Bioavailable Testosterone Levels Research Articles

Diagnostic and prognostic biomarkers of a sellar melanocytic tumor mimicking pituitary adenoma: Case report and literature review

Primary or metastatic melanocytic tumors in the sellar region are rare and can pose a diagnostic challenge. Here we describe a case of a 74-year-old man who underwent radiological investigations for a transient episode of blurred vision. Based on the clinical and endocrinological findings and MRI results, the patient was assumed to have a clinically non-functioning pituitary macroadenoma, which was followed-up over a 2-year period. He did not have any endocrine symptoms or progressive visual deterioration, and no history of past malignancy, including melanoma. Endocrinological investigation was unremarkable; blood hormone levels were within the normal ranges except for low serum total testosterone and bioavailable testosterone levels without symptoms of hypogonadism. The longitudinal MRI follow-up demonstrated a gradual increase in the size of the tumor over the course of 11 months. For this reason, the patient underwent surgery. Pathologic examination including histology, immunohistochemistry and electron microscopy achieved the correct diagnosis of melanocytic tumor of the sellar region morphologic examination is essential in the diagnosis of melanocytic tumors. Hmb-45 is an important diagnostic biomarker in melanocytic lesions. The use and exploration of miRNA, Ki67 and osteopontin are important in understanding the genesis, progression, and prognosis in treatment of patients with melanocytic tumors.

Testosterone and body composition in men after treatment for rectal cancer.

Preoperative radiotherapy for rectal cancer may affect Leydig cell function. However, the diagnosis of posttreatment hypogonadism is complicated as sexual symptoms associated to hypogonadism can rely on adverse events of pelvic radiation and surgery. The objective of this study was to investigate the association of testosterone levels and body composition. The clinical value of such an association is tested subsequently in the study population. This was a longitudinal study with prospective registration during 2010-2012 and 1-year follow up. Men with rectal cancer stage I-III, treated with radiotherapy and surgery, were eligible, and 40 of 53 men were available for analysis. The areas of skeletal muscle and adipose tissue were assessed on a defined section of a computed tomography at baseline and after 1 year. Androgen levels were recorded from morning blood samples. The area of skeletal muscle was related to the level of bioavailable testosterone (P = 0.01) but not to the level of serum testosterone (P = 0.36). The subcutaneous adipose tissue was not related to testosterone levels. Men with posttreatment serum testosterone levels of 8-12 nmol/L and longitudinal loss of psoas muscle area had a significantly increased luteinizing hormone-testosterone ratio compared with those with longitudinal gain of psoas muscle. The area of psoas muscle is related to the unbound fraction of circulating testosterone in men treated for rectal cancer. The longitudinal loss of psoas muscle in men with borderline levels of serum testosterone seems to be an androgen-related symptom associated with compensatory activation of the pituitary-gonadal axis indicating a testicular failure in this group of patients.

Sperm Concentration Is Poorly Associated With Hypoandrogenism in Infertile Men

To evaluate the utility of routine hormone evaluation in all men presenting for infertility by understanding the relationship between sperm concentration and hypoandrogenism. We performed a retrospective cross-sectional study between September 2013 and May 2014 at a tertiary referral center in Utah. Ninety-four men presenting for infertility consecutively between the ages of 18 and 55 years were identified. Our primary outcome was rate of hypoandrogenism among infertile men defined as the baseline total serum testosterone levels <300 ng/dL or bioavailable testosterone (BAT) levels <155 ng/dL. Secondary outcomes included association of normospermia, oligozoospermia, or azoospermia with biochemical or clinical hypoandrogenism. Thirty-nine men (41%) had a total serum testosterone level of <300 ng/dL, and 41 men (43%) had a BAT level <155 ng/dL. Biochemical and symptomatic hypoandrogenism was common; 17 men (18%) had a total testosterone level <300 ng/dL and ≥ 3 positive Androgen Deficiency in Aging Male (ADAM) responses, and 18 men (19%) had a BAT level of <155 ng/dL and ≥ 3 positive ADAM responses. Sperm concentration (normospermia, oligozoospermia, and azoospermia) was not associated with biochemical hypoandrogenism (total testosterone level <300 ng/dL or BAT level <155 ng/dL), symptomatic hypoandrogenism (≥ 3 positive ADAM responses), or sexual dysfunction (Sexual Health Inventory for Men score <21). Hypoandrogenism is common among infertile men, and routine hormonal evaluation may identify hypoandrogenism in many infertile men with otherwise normal semen analysis. Sperm concentration (normospermia, oligozoospermia, and azoospermia) is not well associated with hypoandrogenism in infertile men.

