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Background: Inter‐assay variation between different immunoassays and different mass spectrometry methods hampers the biochemical confirmation of male hypogonadism. Furthermore, some laboratories utilise assay manufacturer reference ranges that do not necessarily mirror assay performance characteristics, with the lower limit of normality ranging from 4.9 nmol/L to 11 nmol/L. The quality of the normative data underlying commercial immunoassay reference ranges is uncertain. Design: A working group reviewed published evidence and agreed upon standardised reporting guidance to augment total testosterone reports. Results: Evidence‐based guidance on appropriate blood sampling, clinical action limits, and other major factors likely to affect the interpretation of results are provided. Conclusions: This article aims to improve the quality of the interpretation of testosterone results by non‐specialist clinicians. It also discusses approaches for assay harmonisation which have been successful in some but not all healthcare systems. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD), recently proposed to be renamed to metabolic dysfunction-associated steatotic liver disease (MASLD), is a major global public health concern, affecting approximately 25–30% of the adult population and possibly leading to cirrhosis, hepatocellular carcinoma, and liver transplantation. The liver is involved in the actions of sex steroids via their hepatic metabolism and production of the sex hormone-binding globulin (SHBG). Liver disease, including NAFLD, is associated with reproductive dysfunction in men and women, and the prevalence of NAFLD in patients with hypogonadism is considerable. A wide spectrum of possible pathophysiological mechanisms linking NAFLD and male/female hypogonadism has been investigated. As therapies targeting NAFLD may impact hypogonadism in men and women, and vice versa, treatments of the latter may affect NAFLD, and an insight into their pathophysiological pathways is imperative. This paper aims to elucidate the complex association between NAFLD and hypogonadism in men and women and discuss the therapeutic options and their impact on both conditions. [ABSTRACT FROM AUTHOR]

Hormonal disorders like PCOS (Polycystic Ovary Syndrome), autoimmune thyroid disease (AITD) including Hashimoto's thyroiditis, male hypogonadism are commonly encountered in clinical practice in the US and worldwide, with rising frequency. These typically affect patients during young or middle age, compared with other common chronic illnesses like type 2 diabetes, hypertension, atherosclerotic cardiovascular disease, where onset may usually be in middle or older age. Multiple studies point to the role of disordered lifestyle health behaviors as contributory to these endocrinopathies, and conversely therapeutic lifestyle changes leading to improvement in signs, symptoms, biochemical markers, and sequelae of these conditions. This article presents 3 different real life case studies of the conditions enlisted above and documents the positive impact of lifestyle improvements on their disease condition. Therapeutic lifestyle behaviors are an extremely useful and important component of management of these familiar endocrinologic disorders, and clinicians need to routinely counsel their patients about healthy lifestyle interventions when treating these common syndromes. [ABSTRACT FROM AUTHOR]

Abstract Background In males with end stage renal disease biochemical hypogonadism is a frequent finding. Testosterone and sex hormone binding globulin (SHBG) have been associated with insulin resistance, a well-known condition in uremia. The aim of the present study was to investigate in males on chronic hemodialysis the relationship of testosterone and SHBG serum levels with insulin resistance. Methods In a cross-sectional study we enrolled men treated with chronic hemodialysis who did not suffer from an acute illness or other endocrinopathy, as well as primary hypogonadism, and were not hospitalised. Diabetes mellitus, diabetic nephropathy or previous transplantation were not exclusion criteria. As controls we used a community-based group of healthy males matched for age and Body Mass Index (BMI). We assessed the BMI (kg/m2) from body weight and height, the body fat content (%) by bioelectrical impedance and serum testosterone (ng/ml), SHBG (nmol/L) and estradiol (pg/ml) by standard methods. Testosterone

Background: In males with end stage renal disease biochemical hypogonadism is a frequent finding. Testosterone and sex hormone binding globulin (SHBG) have been associated with insulin resistance, a well-known condition in uremia. The aim of the present study was to investigate in males on chronic hemodialysis the relationship of testosterone and SHBG serum levels with insulin resistance. Methods: In a cross-sectional study we enrolled men treated with chronic hemodialysis who did not suffer from an acute illness or other endocrinopathy, as well as primary hypogonadism, and were not hospitalised. Diabetes mellitus, diabetic nephropathy or previous transplantation were not exclusion criteria. As controls we used a community-based group of healthy males matched for age and Body Mass Index (BMI). We assessed the BMI (kg/m2) from body weight and height, the body fat content (%) by bioelectrical impedance and serum testosterone (ng/ml), SHBG (nmol/L) and estradiol (pg/ml) by standard methods. Testosterone < 3.25 ng/ml defined biochemical hypogonadism. In non-diabetic males, we calculated the homeostasis model assessment index (HOMA-R), an estimate of insulin resistance, from serum fasting insulin and glucose. Results: 27 men (age 54.4 ± 19 years) on chronic hemodialysis (treatment duration 29.1 ± 14.4 months) and 51 healthy men (age 47.1 ± 9.6 years) were included. In men on hemodialysis vs. healthy men there were increased serum levels of SHBG (40.9 ± 26.9 vs. 27.6 ± 11.9 nmol/L; p = 0.031) and a significantly enhanced frequency of biochemical hypogonadism (22.2 vs. 3.9%; p = 0.011). In cases without diabetes (n = 22) a significant correlation was observed between the HOMA-R (r = -0.586, p = 0.004) and the fasting insulin levels (r = -0.650, p = 0.001) on the one hand and the serum SHBG levels on the other. Conclusions: Our findings confirm enhanced prevalence of biochemical hypogonadism in males on chronic hemodialysis. In non-diabetic cases the serum levels of SHBG correlated with serum insulin and insulin resistance. [ABSTRACT FROM AUTHOR]

Background In male patients with cancer treated with antineoplastic drug, hypogonadism is a neglected cause of diminished quality of life. This condition may be cancer related as well as toxicity related. The role of antineoplastic drug in causing hypogonadism is poorly understood. The aim of this systematic review was to establish the prevalence, nature (primary/secondary), and impact of hypogonadism on quality of life in male patients with cancer on antineoplastic therapy. Methods The search strategy used PubMed, Embase, and Cochrane databases to select articles in English language that described hypogonadism in male patients with cancer. The search period was from January 1, 1945 to February 28, 2023. We included observational studies, case reports or case series and excluded studies concerning hematological malignancies, prostate cancer, female patients, and survivors. Findings Of 4488 records identified, 28 studies met inclusion criteria (17 observational studies, 11 case reports or case series). Anti-angiogenic drugs and crizotinib were found to have a role in the development of hypogonadism. Patients treated with immune checkpoint-inhibitors developed secondary hypogonadism due to immune-related hypophysitis or orchitis. As for active chemotherapy, platinum salts were often associated with hypogonadism, followed by antimetabolites and taxanes. Selected studies were heterogeneous for populations, interventions, and outcomes assessments. Thus, a generalization is difficult. Moreover, the role of concurrent etiologies cannot be excluded in most studies. Conclusion Our research emphasizes the importance of evaluating the gonadal axis before treatment in patients considered at risk and testing it at regular intervals or in case of clinical suspicion. [ABSTRACT FROM AUTHOR]

