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Regular physical activity can enhance immune function and effectively prevents the spread of the cytokine response, thus reducing systemic low-grade inflammation and improving various immune markers. Moreover, regular exercise maintains redox homeostasis in skeletal muscle and other tissues, including immune cells, but the interconnection between the anti-inflammatory effects of exercise with the redox status of immune cells is still poorly understood. With the aim to verify the overall beneficial effect of regular training on the immune system, we have examined the acute and short-term effect of a 5-day exercise program on the modulation of protein and lipid oxidation, antioxidants (i.e., superoxide dismutase-1 (SOD1) and superoxide dismutase-2 (SOD2), glutathione peroxide 1 (GPx1), thioredoxin reductase-1 (TrxR1), and catalase (CAT)), and heat shock protein expression (i.e., heat shock protein-70 (HSP70) and heat shock protein-27 (HSP27)), at both mRNA and protein levels, as well as the activation of the nuclear factor kappa light chain enhancer of activated B cells (NFκB) in peripheral blood mononuclear cells (PBMCs). Moreover, plasmatic markers of oxidative stress, inflammation, and stress response (i.e., protein carbonyl content, interleukin-6 (IL6), interleukin-8 (IL8), interleukin-10 (IL10), interleukin-17E (IL17E), interleukin-17F (IL17F), interleukin-21 (IL21), interleukin-22 (IL22), and interleukin-23 (IL23)) were analyzed in active untrained young adult subjects. Even in the absence of an increased amount of protein or lipid oxidation, we confirmed a PBMC upregulation of SOD1 (1.26±0.07fold change,p<0.05), HSP70 (1.59±0.28fold change,p<0.05), and HSP27 gene expression (1.49±0.09fold change,p<0.05) after 3 hours from the first bout of exercise, followed by an increase in proteins’ amount at 24 hours (SOD1,1.80±0.34fold change; HSP70,3.40±0.58fold change; and HSP27,1.81±0.20fold change,p<0.05) and return to basal levels after the 5 days of aerobic training. Indeed, the posttraining basal levels of oxidized molecules in plasma and PBMCs were statistically lower than the pretraining levels (carbonyl content,0.50±0.05fold change,p<0.01), paralleled by a lower expression of SOD2, Gpx1, and TrxR1, at mRNA (SOD2,0.63±0.06; GPx1,0.69±0.07; and TrxR1,0.69±0.12fold change,p<0.05) and protein (TrxR1,0.49±0.11fold change,p<0.05) levels. These results verified the existence of an early phase of redox adaptation to physical exercise already achievable after 5 days of moderate, regular aerobic training. More interestingly, this phenomenon was paralleled by the degree of NFκB activation in PBMCs and the decrease of plasmatic proinflammatory cytokines IL8, IL21, and IL22 in the posttraining period, suggesting an interconnected, short-term efficacy of aerobic exercise towards systemic oxidative stress and inflammation.

BackgroundProlonged or unaccustomed eccentric exercise may cause muscle damage and depending from its extent, this event negatively affects physical performance.ObjectivesThe aim of the present investigation was to evaluate, in humans, the effect of the flavonoid quercetin on circulating levels of the anabolic insulin-like growth factor 1 (IGF-I) and insulin-like growth factor 2 (IGF-II), produced during the recovery period after an eccentric-induced muscle damage (EIMD).MethodsA randomized, double-blind, crossover study has been performed; twelve young men ingested quercetin (1 g/day) or placebo for 14 days and then underwent an eccentric-induced muscle damaging protocol. Blood samples were collected, and cell damage markers [creatine kinase (CK), lactate dehydrogenase (LDH) and myoglobin (Mb)], the inflammatory responsive interleukin 6 (IL-6), IGF-I and IGF-II levels were evaluated before the exercise and at different recovery times from 24 hours to 7 days after EIMD.ResultsWe found that, in placebo treatment the increase in IGF-I (72 h) preceded IGF-II increase (7 d). After Q supplementation there was a more marked increase in IGF-I levels and notably, the IGF-II peak was found earlier, compared to placebo, at the same time of IGF-I (72 h). Quercetin significantly reduced plasma markers of cell damage [CK (pConclusionsOur data are encouraging about the use of quercetin as dietary supplementation strategy to adopt in order to mitigate and promote a faster recovery after eccentric exercise as suggested by the increase in plasma levels of the anabolic factors IGF-I and IGF-II.

Background: The phosphodiesterase type 5 inhibitor (PDE5I) tadalafil, in addition to its therapeutic role, has shown antioxidant effects in different in vivo models. Supplementation with antioxidants has received interest as a suitable tool for preventing or reducing exercise-related oxidative stress, possibly leading to the improvement of sport performance in athletes. However, the use/abuse of these substances must be evaluated not only within the context of amateur sport, but especially in competitions where elite athletes are more exposed to stressful physical practice. To date, very few human studies have addressed the influence of the administration of PDE5Is on redox balance in subjects with a fitness level comparable to elite athletes, therefore, the aim of this study was to investigate for the first time whether acute ingestion of tadalafil could affect plasma markers related to cellular damage, redox homeostasis, and blood polyamines levels in healthy subjects with an elevated cardiorespiratory fitness level. Methods: Healthy male volunteers (n = 12), with a VO2max range of 40.1–56.0 mL/(kg × min), were administered with a single dose of tadalafil (20 mg). Plasma molecules related to muscle damage and redox-homeostasis, such as creatine kinase (CK), lactate dehydrogenase (LDH), total antioxidant capacity (TAC), reduced/oxidized glutathione ratio (GSH/GSSG), free thiols (FTH), antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)), as well as thiobarbituric acid reactive substances (TBARs), protein carbonyls (PrCAR), and polyamine levels (spermine (Spm) and spermidine (Spd)) were evaluated immediately before and 2, 6 and 24 hours after the acute tadalafil administration. Results: A single tadalafil administration induced an increase in CK and LDH plasma levels 24 after consumption. No effects were observed on redox homeostasis or antioxidant enzyme activities, and neither were they observed on the oxidation target molecules or polyamines levels. Conclusion: Our results show that in subjects with an elevated fitness level, a single administration of tadalafil induced a significant increase in muscle damage target without affecting plasma antioxidant status.

According to the type and duration, physical exercise may influence positively and negatively the secretion of hormones related to the hypothalamic–pituitary–gonadal axis in males. Indeed, although acute exercise induces a rise in testosterone secretion, chronic, high-load/duration physical exercise reduces the activity of the hypothalamic–pituitary–gonadal axis. This different response of sexual hormones in males to physical exercise and training influences sexual and spermatogenetic functions that might be improved, maintained, or impaired.

Physical inactivity and sedentary behavior are risk factors for type 2 diabetes mellitus (T2DM). Therefore, physical exercise (PE) together with medical treatment might be considered as a key strategy to counteract T2DM. Glycemic control is a central objective in the prevention and management of T2DM, and PE might be able to substantially affect the processes that determine it. Just like a drug, exercise can be dosed based on the characteristics of the individual to increase its benefits and reduce side effects. In this brief review, the mechanisms underlying the effects of PE on glucose metabolism in muscle are illustrated, and the effects of modulation of the parameters characterizing this atypical "drug" on glucose homeostasis are described.

