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˙ Effects of Decanoate on VO2max, Running Economy, and Endurance in Rats

KATERINA N. GEORGIEVA and NICKOLAY P. BOYADJIEV Department of Physiology, Medical University Plovdiv, Plovdiv, BULGARIA

ABSTRACT ú GEORGIEVA, K. N., and N. P. BOYADJIEV. Effects of on VO2max, Running Economy, and Endurance in Rats. Med. Sci. Sports Exerc., Vol. 36, No. 8, pp. 1336Ð1341, 2004. Purpose: The aim of the present study was to determine the effects of treatment with an anabolic androgenic (AAS), nandrolone decanoate, on the submaximal running endurance (SRE), ú ú maximum oxygen consumption (VO2max), running economy (VO2submax), and blood oxygen carrying capacity of endurance trained rats. Methods: Forty male Wistar rats were randomly allocated into two groups: a sedentary group and an exercising group training on treadmill for 8 wk. Half of the trained and half of the sedentary rats received weekly either nandrolone decanoate (10 mgákgϪ1)or ú ϭ placebo (Pl) for the last 6 wk of experiment. SRE and VO2max tests were performed several times for all four groups (N 10 each). Red blood cells parameters were measured at the end of the experiment. Results: The trained rats had increased their SRE compared with sedentary rats throughout the experiment. At the end of the trial, the trained rats receiving nandrolone decanoate ran 46% longer than trained rats receiving Pl during the SRE test (P Ͻ 0.05). At the end of the experiment, trained rats had greater maximal time to ú ú ú exhaustion and higher VO2max than those of the sedentary rats but there were no differences in VO2max,VO2submax, and red blood cells parameters between the trained rats receiving nandrolone decanoate and those receiving Pl. Conclusions: Nandrolone decanoate has ú ú no effect on the SRE, VO2max and VO2submax of untrained rats. AAS treatment combined with submaximal training enhances SRE more ú than training alone but exerts no additive effects on VO2max, running economy, and oxygen carrying capacity of blood. The results suggest that this improvement in SRE of trained rats is due to the impact of AAS on other factors involved in exercise adaptation. Key Words: MALE RATS, ANABOLIC ANDROGENIC , OXYGEN CONSUMPTION, RED BLOOD CELLS, SUBMAXI- MAL RUNNING ENDURANCE

nabolic androgenic steroids (AAS), synthetic deriva- Endurance exercise training improves maximum oxygen ú ú tives of the sex hormone , are used in consumption (VO2max) and running economy (VO2submax), Avarious sports to enhance athletic performance. The which are considered key parameters in the improvement of majority of users are strength athletes in professional and submaximal running performance (17). AAS enhance eryth- amateur sports (8); however, there have also been reports of ropoiesis and increase blood volume (21). As oxygen car- ú steroids taken by endurance athletes (e.g., swimmers, cyclists, rying capacity is one of the factors determining VO2max and runners) (14,29). Although there is much research on the effect submaximal running endurance (SRE) (4,11), it seems to be of AAS on strength and power, there are few studies on their a likely mechanism through which SRE can be increased by effect on endurance exercise performance. Several potential AAS (20). The combined effect of endurance training and mechanisms have been suggested to cause the ergogenic ef- AAS treatment on these parameters is not well defined. fects of AAS treatment on endurance trained subjects. One of The effect of AAS on submaximal running performance the possible mechanisms is improvement of skeletal muscle is difficult to study in training athletes because of method- function by increasing protein synthesis (23,27). Another sug- ological limitations and ethical considerations. One of the gested mechanism is that AAS treatment counteracts the cat- first animal studies investigating the effect of AAS on abolic action of high circulating corticosteroid concentrations