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DHEA |
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One of the most abundant steroids in the human body – DHEA is produced by the adrenal glands and then converted into the hormones - estrogen and testosterone. Other common names for DHEA include: dehydroepiandrosterone, dehydroepiandrosterone sulfate; prescription brand names include: Prastera, Fidelin, and Flasterone.
DHEA levels in people peak in the early 20s, and decrease steadily as we age. By the age of 80, the estimated production level of DHEA is about five to ten percent of that during the period of peak production. When orally ingested, DHEA is converted by the intestines and liver into its sulfated form, dehydroespiandrosterone sulfate (DHEAS). In the majority of studies, scientists prefer to measure levels of DHEAS (rather than DHEA) due to its comparative blood plasma stability.
DHEA supplementation is widely popular because lower levels of DHEA have been associated with older populations, as well as with those suffering from: type 2 diabetes, breast cancer, osteoporosis, heart disease, AIDS, adrenal insufficiency, kidney disease, and anorexia. DHEAS measurements are also useful for detecting surplus adrenal activity – an indicator of adrenal cancer or tumors.
Some evidence exists supporting the success of DHEA in treating adrenal insufficiency, systemic lupus erythematosus, and depression. However, the majority of DHEA studies occur over a short period of time, and with a small number of participants. It is unlikely that there will be larger trials with a longer duration of treatment, as DHEA is rapidly converted into testosterone and estrogen may increase the risk of hormone-sensitive cancers such as breast and prostate cancer.
In the United States, purchase of DHEA required a prescription until 1995, when it became widely available as an over-the-counter nutritional supplement. Legislation is underway to re-classify DHEA as a “controlled substance under the category of anabolic steroids.”
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DHEA was first isolated in its free form in human urine by Dr. Adolf Buternandt in 1934. Dr. Buternandt would later win the Nobel Prize for chemistry in 1939. Ten years later, scientists isolated the sulphated form of DHEA – DHEAS. In 1959, Dr. Max Fernand Jayle, Professor of Biochemistry at the Faculty of Medicine of Paris, determined the proportional linear decrease of DHEA with progressive aging.
Following wild media claims about the benefits of DHEA in the 60s – DHEA supplements were taken off the market in the United States in 1985. A prescription was required for DHEA until 1994, when it was reintroduced as a nutritional supplement after the passing of the Dietary Supplement Health and Education Act. To this day, Canada requires a prescription to buy DHEA. In March 2007, a bill was introduced in the US Senate (S. 762) attempting to re-classify DHEA as a controlled substance.
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DHEA is currently being studied as an “anti-aging” hormone due to the direct correlation of decline in DHEA levels with aging markers such as loss of muscle mass, decreased bone density, and decline in immune function. Small amounts of clinical evidence shows that DHEA supplementation: can lead to slight increase in muscle mass in elderly men (aged 60 and over); can lead to a slight increase in sexual feelings in women; may have some skin-protective effects as a topical agent; and may increase the mental function and bone mass in women with Systemic Lupus Erythematosus (an autoimmune disease affecting connecting tissue).
DHEA is being studied as a possible treatment in many other areas, though there currently exists very little evidence showing that it is effective. These other areas of treatment include: alleviation of depression; reduction of insufficient adrenal function (Addison’s disease); HIV/AIDS; Alzheimer’s disease; Chronic Fatigue Syndrome; Crohn’s disease (inflammation of the digestive system); heart disease; schizophrenia; Sjogren’s syndrome (an autoimmune disorder in which immune cells attack and destroy the glands that produce saliva and tears); cervical cancer; cocaine withdrawal; induction of labor; infertility (specifically for women with ovulation disorders); menopausal disorders and symptoms (e.g. hot flashes, vaginal pain, fatigue, and depression); myotonic dystrophy (the wasting of muscles and other bodily systems); partial androgen deficiency (restoring DHEA levels in the elderly); psoriasis; rheumatoid arthritis; post-menopause fibromyalgia; improving immune system function; improving memory function; improving muscle strength and function; improving dementia; amenorrhea associated with anorexia; and alleviation of allergic disorders.
