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Endocrine Response Patterns to Acute Unilateral and Bilateral Resistance Exercise in Men

Migiano, Matthew J1; Vingren, Jakob L2; Volek, Jeff S1; Maresh, Carl M1,3; Fragala, Maren S1; Ho, Jen-Yu1; Thomas, Gwendolyn A1; Hatfield, Disa L5; Häkkinen, Keijo4; Ahtiainen, Juha4; Earp, Jacob E1; Kraemer, William J1,3

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Journal of Strength and Conditioning Research: January 2010 - Volume 24 - Issue 1 - p 128-134
doi: 10.1519/JSC.0b013e3181a92dc5
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It has been well established that heavy resistance exercise can acutely increase anabolic and catabolic hormones in the circulation in men. However, the choices made in the acute program variables influence the magnitude of the response pattern (9,10,12,17,18,26-28). In both rehabilitation and research, single-arm exercise protocols are used where the other arm is not functional or used as a control (24). The endocrine response (i.e., hormones released from a gland into the blood) is dependent on a host of different variables including the amount of muscle mass utilized, which is a function of the choice of exercise and the resistance used (28). Involvement of a small muscle mass, even when exercised vigorously, has been shown to result in no or only minor elevations in circulating testosterone, immunoreactive growth hormone (iGH), and cortisol concentrations (8,28,29). Larger muscle mass involvement allows for greater total volume of work during an exercise session, which appears to influence the metabolic demand that must be reached before endocrine increases are observed (12,26,27). Smilios et al. (27) examined various combinations of sets and repetitions and observed that in general higher volume exercise protocols created a greater acute endocrine response. That study also found that the threshold for hormonal responses appeared to be based more on metabolic demand than on volume per se.

The hormonal milieu at rest and in response to resistance exercise influences the adaptations from resistance training. Recently Kvorning et al. (16) demonstrated that when the resting testosterone concentrations are artificially reduced to castrate levels in men, resistance training-induced strength increases are attenuated and hypertrophy is absent. This pharmaceutical intervention also prevented an acute exercise-induced increase in testosterone; in fact, testosterone was further reduced following a resistance exercise session (17). In contrast, when testosterone and iGH levels are elevated during unilateral arm curl exercise by the inclusion of leg exercises, isometric arm curl strength is augmented following 9 weeks of training (8). An acute resistance exercise-induced increase in anabolic hormones appears to be important for priming the signaling systems, which helps in adaptations from resistance training (21).

Over the past 25 years the use of resistance training programs that involve only 1 limb or side of the body (i.e., unilateral) has gained widespread use within the research community (6,22-24,30). This exercise model is often used because it allows for comparisons between the trained and untrained side within each subject. In addition, this mode of exercise is used by individuals who have had 1 or more limbs amputated. Unilateral resistance exercise, however, drastically reduces the total work performed during each exercise session (∼50% reduction). The reduction in total work with unilateral resistance exercise might attenuate the acute hormonal response to exercise and thus reduce the signal for desired adaptations. Wilkinson et al. (29) have shown that unilateral exercise can induce hypertrophy and strength increases without significant exercise-induced increases in the major anabolic and catabolic hormones. That study did not assess the hormonal response to bilateral exercise, but the bilateral leg press has been shown to induce an acute increase of growth hormone and testosterone (18). In older individuals, it has been shown that when both lower limbs (i.e., thighs) are trained (e.g., unilateral training of both limbs or bilateral training of both limbs) over a 12-week period, specificity exists in that 1 repetition maximum (1RM) is greater when the limb is tested as it was trained (i.e., unilaterally or bilaterally) (6). However, the point of this study is that most studies leave 1 limb untrained to use it as a control limb, or in practical purposes it is not available to be trained. Therefore, what is the response of the endocrine glands to a protocol performed with 1 arm or with both arms? It might be hypothesized that total work may dictate the endocrine response pattern of hormones between the 2 protocols with the intensity, rest periods, and exercise order held constant. Although unilateral exercises can induce hypertrophy and increases in muscle strength (23,24,29,30) it remains to be determined if the endocrine responses from unilateral and bilateral resistance exercise are comparable when only upper-body exercises are used. Therefore, the purpose of this study was to examine the acute endocrine responses to a bilateral and a unilateral resistance exercise protocol consisting of the same dumbbell exercises but different in the volume of exercise.


