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Post-traumatic stress disorder (PTSD) is a debilitating psychological condition that may develop in certain individuals following exposure to life-threatening or traumatic events. Distressing symptoms, including flashbacks, are characterized by disrupted stress responses, fear, anxiety, avoidance tendencies, and disturbances in sleep patterns. The enduring effects of PTSD can profoundly impact personal and familial relationships, as well as social, medical, and financial stability. The prevalence of PTSD varies among different populations and is influenced by the nature of the traumatic event. Recently, zebrafish have emerged as a valuable model organism in studying various conditions and disorders. Zebrafish display robust behavioral patterns that can be effectively quantified using advanced video-tracking tools. Due to their relatively simple nervous system compared to humans, zebrafish are particularly well suited for behavioral investigations. These unique characteristics make zebrafish an appealing model for exploring the underlying molecular and genetic mechanisms that govern behavior, thus offering a powerful comparative platform for gaining deeper insights into PTSD. This review article aims to provide updates on the pathophysiology of PTSD and the genetic responses associated with psychological stress. Additionally, it highlights the significance of zebrafish behavior as a valuable tool for comprehending PTSD better. By leveraging zebrafish as a model organism, researchers can potentially uncover novel therapeutic interventions for the treatment of PTSD and contribute to a more comprehensive understanding of this complex condition. [ABSTRACT FROM AUTHOR]

Functional hypogonadism is a condition characterized by low testosterone concentrations, occurring more commonly in men as they age. The International Prostate Symptom Score (IPSS) is used to categorize the severity of lower urinary tract symptoms (LUTS) and related symptoms in hypogonadal men. Testosterone therapy (TTh) has previously shown potential in improving total IPSS in men with hypogonadism. However, concerns regarding the effects of urinary function following TTh often prevent treatment in hypogonadal men. To explore this further, two population-based single-center, prospective, cumulative registry studies were combined to contribute to a total population of 1176 men with symptoms of hypogonadism. The total population was separated into a TTh group receiving testosterone undecanoate (TU) for up to 12years and a control group that did not receive treatment. IPSS was recorded at both baseline and at final recorded visit for each patient. Long-term TTh with TU in hypogonadal men resulted in significant improvements in IPSS categories, even in patients with severe symptoms at baseline. In the control group, untreated hypogonadal men experienced a worsening of IPSS categories. These data indicate that TTh improves LUTS in men with hypogonadism and suggest that previous concerns regarding urinary function may have been overstated. [ABSTRACT FROM AUTHOR]

Boronic acids/esters have recently emerged in the field of medicinal and pharmaceutical research due to their exceptional oxophilicity, low toxicity, and unique structure. They are known as potent enzyme inhibitors, cancer therapy capture agents, and can mimic certain types of antibodies to fight infections. They have been designed and developed into drugs, and this approach has emerged in the last 20 years. Five boronic acid drugs have been approved by the FDA and Health Canada, two of which are used to treat cancer, specifically multiple myeloma. The purpose of this review is to investigate boronic acid/ester derivatives as potential pharmaceutical agents as well as the mechanism of action. It will concentrate on six types of cancer: multiple myeloma, prostate cancer, breast cancer, lung cancer, cervical cancer, and colon cancer. Some newly developed boron-containing compounds have already demonstrated highly promising activities, but further investigation is required before final conclusions can be drawn. [ABSTRACT FROM AUTHOR]

Background: Functional hypogonadism is a condition in which some, but not all, older men have low testosterone levels. Rather than chronological age per se, the causality of hypogonadism includes obesity and impaired general health (e.g., metabolic syndrome). An association between testosterone deficiency and lower urinary tract symptoms (LUTS) has been reported, yet due to prostate safety concerns, men with severe LUTS (IPSS score > 19) have invariably been excluded from entering testosterone trials. Irrespective, exogenous testosterone has not been demonstrated to cause de novo or worsen mild to moderate LUTS. Objective: This study investigated whether long-term testosterone therapy (TTh) could have a protective effect on improving the symptoms of LUTS in hypogonadal men. However, the exact mechanism by which testosterone exerts is beneficial effect remains uncertain. Patients and methods: In this study 321 hypogonadal patients with an average age of 58.9 ± 9.52 years received testosterone undecanoate in 12-week intervals for 12 years. One hundred and forty-seven of these males had the testosterone treatment interrupted for a mean of 16.9 months before it was resumed. Total testosterone, International Prostate Symptom Scale (IPSS), post-voiding residual bladder volume and aging male symptoms (AMS) were measured over the study period. Results: Prior to TTh interruption, it was observed that testosterone stimulation improved the men's IPSS, AMS and post-voiding residual bladder volume, while their prostate volume significantly increased. During the TTh interruption, there was a significant worsening in these parameters, although the increase in prostate volume continued. When TTh was resumed, these effects were reversed, implying that hypogonadism may require lifelong treatment. [ABSTRACT FROM AUTHOR]

There is overwhelming evidence to suggest that male gender is at a higher risk of developing more severe Covid‐19 disease and thus having poorer clinical outcomes. However, the relationship between testosterone (T) and Covid‐19 remains unclear with both protective and deleterious effects on different aspects of the disease suggested. Here, we review the current epidemiological and biological evidence on the role of testosterone in the process of SARS‐CoV‐2 infection and in mediating Covid‐19 severity, its potential to serve as a biomarker for risk stratification and discuss the possibility of T supplementation as a treatment or preventative therapy for Covid‐19. [ABSTRACT FROM AUTHOR]

