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Effect of testosterone on muscle and muscle protein synthesis
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.
... There are androgen receptors (AR) and two types of estrogen receptors (ERs) in the prostate gland: ER-α and ER-β. AR and ER-α mediate prostate cell proliferation, whereas ER-β inhibits prostate cell proliferation [15,16]. ...
... Increased estrogen upregulates ER-α, and enlarges the prostate [15]. Prostate enlargement in men with a higher ASMI can be explained by the increased activity of testosterone, which activates muscle protein synthesis and facilitates prostate cell growth [16]. We suggest that androgen and estrogen contribute to the enlargement of different segments of the prostate. ...
... This negative feedback causes hypogonadism in men with obesity [20]. In addition, hypogonadism and low ASMI were also related [16]. It is known that testosterone stimulates nitric oxide formation, which plays a role in the dilation of the urethra and bladder neck, and this supports our idea of an association between hypogonadism and bothersome LUTS [21]. ...
Purpose
This study aimed to investigate the practicality of percent body fat (PBF), calculated using bioelectrical impedance analysis (BIA), in predicting benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS).
Methods
This study included 844 men who underwent medical checkups at our institution between 2014 and 2022. Demographic characteristics, serum PSA levels, and prostate volume were collected using TRUS. BPH was defined as a prostate volume ≥ 30 cc. Subjects were divided into two groups according to their quartiles of PBF: the normal PBF group (first to third quartile; PBF < 27.9%) and the high PBF group (fourth quartile; PBF ≥ 27.9%). Characteristics between the groups were compared using the chi-square test and Student’s t-test. Multivariate logistic regression analysis was performed to evaluate risk factors for BPH and severe LUTS.
Results
The prostate volume (25.21 ± 8.4 vs 27.30 ± 9.0, p = 0.005) and percentage of BPH (22.9% vs. 32.1%, p = 0.007) were greater in the high PBF group. After multivariate analysis, old age (OR = 1.066, p < 0.001), higher appendicular skeletal muscle mass index (ASMI) (OR = 1.544, p = 0.001), and PBF ≥ 27.9% (OR = 1.455, p = 0.037) were risk factors for BPH. Larger prostate volume (OR = 1.035, p = 0.002) and PBF ≥ 27.9% (OR = 1.715, p = 0.025) were risk factors for severe LUTS. However, a greater ASMI had a protective effect against severe LUTS (OR = 0.654, p = 0.011).
Conclusions
This study shows that PBF and ASMI are useful for predicting BPH/LUTS. We suggest that lowering PBF to the normal range in a population with high PBF might prevent BPH, while lowering PBF and maintaining adequate ASMI could lower LUTS.
... The CG are related to the appearance and development of depression [240,241], and androgens are known to lower the severity of this disorder [217]. GC are secreted as a response to stress [240], in which body fat and glucose availability are relatively protected [242,243] at the expense of growth and body protein [244], with the maintenance sustained by androgens [238,245]. Nevertheless, the metabolic effects of KT (and T) share (at least in part) the homeostatic growth-promoting effects of GC, insulin and GH [236]. The protein synthesis-linked anabolic nature of T, KT and DHT [245] contrasts with the drive of GC to favor protein scraping to fuel glucose availability [246,247]. ...
... Nevertheless, the metabolic effects of KT (and T) share (at least in part) the homeostatic growth-promoting effects of GC, insulin and GH [236]. The protein synthesis-linked anabolic nature of T, KT and DHT [245] contrasts with the drive of GC to favor protein scraping to fuel glucose availability [246,247]. ...
... Androgens play a critical participation in the regulation of body protein content (including, especially, muscle mass and distribution) [245]. The marked decay of testosterone availability with senescence [298] lowers muscle mass and function [299] down to sarcopenia [300]. ...
Androgens are an important and diverse group of steroid hormone molecular species. They play varied functional roles, such as the control of metabolic energy fate and partition, the maintenance of skeletal and body protein and integrity and the development of brain capabilities and behavioral setup (including those factors defining maleness). In addition, androgens are the precursors of estrogens, with which they share an extensive control of the reproductive mechanisms (in both sexes). In this review, the types of androgens, their functions and signaling are tabulated and described, including some less-known functions. The close interrelationship between corticosteroids and androgens is also analyzed, centered in the adrenal cortex, together with the main feedback control systems of the hypothalamic–hypophysis–gonads axis, and its modulation by the metabolic environment, sex, age and health. Testosterone (T) is singled out because of its high synthesis rate and turnover, but also because age-related hypogonadism is a key signal for the biologically planned early obsolescence of men, and the delayed onset of a faster rate of functional losses in women after menopause. The close collaboration of T with estradiol (E2) active in the maintenance of body metabolic systems is also presented Their parallel insufficiency has been directly related to the ravages of senescence and the metabolic syndrome constellation of disorders. The clinical use of T to correct hypoandrogenism helps maintain the functionality of core metabolism, limiting excess fat deposition, sarcopenia and cognoscitive frailty (part of these effects are due to the E2 generated from T). The effectiveness of using lipophilic T esters for T replacement treatments is analyzed in depth, and the main problems derived from their application are discussed.
... Testosterone, an androgenic steroid hormone, mediates physiological, anatomical and behavioural traits salient to male vertebrate mating effort (Hau, 2007), including spermatogenesis (Steinberger, 1971), muscle anabolism (Griggs et al., 1989) and libido (Isidori et al., 2005). Given the prominent role of aggression in the mating effort of some male vertebrates (Clutton-Brock & Huchard, 2013), testosterone has long been thought to promote aggression (Batrinos, 2012;Collias, 1944). ...
... Notably, causal relationships between testosterone, lean muscle mass and dominance rank are plausibly multidirectional. Testosterone levels likely contribute to greater lean muscle mass (Griggs et al., 1989), thereby increasing competitive ability in intrasexual contests. However, as suggested by population level analyses of humans (Ellison et al., 2002;Trumble et al., 2012), individuals with greater lean muscle mass likely enjoy greater energy intake and improved general health, which supports testosterone secretion. ...
