Dehydroepiandrosterone Supplementation in Elderly Men: The Role of Estrogens Versus Androgens on the Male Skeleton

Lorenz C. Hofbauer, Bruno Allolio and Wiebke Arlt

Division of Gastroenterology and Endocrinology (L.C.H.), Philipps-University, D-35033 Marburg, Germany; and Department of Medicine (B.A., W.A.), Endocrine and Diabetes Unit, University of Wuerzburg, D-97080 Wuerzburg, Germany

Address correspondence to: Lorenz C. Hofbauer, M.D., Division of Gastroenterology, Endocrinology and Metabolism, Department of Medicine, Philipps University, Baldingerstrasse, D-35033 Marburg, Germany. E-mail: . hofbauer{at}post.med.uni-marburg.de

To the editor:

Khosla et al. (1) recently demonstrated that estrogens and androgens may have opposite effects on biochemical markers of bone metabolism in elderly men. In their elegant study, men were rendered acutely hypogonadal using a GnRH agonist and treated with an aromatase inhibitor to block conversion of androgens to estrogens, before receiving 17ß-estradiol alone, testosterone alone, or both 17ß-estradiol and testosterone, to distinguish the differential effects of androgens and estrogens on male bone metabolism (1). Although estrogen replacement in these men increased circulating levels of the antiresorptive decoy receptor osteoprotegerin (OPG), an essential regulator of osteoclast function and bone metabolism (2), androgen replacement suppressed OPG levels (1). Thus, that study has provided further support for the hypothesis that estrogens are essential for bone metabolism in men and that androgens and estrogens have distinct skeletal effects and are not interchangeable (1, 3).

Dehydroepiandrosterone (DHEA) is the crucial precursor of human sex steroid biosynthesis and can be converted toward both androgens and estrogens. In men, oral administration of DHEA increased circulating levels of estrogens and androgen metabolites (4). To gain further insight into the bone-specific action(s) of DHEA, we evaluated serum OPG concentrations in healthy elderly men (n = 22; age range, 50–69 yr) with low endogenous serum DHEA sulfate levels, who were receiving DHEA supplementation at a daily dose of 50 mg for 4 months in a randomized, placebo-controlled crossover trial, as reported elsewhere (5). In this study, DHEA treatment did not affect biochemical markers of bone formation (serum osteocalcin) and resorption (urinary pyridinoline and deoxypyridinoline excretion; Ref. 5), which is consistent with two similar studies (6, 7). Serum OPG concentrations measured with an enzyme-linked immunosorbent assay (Immundiagnostik, Bensheim, Germany) were not significantly different at baseline and after 1 and 4 months of DHEA administration compared with the placebo group.

In conclusion, DHEA administration had no effect on serum OPG levels in healthy elderly men. The results of Khosla et al. (1) suggest a differential response of circulating OPG levels to sex steroid treatment in men. Thus, the observed lack of changes in serum OPG levels during DHEA administration in healthy elderly men may result from a combined stimulatory and inhibitory effect on OPG production due to conversion of DHEA toward both estrogenic and androgenic steroids.

Received April 15, 2002.

References

  1. Khosla S, Atkinson EJ, Dunstan CR, O’Fallon WM 2002 Effect of estrogen versus testosterone on circulating osteoprotegerin and other cytokine levels in normal elderly men. J Clin Endocrinol Metab 87:1550–1554[Abstract/Free Full Text]
  2. Hofbauer LC, Heufelder AE 2000 The role of receptor activator of NF-{kappa}B ligand and osteoprotegerin in the pathogenesis and treatment of metabolic bone diseases. J Clin Endocrinol Metab 85:2355–2363[Free Full Text]
  3. Khosla S, Melton 3rd LJ, Riggs BL 2002 Estrogen and the male skeleton. J Clin Endocrinol Metab 87:1443–1450[Abstract/Free Full Text]
  4. Arlt W, Haas J, Callies F, Reincke M, Hübler D, Oettel M, Ernst M, Schulte HM, Allolio B 1999 Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens. J Clin Endocrinol Metab 84:1700–1706[Abstract/Free Full Text]
  5. Arlt W, Callies F, Koehler I, van Vlijmen JC, Fassnacht M, Strasburger CJ, Seibel MJ, Huebler D, Ernst M, Oettel M, Reincke M, Schulte HM, Allolio B 2001 Dehydroepiandrosterone supplementation in healthy men with an age-related decline of dehydroepiandrosterone secretion. J Clin Endocrinol Metab 86:4686–4692[Abstract/Free Full Text]
  6. Baulieu E-E, Thomas G, Legrain S, Lahlou N, Roger M, Debuire B, Fauconau V, Girard L, Hervy M-P, Latour F, Leaud M-C, Mokrane A, Pihi-Ferrandi H, Trivalle C, de la Lacharrière O, Nouveau S, Rakoto-Arison B, Souberbielle J-C, Raion J, LeBouc Y, Reynaud A, Girerd X, Forette F 2000 Dehydroepiandrosterone (DHEA), DHEA sulfate and aging: contribution of the DHEAge Study to a sociobiomedical issue. Proc Natl Acad Sci USA 97:4279–4284[Abstract/Free Full Text]
  7. Kahn AJ, Halloran B 2002 Dehydroepiandrosterone supplementation and bone turnover in middle-aged to elderly men. J Clin Endocrinol Metab 87:1544–1549[Abstract/Free Full Text]




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