Dihydrotestosterone (DHT) rapidly increase after maximal aerobic exercise in healthy males: the lowering effect of phosphodiesterase's type 5 inhibitors on DHT response to exercise-related stress.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Vitamin D, sport and health: a still unresolved clinical issue.

Vitamin D metabolites have a pleiotropic role in human physiology, both in static and dynamic conditions, and a lot of vitamin D-related biological effects could influence physical and sport performances in athletes. Probably due to different factors (e.g., drugs, doping, nutrition, ultraviolet B radiation exposure), in athletes a very high prevalence of vitamin D inadequacy (i.e., deficiency or insufficiency) has been observed. Vitamin D inadequacy in athletes could be associated with specific health risks and to alterations of functional capacities, potentially influencing the fine adjustment of physical performances during training and sport competitions. When risk factors for vitamin D inadequacy exist, a preventive vitamin D supplementation is indicated, and if a vitamin D inadequacy is diagnosed, its supplementation is recommended. Unfortunately, on these issues many concerns remain unresolved. Indeed, it is not clear if athletes should be classified as a special population at increased risk for vitamin D inadequacy; moreover, in comparison to the non-athletic population, it is still not clear if athletes should have different reference ranges and different optimal target levels for serum vitamin D, if they have additional health risks, and if they need different type of supplementations (doses) for prevention and/or replacement therapy. Moreover, in athletes also the abuse of vitamin D supplements for ergogenic purposes raise different ethical and safety concerns. In this review, the main physio-pathological, functional and clinical issues that relate vitamin D to the world of athletes are described.

The use of prohibited substances for therapeutic reasons in athletes affected by endocrine diseases and disorders: the therapeutic use exemption (TUE) in clinical endocrinology.

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.

Comparative study of testosterone and vitamin D analogue, elocalcitol, on insulin-controlled signal transduction pathway regulation in human skeletal muscle cells.

PURPOSE: Skeletal muscle (Skm) plays a key role in regulating energetic metabolism through glucose homeostasis. Several hormones such as Testosterone (T) and Vitamin D (VD) have been shown to affect energy-dependent cell trafficking by determining Insulin (I)-like effects. AIM: To elucidate possible hormone-related differences on muscular metabolic control, we analyzed and compared the effects of T and elocalcitol (elo), a VD analogue, on the activation of energy-dependent cell trafficking, metabolism-related-signal transduction pathways and transcription of gene downstream targets. METHODS: Human fetal skeletal muscle cells (Hfsmc) treated with T or elo were analyzed for GLUT4 localization, phosphorylation/activation status of AKT, ERK1/2, IRS-1 signaling and c-MYC protein expression. RESULTS: T, similar to elo, induced GLUT4 protein translocation likely in lipid raft microdomains. While both T and elo induced a rapid IRS-1 phosphorylation, the following dynamic in phosphorylation/activation of AKT and ERK1/2 signaling was different. Moreover, T but not elo increased c-MYC protein expression. CONCLUSIONS: All together, our evidence indicates that whether both T and elo are able to affect upstream I-like pathway, they differently determine downstream effects in I-dependent cascade, suggesting diverse physiological roles in mediating I-like response in human skeletal muscle.

Testosterone insulin-like effects: an in vitro study on the short-term metabolic effects of testosterone in human skeletal muscle cells.

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 GSK3ß 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 GSK3ß. 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.

Sport and male sexuality.

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.

Short-term, supra-physiological rhGH administration induces transient DNA damage in peripheral lymphocytes of healthy women.

PURPOSE: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Supra-physiological rhGH administration induces gender-related differences in the hypothalamus-pituitary-thyroid (HPT) axis in healthy individuals.

PURPOSE: 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. METHODS: 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. RESULTS: In males, rhGH administration induced a significant (p < 0.01) early and stable TSH decrease and IGF-I increase, and a delayed FT4 reduction without FT3 modification, suggesting a central regulatory mechanism. In females, rhGH administration induced a significant (p < 0.01) early and transient TSH decrease and IGF-I increase, and a transient reduction in FT4 without any changes in FT3 concentrations. rhGH withdrawal was associated with a prompt normalization of TSH and FT4 levels in males, while in females the effects of rhGH treatment had already disappeared during the last period of treatment. CONCLUSION: We suggest that rhGH inhibits TSH at central level both in males and females. The pattern of normalization was different in the two genders probably due to gonadal steroids modulation on GH-IGF-I axis.

