Dehydroepiandrosterone

• How It Works

  Dehydroepiandrosterone (DHEA) has not been shown effective in treating cancer.

  DHEA is the most abundant hormone secreted by the adrenal glands. Clinical trials have shown that DHEA is effective in treating certain forms of depression and anxiety, lupus, sexual dysfunction, and Addison’s disease. High blood levels of DHEA have been associated with increased risk of breast, ovarian cancers; DHEA supplementation resulted in flare-up of prostate cancer.

• Purported Uses
  • Addison’s disease
    Studies have shown that DHEA is effective in treating Addison’s disease.
  • Alzheimer’s disease
    DHEA was not found to be beneficial for patients with Alzheimer’s disease.
  • Cancer treatment
    Although studies have been done to determine DHEA’s benefits for cancer patients, results are not conclusive.
  • Depression
    DHEA has been shown to reduce symptoms of manic depression.
  • Memory loss
    DHEA is not effective in treating memory loss.
  • Schizophrenia
    Studies have shown that DHEA benefits patients with schizophrenia.
  • Sexual performance
    DHEA has been shown to be effective for erectile dysfunction.
  • Systemic lupus erythematosus
    A few studies have shown that DHEA reduces the number of flare-ups but there was no reduction in overall disease activity.
• Do Not Take If
  • You are taking tamoxifen, as the combination of the two can lead to tamoxifen resistance.
  • You are on hormone replacement therapy, as DHEA has been shown to affect estrogen levels.
• Side Effects
  • Women taking DHEA orally may experience increased facial hair or hair loss, menstrual irregularities and deepening of the voice.
  • Medical literature has documented reports of mania in some patients taking high doses of DHEA orally.
  • DHEA may increase acne.
• Special Point
  • In premenopausal women, high levels of DHEA have been associated with increased risk of ovarian and breast cancers.
  • When taken for an extended period by postmenopausal women, DHEA may increase the risk of breast cancer, especially in obese subjects.
  • Patients with hormone-sensitive cancer should avoid DHEA because the hormone is converted to sex steroids.
  • Patients who are pregnant or breast-feeding should avoid DHEA because of its effect on estrogen levels.
• Brand Name

  Fluasterone

• Scientific Name

  5-androsten-3 beta-ol-17-one, 3 beta-hydroxy-5-androsten-17-one

• Clinical Summary

  The most abundant hormone secreted by the adrenal glands, DHEA circulates in the blood as the sulfate ester, dehydroepiandrosterone-3-sulfate (DHEA-S). Both are precursors for other hormones, including estrogen and androgens ⁽¹⁾. Animal studies indicate that DHEA may have chemopreventive effects ^(2) (3), blocks the development of tumors ⁽⁴⁾, and enhances immune response following hepatitis ⁽⁵⁾ and influenza ⁽⁶⁾ vaccinations. Although it has been postulated that DHEA may play a role in increasing immune response in acquired immune deficiency syndrome (AIDS) ⁽⁷⁾, no antiviral or immunostimulatory effects were observed in HIV-positive participants receiving DHEA ⁽⁸⁾.

  In clinical trials, DHEA was shown effective in treating Addison’s disease ^{(13) (14) (15) (16) (17)}, major depression ⁽⁹⁾, schizophrenia-induced anxiety ⁽¹⁰⁾, systematic lupus erythematosus ⁽¹¹⁾, osteoporosis ⁽¹²⁾, and erectile dysfunction ⁽¹³⁾. Topical application of DHEA in postmenopausal women resulted in increased sebum production and epidermal thickening in the hands and face ⁽¹⁸⁾. However, other studies did not find effectivess of DHEA in treating Alzheimer’s disease ⁽¹⁹⁾, obesity in adolescents ⁽²⁰⁾, or perimenopausal symptoms ⁽²¹⁾. Furthermore, DHEA does not increase muscle mass ⁽²²⁾ or physical performance ⁽²³⁾, enhance insulin secretion or action ⁽²⁴⁾, or improve cognitive performance ⁽²⁵⁾ in elderly individuals.  DHEA supplementation, believed to enhance physical strength, did not improve physical performance or quality of life in a study done in older men and women ⁽²⁶⁾. However conflicting data suggest improvements in cognitive ⁽⁴³⁾ and physical function ⁽⁴⁴⁾ in older women. DHEA has been used to treat sexual dysfunction in postmenopausal women. But results from clinical studies are mixed ^(28) (29). Whether DHEA is effective for treating adrenal insufficiency is not clear ^(41) (42).

