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Introduction: Overweight and obesity are highly prevalent conditions associated with premature morbidity and mortality worldwide. Capsiate, a nonpungent analogue of capsaicin, binds to TRP vanilloid 1 (TRPV1) receptor, which is involved in adipogenesis, and could be effective as a weight-lowering agent., Methods: Eighteen slightly overweight women were enrolled in this randomized, double-blind, placebo-controlled study. Nine patients were included in the capsiate intervention group and received 9 mg/day of capsinoids and 9 patients received placebo for 8 weeks. All patients underwent weight and waist circumference assessment before and after treatment. Body composition and bone mineral density (BMD) were also detected by dual-energy X-ray absorptiometry (DXA)., Results: Fourteen patients completed the study. The treatment with capsiate or placebo for 8 weeks was not associated with significant changes in weight or waist circumference. After treatment, there was a significant improvement in BMD values measured at the spine in the capsiate group (1.158 vs 1.106 g/cm 2 , + 4.7%; p = 0.04), but not in the group treated with placebo. Similarly, the capsiate group showed a 9.1% increase (p = 0.05) in the adipose tissue and an 8.5% decrease in lean mass measured at the supraclavicular level, whereas these changes were not statistically significant in the placebo group., Conclusions: Treatment with capsiate for 8 weeks led to negligible changes in body weight in a small sample of slightly overweight women, but our findings suggest a potential effect of capsaicin on bone metabolism in humans., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Background: Klinefelter syndrome (KS) is frustratingly under-diagnosed. KS have a broad spectrum of clinical features, making it difficult to identify.  OBJECTIVE: We describe KS clinical presentation in a large Italian cohort., Design: This is the first observational cohort study within a national network, the Klinefelter ItaliaN Group (KING). Primary outcomes were to describe the basic clinical features and the actual phenotype of KS in Italy. Secondary outcomes were to determine age at diagnosis and geographical distribution., Methods: We performed a basic phenotyping and evaluation of the hormonal values of 609 adult KS patients., Results: Mean age at diagnosis was 37.4 ± 13.4 years. The overall mean testicular size was 3 ml, and 2.5 ml in both testes in untreated KS group. BMI was 26.6 ± 5.8 kg/m 2 , and 25.5% of KS had metabolic syndrome (MetS). LH and FSH were increased, and mean total testosterone were 350 ± 9.1 ng/dl. A descriptive analysis showed that 329 KS patients were evaluated in Northern Italy, 76 in Central and 204 in Southern Italy. Analysis of variance demonstrated significant statistical differences (p < 0001) between the age at diagnosis of the three geographical groups. Compared with the expected number among male patients matched for age in Italy, only 16% of KS patients received a diagnosis., Conclusions: These data are the results of the only national database available that collects the clinical and hormonal data of the KS patients, currently referred at the KING centers. In Italy the typical KS patient is overweight, with small testes, and elevated LH and FSH. Only 25.5% of them are diagnosed with MetS. Early detection and timely treatment are mandatory., (© 2022. The Author(s).)

Acromegaly is a rare pathology characterized by chronic hypersecretion of Growth Hormone (GH) and Insulin-like Growth Factor-1 (IGF-1) that causes somatic, metabolic, and systemic changes. The somatotropic axis acts physiologically favoring gonadal function, but when GH is produced in excess it has deleterious effects on many aspects of male sexuality. It is widely demonstrated, in fact, that acromegaly induces hypogonadism through different mechanisms, both through direct mass effect on gonadotropic cells and through increased plasma levels of prolactin. Moreover, hypogonadism is also one of the factors linking acromegaly to erectile dysfunction (ED), but also metabolic complications of acromegaly and, probably, GH itself contribute to the genesis of this disorder. There are few data in the literature on the impact of the disease on fertility and testicular volume. Finally, knowledge of the role of GH hypersecretion on the occurrence of prostatic diseases such as benign prostatic hypertrophy and prostatic cancer appears to be of fundamental clinical importance in the long-term management of these patients., (© 2022. The Author(s).)

