You are on page 1of 9

J Appl Physiol 85:2352-2359, 1998.

A. C. Fry, W. J. Kraemer and L. T. Ramsey

You might find this additional information useful... This article cites 34 articles, 11 of which you can access free at: This article has been cited by 5 other HighWire hosted articles: Diagnosing overtraining in athletes using the two-bout exercise protocol R. Meeusen, E. Nederhof, L. Buyse, B. Roelands, G. de Schutter and M. F. Piacentini Br. J. Sports Med., July 1, 2010; 44 (9): 642-648. [Abstract] [Full Text] [PDF] Can we detect non-functional overreaching in young elite soccer players and middle-long distance runners using field performance tests? S. L. Schmikli, M. S. Brink, W. R. de Vries and F. J. G. Backx Br. J. Sports Med., April 19, 2010; 0 (2010): bjsm.2009.067462v1-bjsports67462. [Abstract] [Full Text] Anticipatory responses of catecholamines on muscle force production D. N. French, W. J. Kraemer, J. S. Volek, B. A. Spiering, D. A. Judelson, J. R. Hoffman and C. M. Maresh J Appl Physiol, January 1, 2007; 102 (1): 94-102. [Abstract] [Full Text] [PDF] beta2-Adrenergic receptor downregulation and performance decrements during high-intensity resistance exercise overtraining A. C. Fry, B. K. Schilling, L. W. Weiss and L. Z. F. Chiu J Appl Physiol, December 1, 2006; 101 (6): 1664-1672. [Abstract] [Full Text] [PDF] Early plateaus of power and torque gains during high- and low-speed resistance training of older women J. F. Signorile, M. P. Carmel, S. Lai and B. A. Roos J Appl Physiol, April 1, 2005; 98 (4): 1213-1220. [Abstract] [Full Text] [PDF] Medline items on this article's topics can be found at on the following topics: Endocrinology .. Pituitary Gland Physiology .. Testosterone Oncology .. Growth Hormone Physiology .. Exertion Medicine .. Cortisol Medicine .. Exercise Updated information and services including high-resolution figures, can be found at: Additional material and information about Journal of Applied Physiology can be found at:

Downloaded from on August 7, 2010

This information is current as of August 7, 2010 .

Journal of Applied Physiology publishes original papers that deal with diverse areas of research in applied physiology, especially those papers emphasizing adaptive and integrative mechanisms. It is published 12 times a year (monthly) by the American Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright 1998 by the American Physiological Society. ISSN: 8750-7587, ESSN: 1522-1601. Visit our website at

Pituitary-adrenal-gonadal responses to high-intensity resistance exercise overtraining


A. C. FRY,1 W. J. KRAEMER,2 AND L. T. RAMSEY1 Performance Laboratories, University of Memphis, Memphis, Tennessee 38152; and 2Center for Sports Medicine, Pennsylvania State University, University Park, Pennsylvania 16802 rest intervals, and load) results in a variety of different physiological responses (30). Thus it is likely that overtraining resulting from distinctly different resistance exercise programs may be characterized by different physiological responses. Increased volumes of aerobic exercise (3, 34) and resistance exercise (11, 18, 19) have resulted in decreased concentrations of several hormones at rest. Recent research on the effects of increased resistance exercise relative training intensity (i.e., percentage of maximum) (12, 13) indicates that this type of training stress may be quite different physiologically from increased resistance exercise training volumes. Few resistance exercise training studies have demonstrated actual performance decrements (34); thus overtraining is not present in many investigations. In general, little data are available on the endocrine responses to resistance exercise overtraining and its concomitant performance decrements. Previous endocrine research with increased resistance exercise training stress has monitored only resting hormonal concentrations (18). It has been proposed that the exercise-induced endocrine responses reect different hormonal regulatory mechanisms (14), and recent investigations have included exercise-induced endocrine responses (11, 17, 19). Changes in circulating hormonal concentrations have been proposed as indicators of overtraining (1, 14), although such hormonal changes are not always observed. Because uctuations in strength performance have been associated with altered resting (16, 18) and exercise-induced (27) endocrine proles with resistance exercise, it is possible that changes in hormonal concentrations may serve as markers of an impending state of overtraining. Recently, an exercise protocol has been developed for producing short-term muscular strength decrements with low-volume (i.e., sets repetitions), high-relativeintensity [i.e., percentage of 1-repetition maximum (%1-RM)] resistance exercise (12, 13). Although not intended as a training method for optimal performance, this protocol was designed specically to elicit an overtraining response, thus allowing physiological study of the development of this phenomenon. Therefore, the purpose of this investigation was to determine whether overtraining due to high relative intensity (%1-RM) resistance exercise results in altered resting and exercise-induced circulating hormonal concentrations.