Testosterone’s biological functions are extensive, influencing reproductive and systemic health. It plays a vital role in sexual functions, muscle protein synthesis, bone metabolism, fat distribution, and cardiovascular health. The hormone also affects mood, cognitive function, and erythropoiesis, underscoring its importance in both physical and mental health.Testosterone deficiency, or male hypogonadism, is increasingly recognized as a significant health issue affecting various bodily systems, also in the context of chronic kidney disease (CKD). Recent research indicates a complex interplay between testosterone levels and renal health, suggesting that male hypogonadism may both impact and be impacted by CKD. The latter is characterized by a gradual loss of kidney function, affects millions globally and is often associated with diabetes mellitus, arterial hypertension, and autoimmune diseases. Men with CKD frequently experience lower testosterone levels, which can exacerbate muscle wasting, reduce quality of life, and increase cardiovascular risk. Overall, low testosterone levels in CKD patients are associated with increased morbidity and mortality.Several mechanisms explain the relationship between CKD and testosterone deficiency. The uremic environment in CKD disrupts the hypothalamic-pituitary–gonadal axis, impairing hormone production. Nutritional deficiencies and chronic inflammation common in CKD patients further suppress gonadal function. The consequences of low testosterone in CKD are profound, with studies suggesting that testosterone replacement therapy (TRT) might improve clinical outcomes, though the long-term effects and causal relationships remain under investigation.The potential benefits of TRT in CKD patients might be significant. TRT can enhance muscle mass and strength, address anemia by stimulating erythropoiesis, improve bone density, and possibly offer cardiovascular benefits by improving body composition and insulin sensitivity. General symptoms of male hypogonadism, such as deteriorated psychological, sexual and physical wellbeing, can be improved by TRT. However, these benefits must be weighed against potential risks. TRT may exacerbate fluid retention, arterial hypertension, or exacerbate existing heart failure, particularly in CKD patients with pre-existing cardiovascular comorbidities. Additionally, concerns about the progression of renal disease via several testosterone affected pathways involving renal tubular integrity exist, highlighting the need for careful patient selection and monitoring.Understanding this relationship is crucial for developing comprehensive treatment strategies that address both renal and endocrine dysfunctions, highlighting the need for integrated patient care, which means good collaboration between subspecialists like nephrologists, endocrinologists, urologists and primary care providers, aiming to improve outcomes and quality of life while mitigating adverse effects.

AbstractIntroduction In the past decade, there has been a significant augmentation in the corpus of evidence pertaining to functional hypogonadism. Despite this, prevailing clinical guidelines continue to advise against the universal screening for hypogonadism in middle-aged and elderly males.Findings Numerous randomized controlled trials have scrutinized the effects of testosterone therapy in males afflicted with type 2 diabetes and/or obesity. However, these guidelines uniformly assert that lifestyle modifications and weight reduction should be the primary intervention strategies in overweight and obese males, relegating testosterone therapy to a secondary, selective option. It is extensively documented that testosterone therapy can yield substantial improvements in various metabolic parameters as well as ameliorate symptoms of erectile dysfunction. Moreover, recent studies have demonstrated the potential of testosterone therapy in reversing type 2 diabetes in males with low-normal testosterone levels who are at elevated risk for this condition, in comparison to the outcomes achievable through lifestyle modifications alone.Conclusion This focused review article aims to present a comprehensive update on the latest data concerning the innovative aspects of testosterone therapy in males with functional hypogonadism, particularly in the context of type 2 diabetes and/or obesity. Additionally, it will delve into the cardiovascular safety of such interventions within this high-risk demographic, with a special emphasis on insights gleaned from the TRAVERSE trial.

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Testosterone (T), the principal androgen secreted by the testes, plays an essential role in male health. Male hypogonadism is diagnosed based on a combination of associated clinical signs and symptoms and laboratory confirmation of low circulating T levels. In this review, we have highlighted factors, both biological and analytical, that introduce variation into the measurement of serum T concentrations in men; these need to be considered when requesting T levels and interpreting results. There is an ongoing need for analytical standardisation of T assays and harmonisation of pre- and post-analytical laboratory practices, particularly in relation to the laboratory reference intervals provided to clinicians. Further, there is a need to share with service users the most up-to-date and evidence-based action thresholds for serum T as recommended in the literature. Estimation of free testosterone may be helpful. Causes of secondary hypogonadism should be considered. A comprehensive approach is required in the management of male hypogonadism, including lifestyle modification as well as medication where appropriate. The goal of treatment is the resolution of symptoms as well as the optimisation of metabolic, cardiovascular, and bone health. The advice of an endocrinologist should be sought when there is doubt about the cause and appropriate management of the hypogonadism. [ABSTRACT FROM AUTHOR]

Background: Male hypogonadism may be associated with micropenis and cryptorchidism in newborn, absent or incomplete pubertal development when it occurs during childhood. During puberty, androgen replacement therapy plays a pivotal role in subjects with hypogonadism to induce sexual maturation, growth acceleration, anabolic effects on fat-free mass growth increasing muscle strength, directly and indirectly on the attainment of peak bone mass in young men. Moreover, in newborns with congenital hypogonadism, androgen therapy could be effective to increase genital size. Summary: Testosterone replacement therapy (TRT) represents the cornerstone of the management of hypogonadism in boys. During puberty, replacement therapy needs to be modulated with gradual dosing increase to better mimic the physiologic pubertal development. Currently, intramuscular testosterone (T) esters (in particular testosterone enanthate) and subcutaneous T pellets are the only formulations approved by the US Food and Drug Administration for delayed puberty, while no preparation is approved for long-term use in the adolescent age. Several new T formulations (as transdermal, nasal, subcutaneous, and oral formulation) are recently developed to improve the pharmacokinetic profile and to ease the administration route increasing patient compliance in adult males with hypogonadism. All these formulations are not approved for pediatric age, although some of them are used as "off-label" regimens. This special issue is aimed to illustrate new T formulations and their potential role as replacement therapy in the pediatric population, as well as to highlight investigational areas to contribute to health care improvement in these patients. Key Messages: Despite the lack of evidence-based guidelines regarding the choice of T formulation in the pediatric population, new formulations appear to have a potential role for TRT in adolescent age. They have been designed for adult age with a little flexibility of dosage, although a few formulations may be attractive for pubertal induction and penile enlargement thanks to their greater flexibility and easing of administration. On the other hand, long-acting and stable formulations could meet post-pubertal needs, increasing TRT compliance in a critical phase as the adolescent age. Further controlled, long-term safety, and efficacy studies for all these new T formulations within the pediatric population are needed. [ABSTRACT FROM AUTHOR]

