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271. Current status of testosterone replacement
therapy in men.
Winters SJ
Department of Medicine, University of Pittsburgh Medical
Center, Pa., USA.
winters@med1.dept-med.pitt.edu
Arch Fam Med 1999 May-Jun;8(3):257-63
Testosterone plays an essential role in the development of
the normal male and in the maintenance of many male
characteristics, including muscle mass and strength, bone
mass, libido, potency, and spermatogenesis. Androgen
deficiency occurs with disorders that damage the testes,
including traumatic or surgical castration (primary testicular
failure) or disorders in which the gonadotropin stimulation of
the testes is reduced (hypogonadotropic hypogonadism). The
clinical manifestations of androgen deficiency depend on the
age at onset and the severity and duration of the deficiency.
In adult males, these manifestations may include
reduced body hair, decreased muscle mass and strength,
increased fat mass, decreased hematocrit, decreased libido,
erectile dysfunction, infertility, osteoporosis, and depressed
mood. The forms of androgen replacement currently
available in the United States are intramuscular depot
injections of testosterone esters, oral tablets of
testosterone derivatives, and transdermal patches. For
most patients, androgen replacement therapy with testosterone
is a safe, effective treatment for testosterone
deficiency.
272. Direct effects of estrogens on the endocrine
function of the mammalian testis.
Moger WH
Can J Physiol Pharmacol 1980 Sep;58(9):1011-22
This article reviews literature relevant to the view that
estradiol (E2) synthesized in the testis acts locally to
modify testosterone secretion. Despite a lack of convincing
evidence from in vitro experiments, in vivo experiments with
intact and hypophysectomized animals have demonstrated that
estrogens can inhibit testosterone secretion by acting
directly on the testis. Reduced testosterone
production in estrogen-treated animals probably results from
reduced 17 alpha-hydroxylase and (or) C17-C20 lyase activity.
Estrogen-inhibited steroidogenesis may result from estrogen
binding to high affinity--low capacity estrogen receptors.
Besides being an estrogen target tissue, the testis produces
E2; the cellular site of testicular E2 synthesis remains
controversial. Recent studies indicate that E2 is synthesized
primarily in the Sertoli cells of neonatal rats and in the
Leydig cells of older rats. Follicle-stimulating hormone and
human chorionic gonadotropin (hCG) increase testicular
aromatase activity and E2 concentrations in neonatal and older
rats, respectively. An increase in testicular E2
concentrations, following hCG administration, may be one
mechanism by which testosterone synthesis becomes desensitized
to subsequent hCG stimulation. However, whether
gonadotropin-stimulated testicular E2 synthesis is part of a
physiologically relevant "short" feedback loop that
participates in the regulation of testosterone synthesis
remains to be determined.
273. Direct inhibitory effect of estrogen on the
human testis in vitro.
Namiki M, Kitamura M, Nonomura N, Sugao H, Nakamura M,
Okuyama A, Utsunomiya M, Itatani H,
Matsumoto K, Sonoda T
Department of Urology, Osaka University Medical School,
Japan.
Arch Androl 1988;20(2):131-5
The direct inhibitory effects of estrogens on human
testicular functions were investigated with a testicular organ
culture technique. 125I-labeled human chorionic gonadotropin
(125I-hCG) bindings in testes cultured in media containing
diethylstilbestrol diphosphate (DESDP) began to dose-relatedly
decrease a day after the start of the culture, and this
decrease remained relatively constant during the 5-day
culture. On the other hand, testosterone produced by the
cultured testes time-relatedly decreased during the 5-day
culture. From the above results it may be concluded
that the direct inhibitory effect of estrogens on human
testicular androgen production consists of not only the loss
of testicular hCG receptors but also of other mechanisms at a
distal step from hCG receptor activation.
274. The acute effect of estrogens on testosterone
production appears not to be mediated by testicular estrogen
receptors
Damber J E; Bergh A; Daehlin L; Ekholm C; Selstam G;
Sodergard R
Department of Physiology, University of UMEA, 90187,
UMEA.
Mol Cell Endocr 31 (1). 1983. 105-116.
Scatchard binding analysis was performed to measure the
cytoplasmic estrogen receptor in the testis of rats. After
treatment of rats with the antiestrogen tamoxifen no estrogen
receptor binding was found in testicular low speed supernatant
between 12 and 96 h after treatment. Such tamoxifen-treated
rats were used to study the acute effect of estrogens on
testosterone secretion, both in vivo and in vitro.