Low circulating free and bioavailable testosterone levels as predictors of high-grade tumors in patients undergoing radical prostatectomy for localized prostate cancer

ObjectiveControversy exists regarding the propensity of hypogonadism and metabolic disorders to promote the development of high-risk prostate cancer (PCa). Our aim was to prospectively test whether preoperative circulating testosterone levels, obesity, and metabolic syndrome (MetS) were correlated with aggressive pathological features after radical prostatectomy (RP). Material and methodsOverall, 354 patients undergoing robot-assisted RP at our academic institution, between 2010 and 2013, to treat clinically localized PCa were included in this prospective study. Pelvic lymphadenectomy was performed in 116 (32.8%) patients and confirmed the absence of nodal metastases in all of them. Cardiovascular risk factors and body-mass index (BMI) were used to define MetS and obesity, respectively. Total testosterone (TT) levels were assessed using an immunoassay method, whereas bioavailable testosterone (BT) and free testosterone (FT) levels were estimated using Vermeulen׳s formula. Multivariate logistic regression analyses assessed independent predictors for postoperative aggressive pathological features (i.e., a pathological Gleason score [GS]≥7, extracapsular extension [ECE], seminal vesicle invasion [SVI], and positive surgical margins [PSM]) and GS upgrading. ResultsLow TT, BT, and FT levels were found in 54 (15.2%), 70 (19.8%), and 62 (17.5%) patients, respectively. Median BMI was 26.3kg/m2 (range: 17.4–43.9), and prevalence of MetS was 18.9%. Significantly higher rates of pathological GS≥7 were observed in groups with a low TT level (46.3% vs. 33.3%; P = 0.01), low BT level (44.3% vs. 33.1%; P<0.001), and low FT level (46.8% vs. 32.9%; P = 0.001). Multivariate analyses demonstrated that only low BT and FT levels were independent predictors of pathological GS≥7 (odds ratio [OR] = 1.76; P<0.001 and OR = 1.39; P<0.001, respectively) and GS upgrading (OR = 2.82; P<0.001 and OR = 1.71; P<0.001, respectively), but there was no significant correlation between low circulating testosterone levels and ECE, SVI, or PSM. Furthermore, BMI (OR = 1.28; P = 0.04) and MetS (OR = 1.19; P = 0.01) were only correlated with PSM. ConclusionHypogonadism, obesity, and MetS were not independent predictors of pathological GS ≥7, ECE, or SVI after RP. Our data suggest that only low BT and FT levels, which might logically result in an active androgen-depleted environment, were linked with high-grade PCa.

Association Between Endogenous Sex Hormones and Liver Fat in a Multiethnic Study of Atherosclerosis

