Sex differences in time to fatigue at 100% VO2 peak when normalized for fat free mass.

The purpose of this investigation was to compare sexes for time to fatigue at 100% VO(2)peak in recreationally trained individuals. Ten men (age: 23.4 ± 1.8; height: 177 ± 6.7; body mass: 83.8 ± 11.3; ± SD) and nine women (age: 25.0 ± 2.5; height: 165.6 ± 5.5; body mass: 62.7 ± 6.7) participated in this investigation after providing written consent. One week after assessing VO(2)peak, subjects exercised on an electrically braked cycle ergometer at 100% of VO(2)peak until fatigue. The time taken to fatigue was 48.9% longer for men than women (274 ± 13s vs. 184 ± 14s; p < 0.001, for men and women, respectively). When normalized for fat free mass (ffm; s/kg ffm) no significant differences between men and women were observed (3.99 ± 0.21s/kg ffm vs. 3.72 ± 0.28s/kg ffm for men and women, respectively, p = 0.431). The difference in fatigability between the sexes at this exercise intensity is to a large degree related to the difference in fat free mass.

Timing of the initial muscle biopsy does not affect the measured muscle protein fractional synthesis rate during basal, postabsorptive conditions.

The muscle protein fractional synthesis rate (FSR) is determined by monitoring the incorporation of an amino acid tracer into muscle protein during a constant-rate intravenous tracer infusion. Commonly two sequential muscle biopsies are obtained some time after starting the tracer infusion. However, other protocols, including those with an initial biopsy before starting the tracer infusion to measure the background enrichment and those with only a single biopsy after several hours of tracer infusion have been used. To assess the validity of these approaches, we compared the muscle protein FSR obtained by calculating the difference in [ring-(2)H(5)]phenylalanine and [5,5,5-(2)H(3)]leucine incorporation into muscle protein at approximately 3.5 h after starting the tracer infusion and 1) at 60 min; 2) before starting the tracer infusion (background enrichment); 3) a population average muscle protein background enrichment; and 4) by measuring the tracer incorporation into muscle protein at approximately 3.5 h assuming essentially no background enrichment. Irrespective of the tracer used, the muscle protein FSR calculated from the difference in the muscle protein labeling several hours after starting the tracer infusion and either the labeling at 60 min or the background enrichment were not different (e.g., 0.049 +/- 0.007%/h vs. 0.049 +/- 0.007%/h, respectively, with [(2)H(5)]phenylalanine; P = 0.99). However, omitting the initial biopsy and assuming no background enrichment yielded average FSR values that were approximately 15% (with [(2)H(5)]phenylalanine) to 80% (with [(2)H(3)]leucine) greater (P < or = 0.059); using a population average background enrichment reduced the difference to approximately 3% (P = 0.76) and 22% (P = 0.52) with [(2)H(5)]phenylalanine and [(2)H(3)]leucine, respectively. We conclude that during basal, postabsorptive conditions, valid muscle protein FSR values can be obtained irrespective of the timing of the initial biopsy so long as the protein labeling in two sequential biopsies is measured whereas the single biopsy approach should be avoided.

Dehydroepiandrosterone replacement therapy in older adults: 1- and 2-y effects on bone.

BACKGROUND: Age-related reductions in serum dehydroepiandrosterone (DHEA) concentrations may be involved in bone mineral density (BMD) losses. OBJECTIVE: The objective was to determine whether DHEA supplementation in older adults improves BMD when co-administered with vitamin D and calcium. DESIGN: In year 1, a randomized trial was conducted in which men (n = 55) and women (n = 58) aged 65-75 y took 50 mg/d oral DHEA supplements or placebo. In year 2, all participants took open-label DHEA (50 mg/d). During both years, all participants received vitamin D (16 microg/d) and calcium (700 mg/d) supplements. BMD was measured by using dual-energy X-ray absorptiometry. Concentrations of hormones and bone turnover markers were measured in serum. RESULTS: In men, no difference between groups occurred in any BMD measures or in bone turnover markers during year 1 or year 2. The free testosterone index and estradiol increased in the DHEA group only. In women, spine BMD increased by 1.7 +/- 0.6% (P = 0.0003) during year 1 and by 3.6 +/- 0.7% after 2 y of supplementation in the DHEA group; however, in the placebo group, spine BMD was unchanged during year 1 but increased to 2.6 +/- 0.9% above baseline during year 2 after the crossover to DHEA. Hip BMD did not change. Testosterone, estradiol, and insulin-like growth factor 1 increased in the DHEA group only. In both groups, serum concentrations of bone turnover markers decreased during year 1 and remained low during year 2, but did not differ between groups. CONCLUSION: DHEA supplementation in older women, but not in men, improves spine BMD when co-administered with vitamin D and calcium. This trial was registered at clinicaltrials.gov as NCT00182975.