Further research is needed before firm conclusions can be drawn in any of these areas. Since DHEA is a hormone, most studies designed have small subject populations and short treatment durations. Many more trials are needed before the definitive benefits of DHEA can be fully tallied.
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Sources and Forms of DHEA: |
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DHEA is produced in the body, with the majority being excreted from the adrenal glands and smaller amounts made independently in the brain and ovaries. DHEA in supplemental form is made in a laboratory from diosgenin, an extract found in soybeans and wild yam. While many products tout wild yam supplements as a “natural form” of DHEA, the human body is incapable of converting wild yam to DHEA. This process is only possible in a laboratory setting.
Methods of increasing production of DHEA in the body (without supplementation) can include regular exercise and caloric restriction. Weight loss by means of caloric restriction has been shown to increase serum DHEAS levels in men. DHEA supplements can be purchased in health food stores or online health websites. Officially classified as a nutritional supplement, the FDA has not approved DHEA supplementation for any use. DHEA can be purchased as a capsule, tablet, or injection.
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Recommended Dosage of DHEA: |
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Currently classified as a nutritional supplement, the FDA does not regulate the production of DHEA supplements. Potency and ingredients may vary widely between brands and within brands.
Commonly used doses range from 25 to 200 mg daily. The longest known duration of (safe) daily DHEA usage has been one year. Higher doses of 200 to 500 mg per day have been used as treatment for depression and HIV/AIDS. One small study found that 25 mg a day of DHEA may reduce symptoms of menopause. DHEA creams in 2% concentrations have been shown to increase collagen synthesis in skin. DHEA should never be taken by anyone under the age of 18, as DHEA could interfere with normal hormone balance and growth.
Always consult a medical professional prior to beginning taking any nutritional supplement
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Safety and Side Effects of DHEA: |
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As a precursor hormone to other male and female hormones, there may be side effects associated with its hormonal activities. These hormonal side effects in women may include masculinization, acne, greasy skin, facial hair, hair loss, increased sweating, weight gain (especially in the abdomen), and a deeper voice. Men may develop prominent breasts (gynecomastia), increased blood pressure, wasting of the testicles, increased aggressiveness, and breast tenderness. Both sexes may also experience increased blood sugar levels, increasing insulin resistance, increased cholesterol levels, altered thyroid hormone levels, and other hormonal abnormalities.
DHEA may increase the risk of prostate, breast, or ovarian cancer. Other side effects may include insomnia, agitation, delusions, mania, psychosis, irritability, and nervousness. DHEA may contribute to tamoxifen resistance in breast cancer, and excessive supplementation has been shown to correlate with Cushing’s syndrome (an endocrine disorder due to excessive cortisol). Some medications may deplete natural reserves of DHEA, such as corticosteroids, insulin, opiates, and danazol (for treatment of endometriosis). DHEA may also interfere with the effectiveness of antipsychotic drugs such as chlorpromazine (Thorazine), fluphenazine (Prolixin), and prochlorperazine (Compazine).
DHEA supplementation may increase the effects of: HIV medication AZT, barbiturates, Cisplatic (cancer medication), estrogen and oral contraceptives, testosterone, and benzodiazepines. Those with a history of liver disease, abnormal heart rhythms, or blood clots should avoid DHEA supplements. There have been no studies done on the long-term effects of DHEA supplementation.
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Frequently Asked Questions on DHEA: |
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Does DHEA really have anti-aging benefits?
Due to the steadily decreasing levels of DHEA as we age, scientists often wonder if restoring DHEA amount to “young adult” levels could help reverse aging and its symptoms (e.g., decrease in DHEA, increase in cortisol, decrease in testosterone, decrease in insulin-like growth factor (IGF-I), decrease in growth hormone binding protein (GHBP), etc).
Overall, studies show some inconclusive benefits of oral DHEA supplementation for anti-aging purposes; however, topical DHEA creams have proven to be beneficial for the skin.
