Effects of testosterone enanthate on aggression, risk-taking, competition, mood, and other cognitive domains during 28 days of severe energy deprivation.

RATIONALE: Behavioral effects of testosterone depend on dose, acute versus sustained formulation, duration of administration, personality, genetics, and endogenous levels of testosterone. There are also considerable differences between effects of endogenous and exogenous testosterone. OBJECTIVES: This study was the secondary behavioral arm of a registered clinical trial designed to determine if testosterone protects against loss of lean body mass and lower-body muscle function induced by a severe energy deficit typical of sustained military operations. METHODS: Behavioral effects of repeated doses of testosterone on healthy young men whose testosterone was reduced by severe energy deficit were examined. This was a double-blind, placebo-controlled, between-group study. Effects of four weekly intramuscular injections of testosterone enanthate (200 mg/week, N = 24) or matching placebo (N = 26) were evaluated. Determination of sample size was based on changes in lean body mass. Tasks assessing aggression, risk-taking, competition, social cognition, vigilance, memory, executive function, and mood were repeatedly administered. RESULTS: During a period of artificially induced, low testosterone levels, consistent behavioral effects of administration of exogenous testosterone were not observed. CONCLUSIONS: Exogeneous testosterone enanthate (200 mg/week) during severe energy restriction did not reliably alter the measures of cognition. Study limitations include the relatively small sample size compared to many studies of acute testosterone administration. The findings are specific to healthy males experiencing severe energy deficit and should not be generalized to effects of other doses, formulations, or acute administration of endogenous testosterone or studies conducted with larger samples using tests of cognitive function designed to detect specific effects of testosterone.

Effects of Episodic Food Insecurity on Psychological and Physiological Responses in African American Women With Obesity (RESPONSES): Protocol for a Longitudinal Observational Cohort Study.

BACKGROUND: Food insecurity is a risk factor for multiple chronic diseases, including obesity. Importantly, both food insecurity and obesity are more prevalent in African American women than in other groups. Furthermore, food insecurity is considered a cyclic phenomenon, with episodes of food adequacy (ie, enough food to eat) and food shortage (ie, not enough food to eat). More research is needed to better understand why food insecurity is linked to obesity, including acknowledging the episodic nature of food insecurity as a stressor and identifying underlying mechanisms. OBJECTIVE: The objective of this study is to investigate the episodic nature of food insecurity as a stressor via responses in body weight and psychological and physiological parameters longitudinally and do so in a health-disparate population-African American women. METHODS: We enrolled 60 African American women (food-insecure cohort: n=30, 50%; food-secure cohort: n=30, 50%) aged 18-65 years with obesity (BMI 30-50 kg/m2) to measure (1) daily body weight remotely over 22 weeks and (2) psychological and physiological parameters via clinic assessments at the beginning and end of the 22-week study. Furthermore, we are assessing episodes of food insecurity, stress, hedonic eating, and appetite on a weekly basis. We hypothesize that food-insecure African American women with obesity will demonstrate increased body weight and changes in psychological and physiological end points, whereas food-secure African American women with obesity will not. We are also examining associations between changes in psychological and physiological parameters and changes in body weight and performing a mediation analysis on the psychological parameters assessed at the study midpoint. Psychological questionnaires are used to assess stress; executive function, decision-making, and motivation; and affect and nonhomeostatic eating. Physiological measurements are used to evaluate the levels of cortisol, dehydroepiandrosterone-sulfate (DHEA-S), C-reactive protein, thyroid hormones, blood glucose, glycated hemoglobin, and insulin, as well as allostatic load. RESULTS: This study has completed participant recruitment (n=60). At the time of study enrollment, the mean age of the participants was almost 47 (SD 10.8) years, and they had a mean BMI of 39.6 (SD 5.31) kg/m2. All data are anticipated to be collected by the end of 2023. CONCLUSIONS: We believe that this is the first study to examine changes in body weight and psychological and physiological factors in food-insecure African American women with obesity. This study has significant public health implications because it addresses the cyclic nature of food insecurity to identify underlying mechanisms that can be targeted to mitigate the adverse relationship between food insecurity and obesity and reduce health disparities in minority populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT05076487; https://clinicaltrials.gov/study/NCT05076487. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52193.

