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Mechanical Muscle Function and Lean Body Mass During Supervised Strength Training and Testosterone Therapy in Aging Men with Low-Normal Testosterone Levels

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To examine the effect of strength training and testosterone therapy on mechanical muscle function and lean body mass (LBM) in aging men with low-normal testosterone levels in a randomized, double-blind, placebo-controlled 24-week study. Randomized, double-blind, placebo-controlled. Odense, Denmark. Men aged 60 to 78, with bioavailable testosterone levels of less than 7.3 nmol/L and a waist circumference greater than 94 cm were randomized to testosterone (50–100 mg/d, n = 22) placebo (n = 23) or strength training (n = 23) for 24 weeks. The strength training group was randomized to addition of testosterone or placebo after 12 weeks. Subjects performed supervised strength training (2–3 sets with 6- to 10-repetition maximum loads, 3 times per week). Testosterone levels, maximal voluntary contraction and rate of force development, and LBM were obtained at 0 and at Weeks 12 and 24 of the intervention. No changes in any variables were recorded with placebo. In the strength training group, maximal voluntary contraction increased 8% after 12 weeks (P = .005). During the following 12 weeks of strength training rate of force development increased by 10% (P = .04) and maximal voluntary contraction further increased (P < .001). Mechanical muscle function was unchanged in men receiving only testosterone for 24 weeks. LBM increased only in men receiving testosterone (P = .004). Strength training in aging men with low-normal testosterone levels may improve mechanical muscle function, but this effect occurs without a significant increase in LBM. Clinically, only the combination of testosterone therapy and strength training resulted in an increase in mechanical muscle function and LBM.
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Mechanical Muscle Function and Lean Body Mass During
Supervised Strength Training and Testosterone Therapy in
Aging Men with Low-Normal Testosterone Levels
Thue Kvorning, PhD,* Louise L. Christensen, MD, PhD,
Klavs Madsen, PhD,
Jakob L. Nielsen,
MSc,* Kasper D. Gejl, MSc,* Kim Brixen, MD, PhD,
and Marianne Andersen, MD, PhD
OBJECTIVES: To examine the effect of strength training
and testosterone therapy on mechanical muscle function
and lean body mass (LBM) in aging men with low-normal
testosterone levels in a randomized, double-blind, placebo-
controlled 24-week study.
DESIGN: Randomized, double-blind, placebo-controlled.
SETTING: Odense, Denmark.
PARTICIPANTS: Men aged 60 to 78, with bioavailable
testosterone levels of less than 7.3 nmol/L and a waist cir-
cumference greater than 94 cm were randomized to testos-
terone (50100 mg/d, n =22) placebo (n =23) or strength
training (n =23) for 24 weeks. The strength training
group was randomized to addition of testosterone or pla-
cebo after 12 weeks. Subjects performed supervised
strength training (23 sets with 6- to 10-repetition maxi-
mum loads, 3 times per week).
MEASUREMENTS: Testosterone levels, maximal volun-
tary contraction and rate of force development, and LBM
were obtained at 0 and at Weeks 12 and 24 of the
intervention.
RESULTS: No changes in any variables were recorded with
placebo. In the strength training group, maximal voluntary
contraction increased 8% after 12 weeks (P=.005). During
the following 12 weeks of strength training rate of force
development increased by 10% (P=.04) and maximal vol-
untary contraction further increased (P<.001). Mechanical
muscle function was unchanged in men receiving only tes-
tosterone for 24 weeks. LBM increased only in men receiv-
ing testosterone (P=.004).
CONCLUSION: Strength training in aging men with low-
normal testosterone levels may improve mechanical muscle
function, but this effect occurs without a significant
increase in LBM. Clinically, only the combination of
testosterone therapy and strength training resulted in an
increase in mechanical muscle function and LBM. JAm
Geriatr Soc 61:957–962, 2013.
Key words: testosterone (therapy); strength training;
muscle strength; lean body mass; aging
Testosterone therapy is indicated in primary or second-
ary hypogonadism,
1,2
although there is no consensus
on testosterone treatment in aging men with low-normal
testosterone levels.
3,4
These men often have a decrease in
lean body mass (LBM) and muscle strength and, in most
cases, impaired physical function as well.
5,6
Supraphysio-
logical testosterone therapy in men with low testosterone
levels is associated with an increase in LBM, but a similar
increase in muscle strength does not occur.
7,8
Moreover,
the effect of testosterone therapy on muscle strength and
performance using physiological doses has not been exten-
sively studied, and existing studies are not conclusive. One
study showed improved muscle strength after 12 months
of intervention,
9
and another supported these findings after
only 6 months of intervention, but testosterone levels were
at the high end of the physiological range,
10
but two other
studies reported no effect on muscle strength after 36
1
and
6
11
months of physiological testosterone doses. Accord-
ingly, it has been argued that increases in LBM in elderly
adults are less meaningful without concomitant improve-
ments in performance-related measures (muscle strength).
12
The aim of this study was first to investigate the
effect of strength training on mechanical muscle function
(isometric strength (maximum voluntary contraction
(MVC)), dynamic strength (10-repetition maximum
(RM)), rate of force development (RFD), and jump height
From the *Institute of Sport Science and Clinical Biomechanics, University
of Southern Denmark, Odense;
Department of Endocrinology, Odense
University Hospital and Institute of Clinical Research, University of
Southern Denmark, Odense; and
Section for Sport Science, Aarhus
University, Aarhus, Denmark.
Clinical Trial Registration Number: NCT00700024
Address correspondence to Thue Kvorning, University of Southern
Denmark, Campusvej 55, 5230 Odense M, Denmark.
E-mail: tkvorning@health.sdu.dk
DOI: 10.1111/jgs.12279
JAGS 61:957–962, 2013
©2013, Copyright the Authors
Journal compilation ©2013, The American Geriatrics Society 0002-8614/13/$15.00
(JH)), as well as testosterone levels and LBM in aging
men with low-normal bioavailable testosterone levels. In
addition, the effects of strength training and testosterone
therapy were compared, as well as the effect of combined
testosterone therapy and strength training on the above-
mentioned variables.
METHODS
Details of the study design have been reported else-
where.
13
Briefly, the study was a single-center, random-
ized, double-blind, placebo-controlled study to assess the
effect of testosterone gel and strength training on
mechanical muscle function, body composition, compo-
nents of the metabolic syndrome, and quality of life in
men aged 60 to 78 with low-normal bioavailable
testosterone levels (<7.3 nmol/L)
14
and waist circumfer-
ence greater than 94 cm. Bioavailable testosterone was
chosen because there is strong consensus regarding a
decline in bioavailable testosterone with aging.
15,16
The local ethics committee approved the study, which
was declared in ClinicalTrials.gov (NCT00700024). All
participants gave written informed consent at a screening
visit.
