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Background/Aim: Single-agent tyrosine kinase inhibitors are still prescribed as first-line treatment to a relevant subgroup of patients with metastatic renal cell carcinoma (mRCC). These agents are known to cause disfunction of many endocrine glands (e.g., thyroid). In this two-step trial, we aimed to assess gonadal function among male patients with mRCC treated with sunitinib. Patients and Methods: We enrolled a first cross-sectional cohort of pre-treated (>6 months) patients and a subsequent cohort of treatment-naïve patients who were prospectively followed-up. All patients were screened for hypogonadism and received a Functional Assessment of Cancer Therapy – General (FACT-G) questionnaire at study entry and after 6 months of therapy. Patients who were candidates for testosterone replacement therapy (TRT) also received a FACT-G questionnaire at baseline and 3 months after supplementation. Results: Among the 30 enrolled patients, the prevalence of hypogonadism was found to be higher in those receiving sunitinib for a longer period (27.3% at baseline, 41.7% in the first 6 months, and 68.4% after 9 months of therapy). The testosterone level of patients correlated with quality of life (R=0.32). A total of six patients received TRT, with a significant improvement in their global quality of life after the first 3 months of treatment. Conclusion: An increasing prevalence of hypogonadism was seen among male patients who received long-term treatment with sunitinib. TRT was associated with relevant improvements in quality of life. These findings corroborate similar published observations and encourage the assessment of gonadal function in male patients with mRCC under treatment with sunitinib.

Considerable research has shown that testosterone regulates many physiological systems, modulates clinical disorders, and contributes to health outcome. However, studies on the interaction of testosterone levels with depression and the antidepressant effect of testosterone replacement therapy in hypogonadal men with depression have been inconclusive. Current findings indicate that low circulating levels of total testosterone meeting stringent clinical criteria for hypogonadism and testosterone deficiency induced by androgen deprivation therapy are associated with increased risk for depression and current depressive symptoms. The benefits of testosterone replacement therapy in men with major depressive disorder and low testosterone levels in the clinically defined hypogonadal range remain uncertain and require further investigation. Important considerations going forward are that major depressive disorder is a heterogeneous phenotype with depressed individuals differing in inherited polygenic determinants, onset and clinical course, symptom complexes, and comorbidities that contribute to potential multifactorial differences in pathophysiology. Furthermore, polygenic mechanisms are likely to be critical to the biological heterogeneity that influences testosterone-depression interactions. A genetically informed precision medicine approach using genes regulating testosterone levels and androgen receptor sensitivity will likely be essential in gaining critical insight into the role of testosterone in depression.

Osteoporosis does not only affect postmenopausal women, but also ageing men. The burden of disease is projected to increase with higher life expectancy both in females and males. Importantly, osteoporotic men remain more often undiagnosed and untreated compared to women. Sex steroid deficiency is associated with bone loss and increased fracture risk, and circulating sex steroid levels have been shown to be associated both with bone mineral density and fracture risk in elderly men. However, in contrast to postmenopausal osteoporosis, the contribution of relatively small decrease of circulating sex steroid concentrations in the ageing male to the development of osteoporosis and related fractures, is probably only minor. In this review we provide several clinical and preclinical arguments in favor of a 'bone threshold' for occurrence of hypogonadal osteoporosis, corresponding to a grade of sex steroid deficiency that in general will not occur in many elderly men. Testosterone replacement therapy has been shown to increase bone mineral density in men, however data in osteoporotic ageing males are scarce, and evidence on fracture risk reduction is lacking. We conclude that testosterone replacement therapy should not be used as a sole bone-specific treatment in osteoporotic elderly men. ispartof: REVIEWS IN ENDOCRINE & METABOLIC DISORDERS vol:23 issue:6 pages:1173-1208 ispartof: location:Germany status: published

Serum levels of testosterone (ST) and high-density lipoprotein (HDL) are generally associated with atherosclerosis in male patients over 50 years with critic iliac stenosis (TASC II A and B) and cardiovascular disease with significant changes in HDL and low-density lipoprotein (LDL). In addition to the standard therapy, combined medicamentous therapy and adequate model of exercise are also important factors as medicines can improve HDL levels and primary bypass and endovascular potency impacting positively on improvement of ST or it can be the following testosterone replacement therapy (TRT) comprising cardiovascular disease prevention and vascular treatment as adjunct therapy options after endovascular and vascular surgical procedures. The aim of the study is to identify the association between HDL and ST after surgical and endovascular intervention on the iliac segment (TASCII A and B), as well as cardiovascular risk factors with modified medium activity (MET) 6 (MET), with total duration of 30–60 minutes. It also attempts to remodel a patient behavioral pattern, optimize ST levels and link them to outcomes and patency of vascular procedures on the iliac segment. Materials and methods. 108 selected male patients with cardiovascular disease combined with metabolic syndrome and critical iliac artery stenosis (TASC II A and B) were examined during 2014–2018, 4 years after invasive and minimal invasive treatment (54 patients were treated with surgical Dacron reconstruction and 54 patients – with endovascular treatment on short segment of critical iliac artery stenosis (TASC II A and B). Results. In the total population, no difference was observed in changes of constraint-induced movement therapy between the standard exercise group and the control one after 4 years from baseline. However, there was no significant interaction between the effect of exercise trainings and primary bypass potency within 4 years. Conclusions. Primary effects of endovascular procedure and Dacron bypass revascularization raise the risk of elevated testosterone levels after 4 years of group training but does not provide adequate answers to questions as to whether higher levels of ST have any major influence on primary bypass potency preventing further progression of cardiovascular disease and general symptomatic and asymptomatic atherosclerosis. However, exercise and TRT can be potential adjunctive therapeutic options for a future supporting postsurgical and endovascular illiac treatment in cardiovascular patients with low testosterone levels., Рівень загального тестостерону (ЗТ) і ліпопротеїдів високої щільності (ЛПВЩ) загалом пов’язані з атеросклерозом у пацієнтів-чоловіків віком понад 50 років із критичним клубовим стенозом (TASC II A та B) і серцево-судинними захворюваннями зі значними змінами рівнів ЛПВЩ і ліпопротеїдів низької щільності. Крім стандартної терапії, необхідно поєднувати медикаментозну терапію з адекватною моделлю фізичних вправ, оскільки ліки можуть також бути важливим фактором для підвищення рівня ЛПВЩ, ефективності первинного шунтування та ендоваскулярної терапії, що сприяє підвищенню рівня тестостерону, або це наступний рівень замісної терапії тестостероном (ЗТТ), який передбачає профілактику та лікування серцево-судинних захворювань, і судинної недостатності як варіанти допоміжної терапії після ендоваскулярних і судинних хірургічних процедур. Мета роботи – виявити асоціацію ЛПВЩ і загального тестостерону (ЗТ) після хірургічного та ендоваскулярного втручання клубового сегмента (TASC II A і B), а також факторів серцево-судинного ризику з модифікованою середньою активністю (МЕТ) 6 (МЕТ), загальною тривалістю 30–60 хвилин. Також зроблено спробу змінити модель поведінки пацієнта, оптимізувати рівень ЗT у сироватці крові та зв’язати їх із результатом і прохідністю судинної процедури клубового сегмента. Матеріали та методи. 108 пацієнтів чоловічої статі з серцево-судинними захворюваннями, метаболічним синдромом і критичним стенозом клубової артерії (TASC II A і B) перебували під спостереженням протягом 2014–2018 рр., через 4 роки після інвазивного та мінімального інвазивного лікування (54 пацієнти, яким здійснили хірургічну реконструкцію дакроном, і 54 пацієнти з ендоваскулярним лікуванням короткого сегмента критичного стенозу клубової артерії (TASC II A і B)). Результати. У загальній популяції не виявили різницю за змінами обмежено-індукованої рухової терапії порівняно з вихідним рівнем через 4 роки між групою, де пацієнти виконували стандартні фізичні вправи, і контрольною групою. Втім, протягом 4 років не встановили значущі зв’язки між ефектом фізичних вправ і первинною шунтувальною потенцією. Висновки. Первинна ефективність ендоваскулярної процедури та реваскуляризації дакронового шунтування після чотирьох років групових тренувань підвищує ризик збільшення рівня тестостерону, але не дає адекватної відповіді на запитання про те, чи має якийсь суттєвий вплив на ефективність первинного шунтування та вищий рівень ЗТ, що запобігає наступному прогресуванню серцево-судинних захворювань і загального симптоматичного, безсимптомного атеросклерозу. Втім, при низьких рівнях ЗТ за допомогою фізичних вправ і ЗТТ може бути потенційним варіантом допоміжної терапії для майбутнього підтримувального післяхірургічного й ендоваскулярного лікування пацієнтів із серцево-судинними захворюваннями із низьким рівнем тестостерону.

