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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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