Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

12 Issues per year


IMPACT FACTOR 2016: 3.432

CiteScore 2016: 2.21

SCImago Journal Rank (SJR) 2016: 1.000
Source Normalized Impact per Paper (SNIP) 2016: 1.112

Online
ISSN
1437-4331
See all formats and pricing
More options …
Volume 43, Issue 2 (Apr 2005)

Issues

Delayed effects of short-term transdermal application of 7-oxo-dehydroepiandrosterone on its metabolites, some hormonal steroids and relevant proteohormones in healthy male volunteers

Jarmila Šulcová / Richard Hampl / Martin Hill / Luboslav Stárka / Alois Nováček
Published Online: 2011-09-21 | DOI: https://doi.org/10.1515/CCLM.2005.038

Abstract

Twenty-one healthy male volunteers aged 20–70years were given transdermally 25mg of 7-oxo-dehydroepiandrosterone daily in the form of an emulgel for 8 consecutive days. Morning blood was collected as follows: before application, and after the first, fourth and eighth doses (days 0, 2, 5 and 9), and then at different time intervals after termination of the treatment (days 16, 23, 37, 51, 72 and 100). Cortisol, testosterone, epitestosterone, estradiol, dehydroepiandrosterone and its sulfate, 7α- and 7β-hydroxy-dehydroepiandrosterone, luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin were measured in blood sera. In the course of treatment 7β-hydroxy-dehydroepiandrosterone was significantly increased; testosterone and gonadotropins were lowered, but only after the first dose. All other significant changes were observed duringthe period after termination of the application:7β-hydroxy-dehydroepiandrosterone remained increased for 28days, 7α-hydroxy-dehydroepiandrosterone, testosterone, estradiol and sex hormone-binding globulin were decreased as late as day 63 and 91, respectively. On the other hand, epitestosterone was significantly increased between days 23 and 100. The levels of all other parameters studied were not significantly changed. The study points to an immediate as well as delayed effect of the short-term transdermal application of 7-oxo-dehydroepiandrosterone on relevant hormonal parameters.

Keywords: delayed effect; epitestosterone; 7-hydroxy-dehydroepiandrosterone; 7-oxo-dehydroepiandrosterone; transdermal application

References

  • 1

    Šulcová J, Stárka L. Characterization of microsomal dehydroepiandrosterone 7-hydroxylase from rat liver. Steroids 1968; 12: 113–26. CrossrefGoogle Scholar

  • 2

    Šulcová J, Čapková A, Jirásek JE, Stárka L. 7-Hydroxylation of dehydroepiandrosterone in human foetal liver, adrenals and chorion in vitro. Acta Endocrinol 1968; 59: 1–9. Google Scholar

  • 3

    Šulcová J, Stárka L. 7α-Hydroxylation of dehydroepiandrosterone in human testis and epididymis in vitro. Experientia 1972; 28: 1361–2. Google Scholar

  • 4

    Robinzon B, Michael KK, Ripp SL, Winters SJ, Prough RA. Glucocorticoids inhibit interconversion of 7-hydroxy and 7-oxo metabolites of dehydroepiandrosterone: a role for 11β-hydroxysteroid dehydrogenases? Arch Biochem Biophys 2001; 389: 278–87. Google Scholar

  • 5

    Hampl R, Morfin R, Stárka L. 7-Hydroxylated derivatives of dehydroepiandrosterone: what are they good for? Endocr Regul 1997; 31: 211–28. Google Scholar

  • 6

    Akwa Y, Morfin RF, Robel P, Baulieu BB. Neurosteroid metabolism. 7-Alpha-hydroxylation of dehydroepiandrosterone and pregnenolone by rat brain microsomes. Biochem J 1992; 288: 959–64. Google Scholar

  • 7

    Morfin R, Stárka L. Neurosteroid 7-hydroxylation products in the brain. Int Rev Neurobiol 2001; 46: 79–95. CrossrefGoogle Scholar

  • 8

    Morfin R, Courchay G. Pregnenolone and dehydroepiandrosterone as precursors of native 7-hydroxylated metabolites which increase the immune response in mice. J Steroid Biochem Mol Biol 1994; 50: 91–100. CrossrefGoogle Scholar

