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Endocrine

, Volume 59, Issue 3, pp 538–546 | Cite as

Effects of short-term DHEA intake on hormonal responses in young recreationally trained athletes: modulation by gender

  • Katia CollompEmail author
  • Corinne Buisson
  • Nicolas Gravisse
  • Soraya Belgherbi
  • Zakaria Labsy
  • Manh-Cuong Do
  • Olivier Gagey
  • Sophie Dufay
  • Nancy Vibarel-Rebot
  • Michel Audran
Original Article

Abstract

Background

Dehydroepiandrosterone (DHEA) figures on the World Anti-Doping Agency list of prohibited substances in sport because it is assumed that athletes expect a significant increase in testosterone through DHEA administration. The literature on the hormonal effects of DHEA intake nevertheless appears to be very scant in healthy young subjects, especially women.

Purpose

We examined the effects of DHEA on adrenal and gonadal hormones, IGF1 and free T3 in healthy young male and female recreationally trained volunteers.

Methods

The study followed a double-blind, randomized-order crossover design. Lean healthy young men (n = 10) and women (n = 11), with all women using oral contraceptives, were treated daily with 100 mg of DHEA and placebo for 4 weeks. DHEA, DHEA-sulfate (DHEA-S), androstenedione, total testosterone (Tes), dihydrotestosterone (DHT), SHBG, estrone, cortisol, IGF1, and free T3 were measured before, in the middle and at the end of each treatment, as were blood glucose, liver transaminases and lipid status.

Results

We observed a significant increase in DHEA, DHEA-S, androstenedione, Tes, DHT, and estrone in both men and women in the middle and at the end of DHEA treatment, but the increase in Tes was more marked in women (p < 0.001) than men (p < 0.05). No changes were found in the other parameters, irrespective of gender.

Conclusion

In young athletes, DHEA administration induces significant blood hormonal changes, some modulated by gender, which can be used as biomarkers of doping.

Keywords

DHEA administration Young males Young females Testosterone DHT Androstenedione 

Notes

Acknowledgements

This project was carried out with the support of the World Anti-Doping Agency (WADA) and of the French Anti-Doping Agency (AFLD). The authors wish to express their gratitude to the subjects for their dedicated performance. In addition, we likewise thank Cathy Azulay, Blandine Bedora, Cathy Carmeni, Nathalie Crépin, Noëmie Etes, Dr. Jean Israël, Clotilde Le Tiec, Isabelle Le, Christiane Papelier, and Thierry Poulain for their expert assistance.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest that would prejudice the impartiality of the reported scientific work.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All individual participants included in the study provided written informed consent according to Institutional Review Board guidelines for the protection of human subjects.

