What is it?
DHEA (dehydroepiandrosterone) 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).
What do the advocates say?*
Since it is a precursor to testosterone, dehydroepiandrosterone (DHEA) may help build muscle. However, it is very unusual for anyone under the age of 35 or 40 to have low DHEA levels. As we age, the body’s production of DHEA declines, so people over 40 should ask their physicians to do a blood test to check their DHEA levels. Although it is sold over the counter, it’s best to take DHEA only under the supervision of a physician.
How much is usually taken by dieters?
One double-blind trial found 100 mg per day of DHEA was effective for decreasing body fat in older men,2 and another double-blind trial found 1,600 mg per day decreased body fat and increased muscle mass in younger men.3 However, DHEA has not been effective for improving body composition in women or in other studies of men.4 5 6 7 8 9 10 11
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.12 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.13 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.14 15 Other reports have found this change in women but not in men.16 An increase in testosterone might increase the risk of several cancers, and high amounts of DHEA have caused cancer in animals.17 18 Moreover, a possible link between higher DHEA levels and risks of prostate cancer in humans has been reported.19 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.20
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.21 22 Most,23 24 25 26 27 but not all, studies28 29 30 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.31 32 Elevated DHEA levels have been reported to be associated with both higher,33 and lower risk for ovarian cancer.34 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,35 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.36
The relationship between DHEA, blood pressure, and heart disease is poorly understood. Increased blood levels of DHEAS have been associated with increased blood pressure37 and other cardiovascular risk factors in some,38 but not all,39 studies. One study found that people with hypertension had significantly decreased blood levels of DHEA.40 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).41 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.
*Dieters and weight-management advocates may claim benefits for DHEA based on their personal or professional experience. These are individual opinions and testimonials that may or may not be supported by controlled clinical studies or published scientific articles on DHEA. For more complete and detailed information, including references and safety information, see DHEA as a nutritional supplement.
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. 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.
3. Nestler JE, Barlascini CO, Clore JN, Blackard WG. Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men. J Clin Endocrinol Metab 1988;66:57–61.
4. 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;163:720–7.
5. Wallace MB, Lim J, Cutler A, Bucci L. Effects of dehydroepiandrosterone vs androstenedione supplementation in men. Med Sci Sports Exerc 1999;31:1788–92.
6. Brown GA, Vukovich MD, Sharp RL. Effect of oral DHEA on serum testosterone and adaptations to resistance training in young men. J Appl Physiol 1999;87:2274–83.
7. 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.
8. Vogiatzi MG, Boeck MA, Vlachopapadopoulou E, et al. Dehydroepiandrosterone in morbidly obese adolescents: effects on weight, body composition, lipids, and insulin resistance. Metabolism 1996;45:1011–5.
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11. Usiskin KS, Butterworth S, Clore JN, et al. Lack of effect of dehydroepiandrosterone in obese men. Int J Obes 1990;14:457–63.
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13. Markowitz JS, Carson WH, Jackson CW. Possible dihydroepiandrosterone-induced mania. Biol Psychiatry 1999;45:241–2.
14. 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.
15. Bowers LD. Oral dehydroepiandrosterone supplementation can increase the testosterone/epitestosterone ratio. Clin Chem 1999;45:295–6.
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17. 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.
18. 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.
19. McNeil C. Potential drug DHEA hits snags on way to clinic. J Natl Cancer Inst 1997;89:681–3.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. Barrett-Connor E, Friedlander NJ, Khaw KT. Dehydroepiandrosterone sulfate and breast cancer risk. Cancer Res 1990;50:6571–4.
30. 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.
31. 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.
32. 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.
33. Helzlsouer KJ, Alberg AJ, Gordon GB, et al. Serum gonadotropins and steroid hormones and the development of ovarian cancer. JAMA 1995;274:1926–30.
34. 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.
35. 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.
36. Sahelian R. New supplements and unknown, long-term consequences. Am J Natural Med 1997;4:8 [editorial].
37. 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.
38. 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.
39. 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.
40. 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.
41. 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.