submaximal running performance was conducted on spon- resulting from training (15). Another possibility is that AAS act taneously running male rats (28). This study showed that through the central nervous system, allowing the subjects to combining AAS treatment with voluntary wheel running train harder (3,26). delays fatigue during submaximal exercise and improves SRE by 41% compared with wheel running. The improve- ment in SRE could not be explained by either the increased Address for correspondence: Dr. Katerina Georgieva, Department of Phys- voluntary training distance, the increased skeletal muscle iology, Medical University Plovdiv, 15-A, Vasil Aprilov Blvd., 4000 oxidative capacity, or the increased skeletal muscle glyco- Plovdiv, Bulgaria; E-mail: [email protected]. gen concentration compared with trained controls. It was Submitted for publication August 2003. also found that AAS treatment had no effect on maximal Accepted for publication March 2004. sprint speed and on SRE of untrained rats (28). These data 0195-9131/04/3608-1336 suggest that the increase of submaximal running perfor-

MEDICINE & SCIENCE IN SPORTS & EXERCISE¨ mance is due to the impact of AAS on factors involved in Copyright © 2004 by the American College of Sports Medicine exercise adaptation and not to the fact that subjects train DOI: 10.1249/01.MSS.0000135781.42515.17 harder. Voluntary wheel running is a type of exercise train- 1336 ú Ϫ1 ing which improves SRE, running economy and VO2max of exercised on the treadmill 3 dáwk for 5 min at the same rats similarly to the changes induced by the submaximal speed and elevation as the training group to ensure famil- training on a treadmill (19). Treadmill-trained rats have iarization with treadmill running. The treadmill speed was been employed by other researchers to study the effects of calibrated before each training session. AAS on running performance, but the training and the tests At the beginning of week 3, half of the trained and have been performed using high exercise intensity (with untrained rats were given an anabolic androgenic steroid, additional weight, high speed and high grade of the tread- nandrolone decanoate (ND) 10 mgákgϪ1áwkϪ1 intramuscu- ú ¨ mill belt) and changes in the SRE, VO2max, running econ- larly (Retabolil , Gedeon Richter, Hungary) over a time omy, and blood oxygen carrying capacity have not been period of 6 wk. The other half of the rats were given placebo investigated (25). (Pl, oil vehicle) in the same dose and duration. The injection Studying the changes these parameters undergo under the was administered after the day’s training in m. gluteus combined influence of AAS treatment and endurance tread- medius, applying it alternatively each week in the contralat- mill training will provide new evidence about the AAS eral side. Nandrolone decanoate is a long acting steroid ester effect on endurance exercise performance and the possible and the recommended therapeutic dose of ND in humans mechanisms causing this effect. To our knowledge, the falls within 50Ð100 mg (i.m.) range every 3Ð4 wk (about effects of AAS treatment on these parameters in submaxi- 0.4 mgákgϪ1áwkϪ1) (26). The supraphysiological dose of 10 mal treadmill-trained rats have not been studied. Therefore, mgákgϪ1áwkϪ1 as used in the present study is consistent the aim of the study was to evaluate the separate and with the high doses of AAS reported to have been used by combined effects of treatment with an anabolic androgenic athletes (14,20). steroid and submaximal treadmill training on submaximal As it is assumed that the AAS effect is more pronounced running endurance, maximum oxygen consumption, run- in pretrained individuals (10), treatment with AAS started ning economy, and oxygen carrying capacity in rats. We after the daily exercise reached a duration of 40 min. To hypothesized that AAS can increase SRE, running econ- differentiate exactly the effect of AAS, the absolute