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DHEA

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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.

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. <table id="drugInfoBox" style="CLEAR: right; BACKGROUND: #ffffff; FLOAT: right; MARGIN: 0px 0px 0.5em 1em" cellpadding="1" width="280" align="right" border="0" class="toccolours"> <tbody> <tr> <td align="center" colspan="2"><a class="image" title="" href="http://en.wikipedia.org/wiki/Image:Dehydroepiandrosterone.png"><img height="118" alt="" width="177" longdesc="/pwiki/Image:Dehydroepiandrosterone.png" src="http://upload.wikimedia.org/wikipedia/en/9/98/Dehydroepiandrosterone.png" /></a></td> </tr> <tr> <td align="center" colspan="2"> <div style="FONT-SIZE: medium; LINE-HEIGHT: 167%">Dehydroepiandrosterone</div> </td> </tr> <tr> <td bgcolor="#dddddd" colspan="2">Systematic (<a title="International Union of Pure and Applied Chemistry nomenclature" href="http://en.wikipedia.org/wiki/International_Union_of_Pure_and_Applied_Chemistry_nomenclature">IUPAC</a>) name</td> </tr> <tr> <td style="VERTICAL-ALIGN: top; TEXT-ALIGN: center" bgcolor="#eeeeee" colspan="2">3ß-hydroxy-5-androsten-17-one</td> </tr> <tr> <td bgcolor="#dddddd" colspan="2">Identifiers</td> </tr> <tr> <td width="90" bgcolor="#ddeeff"><a title="CAS registry number" href="http://en.wikipedia.org/wiki/CAS_registry_number">CAS number</a></td> <td bgcolor="#eeeeee"><a class="external text" title="http://www.nlm.nih.gov/cgi/mesh/2006/MB_cgi?term=53-43-0&rn=1" rel="nofollow" href="http://www.nlm.nih.gov/cgi/mesh/2006/MB_cgi?term=53-43-0&rn=1">53-43-0</a></td> </tr> <tr> <td bgcolor="#ddeeff"><a title="Anatomical Therapeutic Chemical Classification System" href="http://en.wikipedia.org/wiki/Anatomical_Therapeutic_Chemical_Classification_System">ATC code</a></td> <td bgcolor="#eeeeee"><a title="ATC code A14" href="http://en.wikipedia.org/wiki/ATC_code_A14">A14</a><a class="external text" title="http://www.whocc.no/atcddd/indexdatabase/index.php?query=A14AA07" rel="nofollow" href="http://www.whocc.no/atcddd/indexdatabase/index.php?query=A14AA07">AA07</a></td> </tr> <tr> <td bgcolor="#ddeeff"><a title="PubChem" href="http://en.wikipedia.org/wiki/PubChem">PubChem</a></td> <td bgcolor="#eeeeee"><~~script type~~span class="reflink plainlinksneverexpand"><a class="external text" title="http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=76" rel="nofollow" href="http:/~~javascript~~/pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=76">76</a></td> </tr> <tr> <td bgcolor="#dddddd" colspan="2">Chemical data</td> </tr> <tr> <td bgcolor="#ddeeff"><a title="Chemical formula" href="http://en.wikipedia.org/wiki/Chemical_formula">Formula</a><~~![CDATA[~~/td> if <td bgcolor="#eeeeee"><a title="Carbon" href="http://en.wikipedia.org/wiki/Carbon">C</a>19<a title="Hydrogen" href="http://en.~~showTocToggle~~wikipedia.org/wiki/Hydrogen">H</a>28<a title="Oxygen" href="http://en.wikipedia.org/wiki/Oxygen">O</a>2  ~~var tocHideText~~ </td> </tr> <tr> <td bgcolor= "~~hide~~#ddeeff"><a title="Molecular mass" href="http://en.wikipedia.org/wiki/Molecular_mass">Mol. mass</a></td> <td bgcolor="#eeeeee">288.43</td> </tr> <tr> <td bgcolor="#dddddd" colspan="2">Physical data</td> </tr> <tr> <td bgcolor="#ddeeff"><a title="Melting point" href="http://en.wikipedia.org/wiki/Melting_point">Melt. point</a></td> <td bgcolor="#eeeeee">148.5 ° ~~showTocToggle~~C (299 °F)~~; }~~ </td> </tr> <tr> <td bgcolor="#dddddd" colspan="2">Pharmacokinetic data</]]td> </~~script~~tr> <tr> <ptd style="VERTICAL-ALIGN: top" bgcolor="#ddeeff"><a title="Bioavailability" href="http://en.wikipedia.org/wiki/Bioavailability">Bioavailability</a></td> <td bgcolor="#eeeeee"> ?</td> </tr> <tr> <td style="VERTICAL-ALIGN: top" bgcolor="#ddeeff"><a title="Drug metabolism" href="http://en.wikipedia.org/wiki/Drug_metabolism">Metabolism</a></td> <td bgcolor="#eeeeee"><a title="Liver" href="http://en.wikipedia.org/wiki/Liver">Hepatic</a></td> </tr> <tr> <td style="VERTICAL-ALIGN: top" bgcolor="#ddeeff"><a title="Biological half-life" href="http://en.wikipedia.org/wiki/Biological_half-life">Half life</a></td> <td bgcolor="#eeeeee">12 hours</td> </tr> <tr> <td style="VERTICAL-ALIGN: top" bgcolor="#ddeeff"><a title="Excretion" href="http://en.wikipedia.org/wiki/Excretion">Excretion</a></td> <td bgcolor="#eeeeee"><a title="Urine" href="http://en.wikipedia.org/wiki/Urine">Urinary</a>:?%</td> </tr> <tr> <td bgcolor="#dddddd" colspan="2">Therapeutic considerations</td> </tr> <tr> <td style="VERTICAL-ALIGN: top" bgcolor="#ddeeff"><a title="Pregnancy category" href="http://en.wikipedia.org/wiki/Pregnancy_category">Pregnancy cat.</a></td> <td bgcolor="#eeeeee"> ? </td> </tr> <tr> <td style="VERTICAL-ALIGN: top" bgcolor="#ddeeff"><a title="Regulation of therapeutic goods" href="http://en.wikipedia.org/wiki/Regulation_of_therapeutic_goods">Legal status</a></td> <td bgcolor="#eeeeee"> Commercially available (<a title="United States" href="http://en.wikipedia.org/wiki/United_States">US</a>) </td> </tr> <tr> <td style="VERTICAL-ALIGN: top" bgcolor="#ddeeff"><a title="Route of administration" href="http://en.wikipedia.org/wiki/Route_of_administration">Routes</a></td> <td bgcolor="#eeeeee"><a title="Mouth" href="http://en.wikipedia.org/wiki/Mouth">Oral</a></td> </tr> </tbody></table><h2p> Synonyms and brand names</h2p>