  DHEA alters some of the activities of the cytochrome P-450 enzyme that metabolizes several drugs ⁽³⁾. In premenopausal women, high levels of DHEA have been associated with increased risk of ovarian ⁽⁷⁾ and breast ⁽²⁷⁾ cancers. High DHEA-S levels have also been shown to contribute to tamoxifen resistance and disease progression in breast cancer ⁽²⁸⁾. A case of cancer flare-up was reported in a patient with advanced prostate cancer undergoing DHEA treatment ⁽²⁹⁾.

• Purported Uses
  • Addison’s disease
  • Alzheimer’s disease
  • Atherosclerosis
  • Cancer treatment
  • Depression
  • Immunostimulation
  • Memory loss
  • Rheumatoid arthritis
  • Schizophrenia
  • Sexual performance
  • Systemic lupus erythematosus (SLE)
  • Weight gain
  • Weight loss
• Mechanism of Action

  DHEA is an endogenous hormone secreted by the adrenal cortex in response to adrenocorticotropin. DHEA is metabolized into androstenedione in the body and may be further converted into either testosterone or estrogen. Low levels of endogenous DHEA have been associated with the following disease states: burn trauma, coronary artery disease, non-insulin-dependent diabetes mellitus, obsessive-compulsive disorder, rheumatoid arthritis, and systemic lupus erythematosus ⁽⁵⁾. Endogenous DHEA concentration peaks around 20 years of age and declines with age.

  DHEA has been shown to stimulate insulin growth factor-1 ⁽¹⁾. G6PD is necessary for nicotinamide adenine dinucleotide phosphate (NADPH) production. DHEA has also been shown to increase levels of interleukin-2 in animal models ⁽⁷⁾. DHEA reduces the effects of inflammatory cytokines such as interleukin-6, which are thought to reduce flares in systemic lupus erythematosus ⁽¹¹⁾. Numerous studies have reported an inverse relationship between DHEA concentration and cardiovascular disease ⁽⁵⁾. DHEA administration improved mental function scores in patients with advanced HIV infection ⁽³²⁾, enhanced influenza vaccination in elderly patients ⁽⁶⁾, and decreased oxidative stress markers in patients with type II diabetes in part by negatively influencing TNF-alpha signaling ⁽³³⁾. Although DHEA-S concentration does not appear to be correlated with cognitive decline in aging men ⁽³⁴⁾, the anti-depressive effects of DHEA may be mediated by GABAA receptor modulation ⁽³⁵⁾. DHEA has also been shown to affect cytochrome P-450 enzymes in the liver ⁽³⁾. The exact effect that this will have on other drugs remains unclear.

  Analogs of DHEA that cannot be converted to androgens and estrogens have been developed and have demonstrated anti-proliferative effects ^(7) (31). DHEA inhibits glucose-6-phosphate dehydrogenase (G6PD) in vitro and blocks the development of tumors in mice ⁽⁴⁾. It was also shown to induce authophagic cell death in human hepatoma cells via a mitogen activated protein kinase (JNK)-transciption factor (Nrf2)-protein complex p62 axis ⁽⁴⁶⁾.But an increase in concentration of sex hormones including DHEA has been shown to increase the risk of breast cancer ⁽³⁰⁾. And prolonged intake of DHEA in postmenopausal women may increase the risk of breast cancer particularly in obese subjects ⁽³⁶⁾. The sulfate ester DHEA-S also stimulates estrogen receptor-positive cell growth ⁽²⁸⁾.

• Contraindications
  • DHEA should not be used with tamoxifen as it can lead to tamoxifen resistance ⁽²⁸⁾.
  • DHEA should not be used by patients on hormone replacement therapy due to estrogenic effects ⁽¹⁾.
• Adverse Reactions

  Case Report (Oral): Reports of mania secondary to supplementation with high doses of DHEA have been reported in the literature ^(39) (40).
  Reported (Oral): Increased acne ⁽¹¹⁾.