inten- omy, and oxygen carrying capacity of endurance treadmill- sity and duration of the exercise of both training groups was trained rats. kept constant from the beginning of treatment with ND/Pl until the end of experiment. Thus, four experimental groups ϭ ϩ MATERIALS AND METHODS were formed (N 10): sedentary rats Pl (SP, controls); sedentary rats ϩ ND (SND); trained rats ϩ Pl (TP), and Animals. Forty male Wistar rats (200Ð220 g) were used trained rats ϩ ND (TND). Two rats of the TP group dropped in this study. They were housed in individual metabolic from experiment because of injuries and training protocol cages and fed standard rat chow and water ad libitum. Body violation. mass and the amount of food intake were measured daily. Submaximal running endurance test. Before the The rats were maintained at an ambient temperature of start of training, after weeks 2 and 6, and at the beginning of 21Ð24¡C with a 12/12-h dark-light cycle. The experimental week 9 all groups were subjected to a submaximal running protocol was approved by the Ethical Committee on Human endurance test. SRE was determined in rats by having them and Animal Experimentation of Medical University, Plo- run at 27 máminϪ1, with 5¡ elevation of the belt until they vdiv. Rat care and all experimental procedures employed could no longer maintain their position on the treadmill belt. were in accordance with the policy statement of the Amer- The time taken to reach this stage was assessed as SRE. ˙ ˙ ican College of Sports Medicine on research with experi- VO2max,VO2submax, and maximum time to ex- mental animals. haustion assessment. At baseline, after week 6, and at Training program and steroid treatment. As run- the beginning of week nine all groups were subjected to ú ning on a treadmill is a skilled activity for rats, before the VO2max test according to Bedford et al. (5). The parameters experiment all rats were exercised on the treadmill (Colum- were measured using the Oxymax gas analyzing system for bus Instruments, Columbus, OH) at a speed of 27 máminϪ1 small animals (Columbus Instruments). The test was always and 5¡ elevation for 5 minádϪ1,3dáwkϪ1 for 2 wk. Such carried out after a 1-d recovery period. The volume of the workload induces no training adaptations (18) but familiar- supplied air was 4.5 LáminϪ1. The gas analyzers were cal- izes the rats with treadmill running and allows selection of ibrated with a reference gas mixture before each test. The ú rats that run spontaneously. About 15% of the rats refused VO2max test protocol involved stepwise increasing of the to run on the treadmill and were discarded from the study at treadmill speed and elevation as follows—I: 15 máminϪ1,5¡ the end of the preliminary stage. elevation; II: 19 máminϪ1,10¡; III: 27 máminϪ1,10¡; IV: 27 Compliant rats were randomized into two groups, seden- máminϪ1,15¡;V:30máminϪ1,15¡; VI: 35 máminϪ1,15¡; tary (N ϭ 20) and trained (N ϭ 20). Trained animals and VII: 40 máminϪ1,15¡. Each step of exercise was 3 min Ϫ1 ú exercised on the treadmill at a speed of 27 mámin ,5¡ long, and oxygen consumption (VO2) was measured at ú Ϫ1 elevation (which is about 70Ð75% VO2max),5dáwk for 8 every minute. Each rat was placed in the chamber 10 min wk. The duration of the exercise was 20 minádϪ1 on the first before exercising, and the lowest value of those measured day and was increased by 5 min every second day. By the during the last 4 min was taken to be the rest consumption. Ϫ1 ú end of the second week, it reached 40 minád and remained The highest VO2 measured at each workload was taken as a ú so until the end of experiment. The untrained rats were measure of each rat’s running economy (VO2submax) for that

