Journal of Gerontology: BIOLOGICAL SCIENCES 2000, Vol. 55A. No. 2, B95-B105

Copvrighl 2000 />v The Geronlological Society of America

Basal Concentrations and Acute Responses of Serum Hormones and Strength Development During Heavy Resistance Training in Middle-Aged and Elderly Men and Women Keijo Hakkinen,1 Arto Pakarinen,2 William J. Kraemer,3 Robert U. Newton,4 and Markku Alen5 'Neuromuscular Research Center and Department of Biology of Physical Activity, University of Jyvaskyla, Finland. Department of Clinical Chemistry, University of Oulu, Finland. 3 Human Performance Laboratory, Ball State University, Muncie, Indiana. 4

School of Exercise Science and Sport Management, Southern Cross University, Australia.

5

Peurunka Medical Rehabilitation and Physical Exercise Centre, Laukaa; and Department of Health Sciences, University of Jyvaskyla, Finland.

Effects of 6 months of heavy resistance training combined with explosive exercises on both basal concentrations and acute responses of total and free testosterone, growth hormone (GH), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), cortisol and sex hormone-binding globulin (SHBG), as well as voluntary neural activation and maximal strength of knee extensors were examined in 10 middle-aged men (M40; 42 ± 2 years), 11 middle-aged women (W40; 39 ± 3 years), 11 elderly men (M70; 72 + 3 years), and in 10 elderly women (W70; 67 ± 3 years). The maximal integrated electromyographic (iEMG) and 1 repetition maximum (RM) knee-extension values remained unaltered in all groups during a 1-month control period with no strength training. During the 6-month training the 1RM values increased in M40 by 27 ± 9% (p < .001), in M70 by 16 ± 6% (p < .001), in W40 by 28 ± 11 % (p < .001),

and in W70 by 24 ± 10% (p < .001). The iEMGs of the vastus lateralis and medialis muscles increased(p < .05-.001) in M40, M70, W40, and W70. No systematic changes occurred during the experimental period in the mean concentrations of serum total and free testosterone, DHEA, DHEAS, GH, cortisol, or SHBG. However, the mean levels of individual serum free testosterone in W70 and serum testosterone in the total group of women correlated with the individual changes recorded in strength during the training (r = .55,p < .05; and r = .43, p < .05). The single exercise session both before and after the training resulted in significant responses in serum total and free testosterone concentrations in both male groups (p < .05-.01), but not in the female groups, as well as in serum GH levels in all groups (p < .05-.01) except W70 (/is). In summary, the present strength training led to great increases in maximal strength not only in middle-aged but also in elderly men and women. The strength gains were accompanied by large increases in the maximal voluntary activation of the trained muscles. None of the groups showed systematic changes in the mean serum concentrations of hormones examined. However, a low level of testosterone, especially in older women, may be a limiting factor in strength development and testosterone could mediate interactions with the nervous system contributing to strength development. The physiological significance of the lack of acute responsiveness of serum GH to heavy resistance exercise in older women for their trainability during prolonged strength training requires further examination.

UMAN muscle mass, strength and power decrease during aging, especially from the sixth decade on in both men

testosterone concentrations, muscle cross-sectional area and

and women (1-3). The decline in muscle mass is thought to be mediated by a reduction in the size and/or number of individual muscle fibres, especially of fast-twitch fibres (1). Age-related declines in strength may also be due to decreased maximal voluntary activation of the agonist muscle and/or changes in antagonist coactivation (4,5), although these neural and associated strength changes may vary between different muscles in relation to their decreased use in daily physical activities (2,6,7). The age-related decreases in muscle mass and strength are not surprising, because aging is very often associated with a decline in the quantity and especially intensity of daily physical activities (8). Further, with aging blood concentrations of circulating

decreasing basal level of blood testosterone in aging females over the years may lead to decreasing anabolic effects on muscles associated possibly with muscle atrophy and decreased

