Drugs

, Volume 74, Issue 11, pp 1195–1207 | Cite as

Dehydroepiandrosterone (DHEA): Hypes and Hopes

  • Krzysztof Rutkowski
  • Paweł Sowa
  • Joanna Rutkowska-Talipska
  • Anna Kuryliszyn-Moskal
  • Ryszard Rutkowski
Review Article

Abstract

Dehydroepiandrosterone (DHEA) and its sulfated form dehydroepiandrosterone sulfate (DHEAS) are the most abundant circulating steroid hormones in humans. In animal studies, their low levels have been associated with age-related involuntary changes, including reduced lifespan. Extrapolation of animal data to humans turned DHEA into a ‘superhormone’ and an ‘anti-aging’ panacea. It has been aggressively marketed and sold in large quantities as a dietary supplement. Recent double-blind, placebo-controlled human studies provided evidence to support some of these claims. In the elderly, DHEA exerts an immunomodulatory action, increasing the number of monocytes, T cells expressing T-cell receptor gamma/delta (TCRγδ) and natural killer (NK) cells. It improves physical and psychological well-being, muscle strength and bone density, and reduces body fat and age-related skin atrophy stimulating procollagen/sebum production. In adrenal insufficiency, DHEA restores DHEA/DHEAS and androstenedione levels, reduces total cholesterol, improves well-being, sexual satisfaction and insulin sensitivity, and prevents loss of bone mineral density. Normal levels of CD4+CD25hi and FoxP3 (forkhead box P3) are restored. In systemic lupus erythematosus, DHEA is steroid-sparing. In an unblinded study, it induced remission in the majority of patients with inflammatory bowel disease. DHEA modulates cardiovascular signalling pathways and exerts an anti-inflammatory, vasorelaxant and anti-remodelling effect. Its low levels correlate with increased cardiovascular disease and all-cause mortality. DHEA/DHEAS appear protective in asthma and allergy. It attenuates T helper 2 allergic inflammation, and reduces eosinophilia and airway hyperreactivity. Low levels of DHEAS accompany adrenal suppression. It could be used to screen for the side effects of steroids. In women, DHEA improves sexual satisfaction, fertility and age-related vaginal atrophy. Many factors are responsible for the inconsistent/negative results of some studies. Overreliance on animal models (DHEA is essentially a human molecule), different dosing protocols with non-pharmacological doses often unachievable in humans, rapid metabolism of DHEA, co-morbidities and organ-specific differences render data interpretation difficult. Nevertheless, a growing body of evidence supports the notion that DHEA is not just an overrated dietary supplement but a useful drug for some, but not all, human diseases. Large-scale randomised controlled trials are needed to fine-tune the indications and optimal dosing protocols before DHEA enters routine clinical practice.

References

  1. 1.
    Lieberman S. An abbreviated account of some aspects of the biochemistry of DHEA, 1934–1995. Ann N Y Acad Sci. 1995;774:1–15.PubMedCrossRefGoogle Scholar
  2. 2.
    Leowattana W. DHEAS as a new diagnostic tool. Clin Chim Acta. 2004;341:1–15.PubMedCrossRefGoogle Scholar
  3. 3.
    Gaby AR. Dehydroepiandrosterone: biological effects and clinical significance. Altern Med Rev. 1996;1:60–9.Google Scholar
  4. 4.
    Nestler JE. DHEA: a coming age. Ann N Y Acad Sci. 1995;774:IX–XI.CrossRefGoogle Scholar
  5. 5.
    Maninger N, Wolkowitz OM, Reus VI, et al. Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). Front Neuroendocrinol. 2009;30:65–91.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Dumas de la Roque E, Quignard JF, Ducret T, et al. Beneficial effect of dehydroepiandrosterone on pulmonary hypertension in a rodent model of pulmonary hypertension in infants. Pediatr Res. 2013;74:163–99.PubMedCrossRefGoogle Scholar
  7. 7.
    Savineau JP, Marthan R, Dumas de la Roque E. Role of DHEA in cardiovascular diseases. Biochem Pharmacol. 2013;85:718–26.PubMedCrossRefGoogle Scholar
  8. 8.
    Webb SJ, Geoghegan TE, Prough RA, et al. The biological actions of dehydroepiandrosterone involves multiple receptors. Drug Metab Rev. 2006;38:89–116.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Traish AM, Kang HP, Saad F, et al. Dehydroepiandrosterone (DHEA): a precursor steroid or an active hormone in human physiology. J Sex Med. 2011;8:2960–82.PubMedCrossRefGoogle Scholar
  10. 10.