Background and Aims: On March 11, 2020, the WHO has declared COVID‐19 a global pandemic, affecting our day‐to‐day lives. Physical distancing and lockdown made significant obstacles to populations, particularly healthcare systems. Most healthcare workers were reallocated to COVID‐19 facilities. Noncommunicable disease patients were given low priority and are at a higher risk of severe COVID‐19 infection, which disrupted the treatment and disease management of these patients. This review aimed to assess the effect of COVID‐19 on different types of noncommunicable diseases and the severity it may cause to patients. Methods: We have conducted a review of the literature on COVID‐19 and noncommunicable diseases from December 2019 until January 2022. The search was done in PubMed and Cochrane for relevant articles using variety of searching terms. Data for study variables were extracted. At the end of the selection process, 46 papers were selected for inclusion in the literature review. Result: The result from this review found that the COVID‐19 pandemic has affected the efficiency of the patient's treatment indirectly by either delaying or canceling sessions, which solidified the need to rely more on telemedicine, virtual visits, and in‐home visits to improve patient education and minimize the risk of exposure to the patients. The major and most common types of noncommunicable diseases are known to be related to the severe outcomes of COVID‐19 infection. It is strongly recommended to prioritize these patients for vaccinations against COVID‐19 to provide them with the protection that will neutralize the risk imposed by their comorbidities. Conclusion: We recommend conducting more studies with larger population samples to further understand the role of noncommunicable diseases (NCDs) in this pandemic. However, this pandemic has also affected the efficiency of NCDs treatment indirectly by delaying or canceling sessions and others. [ABSTRACT FROM AUTHOR]

Testosterone therapy (TTh) is the primary treatment for aging men with functional hypogonadism. Whilst the benefits of testosterone (T) replacement are well-evidenced, the long-term data for TTh on metabolic and endocrine parameters is limited. Here we present the effect of TTh on endocrine parameters in hypogonadal men at a 12-year follow-up. In this single-centre, cumulative, prospective, registry study, 321 hypogonadal men (mean age: 58.9 years) received testosterone undecanoate injections in 12-week intervals for up to 12 years. Blood samples were taken at every other visit to measure levels of total T (TT), calculated free T, sex hormone-binding globulin (SHBG), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone and prolactin. We observed an increase in TT of 15.5 nmol/L (p < 0.0001), a reduction in SHBG of 10.5 nmol/L (p < 0.0001) and an increase in calculated free T of 383.04 pmol/L (p < 0.0001) over the study period. This was accompanied by an increase in estradiol levels by 14.9 pmol/L (p < 0.0001), and decreases in progesterone (0.2 ng/mL, p < 0.0001), LH (10.4 U/L, p < 0.0001) and FSH (8.4 U/L, p < 0.0001) were demonstrated at 12-years. The levels of prolactin remained unchanged. Long-term TTh altered hormonal parameters to predictably modify the endocrine system. These effects were sustained during the entire observation time of 12 years. [ABSTRACT FROM AUTHOR]

Lower urinary tract symptoms (LUTS) are caused by higher tension at the bladder neck level (due to fibrosis or stiffness) or benign prostatic hyperplasia, which causes static obstruction of the bladder outlet. Both forms cause a group of symptoms such as hesitancy, intermittency, weak stream, nocturia, urine frequency, and urgency. Additionally, LUTS (obstructive or irritative symptoms) are common in elderly men with hypogonadism, identified as the reduced testes capability in producing sex steroids and sperm, and are categorized as testosterone deficiency. Even though the mode of action (MoA) of testosterone therapy (TTh) on hypogonadal men needs more researched and understanding, the effectiveness of TTh in the development of male genital organs has been reported in several studies. This review shows the latest updates of TTh in LUTS including potential adverse effects, advantages, and disadvantages. [ABSTRACT FROM AUTHOR]

Background & Aims: The BioNTech‐Pfizer vaccine is the only vaccine offered to children among all available vaccines. However, limited evidence is available about the clinical outcomes of COVID‐19 vaccines, especially among children and adolescents. This review offers a comprehensive and up‐to‐date overview of the BioNTech‐Pfizer vaccine's current information on children and adolescents. Methods: The review was conducted following the PRISMA guidelines; a comprehensive search was performed in PubMed, Scopus, MEDLINE, and EMBASE databases for research publications COVID‐19 published between December 2019 and October 2021. All studies reporting on the outcomes of vaccinating children in their respective institutes were included. Results: A total of 78 vaccinated children and adolescents from six studies were included. The majority of symptomatic vaccinated pediatrics were males (71%). The mean age was 15.6 years, and the BMI was 24.1. The most common clinical symptoms were found in chest pain (35%), fever (32%), and myalgia (17%). The most common cardiac symptom in the EKG results was ST elevation, and 35% of vaccinated pediatrics had elevated serum troponin. The hospitalization, including ICU admission, was lower than in unvaccinated groups. Statistically significant associations (p ≤ 0.05) were found in two symptoms (fever and headache) between the vaccinated and nonvaccinated pediatric groups. Conclusions: Although we found better outcomes in the vaccinated group versus the nonvaccinated pediatric group, more studies are still crucial to further understand the specific etiology underlying postvaccination, particularly myocarditis, psychological impact, and other cardiac clinical symptoms in children and adolescents after receiving the BioNTech‐Pfizer vaccine. [ABSTRACT FROM AUTHOR]