Exercise but not diet-induced weight loss decreases skeletal muscle inflammatory gene expression in frail obese elderly persons.

Many obese elderly persons have impaired physical function associated with an increased chronic inflammatory response. We evaluated 12 wk of exercise (aerobic and resistance) or 12 wk of weight loss (approximately 7% reduction) on skeletal muscle mRNAs for toll-like receptor-4 (TLR-4), mechanogrowth factor (MGF), TNF-alpha, and IL-6 in 16 obese (body mass index 38+/-2 kg/m2) older (69+/-1 yr) physically frail individuals. Vastus lateralis muscle biopsies were obtained at 0 and 12 wk and analyzed by real-time RT-PCR. Body composition was assessed by dual-energy x-ray absorptiometry. Body weight decreased (-7.5+/-1.2 kg, P=0.001) in the weight loss group but not in the exercise group (-0.3+/-0.8 kg, P=0.74). Fat-free mass (FFM) decreased (-2.9+/-0.6 kg, P=0.010) in the weight loss group and increased (1.6+/-0.6 kg, P=0.03) in the exercise group. Exercise resulted in a 37% decrease in TLR-4 mRNA (P<0.05) while weight loss had no significant effect. Additionally, exercise led to a significant (50%) decrease in IL-6 and TNF-alpha mRNA (P<0.05) while weight loss had no effect. Exercise increased MGF mRNA (approximately 2 fold, P<0.05), but weight loss had no effect. In conclusion, exercise but not weight loss had a beneficial effect on markers of muscle inflammation and anabolism in frail obese elderly individuals.

Physiological basis of fatigue.

This work summarizes our knowledge of the physiological basis of fatigue and the effects of exercise and pharmacological interventions on fatigue. Fatigue may be defined as physical and/or mental weariness resulting from exertion, that is, an inability to continue exercise at the same intensity with a resultant deterioration in performance. The concept of deconditioning in patients is discussed as well as the implications for their rehabilitation and exercise. Because fatigue may result from a number of causes, including loss of muscle mass, deconditioning, nutritional deficiencies, oxygen delivery, and anemia, it should be treated comprehensively. Antifatigue therapy should be the standard of care for most chronic conditions associated with fatigue.

Effects of megestrol acetate on pituitary function and end-organ hormone secretion: a post hoc analysis of serum samples from a 12-week study in healthy older men.

BACKGROUND: Megestrol acetate (MA) is a synthetic progestin commonly used to promote weight gain in malnourished older individuals. In small studies, MA administration has been associated with reduced serum cortisol concentrations in patients with cancer or AIDS. The impact of MA on the pituitary secretion of adrenocorticotropic hormone (ACTH) and other hormones is unclear, and the prevalence and extent of hypocortisolemia in older individuals after MA treatment is unknown. A randomized, placebo-controlled study of the effects of testosterone (T) and resistance training (RT) on body composition after MA administration in older men has been reported previously. OBJECTIVE: The purpose of this post hoc analysis was to examine the effect of 12 weeks of MA on pituitary function and end-organ hormone secretion in healthy older individuals using frozen serum samples from that study. METHODS: The previous study was conducted at the Department of Geriatrics, Donald W. Reynolds Center on Aging and the General Clinical Research Center at The University of Arkansas for Medical Sciences, Little Rock, Arkansas. Healthy male volunteers aged 60 to 85 years were recruited from the center and were randomly assigned to 1 of 4 study groups: RT + T, T, RT + placebo (P), or P. Subjects enrolled in the RT groups underwent supervised upper- and lower-body strength-training exercises 3 d/wk at 80% of 1 repetition maximum. Subjects in the groups to receive T received injections of testosterone enanthate 100 mg i.m. QW for 12 weeks. Subjects receiving P were given 1-mL saline injections i.m. QW for 12 weeks. All subjects received MA 800 mg p.o. QD concurrently for 12 weeks. For the present analysis, serum concentrations of the pituitary hormones follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), ACTH, prolactin (PRL), and luteinizing hormone (LH), as well as the end-organ hormones estradiol (E2), cortisol, free T4, and T, were measured in samples obtained at baseline (week 0) and after 12 weeks of MA treatment. RESULTS: Serum samples from 21 men (mean [SD]age, 67.0 [7.3]years; mean [SD] body mass index, 23.1 [10.4] kg/m2; mean [SD] percentage of body fat, 22.5% [8.8%]; RT + T, T, RT + P, and P groups, n = 4, 5, 6, and 6 subjects, respectively) were available from the original study. The mean percentage changes from baseline in serum pituitary hormone concentrations after 12 weeks of MA administration were as follows: TSH, -14.7%; ACTH, -89.5%; PRL, 162.2%; and LH, -49.0%; (P = 0.03, <0.001, <0.001, and <0.001, respectively). The mean (SD) percentage changes from baseline in serum end-organ hormone concentrations with MA at 12 weeks were as follows: E2, 181.6%; and cortisol, -90.8% (both, P < 0.001). In the P and RT + P groups, the mean percentage changes from baseline in T were -84% and -85%, respectively (both, P < 0.001). FSH and free T4 concentrations were not significantly changed. CONCLUSIONS: This analysis of serum samples from healthy older men suggests that MA administration significantly affected the secretion of several pituitary hormones and end-organ hormone synthesis. Most notably, ACTH secretion and serum cortisol levels were statistically significantly suppressed in 20 of 21 subjects, without the development of clinically significant adrenal suppression.