In one randomized double-blind, placebo-controlled trial, 10 men and 9 women were given a daily regimen of 100mg of oral DHEA for six months. After the six month period, all subjects’ DHEA levels were restored to the approximate “young adult” range. IGF-I levels increased in both men and women; cortisol levels were unaltered; GHBP levels declined in women (and not men); fat body mass decreased in men; and knee muscle strength as well as lumbar back strength increased in men.
In the longitudinal Massachusetts Male Aging Study, strength, physical performance, and aging factors are gauged over a period of time in a group of 684 55- to 85-year old men. DHEA supplementation in the group correlated with an increase in physical performance up to a particular “threshold” point. Researchers determined that DHEA supplementation may help older men improve physical performance up to a certain point, and additional supplementation above the threshold point had no effect.
The anti-aging effects of DHEA as a topical agent were also studied. Sixty postmenopausal women were randomized in a double-blind, placebo-controlled study where groups applied topical DHEA cream twice daily in amounts of 0%, .3%, 1%, or 2%. The results suggested that topical DHEA may have an anti-aging effect in the skin in a dose-dependent manner.
The DHEA cream may stimulate the synthesis of collagen and improve the structural profile of the dermis. Another study on topical DHEA showed strong evidence that it protected against ultraviolet-induced cellular damage, as well as increased procollagen synthesis. The topical DHEA formulae had the same effect on both aged and young skin.
Can DHEA help me improve my athletic performance?
While DHEA supplementation may lead to a slight increase in muscle strength in elderly men, there is little evidence proving that DHEA can enhance exercise training effects in healthy individuals.
The Mayo Clinic conducted a 12-week, randomized, double-blind, placebo-controlled trial in which 31 sedentary, postmenopausal, Caucasian women participated. Subjects were divided into two groups: exercise training plus 50 mg per day of DHEA, or exercise training plus placebo. After 12 weeks, both groups exhibited improved physical performance, body composition, and insulin resistance. The DHEA-supplemented group showed no additional benefits compared to the placebo group.
Can DHEA help improve my sexual performance?
Few studies exist confirming a direct correlation between DHEA supplementation and enhanced sexual performance. Two studies – one on a population of men with epilepsy, and the other on 1570 Korean men, were conducted to gauge relative correlation between hormone levels and sexual function. These studies focused mainly on the measurement of blood serum levels of DHEAS, as well as the measurement of quality of life through self-reporting and questionnaires.
The population of men with epilepsy showed extremely low sexual response, sexual desire, erectile function, anxiety and depression, along with extremely low levels of DHEAS. In the population of normal Korean men, sexual dysfunction was also positively associated with risk factors like diabetes, hypertension, heart disease, obesity, and extremely low levels of testosterone and DHEAS.
In a German study 24 women diagnosed with adrenal insufficiency were given a single daily dose of 50 mg of DHEA for a period of four months. Through self-reporting and questionnaires, significant increases were found in: how often the women thought about sex and how interested they were in sexual activity. Though much more research needs to be done in this field, there does seem to be a strong relationship between DHEAS levels and sexual desire and function.
Can DHEA help me to lose weight?
Clear evidence exists that DHEA and DHEAS supplementation does induce weight loss in animals. In one study, researchers administered DHEA to pre-diabetic rats for 17 days, resulting in a remarkable rate of weight loss in the rats. The ability of DHEA has shown to be so effective in stimulating weight loss in animals (specifically rats and dogs) that in England, DHEA supplementation is a common treatment for obese dogs.
The effects of DHEA on weight loss in humans have been limited and contradictory. A study followed the weight loss progression of 18 men and 29 women. The subjects were placed on a diet of 1000 – 1400 cal daily. In the beginning of the experiment, the womens’ serum DHEAS levels were two times that of the mens’. When men lost weight their serum DHEAS increased by 125%, while serum DHEAS levels in women did not change. After the 2 months, the DHEAS levels in both men and women were comparable.
