone in sports. Endocr. Rev. 2019, 40, 1163–1185. [Google Scholar] [CrossRef] [PubMed]
- Siebert, D.M.; Rao, A.L. The use and abuse of human growth hormone in sports. Sports Health 2018, 10, 419–426. [Google Scholar] [CrossRef] [PubMed]
- Pouliou, P.; Ourda, D.; Barkoukis, V.; Palamas, G. Empowering young athletes: Elevating anti-doping education with virtual reality. EAI Endorsed Trans. E-Learn. 2023, 9, 1–13. [Google Scholar] [CrossRef]
- Garimella, P.; Katz, R.; Patel, K.; Kritchevsky, S.; Parikh, C.; Ix, J.; Fried, L.F.; Newman, A.B.; Shlipak, M.G.; Harris, T.B.; et al. Association of serum erythropoietin with cardiovascular events, kidney function decline, and mortality. Circ. Heart Fail. 2016, 9, e002124. [Google Scholar] [CrossRef]
- Shand, B.I.; Buttimore, A.L.; Lynn, K.L.; Bailey, R.R.; Robson, R.A. Effect of hemodialysis and recombinant humanerythropoietin on determinants of blood viscosity. Ren. Fail. 1994, 16, 407–413. [Google Scholar] [CrossRef]
- Christiansen, A.V.; Vinther, A.S.; Liokaftos, D. Outline of a typology of men’s use of anabolic androgenic steroids in fitness and strength training environments. Drugs Educ. Prev. Policy 2017, 24, 295–305. [Google Scholar] [CrossRef]
- Barroso, O.; Mazzoni, I.; Rabin, O. Hormone abuse in sports: The antidoping perspective. Asian J. Androl. 2008, 10, 391–402. [Google Scholar] [CrossRef]
- Ehrnborg, C.; Ohlsson, C.; Mohan, S.; Bengtsson, B. Å.; Rosén, T. Increased serum concentration of IGFBP-4 and IGFBP-5 in healthy adults during one month’s treatment with supraphysiological doses of growth hormone. Growth Horm. IGF Res. 2007, 17, 234. [Google Scholar] [CrossRef]
- Peterman, S.; Niederkofler, E.; Phillips, D.; Krastins, B.; Kiernan, U.; Tubbs, K.; Nedelkov, D.; Prakash, A.; Vogelsang, M.S.; Schoeder, T.; et al. An automated, high-throughput method for targeted quantification of intact insulin and its therapeutic analogs in human serum or plasma coupling mass spectrometric immunoassay with high resolution and accurate mass detection (MSIA-HR/AM). Proteomics 2014, 14, 1445–1456. [Google Scholar] [CrossRef]
- Thomas, A.; Krombholz, S.; Breuer, J.; Walpurgis, K.; Thevis, M. Insulin-mimetic peptides in sports drug testing. Drug Test. Anal. 2023, 15, 1468–1476. [Google Scholar] [CrossRef] [PubMed]
- Botrè, F.; Pavan, A. Enhancement drugs and the athlete. Neurol. Clin. 2008, 26, 149–167. [Google Scholar] [CrossRef]
- Kopel, J.; Sorensen, G.; Griswold, J. A reappraisal of oxandrolone in burn management. J. Pharm. Technol. 2022, 38, 232–238. [Google Scholar] [CrossRef] [PubMed]
- Câmara, L.; Starling, M.; Suzigan, E. The clinical use of anabolic steroid oxandrolone for burn patients: A review. J. Pharm. Res. Int. 2023, 35, 29–35. [Google Scholar] [CrossRef]
- Reeves, P.; Herndon, D.; Tanksley, J.; Jennings, K.; Klein, G.; Mlcak, R.; Clayton, R.P.; Crites, N.N.; Hays, J.P.; Andersen, C.; et al. Five-year outcomes after long-term oxandrolone administration in severely burned children. Shock 2016, 45, 367–374. [Google Scholar] [CrossRef]
