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of Geriatrics, University of Arkansas for Medical Sciences, North Little Rock, Arkansas 72114-1706;
and 6Department of Sport Science, Colorado College, Colorado Springs, Colorado 80913
Kraemer, William J., Keijo Häkkinen, Robert U. New- growth factors [e.g., growth hormone (GH), testoster-
ton, Bradley C. Nindl, Jeff S. Volek, Matthew McCor- one, and insulin-like growth factor (IGF)-I] are also
mick, Lincoln A. Gotshalk, Scott E. Gordon, Steven J. diminished (i.e., somatopause and andropause) (4, 11,
Fleck, Wayne W. Campbell, Margot Putukian, and 16, 22, 33, 42, 46, 56, 61, 62). Over the last 15 years,
William J. Evans. Effects of heavy-resistance training on
resistance training has been a primary intervention
hormonal response patterns in younger vs. older men. J.
Appl. Physiol. 87(3): 982–992, 1999.—To examine the adapta- used to offset the effects of aging by minimizing age-
tions of the endocrine system to heavy-resistance training in related declines in strength, fat-free mass, and func-
younger vs. older men, two groups of men (30 and 62 yr old) tional abilities (2, 14, 18, 20, 54). Campbell et al. (2)
participated in a 10-wk periodized strength-power training demonstrated that resistance training can positively
program. Blood was obtained before, immediately after, and enhance nitrogen retention and whole body muscle
5, 15, and 30 min after exercise at rest before and after protein metabolism in older men. Enhanced protein
training and at rest at ⫺3, 0, 6, and 10 wk for analysis of total turnover favoring the growth of muscle tissue is under
testosterone, free testosterone, cortisol, growth hormone, the homeostatic interactive regulation of the endocrine
lactate, and ACTH analysis. Resting values for insulin-like
system (5, 6, 17, 31, 32, 50, 70). The hormonal changes
growth factor (IGF)-I and IGF-binding protein-3 were deter-
mined before and after training. A heavy-resistance exercise produced by weight-training exercise may be an impor-
test was used to evaluate the exercise-induced responses (4 tant stimulus in older men, contributing to the preven-
sets of 10-repetition maximum squats with 90 s of rest tion of sarcopenia, loss of strength, and loss of func-
between sets). Squat strength and thigh muscle cross- tional abilities. However, data on the effects of strength
sectional area increased for both groups. The younger group training on the acute response patterns of hormonal
demonstrated higher total and free testosterone and IGF-I changes with resistance training in older men are
than the older men, training-induced increases in free testos- limited (5, 18, 54).
terone at rest and with exercise, and increases in resting Heavy-resistance exercise has been shown to be a
IGF-binding protein-3. With training the older group demon-
potent stimulus for acute increases in circulating hor-
strated a significant increase in total testosterone in response
to exercise stress along with significant decreases in resting mones in younger men (5, 23, 24, 30, 36–38, 40, 41, 59).
cortisol. These data indicate that older men do respond with In contrast, heavy-resistance exercise has not been
an enhanced hormonal profile in the early phase of a resis- shown to elicit the same magnitude of hormonal re-
tance training program, but the response is different from sponses in older men (i.e., ⬎60 yr of age) (5, 23, 54, 59).
that of younger men. The importance of circulating hormones resides in the
endocrine; aging; sarcopenia; strength; muscle; andropause; fact that lower amounts of circulating anabolic hor-
somatopause; growth factors mones are thought to influence the age-related decline
in muscle mass and its associated strength capabilities
observed in the sixth decade of life (4, 17, 61, 62).