We conducted a survey during the first pandemic wave of coronavirus disease 2019 (COVID-19) on a large group of osteoporotic patients to evaluate the general conditions of osteoporotic patients and the impact of the pandemic on the management of osteoporosis, finding high compliance to treatments and low COVID-19 lethality., Introduction: During the first pandemic wave of coronavirus disease 2019 (COVID-19), 209,254 cases were diagnosed in Italy; fatalities were 26,892 and were overwhelmingly older patients. The high prevalence of osteoporosis in this age group suggests a potential relationship between SARS-CoV-2 infection and bone metabolism., Methods: In a telephone survey conducted from April to May 2020, patients from the Osteoporosis Center, Clinic of Endocrinology and Metabolic Diseases of Umberto I Hospital (Ancona, Italy), were interviewed to evaluate the general clinical conditions of osteoporotic patients, compliance with osteoporosis medications, COVID-19 prevalence, hospitalization rate, COVID-19 mortality, and lethality., Results: Among the 892 patients interviewed, 77.9% were taking osteoporosis treatment and 94.6% vitamin D supplementation as prescribed at the last visit. COVID-19-like symptoms were reported by 5.1%, whereas confirmed cases were 1.2%. A total number of 33 patients had been in hospital and the hospitalization rate of those who had not discontinued vitamin D supplementation was less than 4%. There were eight deaths, two with a concomitant COVID-19 diagnosis. The prevalence of severe osteoporosis was 50% in total COVID-19 patients and 87.5% in deceased COVID-19 patients. The overall COVID-19 mortality was 0.2%; lethality was 20%, lower than the national rate of the same age group., Conclusions: This large group of osteoporotic patients showed high compliance and lower COVID-19 lethality compared to patients of the same age. Novel approaches such as telemedicine can provide critical support for the remote follow-up of patients with chronic diseases also in the setting of routine care., (© 2022. The Author(s).)

Purpose: Testicular germ cell tumours (TGCTs) is the most common malignancy among young adult males. The etiology is multifactorial and both environmental and genetic factors play an important role in the origin and development of TGCT. Genetic susceptibility may result from the interaction of multiple common and low-penetrance genetic variants and one of the main candidate genes is PDE11A. Many PDE11A polymorphisms were found responsible for a reduced PDE activity in TGCT patients, who often also display impaired hormone and sperm profile. The aim of this study was to investigate testicular function and PDE11A sequence in testicular cancer cases., Methods: Semen analysis was performed in 116 patients with unilateral and bilateral sporadic TGCTs and in 120 cancer-free controls. We also investigated hormone profile and PDE11A polymorphisms using peripheral blood samples., Results: Our data revealed that TGCT patients showed lower testosterone levels, higher gonadotropins levels and worse semen quality than controls, although the mean and the medians of sperm parameters are within the reference limits. PDE11A sequencing detected ten polymorphisms not yet associated with TGCTs before. Among these, G223A in homozygosity and A288G in heterozygosity were significantly associated with a lower risk of testicular tumour and they displayed a positive correlation with total sperm number., Conclusions: Our findings highlight the key role of PDE11A in testis and suggest the presence of an underlying complex and fine molecular mechanism which controls testis-specific gene expression and susceptibility to testicular cancer., (© 2021. The Author(s).)

Even though inflammatory conditions are known to exert adverse effects on bone metabolism, there are no published data regarding SARS-CoV-2 infection and subsequent fracture risk. We present a brief review of the molecular mechanisms linking inflammatory diseases to increased fracture risk/osteoporosis and of the therapeutic strategies that can prevent bone resorption in patients with inflammatory disease, focusing on the RANK-RANKL system. We also make some considerations on gender differences in infection response and on their implications for survival and for the consequences of COVID-19. Several inflammatory cytokines, especially IL-1, IL-6, and TNF-α, stimulate osteoclast activity, favoring bone resorption through the RANK-RANKL system. Data from the previous SARS-CoV outbreak suggest that the present disease also has the potential to act directly on bone resorption units, although confirmation is clearly needed. Even though the available data are limited, the RANK-RANKL system may provide the best therapeutic target to prevent bone resorption after COVID-19 disease. Vitamin D supplementation in case of deficiency could definitely be beneficial for bone metabolism, as well as for the immune system. Supplementation of vitamin D in case of deficiency could be further advantageous. In COVID-19 patients, it would be useful to measure the bone metabolism markers and vitamin D. Targeting the RANK-RANKL system should be a priority, and denosumab could represent a safe and effective choice. In the near future, every effort should be made to investigate the fracture risk after SARS-CoV-2 infection., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Purpose: The prevalence and the etiopathogenesis of thyroid dysfunctions in Klinefelter syndrome (KS) are still unclear. The primary aim of this study was to evaluate the pathogenetic role of hypogonadism in the thyroid disorders described in KS, with the scope to distinguish between patients with KS and hypogonadism due to other causes (Kallmann syndrome, idiopathic hypogonadotropic hypogonadism, iatrogenic hypogonadism and acquired hypogonadotropic hypogonadism after surgical removal of pituitary adenomas) called non-KS. Therefore, we evaluated thyroid function in KS and in non-KS hypogonadal patients., Methods: This is a case-control multicentre study from KING group: Endocrinology clinics in university-affiliated medical centres. One hundred and seventy four KS, and sixty-two non-KS hypogonadal men were enrolled. The primary outcome was the prevalence of thyroid diseases in KS and in non-KS. Changes in hormonal parameters were evaluated. Exclusion criterion was secondary hypothyroidism. Analyses were performed using Student's t test. Mann-Whitney test and Chi-square test., Results: FT4 was significantly lower in KS vs non-KS. KS and non-KS presented similar TSH and testosterone levels. Hashimoto's thyroiditis (HT) was diagnosed in 7% of KS. Five KS developed hypothyroidism. The ratio FT3/FT4 was similar in both groups. TSH index was 1.9 in KS and 2.3 in non-KS. Adjustment for differences in age, sample size and concomitant disease in multivariate models did not alter the results., Conclusions: We demonstrated in KS no etiopathogenic link to hypogonadism or change in the set point of thyrotrophic control in the altered FT4 production. The prevalence of HT in KS was similar to normal male population, showing absence of increased risk of HT associated with the XXY karyotype.