A scalable, virtual weight management program tailored for adults with type 2 diabetes: effects on glycemic control.

BACKGROUND: The objective was to test the efficacy of a scalable, virtually delivered, diabetes-tailored weight management program on glycemic control in adults with type 2 diabetes (T2D). METHODS: This was a single arm, three-site clinical trial. Participants had baseline HbA1c between 7-11% and BMI between 27-50 kg/m2. Primary outcome was change in HbA1c at 24 weeks. Secondary outcomes were changes in body weight, waist circumference, the Diabetes Distress Scale (DDS), quality of life (IWQOL-L), and hunger (VAS). Generalized linear effects models were used for statistical analysis. RESULTS: Participants (n = 136) were 56.8 ± 0.8 y (Mean ± SEM), 36.9 ± 0.5 kg/m2, 80.2% female, 62.2% non-Hispanic white. Baseline HbA1c, weight, and total DDS score were 8.0 ± 0.09%, 101.10 ± 1.47 kg, and 2.35 ± 0.08, respectively. At week 24, HbA1c, body weight, and total DDS decreased by 0.75 ± 0.11%, 5.74 ± 0.50%, 0.33 ± 0.10 units, respectively (all p < 0.001). Also, at week 24, quality of life increased by 9.0 ± 1.2 units and hunger decreased by 14.3 ± 2.4 units, (both p < 0.0001). CONCLUSIONS: The scalable, virtually delivered T2D-tailored weight management program had favorable and clinically meaningful effects on glycemic control, body weight, and psychosocial outcomes.

Bioelectrical impedance phase angle is associated with physical performance before but not after simulated multi-stressor military operations.

Physical performance decrements observed during multi-stressor military operations may be attributed, in part, to cellular membrane dysfunction, which is quantifiable using phase angle (PhA) derived from bioelectrical impedance analysis (BIA). Positive relationships between PhA and performance have been previously reported in cross-sectional studies and following longitudinal exercise training programs, but whether changes in PhA are indicative of acute decrements in performance during military operations is unknown. Data from the Optimizing Performance for Soldiers II study, a clinical trial examining the effects of exogenous testosterone administration on body composition and performance during military stress, was used to evaluate changes in PhA and their associations with physical performance. Recreationally active, healthy males (n = 34; 26.6 ± 4.3 years; 77.9 ± 12.4 kg) were randomized to receive testosterone undecanoate or placebo before a 20-day simulated military operation, which was followed by a 23-day recovery period. PhA of the whole-body (Whole) and legs (Legs) and physical performance were measured before (PRE) and after (POST) the simulated military operation as well as in recovery (REC). Independent of treatment, PhAWhole and PhALegs decreased from PRE to POST (p < 0.001), and PhALegs , but not PhAWhole , remained lower at REC than PRE. PhAWhole at PRE and REC were associated with vertical jump height and Wingate peak power (p < 0.001-0.050), and PhAWhole at PRE was also associated with 3-RM deadlift mass (p = 0.006). However, PhA at POST and changes in PhA from PRE to POST were not correlated with any performance measure (p > 0.05). Additionally, PhA was not associated with aerobic performance at any timepoint. In conclusion, reduced PhA from PRE to POST provides indirect evidence of cellular membrane disruption. Associations between PhA and strength and power were only evident at PRE and REC, suggesting PhA may be a useful indicator of strength and power, but not aerobic capacity, in non-stressed conditions, and not a reliable indicator of physical performance during severe physiological stress.

Metabolic Adaptations and Substrate Oxidation are Unaffected by Exogenous Testosterone Administration during Energy Deficit in Men.