Fry, A. C., W. J . Kraemer, and L. T. Ramsey. Pituitaryadrenal-gonadal responses to high-intensity resistance exercise overtraining. J. Appl. Physiol. 85(6): 23522359, 1998. Weight-trained men [OT ; n 11; age 22.0 0.9 (SE) yr] resistance trained daily at 100% one-repetition maximum (1-RM) intensity for 2 wk, resulting in 1-RM strength decrements and in an overtrained state. A control group (Con; n 6; age 23.7 2.4 yr) trained 1 day/wk at a low relative intensity (50% 1 RM). After 2 wk, the OT group exhibited slightly increased exercise-induced testosterone (preexercise 26.5 1.3 nmol/l, postexercise 29.1 5.9 nmol/l) and testosterone-to-cortisol ratio (preexercise 0.049 0.007 nmol/l, postexercise 0.061 0.006 nmol/l) and decreased exercise-induced cortisol (preexercise 656.1 98.1 nmol/l, postexercise 503.1 39.7 nmol/l). Serum concentrations for growth hormone and plasma peptide F [preproenkephalin (107140)] were similar for both groups throughout the overtraining period. This hormonal prole is distinctly different from what has been previously reported for other types of overtraining, indicating that high-relative-intensity resistance exercise overtraining may not be successfully monitered via circulating testosterone and cortisol. Unlike overtraining conditions with endurance athletes, altered resting concentrations of pituitary, adrenal, or gonadal hormones were not evident, and exercise-induced concentrations were only modestly affected. muscular strength; testosterone; cortisol; growth hormone; peptide F

Downloaded from on August 7, 2010

INCREASED TRAINING VOLUME and/or intensity, which results in physical performance decrements, has been dened as overtraining (12, 14, 33). The physiology of overtraining has been studied for a variety of physical activities (14, 33), with those emphasizing high levels of strength or power being equally susceptible to overtraining compared with other types of activities (14). In general, the physiological mechanisms of overtraining have only recently been elucidated. Although much has yet to be learned regarding the etiology of overtraining, it appears to be quite different when anaerobic activities, such as resistance exercise, are compared with aerobic activities (12, 13). Many of the overtraining symptoms identied for aerobic exercise, such as alterations in sleep patterns, resting heart rates, mood states, and sympathetic activity, have not been reported for anaerobic overtraining protocols (12, 13). Furthermore, altering some of the acute training variables for resistance exercise (i.e., volume of exercise,

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 2352

Subjects. Seventeen men were randomly divided into either an experimental group who overtrained by using high relative weight training intensities (OT; n 11) or a control group who used lower relative weight training intensities (Con; n 6).

8750-7587/98 $5.00 Copyright 1998 the American Physiological Society



Table 1. Subject characteristics of the overtraining and control groups during test 1
Variable OT Con

n Age, yr Height, cm Body mass, kg Relative fat, % Lean body mass, kg Leg weight training experience, yr

11 22.0 0.9 176.6 2.1 83.4 4.9 12.2 1.9 72.2 2.5 4.0 1.0

6 23.7 2.4 175.7 3.1 81.2 5.6 10.0 2.1 72.7 4.3 5.7 2.5

Values are means SE; n, no. of men. OT, overtraining group; Con, control group. Values did not signicantly change during the course of the investigation, P 0.05.

All subjects had performed weight training for the legs for a mean of 4.5 yr, were capable of at least a 1.5 body weight 1 RM for the parallel barbell back squat, had been consistently training immediately before participating in this investigation, and had no history of anabolic steroid use over the previous year. Each subject was apprised of the risks of participation and signed an informed consent statement. These same subjects have been previously described in studies examining performance decrements and catecholamine responses to high intensity resistance exercise overtraining (12, 13). Subject characteristics for both groups are listed in Table 1. Resistance exercise and testing protocols. Lower body training was performed on a squat resistance exercise machine (Southern Xercise, Cleveland, TN). Kinematic characteristics of exercise on this particular squat machine indicate that this exercise is not identical to barbell squats but does instead primarily involve extension at the hips and knees (9). This device was chosen for this study because it utilized an easily learned gross motor pattern involving a large-muscle-group, multijoint activity, within a regulated joint range of motion. Safety of the subject was enhanced because a single person could easily spot maximal lifts in the event of a failed repetition. This machine has also been used in previous longitudinal resistance training studies (12, 13). Lower body resistance exercise was controlled in the present study while current upper body resistance exercise programs were held constant for the duration of the training period. All subjects participated in a 1-wk familiarization phase. Two familiarization sessions were used to acquaint the subjects with proper exercise technique and to perform 1-RM assessments. One-RM test reliability determined from the two familiarization sessions was r 0.96. Exercise sessions on the squat machine were performed during weeks 2 and 3 of the study. The OT group performed a low-volume, high-relative-intensity (%1-

