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1.
Acute effects of high-intensity interval, resistance or combined exercise protocols on testosterone - cortisol responses in inactive overweight individuals.
Velasco-Orjuela, GP, Domínguez-Sanchéz, MA, Hernández, E, Correa-Bautista, JE, Triana-Reina, HR, García-Hermoso, A, Peña-Ibagon, JC, Izquierdo, M, Cadore, EL, Hackney, AC, et al
Physiology & behavior. 2018;:401-409
Abstract
The purpose of this study was to compare the hormonal responses to one session of high-intensity interval training (HIIT, 4 × 4 min intervals at 85-95% maximum heart rate [HRmax], interspersed with 4 min of recovery at 75-85% HRmax), resistance training (RT at 50-70% of one repetition maximum 12-15 repetitions per set with 60s of recovery) or both (HIIT+RT) exercise protocol in a cohort of physical inactivity, overweight adults (age 18-30 years old). Randomized, parallel-group clinical trial among fifty-one men (23.6 ± 3.5 yr; 83.5 ± 7.8 kg; 28.0 ± 1.9 kg/m2), physical inactivity (i.e., <150 min of moderate-intensity exercise per week for >6 months), with abdominal obesity (waist circumference ≥90 cm) or body mass index ≥25 and ≤30 kg/m2 were randomized to the following 4 groups: high-intensity interval training (HIIT, n = 14), resistance training (RT, n = 12), combined high-intensity interval and resistance training (HIIT+RT, n = 13), or non-exercising control (CON, n = 12). Cortisol, total- and free-testosterone and total-testosterone/cortisol-ratio (T/C) assessments (all in serum) were determined before (pre) and 1-min post-exercise for each protocol session. Decreases in cortisol levels were -57.08 (95%CI, -75.58 to -38.58; P = 0.001; ɳ2 = 0.61) and - 37.65 (95%CI, -54.36 to -20.93; P = 0.001; ɳ2 = 0.51) in the HIIT and control group, respectively. Increases in T/C ratio were 0.022 (95%CI, 0.012 to 0.031; P = 0.001; ɳ2 = 0.49) and 0.015 (95%CI, 0.004 to 0.025; P = 0.007; ɳ2 = 0.29) in the HIIT and control group, respectively. In per-protocol analyses revealed a significant change in cortisol levels [interaction effect F(7.777), ɳ2 = 0.33] and T/C ratio [interaction effect F(5.298), ɳ2 = 0.25] between groups over time. Additionally, we showed that in both the intention-to-treat (ITT) and per protocol analyses, HIIT+RT did not change serum cortisol, total or free testosterone. The present data indicate a HIIT reduced cortisol and increased total-testosterone/cortisol-ratio levels significantly in physically inactive adults. Further study is required to determine the biological importance of these changes in hormonal responses in overweight men.
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Vitamin D and calcium supplementation, skeletal muscle strength and serum testosterone in young healthy adult males: Randomized control trial.
Saha, S, Goswami, R, Ramakrishnan, L, Vishnubhatla, S, Mahtab, S, Kar, P, Srinivasan, S, Singh, N, Singh, U
Clinical endocrinology. 2018;(2):217-226
Abstract
BACKGROUND Cholecalciferol and/or calcium supplementation might increase skeletal muscle strength and serum testosterone in young adult males. OBJECTIVE We performed a randomized control trial assessing the effect of cholecalciferol/calcium on skeletal muscle strength and serum testosterone in vitamin D deficient young males. DESIGN Two-by-two factorial RCT. SUBJECT AND INTERVENTION Two-hundred and twenty-eight young males were block-randomized to (i) double-placebo, (ii) calcium/placebo, (iii) cholecalciferol/placebo and (iv) cholecalciferol/calcium. Doses for cholecalciferol were 60 000 IU/wk for 8 weeks followed by 60 000 IU/fortnightly, and doses for elemental calcium were 500 mg/twice daily for 6 months. A total of 180 subjects completed the study protocol. Their ean age, body mass index and baseline 25(OH)D were 20.2 ± 2.2 years, 23.0 ± 3.6 kg/m2 and 21.5 ± 9.5 nmol/L, respectively. MEASUREMENTS Handgrip (primary outcome), pinch-grip strength, distance walked in 6 minutes, dyspnoea-score, quality of life by Short Form 36, serum 25(OH)D, 1,25(OH)2 D, iPTH, total testosterone and free androgen index (FAI). RESULTS After intervention, mean serum 25(OH)D was >75.0 nmol/L in cholecalciferol groups. However, the handgrip strength (29.7 ± 4.4, 29.3 ± 4.6, 30.6 ± 5.0 and 28.8 ± 4.3 kg, P = .28) was comparable in the 4 groups. Subgroups analysis among subjects with baseline serum 25OH)D < 25.0 and <12.0 nmol/L showed similar results. The mean serum testosterone decreased significantly at 6 months; however, delta change was similar in 4 groups. Change in handgrip strength and other outcomes was similar in 4 groups with and without adjustment for delta testosterone and FAI. CONCLUSIONS Six months of cholecalciferol/calcium supplementation had no significant effect on skeletal muscle strength and serum testosterone in young adult males.