INTRODUCTION/PURPOSE: The effects of testosterone on energy and substrate metabolism during energy deficit are unknown. The objective of this study was to determine the effects of weekly testosterone enanthate (TEST; 200 mg·wk -1 ) injections on energy expenditure, energy substrate oxidation, and related gene expression during 28 d of energy deficit compared with placebo (PLA). METHODS: After a 14-d energy balance phase, healthy men were randomly assigned to TEST ( n = 24) or PLA ( n = 26) for a 28-d controlled diet- and exercise-induced energy deficit (55% below total energy needs by reducing energy intake and increasing physical activity). Whole-room indirect calorimetry and 24-h urine collections were used to measure energy expenditure and energy substrate oxidation during balance and deficit. Transcriptional regulation of energy and substrate metabolism was assessed using quantitative reverse transcription-polymerase chain reaction from rested/fasted muscle biopsy samples collected during balance and deficit. RESULTS: Per protocol design, 24-h energy expenditure increased ( P < 0.05) and energy intake decreased ( P < 0.05) in TEST and PLA during deficit compared with balance. Carbohydrate oxidation decreased ( P < 0.05), whereas protein and fat oxidation increased ( P < 0.05) in TEST and PLA during deficit compared with balance. Change (∆; deficit minus balance) in 24-h energy expenditure was associated with ∆activity factor ( r = 0.595), but not ∆fat-free mass ( r = 0.147). Energy sensing (PRKAB1 and TP53), mitochondria (TFAM and COXIV), fatty acid metabolism (CD36/FAT, FABP, CPT1b, and ACOX1) and storage (FASN), and amino acid metabolism (BCAT2 and BCKHDA) genes were increased ( P < 0.05) during deficit compared with balance, independent of treatment. CONCLUSIONS: These data demonstrate that increased physical activity and not exogenous testosterone administration is the primary determinate of whole-body and skeletal muscle metabolic adaptations during diet- and exercise-induced energy deficit.

Metabolomics of testosterone enanthate administration during severe-energy deficit.

INTRODUCTION: Testosterone administration attenuates reductions in total body mass and lean mass during severe energy deficit (SED). OBJECTIVES: This study examined the effects of testosterone administration on the serum metabolome during SED. METHODS: In a double-blind, placebo-controlled clinical trial, non-obese men were randomized to receive 200-mg testosterone enanthate/wk (TEST) (n = 24) or placebo (PLA) (n = 26) during a 28-d inpatient, severe exercise- and diet-induced energy deficit. This study consisted of three consecutive phases. Participants were free-living and provided a eucaloric diet for 14-d during Phase 1. During Phase 2, participants were admitted to an inpatient unit, randomized to receive testosterone or placebo, and underwent SED for 28-d. During Phase 3, participants returned to their pre-study diet and physical activity habits. Untargeted metabolite profiling was conducted on serum samples collected during each phase. Body composition was measured using dual-energy X-ray absorptiometry after 11-d of Phase 1 and after 25-d of Phase 2 to determine changes in fat and lean mass. RESULTS: TEST had higher (Benjamini-Hochberg adjusted, q < 0.05) androgenic steroid and acylcarnitine, and lower (q < 0.05) amino acid metabolites after SED compared to PLA. Metabolomic differences were reversed by Phase 3. Changes in lean mass were associated (Bonferroni-adjusted, p < 0.05) with changes in androgenic steroid metabolites (r = 0.42-0.70), acylcarnitines (r = 0.37-0.44), and amino acid metabolites (r = - 0.36-- 0.37). Changes in fat mass were associated (p < 0.05) with changes in acylcarnitines (r = - 0.46-- 0.49) and changes in urea cycle metabolites (r = 0.60-0.62). CONCLUSION: Testosterone administration altered androgenic steroid, acylcarnitine, and amino acid metabolites, which were associated with changes in body composition during SED.

Testosterone undecanoate administration prevents declines in fat-free mass but not physical performance during simulated multi-stressor military operations.