Objective: This study aimed to investigate the frequency of sexual dysfunction and the effect of short-term testosterone replacement therapy on sexual functions in congenital hypogonadism patients. Furthermore, we sought to reveal the consistency of the self-report scales used for the diagnosis of sexual dysfunction and the relationship between biochemical parameters. Materials and methods: The study was conducted on 47 young male patients aged above 18 years who were diagnosed with hypogonadotropic hypogonadism. Short (IIEF-5) and long (IIEF-15) forms of the International Index of Erectile Function and Arizona Sexual Experiences Scale (ASEX) were applied before treatment under the supervision of a physician. The patients’ blood pressure, height, and weight were measured, and their luteinizing hormone (LH), FSH, and total testosterone levels were recorded. Patients who started their treatments were called for a follow-up checkup after 6 months. Their blood pressure, height, and weight were measured by reapplying the ASEX, IIEF-5, and IIEF-15. In addition, their LH, FSH, and total testosterone levels in the biochemical tests were rerecorded. Results: In this study, the sexual dysfunction status of patients diagnosed with hypogonadotropic hypogonadism before and after treatment was evaluated using the ASEX, IIEF-15, and IIEF-5 scales. A decrease in sexual dysfunction was observed in all three scales after treatment compared with that before treatment. The IIEF-5 and IIEF-15 scales were found to be uncorrelated in terms of the pretreatment values but were correlated in terms of the post-treatment values. Although a correlation was observed between ASEX and IIEF-5 before treatment, no correlation was detected between ASEX and IIEF-15. After the treatment, ASEX was found to be correlated with both IIEF-5 and IIEF-15. The results of the scales indicated the correlation in all categories, except the pretreatment results of the IIEF-15 scale. Conclusion: The results of the current study demonstrated a significant improvement in the sexual function of hypogonadism patients undergoing short-term testosterone therapy. The ASEX, IIEF-5, and IIEF-15 scales used in the diagnosis and follow-up of sexual dysfunction were useful for evaluating sexual functions in hypogonadotropic hypogonadism patients.

(Background) The aim of our study was to evaluate the efficacy and safety of testosterone replacement therapy (TRT) in men with chronic kidney disease and hypogonadism on conservative and hemodialysis treatment. (Methods) The studied population consisted of 38 men on hemodialysis (HD), 46 men with CKD stages II-IV (predialysis group, PreD) and 35 men without kidney disease who were similar in age to others (control group). Serum total testosterone level (TT) was measured, and free testosterone level (fT) was calculated. Hypogonadism criteria according to the EAU definition were fulfilled by 26 men on HD (68.4%) and by 24 men from the PreD group (52%). Testosterone replacement therapy (TRT) with testosterone enanthate in intramuscular injections every 3 weeks was applied in 15 men from HD and in 14 men from PreD. The safety of TRT was monitored by measuring PSA and overhydration. (Results) A significant rise of TT and fT was observed after 3 months of TRT, but no significant changes were observed after 6 and 12 months in the HD and PreD group. An intensity of clinical symptoms of hypogonadism measured by ADAM (androgen deficiency in the ageing male) questionnaire gradually decreased, and the intensity of erectile dysfunction measured by the IIEF-5 (international index of erectile functioning) questionnaire also decreased after 3, 6 and 12 months of TRT in the HD and PreD group. (Conclusions) The applied model of TRT is effective in the correction of clinical signs of hypogonadism without a significant risk of overhydration or PSA changes.

Background: The common pathogenetic relations of type 2 diabetes mellitus (T2DM), testosterone (T) deficiency and non-alcoholic fatty liver disease (NAFLD) have indicated a new direction in the study of their mutual influence. It was found that NAFLD is more pronounced in men with T2DM and hypogonadism than in eugonadal patients and associated with hyperinsulinemia, insulin resistance, impaired lipid metabolism and adipose tissue dysfunction. However, the effects of testosterone replacement therapy (TRT) on the severity of NAFLD in men with hypogonadism have not been studied.Aims: To study the effect of TRT on the severity of NAFLD in men with T2DM and hypogonadism.MATERIALS AND METHODS: Anthropometric data, biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltranspeptidase (GGTP), glucose, immunoreactive insulin, HOMA index, glycosylated hemoglobin, lipidogram), ELISA analysis (total T, LH, sex hormone binding globulin, resistin, adiponectin, leptin), as well as magnetic resonance imaging with determination of the liver fat fraction were examined.Results: The study included 60 men with T2DM and hypogonadism (mean age 54 [49; 57] years), who were randomized into 2 groups: 1 (n=30) - patients who received 1% transdermal T gel (50 mg/day) in addition to standard hypoglycemictherapy; 2 (n=30) - patients who received standard hypoglycemic therapy. The follow-up period was 6 months. T therapy was associated with a decrease in liver enzyme levels: AST by 31%, ALT by 21%, and GGTP by 15.9% (pConclusions: TRT in men with T2DM and hypogonadism is accompanied by regress of inflammatory activity in liver and intensity of hepatocytes steatosis, reflected by decrease in liver enzymes levels and liver fat fraction.

Male hypogonadism is notoriously associated with altered lipid metabolism. In this study, we performed an untargeted mass spectrometry–based profiling of plasma lipids from twenty healthy and twenty hypogonadal men before and after testosterone replacement therapy (TRT) for 60 days. Results demonstrated that hypogonadism was associated with a significant increase in sphingomyelin (SM), whereas phosphatidylcholine (PC) was mainly cleaved by activated phospholipase‐A2 into lysophosphatidylcholine (LPC). In hypogonadal patients, arachidonic acid (AA), also produced through the latter cleavage, was prevalently bio‐transformed into leukotriene B4 (LTB4) and not into endoperoxides from which prostaglandins and thromboxanes are derived. Interestingly, upon testosterone treatment SM, PC and LPC returned to levels similar to controls. Also, AA was newly converted into prostaglandin‐A2, thromboxane‐A2 and 5(S)‐hydroxyeicosatetraenoic acid (HETE), suggesting that testosterone probably plays a role in controlling hypogonadal alterations above reported.

OBJECTIVE: Men with male hypogonadism (MH) experience sexual dysfunction, which improves with testosterone replacement therapy (TRT). However, randomised controlled trials provide little consensus on functional and behavioural symptoms in hypogonadal men; these are often better captured by qualitative information from individual patient experience. METHODS: We systematically searched major electronic databases to identify qualitative data from men with hypogonadism, with or without TRT. Two independent authors performed the selection, extraction, and thematic analysis of data. Quality of eligible studies was assessed using the Critical Appraisals Skills Programme and Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research tools. RESULTS: We analysed data from five studies published in nine reports that assessed a total of 284 participants. Published data were only available within North America, with no ethnic minority or other underserved groups included. In addition to sexual dysfunction, men with MH experienced adverse changes in physical strength, perceptions of masculinity, cognitive function, and quality of life. The experience of MH appeared dependent on the source(s) of educational material. DISCUSSION: We propose a patient-centred approach to clinician interactions rather than focusing on discreet MH symptoms. Current evidence about the experience of MH is limited to North America and predominantly white ethnicity, which may not be broadly applicable to other geographic regions. Broadening our understanding of the MH experience may improve the targeting of information to patients. In addition, a multidisciplinary approach may better address symptoms neither attributable to MH nor alleviated by TRT.