Levels of circulating of sex hormones are associated with glucose metabolism and adiposity, but little is known about their association with ectopic fat. We aimed to characterize the association between circulating sex hormones and liver fat. We conducted a cross-sectional analysis by using data from the Multiethnic Study of Atherosclerosis to assess the association of the circulating levels of bioavailable testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) with fatty liver. Fatty liver was defined as a reduction of ≤40 Hounsfield units, measured by computed tomography, in 2835 postmenopausal women and 2899 men (45-84 years old; white, black, Hispanic, or Chinese) at 6 centers in the United States. Women in the highest tertile of bioavailable testosterone were significantly more likely to have fatty liver than women in the lowest tertile (odds ratio, 1.77; 95% confidence interval, 1.07-2.92). We found an even greater difference for level of estradiol (odds ratio, 2.49; 95% confidence interval, 1.41-4.39) after adjusting for age, race/ethnicity, waist-to-hip ratio, hypertension, total and high-density lipoprotein cholesterol, smoking, insulin sensitivity, and hormone replacement therapy use. Men in the highest tertile of estradiol level were significantly more likely to have fatty liver than men in the lowest tertile (odds ratio, 2.10; 95% confidence level, 1.29-3.40). Men in the highest tertile of SHBG were less likely to have fatty liver than those in the lowest tertile (odds ratio, 0.46; 95% confidence interval, 0.27-0.77). Other associations between hormone levels and fatty liver were not statistically significant. On the basis of a cross-sectional study, postmenopausal women with high levels of bioavailable testosterone are at greater risk for fatty liver. In men, higher levels of SHBG are associated with reduced risk for fatty liver. Higher levels of estradiol are associated with fatty liver in both sexes. This pattern is consistent with the sex-specific associations of sex hormones with other cardiometabolic risk factors.

Osteocalcin and the pituitary-gonadal axis in older men: a population-based study.

Osteocalcin is a well-known marker of bone formation. Recently, mice lacking osteocalcin or its receptor were reported to be subfertile with low testosterone and high luteinizing hormone concentrations. In parallel, in humans, a loss-of-function mutation of the osteocalcin receptor was associated with hypergonadotropic hypogonadism. This suggests that osteocalcin is necessary for normal pituitary-gonadal axis function. Our objective was to determine the association between physiological variations in osteocalcin and the pituitary-gonadal axis in older men. Data were used from the Longitudinal Aging Study Amsterdam (LASA), an ongoing cohort study in a representative sample of the older Dutch population (65-88 years). Serum levels of total (T), free (FT) and bioavailable (bioT) testosterone, luteinizing hormone (LH) and osteocalcin were determined. Data were analysed using linear regression analyses and adjusted for age, BMI, 25-hydroxyvitamin D, parathyroid hormone and vitamin K antagonist use. A total of 614 men participated in the study. The median age was 75·4 (69·8-81·2) years, and the median osteocalcin level was 1·8 (1·3-2·4) nmol/l. Serum osteocalcin was inversely associated with FT (adjusted B = -0·22 ± 0·09 ng/dl, P = 0·012) and bioT (adjusted B = -0·26 ± 0·08 nmol/l, P < 0·01), but not with total T. Furthermore, osteocalcin was positively associated with LH (adjusted B = 0·09 ± 0·03 U/l, P < 0·01). Serum osteocalcin was negatively associated with free and bioavailable testosterone and positively with luteinizing hormone levels.

Puberty and testosterone shape the corticospinal tract during male adolescence.

Some of the known sex differences in white matter emerge during adolescence. Here, we replicate and extend our previous findings of sex differences in the structure of the corticospinal tract (Perrin et al. 2009; Hervé et al. 2009). In a large normative sample of adolescents, we observed age×sex interactions in the signal intensity of T1-weighted (T1W) images (n=941) and in magnetization transfer ratio (MTR; n=761); both features were inversely associated with age in males but not in females. Moreover, we hypothesized that the age-related differences in CST structure exhibited by males would be mediated by differences in puberty stage and levels of bioavailable testosterone. We confirmed this prediction using mediation analysis with bootstrapping. These findings suggest that sex differences in the CST structure observed during male adolescence may be due to multiple processes associated with puberty, including (but not limited to) the rising levels of testosterone.