An emerging branch of research is examining the linkage between Vitamin D and nonskeletal disorders, including endocrine diseases. In this regard, a still little studied aspect concerns the involvement of vitamin D in adrenal gland disorders. Adrenal gland disorders, which might be theoretically affected by vitamin D unbalance, include adrenal insufficiency, Cushing's syndrome, adrenocortical tumors and hyperaldosteronism. In this review, we provide an updated document, which tries to collect and discuss the limited evidence to be found in the literature about the relationship between vitamin D and adrenal disorders. We conclude that there is insufficient evidence proving a causal relationship between vitamin D levels and adrenal disorders. Evidence coming from cross-sectional clinical studies can hardly clarify what comes first between vitamin D unbalance and adrenal disease. On the other hand, longitudinal studies monitoring the levels of vitamin D in patients with adrenal disorders or, conversely, the possible development of adrenal pathologies in subjects affected by impaired vitamin D levels would be able to elucidate this still unclear issue.

Kidney transplant is the treatment of choice for end-stage chronic kidney disease. Kidneys generate 1,25-dihydroxyvitamin D (calcitriol) from 25-hydroxyvitamin D (calcidiol) for circulation in the blood to regulate calcium levels. Transplant patients with low calcidiol levels have an increased risk of metabolic and endocrine problems, cardiovascular disease, type 2 diabetes mellitus, poor graft survival, bone disorders, cancer, and mortality rate. The recommended calcidiol level after transplant is at least 30 ng/mL (75 nmol/L), which could require 1000-3000 IU/d vitamin D3 to achieve. Vitamin D3 supplementation studies have found improved endothelial function and acute rejection episodes. However, since kidney function may still be impaired, raising calcidiol levels may not lead to normal calcitriol levels. Thus, supplementation with calcitriol or an analog, alfacalcidiol, is often employed. Some beneficial effects found include possible improved bone health and reduced risk of chronic allograft nephropathy and cancer.

In the last few years, more attention has been given to the "non-calcemic" effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison's disease, Hashimoto's thyroiditis, Graves' disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases.

Purpose: A large body of evidence suggests a role for vitamin D in conditioning cardiovascular risk. Therefore, it can be hypothesized that vitamin D might also play a role in influencing the metabolic profile of hypogonadal men. In this work, we aimed at evaluating if any relationship exists between vitamin D levels and cardiovascular parameters in male hypogonadism., Methods: Hypogonadal patients attending our andrology unit were retrospectively reviewed. Clinical and biochemical parameters were evaluated., Results: 103 patients were studied (51 non-diabetic and 52 diabetic subjects). Mean age of the whole sample was 65 years (standard error of the mean: 0.62). Significant correlations of age, total testosterone, parathyroid hormone (PTH), calcemia, and 25-OH vitamin D with the metabolic profile were found. In logistic regression models including age, total testosterone, PTH, calcemia and 25-OH vitamin D as independent variables, lower levels of 25-OH vitamin D were associated with high values of body mass index (BMI) [odds ratio (OR) 0.910, p 0.019], insulin (OR 0.918, p 0.034), homeostatic model assessment (HOMA) index (OR 0.918, p 0.030), total cholesterol (OR 0.819, p < 0.001), triglycerides (OR 0.820, p < 0.001), and low-density lipoprotein cholesterol (OR 0.923, p 0.034). In non-diabetic subjects, lower levels of 25-OH vitamin D were associated with high values of BMI, insulin, HOMA, triglycerides, systolic, and diastolic blood pressure. On the other hand, in diabetic subjects, lower levels of 25-OH vitamin D were associated with high values of total cholesterol and triglycerides., Conclusions: Our work shows the influence of vitamin D on cardiovascular profile in male hypogonadism. This effect seems to be more relevant in non-diabetic subjects. If these data were to be confirmed, vitamin D assessment might become mandatory in the clinical evaluation of cardiovascular profile in male hypogonadism.

