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Dehydroepiandrosterone (DHEA)

Also indexed as: DHEA

Illustration

Dehydroepiandrosterone (DHEA) is one of the hormones produced by the adrenal glands. After being secreted by the adrenal glands, it circulates in the bloodstream as DHEA-sulfate (DHEAS) and is converted as needed into other hormones.

Where is it found?

DHEA is produced by the adrenal glands. A synthetic form of this hormone is also available as a supplement in tablet, capsule, liquid, and sublingual form. Some products claim to contain “natural” DHEA precursors from wild yam. However, the body cannot convert these substances into DHEA1 (although a series of reactions in a laboratory can make the conversion).

Dehydroepiandrosterone (DHEA) has been used in connection with the following conditions (refer to the individual health concern for complete information):

Science Ratings Health Concerns
2Stars

Addison’s Disease (to correct deficiency)

Crohn’s disease

Depression

Erectile dysfunction

HIV support (for fatigue and depression)

Lupus

Schizophrenia

Ulcerative colitis
1Star

Alzheimer’s Disease

Chronic fatigue syndrome

Immune Function

Menopause

Multi-infarct dementia

Osteoporosis

Weight loss
3Stars Reliable and relatively consistent scientific data showing a substantial health benefit.
2Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support and/or minimal health benefit.

Who is likely to be deficient?

Meaningful levels of DHEA do not appear in food, and therefore dietary deficiency does not exist. Some people, however, may not synthesize enough DHEA. DHEA levels peak in early adulthood and then start a lifelong descent. By the age of 60, DHEA levels are only about 5–15% of what they were at their peak at younger ages.2 Whether the lower level associated with age represents a deficiency or a normal part of aging that should not be tampered with remains unknown.

People with true adrenal insufficiency (i.e., Addison’s Disease; not the hypothetical adrenal “fatigue” or “burnout” that is sometimes incorrectly referred to as “insufficiency”) have below normal levels of DHEA. When women with adrenal insufficiency were treated with 50 mg of DHEA every morning for three or four months, their DHEA and DHEAS levels returned to normal, with a simultaneous improvement in well-being and sexuality.3 4

Some studies have reported lower DHEA levels in groups of depressed patients.5 6 However, in one trial, severely depressed people were reported to show increases in blood levels of DHEA.7 Despite these contradictory findings, a few clinical trials suggest that at least some people who are depressed may benefit from DHEA supplementation. (See “What does it do?” above for more information about use of DHEA supplements in the treatment of depression.)

People with multi-infarct dementia (deterioration of mental functions resulting from multiple small strokes) may have lower than normal DHEAS levels, according to a preliminary trial.8 In this trial, intravenous injection of 200 mg per day of DHEAS for four weeks increased DHEAS levels and improved some aspects of mental function and performance of daily activities.

People infected with HIV9 and those with insulin-dependent diabetes,10 congestive heart failure,11 multiple sclerosis, 12 asthma,13 14 chronic fatigue syndrome,15 16 rheumatoid arthritis,17 18 19 osteoporosis, and a host of other conditions have been reported to have low levels of DHEA in most,20 but not all, studies.21 22 In most cases, the meaning of this apparent deficiency is not well understood.

Men under 60 years of age with erectile dysfunction have been found to have lower DHEAS levels than men without the condition.23 (See “What does it do?” above for more information about use of DHEA supplements in the treatment of men with erectile dysfunction.)

Most,24 25 26 27 but not all, 28 29 studies have found that people with Alzheimer’s disease have lower blood DHEAS levels than do people without the condition.

How much is usually taken?

Most people do not need to supplement DHEA. The question of who should take this hormone remains controversial. Some experts believe that daily intakes of 5–15 mg of DHEA for women and 10–30 mg for men are appropriate amounts for people with deficient blood levels of DHEA or DHEAS.30 While a few researchers suggest supplementation with as much as 50 mg per day in postmenopausal women,31 others consider this level excessive.32 People should consult a doctor to have DHEA levels monitored before and during supplementation. Healthy people with normal blood levels of DHEA or DHEAS should not take this hormone until more is known about its effects. However, some doctors recommend DHEA supplementation for selected people with depression, autoimmune diseases, or other problems, even if their blood levels are normal.

People with systemic lupus erythematosus (SLE) have been shown to improve after taking 100–200 mg per day of DHEA. Such large amounts should never be taken without medical supervision.

Discrepancies between label claims and actual DHEA content of DHEA supplements have been reported.33 Regrettably, the authors of this report failed to identify which brands were properly labeled and which were not.

Are there any side effects or interactions?

Experts have concerns about the use of DHEA, particularly because long-term safety data do not exist.

