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Dr. Rashel, Integrative Medicine

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Differences in adrenal steroid profile in chronic fatigue syndrome, depression and in health.

Scott LV; Salahuddin F; Cooney J; Svec F; Dinan TG; Department of Psychiatry, Trinity College Medical School, Dublin, Ireland.

J Affect Disord. 1999; 54(1-2):129-37 (ISSN: 0165-0327)

BACKGROUND: Hyperactivity and hypoactivity of the HPA have been forwarded as of pathophysiological relevance in major depressive disorder and chronic fatigue syndrome (CFS), respectively.

METHODS: This study examines cortisol levels in the two disorders, and also assesses levels of the adrenal androgens, dehydroepiandrosterone (DHEA) and its sulphate derivative (DHEA-S), and 17-alpha-hydroxyprogesterone; 15 subjects with CFS diagnosed according to CDC criteria, 15 subjects with DSM III-R major depression and 11 healthy subjects were compared.

RESULTS: DHEA and DHEA-S levels were significantly lower in the CFS compared to the healthy group; DHEA-S levels, but not DHEA, were lower in the depressives; cortisol and 17-alpha-hydroxyprogesterone did not differ between the three groups.

CONCLUSIONS: A potential role for DHEA, both therapeutically and as a diagnostic tool, in CFS, is suggested.


Improvement in self-esteem, mood, and fatigue with DHEA replacement in the treatment of Addison’s Disease

Hunt PJ; Gurnell EM; Huppert FA; Richards C; Prevost AT; Wass JA; Herbert J; Chatterjee VK
Department of Endocrinology, University of Oxford, Radcliffe Infirmary, Oxford, United Kingdom.

J Clin Endocrinol Metab. 2000; 85(12):4650-6 (ISSN: 0021-972X)

Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are adrenal precursors of steroid biosynthesis and centrally acting neurosteroids. Glucocorticoid and mineralocorticoid deficiencies in Addison's disease require life-long hormone replacement, but the associated failure of DHEA synthesis is not corrected. We conducted a randomized, double blind study in which 39 patients with Addison's disease received either 50 mg oral DHEA daily for 12 weeks, followed by a 4-week washout period, then 12 weeks of placebo, or vice versa. After DHEA treatment, levels of DHEAS and Delta(4)-androstenedione rose from subnormal to within the adult physiological range. Total testosterone increased from subnormal to low normal with a fall in serum sex hormone-binding globulin in females, but with no change in either parameter in males. In both sexes, psychological assessment showed significant enhancement of self-esteem with a tendency for improved overall well-being. Mood and fatigue also improved significantly, with benefit being evident in the evenings. No effects on cognitive or sexual function, body composition, lipids, or bone mineral density were observed. Our results indicate that DHEA replacement corrects this steroid deficiency effectively and improves some aspects of psychological function. Beneficial effects in males, independent of circulating testosterone levels, suggest that it may act directly on the central nervous system rather than by augmenting peripheral androgen biosynthesis. These positive effects, in the absence of significant adverse events, suggest a role for DHEA replacement therapy in the treatment of Addison's disease.

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The effects of DHEA 100 mg daily for six months on circulating sex steroids, body composition and muscle strength in age-advanced men and women

Morales AJ; Haubrich RH; Hwang JY; Asakura H; Yen SS; Department of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, USA.

Clin Endocrinol (Oxf). 1998; 49(4):421-32 (ISSN: 0300-0664)

OBJECTIVE: The biological role of the adrenal sex steroid precursors--DHEA and DHEA sulphate (DS) and their decline with ageing remains undefined. We observed previously that administration of a 50 daily dose of DHEA for 3 months to age-advanced men and women resulted in an elevation (10%) of serum levels of insulin-like growth factor-I (IGF-I) accompanied by improvement of self-reported physical and psychological well-being. These findings led us to assess the effect of a larger dose (100 mg) of DHEA for a longer duration (6 months) on circulating sex steroids, body composition (DEXA) and muscle strength (MedX). SUBJECTS AND DESIGN: Healthy non-obese age-advanced (50-65 yrs of age) men (n = 9) and women (n = 10) were randomized into a double-blind placebo-controlled cross-over trial. Sixteen subjects completed the one-year study of six months of placebo and six months of 100 mg oral DHEA daily.

MEASUREMENTS: Fasting early morning blood samples were obtained. Serum DHEA, DS, sex steroids, IGF-I, IGFBP-1, IGFBP-3, growth hormone binding protein (GHBP) levels and lipid profiles as well as body composition (by DEXA) and muscle strength (by MedX testing) were measured at baseline and after each treatment.