  • 9

    Hampl R, Lapčík O, Hill M, Klak J, Kasal A, Nováček A, et al. 7-Hydroxy-dehydroepiandrosterone – a natural antiglucocorticoid and candidate for steroid replacement therapy? Physiol Res 2000; 49(Suppl 1): S107–12. Google Scholar

  • 10

    Chmielewski V, Drupt F, Morfin R. Dexamethasone-induced apoptosis of mouse thymocytes: prevention by native 7alpha-hydroxysteroids. Immunol Cell Biol 2000; 78: 238–46. CrossrefGoogle Scholar

  • 11

    Morfin R, Lafaye P, Cotillon AC, Nato F, Chmielewski V, Pompon D. 7-Alpha-hydroxy-dehydroepiandrosterone and immune response. Ann NY Acad Sci 2000; 917: 971–82. Google Scholar

  • 12

    Liu YY, Yang N, Kong LN, Zuo PP. Effects of 7-oxo-DHEA treatment on the immunoreactivity BALB/c mice subjected to chronic mild stress. Yao Xue Xue Bao 2003; 38: 881–4. Google Scholar

  • 13

    Pelissier MA, Trap C, Malewiak MI, Morfin R. Antioxidant effects of dehydro-epiandrosterone and 7alpha-hydroxydehydroepiandrosterone in the rat colon, intestine and liver. Steroids 2004; 69: 137–44. Google Scholar

  • 14

    Lardy H, Partridge B, Kneer N, Wei Y. Ergosteroids: induction of thermogenic enzymes on liver of rats treated with steroids derived from dehydroepiandrosterone. Proc Natl Acad Sci USA 1995; 92: 6617–9. CrossrefGoogle Scholar

  • 15

    Bobyleva V, Ballei M, Kneer N, Lardy H. The effects of the ergosteroid 7-oxo-dehydroepiandrosterone on mitochondrial membrane potential: possible relationship to thermogenesis. Arch Biochem Biophys 1997; 341: 122–8. Google Scholar

  • 16

    Shi J, Schulze S, Lardy HA. The effects of 7-oxo-DHEA acetate on memory in young and old C57BL/6 mice. Steroids 2000; 65: 124–9. CrossrefGoogle Scholar

  • 17

    Hampl R, Pohanka M, Hill M, Stárka L. The content of four immunomodulatory steroids and major androgens in human semen. J Steroid Biochem Mol Biol 2003; 84: 307–16. CrossrefGoogle Scholar

  • 18

    Skinner SJ, Holdaway IM, Mason BH, Couch RA, Kay RG. Estrogen receptor status, adrenal androgens and 7 alpha-hydroxydehydroepiandrosterone in breast cancer patients. Eur J Cancer Clin Oncol 1984; 20: 1227–31. CrossrefGoogle Scholar

  • 19

    Attal-Khemis S, Dalmeyda V, Michot JL, Rondier M, Morfin R. Increased total 7 alpha-hydroxydehydroepiandrosterone in serum of patients with Alzheimer's disease. J Gerontol A Biol Sci Med Sci 1998; 53: B125–32. Google Scholar

  • 20

    Kim SB, Hill M, Kwak YT, Hampl R, Jo DH, Morfin R. Neurosteroids: cerebrospinal fluid levels for Alzheimer's disease and vascular dementia diagnosis. J Clin Endocrinol Metab 2003; 88: 5199–206. CrossrefGoogle Scholar

  • 21

    Šulcová J, Hill M, Hampl R, MaŠek Z, Nováček A, ČeŠka R, et al. Effects of transdermal application of DHEA on the levels of steroids, gonadotropins and lipids in men. Physiol Res 2000; 49: 685–93. Google Scholar

  • 22

    Šulcová J, Hill M, MaŠek Z, ČeŠka R, Nováček A, Hampl R, et al. Effects of transdermal application of 7-oxo-DHEA on the levels of steroid hormones, gonadotropins and lipids in healthy men. Physiol Res 2001; 50: 9–18. Google Scholar