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Magnesium-Zinc-Calcium-Vitamin D Co-supplementation Improves Hormonal Profiles, Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial.
Maktabi, M, Jamilian, M, Asemi, Z
Biological trace element research. 2018;(1):21-28
Abstract
Data on the effects of magnesium-zinc-calcium-vitamin D co-supplementation on hormonal profiles, biomarkers of inflammation, and oxidative stress among women with polycystic ovary syndrome (PCOS) are scarce. The objective of this study was to assess the effects of magnesium-zinc-calcium-vitamin D co-supplementation on hormonal profiles, biomarkers of inflammation, and oxidative stress in women with PCOS. Sixty PCOS women were randomized into two groups and treated with 100 mg magnesium, 4 mg zinc, 400 mg calcium plus 200 IU vitamin D supplements (n = 30), or placebo (n = 30) twice a day for 12 weeks. Hormonal profiles, biomarkers of inflammation, and oxidative stress were assessed at baseline and at end-of-treatment. After the 12-week intervention, compared with the placebo, magnesium-zinc-calcium-vitamin D co-supplementation resulted in significant reductions in hirsutism (-2.4 ± 1.2 vs. -0.1 ± 0.4, P < 0.001), serum high sensitivity C-reactive protein (-0.7 ± 0.8 vs. +0.2 ± 1.8 mg/L, P < 0.001), and plasma malondialdehyde (-0.4 ± 0.3 vs. +0.2 ± 1.0 μmol/L, P = 0.01), and a significant increase in plasma total antioxidant capacity concentrations (+46.6 ± 66.5 vs. -7.7 ± 130.1 mmol/L, P = 0.04). We failed to find any significant effect of magnesium-zinc-calcium-vitamin D co-supplementation on free androgen index, and other biomarkers of inflammation and oxidative stress. Overall, magnesium-zinc-calcium-vitamin D co-supplementation for 12 weeks among PCOS women had beneficial effects on hormonal profiles, biomarkers of inflammation, and oxidative stress.
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Effects of testosterone supplementation therapy on lipid metabolism in hypogonadal men with T2DM: a meta-analysis of randomized controlled trials.
