The effects of auxiliary substances used in doping on male sexual reproductive function
Keywords:
SARM, peptide hormones, beta-2 adrenergicagonists, amino acid derivatives, myostatin inhibitors, FertilityAbstract
Using pharmacological substances to enhance athletic performance, known as doping, is widespread in sports and bodybuilding. Doping involves substances such as anabolic steroids, selective androgen receptor modulators, peptide hormones, beta-2 adrenergic agonists, and other auxiliary substances that temporarily enhance physical performance. Although perceived as safer alternatives to traditional steroids, they pose significant health risks, including on male reproductive function. The literature was reviewed using electronic databases such as PubMed, Scopus, and Google Scholar, Out of 296 articles published until 2024, 30 were included in the study providing data on the effects of these substances on sexual-reproductive function. Although SARMs do not have adverse effects like steroids, their excessive use can suppress endogenous testosterone production, affecting spermatogenesis. Peptide hormones and beta-2 adrenergic agonists can disrupt hormonal balance, affecting the hypothalamic-pituitary-gonadal (HPG) axis, suppressing the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Myostatin inhibitors and excessive consumption of amino acid derivatives can cause hormonal imbalances and oxidative stress, affecting the quality of seminal material. Auxiliary substances with anabolic effects used in doping can have significant adverse effects on male reproductive health, such as suppression of the HPG axis, decreased testosterone, and impaired spermatogenesis. Further studies are needed to understand the exact mechanisms and long-term impact of these substances on reproductive health.
References
1. BALERCIA, G., et al. Coenzyme Q10 and L-carnitine in idiopathic asthenozoospermia: a placebo-controlled, double-blind randomized trial. In: Fertility and Sterility. 2005, nr. 84(4), pp. 1246-1252. PMID: 16169400 https://doi.org/10.1016/j.fertnstert.2005.03.064
2. BASARIA, S. Androgen abuse in athletes: detection and consequences. In: The Journal of Clinical Endocrinology & Metabolism. 2010, nr. 95(4), pp. 1533-1543. PMID: 20139230 https://doi.org/10.1210/jc.2009-1579
3. BEIGI HARCHEGANI, A., DAHAN, H., et al. Effects of zinc deficiency on impaired spermatogenesis and male infertility: the role of oxidative stress, inflammation and apoptosis. In: Human Fertility (Camb). 2020, nr. 23(1), pp. 5-16. https://doi.org/10.1080/14647273.2018.1494390
4. BOHLIN, K.P., et al. Detection of anabolic agents including selective androgen receptor modulators in samples outside of sport. In: Drug Testing and Analysis. 2023, nr. 20. PMID: 37986708. https://doi.org/10.1002/dta.3600
5. CARNAC, G., VERNUS, B., BONNIEU, A. Myostatin in the pathophysiology of skeletal muscle. In: Current Genomics. 2007, nr. 8(7), pp. 415-422. PMID: 19412331; PMCID: PMC2647158. https://doi.org/10.2174/138920207783591672
6. CHEN, J, et al. A selective androgen receptor modulator for hormonal male contraception. In: Journal of Pharmacology and Experimental Therapeutics. 2005, nr. 312(2), pp. 546-553. https://doi.org/10.1124/jpet.104.075424
7. CLARK, R.V., et al. Safety, pharmacokinetics and pharmacological effects of the selective androgen receptor modulator, GSK2881078, in healthy men and postmenopausal women. In: British Journal of Clinical Pharmacology. 2017, nr. 83(10), pp. 2179-2194. PMID: 28449232 PMCID: PMC5595940 https://doi.org/10.1111/bcp.13316
8. DESAI, A., et al. Understanding and managing the suppression of spermatogenesis caused by testosterone replacement therapy (TRT) and anabolic-androgenic steroids (AAS). In: Therapeutic Advances in Urology. 2022, nr. 14. PMID: 35783920 PMCID: PMC9243576 https://doi.org/10.1177/17562872221105017
9. EFIMENKO, I.V., VALANCY, D., DUBIN, J.M., RAMASAMY, R. Adverse effects and potential benefits among selective androgen receptor modulators users: a cross-sectional survey. In: International Journal of Impotence Research. 2022, nr. 34(8), pp. 757-761. https://doi.org/10.1038/s41443-021-00465-0
10. GUALANO, B., et al. Inappropriate prescription of androgens and sports supplements: a threat to health. In: Journal of Clinical Endocrinology & Metabolism. 2010, nr. 95(3), pp. 1291-1298. PMID: 22101980 https://doi.org/10.1007/s00726-011-1132-7
11. GUTTERIDGE, J.M.C., HALLIWELL, B. Antioxidants: Molecules, medicines, and myths. In: Biochemical and Biophysical Research Communications. 2010, nr. 393(4), pp. 561-564. PMID: 20171167 https://doi.org/10.1016/j.bbrc.2010.02.071
