Download PDF
Int J Sports Med 2007; 28(10): 809-814
DOI: 10.1055/s-2007-964991
Physiology & Biochemistry

© Georg Thieme Verlag KG Stuttgart · New York

Do Non-Steroidal Anti-Inflammatory Drugs Influence the Steroid Hormone Milieu in Male Athletes?

L. Di Luigi1 , C. Rossi2 , P. Sgrò1 , V. Fierro1 , F. Romanelli3 , C. Baldari4 , L. Guidetti5
  • 1Unit of Endocrinology, Department of Health Sciences, University of Rome “IUSM”, Rome, Italy
  • 2First Aid Unit, Department of Health Sciences, University of Rome “IUSM”, Rome, Italy
  • 3Department of Medical Physiopathology, University of Rome “La Sapienza”, Rome, Italy
  • 4Unit of Sport Science, Department of Health Sciences, University of Rome “IUSM”, Rome, Italy
  • 5Unit of Physical Exercise Science, Department of Health Sciences, University of Rome “IUSM”, Rome, Italy
Further Information

Publication History

accepted after revision October 5, 2006

Publication Date:
11 May 2007 (online)

Also available at
    Permissions and Reprints

Abstract

Prostaglandins modulate the hypothalamus-pituitary-adrenal and ‐gonadal axis pathways. We explored the effects of a single course of treatment with acetylsalicylic acid (ASA), an inhibitor of prostaglandin synthesis, on the steroid milieu in athletes. Morning plasma cortisol (F), dehydroepiandrosterone sulphate, free-testosterone, testosterone (T) and their ratios were evaluated before and after the administration of either ASA or placebo in twelve male athletes, when affected by minor musculoskeletal trauma and, as control, after a five/six week wash-out in healthy conditions respectively. One tablet of ASA (800 mg), or placebo, was administered two times daily for 10 days during treatment. All the volunteers suspended exercise training during treatment. The results revealed that compared to placebo, plasma F was significantly lower after ASA treatment (p = 0.023). Furthermore, the comparison of hormone's absolute and percentage of variations (Δ and Δ%) between ASA and placebo treatment showed significant differences respectively for ΔF (p = 0.045), for ΔT (p = 0.047), for ΔT/F (p = 0.042), for ΔF% (p = 0.04) and for ΔT% (p = 0.049). Our data suggest that in comparison to placebo, a short-term ASA treatment is able to influence the plasma steroid milieu in athletes. Due to the observed variability of the individual hormonal patterns, further research is required to substantiate these findings.