Sixty-eight subjects were included in the initial study
(Figure 1),
13
but 12 (one from the testosterone group, two
from the placebo group, nine from the strength training
group) dropped out of the study, and MVC and RFD data
were missing for one person in the testosterone group, so
49 subjects were included in this study, with baseline values
in terms of age, height, and body weight as follows: placebo
(for 24 weeks) (n =16), 67.8 1.3 years, 178.7
2.2 cm, 93.1 3.6 kg; testosterone (for 24 weeks)
(n =19), 66.6 1.0 years, 174.8 1.5 cm, 92.7 2.9
kg; strength training (for the first 12 weeks) (n =14),
67.9 1.6 years, 176.6 1.5 cm, 94.8 2.0 kg; strength
training plus testosterone (for the last 12 weeks) (n =6),
67.2 2.7 years, 175.2 2.4 cm, 98.5 4.0 kg; strength
training plus placebo (for the last 12 weeks) (n =8),
69.5 2.0 years, 177.9 2.0 cm, 91.0 1.0 kg.
Randomization and Blinding
Subjects were randomly assigned to receive testosterone
(n =19) or placebo (n =16) or to engage in strength
training (n =14). After 12 weeks, the strength training
group was randomized into two groups receiving testoster-
one (n =6) or placebo (n =8).
Randomization
n = 68
Placebo
n = 23
Testosterone
n = 22
Placebo
Completed the study
by Frederiksen et al.
2012
n = 18
Exclusion: 5
Placebo
Data from 16 subjects of
the 18 subjects above
who completed the
mechanical muscle
function tests are
presented in the present
study
n = 16
Testosterone
Data from 19 subjects
of the 20 subjects above
who completed the
mechanical muscle
function tests are
presented in the present
study
n = 19
Strength training
Completed the
present study
n = 14
Exclusion: 2
Testosterone
Completed the study
by Frederiksen et al.
2012
n = 20
Strength training
+
testosterone
n = 6
Strength training
+
placebo
n = 8
Week 0
Week 12
Week 24
Study by Frederiksen et al. 2012
Strength training
n = 23
Present stud
y
Exclusion: 2 Exclusion: 1 Exclusion: 9
Figure 1. Flowchart of the study population and overview of the study design.
958 KVORNING ET AL. JUNE 2013–VOL. 61, NO. 6 JAGS
Intervention and Dynamic Strength (10 RM)
Participants in the testosterone group initially received 5 g
of gel containing 50 mg of testosterone (Testim; Ipsen,
Paris, France) per day, and those in the placebo group
received 5 g of gel per day. The study outcomes were
evaluated at baseline and during 12 and 24 weeks of the
intervention (Figure 1).
The training group performed bicycling for 5 minutes
on a cycle ergometer with low resistance (approximately
100 W) and then subjects engaged in a progressive heavy
strength training program of exercises for the entire body.
17
The program was performed three times a week for
24 weeks and consisted of leg presses, knee extensions, leg
curls, chest presses, latissimus pull downs, seeded back
extensions, and seeded crunches. Subjects performed two
sets of leg presses, two sets of knee extensions, and three sets
of each exercise for the upper body. Training load and rest
periods were periodized; thus subjects performed 6 to 10
repetitions with corresponding 6- to 10-RM loads with 2 to
3 minutes of rest between sets and exercises. Familiarization
with the strength training was ensured during the initial
4 weeks with low loading (1520 RM) and volume, and
thereafter, the training loads were increased based on RM
tests at the start of every other week.
All training sessions were supervised, and all subjects
participated in a minimum two of three weekly training ses-
sions, resulting in a mean training adherence of 75 8% at
the end of the training period. Subjects received 0.2 L of
skim chocolate milk (containing 7 g protein, 20 g carbohy-
drate, and 1 g fat) after each strength training session.
Dynamic strength measured as 10 RM leg press and
10 RM knee extension was used for analysis.
MVC and RFD
After a standardized warm-up procedure consisting of
5 minutes on a cycle ergometer and 8 to 10 submaximal
dynamic contractions, biomechanical properties of the knee
extensors of the left thigh were evaluated using a dynamom-
eter (KinCom 500H, software version 4.03; Chattecx Corp.,
Chattanooga, TN). Isometric contractions (MVC) were per-
formed in a fixed position of 70°of knee flexion (0°=full
extension). All settings were recorded and used in subse-
quent tests. Subjects were instructed to contract the knee
extensors as fast and forcefully as possible, with each maxi-
mal isometric contraction lasting 3 seconds. All subjects
performed five trials and had 45 to 60 seconds of recovery
between trials. The trial with the highest absolute torque
value was used for further analysis. The isometric measures
of torque were sampled on an external computer with a
sampling rate of 1,000 Hz and corrected for the influence of
gravity.
18
All measurements were filtered using a 4th order
zero-lag Butterworth low-pass filter (10 Hz cutoff fre-
quency) and analyzed for peak torque and peak rate of force
development (Dtorque/Dtime).
Counter Movement Jump
Subjects performed five maximal counter movement
jumps (CMJ) on a force platform (Kistler 9281 B,
Winterthur, Switzerland). Subjects were initially
instructed on how to perform an optimal CMJ; feedback
was given accordingly during the following tests. The
vertical signal from the force platform was sampled at
1 kHz using an external A/D converter (dt28ez Data
Translation, Austin, TX) and analyzed later using cus-
tomized analysis.
19,20
CMJ trials were analyzed for max-
imal vertical JH on basis of takeoff velocity.
20
Power
was continuously calculated during the CMJ based on
the product of force and velocity, and peak power was
determined as the highest calculated product of the two
variables.
21
Dual X-Ray Absorptiometry
LBM was measured using dual X-ray absorptiometry
(Hologic, Waltham, MA). The coefficient of variation
(CV) was 0.9% for LBM.
Hormone Assays
Testosterone was measured between 8 and 9 a.m. after an
overnight fast. Serum total testosterone was measured using
liquid chromatography tandem mass spectrometry after
ether extraction. For testosterone measurements, the intra-
assay CV was less than 10% for total testosterone greater
than 0.2 nmol/L and less than 30% for total testosterone
in the range between 0.1 and 0.2 nmol/L. Sex hormone
binding globulin was measured using an auto dissociation-
enhanced lanthanide fluorescent immunoassay, and bio-
available testosterone was calculated.
22
Statistical Analysis
The sample size of the study was determined according to
the effect of testosterone on LBM (type 1 error (a)=0.05,
type 2 error (b)=0.1, standard deviation =1.3 kg,
minimal relevant difference =1.3 kg, power (1b)=90%).