Side effects at high intakes (50–200 mg per day) appear to be acne (in over 50% of people), increased facial hair (18%), and increased perspiration (8%). In a preliminary trial, DHEA was also reported to induce less common side effects, including breast tenderness, weight gain, mood alteration, headache, oily skin, and menstrual irregularity in some people.34 Since this trial was not controlled, some of these less common “side effects” might have occurred even with a placebo. A case of mania has been reported in an older man who took 200–300 mg of DHEA per day for six months.35 However, in that case report, other causes of mania could not be ruled out.

Significant increases in testosterone levels in both men and women have been reported in some trials.36 37 Other reports have found this change in women but not in men.38 An increase in testosterone might increase the risk of several cancers, and high amounts of DHEA have caused cancer in animals.39 40 Moreover, a possible link between higher DHEA levels and risks of prostate cancer in humans has been reported.41 At least one person with prostate cancer has been reported to have had a worsening of his cancer, despite feeling better, while taking very high amounts (up to 700 mg per day) of DHEA.42

While younger women with breast cancer may have low levels of DHEA, postmenopausal women with breast cancer appear to have high levels of DHEA, which has researchers concerned.43 44 Most,45 46 47 48 49 but not all, studies50 51 52 have found that as DHEA blood levels increase, so does the risk of breast cancer.

Supplementation with high levels of DHEA (100 mg per day) has adversely affected other indicators of cancer risk in both women and men.53 54 Elevated DHEA levels have been reported to be associated with both higher,55 and lower risk for ovarian cancer.56 The reason for this discrepancy is unknown.

The lack of knowledge about how DHEA supplementation might affect cancer risks provides a reason for caution. Until more is known, people with breast or prostate cancer or a family history of these conditions should avoid supplementing with DHEA.

Although anticancer effects of DHEA have also been reported,57 they involve trials using animals that do not process DHEA the way humans do. Therefore, these positive effects may have no relevance for people.

Some doctors recommend that people taking DHEA have liver enzymes measured routinely. Anecdotes of DHEA supplementation (of at least 25 mg per day) leading to heart arrhythmias have appeared.58

The relationship between DHEA, blood pressure, and heart disease is poorly understood. Increased blood levels of DHEAS have been associated with increased blood pressure59 and other cardiovascular risk factors in some,60 but not all,61 studies. One study found that people with hypertension had significantly decreased blood levels of DHEA.62 Until clinical trials clear up these inconsistencies and confirm its safety, people with hypertension should avoid using DHEA, except under the close supervision of a doctor.

At only 25 mg per day, DHEA has lowered HDL cholesterol while increasing insulin-like growth factor (IGF).63 Decreasing HDL could increase the risk of heart disease. Increasing IGF might increase the risk of breast cancer.

Are there any drug interactions?
Certain medicines may interact with dehydroepiandrosterone. Refer to drug interactions for a list of those medicines.

References:

1. Araghiniknam J, Chung S, Nelson-White T, et al. Antioxidant activity of dioscorea and dehydroepiandrosterone (DHEA) in older humans. Life Sci 1996;59:147–57.

2. Ebeling P, Koivisto VA. Physiological importance of dehydroepiandrosterone. Lancet 1994;343:1479–81.

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

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

5. Barrett-Connor E, von Mühlen D, Laughlin GA, Kripke A. Endogenous levels of dehydroepiandrosterone sulfate, but not other sex hormones, are associated with depressed mood in older women: The Rancho Bernardo Study. J Am Geriatr Soc 1999;47:685–91.

6. Heinz A, Weingartner H, George D, et al. Severity of depression in abstinent alcoholics is associated with monoamine metabolites and dehydroepiandrosterone-sulfate concentrations. Psychiatry Res 1999;89:97–106.

7. Heuser I, Deuschle M, Luppa P, et al. Increased diurnal plasma concentrations of dehydroepiandrosterone in depressed patients. J Clin Endocrinol Metab 1998;83:3130–3.

8. Azuma T, Nagai Y, Saito T, et al. The effect of dehydroepiandrosterone sulfate administration to patients with multi-infarct dementia. J Neurol Sci 1999;162:69–73.

9. Ferrando SJ, Rabkin JG, Poretsky L. Dehydroepiandrosterone sulfate (DHEAS) and testosterone: Relation to HIV illness stage and progression over one year. J Acquir Immune Defic Syndr 1999;22:146–54.

10. Louviselli A, Pisanu P, Cossu E, et al. Low levels of dehydroepiandrosterone sulfate in adult males with insulin-dependent diabetes mellitus. Minerva Endocrinol 1994;19:113–9.

11. Moriyama Y, Yasue H, Yoshimura M, et al. The plasma levels of dehydroepiandrosterone sulfate are decreased in patients with chronic heart failure in proportion to the severity. J Clin Endocrinol Metab 2000;85:1834–40.