RM) exercise protocol on the squat machine each day; this has been shown to elicit an overtraining response characterized by muscular strength decrements (12, 13). Conversely, the Con group performed a low-volume, low-relative-intensity protocol 1 day/wk, designed to maintain muscular strength and to not result in an overtraining syndrome. The resistance exercise and strength test protocols used in the present investigation have been previously described in detail (12, 13) and are presented in Fig. 1. Briey, it was the objective of each exercise session for the OT group to perform resistance exercise at a maximal relative intensity (100% 1 RM) by performing 10 single repetitions at 100% of their 1 RM on the squat machine with 2 min of timed rest between each attempted lift. When a weight could not be lifted, the resistance for subsequent repetitions was decreased by 4.5 kg. The net result was that each of the 10 successful lifts was performed as close to each subjects maximal capability as possible. Each training session began with a controlled warm-up, followed by a 1-RM assessment from which the subsequent resistances were based for that day. This exercise protocol was not meant to mimic traditional training programs used to optimize strength performance but was instead a tool used to elicit an overtraining response with concomitant performance decrements. One exercise session per week was performed by the Con group to allow them to remain familiar with the exercise in a nonstressful manner that would maintain muscular strength throughout the study. A second day each week was devoted to 1-RM testing for the Con group. All exercise sessions for both groups were supervised by at least one member of the research team. Test batteries were administered at the beginning (test 1 ), middle (test 2 ), and end of the 2-wk overtraining period (test 3 ). During each test battery, sets of 10 continuous repetitions at 70% of the current 1-RM load were performed until exhaustion, with 1 min of rest between each set. This test served as the exercise stimulus around which resting and exercise-induced hormonal concentrations were monitored; therefore, the time of day for each of these tests was kept constant for each subject to minimize diurnal endocrine variations. Blood sampling. On reporting for the 70% 1-RM test session, all subjects were placed in a seated position similar to the terminal position on the squat machine. A 20-gauge, 3.2-cm Teon intravenous catheter was inserted in a supercial antecubital vein. The cannula was kept patent with a continuous saline drip (0.9% sodium chloride) at a rate of 45 ml/h. A four-way stopcock was placed in line with the saline drip to permit blood sampling with syringes. A 6-h fast preceded this test session, although subjects were allowed water ad libitum. The subjects remained calmly in their

Downloaded from on August 7, 2010

Fig. 1. Exercise session and testing session timeline for the overtraining (OT) and control (Con) groups. Test battery 1, beginning of 2-wk overtraining period; test battery 2, middle of 2-wk overtraining period; test battery 3, end of 2-wk overtraining period. 1 RM, 1 repetition maximum; Exer, exercise; Quad, quadriceps. * Refers to details in bottom part of gure.



seated position for 30 min. During this time, blood samples were taken after 15 (Pre 1) and 30 min (Pre 2). This was immediately followed by the 70% 1-RM test for repetitions. Immediately on completion of the 70% 1-RM test for repetitions, a postexercise blood sample was taken for determination of peptide-F concentrations. The subjects were then seated for 5 min, after which a nal blood sample was taken (5 min) for determination of the remaining exercise-induced hormonal concentrations. Blood sample preparation. Ten milliliters of whole blood from each sample time were allowed to clot at room temperature and then were centrifuged at 1,500 g and 4C for 15 min. The resulting serum was aliquoted for subsequent analysis of total testosterone, free testosterone, cortisol, and growth hormone. Peptide-F concentrations were determined from a 3-ml whole-blood sample that was immediately placed into a chilled glass test tube (4C) containing EDTA (3 mg) and aprotinin (1,500 kallikrein-inactivating units). Plasma for analysis of peptide F was aliquoted after centrifugation for 15 min at 1,500 g at 4C. One milliliter of whole blood was mixed with heparin sodium, from which a small portion was used to determine hematocrit by using standard microcapillary techniques. The remaining portion was saved for subsequent analysis of total hemoglobin. All aliquots not immediately analyzed were stored at 90C for future analysis. Samples were thawed only once for analysis and were decoded after all analyses were completed (blinded format). Blood analyses. Single-antibody, solid-phase radioimunoassays were used to determine imunoreactivity levels indicative of blood concentrations of testosterone and free testosterone (Diagnostic Products, Los Angeles, CA), and cortisol (Diagnostic Systems, Webster, TX). Radioimunoreactivity was measured with an LKB 1272 Clinigamma automatic gamma counter and data reduction package (Pharmacia LKB Nuclear, Turku, Finland). Variances for the radioimunoassays performed in this investigation were as follows: total testosterone (intra-assay 2.5%, interassay 3.0%), free testosterone (intra-assay 2.5%, interassay 9.6%), and cortisol (intraassay 3.8%, interassay 3.2%). Hormonal concentrations were determined at each sampling time for testosterone-tocortisol and free testosterone-to-cortisol ratios. The percent unbound testosterone was determined from the total testosterone and free testosterone data for each sampling time. An immunoradiometric assay was used for the determination of growth hormone concentrations (Nichols Institute Diagnostics, San Juan Capistrano, CA). All samples were analyzed in duplicate with intra-assay variance of 3.7% and interassay variance of 3.0% for growth hormone. Peptide F was separated from plasma by using a C18 (200-mg) separating column (Peninsula Laboratories, Belmont, CA) and a series of washes (0.1% triuoroacetic acid and 60% acetonitrate in 0.1% triuoroacetic acid). The resulting eluent (3 ml) was then evaporated to dryness by a centrifugal concentrator. Peptide-F concentrations were then measured by using a 3-day doubleantibody, liquid-phase 125I radioimmunoassay (Peninsula Laboratories). All samples were analyzed in duplicate with intra-assay variance of 6.1% and interassay variance of 14.0%. The recovery of peptide F was 85.9%, and the coefficient of regression for the standard concentrations was 0.991. Peptide-F values were then compared with previously reported epinephrine concentrations (13). The molar ratio between circulating peptide-F and epinephrine concentrations was calculated for each sampling time. Changes in the molar ratio over time would suggest different secretory patterns for peptide F and epinephrine. Total whole-blood hemoglobin was determined with a quantitative, calorimetric determination at 540 nm (Sigma Diagnostics, St. Louis, MO) by using a visible spectrophotometer (Pharmacia LKB No-

vaspec II, Uppsala, Sweden). Exercise-induced plasma volume shifts (%) were estimated from changes in hematocrit and hemoglobin by using the methods of Dill and Costill (6). Statistical analyses. All data are presented as means SE. Independent t-tests were used to compare descriptive characteristics of each group. Physical performances were analyzed with 2 3 (group test) mixed-model ANOVAs. Blood variables were analyzed with 2 3 3 (group time test) mixed-model ANOVAs. All ANOVAs were adjusted for unequal sample sizes. Post hoc analyses were performed with Fisher s least signicant difference procedures. The use of parametric statistics for all endocrine-dependent variables was supported by the lack of signicance for both the Kolmogorov-Smirnov test for normality of distributions and the Bartlett test for homogeneity of variances. Signicance was P 0.05 for all analyses.