Male hypogonadism arises from the inadequate production of testosterone (T) by the testes, primarily due to Leydig cell (LC) dysfunction. Small molecules possess several advantages, including high cell permeability, ease of synthesis, standardization, and low effective concentration. Recent investigations have illuminated the potential of small molecule combinations to facilitate direct lineage reprogramming, removing the need for transgenes by modulating cellular signaling pathways and epigenetic modifications. In this study, we have identified a specific cocktail of small molecules, comprising forskolin, DAPT, purmorphamine, 8-Br-cAMP, 20α-hydroxycholesterol, and SAG, capable of promoting the conversion of fibroblasts into Leydig-like cells (LLCs). These LLCs expressed key genes involved in testosterone synthesis, such as Star, Cyp11a1, and Hsd3b1, and exhibited the ability to secrete testosterone in vitro. Furthermore, they successfully restored serum testosterone levels in testosterone-castrated mice in vivo. The small molecule cocktails also induced alterations in the epigenetic marks, specifically H3K4me3, and enhanced chromosomal accessibility on core steroidogenesis genes. This study presents a reliable methodology for generating Leydig-like seed cells that holds promise as a novel therapeutic approach for hypogonadism. [ABSTRACT FROM AUTHOR]

Background: Apo A‐I Leu75Pro amyloidosis is a rare systemic hereditary disease, whose hallmark and earliest involvement is testicular impairment, characterized by hypogonadism and macrorchidism; renal and hepatic involvement are the other characteristics. Objective: To evaluate for the first time the prevalence of osteopenia, osteoporosis and vertebral fractures (VFs) in men with this form of amyloidosis affected by hypogonadism and under long‐term testosterone replacement therapy (TRT). Materials and methods: Retrospective study on 50 men >50 years (median age 64.5) with dual‐energy X‐ray absorptiometry (DXA), hormonal, and biochemical data available at least 3 years after the start of TRT. Serum gonadal hormones and bone markers, lumbar and femoral DXA‐scan with morphometric assay for evaluation of VFs were assessed. Results: At 7.5 years from start of TRT, lumbar and/or femoral osteopenia and osteoporosis were found in 54% and 10% of patients, respectively. Of the men who had the morphometric assay performed, five of 34 (14.7%) had VFs. Compared to patients with normal bone mineral density, men with osteopenia and osteoporosis were older, had lower body mass index, higher sex hormone binding globulin and showed more frequently renal involvement. Multiorgan involvement, without different TRT dosage, was associated with lower testosterone levels. Discussion and conclusion: Men with hypogonadism because of Apo A‐I Leu75Pro amyloidosis under long‐term TRT had a high burden of low bone mass (64%) and VFs (almost 15%). Osteopenia‐osteoporosis was more frequently observed in older patients with multi‐organ disease, which might contribute to impair bone health beyond hypogonadism. [ABSTRACT FROM AUTHOR]

Abstract Background Hypogonadism in older men is often considered as late onset hypogonadism. However, this clinical condition results from primary testicular failure which could be of genetic origin with Klinefelter syndrome being the most common chromosomal abnormality associated with it. Case presentation We report a heterogeneous group of cases who were diagnosed with hypergonadotropic hypogonadism in their adulthood and were found to have rare chromosomal aberrations. All were elderly men (in their 70 s and 80 s) for whom the diagnosis was made during the evaluation of incidental symptoms suggestive of endocrinopathy. The first had hyponatremia; the other two had gynaecomastia and features of hypogonadism noted during admission for various acute medical problems. With respect to their genetic results; the first had a male karyotype with balanced reciprocal translocation between the long arm of chromosome 4 and the short arm of chromosome 7. The second case had a male karotype with one normal X chromosome and an isochrome for the short arm of the Y chromosome. The third case was an XX male with unbalanced translocation between the X & Y chromosomes with retention of the SRY locus. Conclusion Hypergonadotrophic hypogonadism in the elderly, may be due to chromosomal aberrations, resulting in heterogeneous and diverse clinical phenotypes. Vigilance must be exercised when seeing cases with subtle clinical findings. This report suggests that in selected cases of adult hypergonadotropic hypogonadism, chromosomal analysis may be indicated.

Résumé Contexte La fonction érectile dépend d’une interaction complexe entre les facteurs démographiques, métaboliques, vasculaires, hormonaux et psychologiques qui déclenchent la dysfonction érectile (DE). Dans la présente étude, nous avons mené ici une étude transversale évaluant l’impact des maladies chroniques non transmissibles (MNT), de l’hypogonadisme masculin et des facteurs démographiques dans la caractérisation des hommes atteints de dysfonction érectile. Quatre cent trente-trois patients externes consécutifs présentant une dysfonction érectile ont été extraits de la base de données électronique de janvier 2017 à décembre 2019. Le score de l’indice international de la fonction érectile (IIEF) 5 a été utilisé pour diagnostiquer la dysfonction érectile et stratifier sa gravité, les valeurs normalisées de la testostérone sérique (10,5 nM/L) et de l’hormone lutéinisante (LH 9,4 UI/L) pour diagnostiquer et classer l’hypogonadisme masculin, et l’indice de comorbidité de Charlson (ICC) pour évaluer le rôle de chaque MNT sur la DE. Résultats Quarante-six pour cent des participants étaient eugonadiques (EuG), 13% avaient un hypogonadisme organique (OrH) et les 41% restants avaient un hypogonadisme fonctionnel (FuH). Les hommes hypogonadiques avaient un score IIEF 5 significativement plus faible (p < 0,0001) que EuG. Les hommes FuH avait un ICC plus élevé que les hommes OrH et EuG (tous p < .0001). Dans un modèle multivariable, seules la T libre (TL) et la globuline liant les hormones sexuelles (SHBG) ont montré une corrélation directe avec le score IIEF 5 (tous p

A recent study published in the Journal of Clinical Endocrinology & Metabolism examined the impact of testosterone treatment on depressive symptoms in aging men. The study found that testosterone treatment had a modest positive effect on depressive symptoms in men with mild or higher depression scores, but it was ineffective for men with severe depression. However, the improvement in depressive symptoms was less than what would be expected from an effective antidepressant. The study also highlighted the need for caution in prescribing testosterone for aging men without reproductive pathology, as there are more effective therapeutics available for treating depression. [Extracted from the article]