This calculation indicated the need for 15 subjects in each
group. Sample size could not be calculated on the combined
effect of testosterone and strength training because there
was no previous comparable study. The time and treatment
effects of the testosterone, placebo, and strength training
groups were compared at 0, 12, and 24 weeks, and for the
strength training plus testosterone group and strength
training plus placebo groups at 12 and 24 weeks.
Differences were tested using two-way analysis of variance
for repeated measurements. Values are presented as means
and standard errors. P<.05 was considered significant.
RESULTS
The placebo group (n =16) showed no changes in
mechanical muscle function parameters (MVC, RFD, 10
RM, JH), bioavailable testosterone or LBM.
First, the results comparing 12 weeks of strength
training with 12 weeks of testosterone therapy or placebo
are reported (A), and then the results comparing another
12 weeks of strength training combined with testosterone
therapy or placebo with 24 weeks of testosterone therapy
or placebo are reported (B).
JAGS JUNE 2013–VOL. 61, NO. 6 SUPERVISED STRENGTH TRAINING AND TESTOSTERONE THERAPY 959
(A) Mechanical Muscle Function (MVC, RFD,
10 RM, and JH)
Strength training increased MVC by 8% (from 203 11 N
to 219 11 N, P<.001) (Figure 2, upper panel). Strength
training also markedly increased 10 RM in the knee
extension (42%) and leg press exercises (65%) (P<.001,
data not shown). No changes were observed in JH, with an
average JH of 17 cm (data not shown). Likewise, RFD and
peak power in the CMJ test showed only minor,
nonsignificant changes varying from 4% to +4%. MVC,
RFD, and JH were unaffected after 12 weeks of testosterone
therapy.
Bioavailable Testosterone Levels and LBM
Twelve weeks of strength training did not result in differ-
ent bioavailable testosterone levels or LBM from those
with placebo (Table 1), although testosterone therapy
resulted in significantly higher bioavailable testosterone
levels (~50%) and LBM (~3%) than placebo and strength
training (Table 1).
13
(B) Mechanical Muscle Function (MVC, RFD, 10 RM,
and JH)
Another 12 weeks of strength training in the strength
training plus placebo group further improved MVC by
8% (from 215 15 N to 232 17 N; P=.001) (Fig-
ure 2, lower panel) and RFD by 10% (from 2,598 222
Nm/s to 2,855 176 Nm/s; P=.04). Likewise, 10-RM
knee extension (14%) and leg press (9%) improved fur-
ther after an additional 12 weeks of training (strength
training plus placebo group) (P<.001, data not shown).
No changes were observed in JH and peak power.
Another 12 weeks of strength training in the strength
training plus placebo group did not change LBM or bio-
available testosterone (Table 1). Combining testosterone
therapy and strength training in a subset of individuals
(strength training plus testosterone group) during the final
12 weeks, induced further improvements in MVC (5%,
from 224 18 N to 235 18 N; P=.046) and 10-RM
knee extension (9%) and leg press (13%) (P<.001, data
not shown), but similar to those observed in the strength
training plus placebo group. No changes were observed in
JH, RFD and peak power. No significant differences were
observed between the two groups (strength training plus
testosterone group and strength training plus placebo
group)in any of the mechanical muscle function parame-
ters. Another 12 weeks of testosterone therapy did not
change mechanical muscle function parameters in the
testosterone group.
Bioavailable Testosterone Levels and LBM
Bioavailable testosterone increased nonsignificantly by
20% (P=.10) in the testosterone group, and there were
no further changes in LBM (Table 1). Combining testoster-
one therapy and strength training in the strength training
plus testosterone group increased LBM significantly
(P=.01), to the same level as observed in the testosterone
group. A similar pattern was observed for bioavailable
testosterone. A combination of strength training and tes-
tosterone therapy increased bioavailable testosterone from
5.4 0.6 to 10.7 1.6 nmol/L (P=.01 time and treat-
ment effect) and LBM (P=.008 time effect, Figure 2,
lower panel).
DISCUSSION
This 24-week randomized, double-blind, placebo-controlled
study found that aging men with low-normal testosterone
levels may benefit from strength training. The participants
obtained significant increases in MVC and 10 RM during
the first 12 weeks of strength training, although LBM did
not increase significantly. Subjects receiving testosterone
therapy increased bioavailable testosterone levels approxi-
mately 100% and LBM by approximately 2 kg,
13
although
no significant effect on mechanical muscle function was
observed. Combining testosterone therapy and strength
training in a subgroup of men for an additional 12 weeks
did not induce further increases in mechanical muscle func-
tion over strength training alone. Bioavailable testosterone
levels and LBM increased by a magnitude similar to that
seen after 12 weeks of testosterone therapy alone.
13
In
accordance with these results, one randomized study
showed a significant increase in 1-RM leg press strength
after 12 weeks of testosterone therapy and strength training
in frail older men (mean age 78) with low testosterone
levels.
23
The low-normal testosterone levels may explain the
lack of increase in LBM during strength training in the
strength training and strength training plus placebo
groups.
2427
It was therefore expected that testosterone
therapy in combination with strength training would aug-
ment the adaptations to training and hence lead to larger
increases in LBM and mechanical muscle function,
because it has previously been shown in young healthy
men that supraphysiological doses of testosterone
combined with strength training lead to greater gains in
muscle mass and muscle strength than testosterone or
strength training alone,
28
but no additional effect on
mechanical muscle function was found in the strength
training plus testosterone group, although LBM
increased. Supporting these results, another study
reported no additional effect on strength of adding a
higher dose of testosterone therapy (testosterone enant-
hate 100 mg/wk) to strength training for 12 weeks.
23
Accordingly, another study argued that the neuromuscu-
lar adaptations required for translating muscle mass gain
into mechanical muscle function improvements after tes-
tosterone therapy may take longer than 20 weeks when
the only stimulus is normal daily physical activity (with-
out training intervention).
24
Few studies have reported
positive changes in mechanical muscle function during
physiological testosterone therapy.
2,8
Some authors
argued that the use of insensitive tests (e.g., rising from
a chair, 20-m walk) may not detect small increases. Fur-
thermore, most of the subjects in the earlier studies may
have had baseline functional muscular capacities higher
than the tests could detect,
29
whereas in the present
study, measurements of MVC, RFD, and JH were
conducted using criterion standard methods, which are
highly sensitive and measure functionally relevant
960 KVORNING ET AL. JUNE 2013–VOL. 61, NO. 6 JAGS
features such as knee and hip extensor strength and
power.
30
Nevertheless, no effect was found of testoster-
one therapy for 24 weeks on mechanical muscle function
in this study.
In conclusion, strength training improves mechanical
muscle function (MVC, 10 RM, and RFD) in aging men
with low-normal testosterone levels, but this effect occurs
without a significant increase in LBM. There was no addi-
tional effect on strength by combining strength training
and testosterone therapy than with strength training alone.