Testosterone promotes mating effort, which involves intraspecific aggression for males of many species. Therefore, males with higher testosterone levels are often thought to be more aggressive. For mammals living in multimale groups, aggression is hypothesized to link male social status (i.e. dominance rank) and testosterone levels, given that high status predicts mating success and is acquired partly through
aggressive intragroup competition. In male chimpanzees, Pan troglodytes, dominance rank has been repeatedly linked to interindividual variation in testosterone levels, but evidence directly linking interindividual variation in testosterone and aggression is lacking. In the present study, we test both aggression levels and lean muscle mass, as measured by urinary creatinine, as links between dominance rank and testosterone levels in a large sample of wild male chimpanzees. Multivariate analyses indicated that dominance rank was positively associated with total rates of intragroup aggression, average urinary
testosterone levels and average urinary creatinine levels. Testosterone was positively associated with creatinine levels but negatively associated with total aggression rates. Furthermore, mediation analyses showed that testosterone levels facilitated an association between dominance rank and creatinine levels.
Our results indicate that (1) adult male chimpanzees with higher average testosterone levels are often higher ranking but not more aggressive than males with lower testosterone and (2) lean muscle mass links dominance rank and testosterone levels in Ngogo males. We assert that aggression rates are
insufficient to explain links between dominance rank and testosterone levels in male chimpanzees and that other social variables (e.g. male-male relationship quality) may regulate testosterone's links to aggression.
... In that perspective, it has reported that supplementation with 3-OHB (mono-ester compound) in the recovery phase right after exercise stimulates muscle protein synthesis in vivo as well as in vitro 29 and testosterone availability is important for this muscle protein synthesis. 30 With regards to recovery, Holdsworth and colleagues demonstrated higher glycogen synthesis in the presence of 3-OHB (mono-ester) during the recovery period. 31 It is worth noting that different 3-OHB compounds are used as mentioned above, and the effects of 3-OHB on acute performance may not solely depend on the increase in 3-OHB levels but could also be influenced by the specific compound (salt, monoester, diester) used and their possible side effects, which, in turn, may alter performance. ...
... The finding that 3-OHB may influence testosterone is novel and may affect the way 3-OHB is used in training and sports such as cycling. As mentioned above, testosterone is important for muscle synthesis 30 and a declining testosterone may counteract some of the positive muscle related aspects of 3-OHB ingestion such as improved glycogen synthesis. 31 As this study is a very shortterm study, longer trials are needed to confirm whether testosterone remains affected over time or if it is only a pulsatile phenomenon. ...
Ketone bodies, such as 3‐hydroxybutyrate (3‐OHB), have been frequently used by endurance athletes, such as cyclists, to enhance performance and recovery and are recognized for their health benefits and therapeutic effects for decades. Testosterone is a potent regulator of red blood cell production. Evidence suggests that ketone bodies can increase the production of erythropoietin, which stimulates red blood cell production. Therefore, we investigated whether an acute increase in 3‐OHB levels affects testosterone levels in healthy young men. We studied six healthy, young male participants who fasted overnight and were tested twice: (i) after drinking 37.5 g of Na‐D/L‐3‐OHB dissolved in 500 mL of distilled water (KET), and (ii) after drinking 500 mL of placebo saline water (0.9% NaCl) (CTR). During the KET trial, 3‐OHB levels increased to approximately 2.5 mM. Testosterone levels decreased significantly by 20% during KET compared to 3% during CTR. A simultaneous increase in luteinizing hormone was observed in KET. We observed no changes in other adrenal androgens, such as androstenedione and 11‐keto androgens. In conclusion, an acute increase in 3‐OHB levels decreases testosterone levels. Concomitantly, an increase in luteinizing hormone was observed. This suggests that 3‐OHB may counteract some of the beneficial effects of endurance training. Further studies, involving larger sample sizes and performance outcomes, are required to fully understand this phenomenon.
... Steroid hormones play a critical role in modulating energy use, affecting and affected by numerous fitnessrelevant domains including behavior, immune activation, and reproductive physiology. While many hormones modulate caloric demand and utilization, testosterone is particularly important as it influences classic life history trade-offs between energetic investments in growth (e.g., muscle formation), reproduction, and the maintenance of immune function (Bhasin et al., 1996;Folstad & Karter, 1992;Griggs et al., 1989;Jasienska et al., 2017;Muehlenbein & Bribiescas, 2005;Sinha-Hikim et al., 2003). Most testosterone research motivated by life history theory focuses on males, as there are more direct fitness payoffs and tradeoffs in relation to male testosterone and reproductive behavior (Folstad & Karter, 1992;Muehlenbein & Bribiescas, 2005), whereas in vertebrate females, links between energetics and reproduction are not as dependent on testosterone. ...
... T A B L E 3 Association between TEE (kcal/day) and testosterone for n = 20 Tsimane men and N = 11 Hadza men with a limited set of covariates that were collected in both populations. The anabolic effects of testosterone increase protein synthesis (Brodsky et al., 1996;Griggs et al., 1989), as well as muscle cell proliferation via satellite cell activation (Sinha-Hikim et al., 2006), both of which require intensive caloric utilization and diversion of energy stores. Testosterone also increases glucose uptake and utilization in muscle tissue (Tsai & Sapolsky, 1996). ...
Objective:
Testosterone plays a role in mediating energetic trade-offs between growth, maintenance, and reproduction. Investments in a high testosterone phenotype trade-off against other functions, particularly survival-enhancing immune function and cellular repair; thus only individuals in good condition can maintain both a high testosterone phenotype and somatic maintenance. While these effects are observed in experimental manipulations, they are difficult to demonstrate in free-living animals, particularly in humans. We hypothesize that individuals with higher testosterone will have higher energetic expenditures than those with lower testosterone.
Methods:
Total energetic expenditure (TEE) was quantified using doubly labeled water in n = 40 Tsimane forager-horticulturalists (50% male, 18-87 years) and n = 11 Hadza hunter-gatherers (100% male, 18-65 years), two populations living subsistence lifestyles, high levels of physical activity, and high infectious burden. Urinary testosterone, TEE, body composition, and physical activity were measured to assess potential physical and behavioral costs associated with a high testosterone phenotype.
Results:
Endogenous male testosterone was significantly associated with energetic expenditure, controlling for fat free mass; a one standard deviation increase in testosterone is associated with the expenditure of an additional 96-240 calories per day.
Discussion:
These results suggest that a high testosterone phenotype, while beneficial for male reproduction, is also energetically expensive and likely only possible to maintain in healthy males in robust condition.