EFFECTS OF NANDROLONE DECANOATE Medicine & Science in Sports & Exerciseா 1337 ú workload, and at the last step, as VO2max. Rats were removed from the test either when they could no longer maintain their position on the treadmill belt or in the plateau phenomenon (5). ú The time taken to reach VO2max was defined as the maximum running time to exhaustion of each rat (18). Blood analysis. At the beginning of week 9, 10 d after the last administration of ND/Pl and 23Ð25 h after the last ú VO2max test, the rats were sacrificed under narcosis with 10 mgákgϪ1 thiopental i.p. Mixed blood was collected into heparinized tubes for investigation for amount of erythrocytes, mean corpuscular volume, hemoglobin and hematocrit. All parameters were determined by a hematological analyzer Coulter T-660 (Coulter Electronics, Inc., Hialeah, FL). Statistical analysis. To test for the two main effects (exercise training and AAS administration) and for the in- teraction between them, the results of all tests, which were repeated several times during the experiment, were assessed by a two-way factorial analysis of variance for repeated measures. The results obtained only at the end of the ex- periment were analyzed with a two-way factorial analysis of variance. The level of significance was set at P Ͻ 0.05. Tukey post hoc test was applied for intergroup differences. Data are presented as mean Ϯ SEM. FIGURE 1—Submaximal running endurance (min) of experimental groups measured at the beginning of experiment, 2, 6, and 8 wk later. .(TND vs TP by 46%) 0.01 ؍ P < 0.001 (trained vs sedentary); **P* RESULTS Body mass and food intake. At baseline, all rats in group improved their SRE by 18% (P Ͼ 0.05), whereas the the groups had a similar body mass. During the experiment, TND group improved their SRE by 60% (P Ͻ 0.01). There the body weight of all rats gradually increased and at the end were no significant differences in the SRE between both of the experiment the analysis failed to find any significant untrained groups throughout the experiment. differences in their body mass: SP, 346.10 Ϯ 10.70 g; SND, Maximal running performance. There were no dif- 323.30 Ϯ 10.70 g; TP, 323.25 Ϯ 11.96 g; TND, 340.40 Ϯ ferences in the maximum running time to exhaustion in the 10.70 g (P Ͼ 0.05). There were no significant differences incremental maximal treadmill test at the beginning of ex- between the groups in the amount of food taken during the periment (Fig. 2). Endurance training had a significant main experiment (not shown). effect on maximum running performance during the study Submaximal running performance. At baseline, the period. The trained groups increased their maximum run- rats of all groups had similar SRE (P Ͼ 0.05). Endurance ning time to exhaustion in comparison both with the base- training had a significant main effect on SRE measured during the study period (Fig. 1). The trained rats improved significantly their SRE compared with baseline values (P Ͻ 0.01 at week 2, P Ͻ 0.001 at weeks 6 and 8) and compared with the untrained rats SRE measured after 2 wk (91.97 Ϯ 6.85 min vs 35.33 Ϯ 6.46 min, P Ͻ 0.001), 6 wk (107.78 Ϯ 8.39 min vs 34.97 Ϯ 7.91 min, P Ͻ 0.001), and 8 wk (128.39 Ϯ 7.28 min vs 35.10 Ϯ 6.87 min, P Ͻ 0.001) of training. We found no significant effect of ND treatment on SRE of un- trained and trained rats at the end of week 6 of the experiment. ND treatment had a significant main effect (P Ͻ 0.05) on SRE measured at the end of the experiment, and there was a significant interaction (P Ͻ 0.05) of training and AAS treatment. ND treatment had no effect on untrained rats but improved the SRE of the trained group. At the beginning of week 9, TND group had significantly higher SRE than the other groups and TND rats ran 46% longer than TP rats during SRE test (152.15 Ϯ 13.30 min vs 103.90 Ϯ 11.77 min, P Ͻ 0.05). At the end of the experiment, the TP and FIGURE 2—Maximum running time to exhaustion (min) in incremen- tal running test of the experimental groups at the beginning of exper- TND groups had greater SRE than that of SP rats by 196% iment and 6 and 8 wk later. *P < 0.01 (trained vs sedentary); **P < and 336%, respectively. Between weeks 2 and 9 the TP 0.001 (trained vs sedentary).

