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Abstracts

LE Magazine March 2004
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DHEA

Failure of dehydroepiandrosterone to influence energy and protein metabolism
in humans. 

It was reported recently that 4 weeks of dehydroepiandrosterone (DHEA) treatment [5.55 mmol/day (1600 mg/day), orally] reduced body fat and increased lean body mass in healthy men. The present study was performed to examine whether these effects could be explained by increased energy expenditure and muscle protein synthesis. Eight healthy men were given placebo and DHEA (1600 mg/day) for 4 weeks each in a double blind cross-over study. DHEA treatment caused a 9-fold increase in mean plasma DHEA sulfate concentrations, but had no significant effect on body weight or on two indices of lean body mass (total body water and total body potassium). DHEA had no effect on any of the parameters of energy and protein metabolism, including resting metabolic rate, total energy expenditure (estimated by the 2H2(18)O method during the final 2 weeks of each treatment period), leucine flux (an index of whole body proteolysis), the nonoxidized portion of leucine flux (an index of whole body protein synthesis), and the rate of incorporation of leucine into muscle protein. Circulating levels of cholesterol, T3, and T4 also were unaffected by DHEA. These data suggest that DHEA is not an important regulator of energy or protein metabolism in humans.

J Clin Endocrinol Metab. 1990 Nov;71(5):1259-64

Effects of DHEA replacement on bone mineral density and body composition in elderly women and men.
OBJECTIVE: Dehydroepiandrosterone (DHEA) is a precursor for both oestrogens and androgens. Its marked decline with ageing may influence age-related changes in tissues influenced by sex hormones. The aim of this study was to determine the effects of DHEA replacement on bone mineral density (BMD) and body composition in elderly women and men with low serum DHEA sulphate (DHEAS) levels. DESIGN: Prospec-tive 6 month trial of oral DHEA replacement, 50 mg/day. PATIENTS: Experimental subjects were 10 women and eight men, aged 73 +/- 1 years. Control subjects were 10 women and eight men, aged 74 +/- 1 years. MEASUREMENTS: BMD, body composition, serum markers of bone turnover, serum lipids and lipoproteins, oral glucose tolerance, serum IGF-I, total serum oestrogens and testosterone. RESULTS: BMD of the total body and lumbar spine increased (mean +/- SEM; 1.6 +/- 0.6% and 2.5 +/- 0.8%, respectively; both P < or = 0.05), fat mass decreased (- 1.3 +/- 0.4 kg; P < 0.01) and fat-free mass increased (0.9 +/- 0.4 kg; P < or = 0. 05) in response to DHEA replacement. DHEA replacement also resulted in increases in serum IGF-I (from 108 +/- 8 to 143 +/- 7 microg/l; P < 0.01) and total serum testosterone concentrations (from 10.7 +/- 1.2 to 15.6 +/- 1.8 nmol/l in the men and from 2.1 +/- 0.2 to 4.5 +/- 0.4 nmol/l in the women; both P < or = 0.05). CONCLUSIONS: The results provide preliminary evidence that DHEA replacement in those elderly women and men who have very low serum DHEAS levels can partially reverse age-related changes in fat mass, fat-free mass, and BMD, and raise the possibility that increases in IGF-I and/or testosterone play a role in mediating these effects of DHEA.

Clin Endocrinol (Oxf). 2000 Nov;53(5):561-8

Dehydroepiandrosterone supplementation improves endothelial function and insulin sensitivity in men.
The dehydroepiandrosterone (DHEA) concentration decreases with age. There is evidence that DHEA has a protective effect against age-related disorders, including cardiovascular disease. Accordingly, we examined the effect of DHEA supplementation (25 mg/d) on endothelial function, insulin sensitivity, and fibrinolytic activity in 24 men with hypercholesterolemia (mean age, 54 +/- 1 yr). All subjects were enrolled in a randomized, double-blind study. Flow-mediated dilation of brachial artery after transient occlusion, which was expressed as the percent change from the baseline value of the diameter, increased significantly with DHEA supplementation [DHEA: baseline, 3.9 +/- 0.5%; 4 wk, 6.9 +/- 0.7%; 8 wk, 7.9 +/- 0.6%; 12 wk, 8.4 +/- 0.7% (P < 0.01 vs. baseline for all, by ANOVA); placebo: 4.1 +/- 0.6%, 4.5 +/- 0.5%, 3.9 +/- 0.5%, and 4.4 +/- 0.6% (P < 0.01 for all, by ANOVA)]. There was a significant concurrent reduction in the plasma levels of plasminogen activator inhibitor type 1 during DHEA supplementation [DHEA: 9.1 +/- 2.2, 6.4 +/- 2.3, 5.5 +/- 2.8, and 5.1 +/- 2.0 IU/ml (P < 0.01 vs. baseline, by ANOVA); placebo: 9.0 +/- 2.1, 10.4 +/- 2.2, 9.5 +/- 2.2, and 9.6 +/- 2.1 IU/ml (P < 0.01, by ANOVA)]. DHEA supplementation also decreased steady state plasma glucose [DHEA: baseline, 178.9 +/- 12.2; 12 wk, 132.0 +/- 12.8 mg/dl (P < 0.01, by ANOVA); placebo: 181.0 +/- 13.8 and 179.6 +/- 12.4 mg/dl (P < 0.01, by ANOVA)]. In contrast, steady state plasma insulin did not change during the study in either group. The low dose DHEA supplementation improves vascular endothelial function and insulin sensitivity and decreases the plasminogen activator inhibitor type 1 concentration. These beneficial changes have the potential to attenuate the development of age-related disorders such as cardiovascular disease.