... De igual manera, también varía la composición corporal (Bogin, 1994;Wells, 2007). Entre las chicas aumenta la acumulación de tejido adiposo en las aéreas glúteo-femorales debido a los estrógenos (Cameron, 2012;Wells, 2007), y entre los chicos disminuye el tejido adiposo y aumenta la acumulación de masa magra (Rogol et al., 2002), especialmente la masa muscular (Bogin, 1994), debido al aumento de testosterona (Bogin, 1999b;Bribiescas, 2001;Griggs et al., 1989;Wells, 2007). Estos contrastes responden a las diferentes estrategias reproductivas que caracterizan a un sexo o al otro (Apicella, 2014;Bribiescas, 2001;Ellison, 2003Ellison, , 2009Lassek & Gaulin, 2007Wells, 2007), aunque tal tendencia podría ya estar presente en etapas previas (Kirchengast, 2010;Scheffler & Hermanussen, 2018). ...
... Existe un evidente dimorfismo sexual en la especie Homo sapiens atendiendo a la composición corporal (Bogin, 1994;Wells, 2007). Causado por los requerimientos energéticos derivados de las estrategias reproductivas (Caro & Sellen, 1990;Ellison, 2001Ellison, , 2008, las hembras de los mamíferos (Heldstab, van Schaik, & Isler, 2017), y en especial las humanas, tienden a acumular más grasa corporal (Pike & Milligan, 2010) que sus compañeros que, debido a la testosterona (Griggs et al., 1989), aumentan en masa muscular (Bribiescas, 2001;van den Beld, de Jong, Grobbee, Pols, & Lamberts, 2000). ...
Esta tesis doctoral responde al interés de comprender el papel de la energía en las relaciones entre el ser humano y su entorno, siendo la energía la que modela y ajusta las adaptaciones biológicas y conductuales de los organismos terrestres y, por extensión, de la especie humana.
Son varios los estudios dentro de la ecología del comportamiento humano que han utilizado la energía para comprender la adaptación y la adaptabilidad humana. Dicha adaptabilidad es fruto de la flexibilidad que muestra nuestra especie, adquirida gracias a la prolongada inmadurez de Homo sapiens. Sin embargo, son menores los estudios que se han centrado en comprender cómo actúa la energía en la conducta y la biología de los individuos subadultos. Por ello, el principal interés de esta investigación es estudiar cómo afecta la energía a la puesta en marcha de diferentes actividades de subsistencia imprescindibles en los grupos de cazadores y recolectores. Concretamente, se evaluará si el inicio de la división de labores por sexo se explica en base a diferencias en el coste y la eficiencia energética de los distintos individuos. Así mismo, se valorará el papel activo y la productividad de los individuos subadultos dentro de un grupo humano, y si ello se ve limitado por cuestiones energéticas. Finalmente, se analizará si el coste de la locomoción y la velocidad óptima alcanzada por sujetos subadultos puede limitar la movilidad y la puesta en marcha de actividades que dependen de la locomoción en grupos humanos. Con todo, se tratará de conocer si la energía actúa como un limitante a la hora de aprender y desarrollar actividades complejas propias de nuestra especie y cómo afecta esto a las dinámicas energéticas del resto de individuos de un grupo humano.
Para ello se han empleado datos de dos estudios experimentales, llevados a cabo en el Laboratorio de Bioenergía y Análisis del Movimiento del Centro Nacional de Investigación sobre la Evolución Humana (CENIEH). Estos corresponden a 118 voluntarios de entre 7 y 14 años de edad, y recogen diferentes medidas antropométricas, de composición corporal y de gasto energético. Los dos estudios experimentales incluían simulaciones de actividades comunes entre los individuos subadultos de ciertos grupos de cazadores y recolectores de la actualidad, como la recolección y la extracción de recursos y caminar a diferentes velocidades.
Los resultados obtenidos en el conjunto de las pruebas revelan que, tanto la energía gastada, como la eficiencia en una actividad productiva, no explican la diferencia de labores entre sexos, pero tampoco entre edades si se comparan con las velocidades óptimas adultas. Se propone que la división de labores en base al sexo debe responder a otras cuestiones, relacionadas con el aprendizaje temprano en habilidades complejas específicas para cada sexo. Además, debido a la relación entre el gasto energético y el tamaño corporal en actividades productivas en las que se aprenden esas habilidades, los individuos juveniles gozan de una ventaja, ya que comienzan a aprender en una fase en la que el crecimiento corporal se retiene y se consume menos energía porque se tiene un tamaño menor. Por ello, practicar durante esta etapa, supone un ahorro en forma de energía respecto a otras fases en las que se tiene un mayor tamaño corporal y sí se invierte más energía en crecimiento y desarrollo, como en la adolescencia. Por otro lado, el gasto energético de la prueba de extracción de recursos bien se cubriría con el retorno calórico facilitado por diferentes autores, pero no podríamos confirmar que se alcancen ya tasas de productividad adulta. En esta prueba también se ha demostrado que, igual que se observa en el gasto energético del resto de actividades aquí desarrolladas, tampoco existen diferencias entre sexos en la eficiencia derivada de extraer recursos del suelo. Este resultado se ha obtenido al tener en cuenta la tasa de eficiencia (energía gastada/retorno conseguido). Respecto a las actividades que dependen de la locomoción bípeda, no existen diferencias entre sexos en la velocidad óptima, ni el gasto derivado de alcanzar esta velocidad. Por lo tanto, se propone que ambas variables no condicionarían a los individuos aquí estudiados a la hora de acompañar a un grupo adulto de cazadores y recolectores, ni durante la movilidad ni mientras se captan recursos. Por otro lado, la capacidad para alcanzar velocidades óptimas semejantes a las publicadas para individuos adultos, podría suponer a los subadultos ventajas al consumir menos energía por ser más pequeños. No obstante, en determinadas sociedades estos individuos no se involucran en ciertas actividades de manera temprana, por lo que existen otras causas, más allá de la velocidad o el gasto energético, que pueden dificultar la participación de los subadultos en algunas actividades adultas.
Todas estas ventajas han podido propiciar en la especie Homo sapiens un ahorro de energía que directamente, no solo beneficia al individuo subadulto, sino también a otros individuos del grupo. Muchas de las ventajas aquí expuestas se ven acompasadas por la peculiar historia biológica humana. Por ello, otras especies de homininos que hayan requerido del aprendizaje de habilidades complejas para subsistir, se habrían beneficiado de las mismas ventajas que exponemos en esta investigación, solo si hubiesen tenido los mismos patrones de desarrollo y crecimiento encontrados en Homo sapiens.
The main interest of this Ph.D. Dissertation is to understand the key-role of the energy in the relationship between humans and the environment, since energy is the factor that models and adjusts the biological and behavioural adaptations of all living organisms and, by extension, of humans too.