1338 Official Journal of the American College of Sports Medicine http://www.acsm-msse.org line values (P Ͻ 0.001) and with the sedentary rats at week erythrocytes, hemoglobin, hematocrit, and the mean corpus- 6(P Ͻ 0.01) and at the beginning of week 9 of experiment cular volume of erythrocytes (MCV) are presented in Table (P Ͻ 0.001). We found no effect of ND treatment on 1. All values of the red blood cells parameters measured in maximal endurance of both untrained and trained rats. the groups were within the physiologic reference values for Maximum oxygen consumption. Endurance training male Wistar rats (6). There were no significant main effects ú had a significant main effect on VO2max. There were no of training and AAS treatment on the erythrocyte count, but ú Ͻ differences between the groups in the VO2max measured at there was a significant two-way interaction (P 0.05). AAS baseline (P Ͼ 0.05) and after 6 wk (P Ͼ 0.05) (Fig. 3). At treatment for 6 wk elevated the erythrocytes only in the ú Ͻ the end of experiment the trained rats VO2max was higher SND group in comparison with SP (P 0.05), and there than that of the sedentary rats by 4% (73.7 Ϯ 1.1 was no effect on the TND group. Training resulted in higher mLákgϪ1áminϪ1 vs 70.5 Ϯ 1.0 mLákgϪ1áminϪ1; P Ͻ 0.05). red blood cell count only in TP in comparison with SP (P Ͻ Between week 6 and the beginning of week 9, the TP and 0.05), but there was no difference in the erythrocyte count ú Ϯ Ͼ TND rats increased significantly their VO2max (69.7 1.1 between the two trained groups (P 0.05). There was a mLákgϪ1áminϪ1 vs 74.1 Ϯ 1.2 mLákgϪ1áminϪ1, P Ͻ 0.01 significant main effect of training on hemoglobin concen- and 70.1 Ϯ 1.3 mLákgϪ1áminϪ1 vs 73.3 Ϯ 1.8 tration and trained rats had higher hemoglobin than un- mLákgϪ1áminϪ1, P ϭ 0.01). ND treatment had no effect on trained animals (161.56 Ϯ 1.42 gáLϪ1 vs 157.25 Ϯ 1.39 ú Ϫ1 Ͻ VO2max of both untrained and trained rats. gáL ; P 0.05). There was a significant main effect of Running economy. At the end of experiment, the training on hematocrit and trained rats had higher hemato- ú ú Ϯ Ϯ Ͻ VO2submax measured in the first three steps during VO2max crit than sedentary rats (0.50 0.01 vs 0.47 0.01; P test showed no differences between the groups. There was a 0.05). Training had no main effect on MCV. ND treatment main effect of training on running economy during the had a significant main effect on MCV (P Ͻ 0.01), and there fourth step (27 máminϪ1,15¡ elevation) and the trained rats was a significant interaction between training and AAS ú Ͻ had significantly lower VO2submax than the sedentary rats administration (P 0.05). ND treatment had no effect on (65.3 Ϯ 0.9 mLákgϪ1áminϪ1 vs 68.0 Ϯ 0.9 mLákgϪ1áminϪ1; trained rats but SND group had a significantly lower MCV Ͻ ú P 0.05). The VO2submax measured during the fifth, sixth, than the other groups at the end of experiment. The red and seventh steps of exercise intensity were not analyzed blood cells parameters of SND group showed an increase of because of the small and unequal number of measured the number of erythrocytes but with reduced MCV (within values in the groups. There was no effect of ND treatment the normal limits) and without a respective increase in the ú on VO2submax of both untrained and trained rats in the hemoglobin and hematocrit in comparison with the controls. different steps of exercise intensity. There were no differences in red blood cells parameters There was a significant main effect of training on between TP and TND group. ú ú VO2submax when it was analyzed as %VO2max (Fig. 4). At ú the first step the trained rats had lower values of %VO2max DISCUSSION than sedentary by 5% (P Ͻ 0.01), at the second step by 6% (P Ͻ 0.05), at the third step by 7% (P Ͻ 0.01), and at the The fact that there were no differences in the body weight fourth step by 9% (P Ͻ 0.01). There was no effect of ND and the amount of food taken by the rats indicated that the ú treatment on %VO2max of both untrained and trained rats in the different steps of exercise intensity. Oxygen carrying capacity. The results of the study of blood oxygen carrying capacity assessed by the amount of

ú FIGURE 4—Oxygen consumption (%VO2max) of groups at the differ- ent steps of exercise intensity at the end of experiment. Each step lasted FIGURE 3—Maximum oxygen consumption (mL·kg؊1·min؊1)ofthe 3 min: I step (15 mámin؊1, 5¡); II step (19 mámin؊1, 10¡); III step (27 investigated groups measured at the beginning of experiment and 6 mámin؊1, 10¡); and IV step (27 mámin؊1, 15¡). *P < 0.05 (trained vs and 8 wk later. * P < 0.05 (trained vs untrained by 4%). sedentary); **P < 0.01 (trained vs sedentary).

