DHEA

Dehydroepiandrosterone is a steroid hormone, a chemical cousin of testosterone and estrogen.

Study reported in 2006 in Clin Endocrinol. shows that short-term treatment with DHEA increased platelet cGMP production, a marker of NO production, in healthy elderly subjects. This effect is coupled with a decrease in PAI-1 and LDL cholesterol levels as well as an increase in testosterone and E(2) levels. These findings, therefore, suggest that chronic DHEA supplementation would exert antiatherogenic effects, particularly in elderly subjects who display low circulating levels of this hormone.

Studies have shown that DHEA inhibits carcinogenesis in mammary gland and prostate as well as other organs, a process that is not hormone dependent (2006)

Although the analysis is limited by the short follow-up and small number of deaths, results are consistent with the notion that DHEAS level has a sizeable effect on mortality. (2006)

Dehydroepiandrosterone (DHEA), is a natural steroid prohormone produced from cholesterol by the adrenal glands, the gonads, adipose tissue, brain and in the skin (by an autocrine mechanism)]. DHEA is the precursor of androstenedione, testosterone and estrogen. It is the most abundant hormone in the human body.

Dehydroepiandrosterone
Systematic (IUPAC) name
3ß-hydroxy-5-androsten-17-one
Identifiers
CAS number	53-43-0
ATC code	A14AA07
PubChem	76
Chemical data
Formula	C19H28O2
Mol. mass	288.43
Physical data
Melt. point	148.5 °C (299 °F)
Pharmacokinetic data
Bioavailability	?
Metabolism	Hepatic
Half life	12 hours
Excretion	Urinary:?%
Therapeutic considerations
Pregnancy cat.	?
Legal status	Commercially available (US)
Routes	Oral

Synonyms and brand names

Synonyms for Dehydroepiandrosterone are: Dehydroisoandrosterone; 3β-Hydroxy-5-androsten-17-one; 3β-Hydroxyandrost-5-en-17-one; Androstenol; Androstenolone; Dehydroisoandrosterone; Hydroxyandrost-5-en-17-one; Prasterone; trans-Dehydroandrosterone.

Brand names for DHEA include Prastera® and Fidelin®.

 

DHEAS (Dehydroepiandrosterone sulfate)

Dehydroepiandrosterone sulfate (DHEAS, PubChem 12594) is the sulfated version of DHEA, - this conversion is reversibly catalyzed by sulfotransferase (SULT2A1) primarily in the adrenals, the liver, and small intestines. In blood, most DHEA is found as DHEAS with levels that are about 300 times higher than free DHEA. Orally ingested DHEA is converted to its sulfate when passing through intestines and liver. While DHEA levels reach their peak in the early morning hours, DHEAS levels show no diurnal variation.

From a practical point measurement of DHEAS is preferable to DHEA as levels are more stable.

 

Production

Production of DHEA from Cholesterol

DHEA is produced from cholesterol through two cytochrome P450 enzymes. Cholesterol is converted to pregnenolone by the enzyme P450 scc (side chain cleavage) and then another enzyme CYP17A1 converts pregnenolone to 17α-Hydroxypregnenolone and then to DHEA. In humans DHEA is the dominant steroid hormone and precursor of all sex steroids. Humans produce DHEA in greater quantity than any other species. Even non-human primates have not much more than 10% the relative serum level of DHEA seen in humans. The fact that rodents produce so little DHEA makes the results of experiments conducted with these laboratory animals very controversial.

DHEA production is very high during fetal life by the fetal adrenal glands, declines after birth and remains low during childhood. Production begins around 6 years of age, increasing in quantity until peaking in early adulthood, around the age of 25, and declines afterwards to approximately 10% of peak levels by age 80. It is theorized by some that this decline may be due to reduced oxygen and glucose supply to the adrenal glands as a result of age-related atherosclerosis.

 

Role

In a simple view DHEA can be understood as a prohormone for the sex steroids. Its DHEAS variation may be looked at as buffer and reservoir. Its production in the brain suggests that it also has a role as a neurosteroid. As most DHEA is produced by the zona reticularis of the adrenal, it is argued that there is a role in the immune and stress response. DHEA may have more biologic roles.