Several studies within the Human Behavioural Ecology have used the energy to understand human adaptation and adaptability. This adaptability is the main result of human plasticity, acquired thanks to the prolonged immaturity of Homo sapiens. However, fewer studies have focused on understanding how energy affects subadult behaviour and biology. Therefore, the main interest of this research is to study how energy affects the implementation of different essential human behaviours in hunter-gatherer societies. Specifically, it will be evaluated if the onset of division of labour by sex is caused by differences in the efficiency and the energetic demands of different individuals. In addition, the active role and the productivity of non-adult individuals will be assessed, together with possible energetic limitations in this regard. Finally, the cost of locomotion and the optimal speed will be analysed to test if non-adult individuals limit group mobility or the participation in foraging activities involving locomotion. Consequently, it will be discussed if energy is a limitation while learning-by-doing complex activities, commonly practiced by Homo sapiens species, and how this affects the energetic dynamics of a human group.
To achieve this, data from two experimental studies carried out in the Laboratory of Bioenergy and Analysis of the Movement of the CENIEH have been used. Data were obtained from 118 volunteers between 7 and 14 years of age, and referred to different anthropometric, body composition and energy expenditure measurements. The two experimental studies consisted of three trials, simulating common activities among subadult individuals of certain groups of current hunter-gatherers. The recreated activities were a gathering test, a digging tubers trial, and a locomotion activity at different speeds.
The results obtained in all of the experimental studies reveal that the energy
expended and the efficiency in a productive activity do not explain the onset of sex division of labor. It is proposed that the division of labor is caused by other questions related to the early learning in sex-specific complex skills. In addition, due to the relationship between energy expenditure and body size in some productive activities (through which non-adults learn these skills), juvenile individuals have an energetic advantage, because they decelerate the body growth in this phase and they consume less energy due to their smaller body size. Therefore, learning-by-doing at this stage promotes energy savings compared to other phases with a larger body size and a greater somatic investment, like adolescence.
On the other hand, the energy expenditure of digging would be covered with the energetic return reported by other investigations, but we cannot confirm that our individuals have already achieved adult productivity rates. In this test, taking into account the results of the efficiency index (energy expended/items reported) it has also been shown that there are no differences among sexes based on the efficiency of extracting tubers from the ground, as we have observed for the energy expenditure of the rest of the activities carried out here.
Regarding the locomotion test, there are no differences among sexes, or ages when compared with adult values from other studies, neither comparing the optimal walking speed, nor the energy expenditure at this speed. Thus, it is proposed that both variables are not a limitation for the individuals here studied if they would be part of a hunter-gatherer group, neither during the mobility of the group, nor while foraging.
On the other hand, our volunteers reach similar optimal speeds as those reported in the literature for adult individuals. This could constitute and advantage for non-adult individuals, as they are consuming less energy because they are smaller. Nonetheless, in certain societies, non-adult individuals are not involved in some activities anyway, thus there may be other causes, beyond speed or energy costs, that can hinder the
participation of non-adults in some adult activities.
All the mentioned advantages would allow energy savings for Homo sapiens. This savings would directly benefit the non-adult individual, but also the rest of the group. However, most of the advantages highlighted here are linked to the peculiar Homo sapiens Life History. Therefore, the advantages we expose in this research would benefit other extinct species with subsistence complex skills, only if Homo sapiens-like development and growth patterns were already present.
... While directly aiding in spermatogenesis and copulation, testosterone also indirectly acts on reproductive efforts. In general, testosterone in deer aids the development of sexually selected traits (Perez-Rodriguez et al. 2006) and increases muscle mass (Griggs et al. 1989, Ditchkoff 2011, social dominance (Chunwang et al. 2004), and signpost communications to potential mates (Miller et al. 1987;Miller et al. 1998). This relationship between testosterone and sexually selected traits is exacerbated in systems with highly competitive social environments, such as populations with greater densities of mature males (de la Peña et al. 2020). ...
... We observed a positive relationship between testosterone and body size for individuals aged 5.5 years and younger. Given previous literature that demonstrates the positive association between testosterone and muscle mass, protein synthesis, and antler growth (Griggs et al. 1989;Killian et al. 2005), this relationship was unsurprising. During this age period, however, individuals allocate resources to somatic growth, during which, testosterone plays a major role. ...
While hormones such as testosterone are known to drive reproduction and sexually selected traits in many species, research demonstrating a relationship between testosterone and annual or overall reproductive success is sparse. We sought to directly measure how circulating testosterone relates to sexually selected characteristics and reproductive success in a freely breeding population of white-tailed deer (Odocoileus virginanus). We captured individuals during September–March annually from 2007 to 2017 and investigated the association between testosterone and antler size, body size, and annual reproductive success for individuals. We also assessed lifetime patterns from individuals captured multiple years. We found a positive relationship between testosterone and body size, and between testosterone and antler size. However, we found a significant interaction between testosterone and age for both body size and antler size response variables, indicating that as age increases, the aforementioned positive relationships with testosterone diminish. Thus, for deer ≥ 6.5 years of age, testosterone is negatively related to body and antler size. In contrast, annual reproductive success, measured by number of offspring sired and recruited into the breeding population, was positively associated with antler size and body size, but not testosterone, age, or an interaction between testosterone and age. Instead, while an individual’s average lifetime testosterone had no relationship with overall reproductive success, greater variation in lifetime testosterone was positively related to overall reproductive success. Thus, while we found no significant association between testosterone and annual reproductive success directly, testosterone may be indirectly related to reproductive success through its positive association with antler and body size. Furthermore, understanding how testosterone may fluctuate throughout an individual’s lifetime may offer new perspectives in understanding variation in individual reproductive success.
... Testosterone affects many metabolic processes, which have recently been investigated using plasma metabolomics. Metabolites of particular interest include amino acids, as testosterone is an anabolic agent [15], and bile acid metabolism [16]. Testosterone-replacement therapy in hypogonadal men is associated with alterations in acyl-carnitine metabolism and free fatty acid levels in blood cells, with orchiectomy in male mice having opposite metabolic effects [17]. ...
... Although the impact of sex steroids on the metabolome is an intriguing research inquiry, there is a surprising dearth of research on the effects of testosterone more broadly on the metabolome. Testosterone, a known anabolic agent, increases muscle mass and protein synthesis [15], including in transgender individuals [48], although less is known about the effects on the metabolome. Little is known about the effects of supplemental testosterone in cisgender men, although there are several applications for both transgender and cisgender men [49]. ...