Key words

acetylsalicylic acid - cortisol - testosterone - DHEAS - sport - prostaglandins

References

  • 1 Anthonisen M, Knigge U, Kjær A, Warberg J. Histamine and prostaglandin interaction in the central regulation of ACTH secretion.  Neuroendocrinology. 1997;  66 68-74
    PubMedGoogle Scholar
  • 2 Bernardini R, Chiarenza A, Calogero A E, Gold P W, Chrousos G P. Arachidonic acid metabolites modulate rat hypothalamic corticotropin-releasing hormone secretion in vitro.  Neuroendocrinology. 1989;  50 708-715
    PubMedGoogle Scholar
  • 3 Bugajski J, Gadek-Michalska A, Borycz J, Glod R. Effect of indomethacin on nicotine-induced ACTH and corticosterone response.  J Physiol Pharmacol. 1998;  49 165-173
    PubMedGoogle Scholar
  • 4 Cannavò S, Curtò L, Trimarchi F. Exercise-related female reproductive dysfunction.  J Endocrinol Invest. 2001;  24 823-832
    PubMedGoogle Scholar
  • 5 Cavagnini F, Di Landro A, Maraschini C, Invitti C, Pinto M L. Effect of two prostaglandin synthesis inihibitors, indomethacin and acetylsalicylic acid, on plasma ACTH and cortisol levels in man.  Acta Endocrinol. 1979;  91 666-673
    PubMedGoogle Scholar
  • 6 Conn P M, Whorton R, Lazar J. An inhibitor of arachidonic acid metabolism stimulates luteinizing hormone (LH) release from cultured pituitary cells.  Prostaglandins. 1980;  19 873-879
    CrossrefPubMedGoogle Scholar
  • 7 Conte D, Falaschi P, Proietti A, D'Urso R, Citarella F, Nordio M, Romanelli F, Maggi R, Motta M. Role of arachidonate metabolism on the in vitro release of luteinizing hormone and prolactin from anterior pituitary gland: involvement of lipoxygenase pathway.  Neuroendocrinology. 1986;  43 428-434
    PubMedGoogle Scholar
  • 8 Conte D, Nordio M, Fillo S, De Giorgio G, Isidori A, Romanelli F. Aspirin inhibition of naloxone-induced luteinizing hormone secretion in man.  J Clin Endocrinol Metab. 1996;  81 1772-1775
    CrossrefPubMedGoogle Scholar
  • 9 Conte D, Romanelli F, Fillo S, Guidetti L, Isidori A, Franceschi F, Latini M, Di Luigi L. Aspirin inhibits androgen response to chorionic gonadotropin in humans.  Am J Physiol. 1999;  277 E1032-E1037
    PubMedGoogle Scholar
  • 10 Cumming D C, Quigley M E, Yen S S. Acute suppression of circulating testosterone levels by cortisol in men.  J Clin Endocrinol Metab. 1983;  57 671-673
    CrossrefPubMedGoogle Scholar
  • 11 Cumming D C, Wheeler G D, McColl E M. The effects of exercise on reproductive function in men.  Sports Med. 1989;  7 1-17
    PubMedGoogle Scholar
  • 12 Cumming D C. Hormones and athletic performance. Felig P, Baxter JD, Frohman LA Endocrinology and Metabolism. New York; Mc Graw Hill 1995: 1837-1886
    Google Scholar
  • 13 Dave J R, Witorsch R J. Indomethacin decreases both luteinizing hormone binding and fluidity of testicular microsomal membranes in rat.  Prostaglandins Leukot Med. 1983;  12 371-380
    CrossrefPubMedGoogle Scholar
  • 14 De Souza M J, Miller B E. The effect of endurance training on reproductive function in male runners. A “volume threshold” hypothesis.  Sports Med. 1997;  23 357-374
    PubMedGoogle Scholar
  • 15 Di Luigi L, Guidetti L, Pigozzi F, Baldari C, Casini A, Nordio M, Romanelli F. Acute amino acids supplementation enhances pituitary responsiveness in athletes.  Med Sci Sports Exerc. 1999;  31 1748-1754
    PubMedGoogle Scholar
  • 16 Di Luigi L, Guidetti L, Romanelli F, Baldari C, Conte D. Acetylsalicylic acid inhibits the pituitary response to exercise-related stress in humans.  Med Sci Sports Exerc. 2001;  33 2029-2035
    PubMedGoogle Scholar
  • 17 Didolkar A K, Gurjar A, Joshi U M, Sheth A R, Roychowdhury D. Effects of aspirin on blood plasma levels of testosterone, LH and FSH in maturing male rats.  Int J Androl. 1980;  3 312-318
    PubMedGoogle Scholar
  • 18 Dix C J, Habberfield A D, Sullivan M H, Cooke B A. Inhibition of steroid production in Leydig cells by non-steroidal anti-inflammatory and related compounds: evidence for the involvement of lipoxygenase products in steroidogenesis.  Biochem J. 1984;  219 529-537
    PubMedGoogle Scholar
  • 19 Gobbetti A, Zerani M. Pituitary adenylate cyclase-activating polypeptide induces testicular testosterone synthesis through PGE(2) mediation in crested newt, Triturus carnifex.  J Exp Zool. 2002;  293 73-80
    CrossrefPubMedGoogle Scholar
  • 20 Hackney A C. The male reproductive system and endurance exercise.  Med Sci Sports Exerc. 1996;  28 180-189
    PubMedGoogle Scholar
  • 21 Hockings G I, Grice J E, Crosbie G V, Walters M M, Jackson A J, Jackson R V. Aspirin increases the human hypothalamic-pituitary-adrenal axis response to naloxone stimulation.  J Clin Endocrinol Metab. 1993;  77 404-408
    CrossrefPubMedGoogle Scholar
  • 22 Hockings G I, Jackson R V, Grice J E, Crosbie G V, Walters M M, Torpy D J, Jackson A J. Paradoxical inhibition by aspirin of naloxone-induced adrenocorticotropin secretion in myotonic dystrophy.  J Clin Endocrinol Metab. 1994;  78 1424-1427
    CrossrefPubMedGoogle Scholar
