|
241. Relationship of plasma sex hormones to
different parameters of obesity in male subjects.
Kley HK, Edelmann P, Kruskemper HL
Metabolism 1980 Oct;29(11):1041-5
Relationships between plasma sex hormones and different
parameters of obesity (weight, ideal body weight [IBW],
overweight, fat mass, and body surface) were investigated in
70 healthy nonobese and obese males, 20-40 yr of age and with
a body weight of 85%-245% of IBW. Plasma sex hormones remained
unaffected by weight up to approximately 160% of the IBW. Only
in the massively obese subjects was plasma testosterone
decreased to 40% of controls (from 6.2 to 2.5 ng/ml), whereas
free testosterone remained almost constant. On the
other hand, plasma estrone and estradiol exhibited significant
increases in obese subjects, ranging from 31.5 +/- 52.3 +/-
5.8 pg/ml for estrone, and 25.4 +/- 5.4 increasing to 44.7 +/0
5.0 pg/ml for estradiol. Similarly, free estradiol was shown
to significantly increase with obesity in men from 505 +/- 118
to 991 +/- 123 fg/ml (p < 0.001). The ratios of
testosterone/androstenedione, as well as of estradiol/estrone,
were not affected by obesity, suggesting that reduction of the
17-oxo-group of the steroids is not influenced by the amount
of fat tissue. A significant (p < 0.001) correlation was
found between IBW and estrone (r = 0.80) and estradiol (r =
0.75), as well as the ratios of estrone/androstenedione (r =
0.62) and estradiol/testosterone (r = 0.86). This is
consistent in its evidence indicating that fat tissue may be
able to aromatize androgens. In the obese subjects,
there were significant correlations between plasma sex
hormones (testosterone, estrone, estradiol, and free
estradiol) and the parameters of obesity used. Among these,
correlations were best with IBW, overweight, and fat mass (r =
0.74-0.89; p < 0.001); body weight and body surface were
less favorable.
242. The relationship between aromatase activity
and body fat distribution.
Killinger DW; Perel E; Daniilescu D; Kharlip L; Lindsay
WR
Department of Medicine, University of Toronto, Canada.
Steroids (United States) Jul-Sep 1987, 50 (1-3)
p61-72
The metabolism of androstenedione (A) to estrone (E1) and 5
alpha-reduced androgens was studied in stromal cells derived
from human adipose tissue from different body sites. The
tissue was obtained from non-obese patients undergoing
cosmetic liposuction or at the time of surgery for reduction
mammoplasty. The conversion of A to E1 per 1x 10(6)
cells was between 6- and 30-fold greater in the upper thigh,
buttock, and flank than in the abdomen. These
differences were present in primary culture and persisted to
at least the third subculture. Estrogen formation in
breast adipose tissue was similar to that found in cells from
abdominal fat. The formation of 5 alpha-reduced
metabolites (5 alpha-androstenedione, androsterone, and
dihydrotestosterone) varied from patient to patient but was
similar in cells from different body sites. These
studies show that the regional distribution of fat may
influence the metabolism of androgens in adipose tissue, with
upper body fat tending to form a lower ratio of estrogens to 5
alpha-reduced androgens than lower body fat.
243. Effects of a fat-containing meal on sex
hormones in men.
Meikle AW, Stringham JD, Woodward MG, McMurry MP
Department of Internal Medicine, University of Utah School of
Medicine, Salt Lake City.
Metabolism 1990 Sep;39(9):943-6
The effect of a fat-containing meal on plasma sex steroid
concentrations was investigated in normal men. After an
overnight fast on two separate occasions, subjects ingested a
liquid meal containing either a nonnutritive sweetener
(control), or isocaloric meals of mixed calorie sources with
either high-fat content or mixed carbohydrate and protein with
minimal fat. The order of the meals was alternated. Blood
samples were collected at 15-minute intervals and pooled each
hour. Sampling began at 7:00 AM and the test meal was ingested
at 8:00 AM. Sex steroids, including estrone, estradiol,
testosterone, and dihydrotestosterone (DHT), sex
hormone-binding globulin (SHBG) capacity, free testosterone
concentration, and luteinizing hormone (LH) were determined by
either specific radioimmunoassay or dialysis. The
fat-containing meal, but not the nonnutritive or mixed
carbohydrate and protein meal, resulted in a significant (P
less than .01) reduction in total and free testosterone.
Estrogens and luteinizing hormone were unaffected by either
meal. This is the first documentation, to our knowledge, of
the acute effect of a fat-containing meal on sex steroid
concentrations in blood. Our observations suggest that a
fat-containing meal reduces testosterone concentrations
without affecting luteinizing hormone. This might indicate
that fatty acids modulate testosterone production by the
testes.
244. Phytosterol feeding induces alteration in
testosterone metabolism in rat tissues.
Awad Atif B(a); Hartati Maria Sri; Find Carol S
15 Farber Hall, Univ. Buffalo, Buffalo, NY 14214-3000,
USA
Journal of Nutritional Biochemistry 9 ( 12 ): p 712-717 Dec.,
1998
The objective of the present study was to examine the
metabolism of testosterone in rat tissues as influenced by
dietary phytosterols. Testosterone metabolism includes
reductions to more active metabolites or aromatization to
estrogen . Both higher levels of androgens and estrogens are
implicated as risk factors in the development of prostate
cancer. Tissues studied included liver, testis, and
prostate. Feeding 2% phytosterols with 0.2% cholic
acid to rats for 22 days resulted in a 33% reduction in serum
testosterone compared with controls, which received only 0.2%
cholic acid in the diet. 5-alpha-Reductase was
reduced by 41 to 44% and 33% in the liver and prostate,
respectively. No effect of phytosterols was observed in the
testis. Only aromatase activity of the prostate was
reduced by 55% upon feeding phytosterols. It was
concluded that dietary phytosterols may reduce the risk of
prostate cancer by lowering the activities of the enzymes of
testosterone metabolism.