EFFECTS OF NANDROLONE DECANOATE Medicine & Science in Sports & Exerciseா 1339 TABLE 1. Red blood cells parameters of the studied groups at the end of experiment; values are expressed as mean Ϯ SEM. T vs S ND vs Pl T⅐ND (10 ؍ TND (N (8 ؍ TP (N (10 ؍ SND (N (10 ؍ Variable SP (N Erythrocytes (1012⅐LϪ1) 7.86 Ϯ 0.18 8.67 Ϯ 0.22a 8.78 Ϯ 0.21a 8.53 Ϯ 0.24 NS NS * Hemoglobin (g⅐LϪ1) 156.00 Ϯ 1.31 158.50 Ϯ 2.06 163.13 Ϯ 1.98 160.00 Ϯ 2.49 * NS NS Hematocrit (L⅐LϪ1) 0.47 Ϯ 0.01 0.47 Ϯ 0.01 0.51 Ϯ 0.01 0.49 Ϯ 0.01 * NS NS MCV (fL) 59.70 Ϯ 0.98 55.04 Ϯ 0.72b,c 59.19 Ϯ 1.14 58.61 Ϯ 0.64 NS ** * T vs S, trained vs sedentary (main effect of training); ND vs Pl, ND treated vs placebo treated (main effect of ND treatment); T⅐ND, two-way interaction. * P Ͻ 0.05; ** P Ͻ 0.01; a P Ͻ 0.05 (in comparison with SP); bP Ͻ 0.01 (in comparison with SP); cP Ͻ 0.05 (in comparison with TP and TND). training used and/or the treatment with AAS did not impair trained rats at the end of experiment suggests that changes ú the natural growth of the rats, and this is consistent with the in VO2max cannot serve as an accurate predictor of SRE results reported by Van Zyl et al. (28). improvement (18). Thus, the combined effect of submaxi- To our knowledge, this is the first study to show that mal training and AAS treatment on SRE cannot be ex- ú anabolic androgenic steroid treatment combined with plained by changes in VO2max. endurance treadmill training in rats delays fatigue during Our results indicate that treatment with AAS does not submaximal exercise. Our results have shown clearly that change running economy to a greater degree than training ú supraphysiological doses of nandrolone decanoate ad- alone. Higher running economy (lower VO2 at a specific ministered together with submaximal treadmill training intensity of submaximal exercise) is considered an advan- improve the SRE of male rats better than the training tage in endurance sports as it leads to utilization of lower ú alone does. This was proved by the different magnitude percentage of VO2max (17). This increases the running speed ú of SRE improvement of the two trained groups subjected at equal %VO2max and improves sports achievements as- to a stable training identical in intensity and duration sessed by the time (speed) needed to run a specific distance ú during the treatment with AAS/placebo. These results even for trained athletes with similar values for VO2max ú ú corroborate the findings of a study on the combined effect (4,7). Our results for VO2submax presented as %VO2max of AAS and training on SRE of spontaneously running showed that submaximal training induced a better adapta- male rats (28). tion of the trained rats and lowered the degree of utilization In contrast to AAS effect on SRE, treatment with nan- of their oxygen capacity in comparison with the untrained drolone decanoate did not increase the maximal running rats subjected to exercise at the same absolute intensity. time to exhaustion to a greater extent than training alone. There is a clear tendency towards increasing the differences ú These different effects can be accounted for by the fact that in %VO2max between the untrained and trained rats with the performance SRE and maximal running time are dependent increase of exercise intensity. The absence of differences in ú on different mechanisms. Davies et al. (9) report that sprint %VO2max between the two trained groups in this experiment training in rats increases their maximal endurance and max- suggests that although AAS improve the SRE of trained rats, imal sprint speed, whereas it has no affect on muscle oxi- this might not improve performance assessed by the time dative capacity or SRE. Differences in the degree and rate of (speed) needed to run a definite distance in a greater degree change of both parameters in rats have been reported also in than the training alone. submaximal training on treadmill (18). A 6-wk treatment with AAS did not increase the blood These results, supporting previous research (1), show that oxygen carrying capacity of the untrained rats, nor did it AAS treatment does not increase the aerobic power either of increase that of the trained rats, which shows that the effect untrained or endurance trained animals. The values of AAS have on SRE cannot be due to the increase of blood ú VO2max we measured in the study are consistent with the oxygen capacity. Our