LE Magazine August 2002
DHEA/Testosterone
Bioavailable testosterone and
depressed mood in older men: the Rancho Bernardo Study.
A cross-sectional population-based study examined the
association between endogenous sex hormones and depressed mood
in community-dwelling older men. Participants included 856
men, ages 50 to 89 yr, who attended a clinic visit between
1984 to 1987. Total and bioavailable testosterone, total and
bioavailable estradiol, and dihydrotestosterone levels were
measured by radioimmunoassay in an endocrinology research
laboratory. Depressed mood was assessed with the Beck
Depression Inventory (BDI). Levels of bioavailable
testosterone and bioavailable estradiol decreased with age,
but total testosterone, dihydrotestosterone, and total
estradiol did not. BDI scores increased with age. Low
bioavailable testosterone levels and high BDI scores were
associated with weight loss and lack of physical activity, but
not with cigarette smoking or alcohol intake. By linear
regression or quartile analysis the BDI score was
significantly and inversely associated with bioavailable
testosterone (both Ps = 0.007), independent of age, weight
change, and physical activity; similar associations were seen
for dihydrotestosterone (P = 0.048 and P = 0.09,
respectively). Bioavailable testosterone levels were 17% lower
for the 25 men with categorically defined depression than
levels observed in all other men (P = 0.01). Neither total nor
bioavailable estradiol was associated with depressed mood.
These results suggest that testosterone treatment might
improve depressed mood in older men who have low levels of
bioavailable testosterone. A clinical trial is necessary to
test this hypothesis.
J Clin Endocrinol Metab 1999
Feb;84(2):573-7
Dehydroepiandrosterone replacement in
aging humans.
Because so much medical and media attention has been drawn
to the alleged benefits of dehydroepiandrosterone (DHEA) and
its sulfate ester (DHEAS), it is important to evaluate the
effects of replacement therapy objectively using double blind,
cross-over, randomized research methodology. In this
nine-month study, healthy older men (n = 39) received
replacement dose DHEA. Lean body mass, blood hematology,
chemistry and endocrine values, as well as urological and
psychological data were measured. Data showed some mild and
temporary, but significant, changes during oral use of 100 mg
DHEA for three months compared with placebo taken for three
months. Body composition did not change during the six months
of treatment, nor did any urological parameters. Concomitant
with the endocrine changes, some small but, significant,
variations in blood values (blood urea nitrogen, creatinine,
uric acid, alanine transaminase, cholesterol, high density
lipoprotein, and potassium) were found. After cessation of
DHEA and placebo, followed by three months of no treatment,
all values previously found to be altered returned to entry
baseline. Well publicized effects of the drug reported by
others, such as a sense of well-being or improved sexual
function, were not found in this study.
J Clin Endocrinol Metab 1999
May;84(5):1527-33
Serum dehydroepiandrosterone sulfate,
testosterone, and biochemical markers of bone turnover in
elderly Thai men.
The most abundant human steroid, dehydroepiandrosterone
sulfate (DHEAS), may have a multitude of beneficial effects,
but declines with age. It is unclear whether DHEAS deficiency
is an important factor contributing to increased bone
resorption and impaired bone formation that leads to their
bone loss or not. Thus, we investigated serum DHEAS,
testosterone, osteocalcin (N-MID osteocalcin) and C-terminal
telopeptides (beta-CrossLaps) in 121 healthy Thai males
without bone diseases. Thirty-nine males (mean age 31.5 +/-
8.2, range 23 to 42 years) were recruited as the normal adult
group and 82 males (mean age 61.2 +/- 7.0, range 52 to 77
years) were assigned as the elderly group. DHEAS levels were
higher in the adult group compared with the elderly subjects
(296.8 +/- 93.4 vs 172.6 +/- 99.8 microg/dL, p < 0.0001).
Serum osteocalcin concentrations were also higher in the adult
group compared with the elderly males (27.9 +/- 11.1 vs 23.2
+/- 7.9 ng/ml, p = 0.0091). However, serum testosterone and
C-terminal telopeptides levels were not significantly
different between the two groups. We concluded that low DHEAS
concentrations are commonly encountered in elderly males and
may relate to low osteocalcin levels due to the osteoblast
stimulation effects of DHEAS. These findings may be implicated
in the treatment of osteoporosis in elderly men by using
DHEAS.
J Med Assoc Thai 2001 Oct;84 Suppl
2:S570-5
Testosterone and
dehydroepiandrosterone deficiency, general adiposity and
visceral obesity during normal male aging.
Both clinical observations and in vitro studies reveal that
sex steroids are essential factors affecting body fat
accumulation and distribution of healthy men. An excessive
adiposity and visceral obesity are frequently accompanied by
an adrenal and gonadal andropenia among men aged 50 and over.
The relationships between an age-related increase in BMI and
WHR values and an altered androgen-estrogen activity in the
course of normal male aging have not been firmly established,
as not all studies have thus far produced consistent results.