- Ali, K.; Verma, S.; Ahmad, I.; Singla, D.; Saleem, M.; Hussain, M.E. Comparison of complex versus contrast training on steroid hormones and sports performance in male soccer players. J. Chiropr. Med. 2019, 18, 131–138. [Google Scholar] [CrossRef]
- Li, H.; Guo, Y.; Yang, Z.; Roy, M.; Guo, Q. The efficacy and safety of oxandrolone treatment for patients with severe burns: A systematic review and meta-analysis. Burns 2016, 42, 717–727. [Google Scholar] [CrossRef]
- Galba, J.; Piešťanský, J.; Kováč, A.; Olešová, D.; Cehlár, O.; Kertys, M.; Kozlík, P.; Chaľová, P.; Tirčová, B.; Slíž, K.; et al. Fast and sensitive screening of oxandrolone and its major metabolite 17-epi-oxandrolone in human urine by uhplc—Ms/ms with on-line spe sample pretreatment. Molecules 2021, 26, 480. [Google Scholar] [CrossRef]
- Snyder, P.J. Androgens. In Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 11th ed.; Brunton, L.L., Lazo, J.S., Parker, K.L., Eds.; McGraw-Hill: New York, NY, USA, 2006; pp. 1573–1586. [Google Scholar]
- Skjaerlund, J.; Deitemeyer, D.; Yunker, R.; Subbiah, M. Effect of testosterone and oxandrolone on thrombocyte aggregation and synthesis of prostaglandins in thrombocytes and aorta of atherosclerosis-susceptible pigeons. Andrologia 2009, 15, 57–61. [Google Scholar] [CrossRef]
- Jonklaas, J.; Bianco, A.C.; Bauer, A.J.; Burman, K.D.; Cappola, A.R.; Celi, F.S.; Cooper, D.S.; Kim, B.W.; Peeters, R.P.; Rosenthal, M.S.; et al. Guidelines for the treatment of hypothyroidism: Prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid 2014, 24, 1670–1751. [Google Scholar] [CrossRef]
- Hanke, L.; Poeten, P.; Spanke, L.; Britz, S.; Diel, P. The influence of levothyroxine on body composition and physical performance in subclinical hypothyroidism. Horm. Metab. Res. 2022, 55, 51–58. [Google Scholar] [CrossRef] [PubMed]
- Handelsman, D.; Gild, M.; Clifton-Bligh, R.; Speers, N.; Kouzios, D.; McMartin, M.; Desai, R. Thyroid hormone abuse among elite athletes. J. Endocr. Soc. 2023, 7, bvad027. [Google Scholar] [CrossRef] [PubMed]
- Riggs, D.S.; Man, E.B.; Winkler, A.W. Serum iodine of euthyroid subjects treated with desiccated thyroid. J. Clin. Investig. 1945, 24, 722–731. [Google Scholar] [CrossRef] [PubMed]
- Widdowson, W.M.; Gibney, J. The effect of growth hormone replacement on exercise capacity in patients with GH deficiency: A metaanalysis. J. Clin. Endocrinol. Metab. 2008, 93, 4413–4417. [Google Scholar] [CrossRef]
- Duclos, M. Evidence on ergogenic action of glucocorticoids as a doping agent risk. Physician Sportsmed. 2010, 38, 121–127. [Google Scholar] [CrossRef]
- Spiller, H.; James, K.; Scholzen, S.; Borys, D. A descriptive study of adverse events from clenbuterol misuse and abuse for weight loss and bodybuilding. Subst. Abus. 2013, 34, 306–312. [Google Scholar] [CrossRef]
- Kane, A.; Herrera, E.; Niu, Y.; Camm, E.; Allison, B.; Tijsseling, D.; Lusby, C.; Derks, J.B.; Brain, K.L.; Bronckers, I.M.; et al. Combined statin and glucocorticoid therapy for the safer treatment of preterm birth. Hypertension 2023, 80, 837–851. [Google Scholar] [CrossRef]