Male military personnel conducting strenuous operations experience reduced testosterone concentrations, muscle mass, and physical performance. Pharmacological restoration of normal testosterone concentrations may attenuate performance decrements by mitigating muscle mass loss. Previously, administering testosterone enanthate (200 mg/wk) during 28 days of energy deficit prompted supraphysiological testosterone concentrations and lean mass gain without preventing isokinetic/isometric deterioration. Whether administering a practical dose of testosterone protects muscle and performance during strenuous operations is undetermined. The objective of this study was to test the effects of a single dose of testosterone undecanoate on body composition and military-relevant physical performance during a simulated operation. After a 7-day baseline phase (P1), 32 males (means ± SD; 77.1 ± 12.3 kg, 26.5 ± 4.4 yr) received a single dose of either testosterone undecanoate (750 mg; TEST) or placebo (PLA) before a 20-day simulated military operation (P2), followed by a 23-day recovery (P3). Assessments included body composition and physical performance at the end of each phase and circulating endocrine biomarkers throughout the study. Total and free testosterone concentrations in TEST were greater than PLA throughout most of P2 (P < 0.05), but returned to P1 values during P3. Fat-free mass (FFM) was maintained from P1 to P2 in TEST (means ± SE; 0.41 ± 0.65 kg, P = 0.53), but decreased in PLA (-1.85 ± 0.69 kg, P = 0.01) and recovered in P3. Regardless of treatment, total body mass and fat mass decreased from P1 to P2 (P < 0.05), but did not fully recover by P3. Physical performance decreased during P2 (P < 0.05) and recovered by P3, regardless of treatment. In conclusion, administering testosterone undecanoate before a simulated military operation protected FFM but did not prevent decrements in physical performance.NEW & NOTEWORTHY This study demonstrated that a single intramuscular dose of testosterone undecanoate (750 mg) administered to physically active males before a 20-day simulated, multi-stressor military operation increased circulating total and free testosterone concentrations within normal physiological ranges and spared FFM. However, testosterone administration did not attenuate decrements in physical performance across multiple measures of power, strength, anaerobic or aerobic capacity.

Effects of Testosterone on Mixed-Muscle Protein Synthesis and Proteome Dynamics During Energy Deficit.

CONTEXT: Effects of testosterone on integrated muscle protein metabolism and muscle mass during energy deficit are undetermined. OBJECTIVE: The objective was to determine the effects of testosterone on mixed-muscle protein synthesis (MPS), proteome-wide fractional synthesis rates (FSR), and skeletal muscle mass during energy deficit. DESIGN: This was a randomized, double-blind, placebo-controlled trial. SETTING: The study was conducted at Pennington Biomedical Research Center. PARTICIPANTS: Fifty healthy men. INTERVENTION: The study consisted of 14 days of weight maintenance, followed by a 28-day 55% energy deficit with 200 mg testosterone enanthate (TEST, n = 24) or placebo (PLA, n = 26) weekly, and up to 42 days of ad libitum recovery feeding. MAIN OUTCOME MEASURES: Mixed-MPS and proteome-wide FSR before (Pre), during (Mid), and after (Post) the energy deficit were determined using heavy water (days 1-42) and muscle biopsies. Muscle mass was determined using the D3-creatine dilution method. RESULTS: Mixed-MPS was lower than Pre at Mid and Post (P < 0.0005), with no difference between TEST and PLA. The proportion of individual proteins with numerically higher FSR in TEST than PLA was significant by 2-tailed binomial test at Post (52/67; P < 0.05), but not Mid (32/67; P > 0.05). Muscle mass was unchanged during energy deficit but was greater in TEST than PLA during recovery (P < 0.05). CONCLUSIONS: The high proportion of individual proteins with greater FSR in TEST than PLA at Post suggests exogenous testosterone exerted a delayed but broad stimulatory effect on synthesis rates across the muscle proteome during energy deficit, resulting in muscle mass accretion during subsequent recovery.

Effects of testosterone undecanoate on performance during multi-stressor military operations: A trial protocol for the Optimizing Performance for Soldiers II study.

BACKGROUND: Previously, young males administered 200 mg/week of testosterone enanthate during 28 days of energy deficit (EDef) gained lean mass and lost less total mass than controls (Optimizing Performance for Soldiers I study, OPS I). Despite that benefit, physical performance deteriorated similarly in both groups. However, some experimental limitations may have precluded detection of performance benefits, as performance measures employed lacked military relevance, and the EDef employed did not elicit the magnitude of stress typically experienced by Soldiers conducting operations. Additionally, the testosterone administered required weekly injections, elicited supra-physiological concentrations, and marked suppression of endogenous testosterone upon cessation. Therefore, this follow-on study will address those limitations and examine testosterone's efficacy for preserving Solder performance during strenuous operations. METHODS: In OPS II, 32 males will participate in a randomized, placebo-controlled, double-blind trial. After baseline testing, participants will be administered either testosterone undecanoate (750 mg) or placebo before completing four consecutive, 5-day cycles simulating a multi-stressor, sustained military operation (SUSOPS). SUSOPS will consist of two low-stress days (1000 kcal/day exercise-induced EDef; 8 h/night sleep), followed by three high-stress days (3000 kcal/day and 4 h/night). A 23-day recovery period will follow SUSOPS. Military relevant physical performance is the primary outcome. Secondary outcomes include 4-comparment body composition, muscle and whole-body protein turnover, intramuscular mechanisms, biochemistries, and cognitive function/mood. CONCLUSIONS: OPS II will determine if testosterone undecanoate safely enhances performance, while attenuating muscle and total mass loss, without impairing cognitive function, during and in recovery from SUSOPS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04120363.