Because it has been observed in younger men that the
NORMAL AGING IS ASSOCIATED with declines in fat-free alterations in hormonal concentrations may take place
mass, particularly muscle mass (i.e., sarcopenia), and in the early phase of training (67), the question arises
subsequent decrements in muscle strength and func- whether older men can engage similar hormonal mecha-
tional abilities (18–20, 44, 60, 62). With age, plasma nisms in the early phase of a resistance training
concentrations of circulating anabolic hormones and program. Such changes, however, have not been typi-
cally observed (5, 18, 20, 54). This might be due to the
type of resistance training program utilized, inasmuch
The costs of publication of this article were defrayed in part by the
payment of page charges. The article must therefore be hereby
as some protocols have not appeared to be as effective in
marked ‘‘advertisement’’ in accordance with 18 U.S.C. Section 1734 stimulating hormonal responses because of lower inten-
solely to indicate this fact. sity, small muscle mass involvement, and/or longer rest
982 8750-7587/99 $5.00 Copyright r 1999 the American Physiological Society http://www.jap.org
AGING, HORMONES, AND HEAVY-RESISTANCE TRAINING 983
between sets and exercises (16, 24, 34, 36, 38). Further- 0.028 W/kg. MCSA was analyzed from the MRI scans by a
more, only a few studies have presented data on an gradient echo technique, which allows the greatest delinea-
entire ensemble of anabolic and catabolic hormones tion and distinction between muscles. Once the subject was
and acute and chronic responses of resistance exercise positioned within the magnet, the thigh of the dominant leg
and training (23, 54). was supported under the knee to be parallel to the MRI table,
and the feet were strapped together to prevent rotation. A
If the proper resistance training program (e.g., a sagittal image of the thigh was obtained. A 15-slice grid was
periodized program) could enhance the resting and/or placed over the sagittal image, and transaxial images were
exercise-induced responses to resistance exercise, then obtained. Fifteen 1-cm-thick transaxial images were obtained
it might be of therapeutic value for addressing endo- equidistantly between the base of the femoral head and the
crine changes in aging men. The primary purpose of midknee joint of the thigh. All MRI images were then ported
this investigation was to examine the pattern of changes to a Macintosh computer for calculation of total and indi-
in resting and exercise-induced blood hormonal concen- vidual MCSAs with a modified National Institutes of Health
trations in younger and older men before and after a (NIH) image software package. For the MCSA, slice 8 was
periodized resistance training program designed to used (slice 1 being the base of the femoral head). Tissue
enhance muscle size and strength. cross-sectional area was obtained by using the NIH 1.55.20A
Image Analysis pixel-counting program. The same investiga-
tor made all area measurements, and the test-retest reliabil-
METHODS ity intraclass correlation coefficient for this measurement
Subjects. Eight younger [30-yr-old (30Y)] and nine older was R ⫽ 0.99 (21).
[62-yr-old (62Y)] men volunteered to participate in this One-repetition maximum test. Maximal strength was as-
investigation, which was approved by The Pennsylvania sessed using a concentric-only 1-repetition maximum (RM,
State University Institutional Review Board for the Use of i.e., the heaviest load that could be correctly performed once)
Human Subjects. The risks and benefits of the study was squat test on the Plyometric Power System (Norsearch,
thoroughly explained to all subjects, and written informed Lismore, Australia) from a 90° knee angle (37, 73). Warm-up
consent was subsequently obtained. Before inclusion in the consisted of a set of 5–10 repetitions at 40–60% perceived
study, all subjects were medically screened and approved by a maximum. Subjects then rested for ⬃1 min and performed
physician as being healthy (i.e., free from any orthopedic, some light stretching. Thereafter, three to five repetitions
endocrine, or medical problems). None of the subjects was on were performed with 60–80% of the perceived maximum.
any medications during the study. All subjects were physi- Three to four subsequent attempts were then made to deter-
cally active but had not been involved in any previous mine the 1 RM, with 3–5 min of rest between lifts. Proper
structured resistance training programs. Activity question- technique and a complete range of motion were required for
naires were utilized and revealed that all subjects were each successful 1-RM trial. No injuries were observed during
involved in recreational sports and jogging. Pretraining char- the 1-RM testing. The test-retest reliability coefficient for this
acteristics of the experimental subjects were as follows: for test was R ⫽ 0.97.