Injection of estradiol benzoate (50 .mu.g, 24 h prior
to experiment) resulted in a significant depression of basal
and LH[lutropin]-stimulated plasma testosterone levels in
control rats and this effect was unchanged in
tamoxifen-pretreated rats. In vitro,
estradiol-17.beta. also inhibited the LH-induced rise in
testosterone secretion by isolated testicular interstitial
cells. This inhibition was not affected if the rats had
been pretreated with tamoxifen. The inhibitory
effects of exogenous estrogens on testicular testosterone
production are probably not mediated by the estrogen
receptor.
275. The effect of testosterone aromatization on
high-density lipoprotein cholesterol level and postheparin
lipolytic activity.
Zmuda JM; Fahrenbach MC; Younkin BT; Bausserman LL; Terry RB;
Catlin DH; Thompson PD
Department of Medicine, Miriam Hospital, Providence,
RI.
Metabolism (United States) Apr 1993, 42 (4)
p446-50,
Stanozolol, an oral 17 alpha-alkylated androgen, increases
hepatic triglyceride lipase activity (HTGLA) and decreases
high-density lipoprotein cholesterol (HDL-C) levels, whereas
intramuscular testosterone has comparatively little effect. In
the present study, we tested the hypothesis that aromatization
of androgen to estrogen blunts the lipid and lipase effects of
exogenous testosterone. Fourteen male weightlifters
received testosterone enanthate (200 mg/wk intramuscularly),
the aromatase inhibitor testolactone (250 mg four times per
day), or both drugs together in a randomized cross-over
design. Serum testosterone level increased during all three
drug treatments, whereas estradiol level increased only with
testosterone alone (+47%, P < .05),
demonstrating that testolactone effectively inhibited
testosterone aromatization. Testosterone decreased HDL-C(-16%,
P < .05), HDL2-C(-23%, NS), and apoprotein (apo) A-I (-12%,
P < .05) levels, effects that were consistently but not
significantly greater with simultaneous testosterone and
testolactone administration (HDL-C, -20%; HDL2-C, -30%; apo
A-I, -15%; P < .05 for all). In contrast, both testosterone
regimens decreased HDL3-C levels by 13% (P < .05 for both).
HTGLA increased 21% during testosterone treatment and 38%
during combined testosterone and testolactone treatment (P
< .01 for both). Lipoprotein lipase activity (LPLA)
increased only during combined testosterone and testolactone
treatment (+31%, P < .01), suggesting that estrogen
production may counteract the effects of testosterone on
LPLA. Testolactone alone had little effect on any
lipid, lipoprotein, apoprotein, or lipase
concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
276. Effects of estradiol administration in vivo on
testosterone production in two populations of rat Leydig
cells
Keel B.A.; Abney T.O.
Dep. Endocrinol., Med. Coll. Georgia, Augusta, GA 30912
United States
Biochemical and Biophysical Research Communications (United
States) 1982, 107/4 (1340-1348)
The effects of in vivo administration of estradiol on
isolated rat testicular Leydig cells were investigated. Adult
intact rats were injected s.c. with 50 mug/100 g B.W. of
17beta-estradiol or vehicle twice daily for 2 days. Twelve
hours after the last injection, collagenase dispersed
interstitial cells were obtained and Leydig cells were
subsequently isolated on metrizamide gradients. Two distinct
peaks of specific sup 1sup 2sup 5I-hCG binding corresponding
to population I and II Leydig cells were observed. The hCG
binding profile was unaltered as a result of estradiol
treatment. Although twice as much testosterone was produced in
population II, the responsiveness of the two populations to
hCG or dbcAMP in vitro was identical (11- to 13-fold
increase). Estradiol administration in vivo resulted in a
33-48% decrease in basal and stimulated testosterone
production in both populations. These data indicate
for the first time that both population I and II Leydig cells
are sensitive to the direct inhibitory effects of estrogens on
testosterone production. This inhibitory effect was
not associated with an alternation in hCG binding capacity in
either population. Therefore, we conclude that no
functional difference exists between the two populations of
Leydig cells with respect to the action of
estrogens.