J Clin Endocrinol Metab. 2003 Jul;88(7):3190-5

Metabolic effects of 12-month percutaneous dehydroepiandrosterone replacement therapy in postmenopausal women.
We have evaluated the effect of dehydroepiandrosterone (DHEA) replacement therapy in 60- to 70-year-old women (n = 15) who received a single daily percutaneous application of a 10% DHEA cream for 12 months. While anthropometric measurements showed no change in body weight, we observed a 9.8% decrease in subcutaneous skinfold thickness at 12 months (P < 0.05). This was confirmed by measurements of midthigh fat and muscle areas by computed tomography where a 3.8% decrease (P < 0.05) in femoral fat and a 3.5% increase (P < 0.05) in femoral muscular areas were observed at 12 months. There was no significant change in abdominal fat measurements but the waist-to-hip ratio was only 0.83 at the onset of treatment. These changes in body fat and muscular mass were associated with an 11% decrease (P < 0.05) in fasting plasma glucose and a 17% decrease (P < 0.05) in fasting insulin levels. Treatment with DHEA had no adverse effect on the lipid or lipoprotein profile. In fact, an overall trend towards a decrease in total cholesterol and its lipoprotein fractions was observed. Plasma triglycerides were not affected. Plasma high-density lipoprotein (HDL) cholesterol decreased by 8% but the ratio HDL/cholesterol was unchanged by DHEA treatment because of a parallel decrease in total cholesterol. The index of sebum secretion showed a 73% increase (P < 0.05) during the 12 months of DHEA therapy followed by a return to pretreatment values 3 months after cessation of therapy. At the same time, sex hormone-binding globulin levels decreased (P < 0.05) during treatment and returned to pretreatment values 3 months after the end of therapy. Serum gonadotropins were not changed by DHEA treatment. Although not significant, we observed a tendency towards an elevation in serum GH levels. Values of serum IGF-I remained unchanged while plasma IGF-binding protein-3 levels significantly decreased (P < 0.05) during treatment and returned to pretreatment values after cessation of DHEA therapy. The present data clearly indicate the beneficial effects of DHEA therapy in postmenopausal women through its transformation into androgens and/or estrogens in specific intracrine tissues without any significant side effects.

J Endocrinol. 1996 Sep;150 Suppl:S43-50

Replacement of dehydroepiandrosterone enhances T-lymphocyte insulin binding in postmenopausal women.
OBJECTIVE: To demonstrate bioavailability of 3 weeks of oral micronized DHEA and to delineate changes induced on insulin sensitivity, morphometric indexes, and lipoprotein profiles. DESIGN: Oral micronized DHEA (50 mg/d) was administered in 3-week treatments to 11 postmenopausal women in a prospective, placebo-controlled, randomized, blinded, crossover trial with an interarm washout. After dose (23 hour) serum DHEA, DHEAS, testosterone(T), and cortisol levels were measured, as were fasting lipoproteins, oral glucose tolerance tests (OGTT), T-lymphocyte insulin binding and degradation, and urine collagen cross-links. Morphometric changes were determined by hydrostatic weighing. RESULTS: Dehydroepiandrosterone sulfate, DHEA, T, and free T increased up to two times premenopausal levels with treatment. Fasting triglycerides declined; no change in collagen cross-links or morphometric indexes was noted. Oral glucose tolerance test parameters did not change, but both T-lymphocyte insulin binding and degradation increased with DHEA. CONCLUSION: Fifty milligrams per day of oral DHEA gives suprahysiologic androgen levels; 25 mg/d may be more appropriate. Dehydroepiandrosterone enhanced tissue insulin sensitivity and lowered serum triglycerides. Rationale is provided for postmenopausal replacement therapy with this androgen.