Elevation of C-reactive protein during the luteal phase in healthy adolescents

Introduction: Variations in inflammatory markers have been reported in adult women during the luteal phase, but whether these findings are observed during adolescence is unknown. We postulate that higher ultrasensitive C-reactive protein (usCRP) and lower 2-hydroxyestrone (2OHE) levels, an estrogen metabolite with cardioprotective actions, are present during the luteal phase in young women.Aim: To evaluate usCRP levels during the menstrual cycle and to determine its association with 2OHE and 16α-hydroxyestrone (16OHE) in adolescents.Methods: Healthy postmenarcheal adolescents (N = 37) were studied during one menstrual cycle in follicular phase (FP) and luteal phase-like period (LP-L).Results: Elevations in usCRP levels in the LP-L were observed in the entire group and in anovulatory cycles (1.9 ± 1.1 mg/L in FP to 2.5 ± 1.8 mg/L in LP-L; p < 0.0001). Increases in estrone, estradiol, free and bioavailable estradiol, testosterone, usCRP and 2OHE levels were observed in LP-L compared with FP (p < 0.01), with a borderline elevation in IFG-I levels (p = 0.06).Conclusions: We report an elevation of usCRP and 2OHE levels during the luteal phase in healthy adolescents. Elevations of this inflammatory marker in anovulatory adolescents without an increase in 2OHE may play a role in metabolic risks associated with chronic anovulation.

AB19. Testosterone replacement therapy: how safe is it?

AB19. Testosterone replacement therapy: how safe is it?

Efficacy and tolerability of clomiphene citrate in the treatment of obese, subfertile males

Elevated body mass index has been shown to be negatively correlated with total testosterone (TT) and bioavailable testosterone (BT) levels and semen parameters in infertile males. Clomiphene citrate (CC), a selective estrogen receptor modulator, is used in the empiric treatment of subfertile males to increase endogenous testosterone levels and improve semen concentration. We sought to study the efficacy and tolerability of CC for treatment of subfertile males who are obese (BMI>30 kg/m2).

여성의 혈중 남성호르몬 수치와 성기능 장애의 상관관계 연구

Introduction and Aim. Sex hormones might induce significant changes in sexual desire, arousal, orgasm, and satisfaction. Decreased sexual desire and sexual dysfunctions in females have been associated with low levels of androgen. This study was to explore the relationship of sex hormones and sex hormone-binding globulin (SHBG) with female sexual dysfunction. Materials and Methods. Seventy-four women with sexual dysfunction were taken their medical history, personal history and physical examination. A self-reporting questionnaire on sexual problems and satisfaction was administered to them. Also levels of total, free, and bio-available testosterone, LH, FSH, estradiol, DHEAS and SHBG were measured, and free androgen index were calculated. Using Wilcoxon rank-sum test, the hormone levels of the sexual dysfunction groups were compared to those of control group. Nine patients were treated by testogel®. Results. The mean levels of LH, FSH, DHEA and DHEAS were lower in women with lack of sexual desire. The levels of DHEA was lower in the arousal disorder group (p&lt;.05) and lower in the orgasmic disorder group (p&lt;.01) than the control group. Sexual pain disorder groups showed lower estradiol level (p&lt;.05). Among the nine patients receiving testosterone replacement therapy by using testogel®, 4 patients reported that symptoms were improved subjectively, the other 4 patients had not significant change, and the remaining 1 patient stopped the therapy due to side effect. Conclusion. The findings supported the concept that sex hormones significantly affect sexual response in women with sexual dysfunction. An androgenic hormone profile was associated with lack of libido, orgasmic disorder, and estrogen with pain disorder.

Association of serum androgen concentrations with cardiovascular risk factors in elderly male patients with chronic systolic heart failure in China

Objective: To survey the serum androgen concentrations and investigate the relationship between androgen levels and cardiovascular risk factors in elderly male patients with chronic systolic heart failure (HF) in China.Methods: 106 consecutive male patients hospitalized for chronic systolic HF aged from 60 to 87 were enrolled. About 400 healthy age-matched men were compared as a control group. Total testosterone (TT), free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG) were measured. Differences of androgen levels between HF patients and healthy men were determined by t-test and associations of androgen with cardiovascular risk factors were evaluated by partial correlations analyses.Results: Compared with healthy men, TT, FT and DHEAS levels in patients with HF decreased, whereas SHBG level increased significantly (both p < 0.01). TT was negatively correlated with TC, TG and DBP (p < 0.05), FT was negatively correlated with TC, LDL-C and DBP (p < 0.05). SHBG correlated with BMI and smoking history positively (p < 0.05).Conclusions: Level of bio-available testosterone decreased with advancing age, especially in men with HF. Men with low levels of bio-available testosterone had worse profiles of cardiovascular risk factors. Treatment of HF is still challenging and testosterone supplementation therapy may be an effective therapeutic option.