• Herb-Drug Interactions
  • Serum concentrations of DHEA and DHEA-S can be increased by alprazolam, amlodipine, diltiazem, and metformin
  • Serum concentrations of DHEA and DHEA-S can be decreased by dexamethasone, insulin, and morphine ⁽⁵⁾
• Herb Lab Interactions
  • Blood glucose
  • Insulin
  • Testosterone
  • DHEA-S
• References

  1. Mason P. Dietary Supplements. London: Pharmaceutical Press; 2001.

  2. Aoki K, Nakajima A, Mukasa K, et al. Prevention of diabetes, hepatic injury, and colon cancer with dehydroepiandrosterone. J Steroid Biochem Mol Biol. Jun 2003;85(2-5):469-472.

  3. Estabrook RW, Milewich L, Prough RA. Cytochrome P-450s as toxicogenic catalysts: the influence of dehydroepiandrosterone. Princess Takamatsu Symp. 1990;21:33-44.

  4. Gordon GB, Shantz LM, Talalay P. Modulation of growth, differentiation and carcinogenesis by dehydroepiandrosterone. Adv Enzyme Regul. 1987;26:355-382.

  5. Kroboth PD, Salek FS, Pittenger AL, et al. DHEA and DHEA-S: a review. J Clin Pharmacol. Apr 1999;39(4):327-348.

  6. Degelau J, Guay D, Hallgren H. The effect of DHEAS on influenza vaccination in aging adults. J Am Geriatr Soc. Jun 1997;45(6):747-751.

  7. Johnson MD, Bebb RA, Sirrs SM. Uses of DHEA in aging and other disease states. Ageing Res Rev. Feb 2002;1(1):29-41.

  8. Abrams DI, Shade SB, Couey P, et al. Dehydroepiandrosterone (DHEA) effects on HIV replication and host immunity: a randomized placebo-controlled study. AIDS Res Hum Retroviruses. Jan 2007;23(1):77-85.

  9. Wolkowitz OM, Reus VI, Keebler A, et al. Double-blind treatment of major depression with dehydroepiandrosterone. A J Psychiatry. Apr 1999;156(4):646-649.

  10. Strous RD, Maayan R, Lapidus R, et al. Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia. Arch Gen Psychiatry. Feb 2003;60(2):133-141.

  11. 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. Nov 2002;46(11):2924-2927.

  12. Sun Y, Mao M, Sun L, et al. Treatment of osteoporosis in men using dehydroepiandrosterone sulfate. Chin Med J (Engl). Mar 2002;115(3):402-404.

  13. Reiter WJ, Pycha A, Schatzl G, et al. Dehydroepiandrosterone in the treatment of erectile dysfunction: a prospective, double-blind, randomized, placebo-controlled study. Urology. Mar 1999;53(3):590-594; discussion 594-595.

  14. Arlt W, Callies F, van Vlijmen JC, et al. Dehydroepiandrosterone replacement in women with adrenal insufficiency. N Engl J Med. Sep 30 1999;341(14):1013-1020.

  15. 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. May 2001;86(5):1968-1972.

  16. 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. Dec 2000;85(12):4650-4656.

  17. Kim SS, Brody KH. Dehydroepiandrosterone replacement in addison’s disease. Eur J Obstet Gynecol Reprod Biol. Jul 2001;97(1):96-97.

  18. Nouveau S, Bastien P, Baldo F, et al. Effects of topical DHEA on aging skin: a pilot study. Maturitas. Feb 20 2008;59(2):174-181.

  19. Wolkowitz OM, Kramer JH, Reus VI, et al. DHEA treatment of Alzheimer’s disease: a randomized, double-blind, placebo-controlled study. Neurology. Apr 8 2003;60(7):1071-1076.

  20. Vogiatzi MG, Boeck MA, Vlachopapadopoulou E, et al. Dehydroepiandrosterone in morbidly obese adolescents: effects on weight, body composition, lipids, and insulin resistance. Metabolism. Aug 1996;45(8):1011-1015.

  21. 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. Nov 1999;84(11):3896-3902.

  22. 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. Mar 24 2003;163(6):720-727.

  23. Igwebuike A, Irving BA, Bigelow ML, et al. Lack of dehydroepiandrosterone effect on a combined endurance and resistance exercise program in postmenopausal women. J Clin Endocrinol Metab. Feb 2008;93(2):534-538.

  24. Basu R, Dalla Man C, Campioni M, 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. Mar 2007;56(3):753-766.

  25. Wolf OT, Neumann O, Hellhammer DH, et al. Effects of a two-week physiological dehydroepiandrosterone substitution on cognitive performance and well-being in healthy elderly women and men. J Clin Endocrinol Metab. Jul 1997;82(7):2363-2367.