Effects of megestrol acetate on circulating interleukin-15 and interleukin-18 concentrations in healthy elderly men.

BACKGROUND: Interleukin-15 (IL-15) and interleukin-18 (IL-18) are potential regulators of body composition in humans. The authors previously reported that megestrol acetate ingestion causes a large accumulation of adipose tissue and reduces muscle mass. Therefore, the purpose of this investigation was to evaluate the effects of megestrol acetate ingestion on circulating IL-15 and IL-18 concentrations in healthy elderly men. METHODS: All participants received 800 mg of megestrol acetate per day during this 12-week study. Megestrol acetate was combined with testosterone injections (100 mg/week), placebo injections, resistance training, or resistance training and testosterone. Resting IL-15 and IL-18 concentrations were measured by enzyme-linked immunosorbent assay at week 0 (pre), week 6 (mid), and week 12 (post). RESULTS: The time effect for IL-15 was significant (p = .0008), with the mid and post values being significantly greater than the pre value. The change in IL-15 concentration was not significantly related to the change in muscle mass (r = -.31; p > .05), nor was it related to the change in fat mass (r =.17; p > .05). Differences among groups or over time were not significant for IL-18, nor were correlations between pre body weight and pre IL-18 (r = -.03), pre fat mass and pre IL-18 (r = .14), or the change in fat mass and the change in IL-18 (r = -.07). CONCLUSIONS: IL-15 was increased as a result of megestrol acetate ingestion; however, megestrol acetate did not affect circulating IL-18 concentrations, and the change in IL-18 did not correlate with any body composition variables.

Macronutrient considerations for the sport of bodybuilding.

Participants in the sport of bodybuilding are judged by appearance rather than performance. In this respect, increased muscle size and definition are critical elements of success. The purpose of this review is to evaluate the literature and provide recommendations regarding macronutrient intake during both 'off-season' and 'pre-contest' phases. Body builders attempt to increase muscle mass during the off-season (no competitive events), which may be the great majority of the year. During the off-season, it is advantageous for the bodybuilder to be in positive energy balance so that extra energy is available for muscle anabolism. Additionally, during the off-season, adequate protein must be available to provide amino acids for protein synthesis. For 6-12 weeks prior to competition, body builders attempt to retain muscle mass and reduce body fat to very low levels. During the pre-contest phase, the bodybuilder should be in negative energy balance so that body fat can be oxidised. Furthermore, during the pre-contest phase, protein intake must be adequate to maintain muscle mass. There is evidence that a relatively high protein intake (approximately 30% of energy intake) will reduce lean mass loss relative to a lower protein intake (approximately 15% of energy intake) during energy restriction. The higher protein intake will also provide a relatively large thermic effect that may aid in reducing body fat. In both the off-season and pre-contest phases, adequate dietary carbohydrate should be ingested (55-60% of total energy intake) so that training intensity can be maintained. Excess dietary saturated fat can exacerbate coronary artery disease; however, low-fat diets result in a reduction in circulating testosterone. Thus, we suggest dietary fats comprise 15-20% of the body builders' off-season and pre-contest diets. Consumption of protein/amino acids and carbohydrate immediately before and after training sessions may augment protein synthesis, muscle glycogen resynthesis and reduce protein degradation. The optimal rate of carbohydrate ingested immediately after a training session should be 1.2 g/kg/hour at 30-minute intervals for 4 hours and the carbohydrate should be of high glycaemic index. In summary, the composition of diets for body builders should be 55-60% carbohydrate, 25-30% protein and 15-20% of fat, for both the off-season and pre-contest phases. During the off-season the diet should be slightly hyperenergetic (approximately 15% increase in energy intake) and during the pre-contest phase the diet should be hypoenergetic (approximately 15% decrease in energy intake).