Human studies mainly measure the blood serum levels of DHEA during different stages of body weight level (adiposity). In these studies, women demonstrate a direct correlation between higher DHEA levels and higher body weight levels. Men who lost weight did show an increase in DHEAS levels, although HIV-positive men demonstrated a decrease in body weight with decreasing DHEA levels. These findings point to the possible sex-specific mechanism of DHEA.
Although there is a need for more human studies on the effect of DHEA supplementation (as opposed to DHEAS blood levels) and its possible weight loss effects for men – it is likely that there will continue to be a lack of such studies. The ingestion of DHEA supplements may lead to severe side effects, and DHEA as a prescription medication would be un-patentable (thereby making its study in clinical trials a low priority).
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Additional Research on DHEA: |
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Benefits of DHEA
Ding YL, He AH. Expression and roles of corticotrophin-releasing hormone, cortisol and dehydroepiandrosterone sulfate in preterm labor. Zhonghua Fu Chan Ke Za Zhi. 2007 Apr;42(4):239-43.
Konttinen YT, Porola P, Konttinen L, et al. Immunohistopathology of Sjogren’s syndrome. Autoimmun Rev. 206 Nov;6(1):16-20.
Labrie F, Cusan L, Gomez JL, et al. Effect of intravaginal DHEA on serum DHEA and eleven of its metabolites in postmenopausal women. J Steroid Biochem Mol Biol. 2008 Sep;111(3-5):178-94.
Maes M, Mihaylova I, De Ruyter M. Decreased dehydroepiandrosterone sulfate but normal insulin-like growth factor in chronic fatigue syndrome (CFS): relevance for the inflammatory response in CFS. Neuro Endocrinol Lett. 2005 Oct;26(5):487-92.
Poretsky L, Song L, Brillon DJ, et al. Metabolic and Hormonal Effects of Oral DHEA in Premenopausal Women with HIV Infection: A Randomized, Prospective, Placebo-controlled Pilot Study. Horm Metab Res. 2008 Sep 22.
Zandman-Goddard G, Shoenfeld Y. Novel approaches to therapy for systemic lupus erythematosus. Eur J Intern Med. 2000 Jun;11(3):130-134.
Sources of DHEA
Kalimi M, Regelson W. (1999). Dehydroepiandrosterone (DHEA): Biochemical, Physiological, and Clinical Aspects. Berlin, Germany: Walter De Gruyter Inc.
Remer T. Disparate effects of weight reduction by diet on serum dehydroepiandrosterone-sulfate levels in obese men and women. J Clin Endocrinol Metab. 1996 Jul;81(7):2751-2.
Timon R, Olcina G, Munoz D, et al. Determination of urine steroid profile in untrained men to evaluate recovery after a strength training session. J Strength Cond Res. 2008 Jul;22(4):1087-93.
Recommended Dosages of DHEA
Poretsky L, Song L, Brillon DJ, et al. Metabolic and Hormonal Effects of Oral DHEA in Premenopausal Women with HIV Infection: A Randomized, Prospective, Placebo-controlled Pilot Study. Horm Metab Res. 2008 Sep 22.
Shin MH, Rhie GE, Park CH, et al. Modulation of collagen metabolism by the topical application of dehydroepiandosterone to human skin. J Invest Dermatol. 2005 Feb;124(2):315-23.
Stanczyk FZ, Slater CC, Ramos DE, et al. Pharmacokinetics of dehydroepiandrosterone and its metabolites after long-term oral dehydroepiandrosterone treatment in postmenopausal women. Menopause. 2008 Dec 17.
DHEA and Adrenal Insufficiency
Bhagra S, Nippoldt TB, Nair KS. Dehydroepiandrosterone in adrenal insufficiency and ageing. Curr Opin Endocrinol Diabetes Obes. 2008 June;15(3):239-43.
Buford TW, Willoughby DS. Impact of DHEA(S) and cortisol on immune function in aging: a brief review. Appl Physiol Nutr Metab. 2008 Jun;33(3):429-33.
Anti Aging and DHEA
Calvo E, Luu-The V, Morissette J, et al. Pangenomic changes induced by DHEA in the skin of postmenopausal women. J Steroid Biochem Mol Biol. 2008 Dec;112(4-5):186-93.
