Dehydroepiandrosterone (DHEA) – Anti Aging

Dehydroepiandrosterone (DHEA)

Description

Dehydroepiandrosterone (DHEA) is the most abundant hormone secreted by the adrenal glands. It is a steroid hormone and secreted by the zona reticularis of the adrenals. DHEA circulates in the blood as dehydroepiandrosterone-3-sulphate (DHEAS), which is converted as required to DHEA. Production of DHEA in humans normally peaks between the ages of 20 and 30 years, and then begins a steady progressive decline.

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Action

DHEA and DHEAS are the precursors for other hormones, including oestrogens and androgens. The degree of androgenic versus oestrogenieffect of DHEA may depend on the individual’s hormonal status. For example, there is some evidence that DHEA has different effects in pre-menopausal and post-menopausal women.DHEA has also been shown to stimulate insulin growth factor-1 (IGF-1),3 a hormone that stimulates anabolic metabolism, enhances insulin sensitivity, accelerates muscle growth and enhances energy production.

Possible uses

Supplementation with DHEA has been claimed to produce several health benefits including enhancement of immune function, increased muscle mass, improvements in memory and mood, improvement in symptoms of autoimmune disorders such as lupus erythematosus, and to have a general anti-ageing effect. However, evidence for a beneficial effect of DHEA supplements in all these conditions is inconclusive.

Immunity

The first in vivo evidence of an immuno-modulatory effect of DHEA came from a prospective, randomised, double-blind, crossover study involving 11 post-menopausal women with 3-week treatment arms. Results showed that DHEA supplementation reduced T helper cell populations and increased natural killer cell populations. In a single-blind, placebo-controlled study, nine healthy men (mean age 63 years) were supplemented with a placebo for 2 weeks, followed by DHEA 50 mg daily for 20 weeks.5 DHEA stimulated immune function by significantly increasing the number of monocyte and B cells, stimulating B- and T-cell mitogenic response, interleukin-2 secretion and the number and cytotoxicity of natural killer cells. The authors acknowledged that the results of this study had limited application because post-treatment immune response was not measured. However, in two other studies,6,7 DHEA produced no significant effects on antibody response to influenza vaccine.

Body composition

In a double-blind, placebo-controlled study, 10 healthy men were randomised to receive either 1600 mg DHEA or placebo daily for 28 days. Compared with placebo, body fat was reduced significantly, by 31% in the supplemented group, but there was no change in body weight. There was also a 7.5% reduction in LDL cholesterol.8 Furthermore, in another randomised, double-blind, placebo-controlled study in morbidly obese adolescents,9 40 mg DHEA twice a day had no effect on body weight. In two other studies,10,11 DHEA 1600 mg daily Dehydroepiandrosterone for 4 weeks had no significant effect on body weight or lean body mass.

Memory, mood and depression

In a double-blind, placebo-controlled crossover study, 30 healthy subjects aged 40–70 years were randomised to receive in random order either 50 mg DHEA or placebo daily for 3 months each. During DHEA supplementation there was a significant increase in perceived physical and psychological well-being. There was no effect on insulin sensitivity, body fat or libido. In a double-blind, placebo-controlled crossover study, 17 healthy, elderly male subjects received 50 mg DHEA daily or a

placebo for 2 weeks. There was no change in memory or mood in the supplemented group. A Cochrane systematic review14 investigated the effect of DHEA supplementation on cognition and well-being. Five studies matched the reviewers’ criteria, four of which were short-term (DHEA administered for 2 weeks or less) and one where DHEA was given for 3 months.. There was no significant change in ability to perform cognitive tests, or mood or well-being (as assessed by standard scales) in the short-term studies. In the longer-term study, results of an open-ended questionnaire showed that 67% of men and 82% of women reported enhanced well-being with DHEA compared with placebo. The reviewers concluded that present data offer limited support for a beneficial effect of DHEA on well-being, but not on memory or cognitive function. In a double-blind, placebo-controlled study, 32 patients with severe depression, either medication-free or stabilised on anti-depressants, received either DHEA (maximum dose 90 mg daily) or placebo for 6 weeks.. DHEA was associated with a significantly greater decrease in the Hamilton depression rating scale than placebo, and five of the 11 patients treated with DHEA compared with none of the 11 subjects in the placebo group showed a 50% or greater reduction in symptoms of depression. In a small double-blind RCT, DHEA (50 mg twice a day) did not significantly improve cognitive performance or overall ratings of change in severity. A transient effect on cognitive performance may have been seen at month, but this narrowly missed significance.

A study in patients with schizophrenia found that DHEA (up to 100 mg daily) was associated with significant improvement in negative symptoms as well as in depressive and anxiety symptoms in individuals receiving DHA.Plasma levels of DHEA fall with the progression of HIV diseases and DHEA is being investigated for potential benefit. A study in 32 patients with advanced HIV disease found improved mental function scores with DHEA 50 mg daily for 4 months..