Testosterone therapy increased bioavailable testosterone
levels by approximately 100% and increased LBM,
although without any effect on mechanical muscle
function. The lack of improvement in mechanical muscle
function in the strength training plus testosterone group
may be due to lack of statistical power.
Table 1. Bioavailable Testosterone and Lean Body Mass (LBM) at 0 and During 12 and 24 Weeks of Placebo,
Testosterone, and Strength Training
Group
Bioavailable Testosterone (nmol/L) LBM (kg)
Week 0 Week 12 Week 24 Week 0 Week 12 Week 24
Mean (Standard Error)
Placebo (n =16) 4.6 (0.3) 4.1 (0.2) 3.9 (0.2) 66.3 (2.1) 66.2 (2.1) 66.2 (2.1)
Testosterone (n =19)
a
5.1 (0.3) 9.3 (1.1)
b
11.1 (1.4)
b
64.3 (1.8) 66.1 (1.8)
b
66.0 (1.9)
b
Strength training (n =8) 5.5 (0.2) 4.6 (0.2) 4.5 (0.4) 63.4 (2.0) 63.2 (2.2) 63.7 (2.1)
The strength training group consists of subjects who underwent strength training for the first 12 weeks and strength training plus placebo for the final
12 weeks.
a
Significant treatment effect in bioavailable testosterone and LBM (P<.001).
b
Significantly higher than at Week 0 (P<.05).
MVC,% of value at week 0
*
*
**
90
95
100
105
110
115
120
125
130
012 24
Strength training
Testosterone
Placebo
RFD, % of value at week 0
*
90
95
100
105
110
115
120
125
130
Strength training
Testosterone
Placebo
012 24
MVC, % of value at week 0
*
*
95
100
105
110
115
120
125
012 24
Week(s)
Strength training + placebo
Strength training + testosterone
Strength training
Strength training
Lean Body Mass,
% of value at week 0
*
Strength training + placebo
Strength training + testosterone
Strength training
Strength training
90
95
100
105
110
012 24
Week(s)
Figure 2. Upper panel: maximum voluntary contraction (MVC) and rate of force development (RFD) after 24 weeks of strength
training versus testosterone or placebo. Testosterone group, n =18; placebo group, n =16; strength training group, n =14.
*Significant time effect (P<.01). **Significant training effect (P<.01). Lower panel: MVC and lean body mass after 24 weeks
of strength training. After the first 12 weeks of strength training, the subjects continued strength training for another 12 weeks
but were randomized to testosterone or placebo. Values are presented in percentage (%) of value at Week 0. Strength training
plus testosterone group, n =6; strength training plus placebo group, n =8. *Significant time effect (P<.01). No significant
differences were observed between the two groups.
JAGS JUNE 2013–VOL. 61, NO. 6 SUPERVISED STRENGTH TRAINING AND TESTOSTERONE THERAPY 961
ACKNOWLEDGMENTS
The authors would like to thank the Novo Nordisk Foun-
dation (scholarship 2010), Ipsen Scandinavia for kindly
providing Testim and placebo and the Clinical Institute,
University of Southern Denmark.
Conflict of Interest: The editor in chief has reviewed
the conflict of interest checklist provided by the authors
and has determined that the authors have no financial or
any other kind of personal conflicts with this paper.
Author Contributions: Kvorning: study design, meth-
odology, collection of data, analysis and interpretation of
data, statistical analysis, preparation of manuscript. Chris-
tensen, Andersen: study design, methodology, collection of
data, interpretation of data, preparation of manuscript.
Madsen: study design, methodology, analysis and interpre-
tation of data, statistical analysis, preparation of manu-
script. Nielsen, Gejl: collection of data, analysis and
interpretation of data, preparation of manuscript. Brixen:
study design, methodology, preparation of manuscript.
Sponsor’s Role: The sponsor had no role in the design,
methods, subject recruitment, data collections, analysis, or
preparation of the manuscript.
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962 KVORNING ET AL. JUNE 2013–VOL. 61, NO. 6 JAGS
... Several previous studies examined the effect of TRT on muscle function in men with hypogonadism unrelated to opioid therapy. 24,32,33 Our findings of unchanged muscle function during TRT are in line with two previous placebo-controlled RCTs in healthy older (≥60 years) men with hypogonadism. 32,33 In addition, a recent systematic review evaluating the impact of TRT on muscle function in older men without opioid treatment found no effect of TRT on muscle function. ...
... 24,32,33 Our findings of unchanged muscle function during TRT are in line with two previous placebo-controlled RCTs in healthy older (≥60 years) men with hypogonadism. 32,33 In addition, a recent systematic review evaluating the impact of TRT on muscle function in older men without opioid treatment found no effect of TRT on muscle function. 24 However, this review is not aligned with a meta-analysis indicating an average 10.3% increase in lower extremity strength following TRT in older men (≥60 years). ...
... In accordance, interventions combining TRT with physical exercise showed a large increase in muscle strength and muscle function compared to TRT alone. 32,33,[39][40][41][42] This was earlier demonstrated in healthy subjects, 39 COPD patients, 40 and men with hypogonadism. 32,33,42 The combined effect of TRT and physical exercise on muscle function in men with chronic pain should be investigated in future studies. ...
Article
Background : Chronic pain and opioid treatment are associated with increased risk of male hypogonadism and subsequently decreased muscle function. A diagnosis of hypogonadism is based on the presence of low total testosterone (TT) and associated symptoms. The effect of testosterone replacement therapy (TRT) on muscle function in men with chronic pain and low TT remains to be investigated. Objectives : To investigate effects of TRT on muscle function and gait performance in men treated with opioids for chronic non-cancer pain. Materials and methods : Double-blind, placebo-controlled study. 41 men (>18 years) with opioid-treated chronic pain and serum total testosterone <12 nmol/L were randomized to 24 weeks TRT (Testosterone undecanoate injection three times/6 months, n = 20) or placebo injections (n = 21). Muscle function was measured as leg press maximal voluntary contraction (LP-MVC), leg extension power using the Nottingham power rig and handgrip strength using a handheld dynameter. Gait performance was measured at usual and maximal gait speed on a 10-m track. Body composition (lean body mass and fat mass) was determined by Dual-energy X-ray Absorptiometry. Mann-Whitney tests were performed on ∆-values (24–0 weeks) between TRT and placebo. Results : At baseline, median (interquartile range) age was 55 ± 13 years and BMI was 30.7 ± 5.2 kg/m². ∆-muscle function and ∆-gait performance were similar between TRT and placebo. Median ∆-LP-MVC was 174.2 ± 406.7 Newton following TRT and 7.6 ± 419.1 Newton after placebo, p = 0.091. ∆-lean body mass was significantly higher following TRT compared to placebo, 3.6 ± 2.7 vs 0.1 ± 3.5 kg, respectively (p <0.001). Discussion : TRT, compared to placebo, did not improve muscle function or gait performance despite increased lean body mass. Changes in body composition did not infer any changes in muscle function. Conclusion : 24 weeks TRT in opioid treated men with pain-related male hypogonadism did not improve muscle function. This article is protected by copyright. All rights reserved
... Clinical conditions found were: HIV [35][36][37][38][39][40], chronic obstructive pulmonary disease (COPD) [41,42], heart failure (HF) [43,44], spinal cord injury (SCI) [45], kidney failure [46], severe burn [47], obesity [48], hemiplegia [49], and hypogonadism [50]. Seven studies were performed in elderly individuals without a diagnosed clinical condition [32,33,[51][52][53][54][55] and 1 study was conducted in children and teenagers [47]. Only 1 study was performed in healthy adult men, but it employed a bed rest model that induced atrophy and hence was included in our review [56]. ...