During the course of the investigation, descriptive characteristics did not change from the values listed in Table 1 for either the OT or the Con groups. One-RM lifting capabilities for the OT group signicantly decreased 11% compared with the Con group (OT, mean 12.2 kg; Con, mean 1.1 kg) as previously reported (12). The Con group exhibited no signicant changes in 1-RM strength, indicative of the efficacy of their training protocol for maintaining training-specic (1-RM) strength. The results for total testosterone, free testosterone, percent unbound testosterone, and cortisol (Fig. 2); total testosterone-to-cortisol ratio and free testosteroneto-cortisol ratio (Fig. 3); growth hormone (Fig. 4); and peptide F and its molar ratio with epinephrine (Fig. 5) are illustrated in their respective gures. No anticipatory response (Pre 1 vs. Pre 2) was evident for any variable at any time. Testosterone, free testosterone, and growth hormone exhibited signicant exerciseinduced increases for most tests for both groups. The OT group had slightly elevated postexercise total testosterone concentrations by test 3, whereas the Con group exhibited increased concentrations of total testosterone at both rest and postexercise by test 3. No differences for percent unbound testosterone were observed across time for either group or between groups at any time. No changes in resting concentrations of cortisol were observed for either group, and exercise produced no signicant increases, although postexercise cortisol for the OT group had decreased slightly by test 3. Figure 3 illustrates the responses of total testosteroneto-cortisol ratio and free testosterone-to-cortisol ratio. The postexercise ratio of total testosterone to cortisol increased slightly for the OT group at test 3, although the preexercise values were less than for the Con group for this test. This difference between groups appeared to be due to elevated total testosterone concentrations for the Con group rather than to decreased total testosterone for the OT group. Few differences were observed between groups for free testosterone-tocortisol ratio. Growth hormone exhibited similar exercise-induced increases for all three tests, but no differences were observed between the OT and Con groups.

Downloaded from on August 7, 2010



Fig. 2. Resting and exercise-induced responses for testosterone, free testosterone, percent unbound testosterone, and cortisol for both OT (n 11 men) and Con (n 6 men) groups. Values are means SE. Pre 1, 15 min preexercise; Pre 2, immediately preexercise; 5 min, 5 min postexercise. Brackets represent time points compared. * Con and * OT, difference diference between tests, P 0.05. Different from Pre 1 and Pre 2, P 0.05.

Downloaded from on August 7, 2010

Fig. 3. Resting and exercise-induced responses of the testosterone-to-cortisol and free testosterone-to-cortisol ratios for both OT (n 11 men) and Con (n 6 men) groups. Values are means SE. Brackets represent time points compared. * Con and * OT, difference between tests, P 0.05. * Difference between groups, P 0.05.



Fig. 4. Resting and exercise-induced responses of growth hormone for both OT (n 11 men) and Con (n 6 men) groups. Values are means SE. Different from Pre 1 and Pre 2, P 0.05.

Peptide-F concentrations for the OT and Con groups were similar for all tests, and no changes were reported for either group at any sampling time. Molar ratio values between peptide F and previously reported epinephrine values (13) were not different between the OT and Con groups. For all tests, there was a signicant decrease in molar ratio from both preexercise samples (Pre 1 and Pre 2) to immediately postexercise. Mean estimated exercise-induced plasma volume shifts for all subjects and tests were 15.9%. This indicates that the nonsignicant exercise-induced increases of cortisol can be accounted for by plasma volume shifts. Total testosterone, free testosterone, and growth hormone all exhibited exercise-induced concentration increases greater than what can be attributed to plasma volume shifts alone. Although hormonal concentrations can be adjusted for plasma volume shifts (38), this only accounts for one of many regulating mechanisms (30). Because the present study was concerned only with actual circulating hormonal concentrations, and not hormonal kinetics, concentrations were not adjusted for plasma volume shifts, thus permitting comparison with previous overtraining research.