References

  1. 1.
    World Anti-Doping Agency, A list of prohibited substances and methods (2017). https://www.wada-ama.org
  2. 2.
    E. Barrett-Connor, Lower endogenous androgen levels and dyslipidemia in men with non-insulin-dependent diabetes mellitus. Ann. Intern. Med. 117, 807–811 (1992)CrossRefGoogle Scholar
  3. 3.
    P.D. Kroboth, F.S. Salek, A.L. Pittenger, T.J. Fabian, R.F. Frye, DHEA and DHEA-S: a review. J. Clin. Pharmacol. 39, 327–348 (1999)CrossRefGoogle Scholar
  4. 4.
    C. Ohlsson, F. Labrie, E. Barrett-Connor, M.K. Karlsson, O. Ljunggren, L. Vandenput, D. Mellström, A. Tivesten, Low serum levels of dehydroepiandrosterone sulfate predict all-cause and cardiovascular mortality in elderly Swedish men. J. Clin. Endocrinol. Metab. 95, 4406–4414 (2010)CrossRefGoogle Scholar
  5. 5.
    A.M. Traish, H.P. Kang, F. Saad, A.T. Guay, Dehydroepiandrosterone (DHEA) a precursor steroid or an active hormone in human physiology. J. Sex. Med. 8, 2960–2982 (2011)CrossRefGoogle Scholar
  6. 6.
    M.C. Jimenez, Q. Sun, M. Schürks, S. Chiuve, F.B. Hu, J.E. Manson, K.M. Rexrode, Low dehydroepiandrosterone sulfate is associated with increased risk of ischemic stroke among women. Stroke 44, 1784–1789 (2013)CrossRefGoogle Scholar
  7. 7.
    A. Caufriez, R. Leproult, M. L’Hermite-Balériaux, M. Kerkhofs, G. Copinschi, Effects of a 3-week dehydroepiandrosterone administration on sleep, sex steroids and multiple 24-h hormonal profiles in postmenopausal women: a pilot study. Clin. Endocrinol. 79, 716–724 (2013)Google Scholar
  8. 8.
    A.M. Kenny, R.S. Boxer, A. Kleppinger, J. Brindisi, R. Feinn, J.A. Burleson, Dehydroepiandrosterone combined with exercise improves muscle strength and physical function in frail older women. J. Am. Geriatr. Soc. 58, 1707–1714 (2010)CrossRefGoogle Scholar
  9. 9.
    P. Merritt, B. Stangl, E. Hirshman, J. Verbalis, Administration of dehydroepiandrosterone (DHEA) increases serum levels of androgens and estrogens but does not enhance short-term memory in post-menopausal women. Brain Res. 5(1483), 54–62 (2012)CrossRefGoogle Scholar
  10. 10.
    A.J. Morales, J.J. Nolan, J.C. Nelson, S.S. Yen, Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J. Clin. Endocrinol. Metab. 78, 1360–1367 (1994)PubMedGoogle Scholar
  11. 11.
    A.J. Morales, R.H. Haubrich, J.Y. Hwang, H. Asakura, S.S. Yen, The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women. Clin. Endocrinol. 49, 421–432 (1998)CrossRefGoogle Scholar
  12. 12.
    S. Rubino, M. Stomati, C. Bersi, E. Casarosa, M. Luisi, F. Petraglia, A.R. Genazzani, Neuroendocrine effect of a short-term treatment with DHEA in postmenopausal women. Maturitas 28, 251–257 (1998)CrossRefGoogle Scholar
  13. 13.
    B. Stangl, E. Hirshman, J. Verbalis, Administration of dehydroepiandrosterone (DHEA) enhances visual-spatial performance in postmenopausal women. Behav. Neurosci. 125, 742–752 (2011)CrossRefGoogle Scholar
  14. 14.
    D. Von Mühlen, G.A. Laughlin, D. Kritz-Silverstein, J. Bergstrom, R. Bettencourt, Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial. Osteoporos. Int. 19, 699–707 (2008)CrossRefGoogle Scholar
  15. 15.