The effects of androgen substitutive therapy (testosterone and
dehydroepiandrosterone) in elderly men suggest the possible
relationship between androgens and male visceral adiposity;
unfortunately the results of available studies on that issue
are also not consistent. Therefore, there is an urgent need to
comprehensively establish the androgen contribution in the
pathogenesis of male visceral obesity.
Pol Merkuriusz Lek 2001
Aug;11(62):187-90
Testosterone, dehydroepiandrosterone,
insulin-like growth factor 1, and insulin in sedentary and
physically trained aged men.
The influence of physical activity on
dehydroepiandrosterone sulfate (DHEAS), total and free
testosterone (TT and FT, respectively), insulin-like growth
factor I (IGF-1), follicle-stimulating hormone (FSH),
luteinizing hormone (LH) and insulin concentrations in aging
men was investigated. Eight trained and nine sedentary men
aged 60 to 65 years volunteered to participate in this study.
Physical activity was determined during an effort test and
evaluated by the measure of the maximal aerobic power
(W(aer,max)). In the trained aging men, the W(aer,max) was
higher than in the sedentary group of matching age [mean (SD)
206.8 (17.1) W versus 136.6 (12.3) W; P<0.0001]. The fat
percentage was higher in the sedentary (n = 9) than in the
trained (n = 8) group [23.9 (3.2)% versus 14.6 (3.7)%;
P<0.0001]. DHEAS and IGF-1 levels were higher in trained
than in sedentary subjects, respectively 2.04 (1) micromol/l
versus 1.01 (0.68) micromol/l (P=0.02) and 192.1 (40.1) ng/ml
versus 132.8 (31.2) ng/ml (P= 0.003). Insulin levels were
higher in sedentary subjects [11.2 (3.5) mIU/l versus 7.6
(2.2) mIU/l, P=0.03]. No statistical difference was observed
between both groups for FT and total TT values, FSH values and
LH values. IGF-1 was correlated with W(aer,max) (r = 0.64, P =
0.003), and DHEAS was correlated with IGF-1 (r=0.59, P=0.01).
We observed a relationship between fat percentage and each of
the following hormones: IGF-1 (r=-0.50, P=0.03), FT (r=-0.66,
P= 0.002), TT (r=-0.54, P = 0.02) and insulin (r=0.63,
P=0.004). Insulin was inversely correlated with FT (r= -0.66,
P=0.002) and TT (r=-0.47, P=0.05). These results suggest that
regular physical activity could maintain higher DHEAS and
IGF-1 and lean body mass levels in elderly men, and
participate in general well being in older age.
Eur J Appl Physiol 2001
Jul;85(1-2):177-84
Effects of transdermal application of
7-oxo-DHEA on the levels of steroid hormones, gonadotropins
and lipids in healthy men.
The aim of this study was to investigate the effect of
7-oxo-DHEA (dehydroepiandrosterone) on the serum levels of
steroid sexual hormones, gonadotropins, lipids and
lipoproteins in men. 7-oxo-DHEA was applied onto the skin as a
gel to 10 volunteers aged 27 to 72 years for five consecutive
days. The single dose contained 25 mg 7-oxo-DHEA. Serum
concentrations of testosterone, estradiol, cortisol,
androstenedione, luteinizing hormone (LH),
follicle-stimulating hormone (FSH), sex hormone binding
globulin (SHBG), total cholesterol, HDL- and LDL-cholesterol,
triglycerides, apolipoprotein A-I and B and lipoprotein(a)
were measured before the beginning and shortly after the end
of the steroid application. After the treatment, we noted the
following significant changes: a decline of testosterone and
estradiol levels, increase of LH, HDL-cholesterol and
apolipoprotein A-I levels. The decrease of total cholesterol
levels was of the borderline significance. A slight but
significant increase was found in apolipoprotein B and
lipoprotein(a). The most expressive was the fall of the
atherogenic index. We suggest that the gel containing
7-oxo-DHEA might be a suitable drug for improving the
composition of the steroid and lipid parameters in elderly
men.
Physiol Res 2001;50(1):9-18
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: Prospective six 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
The acute effect of dexamethasone on
plasma leptin concentrations and the relationships between
fasting leptin, the IGF-I/IGFBP system,
dehydroepiandrosterone, androstenedione and testosterone in an
elderly population.
OBJECTIVE: To investigate the acute effect of dexamethasone
administration on serum leptin levels and the relationships
between dehydroepiandrosterone (DHEAS), androstenedione,
testosterone and the IGF-I/IGFBP system and leptin levels in
healthy elderly humans. METHODS: In 209 healthy elderly
individuals (95 men, 114 women, aged 55 to 80 years)
measurements were made in the fasting state (0800 h) and after
an overnight dexamethasone suppression test (1 mg p.o. at 2300
h. RESULTS: Mean leptin levels increased from 6.2 +/- 0.4 (SE)
micrograms/l to 7.3 +/- 0.5 (SE) micrograms/l in men and from
18.9 +/- 1.4 (SE) micrograms/l to 23.9 +/- 1.8 (SE)
micrograms/l in women after 1 mg dexamethasone overnight
(‘post treatment’)(P < 0.001 for both sexes).
