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Effect of testosterone on muscle and muscle protein synthesis

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Abstract

We have studied the effect of a pharmacological dose of testosterone enanthate (3 mg.kg-1.wk-1 for 12 wk) on muscle mass and total-body potassium and on whole-body and muscle protein synthesis in normal male subjects. Muscle mass estimated by creatinine excretion increased in all nine subjects (20% mean increase, P less than 0.02); total body potassium mass estimated by 40K counting increased in all subjects (12% mean increase, P less than 0.0001). In four subjects, a primed continuous infusion protocol with L-[1-13C]leucine was used to determine whole-body leucine flux and oxidation. Whole-body protein synthesis was estimated from nonoxidative flux. Muscle protein synthesis rate was determined by measuring [13C]leucine incorporation into muscle samples obtained by needle biopsy. Testosterone increased muscle protein synthesis in all subjects (27% mean increase, P less than 0.05). Leucine oxidation decreased slightly (17% mean decrease, P less than 0.01), but whole-body protein synthesis did not change significantly. Muscle morphometry showed no significant increase in muscle fiber diameter. These studies suggest that testosterone increases muscle mass by increasing muscle protein synthesis.

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... Application of doping among bodybuilders is frequent disregarding the risk of disqualification. Popular substances in bodybuilding include anabolic-androgenic steroids (AAS) which enable an increase of muscle mass by 20% in 12 weeks (Griggs et al. 1985;Saeidinejat et al. 2018). Strict monitoring of drugs application takes place in competitions of, so called, natural bodybuilders federation as in the group the process of hypertrophy is physiologically limited and catabolism of skeletal muscles during preparations for competitions higher if compared to athletes from different federations (Hackett et al. 2013;Chappell et al. 2018). ...
... The factor that may influence metabolism of muscles proteins and an increase of protein demand in bodybuilders' diet can be applying anabolic steroids. Supplementing the diet with anabolic-androgenic steroids (AAS) -testosterone enanthate at 3 mg/kg of body weight once a week for 12 weeks increased synthesis of muscles proteins by 27% (Griggs et al. 1985). A consequence of using AAS are side effects though only 4.7% bodybuilders possess thorough knowledge on their occurrence (Saeidinejat et al. 2018). ...
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Significant factors affecting body composition and consequently professional and amateur bodybuilders’ performance are both training loads and diet. The aim was to assess dissimilarities in anthropometrical traits and body composition between males practicing bodybuilding professionally and as amateurs, considering their diet and training. The study comprised 55 athletes, i.e. 29 professionals attending national championships and 26 amateur bodybuilders. All participants underwent anthropometric measurements involving body height, waist, arm and thigh circumferences and skinfolds covering trunk and extremities. The original nutritional behavior questionnaire and a 24-hour survey were used. An electronic scale was used to measure body weight and body composition was analyzed with the BIA method. In statistical analysis, the Shapiro-Wilk (W-test), t-student and Mann-Whitney U test were applied. An adipose tissue, assessed on the basis of skinfolds was significantly lower in professionals ( p <0.05), whereas lower mean values of body fat free mass (FFM) were found in amateur bodybuilders ( p <0.01). Diet survey presented differentiation both in the amount of consumed protein in the diet (1.98 g/kg), in its percentage participation in the diet (21.2%) in favor of the professionals ( p <0.05). Significant differentiation was between the groups in the amount of consumed fats ( p <0.05). In case of resistance trainings time, energy expenditure and number of trainings were higher for professionals ( p <0.05). Bodybuilders feature better developed muscle mass of extremities and a smaller share of percentage of fat mass in body composition in comparison to amateurs. Professional bodybuilders consume proper amount of carbohydrates and fats and significantly higher level of protein, fiber and energy in diet compared to amateur group. In contrary, higher intake of fats is typical for amateur bodybuilders.
... Evidence supports a key role for elevated levels of androgens in the pathogenesis of PCOS [4][5][6][7][8][9][10][11], which can influence the function of various tissues in the body, including skeletal muscle. Androgen levels are associated with muscle size and strength [12][13][14]. Women with PCOS are reported to have increased lean mass [15][16][17], greater muscle strength [18,19], and enhanced muscle strength after progressive resistance training [20], suggesting a relationship between elevated androgen levels and muscle structure or function in these women. Muscle size is reported to positively correlate with serum androgen levels in women with PCOS [18,21,22], although some did not find a relationship between lean mass and androgen levels [15,16]. ...
... Androgens are well-known to increase muscle mass and strength [12][13][14]. Women with PCOS demonstrate hyperandrogenemia [36][37][38], which may influence muscle structure and function in this population. Analyses of body composition in women with PCOS compared to those without have suggested increased lean mass [15][16][17] and greater leg muscle mass in women with PCOS [39]. ...
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Women with polycystic ovary syndrome (PCOS) are reported to have greater lean mass and insulin resistance. To examine muscular changes in a prenatally androgenized (PNA) rat model for PCOS, Sprague–Dawley rats were exposed to 5 mg testosterone or vehicle daily on gestational days 16–19. At 15 weeks of age, endurance on a rota-rod treadmill was measured. At 16 weeks of age, fasting blood glucose and insulin, hindlimb skeletal muscle mass, muscle fiber cross-sectional area (CSA) and composition, and intra- and peri-muscular lipid droplets were examined. Expression of mitochondrial marker ATP synthase and insulin signaling proteins were also investigated. Compared with controls, PNA female rats demonstrated greater total body and hindlimb muscle weights, greater muscle fiber CSA, and trending reduced time on the rota-rod. An increase in fibers co-expressing the slow and fast isoforms of myosin (90 vs. 86%, p < 0.05) and greater expression of ATP synthase (6-fold, p < 0.005) were observed in the gastrocnemius (GN) muscle. More lipid content was observed in GN and tibialis anterior (TA) muscles. PNA rats had elevated fasting serum insulin (1.9 vs. 1.2 ng/mL, p < 0.005) but comparable fasting glucose. Expression of total and Ser636/9-phosphorylated IRS1 were altered in PNA rat hindlimb muscles. Together, skeletal muscle alterations in hindlimb muscles of a PNA rat model for PCOS may represent consequences of, or adaptations to, insulin resistance in this model.
... Figure 10 shows a simplified scheme of the main hormone-controlled mechanisms regulating glycaemia. In the liver, glucocorticoids increase glucose output [237] and favor lipogenesis [259] and TAG deposition in most tissues [260]; testosterone induces the accrual of protein [261,262] and stabilizes the maintenance of glycaemia [252]. Estrogens favor 2C oxidation [263], increase oxidative metabolism in mitochondria [245], and limit lipogenesis and TAG deposition [264]. ...
... We already know a part of the puzzle, but there are not yet enough dots to draw a sufficiently clear line to understand their real function and help us fight the ravages of our own (effective) systems of protection of energy and protein. In the liver, glucocorticoids increase glucose output [237] and favor lipogenesis [259] and TAG deposition in most tissues [260]; testosterone induces the accrual of protein [261,262] and stabilizes the maintenance of glycaemia [252]. Estrogens favor 2C oxidation [263], increase oxidative metabolism in mitochondria [245], and limit lipogenesis and TAG deposition [264]. ...
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Humans have developed effective survival mechanisms under conditions of nutrient (and energy) scarcity. Nevertheless, today, most humans face a quite different situation: excess of nutrients, especially those high in amino-nitrogen and energy (largely fat). The lack of mechanisms to prevent energy overload and the effective persistence of the mechanisms hoarding key nutrients such as amino acids has resulted in deep disorders of substrate handling. There is too often a massive untreatable accumulation of body fat in the presence of severe metabolic disorders of energy utilization and disposal, which become chronic and go much beyond the most obvious problems: diabetes, circulatory, renal and nervous disorders included loosely within the metabolic syndrome. We lack basic knowledge on diet nutrient dynamics at the tissue-cell metabolism level, and this adds to widely used medical procedures lacking sufficient scientific support, with limited or nil success. In the present longitudinal analysis of the fate of dietary nutrients, we have focused on glucose as an example of a largely unknown entity. Even most studies on hyper-energetic diets or their later consequences tend to ignore the critical role of carbohydrate (and nitrogen disposal) as (probably) the two main factors affecting the substrate partition and metabolism.
... The extant literature is replete with observation of significant rise in cTnT after prolonged intense endurance exercise [93][94][95]. Nevertheless, elevated TnT are considered as indexes of myocardial damage. ...
... Relatively little is known, however, whether high exercise intensity (with shortened durations) may mediate TnT release [94]. Accurate interpretation of TnT concentrations in this context is challenging. ...
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Background and Study Aim. The use of blood parameters in monitoring athletes is an essential but an unstandardized component of managing athletic preparation. This study aims to describe and evaluate typical measurements and responses observed while monitoring elite cyclist during a training camp. The reported observations might contribute in constituting a scientific support for other practitioners to employ. Material and Methods. 35 elite cyclists from the Algerian National team aged 16 – 23 years participated in this study. Peripheral fasting blood samples were collected in resting after 24 hrs of physical inactivity and outside competitions. Complete blood count (CBC) and hormonal index values (Cortisol, Testosterone, Probnp and TnT) were tested twice before and after the training camp. The statistical data were analysed by the SPSS software version 22.0. Results. The observed rates of change were significant (p
... Notwithstanding, the effects of TEST on ribosome biogenesis have been understudied. Indeed, it has been consistently reported that TEST administration increases skeletal muscle protein synthesis (Griggs et al., 1989;Brodsky et al., 1996;Ferrando et al., 1998); however, these studies did not examine the markers of ribosome biogenesis. Two additional studies (Breuer & Florini, 1965;Galavazi & Szirmai, 1971) have demonstrated that ORX results in a marked decrease in LABC ribosome content and TEST administration rescued this effect; however, these pioneering studies from the 1960s and 1970s lacked certain molecular features (i.e. the interrogation of explicit rRNA and/or ribosomalrelated protein expression patterns). ...