Background: Although there are sex differences in metabolomic profiles, little is known about the effects of testosterone on the metabolomic profile of people with a female sex. We evaluated the effect of endogenous versus exogenous testosterone on the plasma metabolomic profile.
Methods: Participants included 20 individuals with a female sex designated at birth. Ten transgender male (TGM) adolescents [age 15.5 + 0.9 years, BMI percentile 74% (32, 94)] were evaluated at baseline and after one month of exogenous testosterone treatment (TGM-1M). TGM-1M were compared to 10 BMI-matched cisgender female adolescents with polycystic ovary syndrome [PCOS, age 15.8 + 1.8 years, BMI 85% (78, 98)]. All participants had fasting laboratory evaluation and targeted fasting plasma metabolomic analysis.
Results: There were no significant differences in metabolomics after 1 month of testosterone therapy in the TGM group. There were significant differences in the targeted metabolomic analysis between the adolescents with PCOS and TGM-1M. Eight bile acids, 5 fatty acids and 2 amino acids were higher in the PCOS group (fold change>2) compared to TGM-1M. Five amino acids, 2 acylcarnitines, and one fatty acid were higher in TGM-1M compared to participants with PCOS. Participants with PCOS had more signs of metabolic syndrome, including higher waist/hip ratio, systolic blood pressure, and dyslipidemia compared to TGM-1M.
Conclusions: Long-term endogenous testosterone exposure in PCOS is associated with an altered metabolic profile and changes in bile acid and fatty acid metabolism relative to short-term exogenous exposure in TGM-1M, suggesting other features, besides testosterone are responsible for the metabolic features of PCOS.
... 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). ...
... In addition to the functional aspects, muscle composition is affected by testosterone secretion [108]. Testosterone is likely to be responsible for muscle growth [109]. Secreted testosterone facilitates protein synthesis, which leads to muscle growth and increased muscle mass [110]. ...
Sarcopenic obesity, low muscle mass, and high body fat are growing health concerns in the aging population. This review highlights the need for standardized criteria and explores nutraceuticals as potential therapeutic agents. Sarcopenic obesity is associated with insulin resistance, inflammation, hormonal changes, and reduced physical activity. These factors lead to impaired muscle activity, intramuscular fat accumulation, and reduced protein synthesis, resulting in muscle catabolism and increased fat mass. Myostatin and irisin are myokines that regulate muscle synthesis and energy expenditure, respectively. Nutritional supplementation with vitamin D and calcium is recommended for increasing muscle mass and reducing body fat content. Testosterone therapy decreases fat mass and improves muscle strength. Vitamin K, specifically menaquinone-4 (MK-4), improves mitochondrial function and reduces muscle damage. Irisin is a hormone secreted during exercise that enhances oxidative metabolism, prevents insulin resistance and obesity, and improves bone quality. Low-glycemic-index diets and green cardamom are potential methods for managing sarcopenic obesity. In conclusion, along with exercise and dietary support, nutraceuticals, such as vitamin D, calcium, vitamin K, and natural agonists of irisin or testosterone, can serve as promising future therapeutic alternatives.
... The results indicated that the free amino acids such as alanine and betaine were significantly higher in NCM and CM than in FM whereas glycine, methionine, and β-alanine acids were significantly higher in NCM than in CM and FM. Testosterone, the primary male sex hormone, can influence protein metabolism (Griggs, 1989), which potentially affects alanine, betaine, and glycine levels. Glycine plays a role in two metabolic processes: protein synthesis and collagen formation (Satyanarayana et al., 2021). ...
Although goat meat has several health benefits than other red meats but comsumers reluctant it due to its unpleasant flavor. This study aimed to investigate the odorant of goat meat as well as compare the quality traits of meat regarding sex status. The loin meats [non-castrated male (NCM), castrated male (CM), and female (FM)] were collected and stored at 4oC in a laboratory refrigerator and analyzed on the 1st, 5th, and 8th consecutive days. The moisture content was the lowest and the protein content was highest in FM (p<0.05). Fat and ash content in NCM and FM were similar while lowest in CM. The L* value was significantly higher in NCM, but there was no significant differences of a* and b* values within groups at initial day. The color intensity increased on the 5th storage day and decreased again after the 8th storage day, except in NCM. NCM displayed the highest TBARS value (p<0.05), whereas CM displayed a higher pH value than other groups throughout the storage period. Indole levels were the highest in NCM (0.031 mg/kg); however, skatole levels were not significant differences across all treatments (p>0.05). No significant difference was observed in the fatty acid composition between NCM and CM (p>0.05), whereas a significant difference was observed in FM (p<0.05). Most of the water-soluble metabolites showed significant differences between sexes. Overall, sex status effects on quality properties of meat and castration can improve the overall sensory acceptance by reducing goaty flavor of Korean native black goat meat.
Keywords: black goat meat; sexes; goaty flavor; water-soluble metabolites; indole
... EMIQ exerts anti-obesity effects (Egawa et al. 2012;Tateishi et al. 2009) and inhibits muscle atrophy (Otsuka et al. 2019). Although the detailed mechanisms underlying these effects are unknown, testosterone, one of the hormones involved in the promotion of muscle synthesis (Griggs et al. 1989), and myostatin, one of the hormones involved in the suppression of muscle synthesis (Lee and McPherron 1999), may be involved. ...
This study investigated the effects of a dietary protein supplement containing enzymatically modified isoquercitrin (EMIQ) on plasma amino-acid levels in healthy people. A randomized double-blind cross-over trial (UMIN000044791) was conducted with a sample of nine healthy individuals. These participants ingested soy protein with or without 42 mg EMIQ for 7 days after performing mild exercise. Plasma amino-acid levels were measured before ingestion and at 15, 30, 45, 60, 90, 120, 180, and 240 min after ingestion on the last day. The concentrations of total amino acids at 0 and 120 min and easily oxidized amino acids at 120 min were significantly higher in the plasma of individuals who consumed 42 mg EMIQ. Oxidative stress levels were lower and plasma testosterone levels were higher in participants who ingested soy protein with 42 mg EMIQ than in those who did not. These results suggest that daily ingestion of soy protein with 42 mg EMIQ can be useful for effective protein absorption.
... Testosterone is a hormone that increases lean muscle mass by increasing muscle synthesis (Griggs et al., 1989). Increased sensitivity to testosterone increases its anabolic effects (Giugliano & Millward, 1987;Swaminath et al., 2002). ...