  • 23 Joris J, Reuter A M, Vrindts-Gevaert Y, Gathy-Meuleman R, Hargreaves K, Franchimont P. Effect of diclofenac on plasma levels of immunoreactive prolactin, follicle stimulating hormone, luteinizing hormone, thyrotropin, and β-endorphin in humans.  Horm Res. 1988;  29 143-146
    PubMedGoogle Scholar
  • 24 Kirschenbaum A, Liotta D R, Yao S, Liu X H, Klausner A P, Unger P, Shapiro E, Leav I, Levine A C. Immunohistochemical localization of cyclooxygenase-1 and cyclooxygenase-2 in the human fetal and adult male reproductive tracts.  J Clin Endocrinol Metab. 2000;  85 3436-3441
    CrossrefPubMedGoogle Scholar
  • 25 Korzekwa A, Jaroszewski J J, Bogacki M, Deptula K M, Maslanka T S, Acosta T J, Okuda K, Skarzynski D J. Effects of prostaglandin F(2alpha) and nitric oxide on the secretory function of bovine luteal cells.  J Reprod Dev. 2004;  50 411-417
    CrossrefPubMedGoogle Scholar
  • 26 Langer P, Foldes O, Michajlovskij N, Jezova D, Klimes I, Michalko J, Zavada M. Short-term effect of acetylsalicylic acid analogue on pituitary-thyroid axis and plasma cortisol level in healthy human volunteers.  Acta Endocrinol. 1978;  88 698-702
    PubMedGoogle Scholar
  • 27 Lanier A B. Use of nonsteroidal anti-inflammatory drugs following exercise-induced muscle injury.  Sports Med. 2003;  33 177-185
    CrossrefPubMedGoogle Scholar
  • 28 Lopez-Ruiz M P, Choi M S, Rose M P, West A P, Cooke B A. Direct effect of arachidonic acid on protein kinase C and LH-stimulated steroidogenesis in rat Leydig cells; evidence for tonic inhibitory control of steroidogenesis by protein kinase C.  Endocrinology. 1992;  130 1122-1130
    CrossrefPubMedGoogle Scholar
  • 29 Neeraja S, Sreenath A S, Reddy P R, Reddanna P. Expression of cyclooxygenase-2 in rat testis.  Reprod Biomed Online. 2003;  6 302-309
    PubMedGoogle Scholar
  • 30 Nye E J, Hockings G I, Grice J E, Torpy D J, Walters M M, Crosbie G V, Wagenaar M, Cooper M, Jackson R V. Aspirin inhibits vasopressin-induced hypothalamic-pituitary-adrenal activity in normal human.  J Clin Endocrinol Metab. 1997;  82 812-817
    CrossrefPubMedGoogle Scholar
  • 31 Ojeda S R, Harms P G, McCann S M. Effect of inhibitors of prostaglandin synthesis on gonadotropin release in the rat.  Endocrinology. 1975;  97 843-854
    PubMedGoogle Scholar
  • 32 Ojeda S R, Naor Z, Negro-Vilar A. The role of prostaglandins in the control of gonadotropin and prolactin secretion.  Prostaglandins Med. 1979;  2 249-275
    CrossrefPubMedGoogle Scholar
  • 33 Przybylowski J, Obodynski K, Lewicki C, Kuzniar J, Zaborniak S, Drozd S, Czarny W, Garmulewicz M. The influence of aspirin on exercise-induced changes in adrenocorticotrophic hormone (ACTH), cortisol and aldosterone (ALD) concentrations.  Eur J Appl Physiol. 2003;  89 177-183
    PubMedGoogle Scholar
  • 34 Raivio T, Dunkel L, Wickman S, Jänne O A. Serum androgen bioactivity in adolescence: a longitudinal study of boys with constitutional delay of puberty.  J Clin Endocrinol Metab. 2004;  89 1188-1192
    CrossrefPubMedGoogle Scholar
  • 35 Reddy G P, Prasad M, Sailesh S, Kumar Y V, Reddanna P. Arachidonic acid metabolites as intratesticular factors controlling androgen production.  Int J Androl. 1993;  16 227-233
    PubMedGoogle Scholar
  • 36 Romanelli F, Valenca M, Conte D, Isidori A, Negro-Vilar A. Arachidonic acid and its metabolites effects on testosterone production by rat Leydig cells.  J Endocrinol Invest. 1995;  18 186-193
    PubMedGoogle Scholar
  • 37 Tilbrook A J, Turner A I, Clarke I J. Effects of stress on reproduction in non-rodent mammals: the role of glucocorticoids and sex differences.  Rev Reprod. 2000;  5 105-113
    PubMedGoogle Scholar
  • 38 Tominaga T, Fukata J, Naito Y, Usui T, Murakami N, Fukushima M, Nakai Y, Hirai Y, Imura H. Prostaglandin-dependent in vitro stimulation of adrenocortical steroidogenesis by interleukins.  Endocrinology. 1991;  128 526-531
    PubMedGoogle Scholar
  • 39 Wang X, Shen C L, Dyson M T, Eimerl S, Orly J, Hutson J C, Stocco D M. Cyclooxygenase-2 regulation of the age-related decline in testosterone biosynthesis.  Endocrinology. 2005;  146 4202-4208
    CrossrefPubMedGoogle Scholar
  • 40 Warden S J. Cyclo-oxygenase-2 inhibitors: beneficial or detrimental for athletes with acute musculoskeletal injuries?.  Sports Med. 2005;  35 271-283
    CrossrefPubMedGoogle Scholar
  • 41 Warren M P, Perlroth N E. The effects of intense exercise on the female reproductive system.  J Endocrinol. 2001;  170 3-11
    CrossrefPubMedGoogle Scholar
  • 42 Zacharieva S, Borissova A M, Andonova K, Stoeva I, Matrozov P. Role of prostaglandin E2 (PGE2) on the corticotropin-releasing hormone (CRH)-induced ACTH release in healthy men.  Horm Metab Res. 1992;  24 336-338
    PubMedGoogle Scholar

Prof. Luigi Di Luigi

Unit of Endocrinology Department of Health Sciences
University of Rome IUSM

Piazza Lauro de Bosis, 15

00194 Roma

Italy

Phone: + 39 06 36 73 35 63

Fax: + 39 06 36 73 32 31

Email: luigi.diluigi@iusm.it

      >