Summary: The current coronavirus disease (COVID‐19) pandemic caused by novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has a male bias in severity and mortality. This is consistent with previous coronavirus pandemics such as SARS‐CoV and MERS‐CoV, and viral infections in general. Here, we discuss the sex‐disaggregated epidemiological data for COVID‐19 and highlight underlying differences that may explain the sexual dimorphism to help inform risk stratification strategies and therapeutic options. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is associated with increased risk of erectile dysfunction. Penile prosthesis implantation is an efficient therapeutic option for erectile dysfunction, but not without risk, as infection remains a prominent concern. This study investigates diabetes mellitus as a risk factor for penile prosthesis implantation infection and the relationship between haemoglobinA1c levels and infection rates. All diabetic patients with erectile dysfunction who underwent penile prosthesis implantation surgery between January 2012 and November 2019 at Hamad Medical Corporation, Qatar, were included in this retrospective observational study. A total of 599 diabetic patients with erectile dysfunction had penile prosthesis implantation. Mean age was 59.69 ± 31.19. Penile prosthesis implantation infection rate was 0.83% (5/599), while the mean haemoglobinA1c level was 7.58 ± 1.45 mmol/l (range: 4.1–12.6). A comparison between diabetic patients with penile prosthesis implantation infection and those without infection revealed no significant difference in the level of haemoglobinA1c between the two groups with mean haemoglobinA1c in patients with infected implants 7.14 and 7.59 for noninfected (p = 0.491). Limitations include retrospective single‐centre design and low‐infection rates reducing sample number. Penile prosthesis implantation infection rate in a large series of diabetic patients was low with no significant association between haemoglobinA1c level and penile prosthesis implantation infection observed. [ABSTRACT FROM AUTHOR]

Purpose: Erectile dysfunction (ED) is associated with testosterone deficiency and is a symptom of functional hypogonadism. A correlation between ED and cardiovascular disease (CVD) has been recognized, and ED has been proposed as an early marker of CVD. However, the relationship between ED and CVD risk in hypogonadism requires clarification and whether testosterone therapy (TTh) can be a beneficial treatment strategy, but long-term data are limited. This study investigates long-term TTh in men with hypogonadism and ED with a history of CVD. Methods: Seventy-seven patients with a history of CVD and diagnosed with functional hypogonadism and erectile dysfunction (erectile function domain score < 21 on the International Index of Erectile Function questionnaire (IIEF questions 1– 5)) were enrolled and TTh effects on anthropometric and metabolic parameters investigated for a maximum duration of 12 years. All men received long-acting injections of testosterone undecanoate at 3-monthly intervals. Eight-year data were analysed. Data collection registry started in November 2004 till January 2015. Results: In hypogonadal men receiving TTh, IIEF increased by 5.4 (p< 0.001). Total weight loss was 23.6 ± 0.6 kg after 8 years. HbA1c had declined by an average of 2.0% (P< 0.0001). Total cholesterol levels significantly declined following TTh after only 1 year (P< 0.0001), and HDL increased from 1.6± 0.5 at baseline to 2± 0.5 mmol/L following 8 years of TTh (P< 0.0001). SBP decreased from 164± 14 at baseline to 133± 9 mmHg, signifying a reduction of 33± 1 mmHg (P< 0.0001). Conclusion: In hypogonadal men with a history of CVD, TTh improves and preserves erectile function over prolonged periods with concurrent sustained improvements in cardiometabolic risk factors. Measuring ED and testosterone status may serve as an important male health indicator predicting subsequent CVD-related events and mortality and TTh may be an effective add-on treatment in secondary prevention of cardiovascular events in hypogonadal men with a history of CVD. [ABSTRACT FROM AUTHOR]

A facile and unprecedented synthesis of 2,3-diiodinated or 2,6-diiodinated diaryl ether/thioether derivatives through regioselective Ullmann-type cross couplings of 5-substituted 1,2,3-triiodobenzenes and phenols/thiophenols is described. Remarkably, the coupling reactions are simply controlled by the type of nucleophiles and the nature of C5 substituent at 1,2,3-triiodoarenes providing the internal or terminal coupling products in high regioselectivity and good isolated yields. Noticeable steric and electronic effects were clearly observed on both 1,2,3-triiodoarenes and nucleophiles. The highest yields were isolated from a combination between either electron-poor 1,2,3-triiodoarenes and phenols or electron-rich 1,2,3-triiodoarenes and thiophenols. The optimized conditions were found to be suitable for several functional groups. Using this methodology, mammary carcinoma inhibitor BTO-956 is prepared in only one step with excellent regioselectivity and good isolated yield. This report discloses the first method to prepare 2,3-diiodinated and 2,6-diiodinated diaryl ethers/thioethers in one step that is efficient, regioselective, and general in scope. The products are truly remarkable precursors for other transformations. [ABSTRACT FROM AUTHOR]

An efficient and unprecedented synthesis of 2,3-diiodinated N-aryl carbamate derivatives through highly regioselective Ullmann-type C–N arylation reactions of 5-substituted-1,2,3-triiodobenzenes and primary carbamates is described. Remarkably, the amination reactions proceeded exclusively at the terminal positions, the less sterically hindered, and the most regioactive positions. The highest yields were isolated from a combination between electron poor 1,2,3-triiodoarenes and ethyl carbamates. The optimized conditions were found to be suitable for many functional groups. This report discloses the first and unprecedented method to make 2,3-diiodinated N-aryl carbamates that is efficient, general in scope, highly regioselective and gives truly remarkable precursors for other transformations. [ABSTRACT FROM AUTHOR]

A facile and unprecedented synthesis of 2,3-diiodinated Narylbenzimidamide derivatives through highly regioselective Buchwald-Hartwig coupling of 5-substituted-1,2,3-triiodobenzene and amidine is described. Remarkably, the amination reactions are proceeded exclusively at the terminal positions, the less sterically hindered, and the most regioactive positions. The highest yields were isolated from a combination between electron-poor 1,2,3-triiodoarenes and electron-poor benzimidamides. The optimized conditions were found to be suitable for many functional groups. This report discloses the first method to make 2,3-diiodinated N-arylbenzimidamides that is efficient, general in scope, highly regioselective, and truly remarkable precursors for other transformations. [ABSTRACT FROM AUTHOR]