Systemic lupus erythematosus

In a double-blind, placebo-controlled study, 28 women with mild to moderate systemic lupus erythematosus (SLE) were randomised to receive 200 mg DHEA or placebo daily for 3 months. In the supplemented group, there were insignificant improvements in SLE Disease Activity Index scores, physicians’ assessment of disease activity and a reduction in the dose of prednisone used. There was a significant improvement in patients’ assessment of disease activity with DHEA compared with placebo.

In an open study, 50 women with mild to moderate SLE were treated with 50–200 mg of DHEA daily for 6–12 months. Supplementation was associated with a significant reduction in disease activity and significant improvement in patient and physician assessment compared to baseline.

In a double-blind RCT, 120 adult women with active SLE received oral DHEA (200 mg daily) or placebo for 24 weeks. DHEA treatment was well tolerated, significantly reduced the number of SLE flares and improved patients’ global assessment of disease activity.

Miscellaneous

There is no evidence that DHEA supplements prevent ageing in humans. Reports have suggested that DHEA might reduce the risk of heart disease. Epidemiological studies have been conflicting, and although some animal and human studies have shown that DHEA may reduce LDL cholesterol and platelet aggregation, controlled trials are needed to assess the effects of DHEA supplementation on cardiovascular risk.

Dehydroepiandrosterone

DHEA has also been reported to improve insulin sensitivity and reduce blood glucose levels, but again results from studies have been conflicting. One small study in 24 menfound that DHEA 25 mg daily improved insulin sensitivity and vascular endothelial function and decreased the plasma activator inhibitor type 1 concentration. The authors concluded that these beneficial changes have the potential

to attenuate the development of age-related disorders such as CVD.

DHEA has also been investigated for an effect on bone turnover. An RCT in young women with anorexia nervosa compared the effects of DHEA with hormone replacement therapy (HRT). In initial analyses, total hip BMD increased significantly and similarly in both treatment groups. Bone formation markers increased transiently at 6–9 months in the DHEA compared with the HRT group and both treatments significantly reduced bone resorption markers. However, both groups gained weight and after correcting for weight gain, there was no treatment effect. In addition, DHEA was associated with improvement in specific psychological parameters. In another study in middle-aged to elderly men, oral DHEA did not affect bone turnover when used for a 6-month period.

It is often claimed that individuals can enhance their muscle capacity by boosting DHEA levels through oral supplementation. A 12-month study in 280 healthy men and women (aged 60–89 years) found that the supplement restored DHEA levels to the normal range for young adults. However, there were no beneficial effects on muscle state.

Conclusion

The role of DHEA supplements in all conditions studied is inconclusive. Some studies have shown that DHEA improves the immune response while others have not..There is no good evidence that DHEA helps to reduce body weight. There is limited evidence that it may improve well-being and reduce symptoms of depression, but it seems to have no effect on memory or cognition. Preliminary evidence suggests that DHEA could improve symptoms of SLE.

 

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Precautions/contraindications

DHEA is contraindicated in individuals who have (or have a history of) prostate cancer or oestrogen-dependent tumours (e.g. breast or uterine cancer). It should be used with caution in patients with diabetes mellitus (because it may alter blood glucose regulation). Blood glucose and doses of insulin and oral hypoglycaemics should be monitored in patients with diabetes.

Pregnancy and breast-feeding

The effects of DHEA in pregnancy and breast-feeding are unknown. It is probably best avoided.

Adverse effects

There is no known toxicity or serious side-effects. However, the safety of long-term administration is unknown. DHEA alters the levels of other hormones, and has both oestrogenic and androgenic activity. Potential side-effects in women are therefore increased facial hair and increased loss of head hair, menstrual irregularities and deepening of the voice. The risk of breast cancer may also be increased, but results from studies are conflicting, with some showing that DHEA may reduce risk while others show that it may increase risk. A review concluded that prolonged intake of DHEA may promote breast cancer in post-menopausal women.26 Potential side-effects in men include an increased risk of prostate

cancer. A study in 22 healthy men27 suggested that doses up to 200 mg daily for 4 weeks were safe and well tolerated. Another study in 24 healthy elderly men and women (67.8 ± 4.3 years) suggested that daily doses of 25 or 50 mg DHEA are safe in elderly subjects. There were no large increases in blood levels of androgens and oestrogens in this study.

Interactions

None reported, but theoretically DHEA could interact with insulin, oral hypoglycaemic agents, oestrogens (including HRT) and androgens.

Dose

DHEA is available in the form of tablets and capsules. The dose is not established. Dietary supplements tend to provide 5–100 mg daily.

References

 

 

Nafziger AN, Bowlin SJ, Jenkins PL, et al. Longitu-

dinal changes in dihydroepiandrosterone sulfate and

concentrations in men and women. J Lab Clin Med

1998; 131: 316–323.

 

Ebeling P, Koivisto VA. Physiological importance

of dehydroepiandrosterone. Lancet 1994: 343;

1479–1481.

 

Casson PR, Santoro N, Elkind-Hirsch K, et al.