245. 24 Hour profiles of circulating androgens and
estrogens in male puberty with and without gynecomastia
Large D M; Anderson D C
Dep. Med., Hope Hosp., Salford M6 8HD, Lancas., Engl.,
UK.
Clin Endocrinology 11 (5). 1979. 505-522.
The possible mechanisms involved in the development of
transient gynecomastia during male puberty were investigated
by studying 24 h profiles of circulating androstenedione (Ao)
and testosterone (T) and their estrogen pairs estrone (E1) and
estradiol (E2), in 8 boys with simple delayed puberty, 11 boys
with pubertal gynecomastia (3 of whom were re-tested after its
spontaneous resolution) and 2 normal adult men. No differences
were observed between the 24 h T and Ao profiles of pubertal
boys with or without gynecomastia; the initial T rise was
nocturnal, associated with sleep. Late in puberty daytime T
levels also rise. A small rise in 24 h Ao was seen, but this
was not closely related to the stage of puberty. The major new
finding was that E2 and to a lesser extent E1 levels are high
relative to T for prolonged periods of the afternoon and
evening (when T levels are lowest) in male puberty. A frequent
finding, seen only in boys with gynecomastia and one who later
developed it, was of elevated and markedly fluctuating levels
of plasma E2, and an absolute increase in the area under the
24 h E2 profile and between the E2 and T profiles. These fell
towards normal in 3 boys who were re-tested after resolution
of gynecomastia. In a minority of subjects T and E2
were quite closely correlated, suggesting that in them rapid
aromatization of T was occurring within or outside the
testis. Normal male puberty is associated with
relative estrogen dominance particularly in the daytime. In
boys with gynecomastia there is an addition often an absolute
elevation of E2 with or without E1, while 24 h T levels are
submaximal. Normal men probably require sustained
adult circulating T levels to prevent their estrogens from
stimulating breast development.
246. The association between moderate alcoholic
beverage consumption and serum estradiol and testosterone
levels in normal postmenopausal women: relationship to the
literature.
Gavaler JS; Van Thiel DH
Department of Medicine, University of Pittsburgh School of
Medicine, PA 15213.
Alcohol Clin Exp Res (United States) Feb 1992, 16 (1)
p87-92
The major source of endogenous estrogens in postmenopausal
women is the aromatization of androgens to estrogens;
because alcohol is known to increase aromatization,
the relationship between moderate alcoholic beverage
consumption and serum estradiol levels was evaluated in 128
normal postmenopausal women. Alcohol intake was based on a
composite of self-report and food record information.
Among the 78.8% of women reporting alcohol use, weekly
intake was 4.8 +/- 0.6 drinks. Among abstainers, estradiol
levels were 100.8 +/- 12.1 pmol/liter, significantly lower
than in alcohol users, 162.6 +/- 11.9 pmol/liter.
Significant bivariate correlations were found between the
logarithm of estradiol and total weekly drinks. In multiple
linear regression analyses inclusion of alcohol as a variable
increased the amount of explained variation in estradiol.
Similar findings were demonstrable when the crude estimator of
aromatization, the estradiol:testosterone ratio logarithm was
the dependent variable. Together, these findings suggest that
moderate alcohol use is an important factor for postmenopausal
estrogen status and may offer a partial explanation for the
reported protective effect of moderate alcohol consumption
with respect to postmenopausal cardiovascular disease risk. (
51 Refs.)
247. Dietary zinc deficiency alters
5-alpha-reduction and aromatization of testosterone and
androgen and estrogen receptors in rat liver.
Om Ae-Son; Chung Kyung-Won(a)
Dep. Anatomical Sci., Univ. Oklahoma Coll. Med., Oklahoma
City, OK 73104, USA
Journal of Nutrition 126 ( 4 ): p 842-848 1996
We studied the effects of zinc deficiency on hepatic
androgen metabolism and aromatization, androgen and estrogen
receptor binding, and circulating levels of reproductive
hormones in freely fed, pair-fed and zinc-deficient rats.
Hepatic conversion of testosterone to
dihydrotestosterone was significantly less, but formation of
estradiol from testosterone was significantly greater in rats
fed the zinc-deficient diet compared with freely fed and
pair-fed control rats. There were significantly lower serum
concentrations of luteinizing hormone, estradiol and
testosterone in rats fed the zinc-deficient diet. No
difference in the concentration of serum follicle-stimulating
hormone was observed between the zinc-deficient group and
either control group. Scatchard analyses of the
receptor binding data showed a significantly higher level of
estrogen receptor in zinc-deficient rats (36.6 +- 3.4 fmol/mg
protein) than in pair-fed controls (23.3 +- 2.2 fmol/mg
protein) and a significantly lower level of androgen binding
sites in rats fed the zinc-deficient diet (6.7 +- 0.7 fmol/mg
protein) than in pair-fed control rats (11.3 +- 1.2 fmol/mg
protein). There were no differences in hepatic
androgen and estrogen receptor levels between freely fed and
pair-fed controls. These findings indicate that zinc
deficiency reduces circulating luteinizing hormone and
testosterone concentrations, alters hepatic steroid
metabolism, and modifies sex steroid hormone receptor levels,
thereby contributing to the pathogenesis of male reproductive
dysfunction.
248. Classification of obese patients and
complications related to the distribution of surplus
fat.
Bjorntorp P
Department of Medicine I, Sahlgren's Hospital, University of
Goteborg, Sweden.
Nutrition (United States) Mar-Apr 1990, 6 (2)
p131-7
The relation between obesity and noninsulin-dependent
diabetes mellitus is established. The weak association between
obesity and cardiovascular disease or stroke might be
attributable to a risk present only in a subgroup of obesity
patients. Recent prospective studies have shown such a group
to be characterized by abdominal localization of adipose
tissue, reviving old empiric observations of such links. The
sex-linked adipose tissue distribution is probably dependent
on a balance between glucocorticoids and sex steroid hormones.