Purpose: Erectile dysfunction (ED) is associated with testosterone deficiency and is a symptom of functional hypogonadism. A correlation between ED and cardiovascular disease (CVD) has been recognized, and ED has been proposed as an early marker of CVD. However, the relationship between ED and CVD risk in hypogonadism requires clarification and whether testosterone therapy (TTh) can be a beneficial treatment strategy, but long-term data are limited. This study investigates long-term TTh in men with hypogonadism and ED with a history of CVD.Methods: Seventy-seven patients with a history of CVD and diagnosed with functional hypogonadism and erectile dysfunction (erectile function domain score <21 on the International Index of Erectile Function questionnaire (IIEF questions 1-5)) were enrolled and TTh effects on anthropometric and metabolic parameters investigated for a maximum duration of 12 years. All men received long-acting injections of testosterone undecanoate at 3-monthly intervals. Eight-year data were analysed. Data collection registry started in November 2004 till January 2015.Results: In hypogonadal men receiving TTh, IIEF increased by 5.4 (p<0.001). Total weight loss was 23.6 ± 0.6 kg after 8 years. HbA1c had declined by an average of 2.0% (P<0.0001). Total cholesterol levels significantly declined following TTh after only 1 year (P<0.0001), and HDL increased from 1.6±0.5 at baseline to 2±0.5 mmol/L following 8 years of TTh (P<0.0001). SBP decreased from 164±14 at baseline to 133±9 mmHg, signifying a reduction of 33±1 mmHg (P<0.0001).Conclusion: In hypogonadal men with a history of CVD, TTh improves and preserves erectile function over prolonged periods with concurrent sustained improvements in cardiometabolic risk factors. Measuring ED and testosterone status may serve as an important male health indicator predicting subsequent CVD-related events and mortality and TTh may be an effective add-on treatment in secondary prevention of cardiovascular events in hypogonadal men with a history of CVD. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD) and both are prevalent in men with testosterone deficiency. Long-term effects of testosterone therapy (TTh) on NAFLD are not well studied. This observational, prospective, cumulative registry study assesses long-term effects of testosterone undecanoate (TU) on hepatic physiology and function in 505 hypogonadal men (T levels ≤350 ng/dL). Three hundred and twenty one men received TU 1000 mg/12 weeks for up to 12 years following an initial 6-week interval (T-group), while 184 who opted against TTh served as controls (C-group). T-group patients exhibited decreased fatty liver index (FLI, calculated according to Mayo Clinic guidelines) (83.6 ± 12.08 to 66.91 ± 19.38), γ-GT (39.31 ± 11.62 to 28.95 ± 7.57 U/L), bilirubin (1.64 ± 4.13 to 1.21 ± 1.89 mg/dL) and triglycerides (252.35 ± 90.99 to 213 ± 65.91 mg/dL) over 12 years. Waist circumference and body mass index were also reduced in the T-group (107.17 ± 9.64 to 100.34 ± 9.03 cm and 31.51 ± 4.32 to 29.03 ± 3.77 kg/m2). There were 25 deaths (7.8%) in the T-group of which 11 (44%) were cardiovascular related. In contrast, 28 patients (15.2%) died in C-group, and all deaths (100%) were attributed to CVD. These data suggest that long-term TTh improves hepatic steatosis and liver function in hypogonadal men. Improvements in liver function may have contributed to reduced CVD-related mortality. [ABSTRACT FROM AUTHOR]

Around 400 million people across the globe will suffer from asthma in the next 10 years. Although most asthmatics use asthma medications regularly, they occasionally visit the emergency department for aggressive treatment amidst family anxiousness. Vitamin D (VD) not only regulates the expression of genes associated with calcium homeostasis, but also the genes associated with cancers, autoimmune diseases, and infection. VD has also non-genomic activities e.g. it is a potentially safe and effective novel strategy for decreasing the asthma episodes and controlling exacerbations. Our review assessed the dose, serum level, duration of administration and outcomes of VD in cases of asthmas. Although a body of research evidences the effectiveness of VD supplementation in asthma, other studies showed the insignificant response of VD to asthma either with low dose or low achieved serum VD levels. Nevertheless, recent reviews suggest that manipulating VD status holds promise for primary prevention and treatment of asthma. Future research on the relationship between VD and asthma should consider utilizing adequate doses of VD preparations for sufficient duration (likely to be >12 months) aiming to achieve appropriate level of serum VD (25-hydroxyvitamin D) concentration (likely to be at least >40 ng/mL). [ABSTRACT FROM AUTHOR]

Objective: Type 2 diabetes (T2D) is a public health threat. Prediabetes represents a window of opportunity for intervention to prevent T2D. Men with T2D and prediabetes often have low testosterone. Since testosterone improves glycemic control in T2D, we investigated whether testosterone therapy (TTh) in men with hypogonadism and prediabetes prevents progression to T2D.Research Design and Methods: Three hundred and sixteen men with prediabetes (defined as HbA1c 5.7-6.4%) and total testosterone levels ≤12.1 nmol/L combined with symptoms of hypogonadism were analyzed. Two hundred and twenty-nine men received parenteral testosterone undecanoate (T-group), and 87 men with hypogonadism served as untreated control subjects. Metabolic and anthropometric parameters were measured twice yearly for 8 years.Results: HbA1c decreased by 0.39 ± 0.03% (P < 0.0001) in the T-group and increased by 0.63 ± 0.1% (P < 0.0001) in the untreated group. In the T-group, 90% achieved normal glucose regulation (HbA1c <5.7%). In the untreated group, 40.2% progressed to T2D (HbA1c >6.5%). TTh was also associated with significant improvements in fasting glucose, triglyceride:HDL ratio, triglyceride-glucose index, lipid accumulation product, total cholesterol, LDL, HDL, non-HDL, triglycerides, and Aging Males' Symptoms (AMS) scale. Significant deterioration in all these parameters was seen in the untreated group. Mortality was 7.4% in the T-group and 16.1% in the untreated group (P < 0.05). The incidence of nonfatal myocardial infarction was 0.4% in the T-group and 5.7% in the untreated group (P < 0.005).Conclusions: Long-term TTh completely prevents prediabetes progression to T2D in men with hypogonadism and improves glycemia, lipids, and AMS score. TTh holds tremendous potential for the large and growing population of men with prediabetes and hypogonadism. [ABSTRACT FROM AUTHOR]

