“A number of biological indices confirmed the lack of harmful consequences of this 50 mg/day DHEA administration over one year, also indicating that this kind of replacement therapy normalized some effects of aging, but does not create “supermen/women” (doping).”
Proceedings of the National Academy of Science USA, 2000; 97:4279-8
Dehydroepiandrosterone (DHEA) is a naturally occurring pro-hormone produced primarily by the adrenal glands, testes in men or ovaries in women, while small amounts are also created in the liver and brain. It is known as a “precursor hormone” since it is produced in large amounts in the body and serves as the progenitor for other hormones to be produced such as estrogen and testosterone. Within both the male and female body, DHEA increases dramatically before puberty in children, usually peaks when we’re in our mid-20s, and drops off from this peak throughout the aging process. By the 40th birthday most people have a mere 50 percent of their former youthful levels. It is currently believed that this dramatic and persistent drop in DHEA is related to the aging process, including loss of muscle mass, weight gain, decreased zeal for life, diminished mental clarity, decreased bone density and countless other signs of aging.
One can succinctly summarize the role of DHEA in the human body as essential for maintaining quality of life and optimal performance. With the dramatic and persistent drop of DHEA levels during the aging process, there is no question that the ability to augment levels is essential and a liberty that should be enjoyed by all those that need to buffer age-related decreased levels or who suffer from health conditions that have been demonstrated to benefit from supplementation.
The clinical research on the use of DHEA is significant and the safety window is broad when used at reasonable and appropriate doses. As the following research summary stated: “Administration of low doses (25 mg) of DHEA positively modulates several endocrine parameters in early and late postmenopausal women, inducing the increase of the androgenic, estrogenic, and progestogenic milieu and reducing the climacteric symptoms, similarly to estroprogestin replacement therapy.”1 Thus, the conclusion is that DHEA can be as effective as hormone replacement therapy at a fraction of the cost to the American Healthcare System.
Basic Biochemistry of DHEA
DHEA and its sulfate ester, dehydroepiandrosterone sulfate (DHEA-S), are interconvertible. The importance of DHEA to human performance is well illustrated by the fact that DHEA is converted to DHEA-S, which serves as a storage form of DHEA.2-3 It is the storage of this dynamic “precursor” pro-hormone that emphasizes its critical biochemical function. When needed, DHEA-S is then converted by the body’s tissues and target organs back to DHEA. It is at the cellular level that DHEA is then converted as needed to other hormones.4
At normal, healthy levels, the concentration of DHEA-S is 100 to 500 times higher than testosterone and 1,000 to 10,000 times higher than estradiol, the body’s most potent estrogen. It is essential to realize that though DHEA serves as a precursor to sex steroid hormones, it does not perform a direct estrogenic or androgenic role.5 Both DHEA and DHEA-S levels are higher in men than in women and they peak at about 20 years of age and decline rapidly after age 25.6 There is a direct correlation with increased mortality and very low levels of DHEA-S in men under the age of 70. Furthermore, men who smoke and have low DHEA-S levels seem to have a mortality risk more than 6 times greater than nonsmokers with high DHEA-S levels.7
The risk of the body accumulating high levels of DHEA with supplementation of 50 mg of DHEA or less is modest at best. The highly esteemed scientifi c journal Proceedings of the National Academy of Science in 2000 reported:
“Two hundred and eighty healthy individuals (women and men 60-79 years old) were given DHEA, 50 mg, or placebo, orally, daily for a year in a double-blind, placebo-controlled study. No potentially harmful accumulation of DHEA-S and active steroids was recorded. Besides the reestablishment of a ‘young’ concentration of DHEA-S, a small increase of testosterone and estradiol was noted, particularly in women, and may be involved in the signifi cantly demonstrated physiologicalclinical manifestations here reported. Bone turnover improved selectively in women over 70 years old, as assessed by the dual-energy x-ray absorptiometry (DEXA) technique and the decrease of osteoclastic activity. A significant increase in most libido parameters was also found in these older women. Improvement of the skin status was observed, particularly in women, in terms of hydration, epidermal thickness, sebum production, and pigmentation. A number of biological indices confirmed the lack of harmful consequences of this 50 mg/day DHEA administration over one year, also indicating that this kind of replacement therapy normalized some effects of aging, but does not create “supermen/women” (doping).”49
