Gender-specific effects of capsiate supplementation on body weight and bone mineral density: a randomized, double-blind, placebo-controlled study in slightly overweight women.

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/cm2, + 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.

First baseline data of the Klinefelter ItaliaN Group (KING) cohort: clinical features of adult with Klinefelter syndrome in Italy.

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/m2, 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.

PDE11A gene polymorphism in testicular cancer: sperm parameters and hormonal profile.

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.

Thyroid function in Klinefelter syndrome: a multicentre study from KING group.

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.

Klinefelter syndrome (KS): genetics, clinical phenotype and 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.

Influence of vitamin D levels on the cardiovascular profile of hypogonadal men.

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.

Diabetes Mellitus-Associated Functional Hypercortisolism Impairs Sexual Function in Male Late-Onset Hypogonadism.

Functional hypercortisolism is generated by conditions able to chronically activate hypothalamic-pituitary-adrenal axis and has been proven to have a negative role in several complications. However, no study has evaluated the possible influence of diabetes mellitus-associated functional hypercortisolism on male hypogonadism and sexual function. We aimed to identify any association of hypothalamic-pituitary-adrenal axis dysregulation measures with testosterone and sexual function in men simultaneously affected by diabetes mellitus and late-onset hypogonadism. Fifteen diabetes mellitus and late-onset hypogonadism subjects suffering from functional hypercortisolism and fifteen diabetes mellitus and late-onset hypogonadism subjects who were free of functional hypercortisolism were retrospectively reviewed. Clinical, hormonal, and sexual parameters were considered. Hypercortisolemic subjects showed higher values of body mass index, waist, and glycated hemoglobin and lower ones of testosterone compared to normocortisolemic ones. All sexual parameters, except for orgasmic function, were significantly worse in hypercortisolemic than in normocortisolemic subjects. Hypercortisolemic patients showed higher values of cortisol after dexamethasone and urinary free cortisol as well as a lesser ACTH response after corticotropin releasing hormone test (ACTH area under curve) compared to normocortisolemic ones. No significant association was found at Poisson regression analysis between hormonal and sexual variables in normocortisolemic patients. In hypercortisolemic subjects, negative and significant associations of cortisol response after corticotropin releasing hormone (cortisol area under curve) with erectile function (ß: -0.0008; p: 0.015) and total international index of erectile function score (ß: -0.0006; p: 0.001) were evident. This study suggests for the first time the impairing influence of the dysregulated hypothalamic-pituitary-adrenal axis on sexual function in diabetes mellitus-associated late-onset hypogonadism.

Influence of the hypothalamic-pituitary-adrenal axis dysregulation on the metabolic profile of patients affected by diabetes mellitus-associated late onset hypogonadism.

BACKGROUND AND AIMS: Functional hypercortisolism (FH) is generated by clinical states able to chronically activate the hypothalamic-pituitary-adrenal (HPA) axis [e.g. diabetes mellitus (DM)]. No study has evaluated FH influence in worsening the metabolic profile of male patients affected by DM-associated hypogonadism. In this retrospective work, we assess the possible association between HPA axis-dysregulation and cardiovascular risk factors in men simultaneously affected by DM and late-onset hypogonadism (LOH). METHODS AND RESULTS: Fourteen DM and LOH subjects affected by FH (Hypercort-DM-LOH) and fourteen DM and LOH subjects who were not suffering from FH (Normocort-DM-LOH) were retrospectively considered. Clinical, hormonal and metabolic parameters were retrieved. All metabolic parameters, except for systolic blood pressure, were significantly worse in Hypercort-DM-LOH than in Normocort-DM-LOH. After adjustment for body mass index, waist and total testosterone, Hypercort-DM-LOH subjects showed significantly worse metabolic parameters than Normocort-DM-LOH ones. In Normocort-DM-LOH, no significant correlation between general/hormonal parameters and metabolic variables was present. In Hypercort-DM-LOH, positive and significant correlations of cortisol area under the curve (AUC) after corticotropin releasing hormone with glycemia, triglycerides and blood pressure were evident; on the other hand, negative and significant correlation was present between cortisol AUC and high density lipoprotein (HDL) cholesterol. The associations of AUC cortisol with glycemia, HDL cholesterol and diastolic blood pressure (DBP) were further confirmed at quantile regression after adjustment for therapy. CONCLUSIONS: FH may determine a worsening of the metabolic profile in DM-associated hypogonadism.

Bone density assessment in a cohort of pediatric patients affected by 22q11DS.

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.

Outcomes of androgen replacement therapy in adult male hypogonadism: recommendations from the Italian society of endocrinology.

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.