In the past few decades, there has been an increased emphasis on plant-based diets. While plant-based diets have many cardiovascular and environmental benefits, little is known about how plant-based diets specifically impact athletic performance and promote muscle growth. Many athletes are reluctant to adopt plant-based diets, fearing that they will lose lean muscle mass due to insufficient protein content. In this research review, we evaluate factors that differentiate plant proteins and meat in regard to optimal lean muscle synthesis. One of the more important differences between plant protein and meat is their amino acid composition. Since meats contain all 9 essential and many nonessential amino acids, they have a more “well-rounded” amino acid composition, thus being more effective at promoting lean muscle growth. A protein source’s amino acid composition, along with other factors such as cell structure, affects its bioavailability. Due to differences in protein bioavailability, different quantities of distinct protein sources may need to be consumed to reach the same anabolic effect. In addition to amino acid compositions, nutrient densities also differ between plant proteins and meats. Although there are some exceptions, plant-based proteins tend to offer a more balanced profile of minerals and nutrients, which also facilitate lean muscle synthesis on the chemical level. Overall, an omnivorous diet may be optimal for muscle growth, but introducing a variety of plant proteins with different amino acid and nutritional profiles can help overcome this variance.
... Elle participe en effet aux processus suivants: régulation de la lipolyse, synthèse d'hémoglobine et érythropoïèse, minéralisation osseuse et paradoxalement soudure des cartilages de conjugaison, augmentation de la synthèse des protéines et enfin développement musculaire. La testostérone serait également impliquée dans la régulation de processus comportementaux (anxiété, agressivité) et cognitifs (mémoire) (Griggs et al., 1989;Bain, 2007). ...
Ce travail de thèse avait pour objectifs d’évaluer les effets de certains antécédents socioprofessionnels sur le développement du syndrome de burnout chez des footballeurs professionnels de la ligue nationale tunisienne de football, de vérifier les effets de l'heure d’entraînement en force sur les variations des concentrations plasmatiques de testostérone (T) et de cortisol (C) ainsi que les rapports T/C chez des athlètes amateurs masculins tunisiens, et aussi d’évaluer les variations des niveaux de ces deux hormones aussi bien que leurs rapports, et les performances physiologiques chez des joueurs de football professionnels de la ligue précitée et ceci au cours d'une saison footballistique.
Dans la première partie de l’étude, nous avons démontré que les joueurs professionnels tunisiens de football souffraient du syndrome de burnout, et que les facteurs ‘Intégration’, ‘Relation avec l’entraîneur’, ‘Age’, ‘Condition matérielle’ et l’Ancienneté’ favorisaient d’une façon significative son déclenchement. La manifestation de ce syndrome semblait être particulièrement la conséquence du développement de ses trois composantes à savoir l’épuisement émotionnel, le cynisme et la réduction de l’accomplissement personnel.
Dans la seconde partie de l’étude, nos résultats ont montré que l'entraînement de force pendant huit semaines induisait une augmentation du T et du rapport T/C, et une diminution du C plasmatiques chez les athlètes amateurs qui s’entraînaient uniquement une seule fois par jour principalement l'après-midi comparativement à ceux qui se soumettaient aux mêmes
exercices physiques deux fois au cours de la journée. Une réduction du T et du rapport T/C, et une augmentation du C plasmatiques ont été observées chez les athlètes qui s’entraînaient toujours successivement le matin et l'après-midi. Le rapport T/C plasmatique a toujours montré dans sa variation diurne une rythmicité circadienne chez tous les athlètes indiquant
ainsi un faible niveau le matin qui devenait optimal l'après-midi.
Dans la troisième partie de l’étude, on a démontré que la concentration de C augmentait à la mi-saison d'environ 23% atteignant ainsi sa valeur optimale au cours de la saison
footballistique chez les joueurs professionnels tunisiens de football. Des augmentations de concentrations significatives ont été notées pour T entre la fin de la saison et la période de
post-préparation d’une part, et la mi-saison d’autre part. Le rapport T/C a augmenté lors de la période de post-préparation puis a diminué au milieu de la saison compétitive. De plus, les
paramètres de performance anaérobie alactique ont diminué significativement en milieu et à la fin de la saison par rapport à son début. D'un point de vue appliqué, cette étude suggère que
les athlètes devraient toujours s'entraîner l'après-midi pour maximiser leurs gains de performance. De plus, la T, le C et le rapport T/C pourraient être utilisés comme indicateurs
de stress et d'état de récupération d'un athlète. Les entraîneurs peuvent utiliser ces paramètres combinés avec d'autres indicateurs pour optimiser les charges de travail et éviter le
surentraînement et l’épuisement.
... Another limitation of this study is the loss of stabilizing muscles surrounding the knee during applied loads. Testosterone has been shown to have more drastic impacts on muscle mass and strength [53,54], so there still could be a greater impact of testosterone on in vivo joint stability between boars and barrows due to greater muscle stabilization. When looking at the functional characteristics of the ACL and its bundles, only sub-failure properties were assessed. ...
Female adolescent athletes are at a higher risk of tearing their anterior cruciate ligament (ACL) than male counterparts. While most work related to hormones has focused on the effects of estrogen to understand the increased risk of ACL injury, there are other understudied factors, including testosterone. The purpose of this study was to determine how surgical castration in the male porcine model influences ACL size and function across skeletal growth. Thirty-six male Yorkshire crossbreed pigs were raised to 3 (juvenile), 4.5 (early adolescent), and 6 months (adolescent) of age. Animals were either castrated (barrows) within 1-2 weeks after birth or were left intact (boars). Post-euthanasia, joint and ACL size were assessed via MRI, and biomechanics were assessed via a robotic testing system. Joint size increased throughout age, yet barrows had smaller joints than boars (p<0.001 for all measures). ACL cross-sectional area (CSA), length, volume, and stiffness all increased with age (p<0.0001), as did ACL anteromedial (AM) bundle percent contribution to resisting applied loads (p=0.012). Boar ACL and AM bundle volumes were 18% (p=0.003) and 24% (p=0.004) larger than barrows across ages. However, CSA, stiffness, and bundle contribution were similar between boars and barrows (p>0.05). The barrows had smaller temporal increases in AM bundle percent function than boars, but these data were highly variable. Thus, early and sustained loss in testosterone leads to subtle differences in ACL morphology, but may not influence measures associated with increased injury risk, such as CSA or bundle forces in response to applied loads.