The former are active mainly on intraabdominal adipose tissues
through the high density of a specific receptor expressing
lipoprotein lipase activity. This effect is counteracted by
female sex steroid hormones, mainly progesterone, which
promote fat deposition in the gluteal-femoral regions,
utilized mainly during pregnancy and lactation.
Testosterone stimulates lipid mobilization through
transcriptional expression of beta-adrenergic receptors via a
specific androgen receptor and also inhibits lipoprotein
lipase activity. Intraabdominal adipose tissues,
drained by the portal vein, have a very sensitive lipolytic
system in men, based on an increased beta-adrenoceptor
activity. This is probably a testosterone effect via the
mechanisms mentioned. With testosterone deficiency, these
mechanisms are less active, permitting accumulation of fat
that can be reversed by testosterone substitution.
Abdominal distribution of fat in men thus is probably
a sign of relative testosterone deficiency.
249. Sex steroids and bone mass in older men.
Positive associations with serum estrogens and negative
associations with androgens.
Slemenda CW, Longcope C, Zhou L, Hui SL, Peacock M, Johnston
CC
Department of Medicine, Indiana University School of
Medicine, Indianapolis, Indiana 46202, USA.
J Clin Invest 1997 Oct 1;100(7):1755-9
The purpose of this study was to determine whether bone
density in older men was associated with serum sex steroids or
sex hormone binding globulin (SHBG). Bone density and sex
steroids were measured in men over age 65 at 6-mo intervals
for an average of 2.1 yr. Bone density was significantly
positively associated with greater serum E2 concentrations
(+0.21 < r < +0.35; 0.01 < P < 0.05) at all
skeletal sites. There were weak negative correlations between
serum testosterone and bone density (-0.20 < r < -0.28;
0.03 < P < 0.10) at the spine and hip. SHBG was
negatively associated only with bone density in the greater
trochanter (r = -0.26, P < 0.05). Greater body weight was
associated with lower serum testosterone and SHBG, and greater
E2. Because of these associations, regression models which
adjusted for age, body weight, and serum sex steroids were
constructed; these accounted for 10-30% of the variability in
bone density, and showed consistent, significant positive
associations between bone density and serum E2 concentrations
in men, even after adjustments for weight and SHBG. These data
suggest that estrogens may play an important role in the
development or maintenance of the male skeleton, much as is
the case for the female skeleton. These data also indicate
that, within the normal range, lower serum testosterone
concentrations are not associated with low bone density in
men.
250. Biotransformation of oral
dehydroepiandrosterone in elderly men: significant increase in
circulating estrogens.
Arlt W, Haas J, Callies F, Reincke M, Hubler D, Oettel M,
Ernst M, Schulte HM, Allolio B
Department of Endocrinology, Medical University Hospital
Wuerzburg, Germany.
J Clin Endocrinol Metab 1999 Jun;84(6):2170-6
The most abundant human steroids, dehydroepiandrosterone
(DHEA) and its sulfate ester DHEAS, may have a multitude of
beneficial effects, but decline with age. DHEA possibly
prevents immunosenescence, and as a neuroactive steroid it may
influence processes of cognition and memory. Epidemiological
studies revealed an inverse correlation between DHEAS levels
and the incidence of cardiovascular disease in men, but not in
women. To define a suitable dose for DHEA substitution in
elderly men we studied pharmacokinetics and biotransformation
of orally administered DHEA in 14 healthy male volunteers
(mean age, 58.8 +/- 5.1 yr; mean body mass index, 25.5 +/- 1.5
kg/m2) with serum DHEAS concentrations below 4.1 micromol/L
(1500 ng/mL). Diurnal blood sampling was performed on 3
occasions in a single dose, randomized, cross-over design
(oral administration of placebo, 50 mg DHEA, or 100 mg DHEA).
The intake of 50 mg DHEA led to an increase in serum DHEAS to
mean levels of young adult men, whereas 100 mg DHEA induced
supraphysiological concentrations [placebo vs. 50 mg DHEA vs.
100 mg DHEA; area under the curve (AUC) 0-12 h (mean +/- SD)
for DHEA, 108 +/- 22 vs. 252 +/- 45 vs. 349 +/- 72 nmol/L x h;
AUC 0-12 h for DHEAS, 33 +/- 9 vs. 114 +/- 19 vs. 164 +/- 36
micromol/L x h]. Serum testosterone and dihydrotestosterone
remained unchanged after DHEA administration. In contrast,
17beta-estradiol and estrone significantly increased in a
dose-dependent manner to concentrations still within the upper
normal range for men [placebo vs. 50 mg DHEA vs. 100 mg DHEA;
AUC 0-12 h for 17beta-estradiol, 510 +/- 198 vs. 635 +/- 156
vs. 700 +/- 209 pmol/L x h (P < 0.0001); AUC 0-12 h for
estrone, 1443 +/- 269 vs. 2537 +/- 434 vs. 3254 +/- 671 pmol/L
x h (P < 0.0001)]. In conclusion, 50 mg DHEA seems to be a
suitable substitution dose in elderly men, as it leads to
serum DHEAS concentrations usually measured in young healthy
adults. The DHEA-induced increase in circulating estrogens may
contribute to beneficial effects of DHEA in men.
251. Lignans from the roots of Urtica dioica and
their metabolites bind to human sex hormone binding globulin
(SHBG).
Schottner M, Gansser D, Spiteller G
Lehrstuhl Organische Chemie I, Universitat Bayreuth,
Germany.