277. Tetrahydroisoquinoline alkaloids mimic direct
but not receptor-mediated inhibitory effects of estrogens and
phytoestrogens on testicular endocrine function. Possible
significance for Leydig cell insufficiency in alcohol
addiction.
Life Sci 1991;49(18):1319-29
Stammel W, Thomas H, Staib W, Kuhn-Velten WN
Abteilung Physiologische Chemie, Universitat Ulm, F.R.
Germany.
Possible effects of various tetrahydroisoquinolines (TIQs)
on rat testicular endocrine function were tested in vitro in
order to prove whether these compounds, some of which have
been claimed to accumulate in alcoholics, may be
mediators of the development of Leydig cell insufficiency, a
well-known side-effect of ethanol ingestion. TIQ
effects on different levels of regulation of testis function
were compared in vitro with estrogen effects, since both
classes of compounds have structural similarities.
Gonadotropin-stimulated testosterone production by testicular
Leydig cells was inhibited by tetrahydropapaveroline and
isosalsoline, the IC50 values (30 microM) being comparable to
those of estradiol (3 microM), 2-hydroxyestradiol (10 microM),
and the phytoestrogens, coumestrol (15 microM) and genistein
(7 microM); salsolinol (85 microM) and salsoline (240 microM)
were less effective, and salsolidine was ineffective. None of
these TIQs interacted significantly with testicular estrogen
receptor as analyzed by estradiol displacement.
However, tetrahydropapaveroline, isosalsoline and
salsolinol competitively inhibited (Ki 130-150
microM) substrate binding to cytochrome P450XVII, one
key enzyme of androgen biosynthesis, with similar
efficiency as the estrogens did (Ki 50-110 microM);
salsoline and salsolidine were again much less effective.
Since the efficient TIQ concentrations in this system are
identical with those reported to generate central-nervous
effects, it is concluded that certain TIQs may amplify
peripheral inhibitory effects of ethanol on testicular
endocrine function by their interaction with at least one
enzyme of the androgen biosynthetic pathway.
278. Fat tissue a steroid reservoir and site of
steroid metabolism
Deslypere J P; Verdonck L; Vermeulen A
Dep. of Endocrinology, Academic Hospital, Univ. of Ghent,
B-9000 Ghent, Belgium.
J Clin Endocrinol Metab 61 (3). 1985. 564-570.
Sex steroid concentrations and 17.beta.-hydroxysteroid
dehydrogenase and aromatase activities were determined in fat
tissue removed at surgery or, to allow comparisons in
different sites, postmortem. Except for dehydroepiandrosterone
(DHEA) sulfate (DHEAS), there existed a positive
tissue/plasma gradient for all steroids studied (testosterone,
androstenedione, DHEA, androstenediol, estrone and estradiol),
suggesting androgen uptake and estrogen synthesis in
situ. Androgen concentrations did not vary according
to site of origin of fat tissue, except that the DHEAS
concentration was significantly lower in abdominal s.c. and
omental fat than in breast, pericardial, or sc pubic fat.
Tissue androgen concentrations were positively correlated with
their plasma concentrations, but tissue and plasma estrogen
concentrations were not correlated. All tissue steroid
concentrations, with the exception of estradiol in men,
decreased with age. Aromatase activity [androstenedione
.fwdarw. estrone; mean maximum velocity, 7.4 .+-. 3.7 (.+-.
SD) fmol estrone/mg protein.cntdot.h] did not vary between
sexes or with site of origin of fat tissue.
17.beta.-Hydroxysteroid dehydrogenase activity (estradiol
.fwdarw. estrone, mean maximum velocity 9.8 .+-. 5.4 pmol/mg
protein.cntdot.h) was higher in fat from women than in that
from men, higher in premenopausal than in postmenopausal
women, and higher in omental than in s.c. fat. Its activity
was noncompetively inhibited in vitro by DHEA and DHEAS in
near-physiological concentrations, and the enzyme activity was
inversely correlated (P < 0.001) with the tissue DHEA and
DHEAS concentrations. Apparently, fat tissue is an
important steroid hormone reservoir; it is the site of active
aromatase and 17.beta.-hydroxysteroid dehydrogenase; and
tissue DHEA(S) may have a modulating effect on tissue estrogen
production.
279. Treatment of men with idiopathic
oligozoospermic infertility using the aromatase inhibitor,
testolactone. Results of a double-blinded, randomized,
placebo-controlled trial with crossover.