... In men, it was earlier than in women. One possible reason is that the secretion of testosterone in men declines with age and affects muscle strength [31,32], and muscle strength in men changed to a much lower level than that in women. Furthermore, in this study, as the characteristics of toe grip strength by gender, because the previous value in men was larger than that in women, the extent of change in men becomes larger. ...
Background
The aim of this study is to examine the age-related changes in the toe grip strength and its differences from hand grip strength and knee extension strength using cross-sectional data.
Methods
Of participants aged 65 years over who underwent health checkups for lifestyle-related diseases in 2018, 307 men and women met the criteria. Toe grip strength, hand grip strength, and knee extension strength were also measured as optional tests. The participants were divided into five groups categorized by every 5 years of age (Group 65–85). The data were analyzed with multiple comparisons using the linear mixed multilevel model to examine the following categories: association between age and muscle strength, differences in the pattern of change, and gender, using the 65–69 years group as a reference.
Results
In men, there were interaction effects between the factors of age and muscle, but in women there were not. Toe grip strength was significantly lower in Group 70, 75, 80, and 85 in men, lower in Group 85 than in 65 in women. Hand grip strength was significantly lower in Group 85 than in 65 in both men and women. There was no significant difference in knee extension strength among the age groups for both men and women.
Conclusions
The decline in toe grip strength may occur earlier and in a different pattern from hand grip strength and knee extension strength in men.
... Testosterone affects muscle mass, bone mass, and physical functions [40,41]. Testosterone has a strong anabolic effect on skeletal muscle, regulates protein metabolism, and is closely related to muscle protein synthesis [42][43][44][45][46]. The increase in testosterone, resulting from treatment with EUAJ, appears to lead to an increase in muscle mass. ...
With aging, men inevitably encounter irreversible changes, including progressive loss of testosterone and physical strength, and increased fat mass. To assess the alleviatory effects of EUAJ on andropause symptoms, including in vivo testosterone deficiency, we administered EUAJ for 6 weeks in 22-week-old Sprague-Dawley rats. Before EUAJ (3:1) (E. ulmoides:A. japonica = 3:1, KGC08EA) administration, testosterone decline in 22-week-old SD rats was confirmed compared to 7-week-old SD rats (NC group). After administration of EUAJ (3:1) at 20, 40, and 80 mg/kg for 6 weeks, testosterone, free testosterone, and mRNA expression levels (Cyp11a1 and Hsd3b1) were significantly increased at 40 mg/kg EUAJ (3:1), whereas mRNA expression levels of Cyp19a1 and Srd5a2 were significantly reduced at this concentration, compared to the control group. Swimming retention time was significantly increased at both 40 mg/kg and 80 mg/kg. In summary, EUAJ (3:1) enhanced testosterone production by increasing bioavailable testosterone, sex hormone-binding globulin (SHBG), and enzymes related to testosterone synthesis at 40 mg/kg. In addition, 80 mg/kg EUAJ (3:1) also increased physical and testicular functions.
... The authors did not detect any complications attributable to testosterone therapy (27). Testosterone administration can positively affect postoperative recovery and rehabilitation by increasing protein synthesis and anabolism of muscle tissues, in addition to modulating the immune system (36,37) (Table 2). Search terms used • "male hypogonadism", "androgen deficiency", "testosterone", "testosterone replacement therapy", "androgen replacement" in combination with "urologic surgery" and "urologic intervention" ...
Background and objective:
Previous studies indicated that the treatment of male hypogonadism can be beneficial for intraoperative and postsurgical outcomes. In this study, we aimed to determine the impact of male hypogonadism on urologic surgeries. We provided an overview of the key studies in the field with the focus on the outcomes of urologic surgeries in hypogonadal men with/without testosterone replacement therapy (TRT).
Methods:
We performed a literature review in PubMed and Google Scholar databases for the most relevant articles pertaining to the outlined topics without placing any limitations on publication years or study designs. We included full-text English articles published in peer reviewed journals between January 1970 and March 2022.
Key content and findings:
Androgen deficiency is a common finding after major urologic surgeries. Although guidelines recommend against TRT in men with prostate carcinoma, recent investigations showed no association between TRT and disease progression and recurrence. Indeed, recent evidence suggested that low androgen levels could be related to high grade prostate carcinoma and increased risk of upgrading from low to high grade disease. Investigations on the application of TRT in benign prostatic hyperplasia (BPH) patients also revealed contrasting results. While some studies suggested higher rates of prostate-related events in men who received TRT, others showed that TRT could alleviate urinary symptoms in hypogonadal men with BPH. Decreased testosterone level is commonly seen in bladder cancer patients. The treatment of perioperative androgen deficiency can reduce postoperative morbidities and lower the risk of recurrence in these patients. Low testosterone levels are observed in approximately half of the men who undergo artificial urinary sphincter (AUS) placement and can increase the risk of complications.
Conclusions:
The role of testosterone treatment in patients with urologic diseases such as prostate carcinoma and BPH is controversial. Further investigations are needed to determine the impact of hypogonadism and TRT on the outcomes of urologic surgeries in patients with androgen deficiency.
... 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. ...
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.
... 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). ...
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.
... 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. ...
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.
... 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. ...
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.
... 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. ...
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.
... 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. ...
... 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. ...
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.
... 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]. ...
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.
... 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). ...
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.
... 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 . ...
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.
... 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. ...
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.
... 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]. ...
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.
... 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]. ...
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.
... 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]. ...
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.
... 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). ...
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.
Objectives
Telomeres are DNA–protein complexes at the ends of linear chromosomes that protect against DNA degradation. Telomeres shorten during normal cell divisions and therefore, telomere length is an indicator of mitotic-cell age. In humans, telomere shortening is a potential biomarker for disease risk, progression and premature death. Physical activity has been associated with longer leukocyte telomere length (LTL) in some studies. In the current study the relationship between LTL, thigh muscle mass and adipose tissue distribution was explored.
Methods
We performed anthropometric measurements and magnetic resonance imaging (MRI) measurements of the thigh in 149 healthy subjects (77 male, 72 female). LTL was measured using qPCR. Additionally, the subjects answered a questionnaire concerning their training behaviour.
Results
In male subjects, LTL was significantly associated with thigh muscle mass, independent of age and body mass index (p=0.006). In addition, a slight association of LTL with weekly endurance units in the male group was found. These relations could not be observed in females.