    S. Yamada, M. Akishita, S. Fukai, S. Ogawa, K. Yamaguchi, J. Matsuyama, K. Kozaki, K. Toba, Y. Ouchi, Effects of dehydroepiandrosterone supplementation on cognitive function and activities of daily living in older women with mild to moderate cognitive impairment. Geriatr. Gerontol. Int. 10, 280–287 (2010)CrossRefGoogle Scholar
  16. 16.
    K.T. Barnhart, E. Freeman, J.A. Grisso, D.J. Rader, M. Sammel, S. Kapoor, J.E. Nestler, The effect of dehydroepiandrosterone supplementation to symptomatic perimenopausal women on serum endocrine profiles, lipid parameters, and health-related quality of life. J. Clin. Endocrinol. Metab. 84, 3896–3902 (1999)PubMedGoogle Scholar
  17. 17.
    M.B. Wallace, J. Lim, A. Cutler, L. Bucci, Effects of dehydroepiandrosterone vs androstenedione supplementation in men. Med. Sci. Sports Exerc. 31, 1788–1792 (1999)CrossRefGoogle Scholar
  18. 18.
    T.C. Liu, C.H. Lin, C.Y. Huang, J.L. Ivy, C.H. Kuo, Effect of acute DHEA administration on free testosterone in middle-aged and young men following high-intensity interval training. Eur. J. Appl. Physiol. 113, 1783–1792 (2013)CrossRefGoogle Scholar
  19. 19.
    P.D. Kroboth, J.A. Amico, R.A. Stone, M. Folan, R.F. Frye, F.J. Kroboth, K.L. Bigos, T.J. Fabian, A.M. Linares, B.G. Pollock, C. Hakala, Influence of DHEA administration on 24-hour cortisol concentrations. J. Clin. Psychopharmacol. 23, 96–99 (2003)CrossRefGoogle Scholar
  20. 20.
    J.E. Nestler, C.O. Barlascini, J.N. Clore, W.G. Blackard, Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men. J. Clin. Endocrinol. Metab. 66, 57–61 (1988)CrossRefGoogle Scholar
  21. 21.
    G.A. Brown, M.D. Vukovich, R.L. Sharp, T.A. Reifenrath, K.A. Parsons, D.S. King, Effect of oral DHEA on serum testosterone and adaptations to resistance training in young men. J. Appl. Physiol. 1999(87), 2274–2283 (1985)Google Scholar
  22. 22.
    Y.H. Liao, K.F. Liao, C.L. Kao, C.Y. Chen, C.Y. Huang, W.H. Chang, J.L. Ivy, J.R. Bernard, S.D. Lee, C.H. Kuo, Effect of dehydroepiandrosterone administration on recovery from mix-type exercise training-induced muscle damage. Eur. J. Appl. Physiol. 113, 99–107 (2013)CrossRefGoogle Scholar
  23. 23.
    S.M. Ostojic, J. Calleja, M. Jourkesh, Effects of short-term dehydroepiandrosterone supplementation on body composition in young athletes. Chin. J. Physiol. 53, 19–25 (2010)CrossRefGoogle Scholar
  24. 24.
    F. González, C.L. Sia, D.M. Bearson, H.E. Blair, Hyperandrogenism induces a proinflammatory TNFα response to glucose ingestion in a receptor-dependent fashion. J. Clin. Endocrinol. Metab. 99, E848–E854 (2014)CrossRefGoogle Scholar
  25. 25.
    H.J. Coelingh Bennink, Y. Zimmerman, E. Laan, H.M. Termeer, N. Appels, A. Albert, B.C. Fauser, J.H. Thijssen, R.H. van Lunsen, Maintaining physiological testosterone levels by adding dehydroepiandrosterone to combined oral contraceptives: I. Endocrine effects. Contraception 96, 322–329 (2017)CrossRefGoogle Scholar
  26. 26.
    S.G. Beckham, C.P. Earnest, Four weeks of androstenedione supplementation diminishes the treatment response in middle aged men. Br. J. Sports Med. 37, 212–218 (2003)CrossRefGoogle Scholar
  27. 27.
    S. Welle, R. Jozefowicz, M. Statt, Failure of dehydroepiandrosterone to influence energy and protein metabolism in humans. J. Clin. Endocrinol. Metab. 71, 1259–1264 (1990)CrossRefGoogle Scholar