RESULTS: Basal serum levels of DHEA, DS, androsternedione (A), testosterone (T) and dihydrotestosterone (DHT) were at or below the lower range of young adult levels. In both sexes, a 100 mg daily dose of DHEA restored serum DHEA levels to those of young adults and serum DS to levels at or slightly above the young adult range. Serum cortisol levels were unaltered, consequently the DS/cortisol ratio was increased to pubertal (10:1) levels. In women, but not in men, serum A, T and DHT were increased to levels above gender-specific young adult ranges. Basal SHBG levels were in the normal range for men and elevated in women, of whom 7 of 8 were on oestrogen replacement therapy. While on DHEA, serum SHBG levels declined with a greater (P < 0.02) response in women (-40 +/- 8%; P = 0.002) than in men (-5 +/- 4%; P = 0.02). Relative to baseline, DHEA administration resulted in an elevation of serum IGF-I levels in men (16 +/- 6%, P = 0.04) and in women (31 +/- 12%, P = 0.02). Serum levels of IGFBP-1 and IGFBP-3 were unaltered but GHBP levels declined in women (28 +/- 6%; P = 0.02) not in men. In men, but not in women, fat body mass decreased 1.0 +/- 0.4 kg (6.1 +/- 2.6%, P = 0.02) and knee muscle strength 15.0 +/- 3.3% (P = 0.02) as well as lumbar back strength 13.9 +/- 5.4% (P = 0.01) increased. In women, but not in men, an increase in total body mass of 1.4 +/- 0.4 kg (2.1 +/- 0.7%; P = 0.02) was noted. Neither gender had changes in basal metabolic rate, bone mineral density, urinary pyridinoline cross-links, fasting insulin, glucose, cortisol levels or lipid profiles. No significant adverse effects were observed.

CONCLUSIONS:  A daily oral 100 mg dose of DHEA for 6 months resulted in elevation of circulating DHEA and DS concentrations and the DS/cortisol ratio. Biotransformation to potent androgens near and slightly above the range of their younger counterparts occurred in women with no detectable change in men. Given this hormonal milieu, an increase in serum IGF-I levels was observed in both genders but dimorphic responses were evident in fat body mass and muscle strength in favour of men. These differences in response to DHEA administration may reflect a gender specific response to DHEA and/or the presence of confounding factor(s) in women such as oestrogen replacement therapy.

The effect of DHEA replacement in prevention and treatment of metabolic syndrome associated with abdominal obesity

Villareal DT, Holloszy JO. Effect of DHEA on abdominal fat and insulin action in elderly women and men: A randomized controlled trial

JAMA. 2004 Nov 10;292(18):2243-8

CONTEXTS: Dehydroepiandrosterone (DHEA) administration has been shown to reduce accumulation of abdominal visceral and protect against insulin resistance in laboratory animals, but it is not known whether DHEA decreases abdominal obesity in humans. DHEA is widely available as a dietary supplement without a prescription.

OBJECTIVES: To determine whether DHEA replacement therapy decreases abdominal fat and improves insulin action in elderly persons.

DESIGN AND SETTING: Randomized, double-blind, placebo controlled trial conducted in a US university- based research center from June 2001-February 2004.

PARTICIPANTS: 56 elderly persons (28 women and 28 men aged 71 [range, 65-78] years) with age-related decrease DHEA level.

INTERVENTION: Participants were randomly assigned to receive 50mg/d of DHEA or matching placebo for 6 months.

MAIN OUTCOME MEASURES: The primary outcome measures were 6-month change in visceral and subcutaneous abdominal fat measured by magnetic resonance imaging and glucose and insulin responses to an oral glucose tolerance test (OGTT)

RESULTS: Of the 56 men and women enrolled, 52 underwent follow-up evaluations. Compliance with the in intervention 97% in the DHEA group and 95% in the placebo group. Based on intention-to-treat analyses, DHEA therapy compared with placebo induced significant decreases in visceral fat area (-13 cm2 vs +3 cm2, respectively; P + .001) and subcutaneous fat (-13 cm2 vs +2cm2, P = .003). The insulin area under the curve (AUC) during the OGTT was significantly reduced after 6 monthgs of DHEA therapy compared with placebo (-1119 muU/ml per 2 hours vs +818 muU/ml per 2 hours, P = .007). Despite the lower insulin levels, the glucose AUC was unchanges, resulting in a significant increase in an insulin sensitivity index in response to DHEA compared with placebo ( +1.4 vs -0.7, P = .005).

CONCLUSION: DHEA replacement could play a role in prevention and treatment of the metabolic syndrome associated with abdominal obesity.