... decrease in phospho-pan rps6) to prevent uncontrolled hypertrophy. Indeed, the human literature also suggests that TEST treatment may decrease translational efficiency as 5-day TEST treatment increases skeletal muscle protein synthesis by 100% (Ferrando et al., 1998), whereas chronic (i.e. 12 weeks) of TEST treatment increases muscle protein synthesis by only 27% (Griggs et al., 1989). Chronic resistance training, another model of rapid muscle hypertrophy, has also been shown to diminish the phosphorylated rps6 response to exercise, and the authors posit that this attenuated translational efficiency response prevents uncontrolled hypertrophy of skeletal muscle (Nader et al., 2014). ...
... Testosterone boosting is helpful for muscle growth (10). Many athletes, especially bodybuilders, try to boost their testosterone levels to increase muscle mass and improve recovery from exercise. ...
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Context: D-Aspartic acid (DAA) is an amino acid found in the brain and reproductive system. Some investigations have reported beneficial effects of DAA on brain function and reproductive system health by increasing testosterone through the hypothalamic-pituitary-gonadal axis. However, its effect on body composition is unknown. Given testosterone's role in muscle growth, this study aimed to evaluate the effect of DAA supplementation on the body composition of trained males. Evidence Acquisition: PubMed, Scopus, Embase, and Web of Science (until 1 August 2021) were searched for this systematic review. Inclusion criteria assumed as clinical trials assessed the effect of DAA on body composition in trained males. After including articles by keywords, the articles were reviewed for meeting the eligibility criteria. Three independent researchers conducted the search and full-text review. Results: Among 134 articles located during the primary search, five articles (47 interventions and 43 controls) were included in the study based on eligibility criteria. All included clinical trials had a low risk of bias. A review of the relevant literature concludes that different doses of DAA (three grams, six grams, 7.12, and 12 grams) in different intervention periods (two weeks, four weeks, and 12 weeks) have no effects on body composition in trained males. Conclusions: DAA supplementation is a low-level booster of testosterone and has no significant effect on the testosterone level in professional male athletes, and cannot alter the body composition.
... Adolescents experience significant changes in hormonal levels (Reiter and Root, 1975). Concerning growth and development, testosterone contributes the most and is significantly elevated in adolescents (Nottelmann et al., 1987;Griggs et al., 1989). Testosterone was shown to have a robust positive effect on cognitive function and brain development (Beauchet, 2006;Nguyen et al., 2013;Hua et al., 2016). ...
Article
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Aerobic, anaerobic, and strength exercises are known to improve various cognitive functions, such as executive functions, pattern separation, and working memory. High-intensity functional training (HIFT) is a form of physical activity that can be modified to any fitness level and elicits greater muscle recruitment than repetitive aerobic exercises, thereby improving cardiovascular endurance, strength, and flexibility. HIFT emphasizes functional, multi-joint movements via high-intensity interval training (HIIT) and muscle-strengthening exercises. It is yet unknown, however, whether HIFT affects cognitive functions in adolescents. To address this question, we subjected adolescents to 3 × 20 min training sessions/week of HIFT for 3 months. The effects of HIFT were tested on performance in: (1) virtual reality (VR)-based spatial learning task; (2) computerized visual pattern separation; and (3) attention span. The control group performed a typical physical class three times per week. The effects on cognition were tested at baseline and following 3 months of HIFT. Three months into the intervention, the HIFT group achieved higher scores in the spatial learning task, pattern separation task, and in the attention span test, compared with controls. These data suggest that HIFT can potentially translate into improving school performance in adolescents.
... Previous research has shown that sexually dimorphic facial features are associated with testosterone during development (Marečková et al., 2013;Roosenboom et al., 2018;Verdonck et al., 1999;Welker et al., 2016;cf. Hodges-Simeon et al., 2016, 2018, 2020 and that testosterone levels are associated with increased aggression during challenge (Gray et al., 2019) and muscle mass (e.g., Griggs et al., 1989). ...
Article
Research has consistently demonstrated that faces manipulated to appear more masculine are perceived as more dominant. These studies, however, have used forced-choice paradigms, in which a pair of masculinized and feminized faces was presented side by side. These studies are susceptible to demand characteristics, because participants may be able to draw the conclusion that faces which appear more masculine should be rated as more dominant. To prevent this, we tested if dominance could be perceived when masculinized or feminized faces were presented individually for only 100 ms. We predicted higher dominance ratings to masculinized faces and better memory of them in a surprise recognition memory test. In the experiment, 96 men rated the physical dominance of 40 facial photographs (masculinized = 20, feminized = 20), which were randomly drawn from a larger set of faces. This was followed by a surprise recognition memory test. Half of the participants were assigned to a condition in which the contours of the facial photographs were set to an oval to control for sexual dimorphism in face shape. Overall, men assigned higher dominance ratings to masculinized faces, suggesting that they can appraise differences in facial sexual dimorphism following very brief exposure. This effect occurred regardless of whether the outline of the face was set to an oval, suggesting that masculinized internal facial features were sufficient to affect dominance ratings. However, participants' recognition memory did not differ for masculinized and feminized faces, which could be due to a floor effect. K E Y W O R D S aggression, dominance, intrasexual competition, sexual dimorphism
... While it seems that estradiol is the most important hormone for bone properties, testosterone is likely to have extra-skeletal effects which influences risk of fracture. Testosterone has great impact on lean body mass (25,26) and low total and free testosterone, but not estradiol, are associated with increased risk of falls in older men (11) . Being testosterone deficient is associated with higher risk of cardiovascular disease, metabolic syndrome and worse physical health in general (13,20) and a higher biological age may also be an explanation of the greater risk of falling. ...
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This study investigates the sex steroid hormone profile in younger men with distal radius fracture (DRF) in order to elucidate if this could explain the low bone density and osteoporosis previously observed. In a case‐control study 73 men with DRF (mean age 38±9; range 20‐51) was compared to 194 age‐matched, population controls. Performed assays: total testosterone (TT), calculated free testosterone (cFT), luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG), and total estradiol (E2). BMD hip and spine were measured. Fracture cases had lower cFT (298 vs 329 pmol/l; p=0.008) but not TT, compared to controls. FSH and SHBG were not statistically different. LH was almost 30% higher (5.7 vs 4.5 IU/l; p<0.001) and a lower E2 was observed (80.0 vs 87.1, p=0.098). Men with DRF had lower E2/SHBG ratio compared to controls (2.3 vs 2.9, p=0.013). A higher proportion of the fracture group had low TT (<10.5 nmol/L) 21% vs 11%, p=0.052, low cFT (<220 pmol/L) 18% vs 8%, p=0.017 and low E2 (<73 pmol/l) 48% vs 35%, p=0.044). Odds ratio for fracture when having low cFT was 2.3 (95% CI 1.02‐5.49, p=0.044) and with low E2 1.7 (95% CI 0.96‐2.96). In this study in young men with distal radius fracture exploring sex hormone levels, we find that sex hormone profiles may be disturbed with lower E2/SHBG ratio, lower cFT and higher luteinizing hormone. Estrogen is a strong determinant of bone mass also in men; hence, low levels of estradiol may be contributing to the observed lower BMD and these differences may be relevant to fracture risk.
... Long-term testosterone administration has well-known physiological effects such as inducing skeletal muscle hypertrophy (Griggs et al., 1989), accelerated lipolysis, and associated reduction of total body fat (Rebuffé-Scrive et al., 1991), as well as accelerated erythropoiesis (Beggs et al., 2014). Consequently, the anabolic androgenic steroid hormone testosterone and its synthetic analogues are some of the most widely used doping substances in both competitive sports (World Anti-Doping Agency, 2019; United States Anti-Doping Agency, 2020) and recreational exercise training (Sagoe et al., 2014). ...
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Purpose: Limited data are available on the acute performance-enhancing effects of single-dose administration of testosterone in healthy humans. Studies of testosterone administrations to healthy humans are rare due to the difficult nature and necessity of close clinical monitoring. However, our unique physiological experimental facilities combined with close endocrinological collaboration have allowed us to safely complete such a study. We tested the hypothesis that an intramuscular injection of 250 mg mixed testosterone esters (TEs) enhances physical performance in strength and power exercises acutely, measured 24 h after injection. Additionally, we investigated whether the basal serum testosterone concentration influences the performance in countermovement jump (CMJ), 30-s all out cycle sprint, and one-arm isometric elbow flexion. Methods: In a randomized, double-blind, placebo-controlled design, 19 eugonadal men received either a TE (n = 9, 23 ± 1 years, 183 ± 7 cm, 83 ± 10 kg) or a PLA (n = 10, 25 ± 2 years, 186 ± 6 cm, 82 ± 14 kg) injection. Hormonal levels and the performance in CMJ, 30-s all out cycle sprint, and one-arm isometric elbow flexion were measured before and 24 h after injection. Results: Firstly, an intramuscular injection of 250 mg mixed TEs did not enhance the vertical jump height in a CMJ test, peak power, mean power, and fatigue index in a 30-s all-out cycle sprint or rate of force development and maximal voluntary contraction in a one-arm isometric elbow flexion 24 h post-injection. Secondly, baseline testosterone levels appeared not to influence performance in strength and power exercises to a large extent in healthy, recreationally active young men. Conclusion: A single intramuscular injection of 250 mg mixed TEs has no acute ergogenic effects on strength and power performance in recreationally active, young men. This novel information has implication for basic physiological understanding. Whether the same applies to an elite athlete population remains to be determined. If so, this would have implications for anti-doping efforts aiming to determine the most cost-efficient testing programs.
... Despite the lack of evidence for differences in male and female astronaut muscle loss during spaceflight, men and women are well-known to have differences in muscle architecture and metabolism, with males having both greater muscle and bone mass, largely as a result of higher levels of the hormone testosterone (Griggs et al. 1989;Ploutz-Snyder et al. 2014). Indeed, studying muscle loss on Earth provides some hints that there may be sex differences in muscle loss in space. ...