the 30Y group, age was 29.8 ⫾ 5.3 yr, body mass was 90.0 ⫾ Acute heavy-resistance exercise test. Each subject was famil-
12.8 kg, height was 177.2 ⫾ 5.3 cm, and percent body fat was iarized with the experimental acute heavy-resistance exer-
18.3 ⫾ 4.6%; for the 62Y group, age was 62 ⫾ 3.2 yr, body cise test (AHRET) and performed the AHRET before and at
mass was 84.3 ⫾ 13.4 kg, height was 177.0 ⫾ 7.3 cm, and the conclusion of the 10-wk training program. The AHRET
percent body fat was 20.4 ⫾ 4.6%. From the information consisted of four sets of 10-RM squats with 90 s of rest
collected, it was observed that physical characteristics and between sets. If because of fatigue on any given set, the
activity background of these subjects were essentially similar, subject failed to perform 10 repetitions, the load was subse-
with the only significant (P ⱕ 0.05) difference between the quently adjusted (e.g., lightened) to allow the completion of 10
two groups being age. repetitions on the following set. The squats were performed
Body composition. Body composition was assessed using with the Plyometric Power System, as previously described
skinfolds. All anthropometric measurements were obtained (73).
by the same investigator on the right side of the subject’s Blood collection and analyses. For the AHRET, blood was
body. Skinfold thicknesses were obtained with a Harpenden obtained preexercise, immediately postexercise (IP), and 5,
skinfold caliper (Country Technology, Gays Mills, WI; 10 15, and 30 min postexercise via an indwelling cannula kept
g/mm constant pressure) at the chest, midaxilla, abdomen, patent with a saline lock 1 wk before training (pre) and at the
suprailium, subscapula, triceps, and thigh following the conclusion of the training program (post). In addition, resting
procedures previously described (45). Repeated trials were blood samples were drawn with similar sterile techniques at
performed until two measures within 1 mm were obtained, ⫺3 wk (3 wk before the start of training) and at 0, 3, 6, and 10
with the mean of these two measures being utilized. A wk during training. The blood samples drawn before training
seven-site skinfold equation was used to estimate body den- were obtained to serve as control comparisons, and for the
sity (29), and percent body fat was subsequently calculated ease of illustration, only the 0-wk values are depicted in
using the Siri equation (66). There was no significant differ- RESULTS. Resting blood samples drawn at ⫺3 and 0 wk were
ence in percent fat between the groups. indistinguishable (P ⬎ 0.05). Blood samples were obtained at
Muscle cross-sectional area. Thigh bone-free muscle cross- different times of the day among subjects but at the same
sectional area (MCSA) of the dominant leg was assessed time of day for each subject during the experiment to limit the
before and after the resistance training program by means of influence of any diurnal variations (1, 11, 28, 64). Blood was
a magnetic resonance imaging (MRI) 0.5-T superconduction drawn after an overnight fast, and dietary intake was moni-
magnet (Picker International, Highland Heights, OH) with tored and recorded across time points. Over the course of the
MR6B software. Images were obtained by alteration of the resting baseline time line, blood was drawn from two 30Y
spin-lattice or longitudinal relaxation time (T1). T1-weighted subjects and one 62Y subject outside the 90-min window from
images were obtained using repetition time of 500 ms, echo week 0 (within 2.5 h). Blood was centrifuged at 1,500 g at
time of 13 ms, radio frequency of 90°, and power absorption of ⫺4°C for 15 min. All serum and plasma samples were then
984 AGING, HORMONES, AND HEAVY-RESISTANCE TRAINING
0.05. men.
AGING, HORMONES, AND HEAVY-RESISTANCE TRAINING 985
Fig. 4. Serial resting concentrations (means ⫾ SD) for growth hormone (A), insulin-like growth factor-I (IGF-I; B),
and IGF-I-binding protein (IGFBP-3; C) during 10 wk of periodized strength and power training. l Significantly
different (P ⱕ 0.05) from corresponding value at 0 wk; # statistically significant difference (P ⱕ 0.05) between 30Y
and 62Y men.