ObjectivesEvaluating the relationship between circulating metabolic biomarkers and semen parameters in obese, overweight and normal-weight patients.MethodsPatients were recruited at the “Andrology and Pathophysiology of Reproduction Unit”, in Santa Maria Goretti Hospital. Divided into three groups were 98 participants (obese, overweight and normal-weight patients) according to BMI and were analyzed for three adipokines and six hormone peptides in blood serum and seminal plasma using Luminex assay. Standard semen analysis was performed for ejaculate volume, sperm concentration, total sperm count, motility, morphology and leukocytes.ResultsIn all groups of subjects, we observed a higher concentration of blood serum c-peptide, GIP, PAI-1, leptin, ghrelin and GLP-1 in comparison to seminal plasma; differently, higher levels in seminal plasma were observed for insulin and visfatin. In comparison to the non-obese subjects, obese subjects showed a higher blood serum concentration of c-peptide, GLP-1, GIP and leptin and a higher concentration of seminal plasma of GIP and insulin. Total sperm count, progressive motility, motility, and atypical forms directly correlated with PAI-1 and visfatin, whereas GLP-1 directly correlated only with total progressive motility.ConclusionObese men showed a different pattern of blood serum and seminal plasma adipokines and hormone peptides concentrations in comparison to normal-weight men. Furthermore, these molecules correlated with functional seminal parameters. Our findings support the option to consider these molecules as new biomarkers and pharmacological targets for a new therapeutic approach in male infertility. However, further studies identifying other potential biomarkers of male infertility with important clinical implication and characterizing their mechanisms of action are mandatory.

Exercise plays an important role in preventing and treating postprandial dysmetabolism. We investigated the postprandial metabolic responses to a standard lunch when a session of aerobic exercise is performed in the early postprandial phase or divided between the pre- and postprandial period. Nine healthy volunteers consumed a standardised mixed lunch and rested for the following 3 h (Con) or performed 40 min of cycling at 65% VO2max after lunch (CPPEx), or two 20-min sessions, one before (SplitEx1) and the other after lunch (SplitEx2), at the same intensity. At 1-h post-lunch, a significant reduction (P

This study was aimed at investigating whether quercetin (Q) may improve the recovery of neuromuscular function and biochemical parameters in the 7 days following an eccentric exercise-induced muscle damage (EEIMD). Sixteen men (25.9 &plusmn, 3.3 y) ingested Q (1000 mg/day) or placebo (PLA) for 14 days following a double-blind crossover study design. A neuromuscular (NM) test was performed pre&ndash, post, 24 h, 48 h, 72 h, 96 h and 7 days after an intense eccentric exercise. The force&ndash, velocity relationship of the elbow flexor muscles and their maximal voluntary isometric contraction (MVIC) were recorded simultaneously to the electromyographic signals (EMG). Pain, joint angle, arm circumference, plasma creatine kinase (CK) and lactate-dehydrogenase (LDH) were also assessed. The results showed that Q supplementation significantly attenuated the strength loss compared to PLA. During the recovery, force&ndash, velocity relationship and mean fibers conduction velocity (MFCV) persisted significantly less when participants consumed PLA rather than Q, especially at the highest angular velocities (p &lt, 0.02). A greater increase in biomarkers of damage was also evident in PLA with respect to Q. Q supplementation for 14 days seems able to ameliorate the recovery of eccentric exercise-induced weakness, neuromuscular function impairment and biochemical parameters increase probably due to its strong anti-inflammatory and antioxidant action.

Few data exist on dihydrotestosterone (DHT) adaptation to exercise-related stress. The aim of the study was to investigate on serum DHT and other androgens’ responses to acute aerobic exercises, and to verify if a long-acting phosphodiesterase’s type 5 inhibitors could influence these responses, as previously observed for salivary testosterone. In a double-blind cross over study, 12 healthy trained male volunteers were submitted to both an acute sub-maximal and maximal exercise tests on cycle ergometer, after randomly receiving a two days placebo or tadalafil administration (20 mg, Cialis®, Ely-Lilly, Indianapolis, IN, USA). Blood sample collections were performed at different time points before and after exercise. Serum DHT, total testosterone (TT), dehydroepiandrosterone sulfate (DHEAS) and luteinizing hormone (LH), were assayed. Serum DHT increase in placebo treatment immediately post maximal aerobic exercise and return to basal values at 60 min of recovery whereas tadalafil administration significantly reduced the DHT increase after exercise. The values of areas under curves showed the increase of TT after acute sub-maximal and maximal exercise and of DHEAS only after acute maximal aerobic exercise independently from treatment. In addition to testosterone, also DHT plays an exercise-related adaptive role during high intensity aerobic exercise, but its rapid useful effects during exercise have to be determined. We hypothesized that the increased androgens secretion during exercise could be mainly related to steroidogenic enzymes modifications in peripheral tissues (i.e., muscles). Moreover, the blunting effect of tadalafil on DHT increase support a possible role of peripheral nitric oxide/GMPc related pathways in influencing physical-stress related DHT metabolism.

Purpose Testosterone by promoting different metabolic pathways contributes to short-term homeostasis of skeletal muscle, the largest insulin-sensitive tissue and the primary site for insulin-stimulated glucose utilization. Despite evidences indicate a close relationship between testosterone and glucose metabolism, the molecular mechanisms responsible for a possible testosterone-mediated insulin-like effects on skeletal muscle are still unknown. Methods Here we used undifferentiated proliferating or differentiated human fetal skeletal muscle cells (Hfsmc) to investigate the short-term effects of testosterone on the insulin-mediated biomolecular metabolic machinery. GLUT4 cell expression, localization and the phosphorylation/activation of AKT, ERK, mTOR and GSK3β insulin-related pathways at different time points after treatment with testosterone were analyzed. Results Independently from cells differentiation status, testosterone, with an insulin-like effect, induced Glut4-mRNA expression, GLUT4 protein translocation to the cytoplasmic membrane, while no effect was observed on GLUT4 protein expression levels. Furthermore, testosterone treatment modulated the insulin-dependent signal transduction pathways inducing a rapid and persistent activation of AKT, ERK and mTOR, and a transient inhibition of GSK3β. T-related effects were shown to be androgen receptor dependent. Conclusion All together our data indicate that testosterone through the activation of non-genomic pathways, participates in skeletal muscle glucose metabolism by inducing insulin-related effects.

The relationships between sport and sexuality in males are of great social and clinical interest, because of sports and motor activities that highly promote social and sexual relationships. Even if few literature exist, two main questions should be taken into account: whether and how physical exercise and sport positively or negatively influence sexual health and behavior and/or whether and how sexual behavior may affect a sub-sequent sport performance. Physical exercise and sport per se can influence, positively or negatively, the hypothalamic-pituitary-testicular axis function and, consequently, the individual's reproductive and/or sexual health. This depends on individual factors such as genetic and epigenetic ones and on different variables involved in the practice of sport activities (type of sport, intensity and duration of training, doping and drug use and abuse, nutrition, supplements, psychological stress, allostatic load, etc.). If well conducted, motor and sport activities could have beneficial effects on sexual health in males. Among different lifestyle changes, influencing sexual health, regular physical activity is fundamental to antagonize the onset of erectile dysfunction (ED). However, competitive sport can lead both reproductive and/or sexual tract damages and dysfunctions, transient (genital pain, hypoesthesia of the genitalia, hypogonadism, DE, altered sexual drive, etc.) or permanent (hypogonadism, DE, etc.), by acting directly (traumas of the external genitalia, saddle-related disorders in cyclists, etc.) or indirectly (exercise-related hypogonadism, drug abuse, doping, stress, etc.). Sexual activities shortly performed before a sport competition could differently influence sport performance. Due to the few existing data, it is advisable to avoid an absolute pre-competition sexual abstinence.