Zhang, KS, Zhao, MJ, An, Q, Jia, YF, Fu, LL, Xu, JF, Gu, YQ
Andrology. 2018;(1):37-46
Abstract
Testosterone supplementation may be effective for the treatment of hypogonadism in men with type 2 diabetes mellitus (T2DM), but the evidence from randomized controlled trials (RCTs) is inconclusive. We aimed to systematically summarize results from intervention studies and assess the effects of testosterone supplementation therapy (TST) on lipid metabolism in RCTs of hypogonadal men with T2DM by meta-analysis. PubMed, Embase, and Cochrane Library databases were searched for studies reporting the effect of TST on lipid metabolism in hypogonadal men with T2DM until December 31, 2016. Seven RCTs from 252 trials, enrolling a total of 612 patients in the experimental and control groups with a mean age of 58.5 years, were included in this study. The pooled results of the meta-analysis demonstrated that TST significantly decreased TC and TG levels in hypogonadal men with T2DM compared with the control group, with mean differences (MDs) of -6.44 (95% CI: -11.82 to -1.06; I2 = 28%; p = 0.02) and -27.94 (95% CI: -52.33 to -3.54; I2 = 76%; p = 0.02). Subgroup analyses revealed that the heterogeneity (I2 = 76%) of TG originated from different economic regions, in which economic development, genetic and environmental factors, and dietary habits affect lipid metabolism of human, with a decrease (I2 = 45%) in developed countries. Additionally, subgroup analyses showed that TST increased HDL-C level in developing countries compared with the control group (MD = 2.79; 95% CI: 0.73 to 4.86; I2 = 0%; p = 0.008), but there was no improvement in developed countries (MD = 1.02; 95% CI: -4.55 to 6.60; I2 = 91%; p = 0.72). However, LDL-C levels were not improved consistently. Because the relationship between lipid metabolism and atherosclerosis is unequivocal, TST, which ameliorates lipid metabolism, may decrease the morbidity and mortality of cardiovascular disease in hypogonadal men with T2DM by preventing atherogenesis.
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Effects of testosterone supplement treatment in hypogonadal adult males with T2DM: a meta-analysis and systematic review.
Zhang, J, Yang, B, Xiao, W, Li, X, Li, H
World journal of urology. 2018;(8):1315-1326
Abstract
PURPOSE Testosterone supplement treatment (TST) is a classic therapy for hypogonadal men with type 2 diabetes mellitus (T2DM), but the effects of TST in different studies are inconsistent. We conducted this meta-analysis to evaluate the precise role of TST in hypogonadal men with T2DM. METHODS PubMed, Embase, Cochrane Library and Web of Science were searched to identify qualified randomized controlled trials (RCTs). Pooled mean differences (MDs) with 95% confidence intervals (CIs) were calculated to measure the specific effects of TST. Trial sequential analysis was performed to verify the pooled results. RESULTS A total of eight RCTs were enrolled in our meta-analysis, including 596 hypogonadal participants with T2DM. Compared with comparators, TST can significantly improve glycemic control by reducing homeostatic model assessment of insulin resistance (MD - 0.79, 95% CI - 1.23 to - 0.34), fasting glucose (MD - 0.98, 95% CI - 1.13 to - 0.54), fasting insulin (MD - 2.47, 95% CI - 3.99 to - 0.95) and HbA1c% (MD - 0.45, 95% CI - 0.73 to - 0.16). In addition, TST can result in a decline in cholesterol (MD - 0.29, 95% CI - 0.38 to - 0.19) and triglyceride (MD - 0.37, 95% CI - 0.59 to - 0.15). CONCLUSION Our results indicated that TST can improve glycemic control and decrease TC and TG in hypogonadal patients with T2DM. We recommend TST during the anti-diabetic therapy in these patients.
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A randomized trial of adjunct testosterone for cancer-related muscle loss in men and women.
Wright, TJ, Dillon, EL, Durham, WJ, Chamberlain, A, Randolph, KM, Danesi, C, Horstman, AM, Gilkison, CR, Willis, M, Richardson, G, et al
Journal of cachexia, sarcopenia and muscle. 2018;(3):482-496
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Abstract
BACKGROUND Cancer cachexia negatively impacts cancer-related treatment options, quality of life, morbidity, and mortality, yet no established therapies exist. We investigated the anabolic properties of testosterone to limit the loss of body mass in late stage cancer patients undergoing standard of care cancer treatment. METHODS A randomized, double-blind, placebo-controlled phase II clinical trial was undertaken to assess the potential therapeutic role of adjunct testosterone to limit loss of body mass in patients with squamous cell carcinoma of the cervix or head and neck undergoing standard of care treatment including chemotherapy and chemoradiation. Patients were randomly assigned in blocks to receive weekly injections of either 100 mg testosterone enanthate or placebo for 7 weeks. The primary outcome was per cent change in lean body mass, and secondary outcomes included assessment of quality of life, tests of physical performance, muscle strength, daily activity levels, resting energy expenditure, nutritional intake, and overall survival. RESULTS A total of 28 patients were enrolled, 22 patients were studied to completion, and 21 patients were included in the final analysis (12 placebo, nine testosterone). Adjunct testosterone increased lean body mass by 3.2% (95% confidence interval [CI], 0-7%) whereas those receiving placebo lost 3.3% (95% CI, -7% to 1%, P = 0.015). Although testosterone patients maintained more favourable body condition, sustained daily activity levels, and showed meaningful improvements in quality of life and physical performance, overall survival was similar in both treatment groups. CONCLUSIONS In patients with advanced cancer undergoing the early phase of standard of care therapy, adjunct testosterone improved lean body mass and was also associated with increased quality of life, and physical activity compared with placebo.