Effect of testosterone on markers of mitochondrial oxidative phosphorylation and lipid metabolism in muscle of aging men with subnormal bioavailable testosterone

Recent studies have indicated that serum testosterone in aging men is associated with insulin sensitivity and expression of genes involved in oxidative phosphorylation (OxPhos), and that testosterone treatment increases lipid oxidation. Herein, we investigated the effect of testosterone therapy on regulators of mitochondrial biogenesis and markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels. Skeletal muscle biopsies were obtained before and after treatment with either testosterone gel (n=12) or placebo (n=13) for 6 months. Insulin sensitivity and substrate oxidation were assessed by euglycemic-hyperinsulinemic clamp and indirect calorimetry. Muscle mRNA levels and protein abundance and phosphorylation of enzymes involved in mitochondrial biogenesis, OxPhos, and lipid metabolism were examined by quantitative real-time PCR and western blotting. Despite an increase in lipid oxidation (P<0.05), testosterone therapy had no effect on insulin sensitivity or mRNA levels of genes involved in mitochondrial biogenesis (PPARGC1A, PRKAA2, and PRKAG3), OxPhos (NDUFS1, ETFA, SDHA, UQCRC1, and COX5B), or lipid metabolism (ACADVL, CD36, CPT1B, HADH, and PDK4). Consistently, protein abundance of OxPhos subunits encoded by both nuclear (SDHA and UQCRC1) and mitochondrial DNA (ND6) and protein abundance and phosphorylation of AMP-activated protein kinase and p38 MAPK were unaffected by testosterone therapy. The beneficial effect of testosterone treatment on lipid oxidation is not explained by increased abundance or phosphorylation-dependent activity of enzymes known to regulate mitochondrial biogenesis or markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels.

Hypogonadism in aged hospitalized male patients: prevalence and clinical outcome

Objective Male hypogonadism is common in the elderly and has been associated with increased risk of mortality. Our objective has been to assess the prevalence of primary and central hypogonadism in elderly male patients admitted to the hospital because of acute illness. We also evaluated the relationships between gonadal dysfunction and in-hospital mortality. Patients and methods 150 patients, aged C65 years, admitted during 2010 and 2011 in our geriatric unit, were studied. Serum concentrations total, bioavailable and free testosterone, as well as of follicle-stimulating hormone and luteinizing hormone were quantified in every patient. Hypogonadism was defined by the presence of serum testosterone levels lower than 200 ng/dl. Results Hypogonadism was found in 80 patients (53.3 %). Serum gonadotropin concentrations were elevated in 43.7 % of these patients, whereas 41.3 % of hypogonadic patients showed normal and 15 % low gonadotropin concentrations. Respiratory tract infection and congestive heart failure were the main causes of hospitalization in hypogonadal men, whereas acute cerebrovascular disease was the main reason for admission in eugonadal patients. Of the 13 patients who died during hospitalization, 12 were hypogonadic. Patients who died showed significantly lower serum levels of total, free and bioavailable testosterone than those found in patients who survived. Conclusion Our results show that about half of patients admitted for acute illness have hypogonadism, mainly of non-hypergonadotropic type. Gonadal hypofunction is significantly related with in-hospital mortality. A low value of serum testosterone may be a predictor for mortality in elderly male patients.