Consequences of Lower DHEA Levels
There are several health conditions that seem more prevalent in individuals with lower DHEA levels. The conditions frequently associated with lower levels of DHEA include; but are not limited to.8, 9, 10
- Anorexia nervosa
- Chronic fatigue
- Congestive heart failure
- Diabetes mellitus Type 2
- Erectile dysfunction
- Kidney disease (End-Stage)
- Systemic lupus erythematosus (SLE)
Circulatory disease is the number one cause of death in the United States and there is now evidence that DHEA can help support the health of the 18,000 miles of the microvascular system within the body. The mechanism for this protective effect appears to arise from the inhibition of thromboxane A2 synthesis in platelets; this decrease in thromboxane A2 is accompanied by increased levels of insulin-like growth factor 1 (IGF-1), cyclic guanosine monophosphate (GMP) and nitric oxide synthesis.11 The ability of DHEA to naturally optimize this essential biochemical pathway and the fact that there is a signifi cant drop in DHEA during aging, may account for the increased frequency of heart disease and the associated escalating economic costs of heart disease during the aging process.
Safe and Natural
Dehydroepiandrosterone when used orally and appropriately in the short-term has been shown in numerous studies to be safe and effective for many months.12, 13, 14, 15, 16, 17
Additional studies have used oral DHEA for 12-24 months.18, 19, 20 Another study, lasting twelve months, investigated intravaginally DHEA use with reported safety in postmenopausal women.21 DHEA is well absorbed orally and possesses a serum half-life of 15 to 38 minutes; whereas the half-life of DHEA-S is longer, at 7-22 hours. The kidneys are the primary route of elimination and account for the clearance of 51 percent to 73 percent of DHEA-S and its metabolic endproducts.12
DHEA Clinical Research Applications
There are over two dozen therapeutic applications for DHEA supplementation. The following are some of the areas that have been studied by researchers and reported in the peer-reviewed medical literature.
Taking low-dose DHEA orally (20-50 mg daily) has been associated with increased sense of well-being, healthier skin and hair and enhanced sexuality in women with low pituitary function.22, 23
Preliminary clinical evidence suggests that oral DHEA might improve symptoms of Addison’s disease.24
Oral DHEA supplementation has been shown to increase epidermal skin thickness, skin hydration, and lessen facial skin discooration in aging women and men.25
Congestive Heart Failure
Clinical researchers have reported, in a study conducted in the year 2000, that: “These results indicate that the plasma levels of DHEA-S are decreased in patients with CHF in proportion to its severity and that oxidative stress is associated with decreased levels of DHEA-S in patients with CHF.”26
Clinical use of DHEA to help lessen symptoms of depression and dysthymia (chronic depression) appear promising as reflected in a 1999 study report that states: “These results suggest that DHEA treatment may have signifi cant antidepressant effects in some patients with major depression.”27, 28
Erectile Dysfunction (ED)
When oral DHEA is taken for 24 weeks, ED symptoms improve along with orgasmic function, libido, and overall satisfaction. Men suffering from ED secondary to high blood pressure or idiopathic causes were those that responded signifi cantly to DHEA treatment.29, 30
A 2003 report concluded, “Administration of low doses (25 mg) of DHEA positively modulates several endocrine parameters in early and late postmenopausal women, inducing the increase of the androgenic, estrogenic, and progestogenic milieu and reducing the climacteric symptoms, similarly to estroprogestin replacement therapy.”31
Oral use of DHEA, 50 mg daily for 6 months, lead to signifi cant weight reduction, less abdominal fat and improved insulin levels. The Journal of the American Medical Association published a report in 2004 that made the following conclusion, “DHEA replacement could play a role in prevention and treatment of the metabolic syndrome associated with abdominal obesity.”32 With approximately 50 million Americans suffering from Metabolic Syndrome according to the Centers for Disease Control (CDC), this application for DHEA could help lessen the current conversion rate to diabetes that is at a staggering 1.5 million new cases per year.