Klinefelter Syndrome (KS) is characterized by an extreme heterogeneity in its clinical and genetic presentation. The relationship between clinical phenotype and genetic background has been partially disclosed; nevertheless, physicians are aware that several aspects concerning this issue are far to be fully understood. By improving our knowledge on the role of some genetic aspects as well as on the KS, patients' interindividual differences in terms of health status will result in a better management of this chromosomal disease. The aim of this review is to provide an update on both genetic and clinical phenotype and their interrelationships., Competing Interests: MB, VR, DP, GB; AF declare that they have no conflict of interest. EAJ has been speaker or consultant for Bayer, Bracco, GSK, Ibsa, Pfizer, Menarini, and Shionogi. Ethical approval This article does not contain any studies with human participants or animals performed by the authors. Informed consent Formal consent is not required.

The influence of androgen receptor (AR) GGC repeat polymorphism on the metabolic profile of men has been much less studied than the one of CAG tract polymorphism. Therefore, in this study, we looked for the association of GGC and CAG tract with cardiovascular risk factors in men. Ninety-eight men followed by our andrological unit were retrospectively reviewed. Clinical and biochemical parameters on cardiovascular risk were considered. AR CAG and GGC polymorphisms were studied. GGC triplets were found to be positively and significantly correlated with several cardiovascular risk factors. On the other hand, inverse and significant correlations of CAG triplets were found with insulin and HOMA. As expected, age was positively correlated with cardiovascular risk, whereas total testosterone was inversely correlated with metabolic profile. Estradiol was not found to be correlated with any of the metabolic parameters. In the total sample, multivariate linear regression analysis confirms the positive and independent association of GGC triplets with glycemia, glycated hemoglobin, total cholesterol, triglycerides and homeostasis model assessment of insulin resistance (HOMA), whereas CAG repeat length is negatively associated with insulin and HOMA. Such associations are also substantially confirmed in non-diabetic subjects, whereas in diabetic patients only the GGC tract seems to be involved in the metabolic profile regulation. Our work shows a relevant role for GGC repeat tract in conditioning male cardiovascular risk, thus rendering necessary a deeper analysis on the role of GGC polymorphism both from the molecular and the clinical point of view.

Objective: Hypoparathyroidism and hypocalcemia are two of the most frequent clinical characteristics of 22q11-deletion syndrome (22q11DS). The aim of this study was to evaluate bone metabolism and density in a cohort of patients affected by 22q11DS., Methods: In 8 pediatric patients (mean age 11.5 years; range 7-16.4) affected by 22q11DS, creatinine, albumin, total and ionized calcium, phosphate, 25(OH) vitamin D, parathyroid hormone, osteocalcin, C-terminal telopeptide and interleukin 6 were assessed. Furthermore, bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry procedure. 14 healthy children were considered as controls., Results: Most of the studied subjects were overweight and lacked quality physical activity. 40 % of the subjects had reduced calcium levels in the absence of related clinical symptoms and all patients also had inadequate levels of Vitamin D. The values of L1-L4 BMD were within the reference range in all patients (z score <2). However, after comparing the age-matched indexes of bone mineralization of patients with those of controls, the former had lower bone mineralization indexes than the latter., Conclusions: In pediatric patients with 22q11DS, an initial and slight bone loss is evident. The incidence of hypocalcemia is underestimated because hypocalcemia is asymptomatic. Several factors contribute to bone impairment in children who still have to achieve bone mass peak. Therefore, we suggest strict monitoring of bone metabolism as well as BMD measurement in patients affected by 22q11DS.