findings agree with the results of data about the Wistar male rats in the methodological study studies conducted with humans (2) and trained horses (16) of Bedford et al. (5) and to the established time parameters in which at least 3 months of AAS treatment are required to ú of change in rats. No change of VO2max was found after 8 increase hemoglobin and/or red cell volume. As oxygen ú wk of treadmill training (18), but increases of 14Ð18% have carrying capacity is one of the factors determining VO2max been reported with 10Ð12 wk of training (18,22). The 4% (4) these data are consistent with the absence of differences ú ú increase of VO2max we established in this study at the in the values of VO2max we found between the TP and TND beginning of week 9 of training suggests that initial changes groups at the end of experiment. have been registered in this parameter. We only observed Our results show that AAS treatment can increase SRE the plateau phenomenon in three rats tested. There are other only in combination with endurance training. Although nan- ú authors reporting similar absence of plateau in the VO2max drolone decanoate failed to have any effects on SRE in test in part (5) or in all studied rats (18). untrained rats, the interaction with training can be inter- The training protocol in this study exerted different ef- preted as AAS speeding up the adaptation processes caused fects on the rate and extent of improvement in SRE and by the training itself. The combined effect of ND and ú VO2max. In the trained rats, SRE increased significantly as training on SRE is not related to changes in variables de- early as during the second week of training whereas the first termining O2 transport to the working muscles. Therefore, ú significant differences in VO2max were found only at the our findings suggest that the improvement of SRE is due to beginning of week 9 of experiment. The slight increase of the impact of AAS on exercise induced peripheral alter- ú VO2max in comparison with the threefold increase of SRE in ations in the skeletal muscles. It does seem that the im-

1340 Official Journal of the American College of Sports Medicine http://www.acsm-msse.org provement of SRE is not due to the higher skeletal muscle treatment with supraphysiological doses of nandrolone de- oxidative capacity because data from other studies suggest canoate, care should be taken when one extrapolates data that AAS treatment on endurance-trained male rats does not from animal models to humans. The abuse of high doses of increase the mitochondrial enzyme activity (24,28) and the AAS by athletes is associated with many somatic and psy- utilization of fats (13) in a greater degree than training chic adverse effects on health (20,29). alone. Although the physiological mechanisms for the AAS In conclusion, the present findings show that treatment induced increase of the submaximal running endurance can- with AAS administered in combination with submaximal not be determined from the data presented here, some po- exercise on a treadmill enhances the SRE of male rats to a tential mechanisms can be suggested. Data from recent greater degree than does the training alone. AAS does not ú studies show that nandrolone decanoate treatment in endur- increase VO2max and the oxygen carrying capacity and does ance treadmill-trained male rats improves contractile re- not improve running economy more than training alone; sponses of skeletal muscles (30) and may improve the therefore, these parameters cannot explain the improvement tolerance to exercise training by increasing the levels of of SRE. These results suggest AAS treatment effects other stress protein HSP72 in fast-twitch fibers (12) more than factors not measured in this study to induce adaptations training alone. Further studies are necessary to investigate leading to the increase of submaximal running endurance. whether these effects of nandrolone decanoate on skeletal muscles of trained male rats are related to the improvement The authors thank Dr. P. Pavlov, Department of Clinical Chem- istry, Medical University Plovdiv, for his assistance with the study. of SRE. Although the present investigation demonstrates the This study was supported by grant 05/2001-02 from Medical improvement of SRE of endurance-trained subjects after University Plovdiv, Plovdiv, Bulgaria.

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