15 min, but not for 30 min into recovery. Interaction was elevated above baseline at all time points in the
effects revealed differences between the 30Y and 62Y 62Y men. In the 30Y men, cortisol was elevated over
men at all time points, except for the pretraining preexercise values at 15 and 30 min. Their IP and 5 and
preexercise value. Also, elevations above preexercise 15 min of recovery time points posttraining were lower
values were observed at IP and at 5 and 15 min than the corresponding pretraining values. Differences
post-AHRET for the 30Y men pre- and posttraining. In between the 30Y and 62Y men were observed posttrain-
the 62Y men the FT values were higher than preexer- ing at IP and 5 min of recovery.
cise values at IP and 15 min post-AHRET pretraining Lactate was significantly elevated above baseline
and at IP and 5 min post-AHRET posttraining. For the values after the AHRET for the 30Y and 62Y men
62Y men the pre-AHRET FT value posttraining was before and after the training program (Fig. 7A). Lactate
greater than the pretraining value.
values were higher for the 30Y than for the 62Y group
Compared with pretraining, for ACTH (Fig. 6A)
at every time measured, except at 30 min post-AHRET
significant reductions after the AHRET were observed
posttraining. In the 30Y men, ACTH was elevated posttraining. Posttraining lactate values were lower
pretraining at IP and at 5 and 15 min; however, than the corresponding pretraining values for the 30Y
posttraining elevations were evident only at IP. In the group at IP and at 5 and 15 min post-AHRET. The 62Y
62Y men, ACTH was elevated pretraining at IP and at 5 men demonstrated no elevations in GH (Fig. 7B) above
min, but only at IP for posttraining. In addition, in the pre-AHRET pre- or posttraining. The 30Y men demon-
30Y men the posttraining values were lower than the strated elevated values pretraining for 5, 15, and 30
corresponding pretraining values at IP and at 5 and 15 min of recovery. Posttraining, in the 30Y men, values
min. For the 62Y men the value was lower at IP were higher at IP and at 5 and 15 min into recovery
posttraining than pretraining. Cortisol was elevated than corresponding preexercise baseline values. For
above pre-AHRET values at every time point for both the 30Y men the 30-min recovery value posttraining
age groups pretraining (Fig. 6B). Posttraining, cortisol was lower than the corresponding pretraining value.
AGING, HORMONES, AND HEAVY-RESISTANCE TRAINING 987
DISCUSSION
main effects for TT (20.3 vs. 15.7 nmol/l) and FT (80 vs.
60 pmol/)] were significantly higher in the 30Y than in
the 62Y group. In addition, area-under-the-curve analy-
sis revealed a greater magnitude of increase in the
exercise-induced responses of FT to a resistance train-
ing stimulus in younger men. These data support the
maintenance of an ‘‘andropause,’’ which is character-
ized by a decrease in testicular Leydig cell numbers,
reductions in secretory capacity, and a decrease in
resting episodic and stimulated gonadotropin secretion
(69–71). Staron et al. (67) demonstrated that resting
concentrations of TT in men averaging 23.5 yr of age
increased over baseline values after just 4 wk of
training. However, other studies have not shown a
training-related increase in resting concentrations of
testosterone. This indicates that, in young men, testos-
terone may exhibit a dynamic homeostatic hormonal
response pattern to resistance training. However, in a
study by Nicklas et al. (54), no alterations in resting
concentrations of TT were observed over 16 wk of
progressive training in men averaging 60 yr of age.
Häkkinen and Pakarinen (25) observed a similar nonre-
sponse in 70-yr-old men. Despite the lack of changes in
hormonal concentrations, they reported significant rela-
tionships between testosterone concentrations and
change in strength with training in the 70-yr-old men
(r ⫽ 0.61). In the present study, although no changes in
resting testosterone were observed with 10 wk of
training in the 62Y men, the 62Y group did demon-
strate an enhanced adaptational ability to stimulate
TT after resistance exercise. This finding is unique and
may be related to the periodized training program;
however, the exact reasons and the physiological mecha-
nism(s) mediating this adaptation remain speculative.