Enomoto M, Adachi H, Fukami A, et al. Serum dehydroepiandrosterone sulfate levels predict longevity in men: 27-year follow-up study in a community-based cohort (Tanushimaru study). J Am Geriatr Soc. 2008 Jun;56(6):994-8.
Lunenfeld B. Endocrinology of the aging male. Minerva Ginecol. 2006 Apr;58(2):153-70.
Morales AJ, Haubrich RH, Hwang JY, Asakura H, Yen SS. 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 Oct;49(4):421-32.
O’Donnell AB, Travison TG, Harris SS, Tenover JL, McKinlay JB. Testosterone, dehydroepiandrosterone, and physical performance in older men: results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2006 Feb;91(2):425-31.
Ohnaka K, Takayanagi R. Hormone replacement Up-to-Date: Adrenopause and DHEA replacement therapy. Clin Calcium. 2007 Sep;17(9):1334-40.
Sanchez J, Perez-Heredia F, Priego T, et al. Dehydroepiandrosterone prevents age-associated alterations, increasing insulin sensitivity. J Nutr Biochem. 2008 Dec:19(12):809-18.
Shin MH, Rhie GE, Park CH, et al. Modulation of collagen metabolism by the topical application of dehydroepiandosterone to human skin. J Invest Dermatol. 2005 Feb;124(2):315-23.
DHEA and Atheletic Performance
Andrade S, Silveira SL, Gomez R, Barros HM, Ribeiro MF. Gender differences of acute and chronic administration of dehydroepiandrosterone in rats submitted to the forced swimming test. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Apr 13;31(3):613-21.
Arlettaz A, Portier H, Lecoq AM, Rieth N, De Ceaurriz J, Collomp K. Effects of short-term prednisone intake during submaximal exercise. Med Sci Sports Exerc. 2007 Sep;39(9):1672-8.
Baume N, Steel G, Edwards T, Thorstensen E, Miller BF. No variation of physical performance and perceived exertion after adrenal gland stimulation by synthetic ACTH (Synacthen) in cyclists. Eur J Appl Physiol. 2008 Nov;104(4):589-600.
Benso A, Broglio F, Aimaretti G, et al. Endocrine and metabolic responses to extreme altitude and physical exercise in climbers. Eur J Endocrinol. 2007 Dec;157(6):733-40.
Igwebuike A, Irving BA, Bigelow ML, Short KR, McConnell JP, Nair KS. Lack of dehydroepiandrosterone effect on a combined endurance and resistance exercise program in postmenopausal women. J Clin Endocrinol Metab. 2008 Feb;93(2):534-8.
Jenkinson DM, Harbert AJ. Supplements and sports. Am Fam Physician. 2008 Nov 1;78(9):1039-46.
Lee WC, Chen SM, Wu MC, et al. The role of dehydroepiandrosterone levels on physiologic acclimatization to chronic mountaineering activity. High Alt Med Biol. 2006 Fall;7(3):228-36.
DHEA and Sexual Health
Ahn TY, Park JK, Lee SW, et al. Prevalence and risk factors for erectile dysfunction in Korean men: results of an epidemiological study. J Sex Med. 2007 Sep;4(5):1269-76.
Arlt W, Callies F, van Vlijmen JC, et al. Dehydroepiandrosterone replacement in women with adrenal insufficiency. N Engl J Med. 1999 Sep 30;341(14):1013-20.
Dhatariya K. Self-reported sexual function in women and androgen levels. JAMA. 2005 Nov 2;294(17):2167-8.
Hamed SA. Neuroendorcrine hormonal conditions in epilepsy: relationship to reproductive and sexual functions. Neurologist. 2008 May;14(3):157-69.
Martinez Jabaloyas JM, Queipo Zaragoza A, Ferrandis Cortes C, et al. Changes in sexual hormones in a male population over 50 years of age. Frequency of low testosterone levels and risk factors. Actas Urol Esp. 2008 Jun;32(6):603-10.