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®.

<h2p> DHEAS (Dehydroepiandrosterone sulfate)</h2p>

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.

<h2p> Production</h2p>

Production of DHEA from Cholesterol</div>

</div>

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.

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.

<h2p> Beneficial Effects</h2p>

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.[1] 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.[2]

Long term supplementation has been shown to improve mood and relieve depression.[3]

It is suggested that DHEA's beneficial effects arise from its antioxidant, antiobesity, antilipofuscin, antilipidperoxidative and thereby anti-aging actions. <a href="javascript:AL_get(this, 'jour', 'Biogerontology.');">Biogerontology.</a> 2008 Feb 29 <h3p>Disputed effects</h3p>Hormonal substitution with DHEA, testosterone, and growth hormone is ineffective as anti-aging medicine, while calcium and vitamin d'effectiveness was confirmed in fracture prevention. <a href="javascript:AL_get(this, 'jour', 'Rev Med Suisse.');">Rev Med Suisse.</a> 2008 Jan 9;4(139):18-20, 22-3 The significance of the hormone in health and disease is not fully established. It is postulated that DHEA supplements are beneficial in alleviating:

<ul>

<li>cardiovascular disease </li>

DHEA and DHEAS are readily available in the United States.

<h2p>Precautions</h2p>

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:

</ul>

<h2p>Contraindication</h2p>

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

<h2p>Increasing endogenous production</h2p>

Regular exercise is known to increase DHEA production in the body.[4][5][6] Caloric restriction has also been shown to increase DHEA in primates.[7]

<ul>

<li>Nutrition through the Life Cycle, Judith E. Brown, <a class="internal" href="http://en.wikipedia.org/w/index.php?title=Special:Booksources&isbn=0534589863">ISBN 0-534-58986-3</a> </li>

<li>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.