MP74-03 LOW FREE AND BIOAVAILABLE TESTOSTERONE LEVELS CAN PREDICT HIGH-GRADE PROSTATE CANCER: PROSPECTIVE, CLINICAL STUDY

You have accessJournal of UrologyProstate Cancer: Markers I1 Apr 2014MP74-03 LOW FREE AND BIOAVAILABLE TESTOSTERONE LEVELS CAN PREDICT HIGH-GRADE PROSTATE CANCER: PROSPECTIVE, CLINICAL STUDY Goksel Bayar, Mustafa Kadihasanoglu, Mustafa Aydin, Umut Sariogullari, Orhan Tanriverdi, and Muammer Kendirci Goksel BayarGoksel Bayar More articles by this author , Mustafa KadihasanogluMustafa Kadihasanoglu More articles by this author , Mustafa AydinMustafa Aydin More articles by this author , Umut SariogullariUmut Sariogullari More articles by this author , Orhan TanriverdiOrhan Tanriverdi More articles by this author , and Muammer KendirciMuammer Kendirci More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2336AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To evaluate the predictive value of blood free and bioavailable levels on the detection of high-grade prostate cancer proven by transrectal prostate biopsy. METHODS A total of 344 patients who underwent transrectal prostate biopsy due to high PSA levels of >2.5 ng/ml or abnormal findings at digital rectal exam were included into this study. Those patients who had been on testosterone replacement or 5-ARI therapies were excluded. Blood samples were taken between 07-10 o’clock for measuring blood total testosterone, PSA, SHBG and albumin levels. The free and bioavailable testosterone levels were calculated by the formula provided by ISSAM. Patients were stratified according to the D’Amico classification by PSA levels and histological outcomes of prostate biopsies as benign, low- medium risk and high-grade prostate cancer. Patients were also divided into five groups according to cancerous biopsy core rate. Mann-Whitney-U and Kruskal-Wallis tests were used for statistical analysis, and p<0.05 was considered as significant. RESULTS Prostate cancer was detected in 155 of 344 (45%) patients. Blood total, free and bioavailable testosterone levels were unable to differentiate benign and malign histology. However, blood free (6.2 vs. 5.2 ng/dl, p= 0.002) and bioavailable testosterone levels (151 vs. 125 ng/dl p= 0.001) were found to be significantly different in men with low-medium and high-risk prostate cancer patients (Table). A correlation could not be found between free and bioavailable testosterone levels and rates of cores with cancer (p= 0.332) (Figure). CONCLUSIONS This study demonstrated that reduced levels of calculated blood free and bioavailable testosterone are associated with an increased risk of high-grade prostate biopsy. We think that blood free and bioavailable testosterone levels can be used to predict high-risk prostate cancer. Low-medium risk prostate cancer High-grade prostate cancer p value Patients no. (n) 96 59 Total Testosterone (ng/dL) 356±132 327±121 0.174 Albumin (g/dL) 4.4±0.3 4.3±0.4 0.161 SHBG (nmol/L) 39.4±14 45.9±18 0.086 Free Testosterone (ng/dL) 6.2±1.9 5.2±1.6 0.002* Bioavailable Testosterone (ng/dL) 151±47 125±43 0.001* © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e856-e857 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Goksel Bayar More articles by this author Mustafa Kadihasanoglu More articles by this author Mustafa Aydin More articles by this author Umut Sariogullari More articles by this author Orhan Tanriverdi More articles by this author Muammer Kendirci More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Testosterone Levels and Sexual Function Disorders in Depressive Female Patients: Effects of Antidepressant Treatment