According to World Health Organization estimates, 5% of the adult population worldwide suffers from depression. In addition to the affective, psychomotor and cognitive symptoms which characterize this mood disorder, sexual dysfunction has been frequently reported among men suffering from depression. The most common sexual manifestations are decreased libido, erectile dysfunction and orgasmic disorder. In addition, epidemiological studies have documented a reduction of testosterone concentrations in men with depression and, for these reasons, depressive disorders appear as one possible cause of male functional hypogonadism. Moreover, some largely used antidepressant medications can cause or worsen sexual complaints, thus depression and its treatments rise several andrological-relevant issues. The other way round, men with hypogonadism can manifest depressed mood, anxiety, insomnia, memory impairment which, if mild, may respond to testosterone replacement therapy (TRT). However, the prevalence of functional hypogonadism in depression, and of depressive symptoms in hypogonadal men, is not known. Severe depressive symptoms do not respond to TRT, while the effect of treating major depression on functional hypogonadism, has not been investigated. Overall, the clinical relevance of each condition to the other, as well as the physiopathological underpinnings of their relationship, are still to be clarified. The present review summarizes current evidence on the influence of testosterone on mood and of depression on the hypothalamic-pituitary-testis axis; the clinical association between male hypogonadism and depression; and the reciprocal effects of respective treatments. [ABSTRACT FROM AUTHOR]

Background: Inter-assay variation between different immunoassays and different mass spectrometry methods hampers the biochemical confirmation of male hypogonadism. Furthermore, some laboratories utilis eassay manufacturer reference ranges that do not necessarily mirror assay performance characteristics, with the lower limit of normality ranging from 4.9 nmol/L to 11 nmol/L. The quality of the normative data underlying commercial immunoassay reference ranges is uncertain. Design: A working group reviewed published evidence and agreed upon standardised reporting guidance to augment total testosterone reports. Results: Evidence-based guidance on appropriate blood sampling, clinical action limits, and other major factors likely to affect the interpretation of results are provided. Conclusions: This article aims to improve the quality of the interpretation of testosterone results by non-specialist clinicians. It also discusses approaches for assay harmonisation which have been successful in some but not all healthcare systems. [ABSTRACT FROM AUTHOR]

BackgroundA novel formulation of oral testosterone undecanoate (TU) was studied in a long- and short-term phase III trial to evaluate safety and efficacy.MethodsHypogonadal men (age 18-65 years; two morning serum testosterone (T)

Abstract Sexual dysfunction, which is defined as ‘difficulty during any stage of the sexual encounter that prevents or impairs the individual or couple from enjoying sexual activity’, is globally prevalent in males with prediabetes and diabetes. It is an early harbinger of cardiovascular diseases and has a profound impact on one's physical, mental, and social health. Among patients with either prediabetes or diabetes, the most common male sexual dysfunctions are hypogonadism, erectile dysfunction, and premature ejaculation. In Asia, although sexual health is an important factor of men's health, it is rarely discussed freely in real‐life practice. Addressing sexual health in Asian males has always been challenging with multiple barriers at the levels of patients and health care providers. Therefore, the assessment and management of sexual dysfunction in routine clinical practice should involve a holistic approach with effective patient–provider communication. In this review, we discuss the epidemiology, pathophysiology, and the management of hypogonadism, erectile dysfunction, and premature ejaculation among males with either prediabetes or diabetes (type 1 and type 2), as well as the evidence gaps across Asia.

Background: Hypogonadism in older men is often considered as late onset hypogonadism. However, this clinical condition results from primary testicular failure which could be of genetic origin with Klinefelter syndrome being the most common chromosomal abnormality associated with it. Case presentation: We report a heterogeneous group of cases who were diagnosed with hypergonadotropic hypogonadism in their adulthood and were found to have rare chromosomal aberrations. All were elderly men (in their 70 s and 80 s) for whom the diagnosis was made during the evaluation of incidental symptoms suggestive of endocrinopathy. The first had hyponatremia; the other two had gynaecomastia and features of hypogonadism noted during admission for various acute medical problems. With respect to their genetic results; the first had a male karyotype with balanced reciprocal translocation between the long arm of chromosome 4 and the short arm of chromosome 7. The second case had a male karotype with one normal X chromosome and an isochrome for the short arm of the Y chromosome. The third case was an XX male with unbalanced translocation between the X & Y chromosomes with retention of the SRY locus. Conclusion: Hypergonadotrophic hypogonadism in the elderly, may be due to chromosomal aberrations, resulting in heterogeneous and diverse clinical phenotypes. Vigilance must be exercised when seeing cases with subtle clinical findings. This report suggests that in selected cases of adult hypergonadotropic hypogonadism, chromosomal analysis may be indicated. [ABSTRACT FROM AUTHOR]

Background: Hypogonadism is a worldwide problem among men causing sexual, physical and mental problems. Testosterone therapy is the first‐choice treatment for male hypogonadism, with several side effects, that is, subfertility. Clomiphene citrate (CC) is an alternative off‐label therapy for a certain group of hypogonadal males, especially for those with an active or future child wish. There is scarce literature in usage of CC for men with hypogonadism. The aim of this retrospective study was to evaluate the effectiveness and safety of CC for hypogonadal males. Methods: In this single‐centre study, men treated with CC for hypogonadism were evaluated retrospectively. Primary outcome was hormonal evaluation including total testosterone (TT), free testosterone (FT), luteinizing hormone (LH) and follicle stimulating hormone (FSH). Secondary outcomes were hypogonadal symptoms, metabolic and lipid parameters, haemoglobin (Hb), haematocrit (Ht), prostate specific antigen (PSA), side effects, the effect of a trial without medication and potential predictors for biochemical and clinical response. Results: In total, 153 hypogonadal men were treated with CC. Mean TT, FT, LH and FSH increased during treatment. TT increased from 9 to 16 nmol/L, with a biochemical increase in 89% of the patients. In patients who continued CC treatment, an increased level of TT persisted after 8 years of treatment. With CC treatment, 74% of the patients experienced hypogonadal symptom improvement. LH at the lower normal range before CC treatment was predictive for better TT response. During CC therapy, few side effects were reported and no clinical important changes in PSA, Hb and Ht were found. Conclusion: Clomiphene citrate is an effective therapy on short and long term, improving both clinical symptoms and biochemical markers of male hypogonadism with few side effects and good safety aspects. [ABSTRACT FROM AUTHOR]