Chapter
Loss of muscle mass and function has been a problem for astronauts since the dawn of the space age. On Earth, muscle is what allows people to move but is also key for maintaining global energy balance in the body. In space, muscle structure and function change, and these changes are mirrored by changes in gene expression. This means that when astronauts return to Earth or land at a destination to be explored, muscle may not function as well as desired. Such poor muscle function potentially jeopardizes mission success and/or astronaut health. Several active and passive countermeasures have been studied in space. While these measures can limit muscle atrophy, none have yet been proven to stop muscle loss in space. Key operational issues with limiting muscle loss in space are making sure proper food and nutrition are provided as well as attempting to allow as much activity as possible. In the absence of allowing physical activity, passive countermeasures may help, but these require validation in ground-based studies of short-term inactivity.
... In the cardiovascular system there is mainly testosterone bound to specific proteins (SHBG, sex hormone binding globulin) and free testosterone. Both of these forms take part in the synthesis of muscle proteins (Griggs et al., 1989). Furthermore, testosterone activates the glucose metabolism-related signalling pathway in skeletal muscle cells via regulation of glucose transporter-4 (GLUT-4), which plays an important role in supplying skeletal muscles with energy substrates when the muscles are working (Sato et al., 2008). ...
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Background Regular exercise leads to changes in muscle metabolism. The consequence of this is the adaptation to higher training loads.The aim of this study was to evaluate biomechanical and biochemical parameters describing the functions of skeletal muscles in periods when changes in training forms were introduced. Methods Seventeen male sweep-oar rowers, members of the Polish national rowing team, participated. The study was carried out at the beginning and at the end of the preparatory period. In the first and second examination measurements of torques of selected muscle groups and blood biochemical analysis were performed. Results There was observed a statistically significant decrease in the relative global force of the right lower limb between both terms of examination. A statistically significant increase in maximum torque was found for torso flexors. In the case of muscles responsible for torso rotation, a statistically significant decrease in the torque values of right torso rotators was observed. A significant difference was found with respect to creatine kinase activity, total testosterone concentration, total testosterone to cortisol ratio and total phenolics concentration ( p < 0.05). Conclusion The study shows that the rowers’ training should be more focused on building the strength of lower limbs to prevent the overload of lumbar spine and that the amount of force developed may be significantly affected by the antioxidant potential of rowers.
... Testosterone has several biological effects, including increased muscle mass, enhanced insulin sensitivity, and lipid use. (27,28) Lack of testosterone would conversely be expected to worsen insulin resistance and increase the delivery of lipotoxic lipids to the liver. The data presented here provide a rationale for studying the potential use of LPCN 1144 to both reverse hypogonadism and improve NAFLD in hypogonadal males. ...
Article
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Hypogonadism affects hepatic lipid metabolism and is expected to promote nonalcoholic fatty liver disease (NAFLD). The aims of this study were to determine (1) the prevalence of NAFLD in hypogonadal males and (2) the impact of correction of hypogonadism by LPCN 1144 (Lipocine, Inc., Salt Lake City, UT), an oral testosterone prodrug, on NAFLD in this population. Data were derived from a multicenter open‐label single‐arm trial of LPCN 1144 for hypogonadal males, in which a subset (n = 36) had serial magnetic resonance imaging–proton density fat fraction measurements (National Clinical Trial 03868059). NAFLD prevalence, defined by magnetic resonance imaging–proton density fat fraction ≥5%, was 66%. Eighty‐one percent of those with baseline liver fat (BL) ≥5% had improvement in liver fat content, and NAFLD resolved in 33% of subjects at 8 weeks (mean relative reduction: 45%) and 48% (mean relative reduction: 55%) after 16 weeks of LPCN 1144 therapy. The reduction in liver fat was greater in those with higher BL (BL ≥5%: 71%; BL ≥8%: 80%; and BL ≥10%: 75%). Normalization rate of alanine aminotransferase and gamma‐glutamyltransferase greater than the upper limit of normal range were 100% and 50% of treated patients, respectively. LPCN 1144 was not associated with major adverse events. Conclusion: Treatment with LPCN 1144 (oral T prodrug) in hypogonadal males with NAFLD resolved NAFLD in approximately half of the affected patients without any safety signals. Further studies are needed to validate its use in hypogonadal males with nonalcoholic steatohepatitis.
... High levels of SHBG indicate that there is likely less free testosterone available to the tissues because more testosterone is bound to SHBG. High levels of SBHG combined with low TT levels likely indicate that there is minimal free testosterone available, which may in turn impede muscle growth and workout recovery (15). Appropriate periworkout nutrition may become more important closer to competition because it may prove to mitigate losses in FFM and help enhance workout recovery when less free testosterone is available to the tissues. ...
Article
We carried out a prospective case study in a high-level amateur natural male bodybuilder throughout preparation for 4 competitions and during the ensuing post-contest recovery period. Laboratory testing was conducted monthly over a 1-year period, which included the following assessments: B-mode ultrasound evaluation of muscle thickness (MT), multi-frequency bioelectrical impedance analysis (MF-BIA), blood pressure (BP) and heart rate (HR) assessment, resting metabolic rate (RMR) via indirect calorimetry, skinfold testing, vertical jump height, isometric lower body strength testing, and a 3-factor eating questionnaire. Blood work (including testosterone, thyroid hormone, sex hormone binding globulin, glomerular filtration rate, blood urea nitrogen, aspartate aminotransferase, alanine aminotransferase, white blood count, albumin/globulin ratio, and lipoprotein A) was obtained separately from an outside lab at 4 timepoints. We also assessed the effectiveness of a carb deplete/carb load peaking strategy employed immediately prior to competition. The participant employed a high-volume, high-frequency, whole-body training program throughout the study period. Average daily nutritional intakes ranged from 1,953 to 3,415 kilocalories; 104 to 386 g carbohydrate; 253 to 263 g protein, and; 57 to 95 g lipid. Body fat was reduced to very low levels (~5%) immediately prior to competition, but this corresponded with a loss of lean mass. Alterations in metabolism, hormonal status, explosive strength, and psychological aspects of eating were observed during pre-contest preparation; however, all of these variables recovered quickly post-competition. The implementation of a carb deplete/carb load peaking strategy acutely increased muscle thickness, and thus may be a viable pre-contest approach to maximize muscular aesthetics.
... *p < 0.05, **p < 0.01, ***p < 0.001 (two-sided t-test, versus control). muscle development as other forms of metabolites (Bhasin et al., 1996;Griggs et al., 1989;Sato, Iemitsu, Aizawa, & Ajisaka, 2008;Shahidi, 2001). The biochemical effects of PDS and PG still require further research. ...
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Saponin derived from natural extracts can alleviate muscle atrophy. Dioscorea nipponica Makino (DNM) is commonly used in herbal medicine and contains various steroidal saponins, although its efficacy and mechanisms of action for treating muscle atrophy remain unknown. Here, differentiated myoblast cells treated with DNM showed increased MyoD and MyoG expression and effectively promoted muscle formation. DNM effectively inhibited muscle atrophy induced by tumor necrosis factor alpha (TNFα) monotherapy, and combination treatment with protodioscin and protogracillin (among the tested DNM constituents) showed a synergistic effect on differentiated myoblast cells. DNM and this combination repressed TNFα-induced increased MuRF1 and Atrogin1/MAFbx expression by inhibiting nuclear factor-kappa B (NF-κB) expression. DNM also effectively promoted the recovery of muscle formation in injured mice. Therefore, DNM and its multi-constituents can potentially be used as therapeutic agents for muscle-related diseases and represent prospective food supplements.
... [16] Testosterone increases muscle mass by increasing muscle protein synthesis. [24] In addition, low testosterone levels in males have been associated with an increased atherosclerosis burden and increased risk of cardiovascular events. [25,26] Atherosclerosis induced by testosterone deficiency in male mice was T-cell-dependent. ...
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The associations between the presence and severity of coronary artery disease (CAD) and measurements of the psoas major muscle (PMM) as assessed by multidetector row coronary computed tomography angiography (MDCT) are not known.We enrolled 793 patients who were clinically suspected to have CAD or had at least one cardiac risk factor and had undergone MDCT. The number of significantly stenosed coronary vessels (VD) and measurements of the PMM index (PMMI) were determined using MDCT.PMMI in the CAD group was significantly lower than that in the non-CAD group in males, but not females. In addition, the levels of PMMI tended to increase as the number of VD decreased in males. When male patients were divided into 2 groups according to median value of age, that is, relatively younger (53.4 ± 9.2 years) and older (72.6 ± 5.7 years) groups, the presence of CAD was independently associated with PMMI in the younger group by a multiple logistic regression analysis. The cut-off level of PMMI that gave the greatest sensitivity and specificity for the diagnosis of CAD in younger males was 8.3 cm/m (sensitivity 0.441, specificity 0.752).In conclusion, PMMI may be an imaging marker for evaluating the presence and/or severity of CAD in males, and particularly in the non-elderly.
... It is well known that testosterone treatment can increase muscle mass (Griggs et al., 1989;Neto et al., 2015;Ottenbacher, Ottenbacher, Ottenbacher, Acha, & Ostir, 2006), where it can cause hypertrophy in skeletal muscle fibres and possibly can also cause muscles' hyperplasia (Sinha-Hikim et al., 2002). On the other hand, testosterone administration showed different effects on fat, where it stimulates the commitment of muscle precursor cells into the myogenic lineage and prevents the differentiation of precursor cells into the adipogenic lineage . ...