Women suffer from depression more frequently than men, which indicates that sex hormones might be involved in the etiology of this disease. The purpose of this study was to assess the relationship between testosterone and depression pathophysiology in depressive women along with sexual function. We also investigated whether antidepressant treatment causes any change in levels of this hormone or in sexual function. Premenopausal female patients aged 25-46 years (n = 52) with diagnosed major depression were included in this study as the patient group, and 25- to 46-year-old premenopausal women without depression (n = 30) were included as the control group. Serum testosterone and sex hormone-binding globulin (SHBG) levels were measured twice, before and after the antidepressant treatment. Bioavailable testosterone (cBT) levels were calculated using the assay results for total testosterone (TT), SHBG, and albumin according to the formulas of Vermeulen et al. Depression severity was measured using the 17-item Hamilton Depression Rating Scale, and sexual function was evaluated with the Arizona Sexual Experience Scale. The mean TT and cBT levels significantly increased in the patient group after the antidepressant treatment (P < 0.001). Pre-treatment TT and cBT levels were significantly lower in the patient group than in the control group (P < 0.001). Similar results were obtained for post-treatment serum TT and cBT levels in the patient and control groups (P > 0.05). There were no significant differences among the groups in terms of SHBG level. The low testosterone levels in depressed women compared with women in the control group and the elevated levels post-pharmacotherapy suggest that testosterone may be involved in depression.

Testosterone deficiency and severity of erectile dysfunction are independently associated with reduced quality of life in men with type 2 diabetes

Erectile dysfunction (ED) and low testosterone levels are common in men with type 2 diabetes (T2D). We have investigated the impact of testosterone on quality of life (QoL) in diabetic men with ED. Men with ED were identified within a study cohort of 355 men with T2D. All subjects completed SF-36 health and Androgen Deficiency of the Aging Male questionnaires. Total tesosterone (TT), bioavailable testosterone (BT) and sex hormone-binding globulin levels of study participants were measured and free testosterone levels were calculated (cFT). A subgroup of 126 ED patients completed the International Index of Erectile Function-5 (IIEF-5) questionnaire. Linear regression analyses were corrected for age, body mass index (BMI), glycosylated haemoglobin (HbA1c), smoking, alcohol consumption and cardiovascular disease (CVD). Total SF-36 scores significantly and positively correlated with TT levels (r = 0.219, p = 0.001), BT levels (r = 0.199, p = 0.004) and cFT levels (r = 0.185, p = 0.007) among men with ED. These trends were strengthened after adjusting for age, BMI, HbA1c, smoking, alcohol consumption and CVD (TT r = 0.359, p = 0.015; BT r = 0.354, p = 0.024 and cFT r = 0.354, p = 0.024). IIEF-5 scores significantly correlated inversely with TT (r = 0.546, p = 0.001), BT (r = 0.506, p = 0.004) and cFT levels (r = 0.532, p = 0.001). A positive linear relationship was observed between IIEF-5 scores and total SF-36 score (r = 0.491, p = 0.003). Patients who reported having ED had an average SF-36 score of 9.1% less than those without ED (p < 0.001). Lower testosterone and greater severity of ED independently correlated with poorer physical function, social function, vitality and decline in general health domains of the SF-36. This is the first study to report that testosterone deficiency and severity of ED are both independently associated with reduced QoL in men with T2D. Furthermore, ED and low testosterone are markers of poor health which impact on an individual's self-perception of their health status.

Hypogonadism in aged hospitalized male patients: prevalence and clinical outcome

Male hypogonadism is common in the elderly and has been associated with increased risk of mortality. Our objective has been to assess the prevalence of primary and central hypogonadism in elderly male patients admitted to the hospital because of acute illness. We also evaluated the relationships between gonadal dysfunction and in-hospital mortality. 150 patients, aged ≥65years, admitted during 2010 and 2011 in our geriatric unit, were studied. Serum concentrations total, bioavailable and free testosterone, as well as of follicle-stimulating hormone and luteinizing hormone were quantified in every patient. Hypogonadism was defined by the presence of serum testosterone levels lower than 200ng/dl. Hypogonadism was found in 80 patients (53.3%). Serum gonadotropin concentrations were elevated in 43.7% of these patients, whereas 41.3% of hypogonadic patients showed normal and 15% low gonadotropin concentrations. Respiratory tract infection and congestive heart failure were the main causes of hospitalization in hypogonadal men, whereas acute cerebrovascular disease was the main reason for admission in eugonadal patients. Of the 13 patients who died during hospitalization, 12 were hypogonadic. Patients who died showed significantly lower serum levels of total, free and bioavailable testosterone than those found in patients who survived. Our results show that about half of patients admitted for acute illness have hypogonadism, mainly of non-hypergonadotropic type. Gonadal hypofunction is significantly related with in-hospital mortality. A low value of serum testosterone may be a predictor for mortality in elderly male patients.