    Simoncini T, Mannella P, Fornari L, et al. Dehydroepiandrosterone modulates endothelial nitric oxide synthesis via direct genomic and non-genomic mechanisms. Endocrinology. 2003;144:3449–55.PubMedCrossRefGoogle Scholar
  11. 11.
    Espinoza J, Montaño LM, Perusquía M. Nongenomic bronchodilating action elicited by dehydroepiandrosterone (DHEA) in a guinea pig asthma model. J Steroid Biochem Mol Biol. 2013;138:174–82.PubMedCrossRefGoogle Scholar
  12. 12.
    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;277:21379–88.PubMedCrossRefGoogle Scholar
  13. 13.
    Liu D, Dillon JS. Dehydroepiandrosterone stimulates nitric oxide release in vascular endothelial cells: evidence for a cell surface receptor. Steroids. 2004;69:279–89.PubMedCrossRefGoogle Scholar
  14. 14.
    Simoncini T, Genazzani AR. Dehydroepiandrosterone, the endothelium, and cardio-vascular protection. Endocrinology. 2007;148:3065–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Olivo HF, Perez-Hernandez N, Liu D, et al. Synthesis and application of a photoaffinity analog of dehydroepiandrosterone (DHEA). Bioorg Med Chem Lett. 2010;20:1153–5.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Liu D, O’Leary B, Iruthayanathan M, et al. Evaluation of a novel photoactive and biotinylated dehydroepiandrosterone analog. Mol Cell Endocrinol. 2010;328:56–62.PubMedCrossRefGoogle Scholar
  17. 17.
    Waschatko G, Kojro E, Zahnow M, et al. Photo-DHEA—a functional photoreactive dehydroepiandrosterone (DHEA) analog. Steroids. 2011;76:502–27.PubMedCrossRefGoogle Scholar
  18. 18.
    Kroboth PD, Salek FS, Pittenger AL, et al. DHEA and DHEA-S: a review. J Clin Pharmacol. 1999;39:327–48.PubMedCrossRefGoogle Scholar
  19. 19.
    Olech E, Merrill JT. DHEA supplementation: the claims in perspective. Cleve Clin J Med. 2005;72:965–966, 968, 970–971.Google Scholar
  20. 20.
    Baulieu EE. Dehydroepiandrosterone (DHEA): a fountain of youth? J Clin Endocrinol Metab. 1996;81:3147–51.PubMedCrossRefGoogle Scholar
  21. 21.
    Binello E, Gordon CM. Clinical uses and misuses of dehydroepiandrosterone. Curr Opin Pharmacol. 2003;3:635–41.PubMedCrossRefGoogle Scholar
  22. 22.
    Burkhardt T, Schmidt NO, Vettorazzi E, et al. DHEA(S): a novel marker in Cushing’s disease. Acta Neurochir (Wien). 2013;155:479–84.PubMedCrossRefGoogle Scholar
  23. 23.
    Kasperska-Zając AE, Brzoza ZK, Koczy-Baron E, et al. Dehydroepiandrosterone in therapy of allergic diseases. Recent Pat Inflamm Allergy Drug Discov. 2009;3:211–3.PubMedCrossRefGoogle Scholar
  24. 24.
    Dhatariya KK, Nair KS. Dehydroepiandrosterone: is there a role for replacement? Mayo Clin Proc. 2003;78:1257–73.PubMedCrossRefGoogle Scholar
  25. 25.
    Valenti G, Denti L, Saccò M, et al. GISEG (Italian Study Group on Geriatric Endocrinology), consensus document on substitution therapy with DHEA in the elderly. Aging Clin Exp Res. 2006;18:277–300.PubMedCrossRefGoogle Scholar
  26. 26.
    Panjari M, Davis SR. DHEA therapy for women: effect on sexual function and wellbeing. Hum Reprod Update. 2007;13:239–48.PubMedCrossRefGoogle Scholar
  27. 27.
    Thompson RD, Carlson M, Thompson RD, et al. Liquid chromatographic determination of dehydroepiandrosterone (DHEA) in dietary supplement products. J AOAC Int. 2000;83:847–57.PubMedGoogle Scholar
  28. 28.
    Yakin K, Urman B. DHEA as a miracle drug in the treatment of poor responders; hype or hope? Hum Reprod. 2011;26:1941–4.PubMedCrossRefGoogle Scholar
  29. 29.