Clark RV, Sherins RJ
Section of Internal Medicine, Emory University Clinic,
Atlanta, Georgia 30322.
Mt Sinai J Med 1997 Jan;64(1):20-5
The hypothesis that increased estradiol production may be
the cause of impaired spermatogenesis in infertile men with
idiopathic oligozoospermia was tested by administering the
aromatase inhibitor, testolactone, and by assessing its
effects on sperm output and fertility. Our study was a
randomized, placebo-controlled double-blind crossover trial.
Subjects (n = 25) with infertility due to unexplained
oligozoospermia were given testolactone (2 g/day) or placebo
for 8 months followed by crossover to the other treatment for
an additional 8 months. Total estradiol and testosterone
levels during testolactone exposure did not change from basal
and placebo values. However, sex hormone-binding
globulin binding capacity consistently decreased (30%, p less
than 0.01) and free testosterone levels increased (36%, p less
than 0.01). Free estradiol values increased but not
significantly. Additionally, LH and FSH serum levels
increased by 15% and 20%, respectively (p less than 0.05), and
17 alpha-hydroxyprogesterone values increased by 90% (p less
than 0.05) during drug administration. Sperm output and semen
quality remained unchanged during either testolactone or
placebo treatment, and no pregnancies occurred during the
16-month study. These data suggest that chronic
administration of testolactone at this dose fails to maintain
aromatase inhibition despite depression of 17,20-desmolase
activity with elevated 17 alpha-hydroxyprogesterone and
depressed SHBG binding capacity with elevation of free
testosterone. Testolactone is not efficacious in the
treatment of idiopathic oligozoospermic infertility.
280. Clinical utility of sex hormone-binding
globulin measurement.
Pugeat M, Crave JC, Tourniaire J, Forest MG
Hospices Civils de Lyon, Laboratoire de la Clinique
Endocrinologique, Hopital de l'Antiquaille, France.
Horm Res 1996;45(3-5):148-55
The high-affinity binding of the sex hormone-binding
globulin (SHBG) for testosterone and to a lesser extent for
estradiol influences the circulating levels of these sex
steroid hormones, their biodisposal to target cells as well as
their mutual balance. Although the regulation of SHBG
is still not completely understood, in vitro studies performed
with human hepatocarcinoma (Hep G2) cells have shown that
estrogens and thyroxine stimulate SHBG secretion, by
increasing the steady state of its mRNA concentrations. These
observations are in good agreement with studies showing that
SHBG levels increase during oral administration of estrogens
as well as in patients with thyrotoxicosis.
Interestingly, SHBG levels are normal in syndromes such as the
abnormal transport of thyroid hormones and/or the syndrome of
thyroid hormone resistance, which can be confused with
thyrotoxicosis. By contrast, the effects of androgens are
controversial. In many patients with hirsutism, SHBG
concentrations are low and correlate negatively with both body
mass index and fasting insulin levels. Because of the
inhibitory effect of both insulin and insulin-like growth
factor-1 on SHBG secretion by Hep G2 cells in vitro, it has
been proposed that SHBG levels could be a marker of insulin
resistance and/or hyperinsulinism in humans. Furthermore, an
increased risk for either noninsulin-dependent diabetes and/or
the overall mortality are associated with decreased SHBG
levels in postmenopausal women. Finally, in men, SHBG levels
are positively correlated with the concentration of
high-density lipoprotein cholesterol. Therefore, the
measurement of SHBG in clinical practice can be a useful
diagnostic tool for: (1) correctly interpretating testosterone
and estradiol serum concentrations; (2) investigating
androgen-estrogen balance in gonadal and sexual
dysfunctions; (3) assessing the peripheral effect of
the hormones which regulate SHBG productions, and (4)
evaluating insulin resistance and cardiovascular risk.
281. Sex hormone binding globulin: origin, function
and clinical significance.
Selby C
Department of Clinical Chemistry, City Hospital, Nottingham,
UK.