Protective effects of testosterone on presynaptic terminals against oligomeric β-amyloid peptide in primary culture of hippocampal neurons.

Increasing lines of evidence support that testosterone may have neuroprotective effects. While observational studies reported an association between higher bioavailable testosterone or brain testosterone levels and reduced risk of Alzheimer's disease (AD), there is limited understanding of the underlying neuroprotective mechanisms. Previous studies demonstrated that testosterone could alleviate neurotoxicity induced by β-amyloid (Aβ), but these findings mainly focused on neuronal apoptosis. Since synaptic dysfunction and degeneration are early events during the pathogenesis of AD, we aim to investigate the effects of testosterone on oligomeric Aβ-induced synaptic changes. Our data suggested that exposure of primary cultured hippocampal neurons to oligomeric Aβ could reduce the length of neurites and decrease the expression of presynaptic proteins including synaptophysin, synaptotagmin, and synapsin-1. Aβ also disrupted synaptic vesicle recycling and protein folding machinery. Testosterone preserved the integrity of neurites and the expression of presynaptic proteins. It also attenuated Aβ-induced impairment of synaptic exocytosis. By using letrozole as an aromatase antagonist, we further demonstrated that the effects of testosterone on exocytosis were unlikely to be mediated through the estrogen receptor pathway. Furthermore, we showed that testosterone could attenuate Aβ-induced reduction of HSP70, which suggests a novel mechanism that links testosterone and its protective function on Aβ-induced synaptic damage. Taken together, our data provide further evidence on the beneficial effects of testosterone, which may be useful for future drug development for AD.

Evaluation of the hypothalamic‐pituitary‐gonadal axis in eugonadal men with type 2 diabetes mellitus

Men with type 2 diabetes mellitus (DM2) have lower testosterone levels and a higher prevalence of hypogonadism. It still remains unclear the mechanism by which there is a relationship between hypogonadism and DM2. The objective was to evaluate the hypothalamic-pituitary-gonadal axis at different levels in eugonadal patients with DM2. Fourteen patients with DM2 (DM2 group) and 15 subjects without DM2 (normal glucose tolerance test) as control group (CG) were included. We assessed: (i) fasting glucose, insulin, Homeostasis Model Assessment (HOMA); (ii) luteinizing hormone (LH) pulsatility through blood collections every 10min for 4h; (iii) gonadotropin-releasing hormone (GnRH) test: basal LH and 30, 60 and 90min after 100μg of i.v. GnRH; (iv) human chorionic gonadotropin (hCG) test: basal total testosterone (TT), bioavailable testosterone (BT), free testosterone (FT), estradiol (E2), bioavailable E2 (BE2) and sex hormone-binding globulin (SHBG) and 72h post 5000IU of i.m. hCG. There were no differences in age, body mass index and waist circumference between groups. Glucose was higher in the DM2 group vs. CG: 131.1±25.5 vs. 99.1±13.6mg/dL, p=0.0005. There were no difference in basal insulin, HOMA, TT, BT, FT, E2, BE2, SHBG and LH levels between groups. The DM2 group had lower LH pulse frequency vs. CG: 0.8±0.8 vs. 1.5±0.5 pulses, p=0.009. Differences in LH pulse amplitude were not found. A negative correlation was found between the number of LH pulses and glucose, r: -0.39, p=0.03. There were no differences in the response of LH to GnRH between groups nor in the response of sexual steroids and SHBG to hCG. Patients with DM2 showed lower hypothalamic pulse frequency without changes in the pituitary response to GnRH nor testicular response to hCG. Glucose levels negatively correlated with the number of LH pulses which suggests a negative effect of hyperglycaemia in the hypothalamic secretion of GnRH.