... The duration of the exercise intervention protocol ranged from 3 weeks to 12 months. The types of exercise found in the studies were resistance training [32,33,[35][36][37][38][39][40][41][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58] steady-state aerobic training [36,42,44,47,48,57] and high-intensity intermittent exercise (HIIT) [43,56]. The administration of testosterone was carried out intramuscularly [32, 35-37, 39-44, 46, 48-50, 55, 56], orally [38,39,42,47,54,57,58] and transdermally [33,45,[51][52][53]. ...
... The types of exercise found in the studies were resistance training [32,33,[35][36][37][38][39][40][41][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58] steady-state aerobic training [36,42,44,47,48,57] and high-intensity intermittent exercise (HIIT) [43,56]. The administration of testosterone was carried out intramuscularly [32, 35-37, 39-44, 46, 48-50, 55, 56], orally [38,39,42,47,54,57,58] and transdermally [33,45,[51][52][53]. Different testosterone formulas were used across the studies, and the dosage and regimen of testosterone ranged from 2 mg per day to 600 mg per week. ...
Article
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Sarcopenia, cachexia, and atrophy due to inactivity and disease states are characterized by a loss of skeletal muscle mass, often accompanied by reduced levels of anabolic hormones (e.g. testosterone). These conditions are associated with an increase in mortality, hospitalization and worsening in quality of life. Both physical exercise (EX) and anabolic-androgenic steroid (AAS) administration can improve the prognosis of patients as they increase physical functionality. However, there is a gap in the literature as to the impact of these therapies on the gains in strength and muscle mass and their implications for patient safety. Accordingly, we performed a random-effects meta-analysis to elucidate the effects of AAS and/or EX interventions on lean body mass (LBM) and muscle strength in conditions involving muscle loss. A systematic search for relevant clinical trials was conducted in MEDLINE, EMBASE, SCOPUS, Web of Science, and SPORTDiscus. Comparisons included AAS vs. Control, EX vs. Control, AAS vs. EX, AAS + EX vs. AAS and AAS + EX vs. EX. A total of 1114 individuals were analyzed. AAS increased LBM (effect size [ES]: 0.46; 95% CI: 0.25, 0.68, P = 0.00) and muscle strength (ES: 0.31; 95% CI: 0.08, 0.53, P = 0.01) when compared to a control group. EX promoted an increase in muscular strength (ES: 0.89; 95% CI: 0.53, 1.25, P = 0.00), with no effect on LBM when compared to the control group (ES: 0.15; 95% CI:-0.07, 0.38, P = 0.17). AAS did not demonstrate statistically significant differences when compared to EX for LBM and muscle strength. The combination of EX + AAS promoted a greater increase in LBM and muscular strength when compared to AAS or EX in isolation. Qualitatively, AAS administration had relatively few side effects. Significant heterogeneity was found in some analyses, which may be explained by the use of different AAS types and EX protocols. Our findings suggest that AAS administration in cachectic and sarcopenic conditions may be a viable interventional strategy to enhance muscle function when exercise is not a possible approach. Moreover, combining AAS with exercise may enhance positive outcomes in this population.
... Conversely, based on our previous epidemiological study (19), men with baseline serum T >14 nmol/L would be less likely to benefit from supplementation with exogenous T so were excluded. Our entry criteria are also in line with recent studies of T treatment in middle-aged and older men for cardiovascular and health benefit (28)(29)(30). Participants proceeded to the graded exercise test if the waist circumference was confirmed as ! 95 cm and BP 150/ 95mmHg during the clinic visit and there were no clinical indications of pituitary, testicular, or prostate disease (as assessed by an endocrinologist). ...
... Further supporting the dose-dependent relationship, studies in younger men combining supraphysiological T treatment and exercise training, have reported strength increases double that of T treatment or exercise alone (21,67). In contrast, studies combining physiological T doses and exercise in young HIV-infected men (68), frail elderly men (44), and generally healthy older men with low-normal serum T concentrations (22,29) have reported T treatment did not augment strength increases observed with Ex. Similarly, although we observed that the combination of T þ Ex resulted in a greater increase in leg press strength compared with P þ NEx, there was no significant difference between Ex groups. ...
Article
Full-text available
As men age, serum testosterone (T) concentrations decrease, as do fitness, strength and lean mass. Whether testosterone treatment confers additive benefit to reverse these changes when combined with exercise training in middle-to-older aged men remains unclear. We assessed the effects of T treatment and exercise, alone and in combination, on aerobic capacity (VO2peak), body composition and muscular strength in men 50-70yrs, waist circumference ≥95cm and low-normal serum T (6-14nmol·L-1). Participants (n=80) were randomised to AndroForte5® (Testosterone 5.0%w/v, 100mg/2mL) cream (T), or matching placebo (P), applied transdermally daily, and supervised centre-based exercise (Ex) or no additional exercise (NEx), for 12-weeks. Exercise increased VO2peak and strength vs non-exercise (VO2peak: T+Ex:+2.5, P+Ex:+3.2mL·kg-1·min-1, P<0.001; leg press: T+Ex:+31, P+Ex:+24kg, P=0.006). T treatment did not affect VO2peak or strength. Exercise decreased total (T+Ex:-1.7, P+Ex-2.3kg, P<0.001) and visceral fat (T+Ex:-0.1, P+Ex:-0.3kg, P=0.003), and increased total (T+Ex:+1.4, P+Ex:+0.7kg, P=0.008) and arm lean mass (T+Ex:+0.5, P+Ex:+0.3kg, P=0.024). T treatment did not affect total or visceral fat, but increased total (T+Ex:+1.4, T+NEx:+0.7kg, P=0.015), leg (T+Ex:+0.3, T+NEx:+0.2kg, P=0.024) and arm lean mass (T+Ex:+0.5, T+NEx:+0.2kg, P=0.046). T+Ex increased arm lean mass (T+Ex:+0.5kg vs P+NEx:-0.0kg, P=0.001) and leg strength (T+Ex:+31 vs P+NEx:+12kg, P=0.032) compared to P+NEx, with no other additive effects. Exercise training was more effective than T treatment in increasing aerobic capacity and decreasing total and visceral fat mass. T treatment at therapeutic doses increased lean mass but conferred limited additional benefit when combined with exercise. Exercise should be evaluated as an anti-ageing intervention in preference to testosterone treatment in men.