Acute endothelial response to testosterone gel administration in men with severe hypogonadism and its relationship to androgen receptor polymorphism: a pilot study.

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 < 0.05), while AI improvement was recorded at 4 and 96 h, also when adjusted for heart rate (AI@75; p < 0.01 and p < 0.001, respectively). Direct relationships between ΔT, ΔDHT and ΔRHI variations (r = 0.37, p < 0.01; r = 0.17, p < 0.05, respectively) as well as between "CAG repeats" length and ΔLnRHI at 96 h (p < 0.03, r (2) = 0.47) were found. An inverse relationship between ΔT and ΔAI (p < 0.01, r = -0.35) and ΔAI@75 (p < 0.01, r = -0.38) were found. CONCLUSION: Administration of TG causes an acute vasodilation and improves arterial stiffness probably due to non-genomic actions of T. Endothelial vasodilatory response was more pronounced depending on higher plasma TT and DHT levels attained. Clinical implications in elderly frail populations are discussed.

Testosterone responses to standardized short-term sub-maximal and maximal endurance exercises: issues on the dynamic adaptive role of the hypothalamic-pituitary-testicular axis.

BACKGROUND: Few and conflicting data on the acute adaptive role of the hypothalamic-pituitary-testicular (HPT) axis to sub-maximal endurance exercise exist. AIMS: 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. SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Subclinical hyperthyroidism and sport eligibility: an exploratory study on cardiovascular pre-participation screening in subjects treated with levothyroxine for multinodular goiter.

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<0.01 and p<0.05, vs HC and UG respectively), b) a thicker left ventricular posterior wall (p<0.05 vs HC, and p<0.05 vs HC and UG, respectively), c) a higher mean HR during the 24-hour Holter ECG (p<0.01 and p<0.05, vs HC and UG respectively), and d) a lower achieved maximum work load (p<0.05, vs HC). No differences in the prevalence of cardiac arrhythmias among groups were observed. Sport eligibility was granted to all except one subject in the TG. CONCLUSIONS: Although some alterations were found in athletes with levothyroxine-induced mild sHT, these are probably of limited clinical relevance and they did not contraindicate sport participation in the majority of cases. Future research to address both health risks and the need for specific evaluations (e.g. free thyroxine, TSH, echocardiography) during the preparticipation screening of athletes with sHT is warranted.

Urinary and serum hormones profiles after testosterone enanthate administration in male hypogonadism: concerns on the detection of doping with testosterone in treated hypogonadal athletes.

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 <2.31 ng/ml). INTERVENTIONS AND MAIN OUTCOME MEASURES: Serum and urinary parameters were evaluated, by radioimmunoassay and gas chromatography-mass spectrometry, before and at different time points for 7/3 weeks after a single administration of testosterone enanthate (250 mg) or placebo, respectively. RESULTS: As partially known, testosterone administration increased, with great individual variability, urinary concentrations of glucuronide testosterone, androsterone, etiocholanolone, 5alpha-androstane- 3alpha,17beta-diol, 5beta-androstane-3alpha,17beta-diol, testosterone/ epitestosterone and testosterone/LH ratios; and decreased epitestosterone and 5alpha-androstane-3beta,17beta-diol/5beta-androstane- 3alpha,17beta-diol ratio. Serum testosterone and dihydrotestosterone increased in all volunteers, and concentrations higher than the upper reference limits were observed in many volunteers until 2 weeks after testosterone administration. CONCLUSION: Whereas the observed prolonged hyperandrogenism partially limited data interpretation, the report ed characteristics of variation of urinary parameters might be used to suspect testosterone misuse in hypogonadal athletes treated with testosterone enanthate. In this sense, while the actual threshold for tes tos terone/epites tos ter one ratio was confirmed to be of reduced usefulness, we suggest a contemporary evaluation of whole urinary androgen metabolites profile and serum androgens, at specific time points after testosterone enanthate administration. Moreover, an adequate tailoring of treatment, to avoid transitory hyperandrogenism, is highly advisable. Further studies on strategies for detecting doping with testosterone in hypogonadal athletes are warranted.

Is explosive performance influenced by androgen concentrations in young male soccer players?

OBJECTIVE: 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. METHODS: 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. RESULTS: Standing long jump length was positively correlated (p<0.05) 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, p<0.05). There was no significant correlation between salivary testosterone concentrations (0.3 (0.1) ng/ml, r = 0.12) and standing long jump. CONCLUSIONS: 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.

