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Gender- and sex- related differences represent a new frontier towards patient-tailored medicine, taking into account that theoretically every medical specialty can be influenced by both of them. Sex hormones define the differences between males and females, and the different endocrine environment promoted by estrogens, progesterone, testosterone, and their precursors might influence both human physiology and pathophysiology. With the term Gender we refer, instead, to behaviors, roles, expectations, and activities carried out by the individual in society. In other words, “gender” refers to a sociocultural sphere of the individual, whereas “sex” only defines the biological sex. In the last decade, increasing attention has been paid to understand the influence that gender can have on both the human physiology and pathogenesis of diseases. Even the clinical response to therapy may be influenced by sex hormones and gender, but further research is needed to investigate and clarify how they can affect the human pathophysiology. The path to a tailored medicine in which every patient is able to receive early diagnosis, risk assessments, and optimal treatments cannot exclude the importance of gender. In this review, we have focused our attention on the involvement of sex hormones and gender on different endocrine diseases.

Sarcopenia is a pathophysiological condition diffused in elderly people; it represents a social issue due to the longer life expectancy and the growing aging population. It affects negatively quality of life and it represents a risk factor for other pathologies, such as diabetes, cardiovascular disease, and obesity. No silver bullet exists to hinder sarcopenia, but it may be counteracted by physical exercise, nutrition, and a proper endocrine milieu. Indeed, we aim to analyze the scientific literature to give to clinician effective advices to counteract sarcopenia. Main text: Physical exercise, proper nutrition, optimized hormonal homeostasis represent the three pillars to fight sarcopenia. Physical exercise represents the most effective remedy to face sarcopenia, in particular if it is combined with a proper diet and with an adequate endocrine milieu. Consistency in training, adequate daily protein intake and eugonadism seems to be the keys to fight sarcopenia. The combination of these three pillars might act synergistically.Optimization of these factors may increase their efficiency; however, scientific data may be sometimes confusing so far. Therefore, we aim to give practical advices to clinician to identify and to highlight the most important aspects in each of these three factors that should be addressed.

Numerosi componenti contribuiscono all’insorgenza e alla progressione della sindrome metabolica e questi fattori differiscono significativamente fra i due sessi. E importante chiarire quali siano i meccanismi molecolari sottostanti a queste differenze correlate al sesso. E inoltre necessario condurre studi che includano anche variabili genere-specifiche (socioculturali, ambientali, ecc.), al fine di identificare criteri specifici per la gestione clinica e farmacologica del paziente.

Premature ejaculation is the most frequent male sexual dysfunction, significantly impairing quality of life of both the patient and the partner and affecting up to one-third of men of every age. In the last years, our knowledge about this topic has greatly increased, and studies on the causes and treatments related to ejaculatory disorders have shed a light on previously uncharted territory. Public interest on sexual dysfunctions has likewise increased in the general population: the time lapse between the first symptoms of sexual dysfunction and the seeking of medical advice has been significantly reduced, whereas demand for a treatment has markedly increased. A role of endocrine regulation has been established in all the aspects of male reproduction; however, the endocrine control of ejaculation is not fully understood. Sex steroid, pituitary, and thyroid hormones have all been advocated as potential candidates in the regulation of the ejaculatory process, but exact mechanisms are not clear yet and further studies are required in order to identify potential targets for treatment.