Copyright of Basic & Clinical Andrology is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Low Energy Availability (LEA) arises from the inability to cover energy needs and requirements of training or normal physiological functions. This value differs from the energy balance, which takes into account the total daily energy intake compared to all the energy expended, regardless of the amount of fat-free mass. Insufficient energy consumption affects recovery, adaptation processes, increases the risk of injury or illness, so all of this can negatively affect performance. This mini-review is written on research articles in Pubmed database related to LEA in endurancetrained men and its impact on performance and testosterone. This article also clarifies the prevalence of LEA in male endurance athletes and its correlation to Relative Energy Deficiency in Sports (RED-S). LEA occurs in male endurance athletes and correlates with decreased testosterone levels, decreased bone density and also Resting Metabolic Rate. In endurancetrained men, there is great potential for the negative consequences of low energy availability. It can also be said that there are possibilities for primary screening, so we recommend regular check-ups of blood markers, body structure and keeping not only training but also dietary records, which can increase awareness of an adequate energy balance. [ABSTRACT FROM AUTHOR]

According to World Health Organization estimates, 5% of the adult population worldwide suffers from depression. In addition to the affective, psychomotor and cognitive symptoms which characterize this mood disorder, sexual dysfunction has been frequently reported among men suffering from depression. The most common sexual manifestations are decreased libido, erectile dysfunction and orgasmic disorder. In addition, epidemiological studies have documented a reduction of testosterone concentrations in men with depression and, for these reasons, depressive disorders appear as one possible cause of male functional hypogonadism. Moreover, some largely used antidepressant medications can cause or worsen sexual complaints, thus depression and its treatments rise several andrological-relevant issues. The other way round, men with hypogonadism can manifest depressed mood, anxiety, insomnia, memory impairment which, if mild, may respond to testosterone replacement therapy (TRT). However, the prevalence of functional hypogonadism in depression, and of depressive symptoms in hypogonadal men, is not known. Severe depressive symptoms do not respond to TRT, while the effect of treating major depression on functional hypogonadism, has not been investigated. Overall, the clinical relevance of each condition to the other, as well as the physiopathological underpinnings of their relationship, are still to be clarified. The present review summarizes current evidence on the influence of testosterone on mood and of depression on the hypothalamic-pituitary-testis axis; the clinical association between male hypogonadism and depression; and the reciprocal effects of respective treatments.

Testosterone (T), the principal androgen secreted by the testes, plays an essential role in male health. Male hypogonadism is diagnosed based on a combination of associated clinical signs and symptoms and laboratory confirmation of low circulating T levels. In this review, we have highlighted factors, both biological and analytical, that introduce variation into the measurement of serum T concentrations in men; these need to be considered when requesting T levels and interpreting results. There is an ongoing need for analytical standardisation of T assays and harmonisation of pre- and post-analytical laboratory practices, particularly in relation to the laboratory reference intervals provided to clinicians. Further, there is a need to share with service users the most up-to-date and evidence-based action thresholds for serum T as recommended in the literature. Estimation of free testosterone may be helpful. Causes of secondary hypogonadism should be considered. A comprehensive approach is required in the management of male hypogonadism, including lifestyle modification as well as medication where appropriate. The goal of treatment is the resolution of symptoms as well as the optimisation of metabolic, cardiovascular, and bone health. The advice of an endocrinologist should be sought when there is doubt about the cause and appropriate management of the hypogonadism.

Abstract Background Hypogonadism is a worldwide problem among men causing sexual, physical and mental problems. Testosterone therapy is the first‐choice treatment for male hypogonadism, with several side effects, that is, subfertility. Clomiphene citrate (CC) is an alternative off‐label therapy for a certain group of hypogonadal males, especially for those with an active or future child wish. There is scarce literature in usage of CC for men with hypogonadism. The aim of this retrospective study was to evaluate the effectiveness and safety of CC for hypogonadal males. Methods In this single‐centre study, men treated with CC for hypogonadism were evaluated retrospectively. Primary outcome was hormonal evaluation including total testosterone (TT), free testosterone (FT), luteinizing hormone (LH) and follicle stimulating hormone (FSH). Secondary outcomes were hypogonadal symptoms, metabolic and lipid parameters, haemoglobin (Hb), haematocrit (Ht), prostate specific antigen (PSA), side effects, the effect of a trial without medication and potential predictors for biochemical and clinical response. Results In total, 153 hypogonadal men were treated with CC. Mean TT, FT, LH and FSH increased during treatment. TT increased from 9 to 16 nmol/L, with a biochemical increase in 89% of the patients. In patients who continued CC treatment, an increased level of TT persisted after 8 years of treatment. With CC treatment, 74% of the patients experienced hypogonadal symptom improvement. LH at the lower normal range before CC treatment was predictive for better TT response. During CC therapy, few side effects were reported and no clinical important changes in PSA, Hb and Ht were found. Conclusion Clomiphene citrate is an effective therapy on short and long term, improving both clinical symptoms and biochemical markers of male hypogonadism with few side effects and good safety aspects.

Low Energy Availability (LEA) arises from the inability to cover energy needs and requirements of training or normal physiological functions. This value differs from the energy balance, which takes into account the total daily energy intake compared to all the energy expended, regardless of the amount of fat-free mass. Insufficient energy consumption affects recovery, adaptation processes, increases the risk of injury or illness, so all of this can negatively affect performance. This mini-review is written on research articles in Pubmed database related to LEA in endurance-trained men and its impact on performance and testosterone. This article also clarifies the prevalence of LEA in male endurance athletes and its correlation to Relative Energy Deficiency in Sports (RED-S). LEA occurs in male endurance athletes and correlates with decreased testosterone levels, decreased bone density and also Resting Metabolic Rate. In endurance-trained men, there is great potential for the negative consequences of low energy availability. It can also be said that there are possibilities for primary screening, so we recommend regular check-ups of blood markers, body structure and keeping not only training but also dietary records, which can increase awareness of an adequate energy balance.