  • 23

    Bičíková M, Hampl R, Putz Z, Stárka L. Comparison of isotope and nonisotope variants of direct cortisol immunoassay. In: Gorog S, editor. Advances in steroid analysis '87. Budapest: Akadémiai Kiadó, 1988:101–6. Google Scholar

  • 24

    Hampl R. Comparison of three immunoassays for testosterone determination. In: Gorog S, editor. Advances in steroid analysis '93. Budapest: Akadémiai Kiadó, 1994:163–9. Google Scholar

  • 25

    Bílek R., Hampl R, Putz Z, Stárka L. Radioimmunoassay of epitestosterone: methodology, thermodynamic aspects and applications. J Steroid Biochem 1987; 28: 723–9. CrossrefGoogle Scholar

  • 26

    Lapčík O, Hampl R, Hill M, Stárka L. Immunoassay of 7-hydroxysteroids: 2. radioimmunoassay of 7α-hydroxy-dehydroepiandrosterone. J Steroid Biochem Mol Biol 1999; 71: 231–7. CrossrefGoogle Scholar

  • 27

    Lapčík O, Hampl R, Hill M, Bičíková M, Stárka L. Immunoassay of 7-hydroxy-steroids: 1. radioimmunoassay of 7β-hydroxy-dehydroepiandrosterone. J Steroid Biochem Mol Biol 1998; 67: 439–45. Google Scholar

  • 28

    Orentreich N, Brind JL, Rizel RL, Vogelman JH. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab 1984; 59: 551–5. CrossrefGoogle Scholar

  • 29

    Šulcová J, Hill M, Hampl R, Stárka L. Age and sex related differences in serum levels of unconjugated dehydroepiandrosterone and its sulphate in normal subjects. J Endocrinol 1997; 154: 57–62. Google Scholar

  • 30

    Baulieu EE. Dehydroepiandrosterone (DHEA): a fountain of youth. J Clin Endocrinol Metab 1996; 81: 3147–51. CrossrefGoogle Scholar

  • 31

    Baulieu EE. Androgens and aging men. Mol Cell Endocrinol 2002; 198: 41–9. Google Scholar

  • 32

    Mortola JF, Yen SS. The effects of oral dehydroepiandrosterone on endocrine-metabolic parameters in postmenopausal women. J Clin Endocrinol Metab 1990; 71: 696–704. CrossrefGoogle Scholar

  • 33

    Casson PR, Andersen RN, Herrod HG, Stentz FB, Straughn AB, Abraham GE, et al. Oral dehydroepiandrosterone in physiologic doses modulates immune function in postmenopausal women. Am J Obstet Gynecol 1993; 169: 1536–9. Google Scholar

  • 34

    Arlt W, Justl HG, Callies F, Reincke M, Hubler D, Oettel M, et al. Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression. J Clin Endocrinol Metab 1998; 83: 1928–34. CrossrefGoogle Scholar

  • 35

    Arlt W, Haas J, Callies F, Reincke M, Hubler D, Oettel M, et al. Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens. J Clin Endocrinol Metab 1999; 84: 2170–6. CrossrefGoogle Scholar

  • 36

    Baulieu EE, Thomas G, Legrain S, Lahlou N, Roger M, Debuire B, et al. Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue. Proc Natl Acad Sci USA 2000; 97: 4279–84. CrossrefGoogle Scholar

  • 37

    Frye RF, Kroboth PD, Kroboth FJ, Stone RA, Folan M, Salek FS, et al. Sex differences in the pharmacokinetics of dehydroepiandrosterone (DHEA) after single- and multiple-dose administration in healthy older adults. J Clin Pharmacol 2000; 40: 596–605. CrossrefGoogle Scholar

  • 38

    Legrain S, Massien C, Lahlou N, Roger M, Debuire B, Diquet B, et al. Dehydroepiandrosterone replacement administration: pharmacokinetic and pharmacodynamic studies in healthy elderly subjects. J Clin Endocrinol Metab 2000; 85: 3208–17. Google Scholar