Performance decrements. The overtraining exercise protocol used in the present study resulted in signicant decrements in 1-RM leg strength (12), indicative of a state of overtraining (14, 33). This phenomenon did not appear to be transient, because OT subjects reported an inability to resume their normal resistance training loads for up to 8 wk after this study, thus requiring a long-term regeneration period. As previously reported, the decreased strength performances for the OT group did not appear to be due to muscle damage, as indicated by serum levels of total creatine kinase or perceptions of muscular soreness (12). Decreased strength performances were a result of the high-relative-intensity training for only the lower body because upper body training was held constant at normal levels for all subjects. Although the onset of overtraining by increased training volume has been studied in endurance athletes (34), previous investigations have not monitored endocrine proles accompanying the onset of overtraining with high-relativeintensity (%1-RM) resistance exercise. The hormonal prole observed in the present study was markedly different from what has been indicated for other types

of overtraining and was generally not altered due to the present overtraining protocol. Total testosterone. Although increased volumes of weight training generally result in decreased resting and exercise-induced (11, 15, 28) total testosterone levels, the increased relative training intensity used by the OT group did not alter preexercise concentrations of total testosterone and actually slightly increased the acute response. On the other hand, the Con group exhibited increased preexercise total testosterone by test 3, which has been observed before with decreased training stress (15). The increased total testosterone concentrations were greater than the plasma volume shifts, suggesting that increased testosterone secretion and/or decreased clearance was responsible for the exercise-induced responses. Exercise-induced testosterone responses are apparently not under hypothalamicpituitary regulation via leutinizing hormone (19). In the present study, the acute testosterone increases were not accompanied by elevated luteinizing hormone concentrations (unpublished observations), although these data are preliminary because they do not account for pulsatility characteristics. The elevated exerciseinduced sympathetic activity previously been reported for the OT group (13) most likely contributed to the augmented acute testsoterone response (7, 23). The augmented exercise-induced total testosterone response with overtraining at test 3 may have been part of an unsuccessful physiological attempt to preserve muscular strength capabilities. Although it is unclear as to the exact mechanism responsible, the relatively low volume of resistance exercise for the OT group may have kept total testosterone from decreasing, contrary to what has been observed with studies of increased resistance training volume (11, 15, 28). Free testosterone. Normal resistance exercise training programs increase resting free testosterone concentrations (2, 18), whereas increased training volumes result in attenuated resting (16, 18, 19) and augmented acute (19) free testosterone. It has been theorized that free testosterone is more sensitive to the stresses of overtraining than is total testosterone (16). Contrary to this suggestion, at no time did the OT protocol in the present study affect concentrations of free testosterone at any sampling time. Exercise-induced increases in free testosterone were usually evident and remained constant throughout the study. Percent unbound testosterone. No changes were observed in the percent unbound testosterone, which is

Downloaded from on August 7, 2010



Fig. 5. Resting and exercise-induced responses of peptide F and molar ratio of peptide F to epinephrine for both OT (n 11 men) and Con (n 6 men) groups. Values are means SE. Different from Pre 1 and Pre 2, P 0.05.

Downloaded from on August 7, 2010

the fraction of total testosterone that is classied as free testosterone. This indicates that changes for testosterone-binding proteins, such as sex hormone-binding globulin (SHBG) and albumin, simply mirrored the changes in circulating total testosterone. It has been suggested that increased free testosterone occurs with exhaustive exercise to compensate for decreased total testosterone concentrations (1). Because it is the unbound fraction of total testosterone that is available for biological activity at the target receptors, this would be an effective method for maintaining the biological activity of testosterone in the presence of decreased total testosterone concentrations (28). This, however, was not evident in the present study. The lack of change for percent unbound testosterone was not unexpected because the association constant for SHBG does not change due to an acute exercise bout (7). Cortisol. Long-term normal resistance exercise programs result in no change or decreased resting (2, 18) and increased exercise-induced cortisol concentrations (29). Contrary to studies of increased resistance training volume (11, 16, 18), the overtraining protocol used in the present study produced no changes in preexercise cortisol concentrations. Of particular interest are the decreased exercise-induced cortisol concentrations for the OT group by test 3, similar to what is seen with increased training volumes (11). The exercise-induced cortisol responses were at all times comparable to or less than the plasma volume shifts, indicating a lack of adrenal cortical response to the exercise stimulus and suggesting that exercise duration may have been too short in the present study (4). It is unlikely that hypothalamic-pituitary regulation via adrenocorticotropic hormone is responsible for the attenuated exercise-induced cortisol response, because the lag time for adrenocorticotropic hormone activation of cortisol is much longer than the cortisol sampling period used in the present study (8). This is further supported by the absence of any changes in adrenocorticotropic hormone levels over the course of the present study (unpublished observations), although these data are preliminary

because they do not account for pulsatility characteristics. Evidence exists of neural control of adrenal cortex activity (22), thus providing a rapid regulatory mechanism of exercise-induced cortisol responses. It is not known, however, whether altered adrenal cortex activity, sympathetic nervous system regulation, or some other physiological mechanism is responsible for the decreased exercise-induced cortisol response of the OT group. Hormonal ratios. It has been suggested that the total testosterone-to-cortisol ratio may be a marker for overtraining with resistance exercise (18). Exercise-induced total testosterone-to-cortisol ratio usually decreases postexercise (10, 11). When resistance exercise training volume is increased, resting and exercise-induced total testosterone-to-cortisol ratio will typically decrease (10, 16, 18), although this pattern is reversed with longterm training and prior exposure to elevated training volumes (10). No decreases of total testosterone-tocortisol ratio were observed in the present study, and differences between the OT and Con groups for resting ratios were due primarily to augmented total testosterone for the Con group only. The resting ratio of biologically available testosterone (i.e., free testosterone) and cortisol (free testosterone-to-cortisol ratio) does not change with normal resistance exercise training volumes or detraining (2). In the present study, few changes in resting or exercise-induced free testosteroneto-cortisol ratio values were observed for either group. Although the OT group experienced performance decrements, decreases in free testosterone-to-cortisol ratio of 30%, or values below 0.35 103, were not observed at any time, contrary to the overtraining markers suggested by Adlercreutz et al. (1). In contrast to reports of endurance activities, neither the testosteroneto-cortisol ratio nor the free testosterone-to-cortisol ratio seems to be an effective marker of high-intensity resistance exercise overtraining. Growth hormone. No previous resistance exercise overtraining research has monitored growth hormone responses. The present data suggest that growth hor-