Testosterone replacement therapy (TRT) has become increasingly popular over the years and there has been an increasing debate on whether testosterone replacement should be offered to older men due to its association with cardiovascular events. In this study, we evaluated the risk of myocardial infarction (MI) associated with TRT in hypogonadal men through a meta-analysis. We carried out the analysis by following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and conducted a literature search utilizing the following databases: Google Scholar, PubMed, Science Direct, Cochrane Library trials, and ClinicalTrials.gov. The search strategy resulted in a total of 782 articles, after applying our inclusion and exclusion criteria. Six observational studies and two randomized controlled trials (RCTs) were included for the analysis. A total of 55,806 hypogonadal men with baseline testosterone levels

In the present study, the initial treatment efficiency of combination therapy using testosterone replacement therapy (TRT), herbal medicine and phosphodiesterase 5 inhibitors (PDE5i) in male patients with late-onset hypogonadism (LOH) were assessed. A total of 21 patients were enrolled and after 12 weeks, the clinical efficacy was evaluated based on improvement of LOH symptoms via laboratory parameters and several questionnaires, including the Ageing Males' Symptoms (AMS) scale. The overall AMS scores, as well as the psychological, physical and sexual AMS factors prior to and after treatment in the TRT, testosterone enanthate (T enanthate) monotherapy and T enanthate + PDE5i treatment groups were significantly improved. In the herbal medicine group, only the AMS physiological factors were significantly improved after treatment compared with the baseline. The improvement of the overall AMS scores, as well as the physiological and sexual AMS factors, were significantly negatively correlated with the free testosterone (FT) value prior to treatment. In conclusion, treatment with combination therapy using TRT, herbal medicine and PDE5i improved AMS scores in patients with LOH syndrome. Particularly in patients with LOH syndrome and low FT, the symptoms were significantly improved following combination therapy.

Klinefelter syndrome (KS) is a common cause of non-obstructive azoospermia (NOA). Advances in fertility preservation (FP) techniques, such as the use of microdissection testicular sperm extraction (micro-TESE), have improved sperm retrieval rates (SRR) up to 40–50% in this population. Age has been suggested to have an impact on FP, postulating that sperm production may deteriorate over time due to germ cell loss. As such, sperm retrieval for patients with KS at a younger age has been proposed to further improve SRR; however, whether such practice pragmatically improves SRR is yet to be determined, and controversy remains with concerns over trauma caused by FP procedures on further impairment of testicular function. There has also been a debate on the ethics of performing FP procedures in the pediatric population. Optimizing FP for patients with KS invariably requires a holistic multidisciplinary approach. This review aimed to evaluate the latest evidence in performing FP in pediatric patients with KS, and discuss the controversy surrounding such practice. Hormonal changes in patients with KS during childhood and the use of hormonal manipulation to optimize SSR in this population have also been reviewed.

Introduction Post-orgasmic illness syndrome is a rare condition that occurs after ejaculation and persists for 2-7 days and is characterized by flu-like symptoms, which can significantly reduce quality of life. Case presentation A 21-year-old unmarried man was referred to our hospital due to flu-like symptoms that developed after ejaculation by masturbation and persisted for about 2 days. The patient's free testosterone level was slightly lower than normal. Nonsteroidal anti-inflammatory drugs were initially administered and helped relieve headache and muscle pain. Thereafter, the patient was able to ejaculate three times a week. In addition, after administering testosterone enanthate once or twice a month, his general fatigue significantly improved, and he could ejaculate every day. Conclusion The pathophysiology of post-orgasmic illness syndrome has not been fully elucidated. The treatments for this condition must be accurately selected according to pathophysiology.

The single most significant risk factor for testosterone deficiency in men is obesity. The pathophysiological mechanisms involved in male obesity-related secondary hypogonadism are highly complex. Obesity-induced increase in levels of leptin, insulin, proinflammatory cytokines and oestrogen can cause a functional hypogonadotrophic hypogonadism with the defect present at the level of the hypothalamic gonadotrophin-releasing hormone (GnRH) neurons. The resulting hypogonadism by itself can worsen obesity, creating a self-perpetuating cycle. Obesity-induced hypogonadism is reversible with substantial weight loss. Lifestyle-measures form the cornerstone of management as they can potentially improve androgen deficiency symptoms irrespective of their effect on testosterone levels. In selected patients, bariatric surgery can reverse the obesity-induced hypogonadism. If these measures fail to relieve symptoms and to normalise testosterone levels, in appropriately selected men, testosterone replacement therapy could be started. Aromatase inhibitors and selective oestrogen receptor modulators are not recommended due to lack of consistent clinical trial-based evidence.

Testosterone replacement therapy (TRT) is recommended for the treatment of most cases of male hypogonadism. Transdermal testosterone (T) gels are commonly used in clinical practice; however, there is little evidence concerning how to monitor dosage to bring and maintain serum T levels in the normal physiologic range.We examined 30 hypogonadal patients undergoing treatment with 40 mg/day transdermal 2% testosterone gel. After a week from treatment onset, all patients underwent a total of four measurements to assess serum total T, bioavailable T and free T at + 2 h (samples A and A') and + 23 h (samples B and B').No significant difference was found concerning total, free and bioavailable T between the two samples taken at the same time points (A vs A' and B vs B'). A repeated-measures mixed effects regression model showed significantly lower serum levels of total, free and bioavailable T at + 23 h compared to + 2 h (total T, β = - 3.050 ± 0.704, p 0.001; free T, β = - 85.187 ± 22.746, p 0.001; bioavailable T, β = - 1.519 ± 0.497, p = 0.003) without a significant between-sample variability. Serum T 3.5 ng/ml at + 2 h was reached in 21/30 patients (70%), but only 11 (36.7%) still had adequate serum T at + 23 h.Assessment of TRT with transdermal gels at its peak and at its minimum could be useful in providing a finely tailored treatment for hypogonadal men, both preventing supra-physiological levels and maintaining adequate concentrations through the day.

Jenny Retzler,1 Adam B Smith,1 Ana Sofia Oliveira Gonçalves,2 Jennifer A Whitty21York Health Economics Consortium, Enterprise House, York YO10 5NQ, UK; 2Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UKObjectives: Differences in testosterone replacement therapy (TRT) gel products may affect patient satisfaction, quality-of-life, and treatment response and adherence. This study investigated preferences for TRT gel in terms of formulation and administration.Methods: 525 male adults aged 45 years and over completed a discrete choice experiment. Respondents made repeated choices between two hypothetical testosterone gel treatments described according to four attributes: form, ease of use, impact of use on showering/swimming, and location/dosage of the application. Choice data were analyzed using a latent class model.Results: Three preference classes were identified. Respondents across all classes displayed a preference for the gel being dispensed in smaller units with accurate dosing, waiting shorter times after the gel application before swimming/showering, and using 2.5 gm of gel to be applied to the inner thigh/abdomen as opposed 5 gm to shoulder/abdomen. The importance of these characteristics differed across classes, with preference class membership predicted by age and education level. For instance, younger men (aged 45–64 years) were more likely to belong to a class that prioritized reduced waiting time before being able to undertake activities. Formulation was not an important driver of choice.Conclusions: Preferences demonstrate a predilection for TRT gel dispensed in small units allowing precise dosing, shorter waiting time after application, and application to the inner thigh/abdomen. However, the strength of importance of these characteristics differs between men. This study highlights the attributes of TRT gel considered important to patient subgroups, and which may ultimately affect treatment response, medication adherence, and patient quality-of-life.Keywords: testosterone replacement therapy, discrete choice experiment, patient preferences