Background Videogame use is increasingly prevalent in people of all ages, and despite the wide amount of scientific evidence proving a role for electronic entertainment in human health, there is no evidence about the relation between use of videogames and sexual health. Aim To investigate the association between use of videogames and male sexual health. Methods We administered the two validated questionnaires, the Premature Ejaculation Diagnostic Tool (PEDT) and the International Index of Erectile Function (IIEF-15), to men 18 to 50 years old recruited through social networks and specific websites. In addition to the questionnaires, volunteers were asked to provide information on their gaming habit and lifestyle. Outcomes An extended version of the IIEF-15 and PEDT, including data about gaming habits and relevant lifestyles. Results From June 18, 2014 through July 31, 2014, 599 men 18 to 50 years old completed the questionnaires. One hundred ninety-nine men reported no sexual activity during the previous 4 weeks; four records were rejected because of inherent errors. The remaining 396 questionnaires were analyzed, with 287 “gamers” (playing >1 hour/day on average) and 109 “non-gamers” providing all the required information. We found a lower prevalence of premature ejaculation in gamers compared with non-gamers (mean PEDT score = 3.57 ± 3.38 vs 4.52 ± 3.7, P < .05, respectively). Analysis of the IIEF-15 showed no significant differences between gamers and non-gamers in the domains of erectile function, orgasmic function, and overall satisfaction. Median scores for the sexual desire domain were higher for non-gamers (median score [interquartile range] 9 [8–9] vs 9 [8–10], respectively; P = .0227). Clinical Implications These results support the correlation between videogame use and male sexual health. Compared with non-gamers, men playing videogames for more than 1 hour/day were less likely to have premature ejaculation but more likely to have decreased sexual desire. Strengths and Limitations This is the first study aimed to assess male sexual health in gamers. We identified an association between PEDT and IIEF scores and videogame use; however, these findings require validation through interventional studies. Furthermore, volunteers were recruited through social networks, thus increasing the risk of recruitment bias. Conclusion To our knowledge, this is the first observational study investigating the link between electronic entertainment and male sexuality, specifically for ejaculatory response and sexual desire.

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.

Carnitine is an amino acid derivative, mainly involved in lipid metabolism in eukaryotes, including mammals. Although frequently advertised as an efficacious treatment for many conditions, ranging from cardiovascular diseases to male infertility, there is little evidence for many of these claims. The role of carnitine in male fertility has been hypothesized based on its anti-apoptotic effects and its elevated concentrations in male genital tract. Several studies have addressed whether and to what extent carnitine supplementation is able to improve spermatogenesis. To the present date, it would seem that L-carnitine and acetyl-L-carnitine are both able to improve some sperm parameters, allowing their use in men with oligoasthenoteratozoospermia. Men who are about to start assisted reproduction techniques might also benefit from administration of both compounds, as some nonconventional sperm parameters, including chromatin condensation, and pregnancy rate seem to be improved by treatment.

Erectile dysfunction is highly prevalent, affecting up to half of men in their 50-70s, and has been variably associated to a variety of causes including unhealthy lifestyles, such as smoking or overweight, or comorbidities such as hypertension, diabetes mellitus, and neurological disorders. General interest toward ED has exploded since the introduction of phosphodiesterase type 5 inhibitors-oral drugs that are widely accepted as the first line treatment in patients suffering from this conditions. In the last decade, the time lapse between first symptoms of sexual disorders and seeking of medical advice has greatly reduced. Unfortunately, none of the PDE5i has been proven curative, but rather acts as a symptomatic treatment. The availability of very active and safe drugs, however, diminished the space for diagnosis and search of etiological treatments. This is particularly true for the several endocrinopathies associated with ED. A number of epidemiological data support an inverse relationship between sexual health and testosterone levels, and it is well accepted that testosterone deficiency is a good marker of sexual and physical frailty. However, several other hormones, including LH, prolactin, TSH, and FT4 are involved in sexual functioning and should be investigated in a proper work-out of ED. Existing guidelines provide information almost entirely focusing on late-onset hypogonadism and therapeutic strategies; this mini-review aims to provide a wider spectrum of the diagnostic endocrine work-out of ED patients unrevealing the complexity of conditions, overt or subclinical, which can affect ED.