Postmenopausal dehydroepiandrosterone adminis-

tration increases free insulin-like growth factor-1

and decreases high density lipoprotein: a six-month

trial. Fertil Steril 1998; 70: 107–110.

 

Casson PR, Andersen RN, Herrod HG, et al.

Oral dehydroepiandrosterone in physiologic doses

modulates immune function in postmenopausal

women. Am J Obstet Gynecol 1993; 169:

1536–1539.

 

Khorram O, Vu L, Yen SS. Activation of immune

function by dehydroepiandrosterone (DHEA) in age-

advanced men. J Gerontol A Biol Sci Med Sci 1997;

52: M1–M7.

 

Degelau J, Guay D, Hallgren H. The effect of

DHEAS on influenza vaccine in aging adults. J Am

Geriatr Soc 1997; 45: 747–751.

 

Ben-Yehuda A, Daneberg HD, Zakay-Rones Z, et

al. The influence of sequential annual vaccination

and of DHEA administration on the efficacy of the

immune response to influenza vaccine in the elderly.

Mech Ageing Dev 1998: 102: 299–306.

 

Nestler JE, Barlascini CO, Clore JN, et al. De-

hydroepiandrosterone 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.

 

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:

1011–1015.

 

Welle S, Jozefowicz R, Statt M. Failure of dehydro-

epiandrosterone to influence energy and protein

metabolism in humans. J Clin Endocrinol Metab

1990; 71: 1259–1264.

 

Usiskin KS, Butterworth S, Clore JN, et al. Lack of

effect of dehydroepiandrosterone in obese men. Int

J Obes 1990; 14: 457–463.

 

Morales AJ, Nolan JJ, Nelson JC, et al. Effects of

replacement dose of DHEA in men and women of

advancing age. J Clin Endocrinol Metab 1994; 78:

1360–1367.

13

Wolf OT, Naumann E, Helhammer DH, et al. Effects

of dehydroepiandrosterone replacement in elderly

men on event-related potentials, memory and well

being. J Gerontol A Biol Med Sci Med Sci 1998; 53:

M385–M3990.

14

Huppert FA, Van Nickerk JK, Herbert J. Dehydro-

epiandrosterone (DHEA) supplementation for

cognition and well being. Cochrane database, issue

2, 2000. London: Macmillan.

15

Wolkowitz OM, Reus VI, Keebler A, et al. Double-

blind treatment of major depression with dehydro-

epiandrosterone. Am J Psychiatry 1999; 156:

646–649.

16

Wolkowitz OM, Kramer JH, Reus VI, et al. DHEA

treatment of Alzheimer’s disease: a randomized,

double-blind, placebo-controlled study. Neurology

2003; 60: 1071–1076.

 

17

Strous RD, Maayan R, Lapidus R, et al. Dehydro-

epiandrosterone augmentation in the management

of negative, depressive, and anxiety symptoms in

schizophrenia. Arch Gen Psychiatry 2003; 60:

133–141.

 

18

Piketty C, Jayle D, Leplege A, et al. Double-blind

placebo-controlled trial of oral dehydroepiandro-

sterone in patients with advanced HIV disease. Clin

Endocrinol 2001; 55: 325–330.

 

19

Van Vollenhoven RF, Engleman EG, McGuire

GL, et al. Dehydroepiandrosterone in systemic

lupus erythematosus. Results of a double-blind,

placebo-controlled, randomised clinical trial. Arthri-

tis Rheum 1995; 38: 1826–1831.

 

20

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:

285–289.

 

21

Chang DM, Lan JL, Lin HY, Luo SF.

Dehydroepiandrosterone treatment of women with

mild-to-moderate systemic lupus erythmatosus: a

multicenter, randomized, double-blind, placebo-

controlled trial. Arthritis Rheum 2002; 46:

2924–2927.

 

22

Kawano H, Yasue H, Kitagawa A, et al.

Dehydroepiandrosterone supplementation improves

endothelial function and insulin sensitivity in

men. J Clin Endocrinol Metab 2003; 88:

3190–3195.

 

23

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:

4935–4941.

 

24

Kahn AJ, Halloran B, Wolkowitz O, Brizendine L.

Dehydroepiandrosterone supplementation and bone

turnover in middle-aged to elderly men. J Clin

Endocrinol Metab 2002; 87: 1544–1549.

 

25 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:

720–727.

 

26 Stoll BA. Dietary supplements of dehydroepiandro-

sterone in relation to breast cancer risk. Eur J Clin

Nutr 1999; 53: 771–775.

 

27 Davidson M, Marwah A, Sawchuk RJ, et al.

Safety and pharmacokinetic study with escalating

doses of 3-acetyl-7-oxo-dehydroepiandrosterone in

healthy male volunteers. Clin Invest Med 2000; 23:

300–310.

 

28 Legrain S, Massien C, Lahlou N, et al. De-

hydroepiandrosterone replacement administration:

pharmacokinetic and pharmacodynamic studies in

healthy elderly subjects. J Clin Endocrinol Metab

2000; 85: 328–317.

 

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