The risk of adverse cardiovascular events and mortality associated with testosterone replacement therapy is controversial. The purpose of this report was to evaluate the effect of testosterone replacement therapy (TRT) in men with secondary hypogonadism on the risk of myocardial infarction (MI), stroke (CVA) or all-cause mortality.A retrospective cohort study was conducted using the Cleveland Clinic's electronic health record. Men ≥40 years of age, with at least two testosterone levels 220 ng/dL, with one level obtained between 7 am and 10 am, were identified. Men with primary hypogonadism, secondary hypogonadism related to overt hypothalamic pituitary pathology, human immunodeficiency virus infection, metastatic cancer, and select contraindications to TRT, were excluded. Men exposed to TRT were matched to controls that were not exposed. A survival analysis was performed on the composite outcome of MI, CVA, or all-cause mortality.One hundred sixty-five patients exposed to TRT (treatment group) were matched with 210 not exposed to TRT (comparison group). The prevalence of established cardiovascular disease (CVD) was 20.0% in the treatment group vs. 17.1% in the comparison group (In hypogonadal men with a modest prevalence of established CVD, TRT was not observed to confer a protective or adverse effect on the risk of MI, CVA or all-cause mortality.Le risque d’événements cardiovasculaires indésirables et de mortalité associé au traitement de substitution de la testostérone est controversé. Le but du présent article est d’évaluer chez les hommes qui présentent un hypogonadisme secondaire l’effet du traitement de substitution de la testostérone (TST) sur le risque d’infarctus du myocarde (IM), d’accident cérébrovasculaire (ACV) ou de mortalité toutes causes confondues.Une étude de cohorte rétrospective a été menée en utilisant les dossiers de santé électroniques de la Clinique Cleveland. Ont été identifiés les hommes âgés de plus de 40 ans qui avaient au moins deux dosages de testostérone inférieurs à 220ng/dl, dont l’un obtenu le matin entre 7 et 10 heures. Ont été exclus les hommes qui présentaient un hypogonadisme primaire, un hypogonadisme secondaire lié à une pathologie hypothalamo-hypophysaire évidente, une infection par le virus de l’immunodéficience humaine, un cancer métastatique, et ceux qui présentaient des contrindications déterminées au TST. Les hommes exposés au TST ont été appariés à des témoins non exposés au TST. Une analyse de survie a été réalisée sur le paramètre composite incluant l’IM, l’AVC et la mortalité toutes causes confondues.165 patients exposés au TST (groupe traité) ont été appariés à 210 hommes non exposés au TST (groupe de référence). La prévalence de maladie cardiovasculaire (MCV) établie était de 20.0% dans le groupe traité versus 17.1% dans le groupe de référence (P=0.478). La médiane (écart interquartile (EI)) de l’âge et de l’indice de masse corporelle (IMC) était respectivement de 55 (49, 62) ans et de 35.6 (32.1, 40.1) kg/m2 dans le groupe traité, et respectivement de 55 (49, 61.7) ans et 36.3 (32.1, 40.8) kg/m2 dans le groupe de référence. Il y eut 12 événements indésirables (7.3%) dans le groupe traité, et 16 (7.6%) dans le groupe de référence. La médiane du temps (en années) des événements composites était de 2.1 (EI 0.9, 4.6) et de 1.8 (EI 0.6, 3.4) respectivement pour les groupes traité et de référence. Aucune différence n’a été observée en ce qui concerne le risque cardiovasculaire entre le groupe traité et le groupe de référence, rapport de risque (RR) 0.81 (Intervalle de Confiance à 95% [IC]: 0.38-1.71;Chez les hommes qui présentent un hypogonadisme et une faible prévalence de maladie cardiovasculaire (MCV) établie, le TST n’apparait pas conférer un effet protecteur ou défavorable sur le risque de d’infarctus du myocarde (IM), d’accident cérébrovasculaire (ACV) ou de mortalité toutes causes confondues.Traitement de substitution de la testostérone, Hypogonadisme masculin, Risque cardiovasculaire, Mortalité.

Introduction Hypogonadotropic hypogonadism is a common disorder associated with type 2 diabetes. Hypogonadotropic hypogonadism in type 2 diabetic patients requires further assessment to understand the etiology, and the possible consequences, complications, and treatment This study aims to highlight the testosterone level in type 2 diabetes mellitus (DM). Moreover, it further emphasizes the association of testosterone with the duration of DM. Materials and method This case-control survey was conducted from September 2020 to March 2021 in the outpatient department of internal medicine in a tertiary care hospital in Pakistan. The experiment group included 200 diabetic male participants aged between 30 and 69 years. In the control group, 200 participants without DM were enrolled in the study. The venous blood sample was collected via phlebotomy and sent to the laboratory to test for total testosterone level. Results The mean total testosterone level was significantly lower in diabetic patients compared to the non-diabetic patients (8.9 ± 5.1 mmol/L vs. 14.1 ± 7.2 mmol/L; p-value

Background: The etiology of benign prostatic hyperplasia and prostate cancer are unknown, with ageing being the greatness risk factor. Methods: This new perspective evaluates the available interdisciplinary evidence regarding prostate ageing in terms of the cell biology of regulation and homeostasis, which could explain the timeline of evolutionary cancer biology as degenerative, inflammatory and neoplasm progressions in these multifactorial and heterogeneous prostatic diseases. Results: This prostate ageing degeneration hypothesis encompasses the testosterone-vascular-inflamm-ageing triad, along with the cell biology regulation of amyloidosis and autophagy within an evolutionary tumorigenesis microenvironment. Conclusions: An understanding of these biological processes of prostate ageing can provide potential strategies for early prevention and could contribute to maintaining quality of life for the ageing individual along with substantial medical cost savings.

Testosterone replacement therapy (TRT) is an industry on the rise in large part due to an increase in direct-to-customer advertising targeting middle-aged men with non-specific symptoms. The biggest problem with unnecessary prescribing is that testosterone therapy is not without side effects. One of the more common adverse effects is erythrocytosis with subsequent thrombosis. It was originally postulated that thrombosis seen in patients on TRT was solely related to increasing in hemoglobin however, new studies demonstrate increasing episodes of thrombosis unrelated to hemoglobin or hematocrit. We report the case of a 38-year-old white male presenting to the clinic with infarction of bilateral feet and digits due to testosterone-induced thrombosis of dermal and epidermal arteries. Laboratory workup including vasculitis panel was negative and complete blood count (CBC) was within appropriate parameters. He was treated with anticoagulation, pain control, and vasodilatory therapy with subsequent improvement of symptoms. There have been many reported cases of testosterone-induced thrombosis of the venous system with occasional involvement of the renal arteries. However, cases involving thrombosis of dermal or epidermal arteries due to testosterone supplementation have never been reported. It could be beneficial to screen potential patients requiring TRT for hypercoagulable states such as Factor V Leiden and lupus anticoagulant.

The pandemic acute respiratory syndrome coronavirus 2 (SARS-CoV-2) named COVID-19 is causing a severe health emergency, and an individual’s hormonal milieu may play an important role in both susceptibility to infection and severity of clinical course. We analyzed the role of testosterone in the immune response, and we hypothesized possible mechanisms to explain the high incidence of COVID-19 infection and a worse clinical course in elderly male patients. Testosterone may impair the immune response, and this effect could explain the greater susceptibility of men to infection. Transmembrane serine protease 2 (TMPRSS2) plays a crucial role in the entry of the virus into the respiratory epithelial cells, leading to COVID-19 disease. It is crucial to emphasize that testosterone levels and chemical castration (e.g. by androgen deprivation therapy for prostate cancer) may have contrasting roles in the phases of COVID-19 infection. Whereas low testosterone levels may be protective against the initial susceptibility (due to a restoration of immunological functions and a block of TMPRSS2), low testosterone may stimulate a worse clinical course in the advanced COVID-19 infection as it could exacerbate or activate the cytokine storm. If testosterone levels play these different roles, it is necessary to carefully identify patients for any indicated testosterone manipulation.