Objective: We developed clinical practice guidelines to assess the individual risk-benefit profile of androgen replacement therapy in adult male hypogonadism (HG), defined by the presence of specific signs and symptoms and serum testosterone (T) below 12 nmol/L., Participants: The task force consisted of eight clinicians experienced in treating HG, selected by the Italian Society of Endocrinology (SIE). The authors received no corporate funding or remuneration., Consensus Process: Consensus was guided by a systematic review of controlled trials conducted on men with a mean T < 12 nmol/L and by interactive discussions. The guidelines were reviewed and sequentially approved by the SIE Guidelines Commission and Executive Committee., Conclusions: We recommend T supplementation (TS) for adult men with severely reduced T levels (T < 8 nmol/L) to improve body composition and sexual function. We suggest that TS be offered to subjects with T < 12 nmol/L to improve glycaemic control, lipid profile, sexual function, bone mineral density, muscle mass and depressive symptoms, once major contraindications have been ruled out. We suggest that lifestyle changes and other available interventions (e.g. for erectile dysfunction) be suggested prior to TS. We suggest that TS should be combined with currently available treatments for individuals at high risk for complications, such as those with osteoporosis and/or metabolic disorders. We recommend against using TS to improve cardiac outcome and limited mobility. We recommend against using TS in men with prostate cancer, unstable cardiovascular conditions or elevated haematocrit. The task force places a high value on the timely treatment of younger and middle-aged subjects to prevent the long-term consequences of hypoandrogenism.

Background: Osteoporosis is a major public health problem also in men and it recognizes hypogonadism as a major cause., Aims: To investigate the possible pathogenetic mechanisms on bone impairment in male hypogonadism and on its improvement in response to testosterone replacement treatment (TRT)., Methods: We retrospectively investigated the hormonal profile and bone mineral density (BMD), evaluated by DXA, in 17 middle-aged hypogonadal men treated for at least 5 years with TRT, compared with 21 recently diagnosed untreated hypogonadal males and 18 age- and BMI-matched healthy subjects., Results: No significant differences in clinical, biochemical and densitometric parameters were found among the three groups, with the exception of 25-OH vitamin D levels that were significantly higher in healthy subjects compared with hypogonadal patients. Untreated patients affected by central hypogonadism, despite similar hormonal levels, displayed significantly lower BMD and decreased LH and 25-OH vitamin D levels, compared with patients with primary hypogonadism. Among the treated patients, BMD parameters were similar regardless of the formulation of TRT., Conclusions: A recent history of central hypogonadism, compared with primary hypogonadism, appears to adversely affect bone health independently of gonadal steroids levels. This could be due to lower LH levels and consequent reduction of vitamin D 25-hydroxylation in the testis.

Introduction: Glucagon-like peptide 1 (GLP-1) is an intestinal hormone secreted after the ingestion of various nutrients. The main role of GLP-1 is to stimulate insulin secretion in a glucose-dependent manner. However, the expression of GLP-1 receptor was found to be expressed in a variety of tissues beyond pancreas such as lung, stomach, intestine, kidney, heart and brain. Beyond pancreas, a beneficial effect of GLP-1 on body weight reduction has been shown, suggesting its role for the treatment of obesity. In addition, GLP-1 has been demonstrated to reduce cardiovascular risk factors and to have a direct cardioprotective effect, fostering heart recovery after ischemic injury. Further, data from both experimental animal models and human studies have shown beneficial effect of GLP-1 on bone metabolism, either directly or indirectly on bone cells., Materials and Methods: We review here the recent findings of the extra-pancreatic effects of GLP-1 focusing on both basic and clinical studies, thus opening future perspectives to the use of GLP-1 analogs for the treatment of disease beyond type 2 diabetes., Conclusion: Finally, the GLP-1 has been demonstrated to have a beneficial effect on both vascular, degenerative diseases of central nervous system and psoriasis.

Impaired male fertility may have a variety of causes, among which asthenozoospermia. In its etiology, several bioactive substances, such as cytokines may be involved. In this context, our aim was to evaluate the expression of interleukin-1β, cyclooxygenase-2, and hypoxia-inducible factor-1α, in spermatozoa isolated from normospermic fertile donors and asthenozoospermic infertile patients. We evaluated twenty-eight infertile patients affected by idiopathic asthenozoospermia and twenty-three normospermic fertile donors, age-matched. Sperm parameters were evaluated; immunohistochemical analysis and enzyme-linked immunosorbent assay were then performed in isolated spermatozoa. Spermatozoa from the asthenozoospermic group presented an increased expression of IL-1β, COX-2, and HIF-1α compared with the normospermic fertile subjects. Our results can lead us to speculate that the increased expression of these substances may influence sperm motility. Nevertheless, further studies are needed in order to assess whether these bioactive mediators have a potential relevance as targets in future therapeutic strategies for the treatment of male infertility.