Ann Clin Biochem 1990 Nov;27 ( Pt 6):532-41
Sex hormone binding globulin (SHBG) is a
glycoprotein possessing high affinity binding for 17
beta-hydroxysteriod hormones such as testosterone and
oestradiol. It is probably synthesized in the liver,
plasma concentrations being regulated by, amongst other
things, androgen/oestrogen balance, thyroid hormones, insulin
and dietary factors, it is involved in transport of sex
steroids in plasma and its concentration is a major factor
regulating their distribution between the protein-bound and
free states. Its detailed role in the delivery of hormones to
target tissues is not yet clear. Plasma SHBG concentrations
are affected by a number of different diseases, high values
being found in hyperthyroidism, hypogonadism, androgen
insensitivity and hepatic cirrhosis in men. Low concentrations
are found in myxoedema, hyperprolactinaemia and syndromes of
excessive androgen activity. Concentrations are also affected
by drugs such as androgens, oestrogens, thyroid hormones and
anti-convulsants. Measurement of SHBG is useful in the
evaluation of mild disorders of androgen metabolism and
enables identification of those women with hirsutism who are
more likely to respond to oestrogen therapy. Testosterone:SHBG
ratios correlate well with both measured and calculated values
of free testosterone and help to discriminate subjects with
excessive androgen activity from normal individuals.
282. Androgens, estrogens, and sex hormone-binding
globulin in middle-aged men.
Longcope C, Goldfield SR, Brambilla DJ, McKinlay J
Department of Obstetrics and Gynecology, University of
Massachusetts Medical School, Worcester 01655.
J Clin Endocrinol Metab 1990 Dec;71(6):1442-6
Although the administration of estrogens and androgens can
affect the concentrations of sex hormone-binding globulin
(SHBG) in men, the relationships between endogenous estrogens
and androgens and SHBG are uncertain. Therefore, in a randomly
selected cohort of 1640 middle-aged men we measured androgen,
estrogen, and SHBG concentrations and obtained the subjects'
weight, ethanol intake, and smoking histories. The data were
analyzed by stepwise multiple regression, with SHBG as the
dependent variable, to compare the role of hormones with that
of other factors in the control of SHBG levels.
Neither estrone or estradiol nor the
testosterone/estradiol ratio was predictive of SHBG
levels. However, SHBG concentrations were positively
correlated with total testosterone and negatively correlated
with percent free and percent albumin-bound testosterone. SHBG
concentrations were negatively correlated with estrone
sulfate, but were positively correlated with the
testosterone/estrone sulfate ratio and the concentrations of
free and albumin-bound testosterone. In addition, in all
models tested age and body mass index (wt/ht2), but not
smoking or ethanol, were strong predictors of SHBG
concentrations. Thus, when present in physiological
amounts in the blood as a result of glandular secretion, there
is a positive relationship between SHBG concentrations and
testosterone and, to a lesser extent, free- and albumin-bound
testosterone, but age and body mass index appear to be more
important in predicting the SHBG concentration.
283. Sex hormone changes in male epileptics.
Toone BK, Wheeler M, Fenwick PB
Clin Endocrinol (Oxf) 1980 Apr;12(4):391-5
Mean plasma levels of LH, FSH, PRL, and sex-hormone binding
globulin (SHBG) were raised in twenty-seven epileptics on
anticonvulsants compared with age matched controls. Sexual
activity appeared to be reduced. Anticonvulsant
therapy results in raised SHBG levels which may be associated
with a lowered free testosterone level as indicated by raised
LH levels and lowered sexual activity.
284. Age, disease, and changing sex hormone levels
in middle-aged men: results of the Massachusetts Male Aging
Study.
Gray A, Feldman HA, McKinlay JB, Longcope C
New England Research Institute, Watertown, Massachusetts
02172.
J Clin Endocrinol Metab 1991 Nov;73(5):1016-25
To evaluate the hypothesis that endocrine profiles change
with aging independently of specific disease states, we
examined the age trends of 17 major sex hormones, metabolites,
and related serum proteins in 2 large groups of adult males
drawn from the Massachusetts Male Aging Study, a
population-based cross-sectional survey of men aged 39-70 yr
conducted in 1986-89. Group 1 consisted of 415 men who were
free of obesity, alcoholism, all prescription medication,
prostate problems, and chronic illness (cancer, coronary heart
disease, hypertension, diabetes, and ulcer). Group 2 consisted
of 1294 men who reported 1 or more of the above conditions.