Purpose We aimed to verify if 1 year-testosterone-replacement therapy could produce a psychopathological recovery and a satisfactory quality of life in Klinefelter syndrome (KS) patients compared to matched healthy controls. Further, we analyzed personality traits and coping strategies, an issue not yet examined in androgen-treated KS patients. We also enquired whether any of the sociodemographic and psychological variables might predict a patient’s general and sexual life satisfaction. Methods The Quality of Life Enjoyment and Satisfaction Questionnaire and the Temperament and Character Inventory-Revised were administered to both 23 KS patients and matched healthy subjects. Psychopathology was investigated by the Symptom Checklist-90-Revised (SCL-90-R) and the Mini-mental State Examination. The COPE Inventory was used to identify cognitive and behavioral strategies to manage disease-related distress. Results In testosterone-treated KS patients, when compared with controls, SCL-90-R subscales analysis evidenced high psychological distress, mainly presented as obsessive thoughts, hanger-hostility, phobias, and psychoticism. Self-directedness and self-transcendence, along with the prevalent use of emotion-focused coping strategies, outlined the personality of our KS patients. Depression and somatization proved to be predictors of general life dissatisfaction. Depression, anger-hostility, and paranoid ideation, instead, emerged as predictors of sexual life dissatisfaction. Conclusion Endocrinologists should cooperate with mental health providers to foster a better outcome of the disease in KS patients.

Contains fulltext : 245049.pdf (Publisher’s version ) (Open Access) BACKGROUND: Knowledge about Klinefelter syndrome (KS) has increased substantially since its first description almost 80 years ago. A variety of treatment options concerning the spectrum of symptoms associated with KS exists, also regarding aspects beyond testicular dysfunction. Nevertheless, the diagnostic rate is still low in relation to prevalence and no international guidelines are available for KS. OBJECTIVE: To create the first European Academy of Andrology (EAA) guidelines on KS. METHODS: An expert group of academicians appointed by the EAA generated a consensus guideline according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. RESULTS: Clinical features are highly variable among patients with KS, although common characteristics are severely attenuated spermatogenesis and Leydig cell impairment, resulting in azoospermia and hypergonadotropic hypogonadism. In addition, various manifestations of neurocognitive and psychosocial phenotypes have been described as well as an increased prevalence of adverse cardiovascular, metabolic and bone-related conditions which might explain the increased morbidity/mortality in KS. Moreover, compared to the general male population, a higher prevalence of dental, coagulation and autoimmune disorders is likely to exist in patients with KS. Both genetic and epigenetic effects due to the supernumerary X chromosome as well as testosterone deficiency contribute to this pathological pattern. The majority of patients with KS is diagnosed during adulthood, but symptoms can already become obvious during infancy, childhood or adolescence. The paediatric and juvenile patients with KS require specific attention regarding their development and fertility. CONCLUSION: These guidelines provide recommendations and suggestions to care for patients with KS in various developmental stages ranging from childhood and adolescence to adulthood. This advice is based on recent research data and respective evaluations as well as validations performed by a group of experts.

Opioids play a pivotal role in managing chronic pain with increasing prescription rates over the last few years. Hence, it is crucial to focus on the adverse effects of narcotics, and one of the lesser-known side effects is hypogonadism. Opioids act on the hypothalamus, pituitary, and directly on the gonads affecting serum testosterone levels. Narcotic-induced androgen insufficiency contributes to sexual dysfunction, infertility, hyperalgesia, and involving various body functions overall, affecting the quality of life. Opioid-induced hypogonadism is very challenging to diagnose for the clinicians, as the patients often under-report the symptoms. There are no established guidelines to analyze androgen insufficiency and dealing with their manifestations successfully. We did a substantial search in PubMed and Google Scholar, using various combinations of keywords to collect data to evaluate the impacts of opioids on serum testosterone levels. This study aims to highlight the clinical significance of opioid-induced androgen deficiency and the diagnostic techniques to recognize and credible treatment alternatives, including testosterone replacement therapy. Health care providers should screen the patients routinely for the signs and symptoms and monitor them often for the hormonal changes to select the patients cautiously for testosterone replacement therapy.

Background Despite the results of the Testosterone Trials, physicians remain uncomfortable treating men with hypogonadism. Discouraged, men increasingly turn to social media to discuss medical concerns. Objective The goal of the research was to apply natural language processing (NLP) techniques to social media posts for identification of themes of discussion regarding low testosterone and testosterone replacement therapy (TRT) in order to inform how physicians may better evaluate and counsel patients. Methods We retrospectively extracted posts from the Reddit community r/Testosterone from December 2015 through May 2019. We applied an NLP technique called the meaning extraction method with principal component analysis (MEM/PCA) to computationally derive discussion themes. We then performed a prospective analysis of Twitter data (tweets) that contained the terms low testosterone, low T, and testosterone replacement from June through September 2019. Results A total of 199,335 Reddit posts and 6659 tweets were analyzed. MEM/PCA revealed dominant themes of discussion: symptoms of hypogonadism, seeing a doctor, results of laboratory tests, derogatory comments and insults, TRT medications, and cardiovascular risk. More than 25% of Reddit posts contained the term doctor, and more than 5% urologist. Conclusions This study represents the first NLP evaluation of the social media landscape surrounding hypogonadism and TRT. Although physicians traditionally limit their practices to within their clinic walls, the ubiquity of social media demands that physicians understand what patients discuss online. Physicians may do well to bring up online discussions during clinic consultations for low testosterone to pull back the curtain and dispel myths.

Background Men who contract coronavirus disease 2019 (COVID-19) appear to have worse clinical outcomes compared with women which raises the possibility of androgen-dependent effects. Aim We sought to determine if testosterone replacement therapy (TRT) is associated with worse clinical outcomes. Methods Through a retrospective chart review, we identified 32 men diagnosed with COVID-19 and on TRT. They were propensity score matched to 63 men diagnosed with COVID-19 and not on TRT. Data regarding comorbidities and endpoints such as hospital admission, intensive care unit admission, ventilator utilization, thromboembolic events, and death were extracted. Chi-square and Kruskal-Wallis tests examined differences in categorical and continuous variables, respectively. Logistic regression analysis tested the relationship between TRT status and the study endpoints. Results There were no statistically significant differences between the 2 groups, and TRT was not a predictor of any of the endpoints on multivariate analysis. Conclusion These results suggest that TRT is not associated with a worse clinical outcome in men diagnosed with COVID-19. Rambhatla A, Bronkema CJ, Corsi N, et al. COVID-19 Infection in Men on Testosterone Replacement Therapy. J Sex Med 2021;18:215–218.

Background. Epidemiological data report that male hypogonadism may play a role in cognitive impairment in elderly. However, the effect of testosterone replacement therapy (TRT) on cognitive abilities in this cluster of patients has not been well established. Methods. PubMed/MEDLINE, Google Scholar, Cochrane Library, and Web of Science were searched by using free text words and medical subject headings terms related with “male hypogonadism”, “late-onset hypogonadism”, elderly, cognition, “mild cognitive impairment”, memory, “testosterone replacement therapy” used in various combinations according to the specific clinical questions. Original articles, reviews, and randomized controlled trials written in English were selected. Results. A long-term TRT could improve specific cognitive functions, such as verbal and spatial memory, cognitive flexibility, and physical vitality. However, randomized controlled trials do not provide positive results, and in most of the cases TRT might not induce beneficial effects on cognitive function in elderly men. Discussion and conclusions. Since the lengthening of life expectancy, the prevalence rate of cognitive decline in elderly men is expected to increase remarkably over the next decade with considerable healthcare and economical concerns. Therefore, this remains a relevant clinical topic and further investigations are needed for clarifying the role of TRT especially in elderly men with hypogonadism.