Introduction and Aim: The relationship between androgen receptor (AR) CAG polymorphism and bone metabolism is highly controversial. We, therefore, aimed to evaluate the independent role of AR CAG repeat polymorphism on bone metabolism improvement induced by testosterone replacement therapy (TRT) in male post-surgical hypogonadotropic hypogonadism, a condition frequently associated with hypopituitarism and in which the effects of TRT have to be distinguished from those resulting from concomitant administration of pituitary function replacing hormones., Methods: 12 men affected by post-surgical hypogonadotropic hypogonadism [mean duration of hypogonadism 8.3 ± 2.05 (SD) months] were retrospectively assessed before and after TRT (from 74 to 84 weeks after the beginning of therapy). The following measures were studied: parameters of bone metabolism [serum markers and bone mineral density (BMD)], pituitary dependent hormones and genetic analysis (AR CAG repeat number)., Results: Total testosterone, estradiol, free T4 (FT4) and insulin-like growth factor-1 (IGF-1) increased between the two phases, while follicle stimulating hormone (FSH) decreased. While serum markers did not vary significantly between the two phases, BMD improved slightly but significantly in all the studied sites. The number of CAG triplets correlated negatively and significantly with all the variations (Δ-) of BMDs. Conversely, Δ-testosterone correlated positively and significantly with all studied Δ-BMDs, while Δ-FSH, Δ-estradiol, Δ-FT4, and Δ-IGF-1 did not correlate significantly with any of the Δ-BMDs. Multiple linear regression analysis, after correction for Δ-testosterone, showed that CAG repeat length was negatively and significantly associated with ∆-BMD of all measured sites., Conclusions: Our data suggest that, in post-surgical male hypogonadotropic hypogonadism, shorter AR CAG tract is independently associated with greater TRT-induced improvement of BMD.

Cardiovascular (CV) disease is one of the most common causes of death in the western populations and, nowadays, its incidence is increasing even in the developing countries; although CV disease affects both sexes, it is more frequent in males in whom it shortens the average life expectancy. In this regard, this difference has been wrongly attributed for many years to the negative effects of testosterone (T); however, nowadays, a large amount of evidence suggests that this hormone may have protective effects on the CV system and that, indeed, the low levels of T could be associated with an increased CV risk and with an augmentation of morbidity and mortality in males. Such an aspect gains great relevance in light of the consideration that T decrease, besides occurring as a consequence of rare pathological conditions, can often take place with natural aging, causing a state of "male menopause", also called late-onset hypogonadism. In this review, we aimed to summarize the present state of the art concerning the association between T deficit and CV disease by analyzing the protective role of T on CV system and the relationship of this hormonal lack with metabolic syndrome, CV morbidity and mortality, and with the CV complications, such as ischemic heart disease, heart failure and stroke, that frequently occur in T deficiency.

Background: Hirsutism is defined as the presence of excessive terminal hair in androgen-dependent areas of a woman's body. Regarding this it has been suggested that Lavender and Tea tree oils may have antiandrogenic activities., Aim: To evaluate therapy based on Lavender and Tea tree oils in women suffering from mild idiopathic hirsutism (IH)., Subjects and Methods: A prospective, open-label, placebo- controlled, randomized study was performed: women affected by mild IH were randomly assigned to receive oil spray containing Lavender and Tea tree oils (group T) (no. = 12) or placebo (group P) (no. = 12) twice a day for 3 months in areas affected by hirsutism. Evaluation of hirsutism was carried out at baseline and after 3 months by Ferriman-Gallwey score and by measuring hair diameter taken from some body areas. A hematological and hormonal evaluation was carried out at baseline and after 3 months., Results: No significant variations were found in any of the hormones studied in groups T and P between baseline and after 3 months. A statistically significant decrease of hirsutism total score and of hair diameter was found in group T, while no statistically significant difference in these two parameters was observed in group P; in group T percentual reduction of hair diameter was significantly greater than in group P., Conclusions: Lavender and Tea tree oils applied locally on skin could be effective in reducing mild IH; this treatment could represent a safe, economic and practical instrument in the cure of this disease.