Phosphodiesterase type 5 inhibitors (PDE5Is), widely known for their beneficial effects onto male erectile dysfunction, seem to exert favorable effects onto metabolism as well. Tadalafil exposure increases oxidative metabolism of C2C12 skeletal muscle cells. A rise in fatty acid (FA) metabolism, requiring more oxygen, could induce a larger reactive oxygen species (ROS) release as a byproduct thus leading to a redox imbalance. The aim of this study was to determine how PDE5I tadalafil influences redox status in skeletal muscle cells to match the increasing oxidative metabolism. To this purpose, differentiated C2C12 skeletal muscle cells were treated with tadalafil and analyzed for total antioxidant capacity (TAC) and glutathione levels as marker of redox status; enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) engaged in antioxidant defense; and lipid peroxidation (TBARS) and protein carbonyls (PrCar) as markers of oxidative damage. Tadalafil increased total intracellular glutathione (tGSH), CAT, SOD, and GPx enzymatic activities while no changes were found in TAC. A perturbation of redox status, as showed by the decrease in the ratio between reduced/oxidized glutathione (GSH/GSSG), was observed. Nevertheless, it did not cause any change in TBARS and PrCar levels probably due to the enhancement in the antioxidant enzymatic network. Taken together, these data indicate that tadalafil, besides improving oxidative metabolism, may be beneficial to skeletal muscle cells by enhancing the enzymatic antioxidant system capacity.

To protect sporting ethics and athletes' health, the World Anti-Doping Agency (WADA) produced the World Anti-Doping Code and The Prohibited List of substances and methods forbidden in sports. In accordance with the International Standards for Therapeutic Use Exemption (ISTUE), to avoid rule violations and sanctions, athletes affected by different endocrine diseases and disorders (e.g., adrenal insufficiency, diabetes, male hypogonadisms, pituitary deficit, thyroid diseases, etc.) who need to use a prohibited substance for therapeutic reasons (e.g., medical treatments, surgical procedures, clinical diagnostic investigations) must apply to their respective Anti-Doping Organizations (ADOs) to obtain a Therapeutic Use Exemption (TUE), if specific criteria are respected. The physicians who treat these athletes (i.e., endocrinologists, andrologists and diabetologists) are highly involved in these procedures and should be aware of their specific role and responsibility in applying for a TUE, and in adequately monitoring unhealthy athletes treated with prohibited substances. In this paper, the prohibited substances commonly used for therapeutic reasons in endocrine diseases and disorders (e.g., corticotropins, beta-blockers, glucocorticoids, hCG, insulin, GnRH, rhGH, testosterone, etc.), the role of physicians in the TUE application process and the general criteria used by ADO-Therapeutic Use Exemption Committees (TUECs) for granting a TUE are described.

Purpose: To indirectly evaluate the effect of androgens on neuromuscular system in humans we analyzed if an induced short-term hypogonadal state (serum total testosterone-TT.

The aim of the present investigation was to test the hypothesis that quercetin (Q) may prevent the strength loss and neuromuscular impairment associated with eccentric exercise-induced muscle damage (EEIMD). Twelve young men (26.1 &plusmn, 3.1 years) ingested either Q (1000 mg/day) or placebo (PLA) for 14 days using a randomized, double-blind, crossover study design. Participants completed a comprehensive neuromuscular (NM) evaluation before, during and after an eccentric protocol able to induce a severe muscle damage (10 sets of 10 maximal lengthening contractions). The NM evaluation comprised maximal voluntary isometric contraction (MVIC) and force&ndash, velocity relationship assessments with simultaneous recording of electromyographic signals (EMG) from the elbow flexor muscles. Soreness, resting arm angle, arm circumference, plasma creatine kinase (CK) and lactate dehydrogenase (LDH) were also assessed. Q supplementation significantly increased the isometric strength recorded during MVIC compared to baseline (+4.7%, p &lt, 0.05). Moreover, the torque and muscle fiber conduction velocity (MFCV) decay recorded during the eccentric exercise was significant lower in Q compared to PLA. Immediately after the EEIMD, isometric strength, the force&ndash, velocity relationship and MFCV were significantly lower when participants were given PLA rather than Q. Fourteen days of Q supplementation seems able to attenuate the severity of muscle weakness caused by eccentric-induced myofibrillar disruption and sarcolemmal action potential propagation impairment.

It is universally accepted that lifestyle interventions are the first step towards a good overall, reproductive and sexual health. Cessation of unhealthy habits, such as tobacco, alcohol and drug use, poor nutrition and sedentary behavior, is suggested in order to preserve/improve fertility in humans. However, the possible risks of physical exercise per se or sports on male fertility are less known. Being “fit” does not only improve the sense of well-being, but also has beneficial effects on general health: in fact physical exercise is by all means a low-cost, high-efficacy method for preventing or treating several conditions, ranging from purely physical (diabetes and obesity) to psychological (depression and anxiety), highly influencing male reproduction. If male sexual and reproductive health could be positively affected by a proper physical activity, inadequate bouts of strength – both excessive intensity and duration of exercise training – are more likely to have detrimental effects. In addition, the illicit use of prohibited drugs (i.e. doping) has reached pandemic proportions, and their actions, unfortunately very often underestimated by both amateur and professional athletes, are known to disrupt at different levels and throughout various mechanisms the male hypothalamic-pituitary-gonadal axis, resulting in hypogonadism and infertility.

The present review provides a comprehensive overview on the erythropoietic and non-erythropoietic effects of rHuEpo on human sport performance, paying attention to quantifying numerically how rHuEpo affects exercise performance and describing physiological changes regarding the most important exercise variables. Much attention has been paid to treatment schedules, in particular, to assess the effects of microdoses of rHuEpo and the prolonged effects on sport performance following withdrawal. Moreover, the review takes into account non-erythropoietic ergogenic effects of rHuEpo, including cognitive benefits of rHuEpo. A significant increase in both Vo2max and maximal cycling power was evidenced in studies taken into account for this review. rHuEpo, administered at clinical dosage, may have significant effects on haematological values, maximal and submaximal physiological variables, whereas few reports show positive effects on exercise perfomance. However, the influence of micro-dose rHuEpo on endurance performance in athletes is still unclear and further studies are warranted.

Purpose Tadalafil, the phosphodiesterase type 5 inhibitor (PDE5I), has been shown to reduce visceral adipose tissue in rabbit and to improve lean mass content in non-obese men. In order to clarify this effect in humans, in the present study we determined the impact of an acute oral tadalafil administration on lipolysis by evaluating plasma free fatty acids (FFAs) and glycerol. FFAs are potential modulator of inflammation response that we evaluated through tumor necrosis factor alpha (TNFα), interleukin 6 (IL6), interleukin 8 (IL8) and interleukin 10 (IL10) plasma levels. Moreover, we determined whether the effects of tadalafil would be reflected in variation of plasma levels of cGMP and NO, two important molecules involved in PDE5Is signaling. Methods Twelve healthy subjects were supplemented with 20 mg of tadalafil or a placebo, in a double-blind, randomized, cross-over design. Blood samples were collected immediately before, and at 2, 6, and 24 hours post ingestion, and assayed for biochemical analysis. Results A condition effect was noted for FFAs and glycerol, with values higher for tadalafil when compared to the placebo group, at 2 and 6 hours post ingestion. No statistically significant effects were noted for glucose, cGMP, nitrate and nitrite. No inflammatory response was induced by tadalafil. Conclusion Tadalafil, in human subjects, increases lipolysis as evidenced by a significant increase in circulating FFAs and glycerol, without affecting the plasma cGMP and NO levels; noticeably, the increase in FFAs did not develop an inflammatory response. Further well-controlled studies are warranted to assess the impact of tadalafil administration on weight/fat loss.