- Buttgereit, F.; Burmester, G.R.; Lipworth, B.J. Optimised glucocorticoid therapy: The sharpening of an old spear. Lancet 2005, 365, 801–803. [Google Scholar] [CrossRef]
- Wibowo, E.; Pollock, P.; Hollis, N.; Wassersug, R. Tamoxifen in men: A review of adverse events. Andrology 2016, 4, 776–788. [Google Scholar] [CrossRef]
- Daher, J.; Mallick, M.; Khoury, D. Prevalence of dietary supplement use among athletes worldwide: A scoping review. Nutrients 2022, 14, 4109. [Google Scholar] [CrossRef]
- Mazzeo, F.; Santamaria, S.; Montesano, P. Gender difference, nutritional supplements and drug use in sport to enhancing performance: An italian revision over the last decade. Sport Mont 2019, 17, 69–73. [Google Scholar] [CrossRef]
- Wenbo, Z.; Yan, Z. The uses of anabolic androgenic steroids among athletes; its positive and negative aspects-a literature review. J. Multidiscip. Healthc. 2023, 31, 4293–4305. [Google Scholar] [CrossRef] [PubMed]
- Pope, H.G.; Wood, R.I.; Rogol, A.; Nyberg, F.; Bowers, L.; Bhasin, S. Adverse health consequences of performance-enhancing drugs: An Endocrine Society scientific statement. Endocr. Rev. 2014, 35, 341–375. [Google Scholar] [CrossRef] [PubMed]
- Gadela, N.; Coban, H.; Wasserman, E.; Schreyer, E.; Jaiswal, A. The tragedy of a strong muscle and a weak heart: Complications of anabolic-androgenic steroid misuse. Cureus 2021, 13, e17389. [Google Scholar] [CrossRef]
- Braillon, A.; Lexchin, J. Off-label drug use. Am. J. Med. Qual. 2016, 31, 285. [Google Scholar] [CrossRef]
- La Gerche, A.; Brosnan, M.J. Drugs in sport—A change is needed, but what? Heart Lung Circ. 2018, 27, 1099–1104. [Google Scholar] [CrossRef]
- Lichtenfeld, J.; Deal, B.; Crawford, S. Sudden cardiac arrest following ventricular fibrillation attributed to anabolic steroid use in an adolescent. Cardiol. Young 2016, 26, 996–998. [Google Scholar] [CrossRef]
- Mędraś, M.; Tworowska, U.; Jóźków, P.; Dumański, A.; Dubiński, A. Postoperative course and anabolic-androgenic steroid abuse–a case report. Anaesthesia 2004, 60, 81–84. [Google Scholar] [CrossRef]
- Baharlou, S.; Boulle, K.; Heijningen, I.; Cervini, I.; Termohlen, P. Standards for aseptic techniques in medical aesthetic practices in the benelux: Consensus recommendations. J. Cosmet. Dermatol. 2022, 22, 289–295. [Google Scholar] [CrossRef]
- La Vignera, S.; Condorelli, R.A.; Cannarella, R.; Duca, Y.; Calogero, A.E. Sport, doping and female fertility. Reprod. Biol. Endocrinol. 2018, 16, 108. [Google Scholar] [CrossRef]
- Souza, G.; Hallak, J. Anabolic steroids and male infertility: A comprehensive review. BJU Int. 2011, 108, 1860–1865. [Google Scholar] [CrossRef] [PubMed]
- Talih, F.; Fattal, O.; Malone, D. Anabolic steroid abuse: Psychiatric and physical costs. Clevel. Clin. J. Med. 2007, 74, 341. [Google Scholar] [CrossRef] [PubMed]
- Solakovic, S.; Serhatlic, H.; Solakovic, N.; Hajrulahovic, F.; Godinjak, A.; Pavlović, R.; Vrcic, M.; Kozina, Z.; Yarymbash, K.; Dorofieieva, O. Therapeutic measures from cardiovascular damage using statins, acetylsalicylic acid during the abuse of irrational cycles of anabolic steroids in bodybuilder Who Were Infected with the COVID-19. Med Res. Arch. 2024, 12. [Google Scholar] [CrossRef]