Experimental Approach to the Problem

This study used a balanced, randomized crossover design in which all subjects completed 2 different upper-body resistance exercise protocols, thus acting as their own controls. Ten recreationally resistance trained men were matched on age, 1RM, and body mass and subsequently randomly assigned to 1 of 2 starting protocol groups. During the first session, one group (n = 5) performed a dominant-arm unilateral exercise protocol, whereas the other group (n = 5) performed a bilateral exercise protocol. One week after the first protocol session, subjects crossed over and performed the other exercise protocol. Blood samples were collected before the warm-up and during the first 30 minutes after the resistance exercise protocol. Blood samples were analyzed for total testosterone, insulin, cortisol, iGH, glucose, and lactate concentrations. With this design, it allowed us to address the question of the endocrine response patterns to using either 1 or 2 arms to perform a resistance exercise protocol with the same intensity, rest period lengths, sets, and order of exercises.


Ten recreationally resistance trained men (18-25 years, 20.4 ± 1.2 years, 175.6 ± 4.5 cm, 81.7 ± 9.3 kg) volunteered to participate in this investigation. Each subject had the experimental risks and benefits carefully explained to them prior to the study. Subsequently each subject signed an institutionally approved informed consent document to participate in the study. This study was approved by the University of Connecticut Institutional Review Board for use of human subjects in research. All subjects had performed resistance training ≥2 times a week for the 1 year preceding the study and had used dumbbell exercises in their training programs. The subjects did not have orthopedic limitations or medical conditions that could influence the outcome of this study and this was determined by a physician. Potential volunteers were screened for and had not used anabolic steroids, growth hormone, or other similar hormonal pharmaceuticals.

Familiarization and 1RM Testing

Each subject was thoroughly familiarized with the exercise protocol and attended familiarization sessions that included 1RM testing to set the exercise intensities for the exercises used in the testing protocols. Subjects were also familiarized with the exercises: dumbbell (db) bench press, bent over db row, db military press, db bicep curl, and db triceps kickback. Subjects performed a standardized warm-up consisting of 5 minutes of cycling on a stationary bike followed by light dynamic upper-body warm-up (arm swings and dynamic stretches); this warm-up protocol was used for all subsequent experimental visits. Following a 5-minute rest period, 1RM for each exercise was estimated using the previously described methods of Epley (4).

Acute Exercise Protocol Testing Sessions

On the 2 acute exercise protocol days, subjects reported to the laboratory in the morning after a 12-hour overnight fast (except water). Urine-specific gravity was measured using refractometry (Model A300CL, Spartan, Japan) to ensure that subjects were euhydrated (urine specific gravity <1.020 g·mL−1). After the warm-up subjects performed 3 sets of 10 repetitions with 80% of their predetermined 1RM for each exercise. Two minutes of rest separated each set and exercise. The total volume of work performed (repetitions*load*sets) during the unilateral protocol was 52.1% of that performed during the bilateral protocol. Blood samples were collected before the warm-up (Pre) and immediately (IP), 5, 15, and 30 minutes postexercise from a catheter inserted in an antecubital forearm vein of the dominant arm. The catheter was kept patent with a 10% heparin lock/saline solution.

Additional Experimental Controls

Participants were instructed to record all their physical activity for the 7 days prior to the first acute exercise session and to repeat their activity from this period during the 7 days leading to the second acute exercise session. Subjects recorded their diet from 3 days prior to the first exercise protocol and repeated this diet before the second exercise protocol. Subjects were instructed to refrain from resistance or exhaustive exercise, alcohol, caffeine, or pain medication (including common pain medication such as Tylenol or Advil) during the 3 days preceding each exercise session. Subjects were asked to otherwise continue their normal physical activity during the study. The time of day was standardized (± 1 hour) to avoid potential confounding influences of circadian patterns.