This study investigated the role of testosterone replacement therapy (TRT) in prostate safety and cancer progression. A cohort of 553 patients, 42 treated and 162 untreated hypogonadal men, and 349 eugonadal men were included. Pathological analysis of prostate biopsies examining the incidence and severity of PCa revealed that: 16.7% of treated hypogonadal men had a positive biopsy, a Gleason score of ≤6 in 71.4% and >6 in 28.6% of men, a predominant score of 3 and tumour staging of II in 85.7% men; 51.9% of untreated hypogonadal men had a positive biopsy, a Gleason score of ≤6 in 40.5% and >6 in 59.5% men, a predominant score of 3 (77.4%) and tumour staging of II (41.7%) or III (40.5%); 37.8% of eugonadal men had a positive biopsy, a Gleason score of ≤6 in 42.4% and >6 in 57.6% of men, a predominant score of 3 (82.6%) and tumour staging of II (44.7%) or III (47.7%). The incidence of positive prostate biopsies was lowest in hypogonadal men receiving TRT, with significantly lower severity of PCa in terms of staging and grading in the same group. These results suggest that TRT might have a protective effect against high-grade PCa. [ABSTRACT FROM PUBLISHER]

We and others have previously shown that testosterone replacement therapy (TRT) results in sustained weight loss in the majority of middle-aged hypogonadal men. Previously, however, a small proportion failed to lose at least 5% of their baseline weight. The reason for this is not yet understood. In the present study, we sought to identify early indicators that may predict successful long-term weight loss, defined as a reduction of at least 5% of total body weight relative to baseline weight (T0), in men with hypogonadism undergoing TRT. Eight parameters measured were assessed as potential predictors of sustained weight loss: loss of 3% or more of baseline weight after 1 year of TU treatment, severe hypogonadism, BMI, waist circumference, International Prostate Symptom Score (IPSS), glycated hemoglobin (HbA1C), age and use of vardenafil. Among the eight measured parameters, three factors were significantly associated with sustained weight loss over the entire period of TU treatment: (1) a loss of 3% of the baseline body weight after 1 year of TRT; (2) baseline BMI over 30; and (3) a waist circumference >102 cm. Age was not a predictor of weight loss. [ABSTRACT FROM PUBLISHER]

Background/objectives: Long-term testosterone therapy (TTh) in men with hypogonadism has been shown to improve all components of the metabolic syndrome. In this study, we investigated the effects of long-term TTh up to 8 years in hypogonadal men with a history of cardiovascular disease (CVD).Patients and Methods: In two urological clinics observational registries, we identified 77 hypogonadal men receiving TTh who also had a history of CVD. The effects of TTh on anthropometric and metabolic parameters were investigated for a maximum duration of 8 years. Any occurrence of major adverse cardiovascular events was reported. All men received long-acting injections of testosterone undecanoate at 3-monthly intervals.Results: In 77 hypogonadal men with a history of CVD who received TTh, we observed a significant weight loss and a decrease in waist circumference and body mass index. Mean weight decreased from 114±13 kg to 91±9 kg, change from baseline: -24±1 kg and -20.2%±0.5%. Waist circumference decreased from 112±8 cm to 99±6 cm, change from baseline: -13±0.3 cm. Body mass index decreased from 37±4 to 29±3, change from baseline: -8±0.2 kg/m(2). Cardio-metabolic parameters such as lipid pattern, glycemic control, blood pressure, heart rate, and pulse pressure all improved significantly and sustainably. No patient suffered a major adverse cardiovascular event during the full observation time.Conclusion: In men with hypogonadism, TTh appears to be effective in achieving sustained improvements in all cardiometabolic risk factors and may be effective as an add-on measure in the secondary prevention of cardiovascular events in hypogonadal men with a history of CVD. [ABSTRACT FROM AUTHOR]

Whether testosterone replacement therapy (TRT) is a lifelong treatment for men with hypogonadism remains unknown. We investigated long-term TRT and TRT withdrawal on obesity and prostate-related parameters. Two hundred and sixty-two hypogonadal patients (mean age 59.5) received testosterone undecanoate in 12-week intervals for a maximum of 11 years. One hundred and forty-seven men had TRT interrupted for a mean of 16.9 months and resumed thereafter (Group A). The remaining 115 patients were treated continuously (Group B). Prostate volume, prostate-specific antigen (PSA), residual voiding volume, bladder wall thickness, C-reactive protein (CRP), aging male symptoms (AMS), International Index of erectile function – erectile function (IIEF-EF) and International Prostate Symptoms Scores (IPSS) were measured over the study period with anthropometric parameters of obesity, including weight, body mass index (BMI) and waist circumference. Prior to interruption, TRT resulted in improvements in residual voiding volume, bladder wall thickness, CRP, AMS, IIEF-EF, IPSS and obesity parameters while PSA and prostate volume increased. TRT interruption reduced total testosterone to hypogonadal levels in Group A and resulted in worsening of obesity parameters, AMS, IPSS, residual voiding volume and bladder wall thickness, IIEF-EF and PSA while CRP and prostate volume were unchanged until treatment resumed whereby these effects were reversed. TRT interruption results in worsening of symptoms. Hypogonadism may require lifelong TRT. [ABSTRACT FROM PUBLISHER]