The mechanism(s) that mediate such an adaptation
in exercise-induced serum testosterone concentrations
in older men could be due to classic increases in
Fig. 7. Responses (means ⫾ SD) of lactate (A) and growth hormone luteinizing hormone (LH) pulsatility or production (34,
(B) after AHRET before and after 10 wk of periodized strength and 46, 51, 69, 71). However, Lu et al. (47) reported that
power training for 30Y and 62Y men. * Significantly different (P ⱕ
0.05) from corresponding preexercise value; # statistically significant
increased testosterone concentrations in male rats dur-
difference (P ⱕ 0.05) between 30Y and 62Y men; l significantly ing exercise were at least partially the result of a direct
different (P ⱕ 0.05) from corresponding pretraining value. (LH-independent) stimulatory mechanism of exercise,
with lactate influencing the secretion of testosterone by
size and muscle strength in just 10 wk. A major finding increasing testicular cAMP production. Recent evi-
of the present study was that the younger men demon- dence also implicates nitric oxide (via vasodilatory
strated a significantly greater increase in the size of the mechanisms) and blood flow patterns impacting testos-
whole thigh, yet the relative gains, at least in strength terone release at the level of the testis (49). The impact
of the knee extensors, were not different between the of these exercise-induced changes in the older men
older and younger groups. The ability of the younger remains unclear but could have contributed to the
men to elicit a greater relative hypertrophic response in increases in muscle size and strength observed in this
10 wk of training in this study appears to be associated study. One might speculate that in older men such
with the differences in the resting and exercise-induced adaptational increases in testosterone may have contrib-
adaptational patterns of the hormones. The other pri- uted to a greater extent to the similar relative changes
mary finding of this study was that the endocrine in strength by the potent influence of testosterone on
system demonstrated a ‘‘plasticity’’ for adaptational neural mechanisms (e.g., increased neurotransmitter
changes in older and younger men in the early phase of synthesis) (36, 51). Neural factors have been demon-
a periodized heavy-resistance training program. strated to be very important, mediating strength in-
In men, testosterone is a potent anabolic hormone creases with short-term resistance training in older
that mediates protein accretion and also enhances men (19, 52, 53). In fact, the similar relative changes in
neural function (6, 51, 70). In general, exercised- strength of the knee extensors with lower magnitudes
induced concentrations of testosterone [e.g., exercise of increases in cross-sectional size of the whole thigh
AGING, HORMONES, AND HEAVY-RESISTANCE TRAINING 989
(and also of the quadriceps femoris, although not mediated by a reduction in ACTH responses to the
statistically different from the 30Y group) in older men resistance exercise stress. The reductions in cortisol
appear to support the theory that neural factors play a have been thought to provide one possible mechanism
great role in explaining 1-RM force production (19, 52, by which protein accretion via reduced degradation in
53, 58). More specifically, both age groups demon- type I muscle fibers is enhanced (8, 36). Older men may
strated smaller increases in the size of the hamstrings also rely on hypertrophy of type I muscle fibers to elicit
than that observed for the quadriceps femoris, and the total muscle hypertrophy due to a loss of type II muscle
62Y group showed a smaller training-induced increase fibers with the aging process (43). Thus the importance
in the hamstring muscle than the respective increase of these changes in cortisol cannot be minimized,
recorded for the 30Y group. Consistent with the present especially in the older men, as a mechanism related to
data, smaller increases in the size of the hamstring tissue hypertrophy and force production abilities. Col-
muscle group than in the quadriceps femoris have been lectively, these data indicate that the older men can
demonstrated in older individuals (65). Because elicit a reduction in the catabolic hormonal responses,
strength of the knee flexors was not recorded, it was not resulting in a more favorable anabolic environment for
possible to evaluate the contribution of neural factors reduced protein degradation or increased protein syn-
to strength development of the hamstrings between the thesis.