... The largest negative effect for free-T was observed by Hakkinen et al. (2002). When comparing to similar duration interventions (Ahtiainen et al., 2015), and similar resistance training programmes (Hakkinen and Pakarinen, 1994;Kraemer et al., 1999;Kvorning et al., 2013), it is difficult to explain these results merely with time course or training variables. Moreover, the study exhibiting the largest positive effect on free-T (Kraemer et al., 1999) used a similar resistance training programme as Hakkinen et al. (2002), and the same detection method (radioimmunoassay [RIA]). ...
... One investigation recruited individuals for their low testosterone , whilst three studies reported low mean starting TT <12 nmol·L −1 (Vaczi et al., 2014;Ahtiainen et al., 2015;Armamento-Villareal et al., 2016), and all included a resistance training intervention. Kvorning et al. (2013) observed a negative SDM for bio-T in aging men with low-normal testosterone, whilst Ahtiainen et al. (2015) reported no change to free-T but a positive change to TT. Armamento-Villareal et al. (2016) reported a substantial change in TT after 12 months but not after 6 months. As such, investigations recruiting biochemically hypogonadal individuals also report inconsistent findings, thus starting testosterone concentrations appears unlikely to influence the response to resistance training. ...
Article
Full-text available
Background: The age-associated decrease in testosterone is one mechanism suggested to accelerate the aging process in males. Therefore, approaches to increase endogenous testosterone may be of benefit. The aim of this paper was to undertake a Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-accordant meta-analysis concerning the effect of exercise on total (TT), bioavailable (bio-T), free (free-T), and salivary (sal-T) testosterone in older males. Methods: Databases were searched up to and including 20th February 2018 for the terms “testosterone AND exercise AND aging AND males,” “testosterone AND exercise AND old AND males,” “testosterone AND training AND aging AND males,” and “testosterone AND training AND old AND males”. From 1259 originally identified titles, 22 studies (randomized controlled trials; RCTs; n = 9, and uncontrolled trials; UCTs; n = 13) were included which had a training component, participants ≥60 years of age, and salivary or serum testosterone as an outcome measure. Meta-analyses were conducted on change to testosterone following training using standardized difference in means (SDM) and random effects models. Results: The overall SDM for endurance training, resistance training, and interval training was 0.398 (95% CI = 0.034–0.761; P = 0.010), −0.003 (95% CI = −0.330–0.324; P = 0.986), and 0.283 (95% CI = 0.030–0.535; P = 0.028), respectively. Resistance training exhibited a qualitative effect of hormone fraction whereby free-T resulted in the greatest SDM (0.253; 95% CI = −0.043–0.549; P = 0.094), followed by TT (0.028; 95% CI = −0.204–0.260; P = 0.813), and resistance training negatively influenced bio-T (−0.373; 95% CI = −0.789–0.042; P = 0.078). Due to the small number of studies, subgroup analysis was not possible for endurance training and interval training studies. Conclusions: Data from the present investigation suggests that resistance training does not significantly influence basal testosterone in older men. Magnitude of effect was influenced by hormone fraction, even within the same investigation. Aerobic training and interval training did result in small, significant increases in basal testosterone. The magnitude of effect is small but the existing data are encouraging and may be an avenue for further research.
... Physical training, as the most effective intervention for sarcopenia, is often used in combination with pharmacological interventions to improve the effectiveness. Although, previous studies of TRT combined with exercise presented inconsistent results (55, 56, 59, 60), several clinical trials showed that the combination treatment can help increase the muscle mass or strength (59,60). A prospective study demonstrated that TRT offers no benefit beyond resistance exercise alone (61). ...
Article
Full-text available
Sarcopenia, characterized by the excessive loss of skeletal muscle mass, strength, and function, is associated with the overall poor muscle performance status of the elderly, and occurs more frequently in those with chronic diseases. The causes of sarcopenia are multifactorial due to the inherent relationship between muscles and molecular mechanisms, such as mitochondrial function, inflammatory pathways, and circulating hormones. Age-related changes in sex steroid hormone concentrations, including testosterone, estrogen, progesterone, and their precursors and derivatives, are an important aspect of the pathogenesis of sarcopenia. In this review, we provide an understanding of the treatment of sarcopenia through the regulation of sex steroid hormones. The potential benefits and future research emphasis of each sex steroid hormone therapeutic intervention (testosterone, SARMs, estrogen, SERMs, DHEA, and progesterone) for sarcopenia are discussed. Enhanced understanding of the role of sex steroid hormones in the treatment for sarcopenia could lead to the development of hormone therapeutic approaches in combination with specific exercise and nutrition regimens.
... 9 A similar beneficial additive effect of testosterone and exercise on performance without weight gain has been observed in older males with low normal blood testosterone. 10 The myotrophic effects of testosterone are dose-dependent in males, and the effect does not wane with age. 11 It is not known whether similar beneficial effects would be seen in males with IBM. ...
... The upregulation and release of such hormones during recovery from resistance exercise indicates that such a response is likely essential for restoring body homeostasis. Work in both animal models and humans with low testosterone has indicated that low testosterone suppresses both the synthesis of myofibrillar proteins by muscle and the accrual of lean body mass (White et al. 2013;Kvorning et al. 2013). A recent review indicated that testosterone interacts in two ways with its receptors to upregulate protein synthesis: genomically, through its interaction with the androgen receptor and nuclear DNA; and non-genomically, through its interaction with a membrane-bound receptor that triggers intracellular signaling (Hooper et al. 2017). ...