Testosterone supplementation upregulates androgen receptor expression and translational capacity during severe energy deficit.

Testosterone supplementation during energy deficit promotes whole body lean mass accretion, but the mechanisms underlying that effect remain unclear. To elucidate those mechanisms, skeletal muscle molecular adaptations were assessed from muscle biopsies collected before, 1 h, and 6 h after exercise and a mixed meal (40 g protein, 1 h postexercise) following 14 days of weight maintenance (WM) and 28 days of an exercise- and diet-induced 55% energy deficit (ED) in 50 physically active nonobese men treated with 200 mg testosterone enanthate/wk (TEST) or placebo (PLA) during the ED. Participants (n = 10/group) exhibiting substantial increases in leg lean mass and total testosterone (TEST) were compared with those exhibiting decreases in both of these measures (PLA). Resting androgen receptor (AR) protein content was higher and fibroblast growth factor-inducible 14 (Fn14), IL-6 receptor (IL-6R), and muscle ring-finger protein-1 gene expression was lower in TEST vs. PLA during ED relative to WM (P < 0.05). Changes in inflammatory, myogenic, and proteolytic gene expression did not differ between groups after exercise and recovery feeding. Mechanistic target of rapamycin signaling (i.e., translational efficiency) was also similar between groups at rest and after exercise and the mixed meal. Muscle total RNA content (i.e., translational capacity) increased more during ED in TEST than PLA (P < 0.05). These findings indicate that attenuated proteolysis at rest, possibly downstream of AR, Fn14, and IL-6R signaling, and increased translational capacity, not efficiency, may drive lean mass accretion with testosterone administration during energy deficit.

Adaptations to exercise in compensators and noncompensators in the E-MECHANIC Trial.

Rating of perceived exertion (RPE) and respiratory exchange ratio (RER) have previously been associated with acute exercise compensation. This study examined adaptations in the RPE and RER with long-term exercise training in individuals who did (noncompensators) and did not (compensators) lose the expected amount of weight. Participants (n = 110, 71.8% women, means ± SD; age 49 ± 12 yr) completed 24 wk of supervised exercise training at 65-85% V̇o2peak to achieve a prescribed dose of 8 kcal·kg body wt-1·wk-1 (8 KKW) or 20 KKW. Participants were categorized as noncompensators (n = 55) or compensators (n = 55) based on the percent of expected weight loss (%EWL) achieved. Changes in RPE and RER during exercise over time (baseline, week 12, week 24) were compared by weight compensation category. Individual %EWL in relation to RPE, RER, and training intensity (%V̇o2peak) was evaluated over the same time period. RPE and RER for a given workload decreased from baseline to week 12 and stabilized through week 24, regardless of weight compensation (time P < 0.0001). Noncompensators had a higher RPE relative to heart rate, which was partly explained by higher %V̇o2peak. RPE and %V̇o2peak both positively predicted %EWL, independent of age, sex, and exercise dose. Training intensity and RPE were positively associated with weight loss on the individual level, warranting further investigation into self-selection in exercise-based programs. Understanding individual heterogeneity in training intensity and behavioral responses may improve future weight management efforts that involve exercise.NEW & NOTEWORTHY In sedentary individuals with overweight and obesity, achievement of expected weight loss from long-term exercise training was associated with individual adaptations in perceived exertion. Contrary to our hypothesis, those with higher relative perceived exertion achieved a larger proportion of their expected weight loss, which was partly explained by a higher self-selected exercise training intensity.

Effects of Testosterone Supplementation on Ghrelin and Appetite During and After Severe Energy Deficit in Healthy Men.