Biochemical Analyses

Hemoglobin and hematocrit were measured in whole blood immediately following blood collection. Whole blood was then centrifuged at 1500 g at 4°C for 15 minutes, and resulting serum or EDTA plasma were aliquoted and stored at −80°C until analyses. Hemoglobin was measured using an automated analyser (Hb201, Hemocue, Lake Forest, California), and hematocrit was measured by centrifugation of heparinized microcapillary tubes. Plasma volume shifts were calculated using the methods of Dill and Costill (2). The plasma volume shift from Pre to IP was −14.1 ± 4.0% and −10.2 ± 4.5% for the bilateral and unilateral condition, respectively. Following IP, the plasma volume shift from Pre gradually decreased for both conditions until it reached 1.1 ± 4.3% for the bilateral condition and 4.2 ± 4.0% for the unilateral condition at 30 minutes postexercise. Circulating hormone concentrations were not corrected for plasma volume changes because the actual molar exposure at the tissue level is what is important and many other concentration mechanisms exist beyond plasma volume effects. Serum total testosterone, serum insulin, and plasma iGH concentrations were measured in duplicate via enzyme immunoassays (EIA) (Diagnostic Systems Laboratories, Inc. Webster, Texas). The sensitivity and coefficient of variance (CV) for each assay were total testosterone 0.14 nmol·L−1 and 5.8%, insulin 1.8 pmol·L−1 and 5.1%, and iGH 0.03 μg·L−1 and 8.8%. Plasma cortisol was measured using EIA (Cayman Chemical, Ann Arbor, Michigan); the sensitivity and CV for this assay were 0.07 mmol·L−1 and 6.8%, respectively. Plasma lactate and glucose were measured using an automated lactate-glucose analyser (2300, YSI, Yellow Springs, Ohio).

Statistical Analyses

Data are presented as mean ± standard deviation. It was determined that an n size of 10 was adequate to defend the 0.05 alpha level of significance with a Cohen probability level of at least 0.80 for each dependent variable (nQuery Advisor software, Statistical Solutions, Saugus, Massachusetts). Intraclass Rs ≥0.80 were determined for test-retest reliability of the dependent variables. Data were analyzed using 2-way analysis of variance (ANOVAs; condition × time) with repeated measures on both factors. When significance was found, Fisher's LSD post hoc test was used to determine pair-wise differences. Significance was set at p ≤ 0.05.


No significant differences were seen in circulating testosterone concentrations between the unilateral and bilateral protocol (Figure 1). Testosterone was significantly decreased at 30 minutes postexercise compared to Pre values (main effect of time, p ≤ 0.05).

Figure 1
Figure 1:
Total testosterone concentrations before (Pre); immediately postexercise (IP); and 5, 15, and 30 minutes into recovery from exercise. *Main effect, significant (p ≤ 0.05) different from Pre. Mean ± SE.

For cortisol response patterns of the 2 protocols (Figure 2), a significant interaction (condition × time) effect was observed. For the unilateral trial only, Pre was higher compared to all postexercise time points. No significant differences were observed for the bilateral trial.

Figure 2
Figure 2:
Cortisol concentrations before (Pre); immediately postexercise (IP); and 5, 15, and 30 minutes into recovery from exercise. *Significant (p ≤ 0.05) different from Pre. Mean ± SE.

A significant interaction effect was observed for iGH (Figure 3). For both the unilateral and the bilateral trial iGH, concentrations were significantly elevated at all postexercise time points compared to Pre. Furthermore, iGH was significantly higher at all postexercise times for the bilateral trial compared to the corresponding time point for the unilateral trial.

Figure 3
Figure 3:
Immunoreactive growth hormone (iGH) concentrations before (Pre); immediately postexercise (IP); and 5, 15, and 30 minutes into recovery from exercise. *Significant (p ≤ 0.05) different from corresponding Pre. †Significantly (p ≤ 0.05) different from corresponding unilateral condition. Mean ± SE.