12. HANDELSMAN, D.J. The adverse effects of gonadotropin abuse in sports. In: Clinical Endocrinology. 2017, nr. 87(5), pp. 601-608. PMID: 20139230 https://doi.org/10.1210/jc.2009-1579
13. HOLT, R.I., SÖNKSEN, P.H. Growth hormone, IGF-I and insulin and their abuse in sport. In: British Journal of Pharmacology. 2008, nr. 154(3), pp. 542-556. PMID: 18376417 PMCID: PMC2439509 https://doi.org/10.1038/bjp.2008.99
14. BOISEN, I.M., HANSEN, L. B., et al. Possible influence of vitamin D on male reproduction. In: The Journal of Steroid Biochemistry and Molecular Biology. 2017, nr. 173, pp. 215-222. ISSN 0960-0760. https://doi.org/10.1016/j.jsbmb.2016.09.023
15. KOZHUHAROV, V.R., IVANOV, K., IVANOVA, S. Dietary Supplements as Source of Unintentional Doping. In: BioMed Research International. 2022. PMID: 35496041; PMCID: PMC9054437. https://doi.org/10.1155/2022/8387271
16. MA, L. , LIU, J. Therapeutic potential of beta2-adrenoceptor agonists in muscle wasting and weakness. In: Biochemical Society Transactions. 2014, nr. 42(6),pp.1450-454.PMID:18834902. https://doi.org/10.1016/j.pharmthera.2008.06.003
17. MACHEK, S.B., CARDACI, T.D., WILBURN, D.T., WIL-LOUGHBY. Considerations, possible contraindications, and potential mechanisms for deleterious effect in recreational and athletic use of selective androgen receptor modulators (SARMs) in lieu of anabolic androgenic steroids: A narrative review. In: Steroids. 2020, nr. 164, 108753. https://doi.org/10.1016/j.steroids.2020.108753
18. MALMIR, M., MEHRANJANI, M.S., FARAJI, T., NOREINI, S.N. Antioxidant effect of Vitamin E on the male rat reproductive system by a high oral dose of Bisphenol-A. In: Toxicology Research and Application. 2021, nr. 5. https://doi.org/10.1177/23978473211005562
19. RENNIE M.J. Claims for the anabolic effects of growth hormone: a case of the emperor's new clothes? In: British Journal of Sports Medicine. 2003, nr. 37(2), pp. 100-105. https://doi.org/10.1136/bjsm.37.2.100
20. SANSONE, A., et al. Sport, doping and male fertility. In: Reproductive Biology and Endocrinology. 2018, nr. 16, 114. PMID: 30415644; PMCID: PMC6231265. https://doi.org/10.1186/s12958-018-0435-x
21. SENGUPTA, P., DUTTA, S., KARKADA, I.R., CHINNI, S.V. Endocrinopathies and Male Infertility. In: Life (Basel). 2021, nr. 12(1), 10. PMID: 35054403; PMCID: PMC8779600. https://doi.org/10.3390/life12010010
22. SHENG-ZHONG H., SONG-SHAN J.I.N, et al. Semen quality and fertilization ability of myostatin-knockout boars. In: Theriogenology. 2019, nr.135,pp.109-114. ISSN:0093-691X. https://doi.org/10.1016/j.theriogenology.2019.05.047
23. SIMITSIDELLIS, I., at al. Selective androgen receptor modulators (SARMs) have specific impacts on the mouse uterus. In: Journal of Endocrinology. 2019, nr. 242(3), pp. 227-239. https://doi.org/10.1530/JOE-19-0153
24. TØTTENBORG, S.S., et al. Semen quality among young healthy men taking protein supplements. In: Fertility and Sterility. 2020, nr. 114(1), pp. 89-96. PMID: 32387273. https://doi.org/10.1016/j.fertnstert.2020.02.103
25. VAUGHAN, D., RITVOS, O., MITCHELL, R., et al. Inhibition of Activin/Myostatin signalling induces skeletal muscle hypertrophy but impairs mouse testicular development. In: European Journal of Translational Myology. 2020, nr. 30(1), 8737. PMID: 32499882; PMCID: PMC7254437. https://doi.org/10.4081/ejtm.2019.8737
26. VERTADIER, N., TRZEPIZUR, W., FAURE, S. Overuse of Short-Acting Beta-2 Agonists (SABAs) in Elite Athletes: Hypotheses to Explain It. In: Sports. 2022, 10, 36. https://doi.org/10.3390/sports10030036
27. VIJAYPRASAD, S., BB, G., BB, N. Effect of vitamin C on male fertility in rats subjected to forced swimming stress. In: Journal of Clinical and Diagnostic Research. 2014, nr. 8(7), HC05-8. PMID: 25177581; PMCID: PMC4149087. https://doi.org/10.7860/JCDR/2014/8432.4622
28. The Prohibited List. World Anti-Doping Agency. 2023. Retrieved from https://www.wada-ama.org/en/prohibited-list.
29. REZAEI, R., WANG, W., WU, Z. et al. Biochemical and physiological bases for utilization of dietary amino acids by young Pigs. In: J Animal Sci Biotechnol. 2013, nr. 4(1), 7. https://doi.org/10.1186/2049-1891-4-7
30. ZHOU, X. Y., MA, J. N., SHEN, Y. Y., et al. Effects of Growth Hormone on Adult Human Gonads: Action on Reproduction and Sexual Function. In: International Journal of Endocrinology. 2023. PMID: 37064267; PMCID: PMC10104746. https://doi.org/10.1155/2023/7492696
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
