Effects of dehydroepiandrosterone (DHEA) supplementation on hormonal, metabolic and behavioral status in patients with hypoadrenalism

Abstract

Oral DHEA administration to patients with hypoadrenalism, in addition to glucocorticoid and mineralcorticoid replacement, may improve both well-being and hormonal/metabolic parameters. Twenty patients (13 men, 7 women, 26276 yr, 11 with Addison’s disease, 9 with central hypoadrenalism) were recruited in a placebocontrolled, randomized study. Hormone levels, carbohydrate and lipid parameters, bone metabolism, body composition and psychological parameters were evaluated at baseline and after treatment with DHEA 50 mg/day or placebo for 4 months. After 4 months of DHEA administration, serum DHEAS levels raised both in men (from 0.71±0.18 to 8.28±1.66 μmol/l, p<0.005) and in women (from 0.25±0.07 to 5.65±1.93 μmol/l, p<0.05). Only in hypoadrenal women an increase in testosterone (T; from 0.4±0.1 to 1.45±0.26 nmol/l, p<0.05) and androstenedione (A; from 0.86±0.34 to 2.05±0.29 nmol/l, p<0.05) levels was observed. In men no significant modifications in T and 17-hydroxyprogesterone (17-OHP) levels were found, whereas serum SHBG significantly decreased. As far as the metabolic parameters are concerned, only in patients with Addison’s disease a significant decrease in total cholesterol and in low-density lipoproteins after 4 months of DHEA administration was found. No changes in glucose metabolism and insulin sensitivity were observed. In basal conditions, mean serum osteocalcin (OC) was normal and significantly decreased after DHEA treatment. A significant reduction in body fat mass percentage (BF%) after DHEA administration was observed. As far as well-being is concerned, DHEA replacement did not cause any relevant variation of subjective health scales and sexuality in both sexes. Our study confirms that DHEA may be beneficial for female patients with hypoadrenalism, mainly in restoring androgen levels. Concerning the health status, more sensitive and specific instruments to measure the effects of DHEA treatment could be necessary.

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References

  1. 1.

    Morales AJ, Nolan JJ, Nelson JC, Yen SSC. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J Clin Endocrinol Metab 1994, 78: 1360–7.

    CAS  PubMed  Google Scholar 

  2. 2.

    Labrie F, Belanger A, Cusan L, Candas B. Physiological changes in dehydroepiandrosterone are not reflected by serum levels of active androgens and estrogens but their metabolites: intracrinology. J Clin Endocrinol Metab 1997, 82: 2403–9.

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Morales AJ, Haubrich RH, Hwang JY, Asakura H, Yen SSC. The effects of six months treatment with 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.

    CAS  Article  Google Scholar 

  4. 4.

    Arlt W, Callies F, van Vlijmen JC, et al. Dehydroepiandros-terone replacement in women with adrenal insufficiency. N Engl J Med 1999, 341: 1013–20.

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Yen SS, Morales AJ, Khorram O. Replacement of DHEA in ageing men and women. Potential remedial effects. Ann NY Acad Sci 1995, 774: 128–42.

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Mortola JF, Yen SS. The effects of oral dehydroepiandroster-one on endocrine-metabolic parameters in post-menopau-sal women. J Clin Endocrinol Metab 1990, 71: 696–04.

    CAS  PubMed  Article  Google Scholar 

  7. 7.

    van Vollenhoven RF, Morabito LM, Engleman EG, McGuire JL. Treatment of systemic lupus erythematosus with dehy-droepiandrosterone: 50 patients treated up to 12 months. J Rheumatol 1998, 25: 285–9.

    PubMed  Google Scholar 

  8. 8.

    Piketty C, Jayle A, Leplege A, et al. Double-blind placebo-controlled trial of oral dehydroepiandrosterone in patients with advanced HIV disease. Clin Endocrinol (Oxf) 2001, 55: 325–30.

    CAS  Article  Google Scholar 

  9. 9.

    Simoncini T, Mannella P, Fornari L, Varone G, Caruso A, Gennazzani AR Dehydroepiandrosterone modulates endothelial nitric oxide synthesis via direct genomic and nongenomic mechanisms. Endocrinology 2003, 144: 3449–55.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Arlt W, Allolio B. Dehydroepiandrosterone replacement therapy. Curr Opin Endocrinol Diabetes 2001, 8: 130–9.

    CAS  Article  Google Scholar 

  11. 11.