H

anabolic hormones and growth factors, e.g., testosterone,

growth hormone (GH), and insulin-like growth factor-1 are diminished (9-14). The correlations observed between serum

strength in middle-aged and older women (11) suggest that the

strength. However, progressive strength training not only in middleaged but also in elderly people can lead to substantial increases in strength performance. This might primarily result from considerable neural adaptations observed especially during the earlier weeks of training (15-17), as indicated by large increases in maximal electromyographic (EMG) activity of trained muscles. In addition to the increased activation of the agonists, strength training can lead to decreases in the coactivation of the antagonists, especially in elderly subjects of both genders (17). It has also been shown with sensitive techniques such as fibre area determination by muscle biopsy, or muscle cross-sectional area B95

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determination by computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound scan, that muscle hypertrophy accounts for the strength gains not only in young but also to some extent in elderly persons (16,18,19). Heavy resistance exercise is known to be a potent stimulus

for acute increases in circulating anabolic hormones in young men, although it has not been shown to elicit the same magnitude of hormonal responses in older men (14,20-22), and very minor or no response in older women (21). No systematic changes have been reported to take place in basal blood concentrations of circulating hormones during strength training for 12 to 16 weeks in older men (20,22,23) or in older women (23). Similarly, the acute exercise-induced minor GH response in 60—62-year-old men has not changed after 12 to 16 weeks of strength training compared to that recorded before the training (20,22). No experimental results about the effects of strength training on possible changes in acute hormone responsiveness in older women have been reported. Because blood concentrations of circulating anabolic hormones and growth factors are also diminished with aging, it was our purpose to examine not only in middle-aged and older men but also in middle-aged and older women the possible effects of strength training on basal concentrations and acute responses of serum hormones and their possible interrelationships with strength gains during a prolonged strength training period of 6 months.

METHODS Subjects The subjects who volunteered for the study were 42 healthy men (M) and women (W). They were divided into two age groups of middle-aged and elderly as follows: M40 (42 ± 2; mean age ± SD years, n = 10), M70 (72 ± 3; n = 11), W40 (39 ± 3; n = 11), and W70 (67 ± 3; n = 10). The percentage of fat in the body was estimated from the measurements of skinfold thickness (24). The subjects were carefully informed about possible risks and discomfort that might result and they signed a written consent form prior to participation in the project. The study was conducted according to the declaration of Helsinki and was approved by the Ethics Committee of the University of Jy vaskyla, Finland. The subjects were healthy and living independently in the town of Jy vaskyla, Finland. They were habitually physically active. To keep themselves fit and as recreation, they took part in various physical activities such as walking, jogging, swimming, hiking, and aerobics for one to two times a week, but they had no background in regular strength training. No medication was being taken by the subjects which would have been expected to affect physical performance or endocrine profile. This work was a part of a larger research project. Some of the results obtained with these subjects from various other measurements conducted during the present follow-up have been published earlier (17), but all the hormonal, strength, and EMG data presented are unique to this part of the investigation.

Experimental Design The duration of the present study was 7 months. The first month of the study (between the measurements at month -1 and at month 0) was used as a control period during which no strength training was carried out but the subjects maintained their

normal recreational physical activities (e.g., walking, jogging, hiking, swimming, and aerobics). The subjects were tested before and after this control period. Thereafter, the subjects started a supervised experimental strength training program for 6 months. The measurements were repeated during the actual training period at 2-month intervals (i.e., months 0,2,4, and 6). Testing

The subjects were carefully familiarized with the testing procedures of voluntary force production of the knee extensor muscles during bilateral extension actions about 1 week before the measurements at month -1. Secondly, during the actual testing, warm-up actions were performed prior to the measurement of the maximal 1 RM (repetition maximum) knee-extension performance. A David 200 dynamometer (David Fitness and Medical Ltd., Finland) was used to measure maximal bilateral concentric force production of the knee extensors (16). The subject was in a