As almost all DHEA is derived from the adrenal glands, blood measurements of DHEAS/DHEA are useful to detect excess adrenal activity as seen in adrenal cancer or hyperplasia, including certain forms of congenital adrenal hyperplasia. Women with polycystic ovary syndrome tend to have normal or mildly elevated levels of DHEAS.

 

Effects

Studies have shown that DHEA is useful in patients with systemic lupus erythematosus. An application of the evidence was reviewed by the FDA in 2001 and is available online. This review also shows that cholesterol and other serum lipids decrease with the use of DHEA (mainly a decrease in HDL-C and triglycerides can be expected in women, p110).

Supplementation with DHEA has been shown to decrease insulin resistance.

Long term supplementation has been shown to improve mood and relieve depression.

 

Disputed effects

The significance of the hormone in health and disease is not fully established. It is postulated that DHEA supplements are beneficial in alleviating:

• cardiovascular disease
• diabetes
• hypercholesterolemia
• obesity
• multiple sclerosis
• Parkinson's disease
• Alzheimer's disease
• disorders of the immune system
• depression
• osteoporosis
• decreased libido
• decreased orgasmic intensity

It is also commercially advertised that DHEA:

• helps decrease insulin resistance
• improves fat metabolism
• increases immune system function
• has anti-aging properties
• increases lean muscle mass

7-Keto™ DHEA, a recently identified metabolite of dehydroepiandrosterone (DHEA) is claimed to be both more effective and safer than DHEA because it does not convert itself into testosterone or estrogens in the body.

DHEA and DHEAS are readily available in the United States.

 

Precautions

Some assert that DHEA should not be supplemented outside specialist centres under careful observation of experts in the field of endocrinology.

Side effects may include:

• Palpitations and other arrhythmias
• extensive growth of body hair, or hirsutism
• Hair loss, especially male pattern baldness
• acne

 

Contraindication

As DHEAS and DHEA are converted to sex steroids, their use is contraindicated in patients with any cancer that is estrogen or testosterone dependent.

 

Increasing endogenous production

Regular exercise is known to increase DHEA production in the body. Caloric restriction has also been shown to increase DHEA in primates.

 

See also

• Steroid hormones
• Testosterone
• Estrogen

 

Further reading

• Nutrition through the Life Cycle, Judith E. Brown, ISBN 0-534-58986-3
• Andus T, et al. Patients with refractory Crohn's disease or ulcerative colitis respond to dehydroepiandrosterone: a pilot study. Aliment Pharmacol Ther. 2003 Feb;17(3):409-14.
  Arlt W, Callies F, Allolio B. DHEA replacement in women with adrenal insufficiency--pharmacokinetics, bioconversion and clinical effects on well-being, sexuality and cognition. Endocr Res. 2000 Nov;26(4):505-11.
  Chang DM, et al. Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002 Nov;46(11):2924-7.
  Gordon CM, et al. Effects of oral DHEA on bone density in young women with anorexia nervosa: a randomized trial. J Clin Endocrinol Metab. 2002 Nov;87(11):4935-41.
  Hackbert L, Heiman JR. Acute dehydroepiandrosterone (DHEA) effects on sexual arousal in postmenopausal women. J Womens Health Gend Based Med. 2002 Mar;11(2):155-62.
  Hirshman E, et al. The effect of dehydroepiandrosterone (DHEA) on recognition memory decision processes and discrimination in postmenopausal women. Psychon Bull Rev. 2003 Mar;10(1):125-34.
  Johannsson G, et al. Low dose DHEA affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial. J Clin Endocrinol Metab. 2002 May;87(5):2046-52.
  Kawano H, et al. DHEA supplementation improves endothelial function and insulin sensitivity in men. J Clin Endocrinol Metab. 2003 Jul;88(7):3190-5.
  Lovas K, et al. Replacement of DHEA in adrenal failure: no benefit for subjective health status and sexuality in a 9-month, randomized, parallel group clinical trial. J Clin Endocrinol Metab. 2003 Mar;88(3):1112-8.
  Percheron G, et al. Effect of 1-year oral administration of DHEA to 60- to 80-year-old individuals on muscle function and cross-sectional area: a double-blind placebo-controlled trial. Arch Intern Med. 2003 Mar 24;163(6):720-7.
  Piketty C, et al. Double-blind placebo-controlled trial of oral DHEA in patients with advanced HIV disease. Clin Endocrinol (Oxf). 2001 Sep;55(3):325-30.
  Sahelian, R, Borken, S. DHEA and cardiac arrhythmia. Ann Intern Med. 1998 Oct 1;129(7):588.
  Sun Y, et al. Treatment of osteoporosis in men using dehydroepiandrosterone sulfate. Chin Med J (Engl). 2002 Mar;115(3):402-4.
  