    Young J, Couzinet B, Khalil N, et al. Panhypopituitarism as a model to study the metabolism of dehydroepiandrosterone (DHEA) in humans. J Clin Endocrinol Metab 1997, 82: 2578–85.

    CAS  PubMed  Google Scholar 

  12. 12.

    Gebre-Medhin G, Husebye ES, Mallmin H. Oral dehydroe-piandrosterone (DHEA) replacement therapy in women with Addison’s disease. Clin Endocrinol (Oxf) 2000, 52: 775–80.

    CAS  Article  Google Scholar 

  13. 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: 4650–6.

    CAS  PubMed  Google Scholar 

  14. 14.

    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin re-sistence and β-cell function from fasting plasma and insulin concentration in man. Diabetologia 1985, 28: 412–9.

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Katz A, Nambi SS, Mather K, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000, 85: 2402–10.

    CAS  PubMed  Article  Google Scholar 

  16. 16.

    Derogatis LR, Lipman RS, Covi L. SCL-90: an outpatient psychiatric rating scale: preliminary report. Psychopharmacol Bull 1973, 9: 13–28.

    CAS  PubMed  Google Scholar 

  17. 17.

    Folstein MF, Robins LN, Helzer J.E. The Mini Mental State Examination. Arch Gen Psychiatry 1983, 40: 812–20.

    CAS  PubMed  Article  Google Scholar 

  18. 18.

    Derogatis LR The Psychosocial Adjustment to Illness Scale (PAIS). J Psychosom Res 1986, 30: 77–91.

    CAS  PubMed  Article  Google Scholar 

  19. 19.

    Johannsson G, Burman P, Wiren L, et al. Low dose dehy-droepiandrosterone affects behavior in hypopituitary an-drogen-deficient women: a placebo-controlled trial. J Clin Endocrinol Metab 2002, 87: 2046–52.

    CAS  PubMed  Article  Google Scholar 

  20. 20.

    Lovas 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: 1112–8.

    CAS  PubMed  Article  Google Scholar 

  21. 21.

    Christiansen JJ, Gravholt CH, Fisker S, et al. Dehydroepian-drosterone supplementation in women with adrenal failure: impact on twenty-four hour GH secretion and IGF-related parameters. Clin Endocrinol (Oxf) 2004, 60: 461–9.

    CAS  Article  Google Scholar 

  22. 22.

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

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Callies F, Fassnacht M, van Vlijmen JC, et al. Dehydroepi-androsterone replacement in women with adrenal insufficiency: effect on body composition, serum leptin, bone turnover, and exercise capacity. J Clin Endocrinol Metab 2001, 86: 1968–72.

    CAS  PubMed  Article  Google Scholar 

  24. 24.

    Kahn AJ, Halloran B. Dehydroepiandrosterone supplementation and bone turnover in middle-age to elderly men. J Clin Endocrinol Metab 2002, 87: 1544–9.

    CAS  PubMed  Article  Google Scholar 

  25. 25.

    Gurnell EM, Chatterjee VK. Dehydroepiandrosterone replacement therapy. Eur J Endocrinol 2001, 145: 103–6.

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Kasperk CH, Wakley GK, Hierl T, Ziegler R. Gonadal and adrenal androgens are potent regulator of human bone cell metabolism in vitro. J Bone Miner Res 1997, 12: 464–71.

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Scheven BA, Milne JS. Dehydroepiandrosterone (DHEA) and DHEA-S interact with 1,25-dihydoxyvitamin D3 (1,25(OH)2D3) to stimulate human osteoblastic cell differentiation. Life Sci 1998, 62: 59–68.

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Nestler JE, Barlascini Co, Clore JN, Blackard WG. Dehy-droepiandrosterone reduces serum low density lipoprotein levels and body fat but does not later insulin sensitivity in normal men. J Clin Endocrinol Metab 1988 66: 57–61.

    CAS  PubMed  Article  Google Scholar 

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Correspondence to B. Ambrosi MD.

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Libè, R., Barbetta, L., Dall’Asta, C. et al. Effects of dehydroepiandrosterone (DHEA) supplementation on hormonal, metabolic and behavioral status in patients with hypoadrenalism. J Endocrinol Invest 27, 736–741 (2004). https://doi.org/10.1007/BF03347515

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Key-words

  • Hypoadrenalism
  • DHEA
  • androgens
  • Addison’s disease