Phosphodiesterase type 5 inhibitors (PDE5i) (e.g., sildenafil, tadalafil, vardenafil, and avanafil) are drugs commonly used to treat erectile dysfunction, pulmonary arterial hypertension, and benign prostatic hyperplasia. PDE5i are not prohibited by the World Anti-Doping Agency (WADA) but are alleged to be frequently misused by healthy athletes to improve sporting performance. In vitro and in vivo studies have reported various effects of PDE5i on cardiovascular, muscular, metabolic, and neuroendocrine systems and the potential, therefore, to enhance performance of healthy athletes during training and competition. This suggests well-controlled research studies to examine the ergogenic effects of PDE5i on performance during activities that simulate real sporting situations are warranted to determine if PDE5i should be included on the prohibited WADA list. In the meantime, there is concern that some otherwise healthy athletes will continue to misuse PDE5i to gain an unfair competitive advantage over their competitors.

Physical exercise is associated with enhanced production of reactive oxygen species, which if uncontrolled can result in tissue injury. Phosphodiesterase type 5 inhibitors (PDE5i) exhibit protective effect against oxidative stress, both in animals and healthy/unhealthy humans. However, the effect of a chronic administration of PDE5i, particularly combined with physical exercise, has never been investigated. The present study was designed to evaluate the effect of the long-acting PDE5i tadalafil on oxidative status and muscle damage after exhaustive exercise in healthy males included in a double-blind crossover trial. Tadalafil, having a putative antioxidant activity, may reduce oxidative damage after strenuous exercise. Each volunteer randomly received two tablets of placebo or tadalafil (20 mg/day) with 36 h of interval before performing exhaustive exercise. After 2 weeks of washout, the volunteers were crossed over. Blood samples were collected immediately before exercise, immediately after, and during recovery (15, 30, 60 min). Plasma total antioxidant status, glutathione homeostasis (GSH/GSSG), malondialdehyde (MDA), protein carbonyls, creatine kinase (CK), lactate dehydrogenase (LDH) and the inflammatory cytokine interleukin 6 were assessed. Tadalafil administration per se affected redox homeostasis (GSH/GSSG −36 %; p

Endogenous glucocorticoids (GC) rapidly increase after acute exercise, and the phosphodiesterase's type 5 inhibitor (PDE5i) tadalafil influences this physiological adaptation. No data exist on acute effects of both acute exercise and PDE5i administration on 11β-hydroxysteroid dehydrogenases (11β-HSDs)-related GC metabolites. We aimed to investigate the rapid effects of exercise on serum GC metabolites, with and without tadalafil administration. A double blind crossover study was performed in eleven healthy male volunteers. After the volunteers randomly received a short-term administration of placebo or tadalafil (20 mg/die for 2 days), a maximal exercise test to exhaustion on cycle ergometer was performed. Then, after a 2-week washout period, the volunteers were crossed over. Blood samples were collected before starting exercise and at 5 and 30 min of recovery (+5-Rec, +30-Rec). Serum ACTH, corticosterone (Cn), cortisol (F), cortisone (E), tetrahydrocortisol (THF), tetrahydrocortisone (THE), cortols, cortolones and respective ratios were evaluated. Pre-Ex THF was higher after tadalafil. Exercise increased ACTH, Cn, F, E, THE, cortols and cortolones after both placebo and tadalafil, and THF after placebo. The F/E ratio increased at +5-Rec and decreased at +30-Rec after placebo. Compared to placebo, after tadalafil lower ACTH, F and Cn, higher THF/F and THE/E, and not E (at +5-Rec) and F/E modifications were observed. Acute exercise rapidly influences serum GC metabolites concentrations. Tadalafil influences both GC adaptation and 11β-HSDs activity during acute exercise. Additional researches on the effects of both exercise and PDE5i on tissue-specific 11β-HSDs activity at rest and during physiological adaptation are warranted.

While a good safety for recombinant human growth hormone (rhGH) therapy at replacement doses is recognized, a possible link between high concentration of the GH-IGF-I axis hormones and side negative effect has been reported. The aim of this pilot study was to assess whether a short-term exposure to supra-physiological doses of rhGH may affect DNA integrity in human lymphocytes (PBL). Eighteen healthy Caucasian female (24.2 ± 3.5 years) were randomly included in a Control (n = 9) and rhGH administration group (n = 9, 3-week treatment). DNA damage (comet assay), chromosomal breaks, and mitotic index in phytohemagglutinin-stimulated PBL were evaluated before (PRE), immediately (POST), and 30 days (POST30) after the last rhGH administration (0.029 mg kg− 1 BW; 6 days/week), together with serum IGF-1 and IGFBP-3 concentrations. rhGH administration increased IGF-I, without evidence of persisting IGF-I and IGFBP-3 changes 30 days after withdrawal. Total DNA breakage (% DNA in tails) was not significantly different in subjects treated with rhGH in comparison with controls, although the rhGH-treated subjects showed an higher percentage of heavily damaged nuclei immediately after the treatment (POST30 vs. PRE: p = 0.003), with a lower mitogenic potential of lymphocytes, detectable up to the POST30 (PRE vs. POST: p = 0.02; PRE vs. POST30: p = 0.007). This pilot study showed that 3 weeks of short-term supra-physiological rhGH administration in healthy women induce a transient DNA damage and mitogenic impairment in PBL. The analysis of DNA damage should be explored as useful tool in monitoring the mid to long-term effects of high rhGH treatment or abuse.

The use of recombinant human growth hormone (rhGH) is a common habit among athletes. While the effects of rhGH administration have been described with contrasting results in males, no data exist in females to date. The aim of the present study was to evaluate the effects of rhGH administration on TSH, FT4 and FT3 levels and the time requested to return to baseline values after treatment withdrawal. Twenty-one healthy trained male and female athletes were treated with 0.03 mg rhGH/kg body mass 6 days/week for 3 weeks. We collected blood samples immediately before the first daily rhGH administration, at 3, 4, 8, 15 and 21 days of treatment and at 3 and 9 days after rhGH withdrawal. In males, rhGH administration induced a significant (p

Introduction A well‐tailored testosterone replacement treatment (TRT) in male hypogonadal athletes plays a pivotal role to restore physiological performances, to reduce health risks, and to guarantee the ethic of competition. Few studies evaluated individual androgens profiles during TRT in trained individuals. Aim The aim of this article was to verify the efficacy in restoring eugonadal serum and urinary androgens profiles after testosterone enanthate (TE) and gel (TG) administration. Methods Ten male Caucasian‐trained volunteers affected by severe hypotestosteronemia ( Main Outcome Measures The main outcome measures of this article were serum total testosterone (TT), dihydrotestosterone (DHT), calculated free and bioavailable testosterone (cFT, cBioT), 17‐β‐estradiol, and urinary glucuronide testosterone metabolites. Results Supraphysiological TT concentrations were observed in 50% of our volunteers until 7 days after TE and in the 4% of total samples after TG. Serum DHT was high both after TE (all volunteers on day 7 and 50% on day 14) and during TG (32% of total samples). A relatively low number of samples showed normal cFT and cBioT both after TE and TG (20–44%, respectively). Urinary metabolites were related to the type of treatment and to serum androgens profile and resulted in the normal ranges from 15% to 60% of total samples. Conclusion Besides well‐known variations of mean serum TT, we showed a high percentage of serum and urinary samples with abnormal androgens, being TG safer than TE. We conclude that monitoring TRT with TT only may be inaccurate because of abnormal fluctuations of other circulating androgens. Further studies to identify the appropriate markers of eugonadism during TRT are highly warranted both in athletes and in non‐athletes. Di Luigi L, Sgro P, Aversa A, Migliaccio S, Bianchini S, Botre F, Romanelli F, and Lenzi A. Concerns about serum androgens monitoring during testosterone replacement treatments in hypogonadal male athletes: a pilot study. J Sex Med 2012;9:873–886.