The long-acting phosphodiesterase inhibitor tadalafil does not influence athletes' VO2max, aerobic, and anaerobic thresholds in normoxia.

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.

Do non-steroidal anti-inflammatory drugs influence the steroid hormone milieu in male athletes?

Prostaglandins modulate the hypothalamus-pituitary-adrenal and -gonadal axis pathways. We explored the effects of a single course of treatment with acetylsalicylic acid (ASA), an inhibitor of prostaglandin synthesis, on the steroid milieu in athletes. Morning plasma cortisol (F), dehydroepiandrosterone sulphate, free-testosterone, testosterone (T) and their ratios were evaluated before and after the administration of either ASA or placebo in twelve male athletes, when affected by minor musculoskeletal trauma and, as control, after a five/six week wash-out in healthy conditions respectively. One tablet of ASA (800 mg), or placebo, was administered two times daily for 10 days during treatment. All the volunteers suspended exercise training during treatment. The results revealed that compared to placebo, plasma F was significantly lower after ASA treatment (p = 0.023). Furthermore, the comparison of hormone's absolute and percentage of variations (Delta and Delta%) between ASA and placebo treatment showed significant differences respectively for DeltaF (p = 0.045), for DeltaT (p = 0.047), for DeltaT/F (p = 0.042), for DeltaF% (p = 0.04) and for DeltaT% (p = 0.049). Our data suggest that in comparison to placebo, a short-term ASA treatment is able to influence the plasma steroid milieu in athletes. Due to the observed variability of the individual hormonal patterns, further research is required to substantiate these findings.

Cortisol, dehydroepiandrosterone sulphate and dehydroepiandrosterone sulphate/cortisol ratio responses to physical stress in males are influenced by pubertal development.

To evaluate the influence of chronological age and pubertal development on the hypothalamus-pituitary-adrenal (HPA) axis response to stress, we studied the possible correlations between male pubertal characteristics and salivary cortisol (C), DHEAS and the DHEAS/C ratio before (pre-stress) and after acute exercise-stress in young male volunteers (no. 87; 13.3+/-2.1 yr). In our overall study population, the mean pre-stress salivary C and DHEAS concentrations, significantly increased after exercise-related stress, whereas the DHEAS/C ratio significantly decreased. Pre-stress salivary C was positively correlated with chronological age, and after-stress salivary C concentration variations were negatively correlated with pubertal stage, mean testis volume and pre-stress salivary DHEAS. Furthermore, salivary DHEAS concentrations and the DHEAS/C ratio, before and after exercise stress, were positively correlated with chronological age, pubertal stage, pre-stress salivary testosterone (T), testis volume and body mass index (BMI). In contrast with late pubertal stages (P4, P5), young individuals at early stages of puberty (P1 to P3) showed higher C increase and lower DHEAS/C ratio after exercise-related stress. In conclusion, since C is also a mediator of stress-related negative effects on health and the DHEAS/C ratio has been hypothesized as an index for the degree to which an individual is buffered against the negative effects of stress, these data might suggest potentially increased stress-related risks at early stages of male puberty.

Diagnosing erectile dysfunction: instruments for endocrine diagnosis.

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 hypogonadism 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.

Androgens and fertility.

Androgens play a pivotal role in the development of the male reproductive tract. The spermatogenesis requires high levels of intratesticular testosterone secreted by the Leydig cells. Testosterone exerts its action through the androgen receptor (AR), which is located both in the cytoplasm and in the nucleus of cells in the target tissue. Severe defects of the AR may result in abnormal male sexual development, while more subtle modifications can be a potential cause of male infertility. Low circulating levels of testosterone can be found in 20-30% of infertile men, but administration of testosterone or gonadotropins does not result in improved sperm production. Abuse of anabolic steroids is a frequent cause of male infertility, and substances such as endocrine disruptors can alter male fertility through an anti androgenic action.

Psychosocial issues of ART in aging male.

The role of androgens in human sexuality as regards the mechanism of erection and the pathogenesis of impotence is under debate. In addition, it is difficult to define the psychosocial impact of both hypogonadism and androgen replacement. However, sexual hormones largely influence mood, well-being, and quality of life. For this reason, despite the methodological difficulties of assessment, testosterone replacement has a deep impact on the social, psychological and sexual life of the treated patient. Considering the obvious characteristic of testosterone as an hormone, it appears evident that the endocrinologist is the unique experienced specialist able to diagnose and treat the hypogonadal men, monitoring potential side effects and following the psychosocial issues of androgen therapy.