Article
Androgenic–anabolic steroids (AASs) are synthetic derivative forms of the hormone testosterone. Sustanon® 250 solution for injection is one of those AASs that is used for low hormone levels and is self‐administered for recreational purposes. This study was conducted to investigate the effects of sustanon on the body weight of male and female rats. Animals were injected different doses of sustanon (vehicle, 1, 3.2, 10, 32 and 100 mg/kg, I.M., once/week, for 6 weeks), and the weights for each animal were obtained. The rats were observed for agitated/aggressive behaviours every other day. In the present study, sustanon injections at 1, 3.2, 10, 32 and 100 mg/kg treatments did not alter body weight in male rats compared to the control group. However, moderately high and supraphysiological doses of sustanon (3.2, 10 and 32 mg/kg) resulted in a significant increase in body weight after 1 month of weekly treatment in female rats. Aggressive/agitated behaviours were observed only in female rats at the period of weight increase. In conclusion, different doses of sustanon did not alter the body weight in male rats after 6 weeks of treatment but doses of 3.2, 10 and 32 mg/kg resulted in a significant increase in body weight of female rats.
... Alternatively, the difference in skull and also muscle volume might be caused by the weekly injections of human chorionic gonadotropin, which induces maturation (Palstra et al., 2005;). This hormone elevates testosterone levels (Winters et al., 1972), which, in turn can increase muscle mass (Griggs et al., 1985). Consequently, the increase in jaw muscle volume, combined with a necessary broadening and heightening of the skull, might stem from elevated testosterone levels following hormonal injections. ...
Article
The European eel (Anguilla anguilla) has been extensively studied, especially because of its highly specialized migratory behaviour associated with substantial phenotypic transformations. During this migration, one of those transformations the eel undergoes is from yellow to silver eel, a process known as silvering. Although the cranial morphology during the earlier glass, elver and yellow eel stages are well studied, little is known about actual morphological changes during the transformation process from the yellow to the silver eel stage. Yet, literature suggests drastic changes in musculoskeletal anatomy. Here, we investigated the cranial musculoskeletal morphology of 11 male European eels at different stages during silvering, resulting both from natural and artificial maturation. Using 3D-reconstructed µCT data of the head, the skull and cranial muscles associated with jaw closing and respiration were studied. Eye size was used as a proxy for the silvering stage. Size-adjusted jaw muscle volumes increased during silvering, although insignificantly. Accordingly, a near-significant increase in bite force was observed. Respiratory muscles size did increase significantly during silvering, however. Considering the eel's long migration, which often includes deep and thus potentially oxygen-poor environments, having a better performing respiratory system may facilitate efficient migration. Both overall skull dimensions and specifically orbit size increased with eye index, suggesting they play a role in accommodating the enlarging eyes during silvering. Finally, artificially matured eels had a wider and taller skull, as well as larger jaw muscles than wild silver eels. This could be caused (a) by different conditions experienced during the yellow eel stage, which are maintained in the silver eel stage, (b) by side effects of hormonal injections or (c) be part of the maturation process as artificially induced silver eels had a higher eye index than the wild silver eels.
... Sex steroid hormones are synthesized not only in the gonads, but also in the adrenal glands and brain. By influencing the reproductive tract, sexual phenotype, and secondary sexual characteristics of male and female animals including humans, sex steroid hormones entirely control the reproductive process: sexual development and maturation, sex-dependent brain differentiation, and sexual behavior [3,[13][14][15]. These steroids affect other tissues in non-reproductive systems that are not traditionally regarded as targets. ...
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Background: Sex steroid hormone receptors are classified into three classes of receptors: estrogen receptors (ER) α and β, androgen receptor (AR), and progesterone receptor (PR). They belong to the nuclear receptor superfamily and activate their downstream genes in a ligand-dependent manner. Since sex steroid hormones are involved in a wide variety of physiological processes and cancer development, synthetic chemical substances that exhibit sex steroid hormone activities have been applied as pharmaceuticals and consumed in large amounts worldwide. They are potentially hazardous contaminants as endocrine disruptors in the environment because they may induce inappropriate gene expression mediated by sex steroid hormone receptors in vivo. Results: To develop simple reporter gene assays with enhanced sensitivity for the detection of sex steroid hormones, we newly established mutant yeast strains lacking the CWP and PDR genes encoding cell wall mannoproteins and plasma membrane drug efflux pumps, respectively, and expressing human ERα, ERβ, AR, and PR. Reporter gene assays with mutant yeast strains responded to endogenous and synthetic ligands more strongly than those with wild-type strains. Sex steroid hormone activities in some pharmaceutical oral tablets and human urine were also detectable in these yeast assays. Conclusions: Yeast reporter gene assay systems for all six steroid hormone receptors, including previously established glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) assay yeasts, are now available. Environmental endocrine disrupters with steroid hormone activity will be qualitatively detectable by simple and easy procedures. The yeast-based reporter gene assay will be valuable as a primary screening tool to detect and evaluate steroid hormone activities in various test samples. Our assay system will strongly support the detection of agonists, antagonists, and inverse agonists of steroid hormone receptors in the field of novel drug discovery and assessments of environmental pollutants.
... Masculinized ☆ Data and materials from all studies, including pre-registration plans for Studies 3-4, are available: https://osf.io/gcpk6/?view_only=88914a8be39d441ba83a83 82f923d821 facial features provide such information for men (Caton, Zhao, Lewis, & Dixson, 2022). Masculinization is rooted in fetal androgen exposure and pubertal testosterone surges, which foster muscle growth and face widening (Griggs et al., 1989;Whitehouse et al., 2015). The resulting upper body strength is associated with masculinized facial features from which perceivers can infer men's actual strength (Holzleitner & Perrett, 2016;Price, Sheehy-Skeffington, Sidanius, & Pound, 2017). ...
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Individuals use facial width-to-height ratio (fWHR) to infer men's formidability. We hypothesized that fWHR assessments would form a basis for men's coalitional value, with high-fWHR men being valuable in roles requiring physical strength. Five studies (N = 1323) tested how perceptions of formidability influence coalitional decisions. In addition to replicating previous findings indicating a preference for high-fWHR men in tasks requiring strength (Study 1), the formidability inference most associated with this high-fWHR preference was perceived strength and not aggressiveness (Studies 2a, 2b). Two pre-registered studies showed that activating competitive motivations increased preferences for high-fWHR allies (Study 3), though this preference appeared driven by a tolerance for high-fWHR men rather than an interest (Study 4). Findings provide evidence for how inferences of fWHR shape interpersonal preferences based on social contexts.
... [27] This study also contributes to the idea that boys have a higher mean value for HGS than girls, [28] probably due to the difference in the kind of activity of each gender. [29] In fact, boys usually have more muscular strength in general than females, mainly due to the difference in the size of the muscle in view of the male testosterone hormone responsible for enhancing that size; specifically, the hormone increases the compose II filaments with more rapid movement of glycolytic proteins. [30] The mean tip-to-tip PS varied as 3.86-3.95 ...
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Aims: The study aimed to assess the percentage difference of hand dimensions and their correlation with grip and pinch strength among school children in Saudi Arabia. Materials and methods: Anthropometric measurements, hand dimensions, grip, and pinch strength measurements were obtained from 200 healthy schoolchildren in both genders aged 6-16 years. A Jamar electronic handgrip dynamometer was used to measure handgrip strength in kg. Pinch dynamometer was used to measure the two-point pinch strength, three-point pinch strength and lateral pinch strength in kg. Hand circumference was measured following hand arch at the maximum palm level. Hand span from the tip of the thumb to the tip of the little finger with the hand opened as broad as possible. Hand length from the tip of the middle finger to the midline of the distal wrist crease. Palm length from the distal wrist crease to the base of the middle finger. Results: The percentage of difference of hand dimensions between both the genders was statistically significant. Both handgrip and pinch strength were significantly correlated with anthropometric measurements and hand dimensions. Body mass index had mild correlation with both handgrip strength and pinch strength (P < 0.05). Age, hand circumference, hand span, hand length and palm length had moderate to strong correlation with both grip and pinch strength (P < 0.01). Conclusion: The current study provides a source of perspective reference values in clinical settings for hand dimensions. The present study showed significant correlations with handgrip and pinch grip strengths among schoolchildren in Saudi Arabia.
... Therefore, it is possible that the muscle mass and strength of the elderly women in the MG were higher than those of the EG because they were more susceptible to the effects of differences in timing (differences in the efficiency of protein intake). In addition, testosterone secretion related to MPS is 10 times higher in men than in women, and muscle mass and strength are known to be higher in men than in women at all ages, despite the decrease in testosterone secretion with aging (27,28). Therefore, men may have been more influenced by other factors, such as testosterone, in muscle synthesis than women, and may have been less affected by the timing of protein intake. ...
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Background: The effects of different intake patterns of meal protein on muscle mass have not been clarified. We cross-sectionally and longitudinally examined the effect of different timing of protein intake on sarcopenia-related factors in older adults. Methods: This cross-sectional study 1 included 219 (male, n = 69, female, n = 150) elderly subjects aged ≥65 years. Subjects who consumed more protein at breakfast than at dinner were grouped into the morning group (MG, n = 76; male, n = 26; female, n = 50), and those who consumed more protein at dinner than at breakfast were grouped into the evening group (EG, n = 143; male, n = 43; female, n = 100). In cross-sectional study 2-1 (female, n = 125), the subjects were classified into four groups according to the number of meals with sufficient protein intake. In cross-sectional studies 2-2 (female, n = 125) and 2-3 (female, n = 27), the subjects were classified into eight groups and three groups according to whether they had consumed sufficient protein at three meals; sarcopenia-related factors were compared. The intervention study was a placebo-controlled, double-blind, randomized controlled trial that included 40 elderly women with low daily breakfast protein intake. The subjects were divided into four groups: morning protein and placebo intake groups and evening protein and placebo intake groups. Each group consumed the test food (containing 10 g milk protein) or placebo in the morning or evening for 12 weeks. Blood indices and physical function were assessed before and after the intervention. Results: Comparing all subjects, MG showed significantly higher handgrip strength than did EG ( P < 0.05). The higher ratio of morning protein intake relative to the total protein intake, the better the muscle mass ( r = 0.452, P < 0.05) and handgrip strength ( r = 0.383, P < 0.05). The intervention study showed an increase in muscle mass with the intake of milk protein in the morning rather than in the evening ( P < 0.05). Conclusions: Protein intake at breakfast might have relatively stronger effects on skeletal muscle mass than at lunch and dinner.