mone is not inuenced by high-intensity resistance exercise overtraining. Although Barron et al. (3) have reported hypothalamic-pituitary dysfunction with aerobically based overtraining, and Urhausen et al. (39) have recently reported attenuated acute growth hormone responses to endurance overtraining, the present data do not indicate altered growth hormone concentrations accompany high-intensity resistance exercise overtraining. Peptide F. Peptide F [preproenkephalin (107140)] is secreted from the adrenal medullary chromaffin cells and is often secreted in response to the same exercise stimuli that cause epinephrine release (31). Previous research has indicated that, although chronic highintensity interval and endurance training in collegiate runners results in augmented acute epinephrine concentrations, acute peptide-F concentrations were attenuated, suggesting that epinephrine and peptide F are not released in equimolar fashion in highly trained elite endurance runners (31). This was in contrast to untrained individuals who exhibited equimolar acute concentrations of circulating peptide F and epinephrine (31). This difference in acute circulating concentrations suggests a possible training adaptation in the production and/or secretory mechanisms of the adrenal chromaffin cells. Peptide F may play a role in regulating the immune response via natural killer cell regulation, neutrophil activation, and coagulation enhancement (21, 35, 40). Such a stimulatory effect on the immune system may counter the immunosuppressive effects of catecholamines and glucocorticoids (21), both of which are elevated with various types of overtraining (13, 14, 33). This immunosuppression may partly explain why overtraining is associated with increased rates of infection (14, 33). No previous studies have recorded the response of peptide F to resistance exercise overtraining. The previously reported increases in acute epinephrine due to this overtraining protocol (13) were not observed for peptide F. These data suggest that peptide F and epinephrine were not secreted in equimolar concentrations due to this overtraining protocol, as indicated by the signicant decrease for the exercise-induced molar ratios. The extremely large epinephrine response to the high-intensity resistance exercise overtraining (13) may have simply overwhelmed the capacity of the adrenal medullary chromaffin cells to secrete peptide F. This also suggests that the requirement for peptide F under these stressful conditions is less than for epinephrine. The absence of an acute peptide-F response could be due to an inadequate exercise stimulus (e.g., duration too short, inadequate work production), as has been previously reported (32), or due to the fact that all of the subjects were previously weight trained, which may have attenuated the acute peptide-F response that has been reported for highly trained endurance runners (31). Whether the lack of peptide-F response is due to the slower processing of peptide F from its precursor molecule compared with epinephrine (26, 37), or whether there are chromaffin cell pools that may contain different ratios of peptide F and epinephrine or may preferentially secrete one particular compound

(31, 32), is not known. It should be noted that the half-life (t ) for peptide-F plasma clearance after secretion from the chromaffin cells is 15 min (24), which allows considerable time for peptide F to interact at its primary site of action, in the circulation (35, 40). The use of a sampling time immediately postexercise was rapid enough to avoid problems with differences in clearance t between peptide F and epinephrine, and was appropriate for determining peak postexercise concentrations of peptide F (31, 32). It should be noted that there is no known change in the clearance rate of peptide F due to exercise intensity or modality (31). Overtraining markers. Previous research has attempted to identify endocrine markers of an impending or concurrent overtraining syndrome for both aerobic (1, 3, 34) and anaerobic activities (18). Because of the lack of association between endocrine and performance alterations, the type of exercise employed in the present study does not readily permit use of hormonal alterations to monitor impending overtraining. The daily exercise protocol used by the OT group (i.e., high relative intensity, low volume) may not acutely activate testicular or adrenal cortex activity to a great extent, as has been demonstrated with a similar resistance exercise protocol (17). This may partly explain the lack of endocrine adaptations to the OT protocol. Therefore, other physiological systems, such as sympathetic nervous system activity (13) or neuromuscular characteristics (12), may need to be monitored to avoid overtraining with short-term, high-intensity resistance exercise with subjects who have previously weight trained. Previous resistance exercise investigations have demonstrated signicant positive correlations between changes for free testosterone (2, 18), total testosterone-tocortisol ratio (19), or free testosterone-to-cortisol ratio (2), and changes for physical performances such as isometric quadriceps force (2, 19), clean-and-jerk 1 RM (18), or a calculated tness index (5). No such correlations were evident for the OT group (unpublished observations). Summary. Circulating testosterone, free testosterone, cortisol, growth hormone, and peptide-F concentrations were not greatly affected by the high-intensity exercise protocol for the OT group. Although decrements in strength performance were readily apparent, these changes were not accompanied by an altered hormonal environment for the OT group. It appears that short-term, high-relative-intensity resistance exercise overtraining may not be successfully monitored via circulating hormonal concentrations.
The authors extend their appreciation to N. Travis Triplett, L. Perry Koziris, Joseph L. Marsit, Femke van Borselen, and J. Michael Lynch for assistance with the data collection and to Steven J. Fleck, Robert S. Staron, and Anne B. Loucks for assistance with the hormonal analyses. Address for reprint requests: A. C. Fry, 135 Roane Field House, University of Memphis, Memphis, TN 38152. Received 15 April 1998; accepted in nal form 23 July 1998. REFERENCES 1. Adlercreutz, H., M. Ha r ko nen, K. Kuoppasalmi, H. Na ve r i, I. Huhtaniemi, H. Tikkanen, K. Remes, A. Dessypris, and J . Karvonen. Effect of training on plasma anabolic and catabolic