12. Kümpfel T, Then Bergh F, Friess E, et al. Dehydroepiandrosterone response to the adrenocorticotropin test and the combined dexamethasone and corticotropin-releasing hormone test in patients with multiple sclerosis. Neuroendocrinology 1999;70:431–8.

13. Weinstein RE, Lobocki CA, Gravett S, et al. Decreased adrenal sex steroid in the absence of glucocorticoid suppression in postmenopausal asthmatic women. J Allergy Clin Immunol 1996;97:1–8.

14. Dunn PJ; Mahood CB; Speed JF; Jury DR. Dehydroepiandrosterone sulphate concentrations in asthmatic patients: pilot study. N Z Med J 1984;97:805–8.

15. Kuratsune H, Yamaguti K, Sawada M, et al. Dehydroepiandrosterone sulfate deficiency in chronic fatigue syndrome. Int J Mol Med 1998;1:143–6.

16. De Becker P, De Meirleir K, Joos E, et al. Dehydroepiandorsterone (DHEA) response to i.v. ACTH in patients with chronic fatigue syndrome. Horm Metab Res 1999;31:18–21.

17. Khalkhali-Ellis Z, Moore TL, Hendrix MJ. Clin Exp Rheumatol 1998;16:753–6.

18. Hall GM, Perry LA, Spector TD. Depressed levels of dehydroepiandrosterone sulphate in postmenopausal women with rheumatoid arthritis but no relation with axial bone density. Ann Rheum Dis 1993;52:211–4.

19. Mateo L, Nolla JM, Bonnin MR, et al. Sex hormone status and bone mineral density in men with rheumatoid arthritis. J Rheumatol 1995;22:1455–60.

20. Gaby AR. Dehydroepiandrosterone: biological effects and clinical significance. Altern Med Rev 1996;1:60–9 [review].

21. Heikkila R, Aho K, Heliovaara M, et al. Serum androgen-anabolic hormones and the risk of rheumatoid arthritis. Ann Rheum Dis 1998;57:281–5.

22. Mileva Zh, Maleeva A, Khristov G. Androstenedione, DHEA sulfate, cortisol, aldosterone and testosterone in bronchial asthma patients. Vutr Boles. 1990;29:84–7 [in Bulgarian].

23. Reiter WJ, Pycha A, Schatzl G, et al. Serum dehydroepiandrosterone sulfate concentrations in men with erectile dysfunction. Urology 2000;55:755–8.

24. Hillen T, Lun A, Reischies FM, et al. DHEA-S plasma levels and incidence of Alzheimer’s disease. Biol Psychiatry 2000;47:161–3.

25. Nasman B, Olsson T, Backstrom T, et al. Serum dehydroepiandrosterone sulfate in Alzheimer’s disease and in multi-infarct dementia. Biol Psychiatry 1991;30:684–90.

26. Sunderland T, Merril CR, Harrington MG, et al. Reduced plasma dehydroepiandrosterone concentrations in Alzheimer’s disease. Lancet 1989;2:570.

27. Yanase T, Fukahori M, Taniguchi S, et al. Serum dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) in Alzheimer’s disease and in cerebrovascular dementia. Endocr J 1996;43:119–23.

28. Birkenhager-Gillesse EG, Derksen J, Lagaay AM. Dehydroepiandrosterone sulphate (DHEAS) in the oldest old, aged 85 and over. Ann N Y Acad Sci 1994;719:543–52.

29. Schneider LS, Hinsey M, Lyness S. Plasma dehydroepiandrosterone sulfate in Alzheimer’s disease. Biol Psychiatry 1992;31:205–8.

30. Gaby AR. Research review. Nutr Healing, 1996;Jan:7.

31. Casson PR, Buster JE. DHEA replacement after menopause: HRT 200 or nostrum of the ‘90s? Contemporary OB/GYN 1997;Apr:119–33.

32. Arlt W, Justl HG, Callies F, et al. Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in healthy young females after dexamethasone suppression. J Clin Endocrinol Metab 1998;83:1928–34.

33. Parasrampuria J, Schwartz K, Petesch R. Quality control of dehydroepiandrosterone dietary supplement products. JAMA 1998;280:1565 [letter].

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

35. Markowitz JS, Carson WH, Jackson CW. Possible dihydroepiandrosterone-induced mania. Biol Psychiatry 1999;45:241–2.

36. 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 1997;82:2263–7.

37. Bowers LD. Oral dehydroepiandrosterone supplementation can increase the testosterone/epitestosterone ratio. Clin Chem 1999;45:295–6.

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

39. Orner GA, Mathews C, Hendricks JD, et al. Dehydroepiandrosterone is a complete hepatocarcinogen and potent tumor promoter in the absence of peroxisome proliferation in rainbow trout. Carcinogenesis 1995;16:2893–8.