Objective: To determine whether resveratrol (Res) can correct osteoporosis induced in a rat model of male hypogonadism. Methods: Thirty-two rats were randomly divided into 4 groups, 8 in each group; 1) a control sham group: underwent a similar surgical procedure for induction of orchiectomy (ORCD) without ligation of any arteries or veins or removal of the testis and epididymis; 2) a control + Res-treated group (Con+Res): underwent sham surgery similar to the control, but was then treated with Res, as described below; 3) an ORCD-induced group: bilateral ORCD surgery as described above, and 4) a ORCD+Res-treated group: bilateral ORCD surgery followed by Res treatment. Res treatment began 4 weeks after ORCD and continued for 12 weeks. After 12 weeks, bone mineral density (BMD) and bone mineral content (BMC) were measured in the tibia and femur of each rat's right hind leg. Blood levels of bone turnover indicators such as deoxypyridinoline (Dpd), N-telopeptide of type I collagen (NTX I), alkaline phosphatase (ALP), and osteocalcin (OC), as well as receptor activator of nuclear factor kappa B (RANK) and osteoprotegerin (OPG) were assessed. Results: ORCD significantly decreased BMD (P<0.01) and significantly increased bone resorption, manifested by increased RANK. In addition, it inhibited serum levels of OPG and OC. Res treatment after ORCD effectively increased serum levels of bone formation markers such as OPG and OC, compared with testisectomized rats (P<0.05). Conclusion: Res could ameliorate bone loss induced by male hypogonadism, possible via restoration of the normal balance between RANK and OPG. [ABSTRACT FROM AUTHOR]

Purpose: To prospectively investigate the effects of treatment with liraglutide, a glucagon-like peptide 1 (GLP1) analog, on reproductive and sexual function in men with metabolic hypogonadism who are of childbearing age. Materials and Methods: To accomplish this purpose, 110 men of childbearing age (18–35 years) with metabolic hypogonadism were enrolled and divided into three groups, according to their desire to have children. Group A was made up of men actively seeking fatherhood, Group B, of men who did not seek fatherhood, and Group C, of men who had already fathered a child. Group A patients were treated with gonadotropins (urofollitropin at 150 IU, three times a week, and human chorionic gonadotropin at 2000 IU, twice a week), Group B patients with liraglutide (3 mg daily), and Group C patients with transdermal testosterone (60 mg per day). All patients were treated for 4 months. Results: Patients treated with liraglutide (Group B) showed significant improvement in conventional sperm parameters, compared to baseline and Group A patients, and in the quality of erectile function compared to baseline and patients of Groups A and C. In addition, they had significantly higher levels of total testosterone and sex hormone-binding globulin serum levels after 4 months of treatment with liraglutide than those achieved by patients in the other two groups at the end of the respective treatments. Finally, Group B patients also showed significantly higher serum gonadotropin levels than the other groups. Conclusions: The results of this study showed, for the first time, the efficacy of liraglutide, a GLP1 analog, for the pharmacological treatment of male patients with metabolic hypogonadism. Liraglutide has also shown advantages over traditional treatments on both reproductive and sexual function and appears to offer greater benefits in terms of metabolic protection. These findings suggest that liraglutide is a useful drug for the treatment of obese males with metabolic hypogonadism. [ABSTRACT FROM AUTHOR]

Long-term data evaluating the efficacy and safety of oral testosterone undecanoate (oral TU; JATENZO) in adult hypogonadal men provides important information for healthcare professionals who prescribe testosterone replacement therapy (TRT). To determine the efficacy and safety of long-term oral TU therapy, including its impact on total testosterone (T) levels and psychosexual functioning. Hypogonadal men, between 18 and 75 years old, (mean age 56.2; 87.2% white) who completed a 12-month, open-label, multicenter, randomized, active-controlled trial were given the opportunity to enroll in a 12-month extension study. Among the 129 eligible TU-treated subjects, 86 chose this option, and 69 completed 24 months of uninterrupted oral TU therapy. The efficacy of oral TU was documented by measuring total serum T concentrations; sexual function was measured using the Psychosexual Daily Questionnaire (PDQ). For safety, liver function tests, cardiovascular endpoints, and prostate health were measured. Over 2 years, total serum T concentrations for patients treated with oral TU were in the eugonadal range (300–1,000 ng/dL [10–35 nmol/L]; mean ± SD: 617 ± 427 ng/dL [21 ± 15 nmol/L]) and increased significantly from baseline (P <.0001). For sexual function, mean score changes versus baseline for all PDQ domains at all time points were significantly improved (P <.0011 for all). For the sexual activity and sexual desire components, patient scores were consistently greater than validated thresholds for clinically meaningful change. Typical T-induced safety changes were observed, including a 3–6 mm Hg increase in systolic blood pressure (P <.05); a slight increase in hematocrit (P <.0001) that stayed <48% throughout the study; no clinically significant changes in prostate-specific antigen levels; and decreased high-density lipoprotein cholesterol (-9.8 ± 0.9 mg/dL from baseline; P <.0001). There were no clinically significant changes from baseline in liver function tests. Over 2 years of treatment, this novel oral TU formulation maintained total T concentrations in mideugonadal ranges, with improvements in sexual function and no clinically significant changes in liver function or other safety concerns previously associated with oral TRT. These are the first long-term data to evaluate the efficacy and safety of a novel formulation of oral TU; the comparative long-term safety of oral TU would be strengthened by confirmatory studies versus other TRT formulations. Oral TU offers a safe and effective long-term treatment option for men with hypogonadism. Honig S, Gittelman M, Kaminetsky J, et al. Two-Year Analysis of a New Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men: Efficacy, Impact on Psychosexual Function, and Safety. J Sex Med 2022;19:1750–1758. [ABSTRACT FROM AUTHOR]

Sexual dysfunction, which is defined as 'difficulty during any stage of the sexual encounter that prevents or impairs the individual or couple from enjoying sexual activity', is globally prevalent in males with prediabetes and diabetes. It is an early harbinger of cardiovascular diseases and has a profound impact on one's physical, mental, and social health. Among patients with either prediabetes or diabetes, the most common male sexual dysfunctions are hypogonadism, erectile dysfunction, and premature ejaculation. In Asia, although sexual health is an important factor of men's health, it is rarely discussed freely in real‐life practice. Addressing sexual health in Asian males has always been challenging with multiple barriers at the levels of patients and health care providers. Therefore, the assessment and management of sexual dysfunction in routine clinical practice should involve a holistic approach with effective patient–provider communication. In this review, we discuss the epidemiology, pathophysiology, and the management of hypogonadism, erectile dysfunction, and premature ejaculation among males with either prediabetes or diabetes (type 1 and type 2), as well as the evidence gaps across Asia. [ABSTRACT FROM AUTHOR]

Compared to women, increasing male age is not accompanied by such marked changes in reproductive function but changes certainly do happen. These include alterations to the hypothalamo-pituitary-testicular axis, with resultant implications for testosterone production and bioavailability as well as spermatogenesis. There is a decline in sexual function as men age, with a dramatic increase in the prevalence of erectile dysfunction after the age of 40, which is a marker for both clinically evident as well as covert coronary artery disease. Despite a quantitative decline in spermatogenesis and reduced fecundability, the male potential for fertility persists throughout adult life, however there are also increasingly recognised alterations in sperm quality and function with significant implications for offspring health. These changes are relevant to both natural and medically assisted conception. [ABSTRACT FROM AUTHOR]