Background: Despite their efficacy in the treatment of benign prostatic hyperplasia (BPH) the popularity of inhibitors of 5α-reductase (5ARI) is limited by their association with adverse sexual side effects. However, the real impact of 5ARI on sex hormones and sexual function is controversial., Aim: To investigate the role of 5ARI therapy on hormonal parameters and sexual function in men already complaining of sexual problems., Materials and Methods: A consecutive series of 3837 men (mean age 63.5±12.8 yr) attending our outpatient clinic for sexual dysfunction was retrospectively studied. Several clinical, biochemical, and instrumental (penile color doppler ultrasound) factors were evaluated., Results: Among the patients studied, 78.7% reported erectile dysfunction, 51.1% hypoactive sexual desire (HSD), 86.7% perceived reduced sleep-related erections (PR-SRE) and 19.1% premature ejaculation. The use of 5ARI was associated with an increased risk of HSD and PR-SR whereas no relationship was found with erectile dysfunction and ejaculation disturbances. Subjects using 5ARI also more frequently had gynecomastia along with reduced SHBG and higher calculated free testosterone levels. All these associations were confirmed in a case-control study comparing 5ARI users with age-body mass index-smoking status and total testosterone-matched controls., Conclusions: Our data indicates that use of 5ARI in men with sexual dysfunction does not significantly exacerbate pre-existing ejaculatory or erectile difficulties, but can further impair their sexual life by reducing sexual drive and spontaneous erection.

Background: The relationship between cardiovascular (CV) diseases (CVD) and testosterone (T) levels in men has not been completely clarified., Aim: To evaluate the association between T levels and CV risk in subjects with erectile dysfunction (ED) and to verify whether their body mass index might (BMI) represents a possible confounder in T-related CV stratification., Material and Methods: A consecutive series of 2269 male patients attending the Outpatient Clinic for ED was studied. The assessment of CV risk was evaluated using the engine derived from the Progetto Cuore study., Results: After adjustment and for BMI and associated morbidities, SHBG-bound and -unbound T levels decreased as a function of CV risk assessed thorough Progetto Cuore risk engine. In addition, a higher prevalence of hypogonadism related symptoms and signs was associated with a higher CV risk. Among factors included in the Progetto Cuore risk engine age, total and HDL cholesterol and diabetes were all significantly associated with CV risk-dependent modification of total and calculated free-T levels. When the relationship between SHBG bound and unbound T and CV risk was evaluated as a function of obesity (BMI>30 kg/m(2)), all the aforementioned associations were confirmed only in non obese patients., Conclusions: Hypogonadism could be associated either with an increased or reduced CV risk, depending on the characteristics of subjects. Low T observed in obese patients might represent the result of higher CV risk rather than a direct pathogenetic mechanism.

Recombinant GH therapy is normally administered to GH-deficient children in order to achieve a satisfactory height - the main target during childhood and adolescence. However, the role of GH does not end once final height has been reached, but continues during the so-called transition period. In this phase of life, the body undergoes several changes, both physical and psychological, that culminate in adulthood. During this period, GH has a part in numerous metabolic functions. These include the lipid profile, where it increases HDL and reduces LDL, with the global effect of cardiovascular protection. It also has important effects on body composition (improved muscle strength and lean body mass and reduced body fat), the achievement of proper peak bone density, and gonad maturation. Retesting during the transition period, involving measurement of IGF-I plus a provocative test (insulin tolerance test or GHRH + arginine test), is thus necessary to establish any persistent GH deficiency requiring additional replacement therapy. The close cooperation of the medical professionals involved in the patient's transition from a pediatric to an adult endocrinologist is essential. The aim of this review is to point out the main aspects of GH treatment on body composition, metabolic and gonad functions in the transition period.

Nearly 70 years after its description, Klinefelter syndrome (KS) remains a largely undiagnosed condition. As its clinical presentation may be subtle, many of those affected may be unaware or diagnosed only during evaluation for hypogonadism and/or infertility. In February 2010 an interdisciplinary panel of specialists met in Abano Terme (Padua, Italy) in a workshop on "Klinefelter Syndrome: diagnosis and clinical management". The main aim of this meeting was to discuss several aspects related to the epidemiology, pathogenesis, and evaluation of KS and to develop a consensus defining its early diagnosis and treatment. In the present consensus we have highlighted the features that may prompt the physicians to look after patients with KS both for the syndrome and correlated diseases. We have provided evidences that, during the different phases of life, there might be some advantages in establishing the diagnosis and starting proper follow-up and treatment. The workshop was carried out under the auspices of the Italian Society of andrology and Sexual Medicine (SIAMS).