40. Metzger C, Mayer D, Hoffmann H, et al. Sequential appearance and ultrastructure of amphophilic cell foci, adenomas, and carcinomas in the liver of male and female rats treated with dehydroepiandrosterone. Toxicol Pathol 1995;23:591–605.

41. McNeil C. Potential drug DHEA hits snags on way to clinic. J Natl Cancer Inst 1997;89:681–3.

42. Jones JA, Nguyen A, Strab M, et al. Use of DHEA in a patient with advanced prostate cancer: a case report and review. Urology 1997;50:784–8.

43. Zumoff B, Levin J, Rosenfeld RS, et al. Abnormal 24-hr mean plasma concentrations of dehydroisoandrosterone and dehydroisoandrosterone sulfate in women with primary operable breast cancer. Cancer Res 1981;41:3360–3.

44. Helzlsouer KJ, Gordon GB, Alberg AJ, et al. Relationship of prediagnostic serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate to the risk of developing premenopausal breast cancer. Cancer Res 1992;52:1–4.

45. Dorgan JF, Longcope C, Stephenson HE, et al. Relation of prediagnostic serum estrogen and androgen levels to breast cancer risk. Cancer Epidemiol Biomarkers Prev 1996;5:533–9.

46. Gordon GB, Bush TL, Helzlsouer KJ, et al. Relationship of serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate to the risk of developing postmenopausal breast cancer. Cancer Res 1990;50:3859–62.

47. Berrino F, Muti P, Micheli A, et al. Serum sex hormone levels after menopause and subsequent breast cancer. J Natl Cancer Inst 1996;88:291–6.

48. Hankinson SE, Willett WC, Manson JE, et al. Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 1998;90:1292–9.

49. Zumoff B, Levin J, Rosenfeld RS, et al. Abnormal 24-hr mean plasma concentrations of dehydroisoandrosterone and dehydroisoandrosterone sulfate in women with primary operable breast cancer. Cancer Res 1981;41:3360–3.

50. Zeleniuch-Jacquotte A, Bruning PF, Bonfrer JM, et al. Relation of serum levels of testosterone and dehydroepiandrosterone sulfate to risk of breast cancer in postmenopausal women. Am J Epidemiol 1997;145:1030–8.

51. Barrett-Connor E, Friedlander NJ, Khaw KT. Dehydroepiandrosterone sulfate and breast cancer risk. Cancer Res 1990;50:6571–4.

52. Bernstein L, Ross RK, Pike MC, et al. Hormone levels in older women: a study of post-menopausal breast cancer patients and healthy population controls. Br J Cancer 1990;61:298–302.

53. Johannes CB, Stellato RK, Feldman HA, et al. Relation of dehydroepiandrosterone and dehydroepiandrosterone sulfate with cardiovascular disease risk factors in women: longitudinal results from the Massachusetts Women’s Health Study. J Clin Epidemiol 1999;52:95–103.

54. 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.

55. Helzlsouer KJ, Alberg AJ, Gordon GB, et al. Serum gonadotropins and steroid hormones and the development of ovarian cancer. JAMA 1995;274:1926–30.

56. Heinonen PK, Koivula T, Pystynen P. Decreased serum level of dehydroepiandrosterone sulfate in postmenopausal women with ovarian cancer. Gynecol Obstet Invest 1987;23:271–4.

57. Schwartz AG. Inhibition of spontaneous breast cancer formation in female C3H (A vy/a) mice by long-term treatment with dehydroepiandrosterone. Cancer Res 1979;39:1129–32.

58. Sahelian R. New supplements and unknown, long-term consequences. Am J Natural Med 1997;4:8 [editorial].

59. Schunkert H, Hense H-W, Andus T, et al. Relation between dehydroepiandrosterone sulfate and blood pressure levels in a population-based sample. Am J Hypertens 1999;12:1140–3.

60. Hautanen A, Manttari M, Manninen V, et al. Adrenal androgens and testosterone as coronary risk factors in the Helsinki Heart Study. Atherosclerosis 1994;105:191–200.

61. Kiechl S, Willeit J, Bonora E, et al. No association between dehydroepiandrosterone sulfate and development of atherosclerosis in a prospective population study (Bruneck Study). Arterioscler Thromb Vasc Biol 2000;20:1094–100.

62. Suzuki M, Kanazawa A, Hasegawa M, et al. A close association between insulin resistance and dehydroepiandrosterone sulfate in subjects with essential hypertension. Endocr J 1999;46:521–8.

63. Casson PR, Santoro N, Elkind-Hirsch K, et al. Postmenopausal dehydroepiandrosterone administration increases free insulin-like growth factor-I and decreases high-density lipoprotein: a six-month trial. Fertil Steril 1998;70:107–10.
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