Albuterol improves response to levodopa and increases skeletal muscle mass in patients with fluctuating Parkinson disease.

Animal studies indicate that beta(2)-adrenergic receptor agonists enhance transport of levodopa across the blood-brain barrier. Preliminary studies showed improved response to levodopa in patients with Parkinson disease (PD) who were given albuterol as adjunctive therapy. Beta(2)-adrenergic agonists may offer additional benefits to PD patients via their skeletal muscle anabolic effects, particularly those who experience decreased muscle strength and weight loss. Nondemented, fluctuating PD patients receiving levodopa but not experiencing severe dyskinesias underwent the following tests at baseline and 14 weeks after treatment with albuterol sulfate (4 mg four times a day, orally): Unified Parkinson's Disease Rating Scale motor, tapping, and stand-walk-sit tests every 30 minutes between 8 am and 5 pm; body composition analyses using whole-body plethysmography and computed tomography of the thigh; muscle strength tests; and the Parkinson's Disease Questionnaire (PDQ-39). Results were analyzed using paired t-tests (2 tailed), repeated-measures analysis of variance, and the Wilcoxon signed-rank test. Seven of 8 enrolled patients completed the study; 1 patient withdrew because of headache and anxiety. The area under the curve for all-day UPDRS motor scores improved by 9.8 +/- 9.1% (mean +/- standard deviation; P < 0.05) and tapping improved by 7.6 +/- 8.1% (P < 0.05). The effect was more pronounced when only the response to the first levodopa dose (area under the curve, 8-11 am) was analyzed: 13.0 +/- 9.8% and 9.8 +/- 9.6% respectively. Thigh muscle cross-sectional area increased significantly as measured by computed tomography (5.3 +/- 3.2%, P < 0.01), as did fat-free mass by whole-body plethysmography combined with total-body water determination (9.5 +/- 2.9%, P < 0.05). There was no significant improvement in the stand-walk-sit test, muscle strength tests, other UPDRS sections, daily OFF time, or PDQ-39. Four patients were rated as having a mild global improvement (+1 point) on a -3 to +3-point scale, and 3 of them chose to continue albuterol beyond the termination of the study. The mean heart rate increased from 78.3 +/- 9.3 beats/minute to 85.6 +/- 8.7 beats/minute (P < 0.05). No laboratory abnormalities or electrocardiographic changes were induced by albuterol in any subject. This open-label pilot study suggests that albuterol increases muscle mass and improves the therapeutic response to levodopa in patients with fluctuating PD. A double-blind, placebo-controlled study is needed to confirm the effects and safety profile of beta(2)-agonists in PD.

Influence of creatine monohydrate ingestion on muscle metabolites and intense exercise capacity in individuals with multiple sclerosis.

OBJECTIVE: To evaluate the effectiveness of ingesting creatine monohydrate in elevating intramuscular creatine stores and improving exercise capacity in individuals with multiple sclerosis (MS). DESIGN: Randomized, double-blind, placebo-controlled, pre-posttrial. SETTING: A university-based exercise physiology laboratory. PARTICIPANTS: Sixteen individuals with relapsing-remitting MS (median Expanded Disability Status Scale score, 4.75; range, 1.5-6.0). INTERVENTION: Eight individuals with MS were randomized to the creatine group (20g/d of creatine monohydrate for 5d), and 8 others were randomized to the placebo group. Needle biopsies were performed on the vastus lateralis at rest before and after treatment. Subjects performed 3 bouts of 30 maximal knee extensions and flexions at 180 degrees /s with 1 minute of recovery between bouts before and after treatment. MAIN OUTCOME MEASURES: Intramuscular total creatine, phosphocreatine, free creatine, and total work output. RESULTS: Creatine ingestion did not significantly elevate intramuscular total creatine, phosphocreatine, or free creatine or improve total work production. CONCLUSION: Creatine ingestion had no significant effect on muscle creatine stores or high-intensity exercise capacity in individuals with MS.