The relationship between varicocele and hypogonadism becomes clearer everyday thanks to the most recent literature, particularly with regards to the impact of varicocele repair on serum testosterone level improvement in hypogonadal patients. We selected English articles published from 1964 to September 2021. The search terms “varicocele” and “hypogonadism” were used as filters. A total of 102 studies have been obtained. For the meta-analysis, the pooled mean differences (MDs) for continuous variables and the ln(OR) were used for data pooling observational studies. A total of 15 articles have been finally included: nine retrospective and six observational. Testosterone levels pre- and after surgery were reported in four studies. There was statistically significant heterogeneity in these studies (chi2 = 267.09, I2 = 72%; p = 0.01). Mean differences of total testosterone was statistically different in men pre- and after-surgery (mean difference = 106.76; p < 0.0001). It is indeed established that altered environments caused by varicocele cause pantesticular insult, but it has not been unequivocally determined whether men with varicocele are at increased risk for the development of clinical hypogonadal symptoms.

Male hypogonadism arises from the inadequate production of testosterone (T) by the testes, primarily due to Leydig cell (LC) dysfunction. Small molecules possess several advantages, including high cell permeability, ease of synthesis, standardization, and low effective concentration. Recent investigations have illuminated the potential of small molecule combinations to facilitate direct lineage reprogramming, removing the need for transgenes by modulating cellular signaling pathways and epigenetic modifications. In this study, we have identified a specific cocktail of small molecules, comprising forskolin, DAPT, purmorphamine, 8-Br-cAMP, 20α-hydroxycholesterol, and SAG, capable of promoting the conversion of fibroblasts into Leydig-like cells (LLCs). These LLCs expressed key genes involved in testosterone synthesis, such as Star, Cyp11a1, and Hsd3b1, and exhibited the ability to secrete testosterone in vitro. Furthermore, they successfully restored serum testosterone levels in testosterone-castrated mice in vivo. The small molecule cocktails also induced alterations in the epigenetic marks, specifically H3K4me3, and enhanced chromosomal accessibility on core steroidogenesis genes. This study presents a reliable methodology for generating Leydig-like seed cells that holds promise as a novel therapeutic approach for hypogonadism.

No meta-analysis is available which has analysed the role of aromatase inhibitors (AIs) in hypogonadism in adult males related to obesity and aging. This meta-analysis intended to address this knowledge gap. Electronic databases were searched for studies involving adult males with hypogonadism. The primary outcomes were changes in total testosterone (TT). Secondary outcomes were alterations in oestradiol, luteinizing hormone (LH), and side-effect profile. From initially screened 177 articles, data from three randomised controlled trials(RCTs) (118 patients) and three uncontrolled studies(52 patients) were analysed. AIs were associated with significantly greater improvement in TT after three months [mean difference (MD) 7.08 nmol/L (95% Confidence Interval (CI): 5.92–8.24); P < 0.01; I2 = 0%], six months [MD 6.61 nmol/L (95% CI: 5.30–7.93); P < 0.01] and 12 months [MD 5.20 nmol/L (95% CI: 3.78–6.62); P < 0.01] therapy. AIs were associated with greater reduction in oestradiol after three months [MD -3.07 pmol/L (95% CI: -5.27– -0.87); P < 0.01; I2 = 40%], six months [MD -5.39 pmol/L (95% CI: -7.18– -3.60); P < 0.01] and 12 months [MD -8.3 pmol/L (95% CI: -15.97– -0.63); P = 0.03] therapy. AIs were associated with greater increase in LH after three months [MD 1.79 IU/L (95% CI: 0.77–2.81); P < 0.01; I2 = 0%], six months [MD 2.20 IU/L (95% CI: 0.29 – 4.11); P = 0.02] and 12 months [MD 1.70 IU/L (95% CI: 0.28–3.12); P = 0.02] therapy. Occurrence of treatment-emergent adverse events[Risk ratio (RR) 1.48 (95% CI: 0.47–4.66); P = 0.45; I2 = 0%] and severe adverse events[RR 2.48 (95% CI: 0.42–14.66); P = 0.32; I2 = 0%] were similar among AIs and controls. Following six-month treatment, AIs were associated with significantly lower bone mineral density (BMD) at lumbar-spine [MD -0.04 gm/cm2 (95% CI: -0.08– -0.01); P = 0.03], but not total hip [MD 0.01 gm/cm2 (95% CI: -0.02–0.04); P = 0.55] and femoral neck [MD 0.02 gm/cm2 (95% CI: -0.01–0.05); P = 0.12] compared to controls. This meta-analysis highlights the good efficacy of AIs in improving TT over 3–12 months of use. Adverse impact on spine bone density remains a concern in obese ageing males and warrants further evaluation.

According to the free hormone hypothesis, biological activity of a certain hormone is best reflected by free rather than total hormone concentrations. A crucial element in this theory is the presence of binding proteins, which function as gatekeepers for steroid action. For testosterone, tissue exposure is governed by a delicate equilibrium between free and total testosterone which is determined through interaction with the binding proteins sex hormone-binding globulin and albumin. Ageing, genetics and various pathological conditions influence this equilibrium, hereby possibly modulating hormonal exposure to the target tissues. Despite ongoing controversy on the subject, strong evidence from recent in vitro, in vivo and human experiments emphasizes the relevance of free testosterone. Currently, however, clinical possibilities for free hormone diagnostics are limited. Direct immunoassays are inaccurate, while gold standard liquid chromatography with tandem mass spectrometry (LC–MS/MS) coupled equilibrium dialysis is not available for clinical routine. Calculation models for free testosterone, despite intrinsic limitations, provide a suitable alternative, of which the Vermeulen calculator is currently the preferred method. Calculated free testosterone is indeed associated with bone health, frailty and other clinical endpoints. Moreover, the added value of free testosterone in the clinical diagnosis of male hypogonadism is clearly evident. In suspected hypogonadal men in whom borderline low total testosterone and/or altered sex hormone-binding globulin levels are detected, the determination of free testosterone avoids under- and overdiagnosis, facilitating adequate prescription of hormonal replacement therapy. As such, free testosterone should be integrated as a standard biochemical parameter, on top of total testosterone, in the diagnostic workflow of male hypogonadism. [ABSTRACT FROM AUTHOR]