Background Recent epidemiological data indicate that there may be a gender predisposition to COVID-19, with men predisposed to being most severely affected, and older men accounting for most deaths. Objectives Provide a review of the research literature, propose hypotheses, and therapies based on the potential link between testosterone (T) and COVID-19 induced mortality in elderly men. Materials and methods A search of publications in academic electronic databases, and government and public health organization web sites on T, aging, inflammation, severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) infection, and COVID-19 disease state and outcomes was performed. Results The link between T, the immune system, and male aging is well-established, as is the progressive decline in T levels with aging. In women, T levels drop before menopause and variably increase with advanced age. Elevated IL-6 is a characteristic biomarker of patients infected with COVID-19 and has been linked to the development of the acute respiratory distress syndrome (ARDS). Thus far, half of the admitted COVID-19 patients developed ARDS, half of these patients died, and elderly male patients have been more likely to develop ARDS and die. Low T is associated with ARDS. These data suggest that low T levels may exacerbate the severity of COVID-19 infection in elderly men. It may also stand to reason that normal T levels may offer some protection against COVID-19. SARS-CoV-2 binds to the angiotensin-converting enzyme 2, present in high levels in the testis. Conclusion At present, it is not known whether low T levels in aging hypogonadal males create a permissive environment for severe responses to COVID-19 infection or if the virus inhibits androgen formation. Given the preponderance of COVID-19 related mortality in elderly males, additional testing for gonadal function and treatment with T may be merited.

“Androgen-driven COVID-19 pandemic theory” from Carlos Gustavo Wambier and coworkers [ 1 ], introduced the plausible role of androgen receptor for SARS-CoV-2 infection and proposed a theory why males seem to be more vulnerable to the disease and have higher mortality [ 6 ], which is very convincing. The physiological roles of TMPRSS2 are currently unknown, but its connection with the androgen receptor gains suspicions about the possible involvement in less good outcome of COVID-19 infection in men. Recently, a great deal of evidence has already suggested that a TMPRSS2...

Since the male secondary sex characters, libido and fertility are attributed to their major androgen hormone testosterone, the sub-optimum levels of testosterone in young adults may cause infertility and irregularities in their sexual behaviour. Such deficiency is often secondary to maladies involving testes, pituitary or hypothalamus that could be treated with an administration of exogenous testosterone. In the last few decades, the number of testosterone prescriptions has markedly increased to treat sub-optimal serum levels even though its administration in such conditions is not yet approved. On account of its associated cardiovascular hazards, the food and drug authority in the United States has issued safety alerts on testosterone replacement therapy (TRT). Owing to a great degree of conflict among their findings, the published clinical trials seem struggling in presenting a decisive opinion on the matter. Hence, the clinicians remain uncertain about the possible cardiovascular adversities while prescribing TRT in hypogonadal men. The uncertainty escalates even further while prescribing such therapy in older men with a previous history of cardiovascular ailments. In the current review, we analysed the pre-clinical and clinical studies to evaluate the physiological impact of testosterone on cardiovascular and related parameters. We have enlisted studies on the association of cardiovascular health and endogenous testosterone levels with a comprehensive analysis of epidemiological studies, clinical trials, and meta-analyses on the cardiovascular risk of TRT. The review is aimed to assist clinicians in making smart decisions regarding TRT in their patients.

Testosterone deficiency (TD) is common and impairs quality of life (QoL) in patients with chronic kidney disease (CKD). However, there are no studies about whether testosterone replacement therapy (TRT) can improve QoL in patients with CKD. Therefore, we investigated the effect of TRT on the QoL of patients with CKD and confirmed the safety of TRT. Twenty-five male patients with stages III–IV CKD whose serum testosterone levels were

Purpose: To characterize the population of hypogonadal men who presented to a tertiary academic urology clinic and evalu-ate risk factors for primary vs. secondary hypogonadism. Materials and Methods: We evaluated all men with International Classification of Diseases-9 diagnosis codes R68.82 and 799.81 for low libido, 257.2 for testicular hypofunction, and E29.1 for other testicular hypofunction at a tertiary academic medical center from 2013 to 2017. We included men who had testosterone (T) and luteinizing hormone (LH) drawn on the same day. We classified men based on T and LH levels into eugonadal, primary, secondary, and compensated hypogonad-ism. Risk factors including age, body mass index (BMI) over 30 kg/m2, current smoking status, alcohol use greater than 5 days per week, and Charlson comorbidity index greater than or equal to 1 were investigated and measured in each group using the eugonadal group for reference. Results: Among the 231 men who had both T and LH levels, 7.4%, 42.4%, and 7.4% were classified as primary, secondary, and compensated hypogonadism, respectively. Only elevated BMI was associated with secondary hypogonadism compared to eugonadal men (median BMI, 30.93 kg/m2 vs. 27.69 kg/m2, p=0.003). BMI, age, comorbidities, smoking, or alcohol use did not appear to predict diagnosis of secondary hypogonadism. Conclusions: Secondary hypogonadism appears to be the most common cause of hypogonadism among men complaining of low T and decreased libido at a tertiary academic medical center. Secondary hypogonadism is associated with elevated BMI and therefore obesity should be used as a marker to evaluate men for both T and LH levels.

Testosterone is an anabolic hormone that is responsible for the development of male sex organs. It also increases muscle mass and fortifies bone density. In addition to being responsible for primary sexual characteristics at birth and puberty (development and changes of sexual organs such as uterus, vagina, penis, and testes), testosterone is also involved in maintaining secondary sexual characteristics. Patients with low testosterone who are symptomatic should be treated with testosterone replacement therapy (TRT) once the diagnosis has been confirmed. The goal of treatment is to improve the symptoms including the physical, sexual, and cognitive health with the aim being to keep the testosterone in the mid-normal limit of the reference range. Male hypogonadism has been increasingly diagnosed and treated in elderly males since the last decade. A proportionate increase in the prescription of testosterone has been seen as well. The relationship of testosterone levels with cardiovascular (CV) outcomes is challenging and has shown conflicting results. Moreover, in patients with established CV disease, those with high CV risk factors including diabetes, or those with significant risk factors for atherosclerotic CV disease (ASCVD), the benefits of TRT should be weighed against the risks of replacement. Risks and benefits of TRT should be discussed with every patient prior to starting or restarting the procedure.

Background: According to the literature, parenteral testosterone replacement therapy (TRT)-induced polycythaemia is associated with cardiovascular events. No or minimal data exist for the prevalence of TRT-induced polycythaemia in lateonset hypogonadism (LOH) patients from South Africa. Polycythaemia is the side effect most frequently associated with parental TRT formulations. Design: This was a quantitative, observational, descriptive, retrospective study. Setting: The study setting was a private practice male clinic in Emalahleni. Subject: An all-inclusive sampling method was used. Outcome measures: The main outcome measure for polycythaemia was haematocrit (Hct). An Hct percentage of > 50% at month 3 (post-treatment initiation) constituted a positive diagnosis for polycythaemia. For the rise in total testosterone (TT) and Hct, the variance was used as documented between pre- and post-treatment initiation. Results: The prevalence of polycythaemia was 34%. A statistically significant increase in both TT and Hct was observed. The Cohen’s d effect size was 0.68 and 0.73, respectively, for TT and Hct. Conclusion: Depot-testosterone undecanoate parenteral formulation induces polycythaemia in LOH patients, where the rise in TT demonstrates the effectiveness of therapy

Low testosterone levels in aging men are associated with insulin resistance. Mitochondrial dysfunction, changes in glycogen metabolism, and lipid accumulation are linked to insulin resistance in skeletal muscle. In this randomized, double‐blinded, placebo‐controlled study, we investigated the effects of six‐month testosterone replacement therapy (TRT) and strength training (ST) on mitochondrial, glycogen, and lipid droplet (LD) content in skeletal muscle of aging men with subnormal bioavailable testosterone (BioT) levels. Mitochondrial, glycogen, and LD volume fractions in muscle biopsies were estimated by transmission electron microscopy. Insulin sensitivity (insulin‐stimulated Rd) and body composition were assessed by euglycemic‐hyperinsulinemic clamp and dual X‐ray absorptiometry, respectively. TRT significantly increased total testosterone levels, BioT, and lean body mass (LBM) (p < 0.05), whereas percent body fat decreased (p < 0.05), and insulin sensitivity was unchanged. Baseline mitochondrial volume fraction correlated inversely with percent body fat (ρ = −0.43; p = 0.003). Δ‐mitochondrial fraction correlated positively with Δ‐total testosterone (ρ = 0.70; p = 0.02), and Δ‐glycogen fraction correlated inversely with Δ‐LBM (ρ = −0.83; p = 0.002) during six‐month TRT, but no significant changes were observed in mitochondrial, glycogen, and LD volume fractions during TRT and ST. In conclusion, in this exploratory small‐scale study, the beneficial effects of six‐month TRT on total testosterone, LBM, and percent body fat were not followed by significant changes in fractions of mitochondria, glycogen, or lipid in skeletal muscle of aging men with lowered testosterone levels. Six‐month ST or combined three‐month ST+TRT did not change intramyocellular mitochondria, glycogen, and LD fractions compared to placebo. However, further studies with a larger sample size are needed.