Testosterone is one of the most abused pseudo-endogenous anabolic steroids in sport doping. The current method adopted to detect the abuse of testosterone and other pseudo-endogenous steroids (endogenous steroids when administered exogenously) is first based on the longitudinal monitoring of several urinary biomarkers, which constitute the so called “steroidal module” of the Athlete Biological Passport (ABP): atypical samples undergo a confirmation analysis based on the measurement of the 13C/12C isotopic ratio of selected target compounds, to distinguish their endogenous or exogenous origin. At the same time, testosterone administration can be allowed in athletes diagnosed with hypogonadism, provided they are granted a therapeutic use exemption by the relevant medical authority. In this pilot study we have investigated whether the approach based on the preliminary determination of the urinary steroid profile, in the format considered in the steroidal module of the ABP, also integrated with the inclusion of the sulfo-conjugates and of additional target steroids, can retain its validity also in the case of hypogonadal athletes. We have studied the effects of a single low dose (40 mg) of testosterone gel (T-gel) on the urinary concentration of the markers of steroidal module of the ABP, as well as on some additional steroid markers. The study was based on the analysis of urinary samples from 19 non-hospitalized hypogonadal men, 10 of them with late-onset hypogonadism (LOH), collected before, after 4 h and after 24 h the transdermal self-administration of 40 mg of T-gel. None of the patient had any co-morbidities possibly affecting the urinary excretion of the steroidal markers. The steroidal markers were quantified by gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) after the enzymatic hydrolysis of the respective glucuro-conjugates and the chemical hydrolysis of the respective sulfo-conjugates. Targeted GC-MS/MS analysis was carried out operating in electron impact (EI) ionization mode, with acquisition in multiple reaction monitoring (MRM) mode. Our preliminary results show that, as expected, the treatment with T-gel leads, in all hypogonadal men, to an increase of the urinary concentration of the glucuro-conjugate metabolites of testosterone and its main metabolites, with special relevance to those with 5α-reduction. Furthermore, samples collected from non-LOH hypogonadal men showed an increase also in the levels of epitestosterone glucuronide, testosterone sulfate and epitestosterone sulfate. Apart from their biochemical and pharmacological relevance, these outcomes could be leveraged to refine the analytical strategy currently followed in the antidoping field for the analysis of the urinary steroidal markers, with potential implications also in other forensic and/or clinical investigations.

Androgenetic alopecia, commonly known as male pattern baldness, is the most common type of progressive hair loss disorder in men. The aim of this paper is to review recent advances in understanding the pathophysiology and molecular mechanism of androgenetic alopecia. Using the PubMed database, we conducted a systematic review of the literature, selecting studies published from 1916 to 2016. The occurrence and development of androgenetic alopecia depends on the interaction of endocrine factors and genetic predisposition. Androgenetic alopecia is characterized by progressive hair follicular miniaturization, caused by the actions of androgens on the epithelial cells of genetically susceptible hair follicles in androgen-dependent areas. Although the exact pathogenesis of androgenetic alopecia remains to be clarified, research has shown that it is a polygenetic condition. Numerous studies have unequivocally identified two major genetic risk loci for androgenetic alopecia, on the X-chromosome AR⁄EDA2R locus and the chromosome 20p11 locus. Candidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms at different genomic loci are associated with androgenetic alopecia development. A number of genes determine the predisposition for androgenetic alopecia in a polygenic fashion. However, further studies are needed before the specific genetic factors of this polygenic condition can be fully explained.

Besides their widely discussed role in empirical therapy of male infertility, antioxidants have been used in experimental studies also for treating male sexual dysfunctions. Oxidative stress is clearly involved in the pathogenesis of infertility: less consisting evidence has been found in regard to its involvement in erectile and ejaculatory dysfunctions. Nitric oxide (NO) is an endothelium-derived relaxing factor, acting as a vasodilator and as an antioxidant: it is also the key molecule involved in obtaining and maintaining an erection. Administration of NO has been investigated as a substitute for phosphodiesterase type 5 (PDE-5) inhibitors or an additional treatment for nonresponders to standard treatments. Furthermore, a possible role for testosterone as a free radical scavenger has been postulated: testosterone replacement therapy might help prevent oxidative stress-related dysfunctions in several organs. Oxidative stress is also involved in some forms of priapism: antioxidants might therefore be helpful in preventing recurrences or in treating vascular damage resulting from ischemia-reperfusion injury.