Article
Full-text available
PurposeResistance exercise induces muscle growth and is an important treatment for age-related losses in muscle mass and strength. Myokines are hypothesized as a signal conveying physiological information to skeletal muscle, possibly to “fine-tune” other regulatory pathways. While myokines are released from skeletal muscle following contraction, their role in increasing muscle mass and strength in response to resistance exercise or training is not established. Recent research identified both local and systemic release of myokines after an acute bout of resistance exercise. However, it is not known whether myokines with putative anabolic function are mechanistically involved in producing muscle hypertrophy after resistance exercise. Further, nitric oxide (NO), an important mediator of muscle stem cell activation, upregulates the expression of certain myokine genes in skeletal muscle.Method In the systemic context of complex hypertrophic signaling, this review: (1) summarizes literature on several well-recognized, representative myokines with anabolic potential; (2) explores the potential mechanistic role of myokines in skeletal muscle hypertrophy; and (3) identifies future research required to advance our understanding of myokine anabolism specifically in skeletal muscle.ResultThis review establishes a link between myokines and NO production, and emphasizes the importance of considering systemic release of potential anabolic myokines during resistance exercise as complementary to other signals that promote hypertrophy.Conclusion Investigating adaptations to resistance exercise in aging opens a novel avenue of interdisciplinary research into myokines and NO metabolites during resistance exercise, with the longer-term goal to improve muscle health in daily living, aging, and rehabilitation.
... Mechanisms of action for testosterone include increasing protein synthesis Ferrando et al., 2003) via Akt/mTOR activation (White et al., 2013) and reduction in adipose stem cells and activation of satellite cell recruitment (Kovacheva et al., 2010). There is strong evidence from intervention studies that treatment with testosterone is effective in increasing lean mass and reducing fat mass (Kenny et al., 2010;Srinivas-Shankar et al., 2010;Kvorning et al., 2013). However, the efficacy of testosterone to improve muscle-specific strength and physical function is less clear (Snyder et al., 1999;Saad et al., 2017). ...
Article
Full-text available
Sarcopenia is the loss of muscle mass, strength, and physical function that is characteristic of aging. The progression of sarcopenia is gradual but may be accelerated by periods of muscle loss during physical inactivity secondary to illness or injury. The loss of mobility and independence and increased comorbidities associated with sarcopenia represent a major healthcare challenge for older adults. Mitochondrial dysfunction and impaired proteostatic mechanisms are important contributors to the complex etiology of sarcopenia. As such, interventions that target improving mitochondrial function and proteostatic maintenance could mitigate or treat sarcopenia. Exercise is currently the only effective option to treat sarcopenia and does so, in part, by improving mitochondrial energetics and protein turnover. Exercise interventions also serve as a discovery tool to identify molecular targets for development of alternative therapies to treat sarcopenia. In summary, we review the evidence linking mitochondria and proteostatic maintenance to sarcopenia and discuss the therapeutic potential of interventions addressing these two factors to mitigate sarcopenia.
Article
Background Long-term testosterone replacement therapy (TRT) increases muscle mass in elderly men with subnormal testosterone levels. However, the molecular mechanisms underlying this effect of TRT on protein balance in human skeletal muscle in vivo remain to be established. Methods Here, we examined skeletal muscle biopsies obtained before and 24-h after the last dose of treatment with either testosterone gel (n = 12) or placebo (n = 13) for 6 months in aging men with subnormal bioavailable testosterone levels. The placebo-controlled, testosterone-induced changes (β-coefficients) in mRNA levels, protein expression and phosphorylation were examined by quantitative real-time PCR and western blotting. Results Long-term TRT increased muscle mass by β = 1.6 kg (p = 0.01) but had no significant effect on mRNA levels of genes involved in myostatin/activin/SMAD or IGF1/FOXO3 signalling, muscle-specific E3-ubiquitin ligases, upstream transcription factors (MEF2C, PPARGC1A-4) or myogenic factors. However, TRT caused a sustained decrease in protein expression of SMAD2 (β = −36%, p = 0.004) and SMAD3 (β = −32%, p = 0.001), which was accompanied by reduced protein expression of the muscle-specific E3-ubiquitin ligases, MuRF1 (β = −26%, p = 0.004) and Atrogin-1/MAFbx (β = −20%, p = 0.04), but with no changes in FOXO3 signalling. Importantly, TRT did not affect muscle fibre type distribution between slow-oxidative (type 1), fast-oxidative (type 2a) and fast-glycolytic (type 2×) muscle fibres. Conclusions Our results indicate that long-term TRT of elderly men with subnormal testosterone levels increases muscle mass, at least in part, by decreasing protein breakdown through the ubiquitin proteasome pathway mediated by a sustained suppression of SMAD-signalling and muscle-specific E3-ubiquitin ligases.
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Improving physical function and mobility in a continuously expanding elderly population emerges as a high priority of medicine today. Muscle mass, strength/power, and maximal exercise capacity are major determinants of physical function, and all decline with aging. This contributes to the incidence of frailty and disability observed in older men. Furthermore, it facilitates the accumulation of body fat and development of insulin resistance. Muscle adaptation to exercise is strongly influenced by anabolic endocrine hormones and local load-sensitive autocrine/paracrine growth factors. GH, IGF-I, and testosterone (T) are directly involved in muscle adaptation to exercise because they promote muscle protein synthesis, whereas T and locally expressed IGF-I have been reported to activate muscle stem cells. Although exercise programs improve physical function, in the long-term most older men fail to comply. The GH/IGF-I axis and T levels decline markedly with aging, whereas accumulating evidence supports their indispensable role in maintaining physical function integrity. Several studies have reported that the administration of T improves lean body mass and maximal voluntary strength in healthy older men. On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and T are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and T, albeit in only a few studies, has resulted in greater efficacy than either hormone alone. Although it is clear that this combined approach is effective, this review concludes that further studies are needed to assess the long-term efficacy and safety of combined hormone replacement therapy in older men before the medical rationale of prescribing hormone replacement therapy for combating the sarcopenia of aging can be established.
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limited information on the prevalence of osteoporosis and VFxs in men in high-risk populations is available. The choice of reference values for dual X-ray absorptiometry (DXA) is debated. We evaluated the prevalence of osteoporosis and vertebral deformities in a population-based sample of men. bone mineral density (BMD) was measured and vertebral deformities assessed using DXA and VFx assessment (VFA), respectively, in a random sample of 600 Danish men aged 60-74 years. Osteoporosis was defined as a T-score of -2.5 or less. the study population was comparable with the background population with regard to age, body mass index and co-morbidity. Osteoporosis was diagnosed in less than 1% of the participants at inclusion. Using Danish and NHANES III reference data, 10.2 and 11.5% of the study population had osteoporosis, respectively. In all, 6.3% participants had at least one VFx. BMD was significantly lower in participants with vertebral deformities, but only 24% of these cases had osteoporosis. osteoporosis and VFxs are prevalent in men aged 60-74 years. Although the majority of deformities were present in individuals without osteoporosis, BMD was lower in patients with VFxs at all sites investigated. Male osteoporosis was markedly underdiagnosed.