Conclusions
In conclusion, we observed a sex-specific association of LTL and thigh muscle mass in healthy males. The reason of this sex-specific association is currently unclear, but could be related to different training effects and/or hormonal pathways in men and women.
Mechanisms underlying mechanical overload-induced skeletal muscle hypertrophy have been extensively researched since the landmark report by Morpurgo (1897) of "work-induced hypertrophy" in dogs that were treadmill-trained. Much of the pre-clinical rodent and human resistance training research to date supports that involved mechanisms include enhanced mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling, an expansion in translational capacity through ribosome biogenesis, increased satellite cell abundance and myonuclear accretion, and post-exercise elevations in muscle protein synthesis rates. However, several lines of past and emerging evidence suggest additional mechanisms that feed into or are independent of these processes are also involved. This review will first provide a historical account as to how mechanistic research into skeletal muscle hypertrophy has progressed. A comprehensive list of mechanisms associated with skeletal muscle hypertrophy is then outlined and areas of disagreement involving these mechanisms are presented. Finally, future research directions involving many of the discussed mechanisms will be proposed.
This study examined whether the relationship between cancer and hand grip strength differs by sex and along the hand grip strength distribution. Using six waves of the Korean Longitudinal Study of Ageing (KLoSA) (N = 9735), sex-stratified unconditional quantile regression models with fixed effects were used to assess sex-specific effects of cancer for patients in different quantiles of the hand grip strength distribution. Cancer diagnosis was negatively associated with hand grip strength for males, but not females, and this sex difference was statistically significant. Quantile regression models showed that the stronger association between cancer and hand grip strength is observed among males with weaker hand grip strength. No statistically significant association was found between hand grip strength and cancer in females across the entire distribution of hand grip strength. This study provided evidence of the heterogeneity in the relationship between cancer and hand grip strength.
Adequate levels of androgens (eugonadism), and specifically testosterone, are vital compounds for male quality of life, longevity, and positive health outcomes. Testosterone exerts its effects by binding to the androgen receptor, which is expressed in numerous tissues throughout the body. Significant research has been conducted on the impact of this steroid hormone on skeletal, muscle and adipose tissues and on the cardiovascular, immune, and nervous systems. Testosterone levels have also been studied in relation to the impact of diseases, aging, nutrition and the environment on its circulating levels. Conversely, the impact of testosterone on health has also been evaluated with respect to its cardiac and vascular protective effects, body composition, autoimmunity and all-cause mortality. The male aging process results in decreasing testosterone levels over time. The exact mechanisms and impact of these changes in testosterone levels with age on health- and life-span are still not completely clear. Further research is needed to determine the optimal testosterone and androgen levels to protect from chronic age-related conditions such as frailty and osteoporosis.
The development and regeneration of skeletal muscle are mediated by satellite cells (SCs), which ensure the efficient formation of myofibers while repopulating the niche that allows muscle repair following injuries. Pannexin 1 (Panx1) channels are expressed in SCs and their levels increase during differentiation in vitro, as well as during skeletal muscle development and regeneration in vivo. Panx1 has recently been shown to regulate muscle regeneration by promoting bleb‐based myoblast migration and fusion. While skeletal muscle is largely influenced in a sex‐specific way, the sex‐dependent roles of Panx1 in regulating skeletal muscle and SC function remain to be investigated. Here, using global Panx1 knockout (KO) mice, we demonstrate that Panx1 loss reduces muscle fiber size and strength, decreases SC number, and alters early SC differentiation and myoblast fusion in male, but not in female mice. Interestingly, while both male and female Panx1 KO mice display an increase in the number of regenerating fibers following acute injury, the newly formed fibers in male Panx1 KO mice are smaller. Overall, our results demonstrate that Panx1 plays a significant role in regulating muscle development, regeneration, and SC number and function in male mice and reveal distinct sex‐dependent functions of Panx1 in skeletal muscle.
Context
Effects of testosterone on integrated muscle protein metabolism and muscle mass during energy deficit are undetermined.
Objective
The objective was to determine the effects of testosterone on mixed-muscle protein synthesis (MPS), proteome-wide fractional synthesis rates (FSR), and skeletal muscle mass during energy deficit.
Design
This was a randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov, NCT02734238).
Setting
The study was conducted at Pennington Biomedical Research Center.
Participants
Fifty healthy men.
Intervention
The study consisted of 14 days of weight maintenance, followed by a 28-day 55% energy deficit with 200 mg testosterone enanthate (TEST, n=24) or placebo (PLA, n=26) weekly, and up to 42 days of ad libitum recovery feeding.
Main Outcome Measures
Mixed-MPS and proteome-wide FSR before (Pre), during (Mid) and after (Post) the energy deficit were determined using heavy water (days 1-42) and muscle biopsies. Muscle mass was determined using the D3-Creatine dilution method.
Results
Mixed-MPS was lower than Pre at Mid and Post (P<0.0005), with no difference between TEST and PLA. The proportion of individual proteins with numerically higher FSR in TEST than PLA was significant by two-tailed binomial test at Post (52/67; P<0.05), but not Mid (32/67; P>0.05). Muscle mass was unchanged during energy deficit, but was greater in TEST than PLA during recovery (P<0.05).
Conclusions
The high proportion of individual proteins with greater FSR in TEST than PLA at Post suggests exogenous testosterone exerted a delayed but broad stimulatory effect on synthesis rates across the muscle proteome during energy deficit, resulting in muscle mass accretion during subsequent recovery.
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.
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.
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.
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.
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.
This study was carried out to investigate the effect of the male hormone testosterone (T) on weight and blood picture of male rabbits. Fifteen (15) adult male rabbits were weighed and divided into 3 groups: a control group (received 100 μl of sesame oil), a low dose group (received 6 mg T/ kg b. w.), and a high dose group (received 12 mg/kg b. w.). The rabbits were injected intramuscularly once a week for 6 weeks. After the end of the injection period, the rabbits were weighed, slaughtered and blood samples collected for analysis. Injection of T caused significant increases in the levels of T and growth hormone in the sera of treated animals. The hormone also caused significant increases in the weights of treated rabbits. The red blood corpuscles count, the hemoglobin concentration, the percent hematocrit and the platelets count were found to significantly increase with the injection of T. The hormone had no significant effect on the mean corpuscular volume, the mean corpuscular hemoglobin, the mean corpuscular hemoglobin concentration and white blood cells. It is concluded that the increases in red blood corpuscles could have a significant effect on the viscosity of the blood, which could also have an effect on the heart function.
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.
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.
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.
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