Megestrol acetate-induced weight gain does not negatively affect blood lipids in elderly men: effects of resistance training and testosterone replacement.

BACKGROUND: Megestrol acetate (MA) has been used to stimulate weight gain in elderly populations, with the majority of the weight gain being adipose tissue. Because of the increased energy intake and adipose tissue accrual with MA, it may have a negative effect on circulating lipids. Thus, in this study we examined the effects of MA--alone and in combination with resistance training and/or testosterone replacement--on blood lipids. METHODS: All subjects (n = 28) received MA and were randomly assigned to one of four groups: 1) placebo (P) injections, 2) resistance training and P (RT+P), 3) weekly injections of testosterone (T; 100 mg/week), or 4) RT and T (RT+T). RESULTS: A significant time effect was observed for total cholesterol (p = 0.0006) and high density lipoprotein (HDL) cholesterol (p = .0003) with the mid and post time points being significantly lower than the pre time points for both variables. For the total cholesterol to HDL ratio, no significant differences between groups or over time (time effect: ) were observed. For triglycerides, there tended to be a time effect (p = .061), with the mid and post time points being lower than the pre time point; however, this effect was not statistically significant. CONCLUSIONS: Because it appears from our data that MA does not cause adverse blood lipid changes, the decision to use it should be based on other factors.

Ibuprofen and acetaminophen: effect on muscle inflammation after eccentric exercise.

PURPOSE: We examined the influence of ibuprofen and acetaminophen on muscle neutrophil and macrophage concentrations after novel eccentric contractions. METHODS: Twenty-four males (25 +/- 3 yr) were divided into three groups that received the maximal over-the-counter dose of either ibuprofen (1200 mg x d-1), acetaminophen (4000 mg x d-1), or a placebo after eccentric contractions of the knee extensors. Biopsies from the vastus lateralis were taken before and 24 h after exercise. Inflammatory cells were quantified in muscle cross-sections using immunohistochemistry. RESULTS: Macrophage concentrations were elevated by 1.5- to 2.5-fold (P < 0.05) at 24 h postexercise relative to preexercise concentrations, whereas neutrophil concentrations were not significantly elevated. Muscle inflammatory cell concentrations were unaffected by treatment with ibuprofen or acetaminophen when compared with placebo. CONCLUSIONS: Maximal over-the-counter doses of ibuprofen or acetaminophen, when administered therapeutically, do not affect muscle concentrations of neutrophils or macrophages 24 h after a novel bout of eccentric contractions.

Effects of testosterone replacement and/or resistance training on interleukin-6, tumor necrosis factor alpha, and leptin in elderly men ingesting megestrol acetate: a randomized controlled trial.

BACKGROUND: Megestrol acetate (MA) has been used to stimulate weight gain in elderly populations with the majority of the gain being adipose tissue. Significant inverse correlations have been reported between weight gain with MA and reductions in circulating the tumor necrosis factor (TNF) alpha receptors. In addition, MA has been shown to reduce circulating interleukin 6 (IL-6) concentrations. We attempted to increase gains in fat-free mass with MA using resistance training and/or testosterone replacement and examined the effects on circulating IL-6, TNF alpha, and leptin in elderly men. METHODS: All subjects received MA and were randomly assigned to one of these four groups: placebo (P) injections; resistance training and P (RT+P); weekly injections of testosterone (T; 100 mg/wk); or RT and T (RT+T). Cytokines were measured by enzyme-linked immunosorbent assay Preinterventions, Midinterventions, and after 12 weeks of the interventions (Post). RESULTS: IL-6 decreased ( p =.03) over time for the T and P groups when compared to the RT+T and RT+P groups. A time effect ( p =.013) was observed for TNF alpha with Mid and Post both being lower than Pre. A hormone by time interaction ( p =.03) was observed for plasma leptin with individuals not on T exhibiting higher concentrations Post than those individuals on T. A positive correlation was observed (r =.60; p <.05) between changes in fat mass and the change in leptin. CONCLUSION: IL-6 was reduced by MA except when RT was undertaken; TNF alpha was reduced over time regardless of group; leptin was higher in individuals not on T than those on T; and the change in plasma leptin was correlated with the change in fat mass.

Body composition in ambulatory women with multiple sclerosis.