BACKGROUND: Severe energy deficits cause interrelated reductions in testosterone and fat free mass. Testosterone supplementation may mitigate those decrements, but could also reduce circulating concentrations of the orexigenic hormone ghrelin, thereby exacerbating energy deficit by suppressing appetite. OBJECTIVE: To determine whether testosterone supplementation during severe energy deficit influences fasting and postprandial ghrelin concentrations and appetite. DESIGN AND METHODS: Secondary analysis of a randomized, double-blind trial that determined the effects of testosterone supplementation on body composition changes during and following severe energy deficit in nonobese, eugonadal men. Phase 1 (PRE-ED): 14-day run-in; phase 2: 28 days, 55% energy deficit with 200 mg testosterone enanthate weekly (TEST; n = 24) or placebo (PLA; n = 26); phase 3: free-living until body mass recovered (end-of-study; EOS). Fasting and postprandial acyl ghrelin and des-acyl ghrelin concentrations and appetite were secondary outcomes measured during the final week of each phase. RESULTS: Fasting acyl ghrelin concentrations, and postprandial acyl and des-acyl ghrelin concentrations increased in PLA during energy deficit then returned to PRE-ED values by EOS, but did not change in TEST (phase-by-group, P < 0.05). Correlations between changes in free testosterone and changes in fasting acyl ghrelin concentrations during energy deficit (ρ = -0.42, P = 0.003) and body mass recovery (ρ = -0.38; P = 0.01) were not mediated by changes in body mass or body composition. Transient increases in appetite during energy deficit were not affected by testosterone treatment. CONCLUSIONS: Testosterone supplementation during short-term, severe energy deficit in healthy men prevents deficit-induced increases in circulating ghrelin without blunting concomitant increases in appetite. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov NCT02734238 (registered 12 April 2016).

Testosterone Administration During Energy Deficit Suppresses Hepcidin and Increases Iron Availability for Erythropoiesis.

CONTEXT: Severe energy deprivation markedly inhibits erythropoiesis by restricting iron availability for hemoglobin synthesis. OBJECTIVE: The objective of this study was to determine whether testosterone supplementation during energy deficit increased indicators of iron turnover and attenuated the decline in erythropoiesis compared to placebo. DESIGN: This was a 3-phase, randomized, double-blind, placebo-controlled trial. SETTING: The study was conducted at the Pennington Biomedical Research Center. PATIENTS OR OTHER PARTICIPANTS: Fifty healthy young males. INTERVENTION(S): Phase 1 was a 14-day free-living eucaloric controlled-feeding phase; phase 2 was a 28-day inpatient phase where participants were randomized to 200 mg testosterone enanthate/week or an isovolumetric placebo/week during an energy deficit of 55% of total daily energy expenditure; phase 3 was a 14-day free-living, ad libitum recovery period. MAIN OUTCOME MEASURE(S): Indices of erythropoiesis, iron status, and hepcidin and erythroferrone were determined. RESULTS: Hepcidin declined by 41%, indicators of iron turnover increased, and functional iron stores were reduced with testosterone administration during energy deficit compared to placebo. Testosterone administration during energy deficit increased circulating concentrations of erythropoietin and maintained erythropoiesis, as indicated by an attenuation in the decline in hemoglobin and hematocrit with placebo. Erythroferrone did not differ between groups, suggesting that the reduction in hepcidin with testosterone occurs through an erythroferrone-independent mechanism. CONCLUSION: These findings indicate that testosterone suppresses hepcidin, through either direct or indirect mechanisms, to increase iron turnover and maintain erythropoiesis during severe energy deficit. This trial was registered at www.clinicaltrials.gov as #NCT02734238.

Effects of testosterone supplementation on body composition and lower-body muscle function during severe exercise- and diet-induced energy deficit: A proof-of-concept, single centre, randomised, double-blind, controlled trial.