  • 39

    Percheron G, Hogrel JY, Denot-Ledunois S, Fayet G, Forette F, Baulieu EE, et al. Effect of 1-year oral administration of dehydroepiandrosterone to 60- to 80year-old individuals on muscle function and cross-sectional area: a double blind placebo-controlled trial. Arch Intern Med 2003; 163: 720–7. Google Scholar

  • 40

    Kroboth PD, Amico JA, Stone RA, Folan M, Frye RF, Kroboth FJ, et al. Influence of DHEA administration on 24-hour cortisol concentrations. J Clin Psychopharmacol 2003; 23: 96–9. CrossrefGoogle Scholar

  • 41

    Labrie C, Flamand M, Bélanger A, Labrie F. High bioavailability of dehydroepiandrosterone administered percutaneously in the rat. J Endocrinol 1996; 150: S107–18. Google Scholar

  • 42

    Diamond P, Cusan L, Gomez J-L, Bélanger A, Labrie F. Metabolic effects of 12-month percutaneous dehydroepiandrosterone replacement therapy in postmenopausal women. J Endocrinol 1996; 150: S43–S50. Google Scholar

  • 43

    Lardy H, Henwood SM, Weeks CE. An acute oral gavage study of 3beta-acetoxyandrost-5-ene-7,17-dione (7-oxo-DHEA-acetate) in rats. Biochem Biophys Res Commun 1999; 254: 120–3. Google Scholar

  • 44

    Henwood SM, Weeks CE, Lardy H. An escalating dose oral gavage study of 3beta-acetoxyandrost-5-ene-7,17-dione (7-oxo-DHEA-acetate) in rhesus monkeys. Biochem Biophys Res Commun 1999; 254: 124–6. Google Scholar

  • 45

    Davidson M, Marwah A, Sawchuk RJ, Maki K, Marwah P, Weeks C, et al. Safety and pharmacokinetic study with escalating doses of 3-beta-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers. Clin Invest Med 2000; 23: 300–10. Google Scholar

  • 46

    Kalman DS, Colker CM, Swain MA, Torina GC, Shi, Q. A randomized, double-blind, placebo controlled study of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy overweight adults. Curr Ther Res Clin Exp 2000; 61: 435–42. Google Scholar

  • 47

    Zenk JL, Helmer TR, Kassen LJ, Kuskowski MA. The effect of 7-Keto Naturalean™ on weight loss: a randomized, double-blind, placebo-controlled trial. Curr Ther Res 2002; 63: 263–72. CrossrefGoogle Scholar

  • 48

    Hampl R, Lapčík O, Hill M, Klak J, Kasal A, Nováček A, et al. 7-Hydroxydehydroepiandrosterone – a natural antiglucocorticoid and a candidate for steroid replacement therapy? Physiol Res 2000; 49(Suppl 1): S107–12. Google Scholar

  • 49

    Hult M, Elleby B, Shafqat N, Svensson S, Rane A, Jornvall H, et al. Human and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol metabolism. Cell Mol Life Sci 2004; 61: 992–9. Google Scholar

  • 50

    Shiotsuki H, Maeda Y, Chijiiwa K. Purification and characterization of 7beta-hydroxysteroid dehydrogenase from rabbit liver microsomes. J Steroid Biochem Mol Biol 2004; 91: 185–90. CrossrefGoogle Scholar

  • 51

    Stárka L, Hampl R, Bičíková M, Jelínek R, Doskočil M. Observations on the biological activity of epitestosterone. Physiol Bohemoslov 1991; 40: 317–26. Google Scholar

  • 52

    Stárka L. Epitestosterone: a review. J Steroid Biochem Mol Biol 2003; 87: 27–34. CrossrefGoogle Scholar

About the article

Corresponding author: Dr. Jarmila Šulcová, Institute of Endocrinology, Národní 8, 116 94 Praha 1, Czech Republic Phone: +420-224-905289, Fax: +420-224-905325,


Received: 2004-09-21

Accepted: 2004-11-10

Published Online: 2011-09-21

Published in Print: 2005-04-01


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2005.038.

Export Citation

©2005 by Walter de Gruyter Berlin New York. Copyright Clearance Center

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Comments (0)

Please log in or register to comment.
Log in