    Kushnir MM, Blamires T, Rockwood AL, et al. Liquid chromatography-tandem mass spectrometry assay for androstenedione, dehydroepiandrosterone, and testosterone with pediatric and adult reference intervals. Clin Chem. 2010;56:1138–47.PubMedCrossRefGoogle Scholar
  30. 30.
    Orentreich N, Brind JL, Rizer RL, et al. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab. 1984;59:551–5.PubMedCrossRefGoogle Scholar
  31. 31.
    Roth GS, Lane MA, Ingram DK, et al. Biomarkers of caloric restriction may predict longevity in humans. Science. 2002;297:811.PubMedCrossRefGoogle Scholar
  32. 32.
    Celec P, Stárka L. Dehydroepiandrosterone: is the fountain of youth drying out? Physiol Res. 2003;52:397–407.PubMedGoogle Scholar
  33. 33.
    Allolio B, Arlt W. DHEA treatment: myth or reality? Trends Endocrinol Metab. 2002;13:288–94.PubMedCrossRefGoogle Scholar
  34. 34.
    Dillon JS. Dehydroepiandrosterone, dehydroepiandrosterone sulfate and related steroids: their role in inflammatory, allergic and immunological disorders. Curr Drug Targets Inflamm Allergy. 2005;4:377–85.PubMedCrossRefGoogle Scholar
  35. 35.
    Saponaro S, Guarnieri V, Pescarmona GP, et al. Long-term exposure to dehydroepiandrosterone affects the transcriptional activity of the glucocorticoid receptor. J Steroid Biochem Mol Biol. 2007;103:129–36.PubMedCrossRefGoogle Scholar
  36. 36.
    Genazzani AD, Stomati M, Bernardi F, et al. Long-term low-dose dehydroepiandrosterone oral supplementation in early and late postmenopausal women modulates endocrine parameters and synthesis of neuroactive steroids. Fertil Steril. 2003;80:1495–501.PubMedGoogle Scholar
  37. 37.
    Alkatib AA, Cosma M, Elamin MB, et al. A systematic review and meta-analysis of randomized placebo-controlled trials of DHEA treatment effects on quality of life in women with adrenal insufficiency. J Clin Endocrinol Metab. 2009;94:3676–81.PubMedCrossRefGoogle Scholar
  38. 38.
    Basu R, Dalla Man C, et al. Two years of treatment with dehydroepiandrosterone does not improve insulin secretion, insulin action, or postprandial glucose turnover in elderly men or women. Diabetes. 2007;56:753–66.PubMedCrossRefGoogle Scholar
  39. 39.
    Christiansen JJ, Bruun JM, Christiansen JS, et al. Long-term DHEA substitution in female adrenocortical failure, body composition, muscle function, and bone metabolism: a randomized trial. Eur J Endocrinol. 2011;165:293–300.PubMedCrossRefGoogle Scholar
  40. 40.
    Hartkamp A, Geenen R, Godaert GL, et al. Effects of dehydroepiandrosterone on fatigue and well-being in women with quiescent systemic lupus erythematosus: a randomised controlled trial. Ann Rheum Dis. 2010;69:1144–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Morales AJ, Nolan JJ, Nelson JC, et al. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J Clin Endocrinol Metab. 1994;78:1360–7.PubMedGoogle Scholar
  42. 42.
    Yen SS, Morales AJ, Khorram O. Replacement of DHEA in aging men and women: potential remedial effects. Ann N Y Acad Sci. 1995;774:128–42.PubMedCrossRefGoogle Scholar
  43. 43.
    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;49:421–32.PubMedCrossRefGoogle Scholar
  44. 44.
    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. 2000;97:4279–84.PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Weiss EP, Shah K, Fontana L, et al. Dehydroepiandrosterone replacement therapy in older adults: 1- and 2-y effects on bone. Am J Clin Nutr. 2009;89:1459–67.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Weiss EP, Villareal DT, Fontana L, et al. Dehydroepiandrosterone (DHEA) replacement decreases insulin resistance and lowers inflammatory cytokines in aging humans. Aging (Albany NY). 2011;3:533–42.PubMedCentralPubMedGoogle Scholar
  47. 47.
    Nouveau S, Bastien P, Baldo F, et al. Effects of topical DHEA on aging skin: a pilot study. Maturitas. 2008;59:174–81.PubMedCrossRefGoogle Scholar
  48. 48.