Aims: Osteogenesis imperfecta (OI) is a rare inherited disorder causing low bone density and increased fragility. Bisphosphonates (BP) are a treatment of choice for OI. Few studies have investigated the long-term effects of BP in OI patients. Thus, aim of our study was to follow up adults affected by OI to evaluate changes in metabolic, clinical situation and safety of long-term neridronic acid therapy, BP authorized for OI treatment. Study design: Longitudinal observational study. Place and duration of the Study: Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition. Year: 2004 - October 2010. Methodology: 68 patients underwent clinical examination, laboratory endocrine/ metabolic, pro-inflammatory cytokines screening, ECG at baseline and every 3 months and bone mineral density evaluation, by DEXA, once a year. Results: Skeletal evaluation showed a significant increase of BMD through follow up. Patients were evaluated for metabolic and cardiovascular risk factors, which were unmodified by long-term therapy. Conclusion: Long-term neridronic acid treatment increases bone density, does not alter metabolic parameters indicating that this therapy can be considered safe and a valid therapeutic option for OI patients.

The effect of recombinant human growth hormone (rhGH) administration on hypothalamic-pituitary-thyroid (HPT) system in healthy trained humans still needs to be fully clarified. Furthermore, whether rhGH abuse could exert undesirable or noxious effect on health is still unclear. In order to evaluate changes in HPT axis variables in time after rhGH administration, 14 well-trained healthy male athletes were treated with rhGH (0.03 mg/kg body weight/day, sc ) administration, 6 days/week for 3 weeks. Morning blood samples were collected immediately before and 3, 4, 8, 15, and 21 days after rhGH administration. A further set of blood samples was taken 3, 6 and 9 days after drug withdrawal. Samples were analyzed for GH-IGF and HPT axis. Significant TSH serum decrease and IGF-I increase occurred early after rhGH administration, without FT 3 content modification and with FT 4 reduction delayed in time. Serum TSH concentrations negatively correlated with IGF-I, IGFBP-3 and IGF-I/IGFBP-3 ratios. rhGH short-term administration in healthy trained subjects induced an early TSH suppression – likely acting at central level through IGF-I – without thyroid function alteration. Further investigations in athletes are necessary to verify whether prolonged TSH suppression, i.e. rhGH intake for longer time, could induce pathologic condition, such as hypothyroidism.

Whereas experimental studies showed that in healthy trained subjects, the phosphodiesterase-5 inhibitor (PDE-5i) sildenafil improves exercise capacity in hypoxia and not in normoxia, no studies on the effects of the long half-life PDE-5i tadalafil exist. In order to evaluate whether tadalafil influences functional parameters and performance during a maximal exercise test in normoxia, we studied 14 healthy male athletes in a double-blind cross-over protocol. Each athlete performed two tests on a cycle ergometer, both after placebo or tadalafil (at therapeutic dose: 20 mg) administration. Oxygen consumption (VO2), blood lactate, respiratory exchange ratio, rate of perceived exertion, arterial blood pressure (BP), heart frequency (HR) and oxygen pulse (VO2/HR) were evaluated before exercise, at individual ventilatory and anaerobic thresholds (IVT and IAT), at VO2max and during recovery. Compared to placebo, a single tadalafil administration significantly reduced systolic BP before and after exercise (p < 0.05), decreased VO2/HR at IVT (13.3 +/- 1.8 vs. 14.5 +/- 2.1 mL . beat (-1); p = 0.03), but did not modify individual VO2max, IVT, or IAT. In healthy athletes, 20 mg of tadalafil does not substantially influence physical fitness-related parameters, exercise tolerance, and cardiopulmonary responses to maximal exercise in normoxia; it remains to be verified if higher doses/prolonged use influence health and/or sport performance in field conditions.

Objective To determine the efficacy of combined l-carnitine and l-acetyl-carnitine therapy in infertile males with oligo-astheno-teratozoospermia. Design Placebo-controlled double-blind randomized trial. Setting University tertiary referral center. Patient(s) Sixty infertile patients (aged 20–40 years) with the following baseline sperm selection criteria: concentration, 10 to 40 × 10 6 /mL; forward motility, Intervention(s) Patients were submitted to a combined treatment of l-carnitine (2 g/d) and l-acetyl-carnitine (1 g/d) or of placebo; the study design was 2 months' wash-out, 6 months of therapy or of placebo, and 2 months' follow-up. Main outcome measure(s) Variation in the semen parameters that were used for patient selection. Result(s) Even though increases were seen in all sperm parameters after combined carnitine treatment, the most significant improvement in sperm motility (both forward and total) was present in patients who had lower initial absolute values of motile sperm ( 6 forward or 6 total motile spermatozoa per ejaculate). Conclusion(s) Combined treatment with l-carnitine and l-acetyl-carnitine in a controlled study of efficacy was effective in increasing sperm motility, especially in groups with lower baseline levels.

Objective To determine the efficacy of L-carnitine therapy in selected cases of male factor infertility. Design Placebo-controlled, double-blind, crossover trial. Setting University tertiary referral center. Patient(s) One hundred infertile patients (ages 20–40 years) with the following baseline sperm selection criteria: concentration, 10–20 × 10 6 /mL; total motility, 10%–30%; forward motility, Intervention(s) Patients underwent L-carnitine therapy 2 g/day or placebo; the study design was 2 months of washout, 2 months of therapy/placebo, 2 months of washout, and 2 months placebo/therapy. Main outcome measure(s) Variation in sperm parameters used in the patients selection criteria, in particular, sperm motility. Result(s) Excluding outliers, a statistically significant improvement in semen quality, greater than after the placebo cycle, was seen after the L-carnitine therapy for sperm concentration and total and forward sperm motility. The increase in forward sperm motility was more significant in those patients with lower initial values, i.e., 6 or 6 of forward motile sperm/ejaculate or sperm/mL. Conclusion(s) Based on a controlled study of efficacy, L-carnitine therapy was effective in increasing semen quality, especially in groups with lower baseline levels. However, these results need to be confirmed by larger clinical trials and in vitro studies.

The phosphodiesterases type 5 (PDE5) inhibitors (PDE5i) (e.g., sildenafil, tadalafil) widely used to treat erectile dysfunction, and for recreational purpose such as sports supplements, may enhance the cGMP-dependent metabolic effects of NO. An increase in NO production, following tadalafil administration, could generate peroxynitrite, the most reactive free radical species causing oxidative injury. We investigate whether the acute supplementation with PDE5i could affect plasma antioxidant status in healthy, physically active humans. A crossover study has been carried out with male volunteers (n=6) supplemented with a single dose of 20 mg tadalafil. Plasma total antioxidant status (TAS) and glutathione (GSH) homeostasis were evaluated immediately before and after 2, 6 and 24 hours of the acute administration.TAS values increased after 2 h (1.01 ± 0.13 Trolox eq. mM) to decrease after 24 h (0.85 ± 0.06) compared to baseline (0.92 ± 0.09). Oxidized glutathione (GSSG) increased from 6 h (3.68 ± 0.55, 4.27 ± 0.97 and 5.09 ± 0.82 GSSG 10-5 M for baseline, 6 h and 24 h respectively). GSH/GSSG ratio decreased (16.85 ± 5.28 and 12.85 ± 2.00 for 6 and 24 h) compared to baseline (18.36 ± 4.92). Our preliminary results show that an acute tadalafil administration affects plasma antioxidant status in healthy physically active men.