For plasma lactate concentrations a significant interaction effect was observed (Table 1). Compared to Pre values, lactate concentrations were significantly increased at all postexercise time points for both trials; however, lactate concentrations were significantly higher at all postexercise time for the bilateral trial compared to the corresponding time point for the unilateral trial. A significant effect of time and a trend (p = 0.098) for an interaction effect (condition × time) were observed for plasma glucose concentrations (Table 1). Glucose concentrations were significantly higher at IP compared to 30 minutes postexercise. A significant effect of time occurred for insulin concentrations (Figure 4). Insulin was significantly higher at IP through 15 minutes postexercise compared to Pre. In general, the change in insulin mirrored that of plasma glucose, although the change in plasma glucose did not reach statistical significance at the 0.05 level.

Table 1
Table 1:
Metabolic biomarkers using unilateral versus bilateral exercise (n = 10).
Figure 4
Figure 4:
Insulin concentrations before (Pre); immediately postexercise (IP); and 5, 15, and 30 minutes into recovery from exercise. *Main effect, significant (p ≤ 0.05) different from Pre. Mean ± SE.


The primary finding of this investigation was that some differences do exist between the acute endocrine response patterns of a bilateral and a dominant-arm unilateral upper-body resistance exercise protocol. The bilateral resistance exercise protocol produced a greater anabolic hormonal response, which was likely a result of the higher volume of work and therefore a larger metabolic demand. The findings of this study indicate that the volume of total work reflected by the amount of muscle mass used will dictate the endocrine signaling patterns to the body tissues. Furthermore, the use of only an upper-body exercise protocol, even when using 80% of 1RM loading, may not be enough to stimulate endocrine release of testosterone from the testicular Leydig cells.

Testosterone may be an important and rapid-signaling molecule for priming the other mechanisms needed for strength increases and muscle hypertrophy from resistance training in men (16,21). When testosterone was reduced to castrate levels, the resistance training-induced increase in isometric strength was eliminated and muscle hypertrophy was attenuated in young men (16). In the present study, testosterone concentrations were not increased for either protocol, yet this may have in part been a result of acute circadian decreases over the hour time frame examined. Other higher volume exercise studies have still observed increases to occur (7,12). A lack of a testosterone response has been shown previously for upper-body unilateral exercise (8,29), but no study has yet examined the testosterone response to bilateral upper-body resistance exercise using dumbbells. In untrained young men, heavy upper-body bilateral barbell resistance exercise can induce an increase in testosterone concentrations (11,28). Barbell exercises allow for a higher absolute load to be used and thus for a higher volume of work to be performed compared to dumbbell exercises. A theoretic threshold for volume or metabolic demand that must be reached before increases in testosterone are observed may exist but has not been directly quantified (7,26,27). In an examination of various combinations of repetition, set, and rest duration schemes it was demonstrated that, generally, higher volumes of work induce a greater testosterone response (27). It appears likely that the volume of work performed in the present study was too low to stimulate a significant endocrine increase in testosterone concentrations.

Circulating growth hormones have important metabolic properties that have been associated with their function and support muscular and skeletal growth (9). In the present study, the iGH concentration (i.e., 22 kD form) was significantly elevated following exercise in both conditions. However, the increase was significantly greater for the bilateral protocol. The iGH moiety has been shown to be responsive to the metabolic demands of exercise and as reflected by the lactic acid response patterns (12). It has been speculated that growth hormone has a permissive or synergistic effect on testosterone's priming and promotion of protein synthesis and that a minimum concentration of growth hormone is needed for the anabolic actions of testosterone (19). Although increases were observed in iGH, they are lower than has been observed following whole-body or large muscle group resistance exercise protocols with a similar rest period length (12,15).