Older men and women with osteoporosis or osteopenia have benefi ted from an oral dose of DHEA at 50-100 mg daily. These study participants experienced increased bone density.33, 34 Likewise, young women with osteoporosis secondary to anorexia nervosa can often benefi t.35
Systemic Lupus Erythematosus (SLE)
Compelling evidence suggests that DHEA administered orally in conjunction with standard medical treatment, can help lessen SLE disease activity, frequency of flare-ups, and the number of glucocorticosteroid doses needed.36, 37, 38, 39, 40, 41
Vaginally, application of DHEA appears to be effective for the treatment of vaginal atrophy in postmenopausal women and may also confer a secondary benefit of increased bone mineral density.42
Common Clinical Dosing in Research Studies
Please note that none of the research presented in this paper is intended to serve as either treatment or diagnosis, but rather a clear demonstration of the safety and efficacy of appropriately used DHEA. In that spirit, the information that follows is simply a refl ection of some representative dosages of DHEA used in clinical trials around the world. It should be noted that in order to conduct a human study, approval by an IRB (Institutional Review Board) is essential to ensure safety. Thus, the IRB process designed to protect participants in research studies must have deemed these dosages to be safe and reasonable.
In postmenopausal women, doses of 25-50 mg daily are commonly used with benefi ts of lessened menopausal symptoms, improved tissue insulin sensitivity and lower serum triglycerides readings.43, 44, 45, 46
In cases of depression, doses of DHEA between 30-90 mg daily have been used, either as a stand alone intervention or in conjunction with standard antidepressant therapy. A double blind clinical trial published in 1999 reported, “These results suggest that DHEA treatment may have significant antidepressant effects in some patients with major depression.”47 An earlier 1997 study reported clinical benefi ts plus improved memory: “These preliminary data suggest DHEA may have antidepressant and promemory effects, and should encourage double-blind trials in depressed patients.”48
A schizophrenia study used increasing doses of DHEA of 25 mg daily for 2 weeks, 25 mg two times daily for 2 weeks, and 50 mg two times daily for 2 weeks. This signifi cant 2003 report of DHEA use and schizophrenia states, “Our preliminary observations report for the fi rst time in double-blind fashion, the effi cacy of DHEA augmentation in the management of negative, depressive, and anxiety symptoms of schizophrenia. The findings from this study raise important issues regarding the role of neurosteroids in general, and DHEA in particular, in the ongoing symptomatology and pharmacotherapy of schizophrenia.”16 Dosing for systemic lupus erythematosus (SLE), can be upwards of 200 mg daily, used as addition to standard SLE medical treatment protocols.27
Bone mineral density studies investigating treatment for osteopenia or osteoporosis often use DHEA levels in the range of 50-100 mg per day.33
An erectile dysfunction study utilizing 50 mg of DHEA daily has been conducted. The researchers’ conclusion was simple, “Our results suggest that oral DHEA treatment may be of benefit in the treatment of ED.”18
In the case of prediabetes, also known as metabolic syndrome, 50 mg taken orally at bedtime was employed.33 The result of this study showed that DHEA replacement could play a role in prevention and treatment of the metabolic syndrome associated with abdominal obesity.
The review of the peer-reviewed medical literature clearly demonstrates not only the safety of appropriately used dosages of DHEA, it also elucidates that DHEA can help tens of millions of people alleviate the symptoms produced by drops in DHEA associated with aging and help mitigate various health conditions by optimizing DHEA levels. Clear and convincing evidence is in the medical literature; in addition, IRB boards from around the world have approved the use of DHEA in human clinical trials with a solid record of both safe and effective use. As discussed earlier in this report and stated so aptly in the findings of one of the world’s most revered medical journals, DHEA is not a “doping substance.” Scientific research has documented that DHEA helps normalize the aging process, a benefi cial liberty that all humanity must be able to freely partake. Therefore, in conclusion, I will once again quote the above study that demonstrates DHEA’s safety:
“A number of biological indices confirmed the lack of harmful consequences of this 50 mg/day DHEA administration over one year, also indicating that this kind of replacement therapy normalized some effects of aging, but does not create “supermen/women” (doping).”49
1 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.