    El-Alfy M, Deloche C, Azzi L, et al. Skin responses to topical dehydroepiandrosterone: implications in antiageing treatment? Br J Dermatol. 2010;163:968–76.PubMedCrossRefGoogle Scholar
  49. 49.
    Shin MH, Rhie GE, Park CH, et al. Modulation of collagen metabolism by the topical application of dehydroepiandrosterone to human skin. J Invest Dermatol. 2005;124:315–23.PubMedCrossRefGoogle Scholar
  50. 50.
    Arlt W, Callies F, van Vlijmen JC, et al. Dehydroepiandrosterone replacement in women with adrenal insufficiency. N Engl J Med. 1999;341:1013–20.PubMedCrossRefGoogle Scholar
  51. 51.
    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;93:400–9.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Dhatariya K, Bigelow ML, Nair KS. Effect of dehydroepiandrosterone replacement on insulin sensitivity and lipids in hypoadrenal women. Diabetes. 2005;54:765–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Coles AJ, Thompson S, Cox AL, et al. Dehydroepiandrosterone replacement in patients with Addison’s disease has a bimodal effect on regulatory (CD4+CD25hi and CD4+FoxP3+) T cells. Eur J Immunol. 2005;35:3694–703.PubMedCrossRefGoogle Scholar
  54. 54.
    Chang DM, Lan JL, Lin HY, et al. Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002;46:2924–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Petri MA, Lahita RG, Van Vollenhoven RF, et al. GL601 Study Group. Effects of prasterone on corticosteroid requirements of women with systemic lupus erythematosus: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 2002;46:1820–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Andus T, Klebl F, Rogler G, et al. Patients with refractory Crohn’s disease or ulcerative colitis respond to dehydroepiandrosterone: a pilot study. Aliment Pharmacol Ther. 2003;17:409–14.PubMedCrossRefGoogle Scholar
  57. 57.
    Altman R, Motton DD, Kota RS, et al. Inhibition of vascular inflammation by dehydroepiandrosterone sulfate in human aortic endothelial cells: roles of PPARalpha and NF-kappaB. Vascul Pharmacol. 2008;48:76–84.PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Bonnet S, Paulin R, Sutendra G, et al. Dehydroepiandrosterone reverses systemic vascular remodelling through the inhibition of the Akt/GSK3-{beta}/NFAT axis. Circulation. 2009;120:1231–40.PubMedCrossRefGoogle Scholar
  59. 59.
    Shufelt C, Bretsky P, Almeida CM, et al. DHEA-S levels and cardiovascular disease mortality in postmenopausal women: results from the National Institutes of Health: National Heart, Lung, and Blood Institute (NHLBI)-sponsored Women’s Ischemia Syndrome Evaluation (WISE). J Clin Endocrinol Metab. 2010;95:4985–92.PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Yu CK, Yang BC, Lei HY, et al. Attenuation of house dust mite Dermatophagoides farinae-induced airway allergic responses in mice by dehydroepiandrosterone is correlated with down-regulation of TH2 response. Clin Exp Allergy. 1999;29:414–22.PubMedCrossRefGoogle Scholar
  61. 61.
    Lin XH, Choi IS, Koh YA, et al. Effects of combined bacille Calmette-Guérin and dehydroepiandrosterone treatment on established asthma in mice. Exp Lung Res. 2009;35:250–61.PubMedCrossRefGoogle Scholar
  62. 62.
    Liou CJ, Huang WC. Dehydroepiandrosterone suppresses eosinophil infiltration and airway hyperresponsiveness via modulation of chemokines and Th2 cytokines in ovalbumin-sensitized mice. J Clin Immunol. 2011;31:656–65.PubMedCrossRefGoogle Scholar
  63. 63.
    Choi IS, Cui Y, Koh YA, et al. Effects of dehydroepiandrosterone on Th2 cytokine production in peripheral blood mononuclear cells from asthmatics. Korean J Intern Med. 2008;23:176–81.PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Shin YS, Takeda K, Gelfand EW. Understanding asthma using animal models. Allergy Asthma Immunol Res. 2009;191:10–8.CrossRefGoogle Scholar
  65. 65.
    Tabata N, Tagami H, Terui T. Dehydroepiandrosterone may be one of the regulators of cytokine production in atopic dermatitis. Arch Dermatol Res. 1997;289:410–4.PubMedCrossRefGoogle Scholar
  66. 66.