Quercetin (Q) functions as antioxidant in vitro, but its effect have been minimally examined in combination with exercise in humans. The purpose of this investigation was to determine the effects of a diet supplemented with 1 g per day of Q for 2 weeks on the erythrocytes oxidative balance before and after an acute bout of eccentric exercise (EE). Fourteen volunteer males were randomly assigned, in a double-blind crossover design, to a placebo or experimental supplemented groups. Blood samples were taken before and after 2 weeks of supplementation under resting and post-exercise conditions. Erythrocytes glutathione (GSH, GSSG, GSH/GSSG), malonaldehyde (TBARs), enzymes antioxidant activities as well as time of hemolysis were evaluated in ex vivo. Quercertin per se did not affect redox homeostasis but increased the time of hemolysis and decreased TBARs levels. Following the EE the Q group displayed a higher GSH/GSSG ratio and a less pronounced increase in TBARs, compared to placebo group. Moreover, we found that GPx enzyme activity were induced after EE only in Q group, while any significant modification of this parameter was detected in placebo group. In conclusion, the Q supplementation may be used as a countermeasure against oxidative stress inducing, in erythrocytes, a cellular adaptation allowing subjects to better cope with the oxidative stress induced by an acute exercise.

Few and conflicting data on the acute adaptive role of the hypothalamic-pituitary-testicular (HPT) axis to sub-maximal endurance exercise exist. To investigate the acute HPT axis responses to standardized endurance exercises in a laboratory setting and the correlations between testosterone and classic adaptive hormones variations. 12 healthy male volunteers were recruited for this experimental study. Serum PRL, GH, ACTH, LH, cortisol, DHEAS, testosterone [total (TT), calculated free (cFT) and bioavailable (cBioT)], SHBG, and respective ratios, were evaluated before and after a 30-min sub-maximal exercise on cycle ergometer at individual anaerobic threshold (IAT) and a maximal exercise until exhaustion. Blood samples were collected before exercise (30, 15 min and immediately before), immediately after and at different time points during recovery (+15, +30 and +60 min) for hormones assays. Oxygen consumption and lactate concentration were evaluated. Testosterone (TT, cFT and cBioT) acutely increased in all volunteers after both exercises. Testosterone increased in parallel to GH after both exercises and to cortisol only after maximal exercise. Differently from other increased hormones, testosterone increases were not correlated to exercise-intensity-related variables. The anabolic/catabolic steroids ratios were higher after sub-maximal exercise, compared to maximal. A 30-min sub-maximal endurance exercise acutely increased serum testosterone similarly to maximal exercise, but without cortisol increases. Exercise-related testosterone peaks should be considered adaptive phenomena, but few data on their short- and long-term effects exist. Investigations on the mechanisms of adaptation to exercise in active individuals with physiological or pathological hypo-testosteronemia are warranted.

BRUNELLI, A., I. DIMAURO, P. SGRO ` , G. P. EMERENZIANI, F. MAGI, C. BALDARI, L. GUIDETTI, L. DI LUIGI, P. PARISI, AND D. CAPOROSSI. Acute Exercise Modulates BDNF and pro-BDNF Protein Content in Immune Cells. Med. Sci. Sports Exerc., Vol. 44, No. 10, pp. 1871–1880, 2012. Purpose: Although several studies have shown that immune cells stimulated by in vitro stress are capable to produce neurotrophins, there is still no evidence whether physiological stress, such as exercise, can modulate the in vivo levels of brain-derived neurotrophic factor (BDNF) in peripheral blood mononuclear cells (PBMCs). Methods: This work investigated whether acute exercise modulates the expression of BDNF, pro-BDNF, and p75 NTR in the PBMCs of 10 healthy young men who performed a cycling incremental test to exhaustion (MAX) or exercised at individual anaerobic threshold (IAT). The PBMC expression of stress response proteins and the level of circulating BDNF, vascular endothelial growth growth factor, platelet-derived growth factor subunit B, basic fibroblast growth factor pro-inflammatory, and anti-inflammatory cytokines were analyzed as well. Results: A major finding is that both sessions of acute exercise regulated the content of BDNF isoforms within PBMCs in a manner related to the physiological stress exerted. Although the pro-BDNF increased after both MAX and IAT protocols, BDNF showed a kinetics dependent on exercise type: MAX induced a 54% protein increase immediately after exercise, followed by a significant drop 60 min after its conclusion (38% lower than the baseline). Differently, in the IAT, BDNF increased significantly up to 75% from the baseline throughout the recovery phase. All physiological parameters, as well as the p75 NTR receptor and the stress-inducible proteins, were also differently regulated by the two exercise conditions. Conclusions: These data supported the hypothesis that PBMCs might produce and secrete BDNF isoforms, as well as modulate the proteins p75 NTR , Bcl-xL, hsp90, hsp27, and >B-crystallin, as part of the physiological stress response induced by acute

Phosphodiesterase type 5 inhibitors may influence human physiology, health, and performance by also modulating endocrine pathways. We evaluated the effects of a 2-day tadalafil administration on adenohypophyseal and adrenal hormone adaptation to exercise in humans. Fourteen healthy males were included in a double-blind crossover trial. Each volunteer randomly received two tablets of placebo or tadalafil (20 mg/day with a 36-h interval) before a maximal exercise was performed. After a 2-wk washout, the volunteers were crossed over. Blood samples were collected at −30 and −15 min and immediately before exercise, immediately after, and during recovery (+15, +30, +60, and +90 min) for adrenocorticotropin (ACTH), β-endorphin, growth hormone (GH), prolactin, cortisol (C), corticosterone, dehydroepiandrosterone-sulfate (DHEAS), and cortisol binding globulin (CBG) assays. C-to-CBG (free cortisol index, FCI) and DHEAS-to-C ratios were calculated. Exercise intensity, perceived exertion rate, O2consumption, and CO2and blood lactate concentration were evaluated. ACTH, GH, C, corticosterone, and CBG absolute concentrations and/or areas under the curve (AUC) increased after exercise after both placebo and tadalafil. Exercise increased DHEAS only after placebo. Compared with placebo, tadalafil administration reduced the ACTH, C, corticosterone, and FCI responses to exercise and was associated with higher β-endorphin AUC and DHEAS-to-C ratio during recovery, without influencing cardiorespiratory and performance parameters. Tadalafil reduced the activation of the hypothalamus-pituitary-adrenal axis during exercise by probably influencing the brain's nitric oxide- and cGMP-mediated pathways. Further studies are necessary to confirm our results and to identify the involved mechanisms, possible health risks, and potential clinical uses.

Appropriate physical activity is one of the bases of healthy lifestyle. In fact, physical exercise and playing sport may be associated with both improvements and injury to both general and reproductive health. A biologically normal testosterone secretion appears fundamental in males to guarantee both a physiological exercise adaptation and safe sport participation. The reproductive system is highly sensitive to the effects of exercise-related stress and the reproductive hormones may both increase and decrease after different acute or chronic exercises. Exercise and sport participation may positively or negatively influence andrological health status depending on the type, intensity and duration of performed physical activity and on individual health status. In addition, prohibited substances administration (e.g. androgenic-anabolic steroids, and so forth) in competitive and non-competitive athletes represents the main cause of iatrogenic andrological diseases. Preventing and treating andrological problems in active healthy and unhealthy individuals is as important as promoting a correct lifestyle. Physicians need to be educated on the relationships between the male reproductive system and sport participation and on the great role of the pre-participation physical examination in the prevention of andrological diseases.