seated position so that the hip angle was 110 degrees. On verbal command the subject performed a concentric knee extension starting from a flexed position of 70 degrees, trying to reach an extension of 160 degrees (at the minimum) against the resistance determined by the loads chosen on the weight stack. In the testing of the maximal load, separate 1 RM contractions were performed. After each repetition the load was increased until the subject was unable to extend the legs to the required position. The last acceptable extension with the highest possible load was determined as 1 RM. In all test conditions the time period of rest between the maximal contractions was always 1.5 minutes. External verbal encouragement was given for each subject. EMG activity during the bilateral knee-extension actions was recorded from the agonist muscles vastus lateralis (VE) and vastus medialis (VM) of the right and left leg separately. Bipolar (20-mm interelectrode distance) surface EMG recording (Beckman miniature-sized skin electrodes 650437, Illinois, USA) was employed. The electrodes were placed longitudinally on the motor point areas determined by an electrical stimulator. EMG signals were recorded telemetrically (Glonner, Biomes 2000). The positions of the electrodes were marked on the skin by small ink tattoos (25). These dots ensured the same electrode positioning in each test over the 7-month experimental period. The EMG signal was amplified (by a multiplication factor of 200; low-pass cut-off frequency of 360 Hz 3dB~') and digitized at a sampling frequency of 1000 Hz by an on-line computer system. EMG was full-wave rectified, integrated (iEMG in mV-s) and time-normalized for 1 s in the concentric action of the 1 RM for the entire range of motion. The iEMG values of the right and the left muscles recorded during the maximal 1 RM action were taken for further analysis. Heavy-Resistance Protocol The heavy-resistance protocol at month 0 before the training period as well as at month 6 after the 6-month training period included the bilateral leg-press exercise on a machine (David 210, David Fitness and Medical Ltd, Finland). In the exercise the subject started from the flexed knee position (70 degrees) and extended the knees concentrically to a full extension (180 degrees) and thereafter lowered the load eccentrically back to the starting position. The actual loads were always the RM for each subject so that the subjects performed 10 repetitions per

AGING, GENDER, SERUM HORMONES AND STRENGTH TRAINING

set with the maximal load possible for a total of 5 sets ( 5 X 1 0

RM). The recovery time between the sets was 3 minutes for all groups. The loads were adjusted during the course of the session due to fatigue so that each subject would be able to perform 10 repetitions at each set. If the load happened to become too heavy, the subject was assisted slightly during the last one to three repetitions of the set, while she/he maintained her/his maximum performance so that the required number of repetitions could be reached and the subjects would also maintain the same contraction time. Blood Samples During the Heavy-Resistance Loading Protocol To examine acute hormone responses to the heavy-resistance loading, blood samples were drawn twice (within 1 hour) during the control day at month 0 and twice (within 1 hour) during the 2nd control day after the training at month 6 from the antecubital vein of each subject. Blood samples were also drawn twice during the 2 heavy-resistance exercise days (pre- and postloading samples within about 1 hour) at month 0 and at month 6. The heavy-resistance protocol was performed between 9.00 AM and 6.00 PM, always at the same time of day for each subject (at the corresponding time of the day as the blood sampling during the controls days) before and after the 6-month training period. The subjects were instructed to maintain their normal food intake prior to the heavy-resistance exercise protocol and to have their last light meal during that day no later than 2 hours before the session. Basal Blood Samples During the 1-Month Control Period and 6-Month Strength Training To examine the basal concentrations of serum hormones, blood samples were drawn from the antecubital vein of each subject after 12 hours of fasting and approximately 8 hours of sleep in the mornings (between 7.30 AM and 8.30 AM) during the 1-month control period (at month -1 and month 0) as well as during the 6-month training period (at months 0,2,4, and 6). Analytical Methods Serum samples for the hormonal analyses were kept frozen at -20°C until assayed. Serum testosterone concentrations were measured by the Chiron Diagnostics ACS: 180 automated chemiluminescence system using ACS: 180 analyzer. The sensitivity of the testosterone assay was 0.42 nrnol-L"1, and the intraassay coefficient of variation was 6.7%. The concentrations of serum free testosterone, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS) were measured by radioimmunoassays using kits obtained from Diagnostic Products Corp. (Los Angeles, CA). Prior to the DHEA assays, serum samples were extracted with dichloromethane. The sensitivity of the free testosterone assay was 0.52 pmol-L"1 and the intra-assay varation was 3.8%. The respective values were 0.10 nmol-L-' and 5.2% for the DHEA assay and 0.06 umol-L-' and 4.5% for the DHEAS assay. The assays of serum cortisol were carried out by radioimmunoassays. The sensitivity of cortisol assay was 0.05 pmol-L'1 and the coefficient of the intra-assay variation was 4.0%. Serum sex hormone-binding globulin (SHBG) concentrations were measured by two-site fluoroimmunometric methods with kits obtained from Wallac (Turku, Finland) using the 1235 AutoDELFIA automatic immunoassay system. The sensitivity of the SHBG assay was 0.5 nmol-L"1