Fertil Steril. 1995 May;63(5):1027-31

Dehydroepiandrosterone sulfate levels in women. Relationships with body mass index, insulin and glucose levels.
OBJECTIVE: Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) are the most abundant steroids in human plasma. Previous studies have shown that administration of DHEA-S is more effective than DHEA in reducing adipose tissue mass and cellularity in rats. Another study suggested that maintaining high levels of DHEA-S might prevent the development of obesity. Therefore, this study aims to determine the relationship of plasma dehydroepiandrosterone sulfate (DHEA-S) levels with respect to obesity, fasting insulin and glucose levels in a cohort of obese and normal weight healthy Saudi women. METHODS: This study was carried out at King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia during the year 2001. A total of 65 healthy volunteers between 19-30 years of age with body mass index (BMI) of 15.35-38.30 kg/m2 were grouped into 26 young obese females of BMI > 27 kg/m2 and 39 young lean females of BMI < 27 kg/m2. Weight, height, waist and hip circumference, fasting blood glucose, insulin and DHEA-S levels were measured. RESULTS: Dehydroepiandrosterone-S levels were found lower in the obese group than in the lean women. In all subjects, DHEA-S levels were related negatively with BMI (p=0.02, correlation co-efficient [r]=-0.25) and hip circumference (p=0.03, r=-0.27). In the obese group, DHEA-S levels showed a significant positive relationship with insulin (p=0.03, r=0.43). No significant relationship was found between DHEA-S and glucose levels in considering either the whole group or the obese women. CONCLUSION: Hip circumference, as a corollary for peripheral obesity, was better associated with DHEA-S than the waist circumference or waist-to-hip ratio. The data indicated that BMI and hip circumference are important factors in explaining DHEA-S variability. Insulin could have an independent regulatory effect on DHEA-S secretion, but glucose metabolism is not related.

Saudi Med J. 2003 Aug;24(8):837-41

Correlation of serum L-carnitine and dehydroepiandrosterone sulphate levels with age and sex in healthy adults.
OBJECTIVES: L-carnitine and dehydroepiandrosterone (DHEA) independently promote mitochondrial energy metabolism. We therefore wondered if an age-related deficiency of L-carnitine or DHEA may account for the declining energy metabolism associated with age. METHODS: we evaluated serum levels of L-carnitine and the sulphated derivative of DHEA (DHEAS) in cross-sectional study of 216 healthy adults, aged 20-95. RESULTS: serum DHEAS levels declined, while total carnitine levels increased with age (P < 0.0001). Total and free carnitine and DHEAS levels were lower in women than men (P < 0.0001). Esterified/free (E/F) carnitine (inversely related to carnitine availability) increased with age in both sexes (P=0.012). CONCLUSION: reduced carnitine availability correlates with the age-related decline of DHEAS levels. These results are consistent with the hypothesis that decreased energy metabolism with age relates to DHEAS levels and carnitine availability.

Age Ageing. 1999 Mar;28(2):211-6

Mental wellbeing and quality of sexual life in women with primary Sjogren’s syndrome are related to circulating dehydroepiandrosterone sulphate.
OBJECTIVES: To evaluate the possible effect of androgen status on sexuality and mental wellbeing in patients with primary Sjogren’s syndrome (pSS). METHODS: Serum levels of dehydroepiandrosterone sulphate (DHEA-S), testosterone (T), androstenedione, sex hormone binding globulin (SHBG), and the SHBG/T ratio were measured in 21 women with pSS. Sexual life was assessed by a Swedish version of the McCoy scale, which covers sexual experience and responsiveness during the past 30 days. A standardised questionnaire, the Psychological General Well-Being Index (PGWB), was used to examine quality of life and psychological symptoms in patients with pSS. RESULTS: Positive correlations were found between DHEA-S serum levels and the total McCoy score (r(s)=0.62; p<0.01), as well as the subscales of this score reflecting arousal (0.59; p<0.05), desire (r(s)=0.52; p<0.05), and satisfaction (r(s)=0.66; p<0.01). Serum DHEA-S concentrations were also related to the total PGWB score (r(s)=0.60; p<0.01) and subscales of this score: depression (r(s)=0.62; p<0.01), wellbeing (r(s)=0.64; p<0.01), general health (r(s)=0.67; p<0.01), and self control (r(s)=0.67; p<0.01). Total McCoy and PGWB scores and their subscales were not related to the serum levels of testosterone and androstenedione or the T/SHBG ratio. CONCLUSIONS: Circulating levels of the weak androgen DHEA-S are positively related to the quality of sexual life and mental wellbeing in women with pSS.

Ann Rheum Dis. 2003 Sep;62(9):875-9

Comparison of immunological and endocrinological markers associated with major depression.
Natural-killer-(NK)-cell activity and blood levels of interleukin 2 (IL-2), dehydroepiandrosterone (DHEA), DHEA sulphate (DHEA-S), and cortisol were measured in 17 patients with major depression and 10 control subjects. Depression severity was evaluated using the Zung Self-rating Depression Scale. NK-cell activity and IL-2 levels were measured using a chromium-51 release test and an enzyme-linked immunosorbent assay, respectively. Radio-immunoassays were used to measure serum cortisol, DHEA and DHEA-S. As would be expected, patients with major depression had a higher score on the Zung Self-rating Depression Scale than healthy controls. Compared with controls, NK-cell activity and levels of cortisol and DHEA were reduced in patients with major depression, whereas IL-2 levels were increased. No difference was observed in DHEA-S levels between patients and controls. A reduction in NK-cell activity and DHEA levels, and an increase in IL-2 levels appear to be associated with major depression. Whether these changes are the cause or the consequence of the depression remains to be determined.

J Int Med Res. 2003 Jan-Feb;31(1):36-41

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