Each age trend was satisfactorily described by a constant
percent change per yr between ages 39-70 yr. Free testosterone
declined by 1.2%/yr, and albumin-bound testosterone by
1.0%/yr. Sex hormone-binding globulin (SHBG), the
major serum carrier of testosterone, increased by 1.2%/yr,
with the net effect that total serum testosterone declined
more slowly (0.4%/yr) than the free or albumin-bound pools
alone. Among the major androgens and metabolites,
androstane-3 alpha,17 beta-diol (androstanediol; 0.8%/yr) and
androstanediol glucuronide (0.6%/yr) declined less rapidly
than free testosterone, while 5 alpha-dihydrotestosterone
remained essentially constant between ages 39-70 yr.
Androstenedione declined at 1.3%/yr, a rate comparable to that
of free testosterone, while the adrenal androgen
dehydroepiandrosterone (3.1%/yr) and its sulfate (2.2%/yr)
declined 2-3 times more rapidly. The levels of testosterone,
SHBG, and several androgen metabolites followed a parallel
course in groups 1 and 2, remaining consistently 10-15% lower
in group 2 across the age range of the study. Subgroup
analyses suggested that obese subjects might be responsible
for much of the group difference in androgen level. Serum
concentrations of estrogens and cortisol did not change
significantly with age or differ between groups. Of the
pituitary gonadotropins, FSH increased at 1.9%/yr, LH
increased at 1.3%/yr, and PRL declined at 0.4%/yr, with no
significant difference between groups 1 and 2.
285. The influence of age, alcohol consumption, and
body build on gonadal function in men.
Sparrow D, Bosse R, Rowe JW
J Clin Endocrinol Metab 1980 Sep;51(3):508-12
Basal plasma levels of testosterone, dihydrotestosterone,
estradiol, and gonadotropins and testosterone-binding capacity
(percent radioactive testosterone bound to protein) were
measured in health carefully screened young (31-44 yr old; n =
44) and older (64-88 yr old; n = 42) male participants in the
Normative Aging Study of the V.A. There was no statistically
significant effect of age on testosterone [younger group, 4.16
+/- 0.27 (SEM) ng/ml; older group, 4.62 +/- 0.32 (SEM) ng/ml]
or the free testosterone index [younger group, 2.05 +/- 0.14
(SEM) ng/ml; older group, 1.76 +/- 0.11 (SEM) ng/ml].
The testosterone-binding capacity was higher in the
older group (younger group, 50.10 +/- 1.18% (SEM);
older group, 60.10 +/- 1.18% (SEM); P less than 0.001). Of the
two products of testosterone metabolism studied, estradiol did
not change with age, while dihydrotestosterone was lower
[young group, 0.25 +/- 0.02 (SEM) ng/ml; older group, 0.20 +/-
0.01 (SEM) ng/ml; P = 0.03] in the older group. FSH levels
were increased among the older men [older group, 92.9 +/- 6.0
(SEM) ng/ml; younger group, 61.1 +/- 5.0 (SEM) ng/ml; P less
than 0.001]. LH levels were not significantly influenced by
age. There was no effect of level of chronic stable alcohol
intake on gonadal function, as estimated by testosterone
levels and the free testosterone index. Analysis of the
relationship between body build and hormone levels indicated
that estradiol levels were highest in gynandromorphic men and
lowest in mesomorphic men.
286. Serum testosterone and sex hormone-binding
globulin concentrations and the risk of prostate carcinoma: a
longitudinal study.
Heikkila R, Aho K, Heliovaara M, Hakama M, Marniemi J,
Reunanen A, Knekt P
Kanta-Hame Central Hospital, Hameenlinna, Finland.
Cancer 1999 Jul 15;86(2):312-5
BACKGROUND: It has been hypothesized that high androgen
levels are determinants of prostate carcinoma.
METHODS: Serum concentrations of testosterone, sex
hormone-binding globulin (SHBG), and androstenedione were
analyzed to determine their role as predictors of prostate
carcinoma in a longitudinal, population-based, nested
case-control study. The serum concentrations of testosterone,
SHBG, and androstenedione were determined from serum samples
collected by the Finnish Mobile Clinic Health Examination
Survey between 1968-1972 and stored at -20 degrees C. During a
follow-up period of 24 years, a total of 166 prostate
carcinoma cases occurred among men who originally were cancer
free. Two controls (matched for age and municipality) were
chosen.