Introduction Worldwide many aging males practice sports. A high prevalence of late-onset male hypogonadism has been observed in general population. Sport-participation influences the neuroendocrine system and may decrease serum testosterone. Aim This preliminary study was designed to estimate the prevalence and the symptoms of undiagnosed testosterone deficiency in aging athletes. Methods This observational survey was performed in 183 caucasian male athletes >50 years, in the setting of pre-participation screening. Pituitary–gonadal hormones and symptoms of hypogonadism were investigated. Serum total testosterone (TT), sex hormone binding globulin, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), free -T4, and thyroid stimulation hormone (TSH) were assayed, and free T, bioactive T, and the LH/TT ratio were calculated. The International Index of Erectile Dysfunction (IIEF-15) and the Center for Epidemiological Studies Depression Scale (CES-D) were administered. Hypogonadal athletes were compared with eugonadal athletes as controls. Main Outcome Measures Prevalence and clinical symptoms of severe (TT Results The mean sample age was 61.9 ± 7.5 years (range 50–75). Severe or mild testosterone deficiency was observed in 12% and 18%, respectively, of overall athletes, with the highest prevalence in athletes >70 years (27.5% and 25.0%, respectively). TT did not correlate with age, training duration, or questionnaire scores. No differences were observed for nonspecific symptoms of hypogonadism, IIEF-15 and CES-D scores between eugonadal and severe hypogonadal athletes. Conclusions Independently of its etiology, a significant percentage of aging athletes had undiagnosed testosterone deficiency. In a relevant number of these cases, testosterone deficiency was not overtly symptomatic. Our results suggest that sport-participation per se can influence the symptoms of hypogonadism. The history of clinical symptoms may be inaccurate to diagnose testosterone deficiency in aging athletes. Future research should address the clinical relevance and the specific risks of testosterone deficiency in aging athletes, and the need of a systematic pre-participation serum testosterone evaluation. Di Luigi L, Sgro P, Fierro V, Bianchini S, Battistini G, Magini V, Jannini EA, and Lenzi A. Prevalence of undiagnosed testosterone deficiency in aging athletes: Does exercise training influence the symptoms of male hypogonadism?

Background: Subclinical hyperthyroidism (sHT) affects cardiovascular (CV) morphology and function; whether such changes can impact on sport eligibility is unclear. Aim: This exploratory study evaluated the CV system and sport eligibility in athletes with levothyroxine-induced sHT, in the setting of mandatory pre-participation screening. Subjects and methods: A full, non-invasive CV screening (history and physical examination, 12-lead ECG, echocardiography, 24-hour Holter ECG, exercise stress test) was performed in two groups of untrained female athletes affected by non-toxic multinodular goiter. One group was taking levothyroxine at mildly suppressive doses (TG) whereas the other was untreated (UG). There was also a group of healthy controls (HC). Results: In TG the following characteristics were observed: a) a higher resting heart rate (HR; p

ObjectiveTo detect exogenous recombinant human GH (rhGH) abuse in female athletes.DesignGH-dependent markers were assayed in serum of 100 female athletes (control group) and in a subgroup of nine female subjects treated with rhGH (0.09 IU/kg body weight, 6 days/week for 3 weeks).MethodsCut-off values (mean+2 s.d.) for IGF1, N-terminal propeptide of type III procollagen (PIIINP) and C-terminal telopeptide of type I collagen (ICTP) were calculated and arbitrary scores (1.5 or 2.0) were assigned to abnormal markers. By using the sum of individual marker scores, positive (≥3) or negative (ResultsNone of the control group obtained a positive score (≥3). Abnormal IGF1, PIIINP and ICTP levels were found in 61.4, 54.5 and 11.4% samples of the treated group. Overall, positive cases were present in 43.2% blood samples drawn in subjects treated with rhGH and in 26% of samples after rhGH withdrawal. The sensitivity of the detection approach was 66.6% at the end of 3-week rhGH treatment and 11.1% at the 15th day of rhGH withdrawal, while the specificity was 100%.ConclusionDetection test for rhGH administration appears less sensitive in female (66.6%) than in male athletes (previous observation, 100% after 3 weeks of comparable rhGH dose), but shows a similar specificity (98.5–100%). Since athletes supposedly use very high doses and long-term administration of rhGH for doping purposes, it is foreseen that the here-in detection test would in future increase its strength.

Objective: To describe serum and urinary hormones, androgens metabolites and testosterone/epitestosterone ratio profiles after testosterone administration in male hypogonadal volunteers, and to evaluate their possible usefulness in detecting doping with testosterone in treated hypogonadal athletes. Design: Controlled open label design vs placebo; pharmacokinetic study. Participants: Ten male volunteers affected by severe hypogonadism (serum testosterone

There is growing interest in the implementation and assessment of strength and conditioning programmes among young children. The purpose of this study was to examine the association between given anthropometric characteristics, pubertal development, salivary androgen hormones and explosive leg power in young soccer players.51 (age range 10-14 years) soccer players were investigated. The relations between age, pubertal developmental stages, testicular volume, weight, height, body fat, fat free mass, salivary DHEAS concentrations, salivary testosterone concentrations and lower limb explosive power were evaluated.Standing long jump length was positively correlated (p0.05) with age (11.7 (SD 1.2) years, r = 0.66), pubertal developmental stages (mode and range: 1 (1-4), r = 0.64), testicular volume (8.8 (5.2) ml, r = 0.58), height (1.50 (0.10) m, r = 0.34), weight (43.7 (9.1) kg, r = 0.34), fat free mass (35.4 (7.2) kg, r = 0.67), salivary DHEAS concentrations (4.4 (1.2) ng/ml, r = 0.38) and negatively correlated with body fat (18.6 (7.0) kg; r = -0.49, p0.05). There was no significant correlation between salivary testosterone concentrations (0.3 (0.1) ng/ml, r = 0.12) and standing long jump.Results of the present investigation demonstrated that age, pubertal developmental stages, testicular volume, weight, height, fat free mass, and salivary DHEAS concentrations were associated with standing long jump performance. In addition, salivary testosterone concentrations were not related to explosive leg power. Results of the present investigation suggest that the teacher/coach should evaluate long jump performance relative to the subject's given biological characteristics, and not simply established standards based on chronological age.

Context: Physical exercise-related stress activates hypothalamus-pituitary-adrenal (HPA) axis; nitric oxide is one of the mediators of the HPA axis response to stress, and phosphodiesterase type 5 inhibitors influences nitric oxide-linked biological activities. Objective: The objective of the study was to investigate whether a single oral long half-life phosphodiesterase type 5 inhibitor (tadalafil) administration influences the HPA axis response to exercise-related stress. Design: This was a double-blind, cross-over trial. Participants: Participants included nine healthy male athletes. Interventions: All subjects performed a maximal exercise test in normoxia, after which they received a single oral administration of tadalafil or placebo. Then after a 2-wk washout period, they were crossed over and repeated the exercise test. Each subject was his own control. Salivary collections, for steroid evaluations [cortisol, dehydroepiandrosterone sulphate (DHEAS), testosterone] and respective ratio calculation (DHEAS to cortisol, testosterone to cortisol, testosterone to DHEAS), were performed before each exercise (Pre-Ex), immediately after (Post-Ex), and at 30 min during recovery. Results: As expected, mean salivary cortisol concentration increased immediately after exercise after both tadalafil and placebo (P = 0.014 and P =0.036 vs. Pre-Ex, respectively); however, the cortisol increase was significantly higher after tadalafil administration (P = 0.034 vs. placebo). Furthermore, an increased salivary testosterone after exercise was observed only after tadalafil administration (P = 0.029 vs. Pre-Ex). No effects of either exercise and/or tadalafil administration on salivary DHEAS concentrations were observed. DHEAS to cortisol and testosterone to cortisol ratios significantly decreased after exercise after tadalafil administration (P = 0.037, and P = 0.02 vs. placebo, respectively). Conclusion: Tadalafil administration amplified the salivary cortisol and testosterone responses to a maximal exercise-related stress in healthy trained humans.