Diabetes mellitus and late-onset hypogonadism: the role of Glu298Asp endothelial nitric oxide synthase polymorphism.

Nitric oxide has been associated with insulin resistance and type 2 diabetes mellitus (DM). An association has been suggested between a single nucleotide polymorphism (Glu298Asp variant) of the endothelial nitric oxide synthase (eNOS) gene and increased risk of DM. However, the role of this polymorphism in favouring DM has not been investigated in hypogonadism, in which low testosterone and obesity are believed to play the major role. We aimed to evaluate whether eNOS gene single nucleotide polymorphism (Glu298Asp variant) might give a relevant contribution also to the onset of hypogonadism-associated DM. 110 men affected by late-onset hypogonadism were retrospectively reviewed. Patients were clinically and biochemically evaluated. Detection of eNOS Glu298Asp polymorphism was performed. After splitting the sample according to the three genetic variants (i.e. eNOSGG , eNOSGT , eNOSTT ), no difference was evident in age, body mass index (BMI) and total testosterone. Conversely, DM prevalence, glycaemia and glycated haemoglobin were significantly higher in eNOSTT than in eNOSGT and eNOSGG . Logistic regression analysis showed that, after adjustment for age, BMI and total testosterone, eNOSTT was positively and significantly associated with DM. Our study suggests that Glu298Asp single nucleotide polymorphism of the eNOS gene may be an independent risk factor for hypogonadism-associated type 2 DM.

Central body fat changes in men affected by post-surgical hypogonadotropic hypogonadism undergoing testosterone replacement therapy are modulated by androgen receptor CAG polymorphism.

BACKGROUND AND AIMS: Little is known about the effect of androgen receptor (AR) gene CAG repeat polymorphism in conditioning body composition changes after testosterone replacement therapy (TRT). In this study, we aimed to clarify this aspect by focussing our attention on male post-surgical hypogonadotropic hypogonadism, a condition often associated with partial or total hypopituitarism. METHODS AND RESULTS: Fourteen men affected by post-surgical hypogonadotropic hypogonadism and undergoing several replacement hormone therapies were evaluated before and after TRT. Dual-energy X-ray absorptiometry (DEXA)-derived body composition measurements, pituitary-dependent hormones and AR gene CAG repeat polymorphism were considered. While testosterone and insulin-like growth factor-1 (IGF-1) levels increased after TRT, cortisol concentration decreased. No anthropometric or body composition parameters varied significantly, except for abdominal fat decrease. The number of CAG triplets was positively and significantly correlated with this abdominal fat decrease, while the opposite occurred between the latter and Δ-testosterone. No correlation of IGF-1 or cortisol variation (Δ-) with Δ-abdominal fat was found. At multiple linear regression, after correction for Δ-testosterone, the positive association between CAG triplet number and abdominal fat change was confirmed. CONCLUSIONS: In male post-surgical hypogonadotropic hypogonadism, shorter length of AR CAG repeat tract is independently associated with a more marked decrease of abdominal fat after TRT.

Vitamin D levels and bone mineral density: are LH levels involved in the pathogenesis of bone impairment in hypogonadal men?

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.

Effects of testosterone replacement therapy on bone metabolism in male post-surgical hypogonadotropic hypogonadism: focus on the role of androgen receptor CAG polymorphism.

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.

GLP-1: benefits beyond pancreas.

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.

Have androgen receptor gene CAG and GGC repeat polymorphisms an effect on sperm motility in infertile men?

Androgens and a normal androgen receptor (AR) are required for normal spermatogenesis. We investigated polyglutamine (CAG) and a polyglycine (GGC) tract in Italian men with defective spermatogenesis. We studied a group of 40 infertile men with spermatogenesis failure without Y-chromosome microdeletions compared with 60 normozoospermic ones. The distributions of both polymorphisms, within the normal range of Caucasian populations, were similar among infertile men and controls. Nonetheless, we observed that the frequency comparison of each CAG allele showed a statistical difference in the allele CAG 22; GGC 17 was the more predominant allele in infertile men than in controls. Moreover, to investigate the hypothesis that semen characteristics are perturbed by androgen receptor allele variants, we tried to detect a link between triplets and sperm motility in all subjects (cases plus controls). Subjects were subdivided into three groups, based on calculated allele frequencies. A significantly decreased motility, related to a longer CAG and GGC tracts, and marked differences between the groups exist for both polymorphisms. Our data highlight a probable relationship between the allele CAG 22/GGC 17 and a defective spermatogenesis in infertile men, suggesting that these polymorphisms might have an important effect on AR function.

Human leucocytes in asthenozoospermic patients: endothelial nitric oxide synthase expression.