Downloaded from on August 7, 2010

PITUITARY-ADRENAL-GONADAL RESPONSES steroid hormones and their response during physical exercise. Int. J. Sports Med. 7, Suppl.: 2728, 1986. Ale n, M., A. Pakarinen, K. Ha kkinen, and P. V. Komi. Responses of serum androgenic-anabolic and catabolic hormones to prolonged strength training. Int. J. Sports Med. 9: 229233, 1988. Barron, J . L., T. D. Noakes, W. Levy, C. Smith, and R. P. Millar. Hypothalamic dysfunction in overtrained athletes. J. Clin. Endocrinol. Metab. 60: 803806, 1985. Brandenberger, G., and M. Follenius. Inuence of timing and intensity of muscular exercise on temporal patterns of plasma cortisol levels. J. Clin. Endocrinol. Metab. 40: 845849, 1974. Busso, T., K. Ha kkinen, A. Pakarinen, H. Kauhanen, P. V. Komi, and J . R. Lacour. Hormonal adaptations and modeled responses in elite weightlifters during 6 weeks of training. Eur. J. Appl. Physiol. 64: 381386, 1992. Dill, D. B., and D. L. Costill. Calculation of percentage changes in volume of blood, plasma, and red cells in dehydration. J. Appl. Physiol. 37: 247248, 1974. Fahrner, C. L., and A. C. Hackney. Effects of endurance exercise on free testosterone concentration and the binding affinity of sex hormone binding globulin (SHBG). Int. J. Sports Med. 19: 1215, 1998. Farrell, P. A. Adrenocorticotropic hormone and exercise. In: Exercise Endocrinology, edited by K. Fotherby and S. B. Pal. New York: de Gruyter, 1985, p. 139156. Fry, A. C., T. A. Aro, J . A. Bauer, and W. J . Kraemer. A kinematic comparison of three barbell squat variations and a squat simulating machine (Abstract). J. Appl. Sport Sci. Res. 5: 162, 1991. Fry, A. C., W. J . Kraemer, M. H. Stone, B. J . Warren, S. J . Fleck, J . T. Kearney, and S. E. Gordon. Endocrine responses to over-reaching before and after one year of weightlifting training. Can. J. Appl. Physiol. 19: 400410, 1994. Fry, A. C., W. J . Kraemer, M. H. Stone, B. Warren, J . T. Kearney, S. J . Fleck, and C. A. Weseman. The effect of amino acid supplementation on testosterone, cortisol, and growth hormone responses to one week of intensive weightlifting. Int. J. Sport Nutr. 3: 306322, 1992. Fry, A. C., W. J . Kraemer, F. van Borselen, J . M. Lynch, J . L. Marsit, E. P. Roy, N. T. Triplett, and H. G. Knuttgen. Performance decrements with high intensity resistance exercise overtraining. Med. Sci. Exerc. Sports 26: 11651173, 1994. Fry, A. C., W. J . Kraemer, F. van Borselen, J . M. Lynch, N. T. Triplett, L. P. Koziris, and S. J . Fleck. Catecholamine responses to short-term, high-intensity resistance exercise overtraining. J. Appl. Physiol. 77: 941946, 1994. Fry, R. W., A. R. Morton, and D. Keast. Overtraining in athletes, an update. Sports Med. 12: 3265, 1991. Ha kkinen, K., K. L. Keskinen, M. Ale n, P. V. Komi, and H. Kauhanen. Serum hormone concentrations during prolonged training in elite endurance-trained and strength-trained athletes. Eur. J. Appl. Physiol. 59: 233238, 1989. Ha kkinen, K., and A. Pakarinen. Serum hormones in male strength athletes during intensive short-term strength training. Eur. J. Appl. Physiol. 63: 194199, 1991. Ha kkinen, K., and A. Pakarinen. Acute hormonal responses to two different fatiguing heavy-resistance protocols in male athletes. J. Appl. Physiol. 74: 882887, 1993. Ha kkinen, K., A. Pakarinen, M. Ale n, H. Kauhanen, and P. V. Komi. Relationships between training volume, physical performance capacity, and serum hormone concentrations during prolonged training in elite weightlifters. Int. J. Sports Med. 8, Suppl.: 6165, 1987. Ha kkinen, K., A. Pakarinen, M. Ale n, H. Kauhanen, and P. V. Komi. Daily hormonal and neuromuscular responses to intensive strength training in 1 week. Int. J. Sports Med. 9: 422428, 1988. Ha kkinen, K., A. Pakarinen, M. Ale n, H. Kauhanen, and P. V. Komi. Neuromuscular and hormonal adaptations in athletes to strength training in two years. J. Appl. Physiol. 65: 24062412, 1988. Hiddinga, H. J ., D. D. Isaak, and R. V. Lewis. Enkephalincontaining peptides processed from the proenkephalin signicantly enhances the antibody-forming cell response to antigens. J. Immun. 152: 37483759, 1994.