  Andus T, et al. Patients with refractory Crohn's disease or ulcerative colitis respond to DHEA: a pilot study. Aliment Pharmacol Ther. 2003 Feb;17(3):409-14.
  Arlt W, Callies F, Allolio B. DHEA replacement in women with adrenal insufficiency--pharmacokinetics, bioconversion and clinical effects on well-being, sexuality and cognition. Endocr Res. 2000 Nov;26(4):505-11.
  Chang DM, et al. DHEA treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002 Nov;46(11):2924-7.
  Gordon CM, et al. Effects of oral dehydroepiandrosterone on bone density in young women with anorexia nervosa: a randomized trial. J Clin Endocrinol Metab. 2002 Nov;87(11):4935-41.
  Hackbert L, Heiman JR. Acute dehydroepiandrosterone (DHEA) effects on sexual arousal in postmenopausal women. J Womens Health Gend Based Med. 2002 Mar;11(2):155-62.
  Hirshman E, et al. The effect of dehydroepiandrosterone (DHEA) on recognition memory decision processes and discrimination in postmenopausal women. Psychon Bull Rev. 2003 Mar;10(1):125-34.
  Johannsson G, et al. Low dose DHEA affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial. J Clin Endocrinol Metab. 2002 May;87(5):2046-52.
  Kawano H, et al. DHEA supplementation improves endothelial function and insulin sensitivity in men. J Clin Endocrinol Metab. 2003 Jul;88(7):3190-5.
  Lovas K, et al. Replacement of DHEA in adrenal failure: no benefit for subjective health status and sexuality in a 9-month, randomized, parallel group clinical trial. J Clin Endocrinol Metab. 2003 Mar;88(3):1112-8.
  Percheron G, et al. Effect of 1-year oral administration of DHEA to 60- to 80-year-old individuals on muscle function and cross-sectional area: a double-blind placebo-controlled trial. Arch Intern Med. 2003 Mar 24;163(6):720-7.
  Piketty C, et al. Double-blind placebo-controlled trial of oral DHEA in patients with advanced HIV disease. Clin Endocrinol (Oxf). 2001 Sep;55(3):325-30.
  Sahelian, R, Borken, S. DHEA and cardiac arrhythmia. Ann Intern Med. 1998 Oct 1;129(7):588.
  Sun Y, et al. Treatment of osteoporosis in men using DHEA sulfate. Chin Med J (Engl). 2002 Mar;115(3):402-4.

External links

• The DHEA Debate: A critical review of experimental data at lef.org (Published 2004){This link is to the web equivalent of an infomercial. Unreliable sponsored analysis)
• DHEA: Ignore the Hype (Published 1996) at Quackwatch
• DHEA Hormone Replacement at benbest.com
• What the Skeptic's Dictionary has to say on DHEA
• Nair K, Rizza R, O'Brien P, Dhatariya K, Short K, Nehra A, Vittone J, Klee G, Basu A, Basu R, Cobelli C, Toffolo G, Dalla Man C, Tindall D, Melton L, Smith G, Khosla S, Jensen M (2006). "DHEA in elderly women and DHEA or testosterone in elderly men". N Engl J Med 355 (16): 1647-59. PMID 17050889.  link
  
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