Hypogonadism may cause veno-occlusive dysfunction (VOD) by structural and biochemical alterations in the cavernosal tissue. The aim of the study was to investigate the effect of testosterone replacement therapy (TRT) on penile hemodynamics in hypogonadal men with erectile dysfunction and VOD.The study included 32 hypogonadal men with erectile dysfunction, having VOD. All patients underwent penile color Doppler ultrasonography (PCDU) at the beginning and 6 months after the initial evaluation. Erectile function was evaluated with the 5-item version of the International Index of Erectile Function (IIEF-5); hypogonadism was evaluated by testosterone measurement and the Aging Male Symptoms (AMS) scale. All patients received transdermal testosterone 50 mg/day for 6 months. Clinical and radiological findings were compared before and 6 months after the TRT.The mean age was 58.81 ± 4.56 (52–69) years. Mean total testosterone levels were 181.06 ± 39.84 ng/dL and 509.00 ± 105.57 ng/dL before and after the therapy, respectively ( p < .001). While all patients had physiological serum testosterone levels (>320 ng/dL) after the therapy, three cases (9.3%) had no clinical improvement of hypogonadism symptoms. Cavernosal artery peak systolic velocity (PSV) and resistive index (RI) significantly increased, and end diastolic velocity (EDV) significantly decreased after TRT. VOD no longer existed in 21 (65.6%) of the cases.This study demonstrated that TRT may restore penile hemodynamics in hypogonadal men with VOD.

Androgens have diverse functions in muscle physiology, lean body mass, the regulation of adipose tissue, bone density, neurocognitive regulation, and spermatogenesis, the male repro- ductive and sexual function. Male hypogonadism, characterized by reduced testosterone, is com- monly seen in ageing males, and has a complex relationship as a risk factor and a comorbidity in age-related noncommunicable chronic diseases (NCDs), such as obesity, metabolic syndrome, type 2 diabetes, and malignancy. Oxidative stress, as a significant contributor to the ageing process, is a common feature between ageing and NCDs, and the related comorbidities, including hypertension, dyslipidemia, hyperglycemia, hyperinsulinemia, and chronic inflammation. Oxidative stress may also be a mediator of hypogonadism in males. Consequently, the management of oxidative stress may represent a novel therapeutic approach in this context. Therefore, this narrative review aims to discuss the mechanisms of age-related oxidative stress in male hypogonadism associated with NCDs and discusses current and potential approaches for the clinical management of these patients, which may include conventional hormone replacement therapy, nutrition and lifestyle changes, ad-herence to the optimal body mass index, and dietary antioxidant supplementation and/or phyto-medicines. info:eu-repo/semantics/openAccess

We present a patient receiving Testopel® implants whose serum testosterone levels, as measured by a CDC certified assay, were accurately predicted by a multi-compartmental model. This is the first time a model has predicted measured serum testosterone levels within 4% of values calculated. To our knowledge, it was also the first time a pharmacokinetic model allowed patient targeted serum levels (peak/trough/average) to be reached within three months., Highlights • Pharmacokinetic model assists in rapid and accurate Testopel® therapy. • HoSt approved assay enables accurate targeting of serum testosterone levels. • Mean, trough, & peak serum testosterone levels calculated with pharmacokinetic model. • Serum testosterone levels predicted from Testopel® absorption and elimination.

Despite considerable public health initiatives in the past century, there remains a significant gender inequality in life expectancy. The Global Burden of Diseases study has highlighted that the life expectancy for men is 70.5 years, compared with 75.6 years for women. This discrepancy in mortality appears to be related to a disproportionately higher number of preventable and premature male deaths. Whilst there has been an increased focus on men's health, as evidenced by the establishment of men's health charities and governmental legislation promoting equality, a recent World Health Organization report has highlighted that there is still a prevailing misconception that the higher rate of premature mortality amongst men is a natural phenomenon. We explore the association of male sexual and reproductive health–related diseases and the potential role of a urologist in addressing gender inequality in life expectancy. Patient summary: In this report, we discuss the causes for the gender gap in life expectancy and highlight that men continue to have a higher rate of premature death than women, which is associated with diseases of the male reproductive system. Furthermore, this not only appears to be related to a number of metabolic and lifestyle factors, but may also be the result of the increased risk of cancer in men with sexual and reproductive health–related diseases. Globally, the life expectancy for men is 5.1 yr less than that of women. We describe the association between diseases of the male reproductive system and cardiovascular disease and cancers, and highlight the important role of a urologist in reducing premature male death.

Cerebral venous sinus thrombosis is a challenging diagnosis due in part to its variable clinical presentation and rarity. The annual incidence ranges from 0.22 to 1.57 per 100,000. The etiology of such disease is related to hypercoagulability states. Although illicit androgen use is a well-known cause of prothrombotic states, its risk of causing cerebral venous sinus thrombosis has been infrequently reported. We present the case of a 33-year-old male with no known past medical history who presented to the emergency department (ED) with persistent seizure activity, neurological deficits, and history of worsening headaches who was found to have an extensive superior sagittal sinus thrombosis on imaging. Radiologic findings demonstrated pathognomonic findings of cord sign and delta sign, the previous being highly specific but of low incidence. An inconclusive hypercoagulability workup prompted further questioning which revealed illicit androgenic anabolic steroid use. Prompt treatment with anticoagulation and anti-seizure medication was pursued with full resolution of his neurologic symptomatology.

Introduction The role of testosterone (T) replacement therapy (TRT) in men is still conflicting. In particular, safety concerns and cardiovascular (CV) risk related to TRT have not been completely clarified yet. Similarly, the clear beneficial effects of TRT are far to be established. Aim To systematically and critically analyze the available literature providing evidence of the benefit-risk ratio derived from TRT in aging men. Methods A comprehensive PubMed literature search was performed to collect all trials, either randomized controlled trials (RCTs) or observational studies, evaluating the effects of TRT on different outcomes. Main Outcome Measure Whenever possible, data derived from RCTs were compared with those resulting from observational studies. In addition, a discussion of the available meta-analyses has been also provided. Results Data derived from RCT and observational studies clearly documented that TRT can improve erectile function and libido as well as other sexual activities in men with hypogonadism (total T Clinical Implications Before prescribing TRT, hypogonadism (total T Strength & Limitations When correctly diagnosed and administered, TRT is safe, and it can improve several aspects of sexual function. However, its role in complicated vasculogenic erectile dysfunction is limited. Conversely, TRT is not recommended for weight reduction and metabolic improvement. Further well-powered studies are advisable to better clarify TRT for long-term CV risk and prostate safety in complicated patients as well as in those curatively treated for prostate cancer. Conclusion TRT results in sexual function improvement when men with hypogonadism (total T

Rationale: Although PSA (prostate-specific antigen)—a tumor marker for prostate cancer—has been reported to be associated with cardiovascular disease (CVD) risk factors, studies on the association of PSA with subclinical and clinical CVD remain limited. Objective: We examined the association of total serum PSA within the reference range with coronary artery calcium (CAC) score and CVD mortality. Methods and Results: A cross-sectional study was performed in 88 203 Korean men who underwent a health checkup exam including cardiac tomography estimation of CAC score. Logistic regression model was used to calculate odds ratios with 95% CIs for prevalent CAC. PSA levels were inversely associated with the presence of CAC. After adjusting for potential confounders, multivariable-adjusted odds ratio (95% CIs) for prevalent CAC comparing PSA quartiles 2, 3, and 4 to the first quartile were 0.96 (0.90–1.01), 0.88 (0.83–0.93), and 0.85 (0.80–0.90), respectively ( P for trend, Conclusions: Serum total PSA levels within the reference range showed an inverse association with subclinical atherosclerosis and CVD mortality in young and middle-aged Korean men, indicating a possible role of PSA as a predictive marker for subclinical and clinical CVD.