Planta Med 1997 Dec;63(6):529-32
Polar extracts of the stinging nettle (Urtica dioica L.)
roots contain the ligans (+)-neoolivil,
(-)-secoisolariciresinol, dehydrodiconiferyl alcohol,
isolariciresinol, pinoresinol, and
3,4-divanillyltetrahydrofuran. These compounds were either
isolated from Urtica roots, or obtained semisynthetically.
Their affinity to human sex hormone binding globulin
(SHBG) was tested in an in vitro assay. In addition,
the main intestinal transformation products of plant lignans
in humans, enterodiol and enterolactone, together with
enterofuran were checked for their activity. All
lignans except (-)-pinoresinol developed a binding affinity to
SHBG in the in vitro assay. The affinity of
(-)-3,4-divanillyltetrahydrofuran was outstandingly high.
These findings are discussed with respect to potential
beneficial effects of plant lignans on benign prostatic
hyperplasia (BPH).
252. Plant constituents interfering with human sex
hormone-binding globulin. Evaluation of a test method and its
application to Urtica dioica root extracts.
Gansser D, Spiteller G
Lehrstuhl Organische Chemie I, Universitat Bayreuth,
Bundesrepublik, Deutschland.
Z Naturforsch [C] 1995 Jan-Feb;50(1-2):98-104
A test system is described, which allows the search for
compounds interfering with human sex hormone-binding globulin
(SHBG) even in complex plant extracts. The method has been
evaluated and applied to Urtica dioica root extracts.
The lignan secoisolariciresinol (5) as well as a
mixture of isomeric (11 E)-9,10,13-trihydroxy-11-octadecenoic
and (10 E)-9,12,13-trihydroxy-10-octadecenoic acids (3 and 4,
resp.) were demonstrated to reduce binding activity of human
SHBG. Methylation of the mixture of 3 and 4 increased
its activity about 10-fold.
253. Testosterone metabolism in primary cultures of
human prostate epithelial cells and fibroblasts.
Delos S; Carsol JL; Ghazarossian E; Raynaud JP; Martin
PM
Laboratoire de Cancerologie Experimentale, Faculte de
Medecine Secteur Nord, Marseille, France.
J Steroid Biochem Mol Biol (England) Dec 1995, 55 (3-4)
p375-83
We compare testosterone (T) metabolism in primary cultures
of epithelial cells and fibroblasts separated from benign
prostate hypertrophy (BPH) and prostate cancer tissues.
In all cultures, androstenedione (delta 4) formed by
oxidation of T by 17 beta-hydroxysteroid dehydrogenase (17
beta-HSD) represented 80% of the metabolites
recovered. The amounts of 5 alpha-dihydrotestosterone
(DHT), formed by reduction of T by 5 alpha-reductase (5
alpha-R), were small: 5 and 2% (BPH) and 8 and 15%
(adenocarcinoma) for epithelial cells and fibroblasts,
respectively. Northern blot analysis of total RNA from
epithelial cells (BPH or adenocarcinoma) attributed the
reductive activity to the 5 alpha-reductase type 1 isozyme and
oxidative activity to the 17 beta-HSD type 2. In cancer
fibroblasts, only little 17 beta-HSD type 2 mRNA was detected.
The 5 alpha-reductase inhibitors, 4-MA (17
beta-(N,N-diethyl)carbamoyl-4-methyl-4 -aza-5
alpha-androstan-3-one) and finasteride, inhibited DHT
formation with a preferential action of 4-MA on epithelial
cells (BPH or adenocarcinoma) and of finasteride on
fibroblasts from adenocarcinoma. Neither inhibitor acted on
delta 4 formation. On the other hand, the
lipido-sterol extract of Serenoa repens (LSESr, Permixon)
inhibited the formation of all the T metabolites studied [IC50
S = 40 and 200 micrograms/ml (BPH) and 90 and 70 micrograms/ml
(adenocarcinoma) in epithelial cells and fibroblasts,
respectively]. These results have important therapeutic
implications when selecting appropriate treatment options for
BPH.
254. Effect of exogenous testosterone on prostate
volume, serum and semen prostate specific antigen levels in
healthy young men.
Cooper CS, Perry PJ, Sparks AE, MacIndoe JH, Yates WR,
Williams RD
Department of Urology, The University of Iowa, Iowa City,
USA.
J Urol 1998 Feb;159(2):441-3
PURPOSE: We investigate and define the effects of exogenous
testosterone on the normal prostate.
MATERIALS AND METHODS: A total of 31 healthy volunteers 21
to 39 years old were randomized to receive either 100, 250 or
500 mg. testosterone via intramuscular injection once a week
for 15 weeks. Baseline measurements of serum testosterone,
free testosterone and prostate specific antigen (PSA) were
taken at week 1. Semen samples were also collected for PSA
content and prostate volumes were determined by transrectal
ultrasound before testosterone injection. Blood was then drawn
every other week before each testosterone injection for the 15
weeks, every other week thereafter until week 28 and again at
week 40. After the first 15 weeks semen samples were again
collected, and prostate volumes were determined by repeat
transrectal ultrasound.
RESULTS: Free and total serum testosterone levels increased
significantly in the 250 and 500 mg. dose groups. No
significant change occurred in the prostate volume or serum
PSA levels at any dose of exogenous testosterone.
Total semen PSA levels decreased following
administration of testosterone but did not reach statistical
significance.
CONCLUSIONS: Despite significant elevations in serum total
and free testosterone, healthy young men do not demonstrate
increased serum or semen PSA levels, or increased prostate
volume in response to exogenous testosterone injections.
255. The effect of exogenous testosterone on total
and free prostate specific antigen levels in healthy young
men.
Cooper CS, MacIndoe JH, Perry PJ, Yates WR, Williams RD
Department of Urology, University of Iowa, Iowa City,
USA.