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We hypothesized that treatment with testosterone (T) and recombinant human growth hormone (rhGH) would increase lean mass (LM) and muscle strength proportionally and an in a linear manner over 16 weeks. This was a multicenter, randomized, controlled, double-masked investigation of T and rhGH supplementation in older (71 ± 4 years) community-dwelling men. Participants received transdermal T at either 5 or 10 g/day as well as rhGH at 0, 3.0 or 5.0 μg/kg/day for 16 weeks. Body composition was determined by dual-energy X-ray absorptiometry (DEXA) and muscle performance by composite one-repetition maximum (1-RM) strength and strength per unit of lean mass (muscle quality, MQ) for five major muscle groups (upper and lower body) at baseline, week 8 and 17. The average change in total LM at study week 8 compared with baseline was 1.50 ± 1.54 kg (P < 0.0001) in the T only group and 2.64 ± 1.7 (P < 0.0001) in the T + rhGH group and at week 17 was 1.46 ± 1.48 kg (P < 0.0001) in the T only group and 2.14 ± 1.96 kg (P < 0.0001) in the T + rhGH group. 1-RM strength improved modestly in both groups combined (12.0 ± 23.9%, P < 0.0001) at week 8 but at week 17 these changes were twofold greater (24.7 ± 31.0%, P < 0.0001). MQ did not significantly change from baseline to week 8 but increased for the entire cohort, T only, and T + rhGH groups by week 17 (P < 0.001). Despite sizeable increases in LM measurements at week 8, tests of muscle performance did not show substantive improvements at this time point.
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No large studies of young men have examined circulating sex hormones in relation to visceral and sc adipose tissues. The aim of this study was to investigate the role of visceral adipose tissue and sc adipose tissue on circulating sex hormones and the impact of obesity on sex hormone reference intervals. Population-based study of 783 Danish 20- to 29-yr-old men was performed using dual-energy x-ray absorptiometry in all men and magnetic resonance imaging in 406 men. Total, bioavailable, and free testosterone, dihydrotestosterone (DHT), total and bioavailable estradiol, SHBG, and LH were measured. In multiple regressions, visceral adipose tissue was an independent, inverse correlate of bioavailable and free testosterone. Subcutaneous adipose tissue correlated negatively with SHBG and positively with bioavailable estradiol adjusted for total testosterone. Both visceral adipose tissue and sc adipose tissue correlated inversely with total testosterone and DHT. Adjusting for SHBG, only visceral adipose tissue remained significantly correlated. Low total testosterone in viscerally obese men was not accompanied by increased LH. The androgen reference intervals were significantly displaced toward lower limits in obese vs. nonobese men (total testosterone: 8.5-29.3 vs. 12.5-37.6 nmol/liter; bioavailable testosterone: 6.1-16.9 vs. 7.6-20.7 nmol/liter; free testosterone: 0.23-0.67 vs. 0.29-0.78 nmol/liter; and DHT: 0.63-2.5 vs. 0.85-3.2 nmol/liter), whereas total estradiol (36.5-166 pmol/liter) and bioavailable estradiol (23.4-120 pmol/liter) reference intervals were not. In obese men, 22.9% had total testosterone less than 12.5 nmol/liter. Visceral adipose tissues correlate independently with bioavailable and free testosterone in young men. The inverse relationship between total testosterone and sc adipose tissue seems to be accounted for by variations in SHBG. The reference intervals for total testosterone, bioavailable testosterone, free testosterone, and DHT are displaced toward lower limits in obese men.
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Ageing in men is associated with changes in levels of sex hormones. To evaluate differences in sex hormones in young and elderly men and the significance of comorbidity and fat mass on sex hormones in elderly men. Cross-sectional. Seven hundred and eighty-three men aged 20–29 years and 600 men aged 60–74 years randomly recruited from the background population. Sex hormones and sex hormone-binding globulin (SHBG) were measured, and reference intervals were determined in healthy individuals in both groups and in elderly men stratified according to whether they were obese or lean (waist circumference ≥102 cm). Sex hormones were lower and SHBG higher in elderly men compared with the young cohort. Lower cut-offs for total testosterone (TT) in healthy, young and elderly men were similar [Lower cut-off (95% CI): Young: 11·7 (11·2–12·1) vs elderly: 11·2 (10·3–12·1) nmol/l], but lower and higher cut-offs of bioavailable testosterone (BT) and free testosterone (FT) were higher in young men. Higher levels of androgens were found in healthy elderly men compared with those with a chronic disease or obesity. Androgens were inversely associated with central fat mass (CFM), whereas SHBG was inversely and directly associated with CFM and lower extremity fat mass, respectively, in both young and elderly men. Reference intervals for TT were comparable in healthy young and elderly men, but reference intervals for FT and BT were lower in elderly men due to higher levels of SHBG. Androgens and SHBG were lower in elderly men with chronic disease and inversely associated with CFM.
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The term frailty describes an age-related state of vulnerable health. The aetiology of this condition is not well understood. A number of mechanisms may contribute to frailty. Amongst these is the possible influence of age-related perturbations of sex hormones, particularly, the fall in testosterone in ageing men. This declining androgenic function has been thought to contribute to the loss of muscle mass (sarcopaenia) and strength that occurs with ageing and thereby underpin the development of frailty. Testosterone replacement has therefore been suggested as a possible intervention to treat frailty. This review summarizes evidence from observational and interventional studies on the effects of testosterone on frailty and its key components including body composition, muscle strength and physical function. Evidence from these studies is considered against study design, methodological issues and in the context of the current understanding of frailty. The role of androgens in the development of frailty and their utility in treating this condition are evaluated. Future research directions for the use of androgens in the treatment of frailty are suggested. The potential interaction between testosterone and other frailty mechanisms and the possibility that secondary components of the sex hormone system may be appropriate frailty biomarkers are also discussed.
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prevalence estimates for chronic diseases and associated risk factors are needed for priority setting and disease prevention strategies. The aim of this cross-sectional study was to estimate the self-reported and clinical prevalence of common chronic disorders in elderly men. a questionnaire was sent to a random sample of 4,975 men aged 60-74 years. An age-stratified randomised sample (n = 1,845) of those with complete questionnaires was invited to participate in a telephone interview (n = 864), followed by physical examination (n = 600). Self-reported data on risk factors and disease prevalence were compared with data from hospital medical records. physical inactivity, smoking and excessive alcohol intake were reported by 27, 22 and 17% of the study population, respectively. Except for diabetes, all the chronic diseases investigated, including hypertension, musculoskeletal and respiratory diseases were underreported by study participants. Erectile dysfunction and hypogonadism were substantially underreported in the study population even though these diseases were found to affect 48 and 21% of the participants, respectively. the study showed a high prevalence of detrimental life style factors including smoking, excessive alcohol consumption and physical inactivity in elderly Danish men. Except for diabetes and respiratory disease, chronic diseases were underreported and in particular erectile dysfunction and osteoporosis were underdiagnosed in the study population, underlining the importance of awareness of chronic diseases among both the general population and physicians.