There was a significant relationship between post-treatment
leptin and dexamethasone levels (men: P = 0.002; women: P <
0.001). The increase in leptin levels after dexamethasone
administration was only partially related to the increase in
plasma insulin concentrations. Cortisol levels were not
related to leptin. In multivariate analyses the relationship
between post-treatment leptin and dexamethasone levels
remained after adjustment for post-treatment insulin levels,
BMI, waist:hip ratio (WHR) and age (men: P < 0.001; women:
P = 0.001). Plasma (free and total) IGF-I and IGFBP-3 levels
were not related to leptin levels in men or women. IGFBP-1
levels were inversely related to leptin levels (P = 0.02), but
this relationship was lost after adjustment for insulin,
and/or BMI. In multivariate analyses the relationship between
leptin and DHEAS was inverse in women (P = 0.04) (after
adjustment for BMI, WHR, insulin and glucose), while there was
no relationship between leptin and DHEAS in men. CONCLUSIONS:
Administration of dexamethasone acutely increased leptin
levels within 9 h in this elderly population. This increase
was only partly related to changes in circulating insulin
concentrations, but was independent of BMI and waist:hip
ratio. No relation existed between leptin and (free or total)
IGF-I and IGFBP-3 in men or women. Dehydroepiandrosterone was
inversely related to leptin in women. These findings suggest a
contributory regulatory role for corticosteroids in modulating
circulating leptin concentrations in elderly healthy
individuals of both sexes, which is at least in part
independent of insulin, BMI and waist:hip ratio.
Dehydroepiandrosterone might play a role in the
gender-specific differences in serum leptin levels.
Clin Endocrinol (Oxf) 1998
May;48(5):621-6
Dehydroepiandrosterone (DHEA), DHEA
sulfate, and aging: contribution of the DHEAge Study to a
sociobiomedical issue.
The secretion and the blood levels of the adrenal steroid
dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS)
decrease profoundly with age, and the question is posed
whether administration of the steroid to compensate for the
decline counteracts defects associated with aging. The
commercial availability of DHEA outside the regular
pharmaceutical-medical network in the United States creates a
real public health problem that may be resolved only by
appropriate long-term clinical trials in elderly men and
women. Two hundred and eighty healthy individuals (women and
men 60 to 79 years old) were given DHEA, 50 mg, or placebo,
orally, daily for a year in a double-blind, placebo-controlled
study. No potentially harmful accumulation of DHEAS and active
steroids was recorded. Besides the reestablishment of a
“young” concentration of DHEAS, a small increase of
testosterone and estradiol was noted, particularly in women,
and may be involved in the significantly demonstrated
physiological-clinical manifestations here reported. Bone
turnover improved selectively in women > 70 years old, as
assessed by the dual-energy x-ray absorptiometry (DEXA)
technique and the decrease of osteoclastic activity. A
significant increase in most libido parameters was also found
in these older women. Improvement of the skin status was
observed, particularly in women, in terms of hydration,
epidermal thickness, sebum production, and pigmentation. A
number of biological indices confirmed the lack of harmful
consequences of this 50 mg/day DHEA administration over one
year, also indicating that this kind of replacement therapy
normalized some effects of aging, but does not create
“supermen/women” (doping).
Proc Natl Acad Sci U S A 2000
Apr11;97(8):42784
Relationship between serum
dehydroepiandrosterone sulfate, androstenedione and sex
hormones in men and women.
Previous reports of a correlation between serum
dehydroepiandrosterone sulfate (DHEAS) and testosterone in
both men and women have led to the suggestion that adrenal and
gonadal secretion are related. In the present study, the
correlation of DHEAS with testosterone and free testosterone
(FT) in both normal men and women was tested. Androstenedione,
estradiol, sex hormone binding globulin (SHBG), and insulin
were also measured and their correlations determined. All
correlations were controlled for age and body mass index. In
the men in the study, DHEAS did not correlate with
testosterone or FT but correlated strongly with
androstenedione. In the women, DHEAS correlated strongly with
testosterone, FT, and androstenedione; androstenedione in turn
correlated strongly with testosterone and FT. DHEAS showed no
correlations with estradiol, SHBG, or insulin in the men or
women. The lack of a correlation between DHEAS and
testosterone in normal men is consistent with the independent
secretion of these hormones by the adrenal and testis,
respectively. The finding of a strong DHEAS-testosterone
correlation in normal women may be explained by parallel
adrenal secretion in response to trophic stimuli, i.e.,
without invoking an adrenal-gonadal interaction
Eur J Endocrinol 1996
Feb;134(2):201-6
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