J Urol 1996 Aug;156(2 Pt 1):438-41; discussion
441-2
PURPOSE: We evaluated the effect of exogenous
testosterone administration on serum total and free prostate
specific antigen (PSA) in healthy young men.
MATERIALS AND METHODS: Nine volunteers received either 100,
250 or 500 mg. testosterone by intramuscular injection each
week for 15 weeks. Blood was drawn every other week for 28
weeks and at week 40. Serum total and free PSA, and total and
free testosterone were measured and compared to baseline
values.
RESULTS: Significant elevations in total and free
testosterone occurred but no significant change in serum total
and free PSA was detected.
CONCLUSIONS: Serum PSA is not responsive to elevated serum
testosterone levels in healthy young men. PSA
metabolism in the normal prostate is unclear but our findings
may have implications for differentiation of pathological
conditions of the human prostate.
256. Prostate-specific antigen and prostate gland
size in men receiving exogenous testosterone for male
contraception.
Wallace EM, Pye SD, Wild SR, Wu FC
MRC Reproductive Biology Unit, Edinburgh, Scotland,
U.K.
Int J Androl 1993 Feb;16(1):35-40
Steroid regimens containing androgens are being
evaluated currently as hormonal contraceptives for men. The
possible non-reproductive effects of such treatment were
assessed during an efficacy trial using a prototype regime of
200 mg testosterone enanthate i.m. weekly. Prostatic function
and size were monitored by regular rectal examination, blood
levels of prostate-specific androgen (PSA) were measured in 30
men and prostatic size was measured by trans-rectal ultrasound
imaging in a representative subgroup of five subjects for 12
months and for a further 6 months after
discontinuation. Despite the sustained rise in serum
levels of testosterone, oestradiol and dihydrotestosterone
during treatment, there was no detectable increase in
prostatic size on rectal examination or any significant change
in blood concentrations of PSA. A small but
significant increase (14.3 +/- 2.0%) in maximal prostate
transverse area was observed in four men while the remaining
one showed no change. Our preliminary data demonstrate the
feasibility and importance of monitoring prostatic function in
the development of androgen-containing male hormonal
contraceptives.
257. Prostate size in hypogonadal men treated with
a nonscrotal permeation-enhanced testosterone transdermal
system.
Meikle AW, Arver S, Dobs AS, Adolfsson J, Sanders SW,
Middleton RG, Stephenson RA, Hoover DR, Rajaram L, Mazer
NA
Department of Medicine, University of Utah, Salt Lake City
84132, USA.
Urology 1997 Feb;49(2):191-6
OBJECTIVES: This study examined the effects of
testosterone replacement using a nonscrotal testosterone
transdermal (TTD) system on prostate size and
prostate-specific antigen (PSA) levels in hypogonadal
men.
METHODS: As part of an open-label, multicenter study,
prostate volume as measured by transrectal ultrasound and PSA
were assessed in 29 hypogonadal men during treatment with
intramuscular testosterone enanthate (+TE), followed by 8
weeks of androgen withdrawal (-T), and then during 1 year of
therapy with Androderm Testosterone Transdermal System, a
nonscrotal permeation-enhanced TTD system (+TTD).
RESULTS: Mean prostate volume decreased significantly from
the +TE period (17 g) compared with the -T period (14 g) (P
< 0.001). Prostate volume increased significantly from the
-T period compared with the +TTD period (18 g) (P < 0.001).
Maximum prostate size, comparable to that measured during +TE
(P = 0.125), was reached by month 3 of +TTD therapy; prostate
volume did not increase further during the remaining 9 months
of +TTD therapy. Prostate volume correlated with age (P <
0.01) during all three periods of observation (+TE: r = 0.69;
-T: r = 0.64; and +TTD: r = 0.55). No patient developed
symptomatic benign prostatic hyperplasia during the treatment
period. PSA levels decreased during androgen withdrawal
compared with levels measured during +TE treatment (P <
0.001) and rose with resumption of androgen therapy with TTD
(P < 0.006). However, PSA levels during +TTD replacement
remained significantly lower (P < 0.001) than during +TE
replacement.
CONCLUSIONS: Physiologic testosterone replacement in
hypogonadal men was achieved using the TTD system. Prostate
size during therapy with TTD was comparable to that reported
for normal men. In these men treated with TTD, PSA levels were
also within the normal range.
258. Effect of oral androstenedione on serum
testosterone and adaptations to resistance training in young
men: a randomized controlled trial.
King DS, Sharp RL, Vukovich MD, Brown GA, Reifenrath TA, Uhl
NL, Parsons KA
Department of Health and Human Performance, Iowa State
University, Ames 50011, USA.
dsking@iastate.edu
JAMA 1999 Jun 2;281(21):2020-8
CONTEXT: Androstenedione, a precursor to testosterone, is
marketed to increase blood testosterone concentrations as a
natural alternative to anabolic steroid use. However, whether
androstenedione actually increases blood testosterone levels
or produces anabolic androgenic effects is not known.
OBJECTIVES: To determine if short- and long-term oral
androstenedione supplementation in men increases serum
testosterone levels and skeletal muscle fiber size and
strength and to examine its effect on blood lipids and markers
of liver function.
DESIGN AND SETTING: Eight-week randomized controlled trial
conducted between February and June 1998.
PARTICIPANTS: Thirty healthy, normotestosterogenic men
(aged 19-29 years) not taking any nutritional supplements or
androgenic-anabolic steroids or engaged in resistance
training.
INTERVENTIONS: Twenty subjects performed 8 weeks of
whole-body resistance training. During weeks 1, 2, 4, 5, 7,
and 8, the men were randomized to either androstenedione, 300
mg/d (n = 10), or placebo (n = 10). The effect of a single
100-mg androstenedione dose on serum testosterone and estrogen
concentrations was determined in 10 men.