In the biosynthesis of steroid hormones the neutral lipid cholesterol, a normal constituent of lipid bilayers is transformed via a series of hydroxylation, oxidation, and reduction steps into a vast array of biologically active compounds: mineralocorticoids, glucocorticoids, and sex hormones. Glucocorticoids regulate many aspects of metabolism and immune function, whereas mineralocorticoids help maintain blood volume and control renal excretion of electrolytes. Sex hormones are essential for sex differentiation in male and support reproduction. They include androgens, estrogens, and progestins. A block in the pathway of steroid biosynthesis leads to the lack of hormones downstream and accumulation of the upstream compounds that can activate other members of the steroid receptor family. This review deals with the clinical consequences of these blocks.

Hypogonadotropic hypogonadism (HH), or secondary hypogonadism, is a clinical condition due to an impairment of the pituitary function, characterized by low testosterone plasma levels associated with normal or low FSH and LH plasma levels. An impairment of gonadotropin secretion and, therefore, a reduced efficiency of spermatogenesis was reported to be frequently associated to conditions different from the classical causes of secondary hypogonadism. These conditions (metabolic, endocrine and eating disorders, physical exercise etc.) have been associated with a non-classical form of HH that could be called "functional" HH (FHH). FHH differs from the classical one by the evidence that gonadotropin levels are in the low-normal range, but are inadequate for the testosterone levels, that often are also in the low-normal range. This commentary aims at reviewing knowledge on the forms of male HH in order to indicate and discuss clinical context, diagnostic and therapeutic approach in the less known non-classical form, i.e. FHH.

We had previously demonstrated that Coenzyme Q10 [(CoQ10) also commonly called ubiquinone] is present in well-measurable levels in human seminal fluid, where it probably exerts important metabolic and antioxidant functions; seminal CoQ10 concentrations show a direct correlation with seminal parameters (count and motility). Alterations of CoQ10 content were also shown in conditions associated with male infertility, such as asthenozoospermia and varicocele (VAR). The physiological role of this molecule was further clarified by inquiring into its variations in concentrations induced by different medical or surgical procedures used in male infertility treatment. We therefore evaluated CoQ10 concentration and distribution between seminal plasma and spermatozoa in VAR, before and after surgical treatment, and in infertile patients after recombinant human FSH therapy. The effect of CoQ10 on sperm motility and function had been addressed only through some in vitro experiments. In two distinct studies conducted by our group, 22 and 60 patients affected by idiopathic asthenozoospermia were enrolled, respectively. CoQ10 and its reduced form, ubiquinol, increased significantly both in seminal plasma and sperm cells after treatment, as well as spermatozoa motility. A weak linear dependence among the relative variations, at baseline and after treatment, of seminal plasma or intracellular CoQ10, ubiquinol levels and kinetic parameters was found in the treated group. Patients with lower baseline value of motility and CoQ10 levels had a statistically significant higher probability to be responders to the treatment. In conclusion, the exogenous administration of CoQ10 increases both ubiquinone and ubiquinol levels in semen and can be effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia.

General dynamic penile color doppler ultrasound (D-PCDU) screening in patients with erectile dysfunction (ED) has been questioned due to an inadequate cost-benefit ratio. The aim of the present study is to evaluate the validity of different risk scores in the identification of patients being screened for arteriogenic ED (AED) at D-PCDU. A consecutive series of 738 patients with ED was studied. AED was defined when peak systolic velocity (PSV) was lower than 25 cm/sec. The assessment of cardiovascular risk was evaluated using different risk engines, derived from the Framingham, the PROCAM and the Progetto Cuore studies. An iterative receiver operator characteristic (ROC) curve analysis was used to determine the most proper threshold for different scales for the screening of AED. Among the patients studied, 52 (7%) had PSV<25 cm/sec. The area under the ROC curves for pathological PSV in relation to cardiovascular risk estimated with different engines was 0.762+/-0.03, 0.716+/-0.03, and 0.667+/-0.03 for Progetto Cuore, Framingham, and PROCAM engines, respectively. Sensitivity and specificity of Progetto Cuore estimated risk were 67%, 71% when a threshold of 15% was chosen. Corresponding figures for Framingham and PROCAM engine were 74%, 57% and 69%, 55%, respectively. If D-PCDU is performed only on patients with cardiovascular risk >15%, who represent about 1/4 of all patients (26.8%), as estimated by Progetto Cuore, about 70% of cases of arteriogenic ED can be identified. Estimated cardiovascular risk, assessed through risk engines, could be used to identify patients who should undergo D-PCDU evaluation for the diagnosis of AED.