3. 4. 5.

6. 7.

8. 9.





14. 15.

16. 17. 18.




22. Holzwarth, M. A., L. A. Cunningham, and N. Kleitman. The role of adrenal nerves in the regulation of adrenocortical function. Ann. NY Acad. Sci. 512: 449464, 1987. 23. J ezova, D., and M. Vigas. Testosterone response to exercise during blockade and stimulation of adrenergic receptors in man. Horm. Res. 15: 141147, 1981. 24. Katzenstein, G. E., D. Lund, P. Schultz, and R. V. Lewis. Target tissue distribution of the proenkephalin peptides F, E and B. Biochem. Biophys. Res. Commun. 146: 1841190, 1987. 25. Kilpatrick, D. L., R. V. Lewis, S. Stein, and S. Undenfriend. Release of enkephalins and enkephalin-containing polypeptides from perfused beef adrenal glands. Proc. Natl. Acad. Sci. USA 77: 74737475, 1981. 26. Kopin, I. J . Catecholamine metabolism (and the biochemical assessment of sympathetic activity). Clin. Endocrinol. Metab. 6: 525549, 1977. 27. Koziris, L. P., A. C. Fry, W. J . Kraemer, M. H. Stone, J . T. Kearney, S. J . Fleck, J . Thrush, S. E. Gordon, and N. T. Triplett. Hormonal and competitive performance responses to an over-reaching stimulus in elite junior weightlifters (Abstract). J. Appl. Sports Sci. Res. 6: 186, 1992. 28. Kraemer, W. J . Hormonal mechanisms related to the expression of muscular strength and power. In: Strength and Power in Sport, edited by P. V. Komi. London: Blackwell Scientic, 1992, p. 6476. 29. Kraemer, W. J ., A. C. Fry, B. J . Warren, M. H. Stone, S. J . Fleck, J . T. Kearney, B. P. Conroy, C. M., Maresh, C. A. Weseman, N. T. Triplett, and S. E. Gordon. Acute hormonal responses in elite junior weightlifters. Int. J. Sports Med. 13: 103109, 1992. 30. Kraemer, W. J ., L. Marchitelli, S. E. Gordon, E. A. Harman, J . E. Dziados, R. Mello, P. N. Frykman, D. McCurry, and S. J . Fleck. Hormonal and growth factor responses to heavy resistance exercise protocols. J. Appl. Physiol. 69: 14421450, 1990. 31. Kraemer, W. J ., B. Noble, B. Culver, and R. V. Lewis. Changes in plasma proenkephalin peptide F and catecholamine levels during graded exercise in men. Proc. Natl. Acad. Sci. USA 82: 63496351, 1985. 32. Kraemer, W. J ., J . F. Patton, H. G. Knuttgen, C. J . Hannan, T. Kettler, S. E. Gordon, J . E. Dziados, A. C. Fry, P. N. Frykman, and E. A. Harman. Effects of high-intensity cycle exercise on sympathoadrenal-medullary response patterns. J. Appl. Physiol. 70: 814, 1991. 33. Kuipers, H., and H. A. Keizer. Overtraining in elite athletes, review and directions for the future. Sports Med. 6: 7992, 1988. 34. Lehmann, M., H. Dickhuth, G. Gendrisch, W. Lazar, M. Thum, R. Kaminski, J . F. Aramendi, E. Peterke, W. Wieland, and J . Keul. Training-overtraining. A prospective, experimental study with experienced middle- and long-distance runners. Int. J. Sports Med. 12: 444452, 1991. 35. Lett, E., S. Gangloff, M. Zimmermann, D. Wachsmann, and J .-P. Klein. Immunogenicity of polysaccharides conjugated to peptides containing T- and B-cell epitopes. Infect. Immun. 62: 785792, 1994. 36. Livett, A. R., D. M. Dean, L. G. Whelan, S. Undenfriend, and J . Rossier. Co-release of enkephalin and catecholamines from cultured adrenal chromaffin cells. Nature 289: 317319, 1981. 37. Phillips, J . H. Chromaffin granule biogenesis and the exocytosis/ endocytosis cycle. In: Stimulus-Secretion Coupling in Chromaffin Cells, edited by K. Rosenheck and P. I. Lelkes. Boca Raton, FL: CRC Press, 1987, vol. I, p. 3249. 38. Schwab, R., G. O. J ohnson, T. J . Housh, J . E. Kinder, and J . P. Weir. Acute effects of different intensities of weight lifting on serum testosterone. Med. Sci. Sports Exerc. 25: 13811385, 1994. 39. Urhausen, A., H. H. W. Gabriel, and W. Kindermann. Impaired pituitary hormonal response to exhaustive exercise in overtrained endurance athletes. Med. Sci. Sports Exerc. 30: 407414, 1998. 40. Vlahos, C. J ., and W. F. Matter. Signal transduction in neutrophil activation phosphatidylinositol 3-kinase is stimulated without tyrosine phosphorylation. FEBS Lett. 309: 242 248, 1992.

Downloaded from on August 7, 2010