Objective In addition to primary and secondary ('classical') hypogonadism, hypogonadism occurring in middle-aged and elderly men has been recognized. There is evidence that restoring T levels to normal improves body weight, serum lipids and glucose levels. Design Observational registry study. Patients Two hundred and sixty-two hypogonadal, middle-aged and elderly, men received testosterone replacement treatment (TRT). After having been on TRT for a mean duration of 65.5 months, TRT was temporarily intermitted in 147 patients for a mean of 16.9 months (Group I) due to cost reimbursement issues and in seven men due to prostate cancer. All these men resumed TRT for a mean period of 14.5 months. Of the cohort, 115 men were treated continuously (designated as Group C). To compare on-treatment to off-treatment periods, three periods of equal duration were defined: pre-intermission (on TRT), during intermission (off TRT) and post-intermission (on TRT after resumption of TRT). For proper comparison, the same periods were analysed for those patients who continued TRT throughout (Group C). Measurements Variables of body weight, glucose metabolism, lipids, blood pressure and C-reactive protein (CRP). Results In Group C there was a continuous improvement of body weight, serum lipids, glucose, HbA1c, blood pressure and CRP. In Group I there was a similar initial improvement which was reversed upon intermission of T administration but which appeared again when T treatment was reinstated. Conclusions Our observation indicates that T administration improves body weight and metabolic factors in men with hypogonadism but withdrawal of T reverses these beneficial effects to appear again when TRT is resumed. [ABSTRACT FROM AUTHOR]

Introduction: The role of testosterone deficiency in erectile dysfunction (ED) is increasingly recognized; however, there is a need to clarify the nature of the relationship between ED and late onset hypogonadism (LOH).Aim: In this study, we sought to determine the correlators of ED severity amongst men with LOH.Methods: 130 patients diagnosed with LOH fulfilling the criteria of total testosterone ≤3.5 ng/ml (<12 nmol/l) and with an erectile function domain score <21 on the International Index of Erectile Function questionnaire (IIEF questions 1-5) were enrolled for a subsequent trial of Testosterone Undecanoate. Demographic data were recorded at baseline.Main Outcome Measures: Subjects completed three standardised questionnaires to assess sexual health including International Prostate Symptom Score (IPSS), Aging Males Symptoms (AMS) and IIEF Sexual Health Inventory for Men (SHIM). Patients were stratified by ED severity with SHIM scores of 1-7 considered severe ED, 8-11 moderate ED and 12-16 mild to moderate. Serum testosterone, sex hormone binding globulin (SHBG) and lipids (total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein) were assessed along with plasma fasting glucose and HbA1c. Weight, BMI and waist circumference were also recorded.Results: A significant association was observed between severity of ED and mean weight (p = 0.000), waist circumference (p = 0.000), triglycerides (p = 0.009), total cholesterol (p = 0.027), HbA1c (p = 0.000), fasting glucose (p = 0.003) and AMS scores (p = 0.043). No significant differences were seen in testosterone fractions and SHBG levels between ED subgroups. A positive correlation existed between the prevalence of diabetes mellitus (type 1 and type 2) and ED severity in this cohort (p = 0.018).Conclusions: The descriptive data of our cohort show that increased severity of ED within LOH patients correlated with an increased waist circumference, hyperglycemia, hypertriglyceridemia, hyperlipidemia and a history of diabetes mellitus. Severe ED functions as a prognostic indicator of co-morbidities in men with LOH. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is often associated with obesity and subnormal serum testosterone (T) levels. Until 5 years ago there was no indication that men with type 1 diabetes mellitus (T1DM) had subnormal serum T. But recent studies indicate that about 10% of men with T1DM suffer from hypogonadism, as a rule aged men and men with obesity. While hypogonadal men with T2DM benefit from normalization of their serum T, this has not been investigated in men with T1DM. Nine men with T1DM, erectile dysfunction and hypogonadism (total testosterone ≤ 12 nmol/L) received testosterone replacement therapy (TRT). In seven men TRT was intermitted: one man with prostate malignancy and six men because of problems of reimbursement. Incidentally, this provided an opportunity to monitor the effects of withdrawal and of the reinstatement of TRT. In all men, glycemic control (serum glucose and HbA1c), weight, waist circumference, lipid profiles and erectile function improved upon TRT. The seven men whose TRT was intermitted showed a deterioration which improved again upon reinstatement of TRT. The data suggest that aging and obese men with T1DM might have subnormal T levels and that their glycemic control, lipid profiles and erectile function might benefit from TRT. [ABSTRACT FROM PUBLISHER]

Purpose: To investigate the potential benefits of testosterone administration to elderly men (>65 years) with late-onset hypogonadism (LOH) in comparison with younger men and to assess the safety of testosterone administration to elderly men. Materials and Methods: A total of 561 hypogonadal men from two registry studies were divided into age groups of =65 years (group Y, n=450; range, 32-65 years) and >65 years (group O, n=111; range, 66-84 years). Following an initial 6-week interval, all men were treated with 3-month injections of parenteral testosterone undecanoate for up to 6 years. Results: Over the 6 years, there was a progressive decrease of body weight and waist circumference. Beneficial effects on lipids and other metabolic factors and on psychological and sexual functioning progressed over the first 24 to 42 months and were sustained. Rather than a deterioration, there was an improvement of urinary parameters. Prostate volume and prostate-specific antigen increased moderately. Hematocrit levels increased but remained within safe margins. Conclusions: The benefits of restoring serum testosterone in men with LOH were not significantly different between men older than 65 years of age and younger men. There were no indications that side effects were more severe in elderly men. The effects on prostate and urinary function and hematocrit were within safe margins. Age itself need not be a contraindication to testosterone treatment of elderly men with LOH. [ABSTRACT FROM AUTHOR]

