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

Abstract

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.

Full text

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 (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 pla-
cebo after 12 weeks. Subjects performed supervised
strength training (2–3 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 (15–20 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 (1–b)=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.
24–27
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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