RESULTS: There was no association between serum
testosterone, SHBG, or androstenedione concentrations and the
occurrence of subsequent prostate carcinoma in the total study
population or in subgroups determined based on age or body
mass index. The association was not strengthened by
simultaneous adjustment for the hormonal variables.
CONCLUSIONS: The results of the current study do not appear
to corroborate the hypothesis that serum testosterone, SHBG,
or androstenedione are determinants of the subsequent
occurrence of prostate carcinoma.
287. Effect of testosterone treatment on body
composition and muscle strength in men over 65 years of
age.
Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Lenrow
DA, Holmes JH, Dlewati A, Santanna J, Rosen CJ, Strom BL
Department of Medicine, University of Pennsylvania School of
Medicine, Philadelphia 19104-6087, USA.
J Clin Endocrinol Metab 1999 Aug;84(8):2647-53
As men age, serum testosterone concentrations decrease, the
percentage of body mass that is fat increases, the percentage
of lean body mass decreases, and muscle strength decreases.
Because these changes are similar to those that occur in
hypogonadal men, we hypothesized that increasing the serum
testosterone concentration of men over 65 yr of age to that in
young men would decrease their fat mass, increase their lean
mass, and increase their muscle strength. We randomized 108
men over 65 yr of age to wear either a testosterone patch or a
placebo patch in a double blind study for 36 months. We
measured body composition by dual energy x-ray absorptiometry
and muscle strength by dynamometer before and during
treatment. Ninety-six men completed the entire 36-month
protocol. Fat mass decreased (-3.0+/-0.5 kg) in the
testosterone-treated men during the 36 months of treatment,
which was significantly different (P = 0.001) from the
decrease (-0.7+/-0.5 kg) in the placebo-treated men. Lean mass
increased (1.9+/-0.3 kg) in the testosterone-treated men,
which was significantly different (P < 0.001) from that
(0.2+/-0.2 kg) in the placebo-treated men. The decrease in fat
mass in the testosterone-treated men was principally in the
arms (-0.7+/-0.1 kg; P < 0.001 compared to the placebo
group) and legs (-1.1+/-0.2 kg; P < 0.001), and the
increase in lean mass was principally in the trunk (1.9+/-0.3
kg; P < 0.001). The change in strength of knee extension
and flexion at 60 degrees and 180 degrees angular velocity
during treatment, however, was not significantly different
between the two groups. We conclude that increasing the serum
testosterone concentrations of normal men over 65 yr of age to
the midnormal range for young men decreased fat mass,
principally in the arms and legs, and increased lean mass,
principally in the trunk, but did not increase the strength of
knee extension and flexion, as measured by dynamometer.
288. Approaches to prostatic cancer chemotherapy
using the Dunning R3327H prostatic adenocarcinoma.
Padilla GM, Petrow V, Marts SA, Mukherji S
Prostate 1985;6(2):129-43
Androgen-responsive cells: To determine if
testosterone or dihydrotestosterone is the main trophic
hormone of prostatic adenocarcinoma, we have treated Dunning
R3327H prostatic adenocarcinoma-bearing rats with 6-methylene
progesterone, which blocks conversion of testosterone to
dihydrotestosterone. Copenhagen-Fisher rats were
treated with steroid (20 mg/Kg daily) immediately following
implantation of tumor and thereafter for 117 days.
There was a 92% inhibition of growth of tumors and a
lesser effect upon prostate and seminal vesicles.
Tumor-free body weights remained unchanged. Both treated and
untreated tumors had equivalent DNA content on a per weight
basis. This result supports the thesis that prostatic
adenocarcinoma requires dihydrotestosterone for growth.
Androgen-insensitive cells: Advanced prostate cancer does not
respond to endocrine therapy but is temporarily controlled by
the cytotoxic steroid estramustine. The latter shows
significant selective binding to prostatic protein. To develop
chemotherapeutic agents that will control androgen-insensitive
cells and possess improved selectivity for prostatic protein,
we have studied a number of steroids for their ability to
displace 3H-labeled estramustine from prostatic cytosolic
proteins. Surprisingly, a carbamido substituent at the C17
position was found to confer significant binding affinity for
prostatic estramustine-binding protein. Extension of this
structural characteristic to the estramustine type of molecule
is being studied.
289. [No Title]
Endocrine News;1996, Vol 21, No. 3, p-2
No abstract.
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