  28. 28.
    K.S. Nair, R.A. Rizza, P. O’Brien, K. Dhatariya, K.R. Short, A. Nehra, J.L. Vittone, G.G. Klee, A. Basu, R. Basu, C. Cobelli, G. Toffolo, C. Dalla Man, D.J. Tindall, L.J. Melton 3rd, G.E. Smith, S. Khosla, M.D. Jensen, DHEA in elderly women and DHEA or testosterone in elderly men. N. Engl. J. Med. 355, 1647–1659 (2006)CrossRefGoogle Scholar
  29. 29.
    R.S. Boxer, A. Kleppinger, J. Brindisi, R. Feinn, J.A. Burleson, A.M. Kenny, Effects of dehydroepiandrosterone (DHEA) on cardiovascular risk factors in older women with frailty characteristics. Age Ageing 39, 451–458 (2010)CrossRefGoogle Scholar
  30. 30.
    M. Srinivasan, B.A. Irving, R.L. Frye, P. O’Brien, S.J. Hartman, J.P. McConnell, K.S. Nair, Effects on lipoprotein particles of long-term dehydroepiandrosterone in elderly men and women and testosterone in elderly men. J. Clin. Endocrinol. Metab. 95, 1617–1625 (2010)CrossRefGoogle Scholar
  31. 31.
    M.L. Kohut, J.R. Thompson, J. Campbell, G.A. Brown, M.D. Vukovich, D.A. Jackson, D.S. King, Ingestion of a dietary supplement containing dehydroepiandrosterone (DHEA) and androstenedione has minimal effect on immune function in middle-aged men. J. Am. Coll. Nutr. 22, 363–371 (2003)CrossRefGoogle Scholar
  32. 32.
    A. Igwebuike, B.A. Irving, M.L. Bigelow, K.R. Short, J.P. McConnell, K.S. Nair, Lack of dehydroepiandrosterone effect on a combined endurance and resistance exercise program in postmenopausal women. J. Clin. Endocrinol. Metab. 93, 534–538 (2008)CrossRefGoogle Scholar
  33. 33.
    T. Elraiyah, M.B. Sonbol, Z. Wang, T. Khairalseed, N. Asi, C. Undavalli, M. Nabhan, O. Altayar, L. Prokop, V.M. Montori, M.H. Murad, Clinical review: The benefits and harms of systemic dehydroepiandrosterone (DHEA) in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 99, 3536–3542 (2014)CrossRefGoogle Scholar
  34. 34.
    K.K. Dhatariya, L.J. Greenlund, M.L. Bigelow, P. Thapa, A.L. Oberg, G.C. Ford, J.M. Schimke, K.S. Nair, Dehydroepiandrosterone replacement therapy in hypoadrenal women: protein anabolism and skeletal muscle function. Mayo. Clin. Proc. 83, 1218–1225 (2008)CrossRefGoogle Scholar
  35. 35.
    G. Gebre-Medhin, E.S. Husebye, H. Mallmin, L. Helström, C. Berne, F.A. Karlsson, O. Kämpe, Oral dehydroepiandrosterone (DHEA) replacement therapy in women with Addison’s disease. Clin. Endocrinol. 52, 775–780 (2000)CrossRefGoogle Scholar
  36. 36.
    J.J. Christiansen, N.H. Andersen, K.E. Sørensen, E.M. Pedersen, P. Bennett, M. Andersen, J.S. Christiansen, J.O. Jørgensen, C.H. Gravholt, Dehydroepiandrosterone substitution in female adrenal failure: no impact on endothelial function and cardiovascular parameters despite normalization of androgen status. Clin. Endocrinol. 66, 426–433 (2007)CrossRefGoogle Scholar
  37. 37.
    T. Yeung, J. Chai, R. Li, V. Lee, P.C. Ho, E. Ng, A double-blind randomised controlled trial on the effect of dehydroepiandrosterone on ovarian reserve markers, ovarian response and number of oocytes in anticipated normal ovarian responders. BJOG 123, 1097–1105 (2016)CrossRefGoogle Scholar
  38. 38.
    G. Corona, G. Rastrelli, V.A. Giagulli, A. Sila, A. Sforza, G. Forti, E. Mannucci, M. Maggi, Dehydroepiandrosterone supplementation in elderly men: a meta-analysis study of placebo-controlled trials. J. Clin. Endocrinol. Metab. 98, 3615–3626 (2013)CrossRefGoogle Scholar