In a basic study at the Andrology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy, we evaluated the pattern of mRNA endothelial nitric oxide synthase (eNOS) expression in human blood leucocytes isolated from normozoospermic fertile and asthenozoospermic infertile men to elucidate any pathogenic involvement in sperm cell motility. Forty infertile men with idiopathic asthenozoospermia and 45 normozoospermic fertile donors, age-matched, were included. Semen parameters were evaluated, and expression analysis of mRNA was performed in human leucocytes using reverse transcription polymerase chain reaction. Sperm volume, count, motility and morphology were determined, and eNOS expression and Western blotting analyses were performed. A positive correlation was observed between the concentrations of NO and the percentage of immotile spermatozoa. The mRNA of eNOS was more expressed in peripheral blood leucocytes isolated from asthenozoospermic infertile men versus those of fertile normozoospermic men (7.46 ± 0.38 versus 7.06 ± 0.56, P = 0.0355). A significant up-regulation of eNOS gene in peripheral blood leucocytes was 1.52-fold higher than that of fertile donors. It is concluded that eNOS expression and activity are enhanced in blood leucocytes in men with idiopathic asthenozoospermia.

Y-chromosome microdeletions are not associated with SHOX haploinsufficiency.

STUDY QUESTION: Are Y-chromosome microdeletions associated with SHOX haploinsufficiency, thus representing a risk of skeletal anomalies for the carriers and their male descendents? SUMMARY ANSWER: The present study shows that SHOX haploinsufficiency is unlikely to be associated with Y-chromosome microdeletions. WHAT IS KNOWN ALREADY: Y-chromosome microdeletions are not commonly known as a major molecular genetic cause of any pathological condition except spermatogenic failure. However, it has been recently proposed that they are associated not only with infertility but also with anomalies in the pseudoautosomal regions (PAR), among which SHOX haploinsufficiency stands out with a frequency of 5.4% in microdeletion carriers bearing a normal karyotype. This finding implies that sons fathered by men with Y-chromosome defects will not only exhibit fertility problems, but might also suffer from SHOX-related conditions. STUDY DESIGN: Five European laboratories (Florence, Münster, Barcelona, Padova and Ancona), routinely performing Y-chromosome microdeletion screening, were enrolled in a multicenter study. PARTICIPANTS/MATERIALS, SETTING, METHODS: PAR-linked and SHOX copy number variations (CNVs) were analyzed in 224 patients carrying Y-chromosome microdeletions and 112 controls with an intact Y chromosome, using customized X-chromosome-specific array-CGH platforms and/or qPCR assays for SHOX and SRY genes. MAIN RESULTS AND THE ROLE OF CHANCE: Our data show that 220 out of 224 (98.2%) microdeletion carriers had a normal SHOX copy number, as did all the controls. No SHOX deletions were found in any of the examined subjects (patients as well as controls), thus excluding an association with SHOX haploinsufficiency. SHOX duplications were detected in 1.78% of patients (n = 4), of whom two had an abnormal and two a normal karyotype. This might suggest that Y-chromosome microdeletions have a higher incidence for SHOX duplications, irrespective of the patient's karyotype. However, the only clinical condition observed in our four SHOX-duplicated patients was infertility. LIMITATIONS, REASONS FOR CAUTION: The number of controls analyzed is rather low to assess whether the SHOX duplications found in the two men with Y-chromosome microdeletions and a normal karyotype represent a neutral polymorphism or are actually associated with the presence of the microdeletion. WIDER IMPLICATIONS OF THE FINDINGS: Men suffering from infertility due to the presence of Y-chromosome microdeletions can resort to artificial reproductive technology (ART) to father their biological children. However, infertile couples must be aware of the risks implied and this makes genetic counseling a crucial step in the patient's management. This study does not confirm previous alarming data that showed an association between Y-chromosome microdeletions and SHOX haploinsufficiency. Our results imply that deletion carriers have no augmented risk of SHOX-related pathologies (short stature and skeletal anomalies) and indicate that there is no need for radical changes in genetic counseling of Yq microdeletion carriers attempting ART, since the only risk established so far for their male offspring remains impaired spermatogenesis. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Italian Ministry of University (grant PRIN 2010-2012 to C.K.), Tuscan Regional Health Research Program ('Progetto Salute 2009') to G.F., the Spanish Ministry of Health (grant FIS-11/02254) and the European Union 'Reprotrain' Marie Curie Network (project number: 289880 to C.K.). The authors declare that no conflicting interests exist.

Possible efficacy of Lavender and Tea tree oils in the treatment of young women affected by mild idiopathic hirsutism.

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.