2 Moffat SD, Zonderman AB, Harman M, et al. The relationship between longitudinal declines in dehydroepiandrosterone sulfate concentrations and cognitive performance in older men. Arch Int Med 2000;160:2193-8.
3 Pepping J. DHEA: dehydroepiandrosterone. Am J Health Syst Pharm 2000;57:2048-50, 2053-4, 2056.
4 Oelkers W. Dehydroepiandosterone for adrenal insuffi ciency (editorial). N Engl J Med 1999;341:1073-4.
5 Tchernof A, Labrie F. Dehydroepiandrosterone, obesity and cardiovascular disease risk: a review of human studies. Eur J Endocrinol 2004;151:1-14.
6 Villareal DT, Holloszy JO. Effect of DHEA on abdominal fat and insulin action in elderly women and men. JAMA 2004;292:2243-8.
7 Mazat L, Lafont S, Berr C, et al. Prospective measurements of dehydroepiandrosterone sulfate in a cohort of elderly subjects: relationship to gender, subjective health, smoking habits, and 10-year mortality. Proc Natl Acad Sci U S A 2001;98:8145-50.
8 Kroboth PD, Salek FS, Pittenger AL, et al. DHEA and DHEA-S: A review. J Clin Pharmacol 1999;39:327-48.
9 Kuratsune H, Yamaguti K, Sawada M, et al. Dehydroepiandrosterone sulfate defi ciency in chronic fatigue syndrome.
Int J Mol Med 1998;1:143-6.
10 Reiter WJ, Pycha A, Schatzl G, et al. Serum dehydroepiandrosterone sulfate concentrations in men with erectile dysfunction. Urology 2000;55:755-8.
11 Pepping J. DHEA: dehydroepiandrosterone. Am J Health Syst Pharm 2000;57:2048-50, 2053-4, 2056.
12 Arlt W, Callies F, van Vlijmen JC, et al. Dehydroepiandosterone replacement in women with adrenal insuffi ciency. N Engl J Med 1999;341:1013-20.
13 Casson PR, Andersen RN, Herrod HG, et al. Oral dehyroepiandosterone in physiologic doses modulates immune function in
postmenopausal women. Am J Obstet Gynecol 1995;1536-9.
14 Wit JM, Langenhorst VJ, Jansen M, et al. Dehydroepiandrosterone sulfate treatment for atrichia pubis. Horm Res 2001;56:134-9.
15 Strous RD, Maayan R, Lapidus R, et al. Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia. Arch Gen Psychiatry 2003;60:133-41.
16 Stomati M, Monteleone P, Casarosa E, et al. Six-month oral dehydroepiandrosterone supplementation in early and late postmenopause. Gynecol Endocrinol 2000;14:342-63.
17 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) 2001;55:325-30.
18 Van Vollenhoven RF, Morabito LM, Engleman EG, et al. Treatment of systemic lupus erythematosus with dehydroepiandrosterone: 50 patients treated up to 12 months. J Rheumatol 1998;25:285-9.
19 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 U S A 2000;97:4279-84.
20 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.
21 Labrie F, Diamond P, Cusan L, et al. Effect of 12 month dehydroepiandrosterone replacement therapy on bone, vagina, and
endometrium in postmenopausal women. J Clin Endocrinol Metab 1997;82:3498-505.
22 Arlt W, Callies F, van Vlijmen JC, et al. Dehydroepiandosterone replacement in women with adrenal insuffi ciency. N Engl J Med 1999;341:1013-20.
23 Johannsson G, Burman P, Wiren L, et al. Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-defi cient women: a placebo-controlled trial. J Clin Endocrinol Metab 2002;87:2046-52.
24 Kim SS, Brody KH. Dehydroepiandrosterone replacement in Addison’s disease. Eur J Obstet Gynecol Reprod Biol 2001;97:96-7.
25 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 U S A 2000;97:4279-84.
26 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.