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Active and passive recovery influence responses of luteinizing hormone and testosterone to a fatiguing strength loading.
Taipale, RS, Kyröläinen, H, Gagnon, SS, Nindl, B, Ahtiainen, J, Häkkinen, K
European journal of applied physiology. 2018;(1):123-131
Abstract
The purpose of this study was to examine the acute hormonal and muscular responses to a strenuous strength loading [bilateral leg press (LP) 10 × 10 1RM] followed by loading-specific active (AR, n = 7, LP 10 × 10 × 30% 1RM) or passive (PR, n = 11, seated) recovery. The subjects were men age: 26 ± 4 years, height: 174 ± 8 cm, body mass: 75 ± 13 kg. After control measurements, experimental measurements were conducted at pre- and post-loading as well as post-recovery and next morning. A significantly higher absolute concentration (p < 0.05) of serum luteinizing hormone (LH) was observed in AR than PR at next morning while no differences were observed in serum testosterone (T), cortisol (C) or sex hormone binding globulin (SHBG). Significant differences in relative hormonal responses to the loading were observed at next morning with greater responses observed in AR than in PR in terms of LH, and T (p < 0.05). Maximal bilateral isometric force (MVC) and countermovement jump height (CMJ) decreased significantly (p < 0.001) from the control measurements in both AR and PR but returned to control levels by next morning. No between-group differences were observed in mean absolute or relative changes in MVC or CMJ. From a hormonal perspective, the present AR method appears to have had some favorable effects following the strenuous strength loading; however, acute decreases in muscular force production did not significantly differ between groups. These results provide insight into the development of training programs that may help to support the performance of individuals involved in strenuous tasks.
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Hepatic actions of androgens in the regulation of metabolism.
Birzniece, V
Current opinion in endocrinology, diabetes, and obesity. 2018;(3):201-208
Abstract
PURPOSE OF REVIEW The purpose of this review is to summarize recent findings on hepatic actions of androgens in the regulation of protein, lipid and glucose metabolism. The rationale for liver-targeted testosterone use will be provided. RECENT FINDINGS Liver-targeted testosterone administration, via the oral route, induces protein anabolic effect by reducing the rate of protein oxidation to a similar extent to that of systemic testosterone administration. Recent evidence indicates that testosterone exerts whole-body anabolic effect through inhibition of nitrogen loss via the hepatic urea cycle. Several hepatic effects of androgens, particularly on glucose metabolism, are direct and take place before any changes in body composition occur. This includes an increase in insulin secretion and sensitivity, and reduction in hepatic glucose output by testosterone. Furthermore, lack of testosterone in the liver exacerbates diet-induced impairment in glucose metabolism. In the liver, androgens induce the full spectrum of metabolic changes through interaction with growth hormone or aromatization to estradiol. SUMMARY Liver-targeted testosterone therapy may open up a new approach to achieve whole-body anabolism without systemic side-effects. Aromatizable androgens may be superior to nonaromatizable androgens in inducing a complex spectrum of direct, estrogen-mediated and other hormone-mediated effects of androgens.
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Effects of β-alanine supplementation on physical performance, cognition, endocrine function, and inflammation during a 24 h simulated military operation.