BACKGROUND: Severe energy deficits during military operations, produced by significant increases in exercise and limited dietary intake, result in conditions that degrade lean body mass and lower-body muscle function, which may be mediated by concomitant reductions in circulating testosterone. METHODS: We conducted a three-phase, proof-of-concept, single centre, randomised, double-blind, placebo-controlled trial (CinicalTrials.gov, NCT02734238) of non-obese men: 14-d run-in, free-living, eucaloric diet phase; 28-d live-in, 55% exercise- and diet-induced energy deficit phase with (200 mg testosterone enanthate per week, Testosterone, n = 24) or without (Placebo, n = 26) exogenous testosterone; and 14-d recovery, free-living, ad libitum diet phase. Body composition was the primary end point; secondary endpoints included lower-body muscle function and health-related biomarkers. FINDINGS: Following energy deficit, lean body mass increased in Testosterone and remained stable in Placebo, such that lean body mass significantly differed between groups [mean difference between groups (95% CI), 2.5 kg (3.3, 1.6); P < .0001]. Fat mass decreased similarly in both treatment groups [0.2 (-0.4, 0.7), P = 1]. Change in lean body mass was associated with change in total testosterone (r = 0.71, P < .0001). Supplemental testosterone had no effect on lower-body muscle function or health-related biomarkers. INTERPRETATION: Findings suggest that supplemental testosterone may increase lean body mass during short-term severe energy deficit in non-obese, young men, but it does not appear to attenuate lower-body functional decline. FUNDING: Collaborative Research to Optimize Warfighter Nutrition projects I and II, Joint Program Committee-5, funded by the US Department of Defence.

Effects of Increasing Exercise Intensity and Dose on Multiple Measures of HDL (High-Density Lipoprotein) Function.

OBJECTIVE: Measures of HDL (high-density lipoprotein) function are associated with cardiovascular disease. However, the effects of regular exercise on these measures is largely unknown. Thus, we examined the effects of different doses of exercise on 3 measures of HDL function in 2 randomized clinical exercise trials. APPROACH AND RESULTS: Radiolabeled and boron dipyrromethene difluoride-labeled cholesterol efflux capacity and HDL-apoA-I (apolipoprotein A-I) exchange were assessed before and after 6 months of exercise training in 2 cohorts: STRRIDE-PD (Studies of Targeted Risk Reduction Interventions through Defined Exercise, in individuals with Pre-Diabetes; n=106) and E-MECHANIC (Examination of Mechanisms of exercise-induced weight compensation; n=90). STRRIDE-PD participants completed 1 of 4 exercise interventions differing in amount and intensity. E-MECHANIC participants were randomized into 1 of 2 exercise groups (8 or 20 kcal/kg per week) or a control group. HDL-C significantly increased in the high-amount/vigorous-intensity group (3±5 mg/dL; P=0.02) of STRRIDE-PD, whereas no changes in HDL-C were observed in E-MECHANIC. In STRRIDE-PD, global radiolabeled efflux capacity significantly increased 6.2% (SEM, 0.06) in the high-amount/vigorous-intensity group compared with all other STRRIDE-PD groups (range, -2.4 to -8.4%; SEM, 0.06). In E-MECHANIC, non-ABCA1 (ATP-binding cassette transporter A1) radiolabeled efflux significantly increased 5.7% (95% CI, 1.2-10.2%) in the 20 kcal/kg per week group compared with the control group, with no change in the 8 kcal/kg per week group (2.6%; 95% CI, -1.4 to 6.7%). This association was attenuated when adjusting for change in HDL-C. Exercise training did not affect BODIPY-labeled cholesterol efflux capacity or HDL-apoA-I exchange in either study. CONCLUSIONS: Regular prolonged vigorous exercise improves some but not all measures of HDL function. Future studies are warranted to investigate whether the effects of exercise on cardiovascular disease are mediated in part by improving HDL function. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00962962 and NCT01264406.

Why patients seek bariatric surgery: does insurance coverage matter?

Despite increasing prevalence of bariatric surgery, little is known about why patients seek out this treatment option. Heads Up is an observational study sponsored by a large benefits management group that examines surgical and nonsurgical approaches to weight management in obese adults. This study examined patients' reasons for choosing surgery. The sample included 360 adult obese patients seeking bariatric surgery who were invited to volunteer for a surgical or a medical weight loss program by their insurer. Participants rank ordered their top three reasons as a deciding factor for choosing to consider surgery. The top three reasons were concerns regarding health (52%), current obesity-related medical conditions (28%), and improved physical fitness (5%). Overall, 13% endorsed insurance coverage as one of their top three choices. When insurance coverage is assured, health and functionality issues were the major reasons reported for obese adults choosing to undergo bariatric surgery.