Klinefelter syndrome (KS), karyotype 47, XXY, is a common cause of hypogonadism in males. Patients with this condition often experience symptoms of gonadal failure, which can precipitate gender identity challenges. Treatment with testosterone replacement therapy (TRT) can combat these symptoms by improving sexual function, muscle mass, bone health, and virilization, thereby enhancing the quality of life (QOL). Although TRT is often employed in patients with KS, there is a concern that the application of exogenous testosterone may increase the risk of prostate adenocarcinoma development and progression. We report the case of a 58-year-old male with KS who is also diagnosed with prostate adenocarcinoma and wished to remain on TRT post-radiation therapy in support of his gender identity and QOL. We describe the challenges this patient faced when balancing a rising prostate-specific antigen level and risk of cancer recurrence with his QOL.

The initiation and maintenance of reproductive capacity in humans is dependent on pulsatile secretion of the hypothalamic hormone GnRH. Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder that results from the failure of the normal episodic GnRH secretion, leading to delayed puberty and infertility. CHH can be associated with an absent sense of smell, also termed Kallmann syndrome, or with other anomalies. CHH is characterized by rich genetic heterogeneity, with mutations in >30 genes identified to date acting either alone or in combination. CHH can be challenging to diagnose, particularly in early adolescence where the clinical picture mirrors that of constitutional delay of growth and puberty. Timely diagnosis and treatment will induce puberty, leading to improved sexual, bone, metabolic, and psychological health. In most cases, patients require lifelong treatment, yet a notable portion of male patients (approximate to 10% to 20%) exhibit a spontaneous recovery of their reproductive function. Finally, fertility can be induced with pulsatile GnRH treatment or gonadotropin regimens in most patients. In summary, this review is a comprehensive synthesis of the current literature available regarding the diagnosis, patient management, and genetic foundations of CHH relative to normal reproductive development.

The age-related decline of serum T occurs in ~20–30% of adult men and it is today defined as late-onset hypogonadism (LOH). In the elderly, such decline becomes more prevalent (up to 60%) and shows-up with erectile dysfunction (ED) and hypoactive sexual desire. A large body of experimental evidences have shown that the combination of T replacement therapy (TRT) and phosphodiesterase type 5 inhibitors (PDE5i) is, usually, effective in restoring erectile function in patients with LOH and ED who have not responded to monotherapy for sexual disturbances. In fact, PDE5is potentiate the action of nitric oxide (NO) produced by endothelial cells, resulting in a vasodilator effect, while T facilitates PDE5i effects by increasing the expression of PDE5 in corpora cavernosa. Meta-analytic data have recognized to PDE5i a protective role on the cardiovascular health in patients with decreased left ventricular ejection fraction. In addition, several studies have shown pleiotropic beneficial effects of these drugs throughout the body (i.e., on bones, urogenital tract and cerebral, metabolic, and cardiovascular levels). TRT itself is able to decrease endothelial dysfunction, oxidative stress and inflammation, thus lowering the cardiovascular risk. Furthermore, untreated hypogonadism could be the cause of PDE5i ineffectiveness especially in the elderly. For these reasons, aging men complaining ED who have LOH should undergo TRT before or at the moment when PDE5i treatment is started.

Late-onset hypogonadism (LOH) is the term used to describe the decline in serum testosterone levels associated with increasing age in men above 40 years. A number of symptoms are attributed to LOH, but the most common association is that of sexual dysfunction. LOH has recently come under greater scrutiny with the widespread use of testosterone therapy, and concerns regarding the efficacy and safety of testosterone replacement therapy have been raised. In particular, the cardiovascular safety and the beneficial effects of testosterone replacement therapy on general health have been questioned. This review will give an overview of the current evidence for the relationship of LOH and male sexual dysfunction.

Male hypogonadism is a clinical syndrome characterized by low testosterone and symptoms of androgen deficiency. Prostate cancer remains a significant health burden and cause of male mortality worldwide. The use of testosterone replacement therapy drugs is rising year-on-year for the treatment of androgen deficiency and has reached global proportions. As clinicians, we must be well versed and provide appropriate counseling for men prior to the commencement of testosterone replacement therapy. This review summarizes the current clinical and basic science evidence in relation to this commonly encountered clinical scenario. There is gathering evidence that suggests, from an oncological perspective, that it is safe to commence testosterone replacement therapy for men who have a combination of biochemically confirmed androgen deficiency and who have either had definitive treatment of their prostate cancer or no previous history of this disease. However, patients must be made aware and cautioned that there is a distinct lack of level 1 evidence. Calls for such studies have been made throughout the urological and andrological community to provide a definitive answer. For those with a diagnosis of prostate cancer that remains untreated, there is a sparsity of evidence and therefore clinicians are “pushing the limits” of safety when considering the commencement of testosterone replacement therapy.

Male hypogonadism is a clinical syndrome characterized by low testosterone and symptoms of androgen deficiency. Prostate cancer remains a significant health burden and cause of male mortality worldwide. The use of testosterone replacement therapy drugs is rising year-on-year for the treatment of androgen deficiency and has reached global proportions. As clinicians, we must be well versed and provide appropriate counseling for men prior to the commencement of testosterone replacement therapy. This review summarizes the current clinical and basic science evidence in relation to this commonly encountered clinical scenario. There is gathering evidence that suggests, from an oncological perspective, that it is safe to commence testosterone replacement therapy for men who have a combination of biochemically confirmed androgen deficiency and who have either had definitive treatment of their prostate cancer or no previous history of this disease. However, patients must be made aware and cautioned that there is a distinct lack of level 1 evidence. Calls for such studies have been made throughout the urological and andrological community to provide a definitive answer. For those with a diagnosis of prostate cancer that remains untreated, there is a sparsity of evidence and therefore clinicians are "pushing the limits" of safety when considering the commencement of testosterone replacement therapy.

Objective Late-onset hypogonadism, or androgen deficiency in the aging male, is a significant cause of morbidity in older men. Many men in the low normal or equivocal range for low testosterone level exhibit signs and symptoms of hypogonadism. Serum testosterone is an imperfect maker for hypogonadism as symptoms vary greatly within the low to low normal range in addition to variations among testosterone assays. Perineal ultrasound can be effectively used to examine the bulbocavernosus muscle (BCM), an androgenized tissue that may be impacted by androgen receptor activity. Methods This study was a retrospective analysis of men who underwent perineal ultrasound for hypogonadism. The ultrasound data were used to calculate the area of the BCM and correlate it with indices of hypogonadismin symptomatic men including free and total testosterone and dual-energy X-ray absorptiometry (DEXA). Results The results demonstrate that there is a significant correlation between total and free testosterone and BCM area in hypogonadal patients. Comparison between BCM area and total testosterone showed R 2 = 0.061 and p = 0.0187 and comparison between BCM area and free testosterone showed R 2 = 0.0957 and p = 0.0034. In addition, low BCM was also correlated with DEXA results showing osteoporosis and osteopenia ( R 2 = 0.2239, p = 0.0027). Conclusion There has been recent controversy over the safety of testosterone replacement therapy. This might be particularly important in men with hypogonadal symptoms but a low normal testosterone level. Our study investigated the use of perineal ultrasound to measure BCM as a surrogate marker for poor androgenized men presenting with hypogonadism.

The article presents a review of the literature, which indicate the current understanding of the clinical significance of late onset hypogonadism and types of its correction. The results of studies demonstrate the efficacy and safety of hormone replacement therapy. The authors point to the need for health care professionals to understand and see the benefits of substitution treatment. But the priority in the appointment and monitoring of therapy should be for the urologist and endocrinologist.