MAIN OUTCOME MEASURES: Changes in serum testosterone and
estrogen concentrations, muscle strength, muscle fiber
cross-sectional area, body composition, blood lipids, and
liver transaminase activities based on assessments before and
after short- and long-term androstenedione administration.
RESULTS: Serum free and total testosterone concentrations
were not affected by short- or long-term androstenedione
administration. Serum estradiol concentration (mean [SEM]) was
higher (P<.05) in the androstenedione group after 2 (310
[20] pmol/L), 5 (300 [30] pmol/L), and 8 (280 [20] pmol/L)
weeks compared with resupplementation values (220 [20]
pmol/L). The serum estrone concentration was significantly
higher (P<.05) after 2 (153 [12] pmol/L) and 5 (142 [15]
pmol/L) weeks of androstenedione supplementation compared with
baseline (106 [11] pmol/L). Knee extension strength increased
significantly (P<.05) and similarly in the placebo (770
[55] N vs 1095 [52] N) and androstenedione (717 [46] N vs 1024
[57] N) groups. The increase of the mean cross-sectional area
of type 2 muscle fibers was also similar in androstenedione
(4703 [471] vs 5307 [604] mm2; P<.05) and placebo (5271
[485] vs 5728 [451] mm2; P<.05) groups. The significant
(P<.05) increases in lean body mass and decreases in fat
mass were also not different in the androstenedione and
placebo groups. In the androstenedione group, the serum
high-density lipoprotein cholesterol concentration was reduced
after 2 weeks (1.09 [0.08] mmol/L [42 (3) mg/dL] vs 0.96
[0.08] mmol/L [37 (3) mg/dL]; P<.05) and remained low after
5 and 8 weeks of training and supplementation.
CONCLUSIONS: Androstenedione supplementation does not
increase serum testosterone concentrations or enhance skeletal
muscle adaptations to resistance training in
normotestosterogenic young men and may result in adverse
health consequences.
259. Severe sexual impairment produced by morbid
obesity. Report of a case.
Blum I; Marilus R; Barasch E; Sztern M; Bruhis S; Kaufman
H
Department of Medicine C, Rokach (Hadassah) Hospital,
Tel-Aviv, Israel.
Int J Obes (England) 1988, 12 (3) p185-9
A 45-year-old man, was admitted for investigation of severe
sexual impairment. During 20 years of marriage, he had had no
normal sexual intercourse and the couple was childless.
Physical examination disclosed a severely obese man (weight
300 kg, height 1.75 m), with a relatively small and
invaginated penis and small (5 ml) soft testes. Laboratory
examinations disclosed the following: low serum testosterone
(1 ng/ml), with a reduced response to HCG (3.8 ng/ml). Sex
hormone binding globulin was at the lower limit of normal
(0.38 microgram/dl), serum free testosterone was low (0.98% of
total testosterone) as well as non-SHBG bound testosterone
(22% of total testosterone). Daily total urinary estrogen
excretion was increased (107 micrograms), the plasma estrone
(78 pg/ml) and estradiol (74 pg/ml) were elevated. The
gonadotropins were normal and responded adequately to LRH.
Plasma growth hormone was decreased, prolactin, T4 and adrenal
steroids were normal and responded normally to stimuli and
inhibitors. Chromosomal constitution was 46XY. Thus,
in this man the marked obesity produced a significant increase
in estrogens which subsequently induced a severe decrease in
testosterone and its free counterpart in excessive impairment
of sexual function.
260. The Testosterone Syndrome
Shippen and Fryer
1998 M. Evans and Company New York, NY
No abstract.
261. Sex hormones and coronary artery
disease.
Chute CG, Baron JA, Plymate SR, Kiel DP, Pavia AT, Lozner EC,
O'Keefe T, MacDonald GJ
Department of Medicine, Dartmouth-Hitchcock Medical Center,
Hanover, New Hampshire 03756.
Am J Med 1987 Nov;83(5):853-9
Published erratum appears in Am J Med 1988
Jul;85(1):129
Previous investigators have found an increased risk of
coronary heart disease in men with high levels of circulating
estrogens. To elucidate further this relationship, a
case-control study of atherosclerotic coronary artery disease
(ASCAD) and sex hormones was undertaken in male patients.
Hormone levels in men with severe ASCAD documented at
angiography were compared with those in men found to be
virtually free from disease and with those in a group of
control subjects without signs or symptoms of ASCAD.
Significantly lower total testosterone levels were
observed among men with severe ASCAD compared with either
control group; the free testosterone level was
significantly lower than in angiographically disease-free
control subjects. The same pattern of hormone levels persisted
after control of covariates. Epidemiologic analysis
demonstrated a fivefold decrease in risk for severe ASCAD
between the lowest and the highest quartile of total
testosterone. No overall pattern of association was seen
between ASCAD and free or total estrogens.
262. Serum estrogen levels in men with acute
myocardial infarction.
Klaiber EL, Broverman DM, Haffajee CI, Hochman JS, Sacks GM,
Dalen JE
Am J Med 1982 Dec;73(6):872-81
Serum estradiol and serum estrone levels were assessed in
29 men in 14 men in whom myocardial infarction was ruled out;
in 12 men without apparent coronary heart disease but
hospitalized in an intensive care unit; and in 28 men who were
not hospitalized and who acted as control subjects. (The 12
men who were hospitalized but who did not have coronary heart
disease were included to control for physical and emotional
stress of a severe medical illness.) Ages ranged from 21 to 56
years. Age, height, and weight did not differ significantly
among groups. Blood samples were obtained in the patient
groups on each of the first three days of hospitalization.
The serum estrone level was significantly elevated in
all four patient groups when compared with that in the control
group. Estrone level, then, did not differentiate
patients with and without coronary heart disease.