    Koziol-White CJ, Goncharova EA, Cao G, et al. DHEA-S inhibits human neutrophil and human airway smooth muscle migration. Biochim Biophys Acta. 2012;1822:1638–42.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Wenzel SE, Robinson CB, Leonard JM, et al. Nebulized dehydroepiandrosterone-3-sulfate improves asthma control in the moderate-to-severe asthma results of a 6-week, randomized, double-blind, placebo-controlled study. Allergy Asthma Proc. 2010;31:461–71.PubMedCrossRefGoogle Scholar
  68. 68.
    Chan CC, Liou CJ, Xu PY, et al. Effect of dehydroepiandrosterone on atopic dermatitis-like skin lesions induced by 1-chloro-2,4-dinitrobenzene in mouse. J Dermatol Sci. 2013;72:149–57.PubMedCrossRefGoogle Scholar
  69. 69.
    Kasperska-Zajac A, Brzoza Z, Rogala B. Lower serum concentration of dehydroepiandrosterone sulphate in patients suffering from chronic idiopathic urticaria. Allergy. 2006;61:1489–90.PubMedCrossRefGoogle Scholar
  70. 70.
    Kasperska-Zajac A, Brzoza Z, Rogala B. Serum concentration of dehydroepiandrosterone sulphate in female patients with chronic idiopathic urticaria. J Dermatol Sci. 2006;41:80–1.PubMedCrossRefGoogle Scholar
  71. 71.
    Brzoza Z, Kasperska-Zajac A, Badura-Brzoza K, et al. Decline in dehydroepiandrosterone sulfate observed in chronic urticaria is associated with psychological distress. Psychosom Med. 2008;70:723–8.PubMedCrossRefGoogle Scholar
  72. 72.
    Kasperska-Zajac A, Brzoza Z, Rogala B. Plasma concentration of interleukin 6 (IL-6), and its relationship with circulating concentration of dehydroepiandrosterone sulfate (DHEA-S) in patients with chronic idiopathic urticaria. Cytokine. 2007;39:142–6.PubMedCrossRefGoogle Scholar
  73. 73.
    Kamel-Sabry MK, Farres MN, Melek NA, et al. Prolactin and dehydroepiandrosterone sulfate: are they related to the severity of chronic urticaria? Arch Med Res. 2013;44:21–6.PubMedCrossRefGoogle Scholar
  74. 74.
    Blauer KL, Poth M, Rogers WM, et al. Dehydroepiandrosterone antagonizes the suppressive effects of dexamethasone on lymphocyte proliferation. Endocrinology. 1991;129:3174–9.PubMedCrossRefGoogle Scholar
  75. 75.
    Daynes RA, Dudley DJ, Araneo BA. Regulation of murine lymphokine production in vivo: II. Dehydroepiandrosterone is a natural enhancer of interleukin 2 synthesis by helper T cells. Eur J Immunol. 1990;20:793–802.PubMedCrossRefGoogle Scholar
  76. 76.
    Harding G, Mak YT, Evans B, et al. The effects of dexamethasone and dehydroepiandrosterone (DHEA) on cytokines and receptor expression in a human osteoblastic cell line: potential steroid-sparing role for DHEA. Cytokine. 2006;36:57–68.PubMedCrossRefGoogle Scholar
  77. 77.
    Buoso E, Lanni C, Molteni E, et al. Opposing effects of cortisol and dehydroepiandrosterone on the expression of the receptor for Activated C Kinase 1: implications in immunosenescence. Exp Gerontol. 2011;46:877–83.PubMedCrossRefGoogle Scholar
  78. 78.
    Kasperska-Zajac A. Asthma and dehydroepiandrosterone (DHEA): facts and hypotheses. Inflammation. 2010;33:320–4.PubMedCrossRefGoogle Scholar
  79. 79.
    Martinez FJ, Donohue JF, Rennard SI. The future of chronic obstructive pulmonary disease treatment: difficulties of and barriers to drug development. Lancet. 2011;378:1027–37.PubMedCrossRefGoogle Scholar
  80. 80.
    Eusebio MO, Grzelewski T, Pietruczuk M, et al. The patents on glucocorticosteroids and selected new therapies for the management of asthma in children. Recent Pat Inflamm Allergy Drug Discov. 2011;5:57–65.PubMedCrossRefGoogle Scholar
  81. 81.
    Kannisto S, Laatikainen A, Taivainen A, et al. Serum dehydroepiandrosterone sulfate concentration as an indicator of adrenocortical suppression during inhaled steroid therapy in adult asthmatic patients. Eur J Endocrinol. 2004;150:687–90.PubMedCrossRefGoogle Scholar
  82. 82.
