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Dehydroepiandrosterone and its sulfate

George P Chrousos, MD
Section Editor
André Lacroix, MD
Deputy Editor
Kathryn A Martin, MD


Adrenal production of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA sulfate or DHEA-S) is substantial in both men and women. The production of both is greatest among young adults, and it declines progressively with age. At their peak at age 25 years, serum DHEA concentrations range from 0.2 to 0.9 mcg/dL (7 to 31 nmol/L), 10-fold lower than those of cortisol, and serum DHEA-S concentrations range from 75 to 370 mcg/dL (2 to 10 µmol/L), 20-fold higher than those of cortisol. By age 80 years, the concentrations are only about 20 percent of those at age 25 years [1-3].

DHEA is converted to DHEA-S in the adrenal and liver, both of which contain a sulfotransferase. The former is produced from the latter in peripheral tissues that contain a sulfatase. In the adrenal glands and peripheral tissues such as hair follicles, prostate, external genitalia, and adipose tissue, small amounts of DHEA and DHEA-S are converted to more active androgens such as androstenedione, androstenediol, testosterone, and 5-dihydrotestosterone, and estrogens such as estradiol and estrone. These hormones then exert their usual androgenic and estrogenic effects via the androgen and estrogen receptors, respectively. In women, adrenal production of DHEA and DHEA-S contributes substantially to overall androgen production and effects; in men the adrenal contribution is very small.

DHEA has been proposed to have many actions, including vasodilatory, anti-aging, anti-inflammatory, anti-atherosclerotic actions and anti-depressant, and it is widely available in stores that sell health foods and nutritional supplements. However, quality control of these products has been shown to be quite poor [4,5].

The possible sites of action and clinical uses of DHEA are reviewed here. Measurements of adrenal androgens and the causes and effects of excess endogenous production of DHEA and DHEA-S are discussed separately. (See "Adrenal hyperandrogenism".)


Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) act, after conversion to androgens and estrogens, by activating androgen and estrogen receptors, respectively, as noted above.


