Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: Contribution of the DHEAge Study to a sociobiomedical issue

  1. Etienne-Emile Baulieua,b,
  2. Guy Thomasc,
  3. Sylvie Legraind,
  4. Najiba Lahloue,
  5. Marc Rogere,
  6. Brigitte Debuiref,
  7. Veronique Faucounaug,
  8. Laurence Girardh,
  9. Marie-Pierre Hervyi,
  10. Florence Latourj,
  11. Marie-Céline Leaudk,
  12. Amina Mokranel,
  13. Hélène Pitti-Ferrandim,
  14. Christophe Trivallef,
  15. Olivier de Lacharrièren,
  16. Stephanie Nouveaun,
  17. Brigitte Rakoto-Arisono,
  18. Jean-Claude Souberbiellep,
  19. Jocelyne Raisonq,
  20. Yves Le Boucr,
  21. Agathe Raynaudr,
  22. Xavier Girerdq, and
  23. Françoise Foretteg,j
  1. aInstitut National de la Santé et de la Recherche Médicale Unit 488 and Collège de France, 94276 Le Kremlin-Bicêtre, France; cInstitut National de la Santé et de la Recherche Médicale Unit 444, Hôpital Saint-Antoine, 75012 Paris, France; dHôpital Bichat, 75877 Paris, France; eHôpital Saint-Vincent de Paul, 75014 Paris, France; fHôpital Paul Brousse, 94804 Villejuif, France; gFondation Nationale de Gérontologie, 75016 Paris, France; hHôpital Charles Foix, 94205 Ivry, France; iHôpital de Bicêtre, 94275 Bicêtre, France; jHôpital Broca, 75013 Paris, France; kCentre Jack-Senet, 75015 Paris, France; lHôpital Sainte-Perine, 75016 Paris, France; mObservatoire de l'Age, 75017 Paris, France; nL'Oréal, 92583 Clichy, France; oInstitut de Sexologie, 75116 Paris, France; pHôpital Necker, 75015 Paris, France; qHôpital Broussais, 75014 Paris, France; and rHôpital Trousseau, 75012 Paris, France
  1. Contributed by Etienne-Emile Baulieu

Abstract

The secretion and the blood levels of the adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) decrease profoundly with age, and the question is posed whether administration of the steroid to compensate for the decline counteracts defects associated with aging. The commercial availability of DHEA outside the regular pharmaceutical–medical network in the United States creates a real public health problem that may be resolved only by appropriate long-term clinical trials in elderly men and women. Two hundred and eighty healthy individuals (women and men 60–79 years old) were given DHEA, 50 mg, or placebo, orally, daily for a year in a double-blind, placebo-controlled study. No potentially harmful accumulation of DHEAS and active steroids was recorded. Besides the reestablishment of a “young” concentration of DHEAS, a small increase of testosterone and estradiol was noted, particularly in women, and may be involved in the significantly demonstrated physiological–clinical manifestations here reported. Bone turnover improved selectively in women >70 years old, as assessed by the dual-energy x-ray absorptiometry (DEXA) technique and the decrease of osteoclastic activity. A significant increase in most libido parameters was also found in these older women. Improvement of the skin status was observed, particularly in women, in terms of hydration, epidermal thickness, sebum production, and pigmentation. A number of biological indices confirmed the lack of harmful consequences of this 50 mg/day DHEA administration over one year, also indicating that this kind of replacement therapy normalized some effects of aging, but does not create “supermen/women” (doping).

Footnotes

  • b To whom reprint requests should be addressed. E-mail: baulieu{at}kb.inserm.fr.

  • § S.L., Christine Massien, N.L., M.R., B.D., Bertrand Diquet, Gilles Chatellier, Michel Azizi, V.F., Hervé Porchet, F.F., and E.-E.B., unpublished work.

  • Abbreviations:
    DHEA,
    dehydroepiandrosterone;
    DHEAS,
    DHEA sulfate;
    Testo,
    testosterone;
    ADG,
    5α-androstan-3α,17β-diol glucuronide;
    E2,
    estradiol;
    PSA,
    prostate-specific antigen;
    M0,
    M6, and M12, months 0, 6, and 12;
    IGF-1,
    insulin-like growth factor 1;
    HDL,
    high density lipoprotein;
    BMD,
    bone mineral density;
    Oc,
    osteocalcin;
    baP,
    bone alkaline phosphatase;
    CTx,
    C-terminal telopeptide of type I collagen
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