27 Wolkowitz OM, Reus VI, Keebler A, et al. Double-blind treatment of major depression with dehydroepiandosterone. Am J Psychiatry 1999;156:646-9.
28 Bloch M, Schmidt PJ, Danaceau MA, et al. Dehydroepiandrosterone treatment of midlife dysthymia. Biol Psychiatry 1999;45:1533-41.
29 Reiter WJ, Pycha A, Schatzl G, et al. Dehydroepiandosterone in the treatment of erectile dysfunction: A prospective, double-blind, randomized, placebo-controlled study. Urol 1999;53:590-5.
30 Reiter WJ, Schatzl G, Mark I, et al. Dehydroepiandrosterone in the treatment of erectile dysfunction in patients with different organic etiologies. Urol Res 2001;29:278-81.
31 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.
32 Villareal DT, Holloszy JO. Effect of DHEA on abdominal fat and insulin action in elderly women and men. JAMA 2004;292:2243-8.
33 Sun Y, Mao M, Sun L, et al. Treatment of osteoporosis in men using dehydroepiandrosterone sulfate.Chin Med J (Engl)
34 Villareal DT, Holloszy JO, Kohrt WM. Effects of DHEA replacement on bone mineral density and body composition in elderly women and men. Clin Endocrinol (Oxf) 2000;53:561-8.
35 Gordon CM, Grace E, Emans SJ, et al. Effects of oral dehydroepiandrosterone on bone density in young women with anorexia nervosa: a randomized trial. J Clin Endocrinol Metab 2002;87:4935-41.
36 Van Vollenhoven RF, Morabito LM, Engleman EG, et al. Treatment of systemic lupus erythematosus with ehydroepiandrosterone: 50 patients treated up to 12 months. J Rheumatol 1998;25:285-9.
37 Van Vollenhoven RF, Engleman EG, McGurie JL. Dehydroepiandrosterone in Systemic Lupus Erythematosus. Arth
38 van Vollenhoven RF, Engleman EG, McGuire JL. Dehydroepiandrosterone in systemic lupus erythematosus. Arthritis
39 van Vollenhoven RF, Park JL, Genovese MC, et al. A double-blind, placebo-controlled, clinical trial of dehydroepiandrosterone in severe lupus erythematosus. Lupus 1999;8:181-7.
40 Petri MA, Mease PJ, Merrill JT, et al. Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus. Arthritis Rheum 2004;50:2858-68.
41 Petri MA, Lahita RG, Van Vollenhoven RF, et al. 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.
42 Labrie F, Diamond P, Cusan L, et al. Effect of 12 month dehydroepiandrosterone replacement therapy on bone, vagina, and
endometrium in postmenopausal women. J Clin Endocrinol Metab 1997;82:3498-505.
43 Casson PR, Faquin LC, Stentz FB. Replacement of dehydroepiandrosterone enhances T-lymphocyte insulin binding in
postmenopausal women. (abstract) Fertil Steril 1995;63:1027-31.
44 Morales AJ, Haubrich RH, Hwang JY, et al. The effect of six months treatment with 100 mg daily dose of ehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women. [Abstract] Clin Endocrinol (Oxf)1998;49:421-32.
45 Casson PR, Andersen RN, Herrod HG, et al. Oral dehyroepiandosterone in physiologic doses modulates immune function in
postmenopausal women. Am J Obstet Gynecol 1995;1536-9.
46 Barnhart KT, Freeman E, Grisso JA, et al. The effect of dehydroepiandrosterone supplementation to symptomatic perimenopausal women on serum endocrine profi les, lipid parameters, and healthrelated quality of life. J Clin Endocrinol Metab 1999;84:3896-902.
47 Wolkowitz OM, Reus VI, Keebler A, et al. Double-blind treatment of major depression with dehydroepiandosterone. Am J Psychiatry 1999;156:646-9.
48 Wolkowitz OM, Reus VI, Manfredi F, et al. Dehydroepiandrosterone (DHEA) treatment of depression. [Abstract]
Biol Psychiatry 1997;41:311-8.
49 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 U S A 2000;97:4279-84.