- Lehmann, S.; Thomas, A.; Schiwy-Bochat, K.H.; Geyer, H.; Thevis, M.; Glenewinkel, F.; Rothschild, M.A.; Andresen-Streichert, H.; Juebner, M. Death after misuse of anabolic substances (clenbuterol, stanozolol and metandienone). Forensic Sci. Int. 2019, 303, 109925. [Google Scholar] [CrossRef]
- Klötz, F.; Garle, M.; Granath, F.; Thiblin, I. Criminality among individuals testing positive for the presence of anabolic androgenic steroids. Arch. Gen. Psychiatry 2006, 63, 1274–1279. [Google Scholar] [CrossRef]
- Placidi-Frot, D. International Conventions Applicable to the Trade in Illicit Medical Products: A Political Scientist’s View. In Université Paris-Saclay Graduate School of Law, Proceedings of 1st International Summer School; IEDP—Institut d’Etudes de Droit Public: Sceaux, France, 2023. [Google Scholar]
- Layachi, O.B. International and National Obligations to Protect from the Risks of Pharmaceutical Crime: The Crime of Counterfeit Pharmaceutical Products in the COVID-19 Crisis. Syst. Rev. Pharm. 2020, 11, 648. [Google Scholar]
- Holubeck, P.; Eksi, A.; Gillett, K.; O’Hara, J.; McGoldrick, D.; Brown, D.; McCarthy, A.D. Social interest data as a proxy for off-label performance-enhancing drug use: Implications and clinical considerations. Cureus 2024, 16, e52011. [Google Scholar] [CrossRef]
- Sivalokanathan, S.; Małek, Ł.; Malhotra, A. The cardiac effects of performance-enhancing medications: Caffeine vs. anabolic steroids. Diagnostics 2020, 11, 324. [Google Scholar] [CrossRef]
- Andlin-Sobocki, P.; Wittchen, H.U. Cost of affective disorders in Europe. Eur. J. Neurol. 2005, 12, 34–38. [Google Scholar] [CrossRef]
- Sampaio, F.; Ssegonja, R.; Thiblin, I.; Nystrand, C. A model for evaluating the economic value of prevention programs for illicit use of anabolic androgenic steroids. Health Policy 2021, 125, 807–813. [Google Scholar] [CrossRef]
- Savulescu, J.; Creaney, L.; Vondy, A. Should athletes be allowed to use performance enhancing drugs? BMJ 2013, 347, f6150. [Google Scholar] [CrossRef]
- Monaghan, L. Bodybuilding, Drugs and Risk; Routledge: London, UK, 2002. [Google Scholar]
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Silva, V.; Madeira, R.; Joaquim, J.; Matos, C. Safety Implications of Off-Label Medication Use in Athletes: A Narrative Review. Medicines 2024, 11, 20. https://doi.org/10.3390/medicines11080020
Silva V, Madeira R, Joaquim J, Matos C. Safety Implications of Off-Label Medication Use in Athletes: A Narrative Review. Medicines. 2024; 11(8):20. https://doi.org/10.3390/medicines11080020
Chicago/Turabian StyleSilva, Vítor, Ricardo Madeira, João Joaquim, and Cristiano Matos. 2024. "Safety Implications of Off-Label Medication Use in Athletes: A Narrative Review" Medicines 11, no. 8: 20. https://doi.org/10.3390/medicines11080020
APA StyleSilva, V., Madeira, R., Joaquim, J., & Matos, C. (2024). Safety Implications of Off-Label Medication Use in Athletes: A Narrative Review. Medicines, 11(8), 20. https://doi.org/10.3390/medicines11080020