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Literature review current through: Jul 2017. | This topic last updated: Oct 22, 2013.
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  1. Nippoldt TB, Nair KS. Is there a case for DHEA replacement? Baillieres Clin Endocrinol Metab 1998; 12:507.
  2. Oelkers W. Dehydroepiandrosterone for adrenal insufficiency. N Engl J Med 1999; 341:1073.
  3. Kroboth PD, Salek FS, Pittenger AL, et al. DHEA and DHEA-S: a review. J Clin Pharmacol 1999; 39:327.
  4. Parasrampuria J, Schwartz K, Petesch R. Quality control of dehydroepiandrosterone dietary supplement products. JAMA 1998; 280:1565.
  5. Thompson RD, Carlson M, Thompson RD, Carlson M. Liquid chromatographic determination of dehydroepiandrosterone (DHEA) in dietary supplement products. J AOAC Int 2000; 83:847.
  6. Sousa A, Ticku MK. Interactions of the neurosteroid dehydroepiandrosterone sulfate with the GABA(A) receptor complex reveals that it may act via the picrotoxin site. J Pharmacol Exp Ther 1997; 282:827.
  7. Johansson T, Le Grevès P. The effect of dehydroepiandrosterone sulfate and allopregnanolone sulfate on the binding of [(3)H]ifenprodil to the N-methyl-d-aspartate receptor in rat frontal cortex membrane. J Steroid Biochem Mol Biol 2005; 94:263.
  8. Forman BM, Tzameli I, Choi HS, et al. Androstane metabolites bind to and deactivate the nuclear receptor CAR-beta. Nature 1998; 395:612.
  9. Liu D, Dillon JS. Dehydroepiandrosterone activates endothelial cell nitric-oxide synthase by a specific plasma membrane receptor coupled to Galpha(i2,3). J Biol Chem 2002; 277:21379.
  10. Takebayashi M, Hayashi T, Su TP. A perspective on the new mechanism of antidepressants: neuritogenesis through sigma-1 receptors. Pharmacopsychiatry 2004; 37 Suppl 3:S208.
  11. Arlt W, Callies F, van Vlijmen JC, et al. Dehydroepiandrosterone replacement in women with adrenal insufficiency. N Engl J Med 1999; 341:1013.
  12. Callies F, Fassnacht M, van Vlijmen JC, et al. Dehydroepiandrosterone replacement in women with adrenal insufficiency: effects on body composition, serum leptin, bone turnover, and exercise capacity. J Clin Endocrinol Metab 2001; 86:1968.
  13. Hunt PJ, Gurnell EM, Huppert FA, et al. Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison's disease in a randomized, double blind trial. J Clin Endocrinol Metab 2000; 85:4650.
  14. Gurnell EM, Hunt PJ, Curran SE, et al. Long-term DHEA replacement in primary adrenal insufficiency: a randomized, controlled trial. J Clin Endocrinol Metab 2008; 93:400.
  15. Gebre-Medhin G, Husebye ES, Mallmin H, et al. Oral dehydroepiandrosterone (DHEA) replacement therapy in women with Addison's disease. Clin Endocrinol (Oxf) 2000; 52:775.
  16. Løvås K, Gebre-Medhin G, Trovik TS, et al. Replacement of dehydroepiandrosterone in adrenal failure: no benefit for subjective health status and sexuality in a 9-month, randomized, parallel group clinical trial. J Clin Endocrinol Metab 2003; 88:1112.
  17. Dhatariya K, Bigelow ML, Nair KS. Effect of dehydroepiandrosterone replacement on insulin sensitivity and lipids in hypoadrenal women. Diabetes 2005; 54:765.
  18. Johannsson G, Burman P, Wirén L, et al. Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial. J Clin Endocrinol Metab 2002; 87:2046.
  19. Brooke AM, Kalingag LA, Miraki-Moud F, et al. Dehydroepiandrosterone improves psychological well-being in male and female hypopituitary patients on maintenance growth hormone replacement. J Clin Endocrinol Metab 2006; 91:3773.
  20. Rice SP, Agarwal N, Bolusani H, et al. Effects of dehydroepiandrosterone replacement on vascular function in primary and secondary adrenal insufficiency: a randomized crossover trial. J Clin Endocrinol Metab 2009; 94:1966.
  21. Suzuki T, Suzuki N, Engleman EG, et al. Low serum levels of dehydroepiandrosterone may cause deficient IL-2 production by lymphocytes in patients with systemic lupus erythematosus (SLE). Clin Exp Immunol 1995; 99:251.
  22. Forsblad-d'Elia H, Carlsten H, Labrie F, et al. Low serum levels of sex steroids are associated with disease characteristics in primary Sjogren's syndrome; supplementation with dehydroepiandrosterone restores the concentrations. J Clin Endocrinol Metab 2009; 94:2044.
  23. Barnhart KT, Freeman E, Grisso JA, et al. 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 1999; 84:3896.
  24. Morales AJ, Nolan JJ, Nelson JC, Yen SS. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J Clin Endocrinol Metab 1994; 78:1360.
  25. Labrie F, Diamond P, Cusan L, et al. Effect of 12-month dehydroepiandrosterone replacement therapy on bone, vagina, and endometrium in postmenopausal women. J Clin Endocrinol Metab 1997; 82:3498.
  26. Morales AJ, Haubrich RH, Hwang JY, et al. 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 (Oxf) 1998; 49:421.
  27. Flynn MA, Weaver-Osterholtz D, Sharpe-Timms KL, et al. Dehydroepiandrosterone replacement in aging humans. J Clin Endocrinol Metab 1999; 84:1527.
  28. Arlt W, Callies F, Koehler I, et al. Dehydroepiandrosterone supplementation in healthy men with an age-related decline of dehydroepiandrosterone secretion. J Clin Endocrinol Metab 2001; 86:4686.
  29. Nair KS, Rizza RA, O'Brien P, et al. DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med 2006; 355:1647.
  30. Baulieu EE, Thomas G, Legrain S, et al. Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue. Proc Natl Acad Sci U S A 2000; 97:4279.
  31. Percheron G, Hogrel JY, Denot-Ledunois S, et al. Effect of 1-year oral administration of dehydroepiandrosterone to 60- to 80-year-old individuals on muscle function and cross-sectional area: a double-blind placebo-controlled trial. Arch Intern Med 2003; 163:720.
  32. Apostolova G, Schweizer RA, Balazs Z, et al. Dehydroepiandrosterone inhibits the amplification of glucocorticoid action in adipose tissue. Am J Physiol Endocrinol Metab 2005; 288:E957.
  33. Villareal DT, Holloszy JO. Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial. JAMA 2004; 292:2243.
  34. Jankowski CM, Gozansky WS, Schwartz RS, et al. Effects of dehydroepiandrosterone replacement therapy on bone mineral density in older adults: a randomized, controlled trial. J Clin Endocrinol Metab 2006; 91:2986.
  35. Wolkowitz OM, Kramer JH, Reus VI, et al. DHEA treatment of Alzheimer's disease: a randomized, double-blind, placebo-controlled study. Neurology 2003; 60:1071.
  36. Huppert FA, Van Niekerk JK. Dehydroepiandrosterone (DHEA) supplementation for cognitive function . Cochrane Database Syst Rev 2001; :CD000304.
  37. Labrie F, Archer D, Bouchard C, et al. Serum steroid levels during 12-week intravaginal dehydroepiandrosterone administration. Menopause 2009; 16:897.
  38. Labrie F, Archer D, Bouchard C, et al. Intravaginal dehydroepiandrosterone (Prasterone), a physiological and highly efficient treatment of vaginal atrophy. Menopause 2009; 16:907.
  39. The Medical Letter May 9, 2005; 47:37.
  40. Sahelian R, Borken S. Dehydroepiandrosterone and cardiac arrhythmia. Ann Intern Med 1998; 129:588.