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and the intra-assay variation was 4.4%. Concentrations of growth hormone (GH) were measured using radioimmunoassay kits from Pharmacia Diagnostics (Uppsala, Sweden). The sensitivity of the GH assay was 0.2 ug-L"1 and the intra-assay variation was 2.5-5.1 %. All samples for each test subject were analyzed in the same assay for each hormone. Blood lactate concentrations were determined using a lactate analyzer (model 640, Roche, Switzerland). Experimental Strength Training Program The subjects participated in a supervised 6-month strengthtraining period. Each training session included two exercises for the knee-extensor muscles (the bilateral leg-press exercise and the bilateral and/or unilateral knee-extension exercise on the David 200 machine) and four to five other exercises for the other main muscle groups of the body (the bench press and/or the seated press and/or lateral pull-down exercise for the upper body; the sit-up exercise for the trunk flexors and/or another exercise for the trunk extensors; and the bilateral elbow- and/or knee-flexion exercise). During the first 2 months of the training the subjects trained twice a week with loads of 50 to 70% of the 1 RM. The subjects performed 10 to 15 repetitions per set and performed three to four sets of each exercise. During the 3rd and 4th months of training the subjects still trained two times a week. The loads were 50 to 60% and 60 to 70% of the maximum by month 3 and 50 to 60% and 70 to 80% by month 4. In the two exercises for the leg-extensor muscles, the subjects now performed either 8 to 12 repetitions per set (at lower loads) or 5 to 6 repetitions per set (higher loads) and performed three to five sets. In the other four exercises the subjects performed 10 to 12 repetitions per set and performed three to five sets. During the last 2 months of training (months 5-6), two different load ranges were used in the two exercises for the leg extensors so that the subjects completed three to six repetitions per set with the loads of 70 to 80% of the maximum and 8 to 12 repetitions per set with the loads of 50 to 60%. The total number of sets varied between four and six. In the other four exercises the subjects performed 8 to 12 repetitions per set and performed three to five sets altogether. The strength-training program was a combination of heavy resistance and "explosive" strength training. A major part of the knee-extension exercises was performed using the basic principles of heavy resistance training, but a part (20%) of these exercises with light loads (50 to 60% of the maximum) was performed so that each repetition of each set was executed as "explosively" as possible (rapid muscle actions). The overall amount of training was progressively increased until the 5th month, at which point it was slightly reduced for the final month of the 6-month training period. During the 6-month experimental training period the subjects continued taking part in physical activities such as walking, jogging, swimming, hiking, or gymnastics one to two times per week in a similar manner to what they were accustomed to before this experiment. Statistical Analyses Standard statistical methods were used for the calculation of means, standard deviations (SD), standard errors (SE), and Pearson product moment correlation coefficients. The data were then analyzed utilizing multivariate analysis of variance

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(MANOVA) with repeated measures. Probability-adjusted t tests were used for pairwise comparisons when appropriate. The p < .05 criterion was used for establishing statistical significance.

Maximal Strength (1RM) (kg)

M40

RESULTS Physical Characteristics Body mass and the percentage of body fat remained statistically unaltered during the 6-month strength-training period in

all subject groups with pre- and post-training values of 83 ± 14 kg (mean and SD) and 84 ± 15 kg and 19 ± 4% and 19 ± 5% (and of 178 ± 7 cm for body height) in M40, 80 ± 10 kg and 80 ± 10 kg and 24 ± 4% and 23 ± 5% (172 ± 7 cm) in M70, 62 ± 8

kg and 62 ± 8 kg and 26 ± 6% and 26 ± 6% (163 ± 5 cm) in W40, and 66 ± 7 kg and 66 ± 7 kg and 34 ± 3% and 34 ± 5% (159 ± 6 cm) in W70, respectively.

M70

90 120

W40 110

100

90

W70 80

Maximal Strength and iEMGs

The 1 RM bilateral knee-extension values remained statistically unaltered in all groups during the 1-month control period (Figure 1). During the 6-month training the 1 RM values improved in M40 by 27 ± 9% (mean and SD)(p< .001), in M70 by 16±6%(/?