... 6 Testosterone enhances muscle protein synthesis and increases muscle mass. 23 Therefore, in comparison with males, females gain less lean mass during puberty and have less muscle mass in adulthood. [24][25][26] Creatinine is produced nonenzymatically and irreversibly from muscle creatine at a constant daily rate and filtered out of the blood by the renal glomeruli with minimal tubular reabsorption. ...
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Purpose: Older individuals are at high risk for hypernatremia. However, actual data on serum sodium levels and differences between the sexes remain unclear in the older Japanese population. This study aimed to describe the data regarding serum sodium level and hypernatremia prevalence and to investigate whether female sex is associated with an increased risk of hypernatremia. Patients and methods: We retrospectively analyzed the data of adults aged ≥65 years without severely reduced kidney function who underwent an annual health checkup in 2019. Serum sodium levels were investigated as the outcome and corrected for glucose, if necessary. Clinical characteristics were compared between women and men. Results: In the 903 participants consisting of 273 women and 630 men who were enrolled in this study, the overall prevalence of hypernatremia, defined as a serum sodium level ≥145 mmol/L, was 12.5%. Female participants showed significantly more frequent hypernatremia than male participants (17.6% vs 10.3%, p = 0.003) and higher serum sodium levels (median [interquartile range]; 143.0 [142.0, 144.0] vs 142.4 [141.5, 144.0], p <0.001). Serum creatinine (sCr), but not estimated glomerular filtration rate (eGFR), was correlated with serum sodium levels (rs = -0.108, p = 0.001). In the binary logistic regression analysis, female sex was significantly associated with hypernatremia (odds ratio, 1.89; 95% confidence interval, 1.23-2.89; p = 0.004) even after adjusting for age, alcohol use, antihypertensive agent use, body mass index, and winter season. The association between female sex was reduced and no longer significant after adjusting for sCr, although the association remained unchanged after adjustment for eGFR. Conclusion: One-eighth of the older community dwellers in Japan exhibits hypernatremia after an overnight fast, and female sex is a significant risk factor. Since sCr is a surrogate of muscle mass, smaller muscle mass possibly mediates the association between female sex and hypernatremia.
... Many studies have been done that support the beneficial effects, both direct and indirect, of testosterone on skeletal muscles. [22,23] It binds to the androgen receptor directly, and this complex translocates to the nucleus to increase muscle protein synthesis. [24] Testosterone affects muscle fiber by acting at multiple steps in the pathways that regulate muscle protein synthesis and breakdown as well as the commitment and differentiation of pluripotent stem cells. ...
... One of the factors that causes muscle hypertrophy at a relatively early stage is the high sensitivity of the masseter muscle to testosterone. Testosterone has the effect of promoting protein synthesis in muscle [35]. In a study of rats, injection of testosterone increased masseter muscle mass by 38%, which was reportedly more sensitive than other muscles [36]. ...
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Maintaining oral function is important in older individuals with missing teeth for leading a healthy and independent life. This study aimed to evaluate whether simple isometric exercises can maintain and improve oral function (maximum occlusal force [MOF], masticatory ability [MA]) and masticatory muscle properties (masseter muscle thickness [MMT] and echo intensity [MMEI]) in older adults in the maintenance phase of removable prosthetic treatment. Participants were randomly allocated into intervention and control groups. The intervention group was instructed to perform maximum clenching for 10 s, whereas the control group was instructed to tap the teeth at an arbitrary speed for 10 s. Both were repeated five times at an interval of 5 s between each activity and twice a day for 4 weeks. The outcomes were measured after a month of exercise. The intervention group showed significant improvement in MOF, MMT during contraction, and MMEI during contraction. There was no significant difference in the MA and MMEI at rest. In the control group, no improvement was observed in any of the parameters. When the isometric exercises were performed using a mouthpiece, there was improvement in oral function and masseter muscle properties in older individuals with Eichner B status who used dentures.
... It also appears to act on substrates in the brain to increase aggression and competitiveness [145]. While not studied directly, higher testosterone concentrations may be ergogenic in ultra-endurance competition: directly, due to its association with hemoglobin concentrations [144], mitochondrial function [146], and lipid metabolism [147]; and indirectly, by augmenting muscle protein synthesis and thereby facilitating recovery [148]. Importantly, males exhibit a 30-fold increase in circulating testosterone from puberty, resulting in levels that are 15-20 times higher in adult males than females [149]. ...
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Ultra-endurance has been defined as any exercise bout that exceeds 6 h. A number of exceptional, record-breaking performances by female athletes in ultra-endurance sport has roused speculation that they might be predisposed to success in such events. Indeed, while the male-to-female performance gap in traditional endurance sport (e.g., marathon) remains at ~10%, the disparity in ultra-endurance competition has been reported as low as 4% despite the markedly lower number of female participants. Moreover, females generally outperform males in extreme-endurance swimming. The issue is complex, however, with many sports-specific considerations and caveats. This review summarizes the sex-based differences in physiological functions and draws attention to those which likely determine success in extreme exercise endeavors. The aim is to provide a balanced discussion of the female versus male predisposition to ultra-endurance sport. Herein, we discuss sex-based differences in muscle morphology and fatigability, respiratory-neuromechanical function, substrate utilization, oxygen utilization, gastrointestinal structure and function, and hormonal control. The literature indicates that while females exhibit numerous phenotypes that would be expected to confer an advantage in ultra-endurance competition (e.g., greater fatigue-resistance, greater substrate efficiency, and lower energetic requirements), they also exhibit several characteristics that unequivocally impinge on performance (e.g., lower O2-carrying capacity, increased prevalence of GI distress, and sex-hormone effects on cellular function/ injury risk). Crucially, the advantageous traits may only manifest as ergogenic in the extreme endurance events which, paradoxically, are the races that females less often contest. The title question should be revisited in the coming years when/if the number of female participants increases.
... Hyperinsulinemia and insulin resistance are also common in liver cirrhosis; increased insulin levels induce satiety, leading to a reduction in energy intake [127]. Testosterone is reduced in about 90% of men with liver cirrhosis [128] and plays an important role in protein synthesis and protein breakdown [129]. ...
Article
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Liver cirrhosis is an increasing public health threat worldwide. Malnutrition is a serious complication of cirrhosis and is associated with worse outcomes. With this review, we aim to describe the prevalence of malnutrition, pathophysiological mechanisms, diagnostic tools and therapeutic targets to treat malnutrition. Malnutrition is frequently underdiagnosed and occurs-depending on the screening methods used and patient populations studied-in 5-92% of patients. Decreased energy and protein intake, inflammation, malabsorption, altered nutrient metabolism, hypermetabolism, hormonal disturbances and gut microbiome dysbiosis can contribute to malnutrition. The stepwise diagnostic approach includes a rapid prescreen, the use of a specific screening tool, such as the Royal Free Hospital Nutritional Prioritizing Tool and a nutritional assessment by dieticians. General dietary measures-especially the timing of meals-oral nutritional supplements, micronutrient supplementation and the role of amino acids are discussed. In summary malnutrition in cirrhosis is common and needs more attention by health care professionals involved in the care of patients with cirrhosis. Screening and assessment for malnutrition should be carried out regularly in cirrhotic patients, ideally by a multidisciplinary team. Further research is needed to better clarify pathogenic mechanisms such as the role of the gut-liver-axis and to develop targeted therapeutic strategies.
... Of note, these processes are not only energy-consuming, but also yield side-products, i.e. "waste". For example, cellular protein synthesis (which is stimulated by testosterone (Griggs et al., 1989)) is inevitably paralleled by a certain accumulation of defective and/or misfolded proteins requiring clearance. This is accomplished by maintenance programs (e.g. ...
Article
The growing life expectancy in modern societies has raised scientific interest in identifying medical interventions to alleviate age-associated pathologies such as vascular calcification, cognitive decline, sarcopenia, osteoporosis and sexual dysfunction. Although no such single treatment has thus far been established in humans, some clinicians and patients have set their hopes on testosterone replacement therapy (TRT) as a potential “fountain of youth” for aging men. While TRT has proven effective in ameliorating distinct symptoms of late-onset hypogonadism (LOH), its safety remains to be demonstrated. Besides humans, multiple other species exhibit age-related reductions in circulating testosterone levels, raising the question whether such changes are an inherent, pathological feature of growing organismal age or rather reflect an adaptive response. In this manuscript, we apply key principles of evolutionary medicine to testosterone biology and LOH to provide a novel perspective on these two fields. Additionally, we discuss insightful data derived from the animal kingdom to illustrate the plasticity of individual testosterone trajectories across the lifespan, outline cost-benefit-considerations of TRT in LOH and highlight potential caveats of such therapies.
... One of the factors that causes muscle hypertrophy at a relatively early stage is the high sensitivity of the masseter muscle to testosterone. Testosterone promotes protein synthesis in the muscle 36 . In a study of rats, injection of testosterone increased the masseter muscle mass by 38%, which was reportedly more sensitive than other muscles 37 . ...