Serum estradiol levels were significantly elevated in
the groups with myocardial infarction, unstable angina, and in
the group in whom myocardial infarction was ruled
out. However, estradiol levels were not significantly
elevated in the group in the intensive care unit without
coronary heart disease when compared to the level in the
normal control group. Serum estradiol levels, then, were
elevated in men with confirmed or suspected coronary heart
disease but were not elevated in men without coronary heart
disease even under the stressful conditions found in an
intensive care unit. Serum estradiol levels were significantly
and positively correlated (p less than 0.03) with serum total
creatine phosphokinase levels in the patients with myocardial
infarction. The five patients with myocardial infarction who
died within 10 days of admission had markedly elevated serum
estradiol levels. The potential significance of these serum
estradiol elevations is discussed in terms of estradiol's
ability to enhance adrenergic neural activity and the
resultant increase in myocardial oxygen demand.
263. Variability in plasma oestrogen concentrations
in men with a myocardial Infarction.
Lindholm J, Eldrup E, Winkel P
Department of Internal Medicine and Endocrinology, Herlev
University Hospital, Copenhagen.
Dan Med Bull 1990 Dec;37(6):552-6
Several studies have reported high levels of
oestrogens--especially oestradiol--in plasma in men surviving
an acute myocardial infarction (AMI). We have measured plasma
levels of the two major oestrogens, oestrone and oestradiol,
for three days during the acute AMI and at three months after
discharge. Patients admitted to a coronary care unit with
ischaemic heart disease without proof of an infarction and
patients without evidence of heart disease served as controls.
We found significantly higher oestrone levels during the acute
infarction than at three months afterwards and also higher
than in men without AMI. Men who died shortly after
admission had grossly elevated plasma oestrone
concentrations. As oestrone levels were correlated to
excretion of catecholamines and cardiac enzyme levels in
plasma and as circulating levels of oestrone are influenced by
ACTH, the hyperoestronaemia may reflect stress-induced
increased adrenocortical activity. Plasma oestradiol
concentrations in men with AMI decreased significantly during
the first three days after admission. In men given no
medication oestradiol concentrations did not differ
significantly from those in the control groups. Three months
after the infarction, the median plasma oestradiol (but not
oestrone) concentrations were significantly elevated, but not
if only data from men given no medication were considered.
264. Relationships of plasminogen activator
inhibitor activity and lipoprotein(a) with insulin,
testosterone, 17 beta-estradiol, and testosterone binding
globulin in myocardial infarction patients and healthy
controls.
Marques-Vidal P, Sie P, Cambou JP, Chap H, Perret B
MONICA-Observatoire Regional de la Sante de Midi-Pyrenees,
INSERM U326, C.H.U. Purpan, Toulouse, France.
J Clin Endocrinol Metab 1995 Jun;80(6):1794-8
The relationships between plasminogen activator inhibitor
(PAi) activity and lipoprotein(a) [Lp(a)] and insulin,
testosterone, 17 beta-estradiol, and testosterone binding
globulin (TEBG) were assessed in 42 myocardial infarction male
patients and 74 healthy controls. Patients had higher levels
of insulin than did controls (87 +/- 30 vs. 75 +/- 28 pmol/L,
respectively; P < 0.04), and no differences were found in
levels of PAi activity, testosterone, 17 beta-estradiol, and
TEBG. Lp(a) levels greater than 0.3 g/L were more frequent in
patients than in controls (P < 0.002). In all
subjects, PAi activity levels were significantly and
positively correlated with body mass index (r = 0.20, P <
0.05), triglycerides (r = 0.38, P < 0.0001), and insulin (r
= 0.27, P < 0.005) and were negatively correlated with
testosterone (r = -0.28, P < 0.005) and TEBG (r = -0.42, P
< 0.001). Stepwise multiple regression analysis
showed triglyceride, insulin, and TEBG levels to be
significantly related to PAi activity. No significant
correlations were found between Lp(a) levels and all hormonal
variables studied and between Lp(a) and PAi activity (r =
-0.06, P < 0.58). These results suggest that TEBG is
significantly and independently related to PAi levels.
265. Sex hormones, insulin, lipids, and prevalent
ischemic heart disease.
Lichtenstein MJ, Yarnell JW, Elwood PC, Beswick AD, Sweetnam
PM, Marks V, Teale D, Riad-Fahmy D
Am J Epidemiol 1987 Oct;126(4):647-57
The relations between estradiol, testosterone, insulin,
lipids, and prevalent ischemic heart disease were examined
using the cross-sectional data from the Caerphilly Heart
Disease Study, a cohort of 2,512 men (aged 45-59 years)
surveyed between 1978 and 1982. Endogenous levels of estradiol
were associated directly with high density lipoprotein (HDL)
cholesterol (r = 0.106, p less than 0.001), but this relation
was removed after adjustment for testosterone and insulin
levels. Estradiol was not associated with prevalent ischemic
heart disease. Endogenous levels of testosterone were
associated directly with HDL cholesterol (r = 0.148, p less
than 0.001) and inversely with triglyceride (r = -0.217, p
less than 0.001). Persons with prevalent ischemic
heart disease had significantly lower testosterone levels than
persons without ischemic heart disease (mean levels 20.9 vs.
22.0 nmol/liter, p less than 0.01). These relations were
confounded by associations with insulin. The
associations between testosterone and the lipids persist after
adjusting for body mass index, age, and insulin. The
association between testosterone and prevalent ischemic heart
disease was reduced after adjusting for insulin and/or
triglyceride levels. The results suggest that insulin and
testosterone may have an interdependent regulatory effect on
lipid metabolism. The effect of testosterone on
ischemic heart disease appears to be primarily mediated
through its association with insulin. Future work on
sex hormones and ischemic heart disease will need to account
for the effects of insulin.
266. The determination of serum estradiol,
testosterone and progesterone in acute myocardial
infarction.