OBJECTIVE: To compare whole-body fat mass and fat-free mass (FFM) in ambulatory patients with multiple sclerosis (MS) and control subjects without MS. DESIGN: Nonrandomized controlled trial or cross-sectional study. SETTING: An exercise physiology laboratory at a medical school. PARTICIPANTS: Seventeen ambulatory patients with MS and 12 control subjects (all subjects were women). The median Expanded Disability Status Scale (EDSS) score was 4.0 for the individuals with MS. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Whole-body percentage of fat-free mass (%FFM), percentage of body fat (%BF), FFM, and fat mass. RESULTS: A significant difference in age was observed between the groups; thus, age was used as a covariate in the body composition analyses. No significant differences were observed between the groups in %BF: 32.5+/-13.9 and 27.8+/-5.6 (P=.54) for MS and controls, respectively, or %FFM, 67.1+/-14.9 and 71.3+/-12.4 (P=.42) for MS and controls, respectively. For individuals with MS, no significant relation was observed between EDSS score and %BF (P=.24) or between EDSS score and %FFM (P=.24). CONCLUSION: No significant differences were observed in body composition between ambulatory MS patients and controls. Furthermore, the EDSS score was not a significant predictor of %BF or %FFM for people with MS.

The effects of a pre-exercise feeding with or without fungal carbohydrases (Carbogen) on blood parameters and exercise performance in elite cyclists: a preliminary study.

The effect of fungal carbohydrases (Carbogen[C]) consumed with a meal replacement bar (MBR) on glucose metabolism and exercise performance was determined in 5 male competitive cyclists. After a 12-hour fast, subjects performed two 60-min cycling bouts at 80% VO2max followed by a time-to-exhaustion (TE) ride at 100% VO2max. One hour prior to each cycling bout, subjects ingested a MRB + 160-mg C or 160-mg CaCO3 placebo (PL) in a double-blind, counterbalanced fashion. Blood was drawn for determination of glucose, insulin, and lactate at: fasting, 1 hour post-feeding, minutes 30 and 60 of exercise, and after TE. Two-way ANOVA revealed a significant (p <.05) treatment and time effect for glucose, with C being higher than PL. Interaction effects were observed for insulin and lactate. An increase in TE (min) at 100% VO2max was observed in the C versus PL trial (6.3 3.4 vs. 4.4 2.9, p <.001). A MRB+C may benefit cyclists due to increased BG and improved exercise performance.

Fatigue during high-intensity intermittent exercise: application to bodybuilding.

Resistance exercise is an activity performed by individuals interested in competition, those who wish to improve muscle mass and strength for other sports, and for individuals interested in improving their strength and physical appearance. In this review we present information suggesting that phosphocreatine depletion, intramuscular acidosis and carbohydrate depletion are all potential causes of the fatigue during resistance exercise. In addition, recommendations are provided for nutritional interventions, which might delay muscle fatigue during this type of activity.

Effects of testosterone replacement and/or resistance exercise on the composition of megestrol acetate stimulated weight gain in elderly men: a randomized controlled trial.

Megestrol acetate (MA) (Bristol-Myers Squibb Co., Princeton, NJ) increases weight gain in AIDS and cancer patients and in age-related cachexia; however, the weight gain is predominately fat. We determined if adding resistance exercise and/or testosterone (T) replacement to MA administration would result in a more favorable body composition change than MA alone. Thirty older men (aged 67.0 +/- 5.8) completed this 12-wk study. All subjects received MA and were randomly assigned to one of the following groups: placebo (P) injections, resistance training (RT) and P (RT + P), weekly injections of T (100 mg/wk) or, RT and T (RT + T). The mean increase in body weight for all groups combined was 3.8 kg (P < 0.0001), but this increase was not different between groups. There was a significant interaction for the change in thigh muscle cross-sectional area (P = 0.0006). Thigh muscle cross-sectional area was significantly reduced from baseline by 5.20 [1.62] cm(2) (P = 0.05) in P which was not prevented in T [-4.44 (1.66) cm(2) from baseline; P = 0.04]. RT prevented this decline [+0.61 (1.41) cm(2) from baseline]. Muscle cross-sectional area increased 4.51 (1.69) cm(2) from baseline in RT + T (P = 0.002 vs. P and P = 0.002 vs. T). Despite significant weight gain, MA appears to have an antianabolic effect on muscle size even when combined with T replacement. Resistance exercise attenuated this reduction in muscle mass and when combined with T had an anabolic effect on muscle mass.