Article
Full-text available
Maintaining oral function in older individuals with missing teeth is important for leading a healthy and independent life. This study aimed to evaluate whether simple isometric exercises can maintain and improve the oral function [maximum occlusal force (MOF) and masticatory ability (MA)] and the masticatory muscle properties [masseter muscle thickness (MMT) and echo intensity (MMEI)] in older adults during the maintenance phase of removable prosthetic treatment. Participants were randomly categorized into the intervention and control groups. The mouthpieces were distributed, and participants were instructed to use them for exercising. The intervention group was instructed to perform maximum clenching for 10 s, whereas the control group was instructed to tap the teeth at an arbitrary speed for 10 s. Both were repeated five times at an interval of 5 s between each activity and twice daily for 4 weeks. The outcomes were measured after a month of exercise. The intervention group showed a significant improvement in the MOF, MMT during contraction, MMT at rest and MMEI during contraction. There were no significant differences in the MA and MMEI at rest. In the control group, no improvement was observed in any of the parameters. When the isometric exercises were performed using a mouthpiece, there was an improvement in the oral function and masseter muscle properties in older individuals with Eichner B status who used dentures.
... In men, supraphysiological doses of testosterone, combined with strength training, increase fat-free mass and muscle size and strength 50 as well as increase protein synthesis and net muscle protein balance. 51 In sports, androgens induce performance 52 In TM, fractional anisotropy increases might reflect a greater richness in axonal microtubules and macromolecules. Consequently, we proposed a process in brain cells that would be like the anabolic one described in the muscle. ...
Article
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Transgender men (TM) experience an incongruence between the female sex assigned when they were born and their self-perceived male identity. Some TM seek for a gender affirming hormone treatment (GAHT) to induce a somatic transition from female to male through continuous administration of testosterone. GAHT seems to be relatively safe. However, testosterone produces structural changes in the brain as detected by quantitative magnetic resonance imaging. Mainly, it induces an increase in cortical volume and thickness and subcortical structural volume probably due to the anabolic effects. Animal models, specifically developed to test the anabolic hypothesis, suggest that testosterone and estradiol, its aromatized metabolite, participate in the control of astrocyte water trafficking, thereby controlling brain volume.
... 46 Testosterone and sarcopenia in chronic kidney disease Uraemic patients have significantly lower free testosterone. 47,48 The CKD population is at high risk for muscle atrophy and sarcopenia due to both the existing testosterone deficiency and the resulting complications of CKD, inflammation, and malnutrition ( Figure 3). Although there are no randomized controlled trial (RCT) evaluating the relationship between testosterone levels and sarcopenia in CKD patients in the literature the effect of testosterone replacement on sarcopenia has been investigated based on the very high probability of this relationship. ...
Article
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Sarcopenia or muscle wasting is a progressive and generalized skeletal muscle disorder involving the accelerated loss of muscle mass and function, often associated with muscle weakness (dynapenia) and frailty. Whereas primary sarcopenia is related to ageing, secondary sarcopenia happens independent of age in the context of chronic disease states such as chronic kidney disease (CKD). Sarcopenia has become a major focus of research and public policy debate due to its impact on patient's health‐related quality of life, health‐care expenditure, morbidity, and mortality. The development of sarcopenia in patients with CKD is multifactorial and it may occur independently of weight loss or cachexia including under obese sarcopenia. Hormonal imbalances can facilitate the development of sarcopenia in the general population and is a common finding in CKD. Hormones that may influence the development of sarcopenia are testosterone, growth hormone, insulin, thyroid hormones, and vitamin D. Although the relationship between free testosterone level that is low in uraemic patients and sarcopenia in CKD is not well‐defined, functional improvement may be seen. Unlike testosterone, it is known that vitamin D is associated with muscle strength, muscle size, and physical performance in patients with CKD. Outcomes after vitamin D replacement therapy are still controversial. The half‐life of growth hormone (GH) is prolonged in patients with CKD. Besides, IGF‐1 levels are normal in patients with Stage 4 CKD—a minimal reduction is seen in the end‐stage renal disease. Unresponsiveness or resistance of IGF‐1 and changes in the GH/IGF‐1 axis are the main causes of sarcopenia in CKD. Low serum T3 level is frequent in CKD, but the net effect on sarcopenia is not well‐studied. CKD patients develop insulin resistance (IR) from the earliest period even before GFR decline begins. IR reduces glucose utilization as an energy source by hepatic gluconeogenesis, decreasing muscle glucose uptake, impairing intracellular glucose metabolism. This cascade results in muscle protein breakdown. IR and sarcopenia might also be a new pathway for targeting. Ghrelin, oestrogen, cortisol, and dehydroepiandrosterone may be other players in the setting of sarcopenia. In this review, we mainly examine the effects of hormonal changes on the occurrence of sarcopenia in patients with CKD via the available data.
... Beards are strikingly sexually dimorphic, appearing first in late childhood, developing further under the actions of androgens during puberty, with full expression typically evident at young adulthood (Randall, 2008). While muscularity and masculine craniofacial shape require testosterone for their expression (Griggs et al., 1989;Whitehouse et al., 2015), facial hair develops as testosterone is converted into dihydrotestosterone via the enzyme 5-alpha reductase 2 (Randall, 2008). How androgens exert effects on the density, patterning, and distribution of facial hair is genetically determined (Adhikari et al., 2016). ...
Article
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Objectives To test whether intra-sexual selection has influenced perceptions of male facial hair. We predicted that beards would increase the speed and accuracy of perceptions of angry but not happy facial expressions. We also predicted that bearded angry faces would receive the highest explicit ratings of masculinity and aggressiveness, whereas higher prosociality ratings would be ascribed to clean-shaven happy faces.MethodsA total of 106 participants, ranging from 17 to 59 years of age (M = 27.27, SD = 10.03); 59 were female and 47 were male (44.3%) completed an emotion categorization tasks and an explicit ratings task. Participants viewed faces of the same men when bearded, clean-shaven, and 10 days of natural growth (i.e. stubble) when posing angry and happy facial expressions.ResultsAngry facial expressions were categorised most rapidly and with the greatest accuracy on bearded faces, followed by faces with stubble then clean-shaven faces. Conversely, happy facial expressions were categorised most rapidly and with the greatest accuracy on clean-shaven faces, followed by stubbled faces then bearded faces. Irrespective of facial expression, full bearded faces received the highest ratings of masculinity followed by faces with stubble then clean-shaven faces. Aggressiveness ratings were highest for angry faces with full beards, followed by angry faces with stubble, with clean-shaven angry faces receiving the lowest ratings. In contrast to our prediction, bearded smiling faces were rated as significantly more prosocial than stubbled and clean-shaven smiling faces.Conclusions These findings contribute further evidence that men’s beardedness represents an intra-sexually selected badge of status that enhances nonverbal threat potentially by augmenting underlying masculine facial structures.
... Testosterone is a major androgen secreted endogenously that interacts with skeletal muscle cells through binding to ARs. Testosterone levels gradually decrease after 30 years of age, and this decrease is associated with a decline in muscle mass and strength [38,39]. Furthermore, testosterone promotes regeneration by activating satellite cells [40]. ...
Article
Sarcopenia is a disease characterized by age-related decline of skeletal muscle mass and function. The molecular mechanisms of the pathophysiology of sarcopenia form a complex network due to the involvement of multiple interconnected signaling pathways. Therefore, signaling receptors are major targets in pharmacological strategies in general. To provide a rationale for pharmacological interventions for sarcopenia, we herein describe several druggable signaling receptors based on their role in skeletal muscle homeostasis and changes in their activity with aging. A brief overview is presented of the efficacy of corresponding drug candidates under clinical trials. Strategies targeting the androgen receptor, vitamin D receptor, Insulin-like growth factor-1 receptor, and ghrelin receptor primarily focus on promoting anabolic action using natural ligands or mimetics. Strategies involving activin receptors and angiotensin receptors focus on inhibiting catabolic action. This review may help to select specific targets or combinations of targets in the future.
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BACKGROUND: The aim of this study was to determine the interrelationship between the resting serum testosterone (T) levels of female athletes from different types of sporting events and their athletic success. METHODS: The study involved 599 Russian international-level female athletes (95 highly elite, 190 elite, and 314 sub-elite; age: 16-35 years) and 298 age-matched female controls. The athlete cohort was stratified into four groups according to event duration, distance, and type of activity: 1) endurance athletes, 2) athletes with mixed activity, 3) speed/strength athletes, and 4) sprinters. Athletic success was measured by determining the level of achievement of each athlete. RESULTS: The mean (SD) T levels of athletes and controls were 1.65 (0.87) and 1.76 (0.6) nmol/L (P=0.057 for difference between groups) with ranges of 0.08-5.82 and 0.38-2.83 nmol/L in athletes and controls, respectively. T levels were positively associated with athletic success in sprinters (P=0.0002 adjusted for age) only. Moreover, none of the sub-elite sprinters had T>1.9 nmol/L, while 50% of elite and highly elite sprinters had T>1.9 nmol/L (OR=47.0; P<0.0001). CONCLUSIONS: Our data suggest that the measurement of the serum T levels significantly correlates with athletic success in sprinters but not other types of athletes and in the future may be useful in the prediction of sprinting ability.
Thesis
Afin d’évaluer la qualité alimentaire et l’efficacité métabolique des aliments mixtes combinant différentes sources protéiques végétales ou des sources protéiques végétales/animales, deux aliments de base, les pâtes alimentaires et les gels laitiers, ont été choisis comme vecteurs et ont été enrichis par des farines ou des protéines de légumineuses. La structure de la fraction protéique des aliments mixtes a été étudiée à l’échelle moléculaire. La relation entre cette structure et la digestibilité in vitro et in vivo des protéines a été évaluée. L’effet de la formulation et/ou du procédé de fabrication de ces aliments mixtes sur le métabolisme protéique in vivo a été étudié chez des rats jeunes en croissance et des rats âgés. Le changement de la formulation des pâtes alimentaires, c'est à dire l’incorporation de trois farines de légumineuses différentes (féverole, lentille ou pois cassé), génère des modifications de structure du réseau protéique influençant la digestibilité des protéines. Les études animales montrent que la qualité alimentaire des pâtes enrichies en légumineuses est comparable à celle d’une protéine animale comme la caséine et ce, quel que soit le type de légumineuses utilisé. La rétention protéique corporelle et la synthèse protéique musculaire des rats âgés, consommant des régimes iso- protéiques à base de pâtes alimentaires enrichies en légumineuses ou de caséine, sont comparables. Elles restent cependant inférieures à celles induites par les protéines solubles du lait. L’utilisation de gels laitiers enrichis en protéines de féverole chez le rat a révélé un effet de la formulation et du procédé de gélification sur la digestion et la rétention protéiques. La digestibilité in vivo des protéines est plus élevée chez les rats consommant le régime contenant le gel fermenté mixte composé de protéines de caséine et de féverole comparativement à son homologue de même composition mais acidifié par voie chimique. La rétention protéique est encore améliorée chez les rats ayant consommé le régime contenant le gel fermenté composé de protéines de caséine, de féverole et de lactosérum. Ces aliments enrichis en légumineuses, riches en protéines, équilibrés en acides aminés indispensables commencent à être disponibles sur le marché. Ils pourraient être proposés à la population âgée notamment dans des situations physiopathologiques impliquant une perte de protéines corporelles.