Varanoske, AN, Wells, AJ, Kozlowski, GJ, Gepner, Y, Frosti, CL, Boffey, D, Coker, NA, Harat, I, Hoffman, JR
Physiological reports. 2018;(24):e13938
Abstract
Sustained military operations (SUSOPs) are associated with performance decrements and cognitive dysfunction. β-Alanine (BA) supplementation may have a role in increasing soldier resiliency by enhancing muscle-buffering capacity and reducing oxidative stress. The purpose of this study was to examine the effects of BA on physical performance, cognition, endocrine function, and inflammation during a 24 h simulated SUSOP. Nineteen males were randomized into one of two groups: BA (n = 10) or placebo (n = 9; PLA) (12 g/day) for 14 days preceding the 24 h SUSOP. Assessments were performed at 0 h (0H), 12 h (12H), and 24 h (24H) during the SUSOP. No changes in visual tracking ability, jump power, or upper-body muscular endurance were observed between groups or time points (P's > 0.05). Increases in subjective feelings of soreness and fatigue were noted at 12H compared to 0H (P < 0.05) in PLA, but not in BA. Visual reaction time for PLA was slower at 24H compared to 0H (P = 0.035), and PLA made more errors on reaction time testing at 12H compared to BA (P = 0.048), but motor reaction time was faster (P = 0.016) for PLA. Simulated litter carry and 1 km run completion times increased at 24H compared to 0H in both groups (P < 0.05), however, PLA had a longer 1 km time compared to BA at 24H (P = 0.050). Increases in inflammatory and endocrine markers were observed over the SUSOP, with no differences between groups. BA supplementation appears to maintain some aspects of cognition and physical performance during a 24 h SUSOP, with no effects on endocrine function or inflammation.
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Elevated luteinizing hormone despite normal testosterone levels in older men-natural history, risk factors and clinical features.
Eendebak, RJAH, Ahern, T, Swiecicka, A, Pye, SR, O'Neill, TW, Bartfai, G, Casanueva, FF, Maggi, M, Forti, G, Giwercman, A, et al
Clinical endocrinology. 2018;(3):479-490
Abstract
OBJECTIVE Elevated luteinizing hormone (LH) with normal testosterone (T) suggests compensated dysregulation of the gonadal axis. We describe the natural history, risk factors and clinical parameters associated with the development of high LH (HLH, LH >9.4 U/L) in ageing men with normal T (T ≥ 10.5 nmol/L). DESIGN, PATIENTS AND MEASUREMENTS We conducted a 4.3-year prospective observational study of 3369 community-dwelling European men aged 40-79 years. Participants were classified as follows: incident (i) HLH (n = 101, 5.2%); persistent (p) HLH (n = 128, 6.6%); reverted (r) HLH (n = 46, 2.4%); or persistent normal LH (pNLH, n = 1667, 85.8%). Potential predictors and changes in clinical features associated with iHLH and rHLH were analysed using regression models. RESULTS Age >70 years (OR = 4.12 [2.07-8.20]), diabetes (OR = 2.86 [1.42-5.77]), chronic pain (OR = 2.53 [1.34-4.77]), predegree education (OR = 1.79 [1.01-3.20]) and low physical activity (PASE ≤ 78, OR = 2.37 [1.24-4.50]) predicted development of HLH. Younger age (40-49 years, OR = 8.14 [1.35-49.13]) and nonsmoking (OR = 5.39 [1.48-19.65]) predicted recovery from HLH. Men with iHLH developed erectile dysfunction, poor health, cardiovascular disease (CVD) and cancer more frequently than pNLH men. In pHLH men, comorbidities, including CVD, developed more frequently, and cognitive and physical function deteriorated more, than in pNLH men. Men with HLH developed primary hypogonadism more frequently (OR = 15.97 [5.85-43.60]) than NLH men. Men with rHLH experienced a small rise in BMI. CONCLUSIONS Elevation of LH with normal T is predicted by multiple factors, reverts frequently and is not associated with unequivocal evidence of androgen deficiency. High LH is a biomarker for deteriorating health in aged men who tend to develop primary hypogonadism.