Purpose: Many men with 'late-onset hypogonadism' (LOH) experience lower urinary tract symptoms (LUTS) that can be distressing and may decrease quality of life. LUTS often appear in men when testosterone levels begin to decline, which could be a significant association. We investigated whether testosterone replacement could alleviate LUTS in men with LOH. Methods: Two hundred and sixty-one hypogonadal patients (mean age 59.5 years) presenting with erectile dysfunction, having also been evaluated for LUTS, received a single testosterone undecanoate injection at day 1, at week 6 and quarterly thereafter. Parameters, including International Prostate Symptom Score (IPSS), post-voiding residual urine volume, transrectal ultrasound, prostate volume and prostate-specific antigen were measured at each treatment visit. Two hundred and fifty-nine patients were included in the full analysis set. These were subsequently divided into weight losers (L ≥ 5 % weight loss at last visit from baseline) and non-losers (NL). t test analyses were used to compare the IPSS means of these subgroups. The potentially confounding effect on IPSS of using the phosphodiesterase-5 inhibitor (PDE5i) vardenafil was also accounted for. Results: Mean IPSS showed a significant decrease with time following initiation of testosterone treatment ( p < 0.05). No significant differences were observed in either IPSS between L and NL groups or in mean IPSS between vardenafil users and non-users. Conclusion: Testosterone replacement is associated with improvements in LUTS which are not confounded by weight loss or PDE5i. The mechanisms of this association require further investigation. [ABSTRACT FROM AUTHOR]

To investigate effects of long-term testosterone (T) therapy in obese men with T deficiency (TD) and type 2 diabetes mellitus (T2DM), data were collected from two observational, prospective, and cumulative registry studies of 561 men with TD receiving T therapy for up to 6 years. A subgroup of obese hypogonadal men with T2DM was analyzed. Weight, height, waist circumference (WC), fasting blood glucose (FBG), glycated haemoglobin (HbA1c) blood pressure, lipid profile, C-reactive protein (CRP), and liver enzymes were measured. A total of 156 obese, diabetic men with T deficiency, aged 61.17 ± 6.18 years, fulfilled selection criteria. Subsequent to T therapy, WC decreased by 11.56 cm and weight declined by 17.49 kg (15.04%). Fasting glucose declined from 7.06 ± 1.74 to 5.59 ± 0.94 mmol/L (P < 0.0001 for all). HbA1c decreased from 8.08 to 6.14%, with a mean change of 1.93%. Systolic and diastolic blood pressure, lipid profiles including total cholesterol: HDL ratio, CRP, and liver enzymes all improved (P < 0.0001). Long-term T therapy for up to 6 years resulted in significant and sustained improvements in weight, T2DM, and other cardiometabolic risk factors in obese, diabetic men with TD and this therapy may play an important role in the management of obesity and diabetes (diabesity) in men with T deficiency. [ABSTRACT FROM AUTHOR]

The objective was to examine the effects of testosterone administration on symptom scores of lower urinary tract symptoms (LUTS). The literatures on the epidemiological association between the metabolic syndrome, erectile failure and (LUTS) were reviewed. In men with the metabolic syndrome and erectile failure, often lower-than-normal testosterone levels are found. This is less clear for men with LUTS, but the relationship between testosterone and LUTS might be indirect and based on the association of the metabolic syndrome with an overactivity of autonomic nervous system. This overactivity may play a key role in increasing the severity of LUTS above an intrinsic basal intensity that is determined by the genitourinary factors in aging men. Androgen receptors are present in the epithelium of the urethra and the bladder. Testosterone may play a role in the reflex activity of the autonomic nervous system in the pelvis, or may interact with postsynaptic non-genomic receptors suppressing detrusor activity. Human neurons in the wall of the bladder contain nitric oxide synthase. Similar to the penis, testosterone has an impact on nitric oxide synthase. Some studies investigating the effects of normalizing testosterone levels in elderly men have found a positive effect on variables of the metabolic syndrome and, simultaneously, on scores of the International Prostate Symptoms Score (IPSS) which is worthy of further investigation in randomized, controlled and sufficiently powered clinical trials. [ABSTRACT FROM AUTHOR]

Introduction and objective. Androgen deprivation therapy of prostate cancer with luteinizing hormone releasing hormone agonists may result in loss of bone mass, changes in body composition and a deterioration of arterial stiffness. The present study monitored the effects of androgen deprivation therapy in men with insulin-dependent diabetes on glycaemic control and on biochemical cardiovascular risk markers. Methods. Twenty-nine patients from a urology practice were included. All men had insulin-dependent diabetes mellitus prior to being diagnosed with metastatic prostate cancer. In a retrospective analysis, levels of fasting glucose, haemoglobin A1c, insulin requirements, total cholesterol, HDL, LDL, triglycerides, fibrinogen, PAI-1, tPA and C-reactive protein were obtained on at least eight occasions over a period of up to 24 months. Results. Glycaemic control worsened substantially with increases of serum glucose requiring increases in insulin dosages. HbA1c levels rose indicating impaired glycaemic control. All biochemical cardiovascular risk markers deteriorated. Conclusion. In men with insulin-dependent diabetes, androgen deprivation therapy may have negative effects on their glycaemic control and may aggravate the biochemical risk profile of cardiovascular disease to which diabetics are predisposed. These observations are in agreement with the emerging role of low levels of testosterone in metabolic syndrome and insulin resistance. [ABSTRACT FROM AUTHOR]