Article
This study was conducted to investigate the effect of dietary daidzein (DAI) supplementation on growth performance, carcass traits, and meat quality in growing-finishing pigs. Seventy-two DLY (Duroc × Landrace × Yorkshire) male castrated growing-pigs were randomly assigned to four treatments, and fed with a basal diet (CON) or basal diet containing different doses of DAI (12.5, 37.5, and 62.5 mg/kg). Results showed that DAI supplementation significantly increased (P < 0.05) the average daily gain (ADG). Moreover, DAI not only elevated the serum insulin-like growth factors-1 (IGF-1) and testosterone concentrations (P < 0.05), but also elevated the superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC). Interestingly, DAI supplementation at high dose (62.5 mg/kg) significantly increased the intramuscular fat (IMF) content but reduced the fat content in liver (P < 0.05). The drip loss and shear force were both decreased in pigs treated with 62.5 mg/kg DAI (P < 0.05). DAI supplementation elevated the expression level of MyHC I and decreased the expression level of MyHC IIb in longissimus thoracis (P < 0.05). Importantly, DAI altered the expression profiles of critical metabolic genes in the longissimus thoracis and liver. The phosphoenolpyruvate carboxykinase (PEPCK) and hormone-sensitive lipase (HSL) genes were downregulated in the longissimus thoracis (P < 0.05). However, the expression levels of fatty acid synthase (FASN) and acetyl CoA carboxylase 1 (ACC1) genes were upregulated by DAI (P < 0.05). In the liver, DAI elevated the expression level of glucokinase (GCK) but decreased the expression level of ACC1 (P < 0.05). These results not only indicate a beneficial effect of dietary DAI supplementation on growth performance but also offer potential mechanisms behind the DAI-regulated meat quality in pigs.
Chapter
Osteosarcopenia is a growing healthcare challenge. This is compounded by a lack of pharmacological strategies to treat both muscle and bone simultaneously. While there are no approved medications for osteosarcopenia, there are some compounds that are known to have a dual role in the treatment of muscle and bone. This chapter discusses the relevant literature, the efficacy, and the challenges surrounding these agents, as well as identifying avenues of future research. Agents of the androgen and endocrine axes repurposed antifracture medications, and factors involved in the crosstalk in muscle and bone are discussed. While there are a number of promising opportunities for future research, as yet there is no clear front-runner in the race to a treatment. More research into the relationship between muscle and bone is required to identify key components of their intertwined physiologies in order to identify the critical factors and pathways that might regulate the disease.
Chapter
Sex steroids, comprising of the androgens, estrogens, and progestogens, are fundamentally important to the development of muscle, bone, and fat across the life course. Each has roles that differ between these tissues, the male and female sexes, and developmental stage. It is the differential production of sex steroids and expression of their receptors that mediates much of the pubertal development in muscle, bone, and fat, which in turn determines the typical dimorphic sexual phenotypes. It is similar to how this differential production changes over time that is responsible for much of the typical sex-specific changes seen with normal aging. This chapter considers the sex-specific production of sex steroids and their effects upon each muscle, bone, and fat. It additionally covers the developmental changes in sex steroid production, and how this contributes to age-related changes in these three tissues.
Article
Background 11β-methyl-19-nortestosterone (11β-MNT) is a modified testosterone (T) with androgenic and progestational activity. A single oral dose of the prodrug, 11β-MNT dodecylcarbonate (11β-MNTDC), was well-tolerated in healthy men. Methods We conducted a randomized, double-blind study at two academic medical centers. 42 healthy men (18-50 years) were randomized to receive oral placebo or 11β-MNTDC, 200 or 400 mg daily, for 28 consecutive days. Primary outcome (safety and tolerability) measures were assessed twice per week. Subjects underwent serial blood sampling over 24h on Days 1 and 28 to assess secondary outcomes: pharmacokinetics (serum drug concentrations); pharmacodynamics of 11β-MNTDC (serum sex steroids and gonadotropins); and mood and sexual function (via validated questionnaires). Results There were no serious adverse events. No participants discontinued due to an adverse event or laboratory test abnormality. 11β-MNTDC resulted in a dose-related increase in serum 11β-MNTDC and 11β-MNT concentrations sustained over 24h. Administration of 11β-MNTDC resulted in a marked suppression of serum gonadotropins, T, calculated free T, E2 and SHBG over the treatment period (p<0.01). Adverse effects that may be related to 11β-MNTDC included weight gain, acne, headaches, fatigue, and mild mood changes, with 5 men reporting decreased libido and 3 decreased erectile/ejaculatory function. Serum LDL-cholesterol, weight (~2 kg), hematocrit, and hemoglobin increased and serum HDL-cholesterol decreased in both 11β-MNTDC groups. Conclusion Daily oral 11β-MNTDC for 28 days in healthy men markedly suppressed serum gonadotropin and testosterone concentrations without serious adverse effects. These results warrant further evaluation of 11β-MNTDC as a potential male oral contraceptive.
Thesis
Testosterone esters and clenbuterol are among the most frequently used doping substances in elite and recreational sports. Direct detection in urine and blood samples is hampered by the costs of collection, transportation and analysis, and the rapid hydrolysis of testosterone esters in blood. Indirect detection of testosterone by the ‘Athlete Biological Passport’ (ABP) steroidal module is limited by both the associated costs and confounding factors. Therefore, the present thesis aimed to improve the time- and cost-efficiency in doping analysis by evaluating 1) the applicability of dried blood spots (DBS) as a complementary sample matrix and 2) whether the hematological module of the ABP can be used to indicate doping of testosterone and thereby increase detection, given the erythropoietic effect of testosterone, and 3) by determining the most cost-efficient anti-doping testing program based on detection windows and performance-enhancing effects. In Paper I-III, DBS, urine and blood samples from men receiving two intramuscular injections of Sustanon® 250 (n = 9) or placebo (n = 10) in a randomized, placebo-controlled design were analyzed for direct and indirect detection of testosterone esters and assessment of serum levels of reproductive hormones. In Paper III, the performances in countermovement jump, 30-s all out cycle sprint and one-arm isometric elbow flexion were measured before and 24 h after the first Sustanon® injection. In Paper IV, DBS and urine samples from 6 healthy men receiving a single oral dose of 80 µg clenbuterol were collected and analyzed for detection of clenbuterol. Paper II and IV demonstrated that the DBS assays allow for detection up to 14 days after an intramuscular injection of 250 mg Sustanon®, and for at least 3 days after an oral ingestion of 80 µg clenbuterol, with 100% specificity. Further, preliminary data suggest that DBS-sampling is well accepted by athletes. Additionally, Paper IV showed that clenbuterol can be detected for at least 10 days in urine after ingestion of 80 µg of drug. Paper I demonstrated that some hematological biomarkers are affected by testosterone administration, and that the largest changes occur 3-10 days after an injection. Paper III showed that a single injection of testosterone esters do not enhance human performance acutely in a countermovement jump test, a one-arm isometric elbow flexion test nor a 30-sec cycle sprint test. In conclusion, the DBS analyses of testosterone esters and clenbuterol appear to have sufficient specificity and sensitivity to be implemented in routine doping control in elite and recreational sports. Given the longer detection windows for clenbuterol in urine, urine is expected to remain as the preferred sample matrix for clenbuterol analysis. However, the implementation of DBS sampling could improve time- and costefficiency while reducing intrusiveness, and thereby allow for higher frequency of testing, or testing of a large number of athletes in a short time, with the aim of increasing detection and deterrence. Further, changes in markers in the hematological module could be indicative of testosterone doping, and should be considered an additional tool for targeted follow-up sample collection and confirmatory analysis. Moreover, since testosterone did not have any acute performance-enhancing effects in power/strength exercises, athletes are likely not to have an advantage if administering a single dose of testosterone esters immediately before or during a competition in power/strength sports. ISBN 978-87-7209-334-5
Article
The main estrogens: estradiol, estrone, and their acyl-esters have been studied essentially related to their classical estrogenic and pharmacologic functions. However, their main effect in the body is probably the sustained control of core energy metabolism. Estrogen nuclear and membrane receptors show an extraordinary flexibility in the modulation of metabolic responses, and largely explain gender and age differences in energy metabolism: part of these mechanisms is already sufficiently known to justify both. With regard to energy, the estrogen molecular species act essentially through four key functions: (1) Facilitation of insulin secretion and control of glucose availability; (2) Modulation of energy partition, favoring the use of lipid as the main energy substrate when more available than carbohydrates; (3) Functional protection through antioxidant mechanisms; and (4) Central effects (largely through neural modulation) on whole body energy management. Analyzing the different actions of estrone, estradiol and their acyl esters, a tentative classification based on structure/effects has been postulated. Either separately or as a group, estrogens provide a comprehensive explanation that not all their quite diverse actions are related solely to specific molecules. As a group, they constitute a powerful synergic action complex. In consequence, estrogens may be considered wardens of energy homeostasis.