Sirtuins are NAD+ dependent deacetylases that play a key role in the regulation of many processes related to homeostasis, such as the regulation of metabolism, apoptosis, DNA repair and inflammatory response. Studies on humans reported a relation between the alteration of their expression and the incidence of various diseases such as metabolic, cardiovascular, cancer and neurodegenerative diseases. According with these findings the maintenance of their optimal level of activity is considered important to ensure a low risk of pathologies related with the aging process. Indeed, SIRT1 has been correlated with the redox homeostasis maintenance and with the levels of oxidative damage, such as those affecting telomeric sequences of DNA. The aim of this study is to verify the correlation between sirtuins’ expression, histone deacetylation and redox status in young and old monozygotic twins. For this study we took advantage from blood samples of young (20-40 years old) and old (70-80 years old) monozygotic twins couple, where we analysed the expression of SIRT1 and SIRT2, Lysine acetylation proteins and Histone H4 acetylation, the protein oxidation through the detection of carbonyl groups have been analysed in PBMCs, plasma level of oxidized and reduced glutathione. The putative increase of SIRT1 and SIRT2 levels that should also lead to an improvement in redox and inflammatory homeostasis, hormonal response to stress, and in the maintenance of telomeric DNA sequences could open an interesting view in this field. Particularly the twin model can help to better understand the interaction between genetic and epigenetic effects in the age-related mechanisms.

BACKGROUND: The aims of our study were to investigate the short- and long-term effects of chemo- or radiotherapy on spermatogenesis in patients with testicular cancer and to establish any correlation between pre-therapy sperm parameters, histotype and treatment type/intensity and the progress of spermatogenesis during the post-therapy period. METHODS: We evaluated 166 patients affected by testicular cancer, who cryobanked about 1 month after the removal of the cancerous testis and before beginning chemo- (CH group; n = 71) or radiotherapy (RT group; n = 95). RESULTS: For the CH group, there was a statistically significant decrease in sperm parameters, which was most significant 3 months after the end of chemotherapy. For the RT group, this decrease was most relevant 6 months after the end of radiotherapy. Two years after therapy, 3% of the CH group and 6% of the RT group remained azoospermic. To evaluate whether spermatogenesis recovery is a function of baseline semen quality, we divided each group into two subgroups by pre-therapy total sperm count (A

We investigated the relationship between oxidative stress and diabetic erectile dysfunction.A total of 23 patients with a mean +/- SD age of 56.7 +/- 5.6 years, a history of type 2 diabetes for 10.0 +/- 8.3 years and erectile dysfunction, as tested by the International Index of Erectile Function questionnaire, but without vascular and neurological complications, and 15 age matched patients with diabetes without erectile dysfunction were recruited. Circulating monocyte oxidative activity by cytofluorometry, and endothelin-1, intercellular adhesion molecule-1, plasminogen activator inhibitor-1 by enzyme linked immunosorbent assay were evaluated in all patients in the study.Monocyte free radical production, and total and low density lipoprotein cholesterol were higher in patients with than in those without erectile dysfunction (p0.03,0.02 and0.05, respectively). In all patients the International Index of Erectile Function score inversely correlated with low density lipoprotein (p0.05), while in patients with erectile dysfunction it negatively correlated with age (p0.03), body mass index (p0.02), endothelin-1 (p0.02) and intercellular adhesion molecule-1 (p0.05). Endothelin-1, intercellular adhesion molecule-1 and plasminogen activator inhibitor-1 were not different in patients with diabetes with and without erectile dysfunction.In men with type 2 diabetes who have erectile dysfunction but are asymptomatic for cardiovascular disease oxidative activation of monocytes is increased and it is related to other risk factors of endothelial dysfunction.

OVER TRIAL OF CARNITINE THERAPY IN SELECTED CASES OF MALE INFERTILITY Francesco Lombardo, Loredana Gandini, University of Rome "La Sapienza", Ashok Agarwal, Cleveland Clinic Foundation, Paolo Sgro, Franco Dondero, Andrea Lenzi, University of Rome "La Sapienza" Objective: Carnitine has been demonstrated in several uncontrolled clinical trials over the past decade to have beneficial effects on semen quality in patients with idiopathic male-factor etiologies. The goal of our study was to determine the efficacy of L-carnitine therapy on semen quality in selected cases of male infertility.

Purpose Testosterone (T) exerts different effects on the cardiovascular system. Despite this knowledge, the acute vascular effect of androgen remains still poorly understood. Methods We investigated the acute effects of T on vascular function in ten men (18–40 years age) with hypogonadism and severe hypotestosteronemia [serum total testosterone (TT) = 0.6 ± 0.3 ng/mL]. In a 4-day double-blind, randomized, placebo-controlled crossover study, we administered 80 mg daily dose of transdermal-T gel (TG) and evaluated endothelial variations with Endopat2000 (reactive hyperemia index, RHI and the augmentation index, AI); also, CAG repeat polymorphism in exon 1 of the androgen receptor gene was investigated. Results After TG administration, RHI significantly improved at 4 h (p

Endocrine factors represent an important and potentially treatable cause of sexual dysfunction. The availability of a correct endocrinological diagnosis allows correct identification of most cases of sexual dysfunction in which the endocrine apparatus is involved. Not only the most frequent causes of endocrine sexual dysfunction, such as hypogonadisin and hyperprolactinaemia, but almost all extra-gonadal endocrinopathies (hyper-and hypothyroidism, hyper- and hypocortisolism, steroidal secreting tumours, etc.) may have importance to a greater or lesser extent in sexual function. It is, therefore, necessary that the diagnostic process for sexual dysfunctions of an endocrine nature be as integrated and wide as possible, especially as such pathologies are normally extremely responsive to medical or surgical therapy.

Hyperhomocysteinemia is considered one of the most important cardiovascular risk factors increasing considerably the risk of stroke and myocardial infarction. With respect to endothelial function, direct effects of hyperhomocysteinemia on vascular endothelial cells have been demonstrated through the reduction of endothelial nitric oxide production. In this paper, we report the case of a young man with homozygote genotype mutated with 5-methylenetetrahydrofolate reductase (MTHFR) thermolabile variant who, in the absence of relational stress, developed an erectile dysfunction (ED) refractory to the vasoactive type-V phosphodiesterase (PDE5) inhibitor therapy. After one month of treatment with 5 mg/day folic acid and 1000 microg/day cyanocobalamin, the patient restarted the assumption of 50 mg sildenafil, obtaining satisfying erections during sexual intercourse. We suggest that hyperhomocysteinemia may interfere with penile blood supply and, thus, be responsible for ED. If this relationship is confirmed, plasma levels and urinary homocysteine (HCy) should be evaluated in selected young patients with vascular ED. Furthermore, careful attention should be given to the risk of ED when dealing with this metabolic disturbance.