Aksut SV, Aksut G, Karamehmetoglu A, Oram E
Jpn Heart J 1986 Nov;27(6):825-37
The levels of serum estradiol, testosterone and
progesterone were determined in 13 cases of acute myocardial
infarction. Thirteen intensive care patients without coronary,
hepatic or renal disease, 13 cases of unstable angina and 15
normal subjects. The patients were males ranging from 24 to 56
years of age, the average being 40.4 years. The levels
of serum estradiol in the acute myocardial infarction and
unstable angina groups were significantly higher than in the
normal group, and no difference was found between the
normal and intensive care patient. The testosterone
levels were significantly lower in the acute myocardial
infarction and unstable angina groups than in the normal
group. Progesterone levels increased in acute myocardial
infarction patients. The estradiol: testosterone ratio was
considerably elevated in the acute phase of myocardial
infarction, and in unstable angina patients. No
difference was found between the intensive care patient and
normal groups.
267. Serum estradiol and testosterone levels
following acute myocardial infarction in men.
Tripathi Y, Hegde BM
Department of Physiology, Kasturba Medical College,
Mangalore.
Indian J Physiol Pharmacol 1998 Apr;42(2):291-4
The present study examined serum testosterone and estradiol
levels on the day of admission, 5th and on 10th day following
acute myocardial infarction in men. Controls were matched for
age and body mass index. Testosterone levels were low
on the day of admission and remained statistically unchanged
on 5th and 10th day as compared to controls. On the contrary,
estradiol levels were significantly higher on the day of
admission. A significant decrease in estradiol concentration
in comparison to the levels on the day of admission was
observed on 10th day post myocardial infarction.
However, the estradiol levels on 10th day were significantly
higher than control subjects. The results of the study
suggest that in acute myocardial infarction, hyperestrogenemia
is associated with hypotestosteronemia.
268. Oestradiol levels in diabetic men with and
without a previous myocardial infarction.
Small M, MacRury S, Beastall GH, MacCuish AC
University Department of Medicine, Royal Infirmary,
Glasgow.
Q J Med 1987 Jul;64(243):617-23
Elevated oestradiol levels have been found in men with a
previous myocardial infarction and it has been suggested that
hyperoestrogenaemia may explain partly the increased risk of
coronary heart disease in diabetes mellitus. Therefore we have
measured concentrations of oestradiol and testosterone (the
main substrate for oestradiol) in a group of diabetic men with
a previous myocardial infarction (n = 15), a matched group of
diabetic men without overt cardiovascular disease (n = 13) and
a group of healthy, non-diabetic men (n = 15). The
diabetics had elevated oestradiol levels (p less than 0.03)
despite lower testosterone levels (p less than 0.02) compared
with control subjects. In the diabetic patients, a correlation
between oestradiol and testosterone was found (r = 0.55, p
less than 0.02) which suggested that the elevated oestradiol
levels were only partly derived from the aromatization of
testosterone. There were no differences in oestradiol
or testosterone levels between the two diabetic groups. This
study has shown that endogenous hyperoestrogenaemia is a
consistent finding in diabetic men, irrespective of whether
they have or have not sustained a previous myocardial
infarction. The source of the raised oestradiol levels is
uncertain. It is unclear whether hyperoestrogenaemia can be
regarded as a risk for myocardial infarction in diabetic
men.
269. Sex hormones and hemostatic risk factors for
coronary heart disease in men with hypertension.
Phillips GB, Jing TY, Resnick LM, Barbagallo M, Laragh JH,
Sealey JE
Department of Medicine, Columbia University College of
Physicians and Surgeons, St Luke's-Roosevelt Hospital Center,
New York, New York.
J Hypertens 1993 Jul;11(7):699-702
OBJECTIVE AND DESIGN: It has been hypothesized that risk
factors for coronary heart disease in men are linked and that
the underlying factor linking them may be an alteration in the
sex hormone milieu. As a test of this hypothesis, sex hormones
and fibrinogen, factor VII and plasminogen activator inhibitor
(PAI-1), hemostatic factors recently shown to be risk factors
for myocardial infarction, were measured in men with
hypertension and in healthy control subjects.
RESULTS: The fasting serum testosterone and free
testosterone levels were decreased and the plasma factor VII
and PAI-1 levels increased in the men with
hypertension.
CONCLUSION: These findings are consistent with the stated
hypothesis.
270. [Plasma testosterone, free testosterone
fraction LH and FSH in males during the early stage of acute
myocardial infarction].
Geisthovel W, Perschke B, von zur Muhlen A, Klein H
Z Kardiol 1979 Nov;68(11):776-83
In 18 males (age 49--79 yrs) without endocrine diseases,
testosterone, free testosterone fraction, LH, FSH and cortisol
(as indicator for stress) were determined in the early stage
of an acute myocardia infarction. Blood was taken on admission
as well as every 4 hours up to meanly 43 hours. The patients
were separated in 2 groups for proving whether alterations of
the parameters may depend on the severity of the myocardial
infarction (group A=severe infarction; group B=not severe
infarction). Testosterone showed a rapid decrease in
the first 11 hours after admission, which continued less
striking to the end of the investigation. Testosterone was
significantly decreased in group A in comparison to group
B. LH and FSH in both groups together were remarkably
reduced during the whole time. Whereas group A demonstrated a
tendency to decreased values in comparison to group B for LH,
there were not any essential differences between the two
groups for FSH. The free testosterone fraction was not
altered. Cortisol in group A was twice as high as in group B
during the entire investigation. The systolic pressure in
group A was generally lower than in group B during the whole
time. The results demonstrate an important reduction of the
secretion of testosterone, LH and FSH during the early stage
of the acute myocardial infarction. The testosterone
suppression seems to be dependent on the severity of the
myocardial infarction. These alterations may be caused
by a general impaired perfusion as a consequence of myocardial
infarction and a suppressive effect of increased cortisol
values on testosterone levels.
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