Article
Spinal and bulbar muscular atrophy (SBMA) is a rare, X-linked neuromuscular disease characterised by lower motor neurons degeneration, slowly progressive myopathy and multisystem involvement. SBMA is caused by trinucleotide repeat expansion in the first exon of the androgen receptor (AR) gene on chromosome X that encodes a polyglutamine (polyQ) tract in the AR protein. Disease onset occurs between 30–60 years of age with easy fatigability, muscle cramps, and weakness in the limbs. In addition to neuromuscular involvement, in SBMA phenotype, many non-neural manifestations are present. Recently, some studies have reported a high prevalence of metabolic and liver disorders in patients with SBMA. Particularly, fatty liver and insulin resistance (IR) have been found in many SBMA patients. The alteration of AR function and the androgen insensitivity can be involved in both fatty liver and IR. In turn, IR and liver alterations can influence neuromuscular damage through different mechanisms. These data lead to consider SBMA as a metabolic as well as a neuromuscular disease. The mechanism of metabolic alterations, their link with the neuromuscular damage, the effects on the course of disease and their treatment will have to be yet fully clarified.
Article
Sex steroids are involved in biological functions that encompass from the complete sexual development of individuals up to the deregulation of metabolic pathways leading to some pathologies. Steroids are present in blood at low concentration levels from pg mL⁻¹ to ng mL⁻¹. For this reason, a high sensitive and selective method based on gas chromatography–negative chemical ionization–tandem mass spectrometry (GC–NCI–MS/MS) is here proposed to quantify either androgens (androstenedione, dehydroepiandrosterone, dihydrotestosterone and testosterone), estrogens (estrone and estradiol) and a progestogen (progesterone) in human plasma. The sample preparation steps, protein precipitation and solid phase extraction, were optimized to ensure the sample matrix removal and to extract steroids with high efficiency. The NCI–MS/MS detection approach was compared with that based on electron impact to evaluate the incidence of the ionization source in the determination of steroids. The quantification limits for determination of these analytes were in a range from 10 pg mL⁻¹ to 5 ng mL⁻¹, with a high sensitivity for estrogens, typically found at low concentrations. The proposed method was tested for the determination of steroids in male blood samples, in which 6 out of 7 steroids were detected and quantified to report concentration values in agreement with those described in the literature.
Article
Background: Transgender individuals often require gender-affirming interventions, such as endogenous sex hormone inhibition or gender affirming hormone therapy while there is discordance between their body and gender identity. However, a recent study found that the incidence of cardiovascular events is higher in transgender patients receiving cross-sex hormone therapy. The aim of this study was to investigate the metabolic effects of an altered sex hormone profile. Methods: This retrospective study, conducted in a referral center in Northern Taiwan, analyzed metabolic changes over time in 65 trans masculine and 45 trans feminine persons. The transgender individuals were examined at four time points: before the gender affirming hormone therapy, as well as three, six, and twelve months following treatment. Results: Compared to baseline measurements, the trans masculine patients showed significant increases in body mass index (22.6±0.3 vs. 23.3±0.4 kg/m2; p<0.001; t=3M), low-density lipoprotein cholesterol (124.3±3.7 vs. 131.3±3.9 mg/dL; p=0.03; t=12M), creatinine (0.75±0.01 vs. 0.83±0.14 mg/dL; p<0.001; t=12M), and hemoglobin (13.5±0.7 vs. 15.2±0.2 g/dL; p<0.001; t=12M), as well as decreased high-density lipoprotein cholesterol (57±2.1 vs. 51±2.0 mg/dL; p<0.001; t=12M). The trans feminine patients had reduced low-density lipoprotein cholesterol (104.2±3.2 vs. 100.8±3.5 mg/dL; p=0.05; t=3M), hemoglobin (14.0±0.1 vs. 13.5±0.1 g/dL; p=0.008; t=12M), and creatinine (0.82±0.01 vs. 0.79±0.14 mg/dL; p<0.001; t=3M) compared to baseline data. In addition, most of these metabolic effects persisted during the follow-up period. Conclusion: This observational, retrospective study revealed that gender affirming hormone therapy increased the relative cardiovascular risk in trans masculine individuals.
Article
The observation that 64% of English adults are overweight or obese despite a rising prevalence in weight-loss attempts suggests our understanding of energy balance is fundamentally flawed. Weight-loss is induced through a negative energy balance; however, we typically view weight change as a static function, in that energy intake and energy expenditure are independent variables, resulting in a fixed rate of weight-loss assuming a constant energy deficit. Such static modelling provides the basis for the clinical assumption that a 14644 kJ (3500 kcal) deficit translates to a 1 lb weight-loss. However, this ‘3500 kcal (14644 kJ) rule’ is consistently shown to significantly overestimate weight-loss. Static modelling disregards obligatory changes in energy expenditure associated with the loss of metabolically active tissue, i.e. skeletal muscle. Additionally, it disregards the presence of adaptive thermogenesis, the underfeeding-associated fall in resting energy expenditure beyond that caused by loss of fat-free mass. This metabolic manipulation of energy expenditure is observed from the onset of energy restriction to maintain weight at a genetically pre-determined set point. As a result, the observed magnitude of weight-loss is disproportionally less, followed by earlier weight plateau, despite strict compliance to a dietary intervention. By simulating dynamic changes in energy expenditure associated with underfeeding, mathematical modelling may provide a more accurate method of weight-loss prediction. However, accuracy at an individual level is limited due to difficulty estimating energy requirements, physical activity and dietary intake in free-living individuals. In the present paper, we aim to outline the contribution of dynamic changes in energy expenditure to weight-loss resistance and weight plateau.
Chapter
Sex hormone disturbances are very common in athletes, the most frequent of which is hyperandrogenism. The high prevalence of hyperandrogenism is due mostly to the high prevalence of polycystic ovary syndrome (PCOS) among female athletes, and the high intake of anabolic-androgenic steroids in athletes in general. Other rare causes include disorders in sex differentiation. Athletes with hyperandrogenism have a competitive advantage over athletes with a normal androgen level. The improvement in physical strength and exercise endurance is due primarily to the hypertrophic myogenic effect of testosterone. Female athletes with hyperandrogenism suffer from adverse events such as athletic amenorrhea, hirsutism, male baldness, and change in voice quality. Dysphonia in affected patients is described as deepening of the voice, voice breaks, and voice instability. These voice changes are attributed to functional and structural laryngeal changes, the most common of which are an increase in muscle tissue versus connective tissue ratio, muscle incoordination, and proprioceptive dysfunction with impairment in muscle memory.
Article
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Objective Low testosterone in men (hypogonadism) is associated with obesity and type II diabetes. Testosterone replacement therapy has been shown to reverse these effects. However, the mechanisms by which testosterone regulates total fat mass, fat distribution and metabolic health are unclear. In this study, we clarify the impact of hypogonadism on these parameters, as well as parse the role of testosterone from its downstream metabolites, dihydrotestosterone (DHT) and estradiol, in the regulation of depot-specific adipose tissue mass. Methods To do this, we utilized mouse models of male hypogonadism coupled with hormone replacement therapy, magnetic resonance imaging (MRI), glucose tolerance tests (GTTs), flow cytometry and immunohistochemical techniques. Results We find that castrated mice develop increased fat mass, reduced muscle mass and impaired glucose metabolism compared to gonadally intact males. Interestingly, obesity is further accelerated in castrated mice fed a high fat diet, suggesting hypogonadism increases susceptibility to obesogenesis when dietary consumption of fat is elevated. By performing hormone replacement therapy in castrated mice, we show that testosterone impedes visceral and subcutaneous fat mass expansion. Whereas testosterone-derived estradiol selectively blocks visceral fat growth and DHT selectively blocks the growth of subcutaneous fat. These effects are mediated by depot-specific alterations in adipocyte size. In addition, we show that high fat diet induced adipogenesis is elevated in castrated mice and that this can be rescued by androgen treatment. Obesogenic adipogenesis is also elevated in mice where androgen receptor activity is inhibited. Conclusion These data indicate hypogonadism impairs glucose metabolism and increases obesogenic fat mass expansion through adipocyte hypertrophy and adipogenesis. In addition, our findings highlight distinct roles for testosterone, DHT and estradiol in the regulation of total fat mass and fat distribution and reveal that androgen signaling blocks obesogenic adipogenesis in vivo.
Article
Steroidogenesis is a set of metabolic reactions where the enzymes play a key role to control the physiological levels of steroids. A deficiency in steroidogenesis induces an accumulation and/or insufficiency of steroids in human blood and can lead to different pathologies. This issue added to the low levels of steroids (pg mL⁻¹ to ng mL⁻¹) in this biofluid make of their determination an analytical challenge. In this research, we present a high-throughtput and fully automated method based on solid-phase extraction on-line coupled to liquid chromatography with tandem mass spectrometry detection (SPE–LC–MS/MS) to quantify estrogens (estrone and estradiol), androgens (testosterone, androstenedione, dihydrotestosterone and dehydroepiandrosterone), progestogens (progesterone, pregnenolone, 17-hydroxyprogesterone and 17-hydroxypregnenolone), glucocorticoids (21-hydroxyprogesterone, 11-deoxycortisol, cortisone, corticosterone and cortisol) and one mineralocorticoid (aldosterone) in human serum. The performance of the SPE step and the multiple reaction monitoring (MRM) mode allowed reaching a high sensitivity and selectivity levels without any derivatization reaction. The fragmentation mechanisms of the steroids were complementary studied by LC–MS/MS in high-resolution mode to confirm the MRM transitions. The method was characterized with two SPE sorbents with similar physico-chemical properties. Thus, limits of quantification were at pg mL⁻¹ levels, the variability was below 25% (except for pregnenolone and cortisone), and the accuracy, expressed as bias, was always within ±25%. The proposed method was tested in human serum from ten volunteers, who reported levels for the sixteen target steroids that were satisfactorily in agreement with the physiological ranges reported in the literature.
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