The mean age of the world population has steadily increased in the last decades, as a result of increased life expectancy and reduced birth rate. Global aging has led to a greater worldwide cost for healthcare: hormonal alterations contribute to the pathogenesis of several conditions and might cause a significant reduction in the perceived sense of well-being. Menopause is archetypal of hormonal alterations occurring during aging: in males, sex hormones do not decrease abruptly, yet testosterone levels decrease steadily and continuously during aging, ultimately resulting in late-onset hypogonadism. Treatment of this condition might mitigate most symptoms; however, testosterone replacement therapy (TRT) should be prescribed only in selected patients and it should not be considered as an antiaging treatment. In recent years, different authors have questioned health risks associated with testosterone treatment; while position statements from many scientific societies seem to be reassuring, the Food and Drug Administration has issued a warning in regard to the possible side effects of this therapy. We aim to review recent controversies and discoveries in regard to TRT.

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

In recent years, many studies have focused on the effect of oxidative stress, reactive oxygen species (ROS) and antioxidants on the male eproductive system. Under physiological conditions, sperm produces small amounts of ROS, which are needed for fertilisation, acrosome reaction and capacitation. However, if an increased production of ROS is not associated with a similar increase in scavenging systems, peroxidative damage of the sperm plasma membrane and loss of DNA integrity typically occur, which leads to cell death and reduced fertility. Furthermore, since there is no linear correlation between sperm quality and pregnancy rates, an improvement in semen parameters should not be the sole outcome considered in studies of antioxidant therapies. A definitive conclusion regarding the benefit of these therapies is difficult to obtain, as most of the previous studies lacked control groups, considered different antioxidants in different combinations and doses, or did not evaluate pregnancy rates in previously infertile couples. Even if beneficial effects were reported in a few cases of male infertility, more multicentre, double-blind studies performed with the same criteria are necessary for an increased understanding of the effects of various antioxidants on fertility.

L’attivita fisica rappresenta un caposaldo nella definizione di un corretto stile di vita. L’esercizio, infatti, si e dimostrato utile, se non imprescindibile, nella prevenzione e nella terapia di molte patologie a decorso cronico e delle loro complicanze. La relazione fra sport e ormoni e biunivoca: il sistema endocrino regola l’omeostasi del corpo umano durante l’esercizio fisico e, a sua volta, l’esercizio fisico rappresenta un potente modulatore della funzionalita del sistema endocrino. Un’adeguata secrezione ormonale e necessaria a garantire tanto una risposta fisiologica all’esercizio, quanto una sana partecipazione all’attivita fisica. Patologie del sistema endocrino possono comportare tanto un calo delle prestazioni, quanto un detrimento alla salute di numerosi organi e sistemi. La salute dello sport si traduce anche nell’educazione a non eccedere con l’attivita fisica. In letteratura e stato evidenziato come per entrambi i sessi un eccessivo esercizio fisico non comporti vantaggi in termini di salute sessuale e riproduttiva ma favorisca invece l’insorgenza di nuove problematiche. L’erronea convinzione che solo una carenza ormonale sia associata a un calo del rendimento fisico ha portato all’uso a scopo illecito di un elevato numero di sostanze. E opportuno sottolineare che l’uso di questi prodotti “dopanti” assunti per migliorare le prestazioni puo non solo non tradursi in un vantaggio in termini di performance sportiva ma, al contrario, comporta seri danni per la salute della persona e dell’atleta. Tra le sostanze piu frequentemente “abusate” nel mondo dell’attivita sportiva vanno sicuramente annoverati gli steroidi anabolizzanti. Prevenire e trattare le patologie ormonali e istruire gli atleti a una sana “salute dello sport” sono due necessita non solo per lo specialista endocrinologo, ma per ogni operatore coinvolto nel mondo dello sport e piu in generale dell’attivita motoria.