Miwa Y, Kaneda T, Yokoyama O. Association between lower urinary tract symptoms and serum levels of sex hormones in men. Urology. 2008 Sep:72(3):552-5.
Molleken D, Richter-Appelt H, Stodieck S, Bengner T. Sexual quality of life in epilepsy: correlations with sex hormone blood levels. Epilepsy Behav. 2009 Jan;14(1):226-31.
Panjari M, Davis SR. DHEA therapy for women: effect on sexual function and well-being. Hum Reprod Update. 2007 May-Jun;239-48.
Talbot JA, Sheldrick R, Caswell H, Duncan S. Sexual function in men with epilepsy: how important is testosterone? Neurology. 2008 Apr 15;70(16):1346-52.
DHEA and Weight Loss
Christeff N, Melchior JC, Mammes O, et al. Correlation between increased cortisol :DHEA ration and malnutrition in HIV-positive men. Nutrition. 1999 Jul-Aug;15(7-8):534-9.
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 Nov;87(11):4935-41.
Jakubowicz DJ, Beer NA, Beer RM, Nestler JE. Disparate effects of weight reduction by diet on serum dehydroepiandrosterone-sulfate levels in obese men and women. J Clin Endocrinol Metab. 1995 Nov;80(11):3373-6.
Kimura M, Tanaka S, Yamada Y, et al. Dehydroepiandrosterone decreases serum tumor necrosis factor-alpha and restores insulin sensitivity: independent effect from secondary weight reduction in genetically obese Zucker fatty rats. Endocrinology. 1998 Jul;139(7):3249-53.
Kopp HP, Krzyzanowska K, Schernthaner GH, Kriwanek S, Schernthaner G. Relationship of androgens to insulin resistance and chronic inflammation in morbidly obese premenopausal women: studies before and after vertical banded gastroplasty. Obes Surg. 2006 Sep;16(9):1214-20.
Kurzman ID, Panciera DL, Miller JB, MacEwan EG. The effect of dehydroepiandrosterone combined with a low-fat diet in spontaneously obese dogs: a clinical trial. Obes Res. 1998 Jan;6(1):20-8.
Leenen R, van der Kooy K, Seidell JC, Deurenberg P, Koppeschaar HP. Visceral fat accumulation in relation to sex hormones in obese men and women undergoing weight loss therapy. J Clin Endocrinol Metab. 1994 Jun;78(6):1515-20.
Lemieux C, Picard F, Labrie F, Richard D, Deshaies Y. The estrogen antagonist EM-652 and dehydroepiandrosterone prevent diet- and ovariectomy-induced obesity. Obes Res. 2003 Mar;11(3):477-90.
MacEwen EG, Kurzman ID. Obesity in the dog: role of the adrenal steroid dehydroepiandrosterone (DHEA). J Nutr. 1991 Nov;121(11 Suppl):S51-5.
McTiernan A, Rajan KB, Tworoger SS, et al. Adiposity and sex hormones in postmenopausal breast cancer survivors. J Clin Oncol. 2003 May 15;21(10):1961-6.
Pasquali R, Casimirri F, Melchionda N, et al. Weight loss and sex steroid metabolism in massively obese man. J Endocrinol Invest. 1988 Mar;11(3):205-10.
Ram E, Vishne T, Diker D, et al. Impact of gastric banding on plasma ghrelin, growth hormone, cortisol, DHEA and DHEA-S levels. Obes Surg. 2005 Sep;15(8):1118-23.
Reinehr T, de Sousa G, Roth CL, Andler W. Androgens before and after weight loss in obese children. J Clin Endocrinol Metab. 2005 Oct;90(10):5588-95.
Remer T. Disparate effects of weight reduction by diet on serum dehydroepiandrosterone-sulfate levels in obese men and women. J Clin Endocrinol Metab. 1996 Jul;81(7):2751-2.
Ryu JW, Kim MS, Kim CH, et al. DHEA administration increases brown fat uncoupling protein 1 levels in obese OLETF rats. Biochem Biophys Res Commun. 2003 Apr 4;303(2):726-31.
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