  26. Nair KS, Rizza RA, O’Brien P, et al. DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med. Oct 19 2006;355(16):1647-1659.

  27. Morris KT, Toth-Fejel S, Schmidt J, et al. High dehydroepiandrosterone-sulfate predicts breast cancer progression during new aromatase inhibitor therapy and stimulates breast cancer cell growth in tissue culture: a renewed role for adrenalectomy. Surgery. Dec 2001;130(6):947-953.

  28. Panjari M, Bell RJ, Jane F, et al. A randomized trial of oral DHEA treatment for sexual function, well-being, and menopausal symptoms in postmenopausal women with low libido. J Sex Med. Sep 2009;6(9):2579-2590.

  29. Genazzani AR, Stomati M, Valentino V, et al. Effect of 1-year, low-dose DHEA therapy on climacteric symptoms and female sexuality. Climacteric. Dec 2011;14(6):661-668.

  30. Calhoun K, Pommier R, Cheek J, et al. The effect of high dehydroepiandrosterone sulfate levels on tamoxifen blockade and breast cancer progression. Am J Surg. May 2003;185(5):411-415.

  31. Jones JA, Nguyen A, Straub M, et al. Use of DHEA in a patient with advanced prostate cancer: a case report and review. Urology. Nov 1997;50(5):784-788.

  32. Key T, Appleby P, Barnes I, et al. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst. Apr 17 2002;94(8):606-616.

  33. McNeil C. Potential drug DHEA hits snags on way to clinic. J Natl Cancer Inst. May 21 1997;89(10):681-683.

  34. Piketty C, Jayle D, Leplege A, et al. Double-blind placebo-controlled trial of oral dehydroepiandrosterone in patients with advanced HIV disease. Clin Endocrinol (Oxf). Sep 2001;55(3):325-330.

  35. Brignardello E, Runzo C, Aragno M, et al. Dehydroepiandrosterone administration counteracts oxidative imbalance and advanced glycation end product formation in type 2 diabetic patients. Diabetes Care. Nov 2007;30(11):2922-2927.

  36. Moffat SD, Zonderman AB, Harman SM, et al. The relationship between longitudinal declines in dehydroepiandrosterone sulfate concentrations and cognitive performance in older men. Arch Intern Med. Jul 24 2000;160(14):2193-2198.

  37. Genud R, Merenlender A, Gispan-Herman I, et al. DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System. Neuropsychopharmacology. May 21 2008.

  38. Stoll BA. Dietary supplements of dehydroepiandrosterone in relation to breast cancer risk. Eur J Clin Nutr. Oct 1999;53(10):771-775.

  39. Arlt W, Justl HG, Callies F, et al. Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression. J Clin Endocrinol Metab. Jun 1998;83(6):1928-1934.

  40. Legrain S, Massien C, Lahlou N, et al. Dehydroepiandrosterone replacement administration: pharmacokinetic and pharmacodynamic studies in healthy elderly subjects. J Clin Endocrinol Metab. Sep 2000;85(9):3208-3217.

  41. Dean CE. Prasterone (DHEA) and mania. Ann Pharmacother. Dec 2000;34(12):1419-1422.

  42. Markowitz JS, Carson WH, Jackson CW. Possible dihydroepiandrosterone-induced mania. Biol Psychiatry. Jan 15 1999;45(2):241-242.

  43. Gurnell EM, Hunt PJ, Curran SE, et al. Long-term DHEA replacement in primary adrenal insufficiency: a randomized, controlled trial. J Clin Endocrinol Metab. Feb 2008;93(2):400-409.

  44. Labrie F, Belanger A, Belanger P, et al. Metabolism of DHEA in postmenopausal women following percutaneous administration. J Steroid Biochem Mol Biol. Feb 2007;103(2):178-188.

  45. Christiansen JJ, Andersen NH, Sorensen KE, et al. Dehydroepiandrosterone substitution in female adrenal failure: no impact on endothelial function and cardiovascular parameters despite normalization of androgen status. Clin Endocrinol (Oxf). Mar 2007;66(3):426-433.

  46. Vegliante R, Desideri E, Di Leo L, Ciriolo MR. Dehydroepiandrosterone triggers autophagic cell death in human hepatoma cell line HepG2 via JNK-mediated p62/SQSTM1 expression. Carcinogenesis. 2016 Jan 13. pii: bgw003. [Epub ahead of print]