    Fusi FM, Ferrario M, Bosisio C, et al. DHEA supplementation positively affects spontaneous pregnancies in women with diminished ovarian function. Gynecol Endocrinol. 2013;29:940–3.PubMedCrossRefGoogle Scholar
  83. 83.
    Labrie F, Archer D, Bouchard C, et al. Intravaginal dehydroepiandrosterone (Prasterone), a physiological and highly efficient treatment of vaginal atrophy. Menopause. 2009;16:907–22.PubMedCrossRefGoogle Scholar
  84. 84.
    Labrie F, Archer D, Bouchard C, et al. Effect of intravaginal dehydroepiandrosterone (Prasterone) on libido and sexual dysfunction in postmenopausal women. Menopause. 2009;16:923–31.PubMedCrossRefGoogle Scholar
  85. 85.
    Davis SR, Panjari M, Stanczyk FZ. Clinical review: DHEA replacement for post-menopausal women. J Clin Endocrinol Metab. 2011;96:1642–53.PubMedCrossRefGoogle Scholar
  86. 86.
    Corona G, Rastrelli G, Giagulli VA, et al. Dehydroepiandrosterone supplementation in elderly men: a meta-analysis study of placebo-controlled trials. J Clin Endocrinol Metab. 2013;98:3615–26.PubMedCrossRefGoogle Scholar
  87. 87.
    Grossman A, Johannsson G, Quinkler M, et al. Therapy of endocrine disease: perspectives on the management of adrenal insufficiency: clinical insights from across Europe. Eur J Endocrinol. 2013;169:165–75.CrossRefGoogle Scholar
  88. 88.
    Hyman JH, Margalioth EJ, Rabinowitz R, Tsafrir A, et al. DHEA supplementation may improve IVF outcome in poor responders: a proposed mechanism. Eur J Obstet Gynecol Reprod Biol. 2013;168:49–53.PubMedCrossRefGoogle Scholar
  89. 89.
    Yilmaz N, Uygur D, Inal H, et al. Dehydroepiandrosterone supplementation improves predictive markers for diminished ovarian reserve: serum AMH, inhibin B and antral follicle count. Eur J Obstet Gynecol Reprod Biol. 2013;169:257–60.PubMedCrossRefGoogle Scholar
  90. 90.
    Kara M, Aydin T, Aran T, et al. Does dehydroepiandrosterone supplementation really affect IVF-ICSI outcome in women with poor ovarian reserve? Eur J Obstet Gynecol Reprod Biol. 2014;173:63–5.PubMedCrossRefGoogle Scholar
  91. 91.
    Strauss S, Greve T, Ernst E, et al. Administration of DHEA augments progesterone production in a woman with low ovarian reserve being transplanted with cryopreserved ovarian tissue. J Assist Reprod Genet. 2014;31:645–9.PubMedCrossRefGoogle Scholar
  92. 92.
    Sunkara SK, Pundir J, Khalaf Y. Effect of androgen supplementation or modulation on ovarian stimulation outcome in poor responders: a meta-analysis. Reprod Biomed Online. 2011;22:545–55.PubMedCrossRefGoogle Scholar
  93. 93.
    Narkwichean A, Maalouf W, Campbell BK, et al. Efficacy of dehydroepiandrosterone to improve ovarian response in women with diminished ovarian reserve: a meta-analysis. Reprod Biol Endocrinol. 2013;11:44.PubMedCentralPubMedCrossRefGoogle Scholar
  94. 94.
    ChEBI: the database and ontology of Chemical Entities of Biological Interest. Dehydroepiandrosterone (CHEBI 28689). Available from http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5881. Accessed 5 July 2014.
  95. 95.
    ChEBI: the database and ontology of Chemical Entities of Biological Interest. Dehydroepiandrosterone sulfate (CHEBI 16814). Available from http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=12594&loc=ec_rcs. Accessed 5 July 2014.

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Krzysztof Rutkowski
    • 1
  • Paweł Sowa
    • 2
  • Joanna Rutkowska-Talipska
    • 3
  • Anna Kuryliszyn-Moskal
    • 3
  • Ryszard Rutkowski
    • 4
  1. 1.Department of Allergy, Box 40, Clinic 2aCambridge University Hospitals NHS Foundation TrustCambridgeUK
  2. 2.Department of Public HealthMedical UniversityBialystokPoland
  3. 3.Department of RehabilitationMedical UniversityBialystokPoland
  4. 4.Department of Respiratory Diagnostic and BronchoscopyMedical UniversityBialystokPoland

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