  39. 39.
    F. Labrie, DHEA, important source of sex steroids in men and even more in women. Prog. Brain Res. 182, 97–148 (2010)CrossRefGoogle Scholar
  40. 40.
    WADA, Technical document reporting and evaluation guidance for testosterone, epitestosterone, T/E ratio and other endogenous steroids: TD2016EAAS, World Anti-Doping Agency (WADA), Montreal (2016).Google Scholar
  41. 41.
    M. Schönfelder, H. Hofmann, T. Schulz, T. Engl, D. Kemper, B. Mayr, C. Rautenberg, R. Oberhoffer, D. Thieme, Potential detection of low-dose transdermal testosterone administration in blood, urine, and saliva. Drug. Test. Anal. 8, 1186–1196 (2016)CrossRefGoogle Scholar
  42. 42.
    H. Lund, A.H. Snilsberg, T.G. Halvorsen, P. Hemmersbach, L. Reubsaet, Comparison of newly developed immuno-MS method with existing DELFIA(®) immunoassay for human chorionic gonadotropin determination in doping analysis. Bioanalysis 5, 623–630 (2013)CrossRefGoogle Scholar
  43. 43.
    M. Okano, Y. Nishitani, M. Sato, S. Kageyama, Effectiveness of GH isoform differential immunoassay for detecting rhGH doping on application of various growth factors. Drug Test. Anal. 4, 692–700 (2012).CrossRefGoogle Scholar
  44. 44.
    S.C. Voss, N. Robinson, M. Alsayrafi, P.C. Bourdon, Y.O. Schumacher, M. Saugy, S. Giraud, The effect of a period of intense exercise on the marker approach to detect growth hormone doping in sports. Drug. Test. Anal. 6, 582–586 (2014)CrossRefGoogle Scholar
  45. 45.
    P. Fénichel, F. Paris, P. Philibert, S. Hiéronimus, L. Gaspari, J.Y. Kurzenne, P. Chevallier, S. Bermon, N. Chevalier, C. Sultan, Molecular diagnosis of 5α-reductase deficiency in 4 elite young female athletes through hormonal screening for hyperandrogenism. J. Clin. Endocrinol. Metab. 98, E1055–E1059 (2013)CrossRefGoogle Scholar
  46. 46.
    S. Bermon, P.Y. Garnier, A.L. Hirschberg, N. Robinson, S. Giraud, R. Nicoli, N. Baume, M. Saugy, P. Fénichel, S.J. Bruce, H. Henry, G. Dollé, M. Ritzen, Serum androgen levels in elite female athletes. J. Clin. Endocrinol. Metab. 99, 4328–4335 (2014)CrossRefGoogle Scholar
  47. 47.
    F. Ponzetto, F. Mehl, J. Boccard, N. Baume, S. Rudaz, M. Saugy, R. Nicoli, Longitudinal monitoring of endogenous steroids in human serum by UHPLC-MS/MS as a tool to detect testosterone abuse in sports. Anal. Bioanal. Chem. 408, 705–719 (2016)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Katia Collomp
    • 1
    • 2
    • 3
    Email author
  • Corinne Buisson
    • 3
  • Nicolas Gravisse
    • 1
    • 2
  • Soraya Belgherbi
    • 4
  • Zakaria Labsy
    • 1
    • 2
  • Manh-Cuong Do
    • 1
    • 2
  • Olivier Gagey
    • 1
    • 2
  • Sophie Dufay
    • 5
  • Nancy Vibarel-Rebot
    • 1
    • 2
  • Michel Audran
    • 3
  1. 1.CIAMS, Univ. Paris-SudUniversité Paris-SaclayOrsayFrance
  2. 2.CIAMSUniversité OrléansOrléansFrance
  3. 3.Département des AnalysesAFLDChatenay-MalabryFrance
  4. 4.Service de Médecine PréventiveUniv. Paris-Sud, Université Paris-SaclayOrsayFrance
  5. 5.Laboratoire de Développement AnalytiqueAGEPSParisFrance

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