30Y and 62Y men in this study. In this study no significant changes in GH were
Resting FT concentrations were higher in the youn- observed for resting concentrations throughout the
ger men through most of the training period, and the training program for younger or older subjects. This
younger men again showed the ability to elicit a higher result is supported by similar findings in the literature
exercise-induced response of FT than the older men. (5, 15, 25, 26, 54, 67). The lactate response to exercise
Häkkinen and Pakarinen (25) previously demonstrated was lower in the older than in the younger men with
the importance of biologically active FT for trainability use of the same relative exercise stress. The younger
in younger men. Testosterone circulates in a bound men also demonstrated a slightly reduced lactate re-
form in the blood primarily with sex hormone-binding sponse to the same relative exercise intensity after
globulin or albumin. Although the free hormone (FT is training, and this may partially explain the trend for
considered both the testosterone that is circulating some of the postexercise GH values to be lower, inas-
unbound and the testosterone that circulates bound to much as acid-base mechanisms have been shown to be
albumin) has been thought to be regulated by TT, the related to GH release (15). Although no changes have
bound testosterone complex, with a larger molecular typically been observed for resistance training studies
weight, has been shown to be unable to traverse the in GH adaptations of older men, GH responses follow-
capillary endothelium and penetrate the plasma mem- ing constant exercise responses after endurance-type
brane to interact with the regulatory elements of the training are reduced (72). Because of the pulsatile
nucleus (27, 36, 48, 57). Thus higher FT in the blood nature of GH, single resting measures must be inter-
appears to indicate an improved ‘‘bioactivity status’’ for preted cautiously, especially in younger men, who show
the younger men (51, 55, 56). Overall, a greater andro- a much more prominent pulsatile secretion (11, 71).
genic environment for the younger men at rest and Our data are consistent with the findings of other
after exercise sessions appears to support the higher resistance training studies of GH in older and younger
overall magnitude of the observed increase in thigh men (5, 25, 54, 67). In general, significant increases in
muscle size. In addition, these data give potential the pattern of exercise-induced GH after resistance
insights into the age-related differences in the develop- exercise were observed for only the 30Y group. This is
ment of muscle tissue with short-term training pro- in agreement with previous studies in which exercise
grams, although this difference may not hold true to the did not induce a GH response in older men (5, 54) and in
same extent for all muscles or muscle groups. Thus which the GH response was reduced after resistance
there appears to be an age-related advantage in FT- training at some but not all times of recovery (63).
mediated mechanism(s) to respond to a resistance These results may be in part due to differences in age of
training program in the early phases of training. the subjects or differences in the training programs
Another important finding of this study was that the (i.e., total sets, repetitions, rest periods, and exercises).
amount of cortisol produced at resting levels was There is only a rudimentary understanding of the
reduced and the response to the resistance exercise effects of exercise and aging on the physiological mecha-
stress was lower in the older men. The decrease in nisms underlying ‘‘somatopause’’ (i.e., the diminish-
resting concentrations of cortisol throughout the train- ment of the GH-IGF-I system) (4, 61). Because this
ing program in the older men without significant endocrine axis has been thought to be of great impor-
changes in the ACTH concentrations indicates that the tance in maintaining the integrity of the musculoskel-
ACTH receptors in the adrenal gland may have been etal system, it is conceptually pragmatic to suggest that
‘‘downregulated’’ (27, 35). With training, reductions in exercise regimens should attempt to target it. GH also
the response of cortisol to resistance exercise stress exhibits a great deal of molecular heterogeneity, and
were observed in only the younger men. In an earlier the standard RIA focuses on the 22-kDa variant (3, 10,
study, Staron et al. (67) showed a similar response in 68). This is an especially important point for future
younger men. These changes in exercise-induced corti- studies, when it is considered that the higher molecular
sol responses observed after exercise are apparently weight species of GH could possess greater biological
990 AGING, HORMONES, AND HEAVY-RESISTANCE TRAINING
activity and that the lack of changes or reductions in Address for reprint requests and other correspondence: W. J.
the immunoreactive GH may not present the complete Kraemer, Human Performance Laboratory, Ball State University,
Muncie, IN 47306 (E-mail: wkraemer@bsu.edu).
picture of the adaptational responses of GH variants to
resistance exercise training (3, 10, 15, 68). Received 10 August 1998; accepted in final form 7 April 1999.
Similar to other studies, IGF-I was lower in the 62Y
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