Circulating iGH concentrations are related to volume of work and the amount of muscle mass used during exercise (7,12,14,18,20,27). The addition of a lower-body exercise to a unilateral upper-body resistance exercise protocol has demonstrated an augmented iGH response (8). In the present study, the increase in iGH followed a similar pattern to the increase in lactate, which has already been demonstrated in full-body resistance exercise protocols (12). The reduction in blood pH occurring concurrently with increases in circulating lactate concentrations during exercise has been shown to increase iGH secretion from the anterior pituitary (3). The larger increase in iGH found with the bilateral protocol could be explained by the larger metabolic demand and accompanying augmented reduction in pH compared to the unilateral protocol.

Insulin, another hormone with potentially anabolic interactions, is regulated by blood glucose and amino acid concentrations in the blood (14). The unilateral and bilateral protocol exhibited a similar exercise-induced increase in insulin concentrations. To optimize the potent anabolic effects of insulin, blood glucose or amino acids must be increased by ingestion of these nutrients prior to the exercise session (1,15). Subjects in the present study fasted for 12 hours prior to exercise; thus a direct effect of nutritional intake did not affect the circulating insulin concentrations. Potentially, the increases in insulin seen in this study (while the subjects were in a fasted state) might be related to the trend for an increase in glucose induced by the exercise protocols. Insulin appears to play a greater role in protein synthesis after resistance exercise compared to after nonresistance exercise. This could be a result of the increased muscle damage that resistance exercise's eccentric component can produce (5). Thus, there might also be an as yet unidentified feedback mechanism from the tissue involved in the exercise resulting in insulin release from the pancreas.

Cortisol was largely unaffected by the 2 different resistance exercise protocols. In the unilateral protocol cortisol decreased from Pre to IP exercise and thus appeared to have been elevated at Pre for this condition. This apparently elevated concentration at Pre might have been a result of psychological factors or arousal for the subsequent exercise protocol. It is unclear, however, why the same effect was not observed during the bilateral protocol. A balanced cross-over design was used to assign the order of the exercise protocols so an equal number of subjects completed each condition first. The lack of a cortisol response was likely a result of the training status of the subjects and the low volume in both exercise sessions. Although there were no exercise-induced increases in cortisol for either protocol, cortisol concentrations for the bilateral condition were maintained at Pre values during recovery, whereas cortisol concentrations were reduced for the unilateral condition during recovery. This indicates that the cortisol responses differed between the 2 protocols and dramatically differed from whole-body or large muscle mass protocols where dramatic increases occur (10,12-15), whereas the involvement of small muscle groups does not induce a cortisol response (8). It is pure speculation that the lack of a cortisol response could also be a result of the training status of the participants. This is because cortisol increases from resistance exercise are more pronounced at the beginning of a resistance training program and have been shown to decrease with chronic resistance training (20). Additionally, a circadian decrease might have occurred, yet one would have expected the same effects for both protocols and, as noted before, dramatic increases have been observed over this same time period with large muscle group and whole-body resistance exercise workouts (14).

Practical Applications

The results of this investigation demonstrate that when using a 1-arm-only exercise protocol, whether for experimental manipulation or for training purposes, the endocrine signaling is different from a 2-arm protocol. Furthermore, the magnitude of the endocrine responses are lower than has been observed with full-body and or large muscle mass squat workout protocols using rest periods of 2 minutes or less. The findings of this investigation also support the creative use of the acute program variable, “order of exercise,” in that the consummate principle of starting with large muscle group exercises first, such as the squat, leg press, or power cleans, may in fact optimize the workout. This would be accomplished by increasing the concentrations of hormones prior to the smaller muscle group exercises being performed. This would dramatically increase the molar concentrations in blood perfusing the smaller muscles and augment a variety of signaling effects than when starting with the small muscle group exercises. Finally, for experimental purposes, the use of a 1-arm-only exercise protocol along with a nonexercising arm as a control, the single-arm model would most likely rely on other redundant signaling mechanisms for anabolic stimuli in addition to neural factors in mediating changes in strength and size of the muscle (25). Therefore, the underlying mediating mechanism(s) for adaptations in strength and hypertrophy that are observed in the experiment even at the level of genetic expression would be potentially different when using 1-arm versus 2-arm protocols because of differences in endocrine releases.


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endocrine; androgens; glucocorticoids; neuromuscular rehab protocols

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