Administration of testosterone undecanoate (TU) over 12 months to men with sexual dysfunction and signs of the metabolic syndrome, restored their plasma testosterone (T) levels to the mid-range of reference values. This had a beneficial effect on their sexual functioning as evidenced by an improvement of their scores on the International Index of Erectile Function. The scores on the Aging Male Symptoms score, AMS, were also improved. Most impressive were the improvements in the parameters of the metabolic syndrome; they all improved and appeared largely correlated (i.e., decline in waist circumference with declines of plasma cholesterol and LDL and increase in plasma HDL). Sex hormone binding globulin, SHBG, may be considered as an indicator of the severity of the metabolic syndrome; levels of SHBG initially fell, probably as a result of rising plasma T levels. But over the last six months of the observation period when plasma T rose further, there was a significant increase in plasma SHBG which may be interpreted to indicate an improvement of the metabolic syndrome. Blood pressure improved slightly but significantly. In this cohort of elderly men (54-76 years; median 64 years) there were no safety concerns over a one year period of T administration. Prostate specific antigen, PSA, levels remained stable; the International Prostate Symptoms Score, IPSS, improved slightly. Liver functions and plasma glucose remained stable. Hemoglogin and hematocrit values increased significantly but remained within reference values. [ABSTRACT FROM AUTHOR]

New treatment modalities for testosterone deficiency have evolved, such as the gels and the long-acting parenteral testosterone undecanoate (TU). Both fulfill the criteria of adequate androgen therapy, have proven to be effective in ameliorating sexual functions in young and elderly men, and are safe. Their mode of administration could not be more divergent; the gel requires daily application, but TU is administered every 12 weeks intramuscularly. A patient receiving long-acting TU being at higher risk when diagnosed with prostate carcinoma than one being treated with a gel is no longer believed, because the delay between diagnosing and treating prostate carcinomas almost always exceeds the duration of action of TU, which is 12 to 14 weeks. So, TU appears to be a viable alternative to the gels and will be preferred by many patients as a lesser interference with their daily lives. [ABSTRACT FROM AUTHOR]

Sexual potency declines with age, as does the efficiency of erection. Many studies show that different patterns of erectile dysfunction (ED), varying from occasional inability to obtain a full erection, impairment throughout intercourse and total absence of erectile response, might not be triggered by psychological factors only. Recent research indicates that ED relies on organic causes, and has challenged the development of new therapies. One therapeutic approach in patients who have testosterone deficiency is based on androgen therapy. Thus, we reviewed data on testosterone-induced effects relative to erectile function, summarizing the results from studies reported in 1991–2006 on testosterone therapy in patients with ED and hypogonadism, with a special focus on men not responding to phosphodiesterase-5 (PDE-5) inhibitors. We searched several computerized databases parallel with printed bibliographic references. Many studies have established animal models, which confirm that testosterone is important in modulating the central and peripheral regulation of ED. Testosterone deprivation has a strong negative impact on the structure of penile tissues and erectile nerves, which can be prevented by androgen administration. Combined therapy regimens with PDE-5 inhibitors and testosterone might improve ED in patients with hypogonadism of different causes. Thus, androgen treatment in hypogonadic patients, including those unresponsive to PDE-5 inhibitors, often results in an improvement of ED. Testosterone therapy is safe and convenient, while rapidly correcting low testosterone levels. [ABSTRACT FROM AUTHOR]

Testosterone (T) as a compound for treatment of T deficiency has been available for almost 70 years, but the pharmaceutical formulations have been less than ideal. Traditionally, injectable T esters have been used for treatment, but they generate supranormal T levels shortly after the 2-3 weekly injection interval. T levels then decline very rapidly, becoming subnormal during the days preceding the next injection. The rapid fluctuations in plasma T are subjectively experienced as disagreeable. T undecanoate (TU) is a new injectable T preparation with a considerably better pharmacokinetic profile. After two initial injections separated by a 6-week interval, the following intervals between two injections are generally 12 weeks, eventually amounting to a total of four injections per year. Plasma T levels with this preparation are nearly always in the range of normal men, as are its metabolic products estradiol and dihydrotestosterone (DHT). It reverses the effects of hypogonadism on bone and muscle and metabolic parameters, and on sex functions. It is suitable for male contraception. Its safety profile is excellent because of the continuous normalcy of plasma T levels. No polycythemia has been observed and no adverse effects on lipid profiles. Prostate safety parameters are well within reference limits. TU is a valuable treatment option of androgen deficiency. [ABSTRACT FROM AUTHOR]

Recently, testosterone undecanoate (TU), a new parenteral testosterone (T) preparation has been introduced. Two of its distinctive features are (a) its prolonged action: after two initial loading injections 6 weeks apart, usually only one injection every 12 weeks is needed (b) over the full interval between two injections, plasma T levels are in the physiological range. New research presents convincing evidence that T has profound effects on tissues of the penis involved in the mechanism of erection and that testosterone deficiency impairs the anatomical and physiological substrate of erectile capacity, which is, at least, in part reversible upon androgen therapy. Our studies with TU demonstrated that venous leakage could be corrected with T treatment in a number of patients. We further could show that sexual functions, in a substantial number of elderly men, can be restored with treatment with T only. So, these results argue for determination of T levels in elderly men with sexual problems. If the levels are subnormal, T treatment is warranted. [ABSTRACT FROM AUTHOR]

A response from the author of the article "Effects of long-term testosterone therapy on patients with "diabesity": results of observational studies of pooled analyses in obese hypogonadal men with type 2 diabetes" that was published in the previous issue is presented.