No meta-analysis is available which has analysed the role of aromatase inhibitors (AIs) in hypogonadism in adult males related to obesity and aging. This meta-analysis intended to address this knowledge gap. Electronic databases were searched for studies involving adult males with hypogonadism. The primary outcomes were changes in total testosterone (TT). Secondary outcomes were alterations in oestradiol, luteinizing hormone (LH), and side-effect profile. From initially screened 177 articles, data from three randomised controlled trials(RCTs) (118 patients) and three uncontrolled studies(52 patients) were analysed. AIs were associated with significantly greater improvement in TT after three months [mean difference (MD) 7.08 nmol/L (95% Confidence Interval (CI): 5.92–8.24); P < 0.01; I2 = 0%], six months [MD 6.61 nmol/L (95% CI: 5.30–7.93); P < 0.01] and 12 months [MD 5.20 nmol/L (95% CI: 3.78–6.62); P < 0.01] therapy. AIs were associated with greater reduction in oestradiol after three months [MD -3.07 pmol/L (95% CI: -5.27– -0.87); P < 0.01; I2 = 40%], six months [MD -5.39 pmol/L (95% CI: -7.18– -3.60); P < 0.01] and 12 months [MD -8.3 pmol/L (95% CI: -15.97– -0.63); P = 0.03] therapy. AIs were associated with greater increase in LH after three months [MD 1.79 IU/L (95% CI: 0.77–2.81); P < 0.01; I2 = 0%], six months [MD 2.20 IU/L (95% CI: 0.29 – 4.11); P = 0.02] and 12 months [MD 1.70 IU/L (95% CI: 0.28–3.12); P = 0.02] therapy. Occurrence of treatment-emergent adverse events[Risk ratio (RR) 1.48 (95% CI: 0.47–4.66); P = 0.45; I2 = 0%] and severe adverse events[RR 2.48 (95% CI: 0.42–14.66); P = 0.32; I2 = 0%] were similar among AIs and controls. Following six-month treatment, AIs were associated with significantly lower bone mineral density (BMD) at lumbar-spine [MD -0.04 gm/cm2 (95% CI: -0.08– -0.01); P = 0.03], but not total hip [MD 0.01 gm/cm2 (95% CI: -0.02–0.04); P = 0.55] and femoral neck [MD 0.02 gm/cm2 (95% CI: -0.01–0.05); P = 0.12] compared to controls. This meta-analysis highlights the good efficacy of AIs in improving TT over 3–12 months of use. Adverse impact on spine bone density remains a concern in obese ageing males and warrants further evaluation. [ABSTRACT FROM AUTHOR]

Male hypogonadism is a clinical syndrome which is the result of insufficient production of the sex hormone testosterone by the testicles and the number of spermatozoa. The article reveals modern views on the physiology and pathophysiology of testosteroneogenesis in the male organism, provides information on the etiology, pathogenesis, classification, diagnosis and modern treatment of hypogonadism in men. Literature on the results of global and European researches in recent years, as well as materials of the Guideline of the European Association of Urology for 2022, were used in the article. An individual therapeutic approach to each patient with hypogonadism was demonstrated. The importance of diagnosis of chronic and systemic comorbid diseases that cause the risk of hypogonadism, the need to determine the body mass index and the measurement of waist circumference, the size of the testicles, the penis and the presence of secondary sexual characteristic was established. The article includes necessary biochemical and instrumental studies for the diagnosis of hypogonadism. Specific contraindications for hormone replacement therapy are identified. Absolute contraindications for testosterone therapy are indicated: topically widespread or metastatic prostate cancer (PC), breast cancer of men; men who desire to have children; hematocrit level > 54%; uncontrolled or poorly controlled stagnant heart failure. Relative contraindications include IPSS>19, initial hematocrit of 48-50 %, venous thromboembolism in a family history. The article also provides recommendations for testosterone therapy. It has been proven that testosterone therapy improves mild forms of erectile dysfunction (ED) and libido in men with hypogonade states; improves the frequency of sexual intercourses, orgasm and general pleasure; increases low-fat mass, reduces fat and improves insulin resistance; normalizes body weight, waist circumference and lipid profile; relieves the symptoms of depression in men with hypogonadism; improves bone mineral density. It has been demonstrated that the use of testosterone therapy in eugonadal men is not indicated. Testosterone therapy should be used as first-line treatment in patients with symptomatic hypogonadism and moderate ED. In addition, it is necessary to use a combination of type 5 phosphodiesterase inhibitors and testosterone treatment in more severe ED forms. It is also necessary to use standard medical treatments for severe symptoms of depression and osteoporosis. The therapy of hypogonadism, non-medication and medication, the necessary medicines and the peculiarities of their use are widely described. The article shows that weight loss due to low-calorie diet and regular physical activity leads to a slight improvement in testosterone levels, testosterone gels and prolonged injection drugs are testosterone drugs have the best safety profile, and gonadotropin treatment can be used in men with secondary hypogonadism. It is noted that before the treatment with testosterone, it is necessary to treat organic causes of hypogonadism (for example, pituitary tumors, hyperprolactinemia, etc.), improve lifestyle and reduce body weight in persons with obesity; cancel drugs that can impair testosterone production. Much attention is paid to the risk factors by the treatment with testosterone. Testosterone therapy is contraindicated for men with secondary hypogonadism who wish fertility, men with active PC or breast cancer. Restoration of testosterone concentration in serum relieves the symptoms and signs of hypogonadism in men after 3 months of treatment. Therefore, testosterone therapy leads to improvement of the quality of patient’s life. [ABSTRACT FROM AUTHOR]

The article comments on the TRAVERSE study, a randomized, placebo-controlled trial designed to determine the cardiovascular risk of testosterone therapy in men. It summarizes findings of the study including absence of significant difference in the rate of composite cardiovascular events and the association of testosterone therapy with high incidence of nonfatal arrhythmias and atrial fibrillation. It argues that the study design has created a switchback in the management of male hypogonadism.

Male-obesity-associated secondary hypogonadism (MOSH) is a very prevalent entity that may resolve after marked weight loss. Adiponectin (APN) is an adipokine with anti-inflammatory properties that regulates metabolism. Low-circulating APN is associated with obesity, diabetes, and cardiovascular risk, along with circulating testosterone. We aimed to evaluate APN changes in men with MOSH (low circulating free testosterone (FT) with low or normal gonadotropins) and without it after metabolic surgery. We look for their possible association with cardiovascular risk measured by carotid intima-media thickness (cIMT). We included 60 men (20 submitted to lifestyle modification, 20 to sleeve gastrectomy, and 20 to gastric bypass) evaluated at baseline and 6 months after. The increase in APN at follow-up was reduction in patients with persistent MOSH (n = 10) vs. those without MOSH (n = 30) and MOSH resolution (n = 20), and the former did not achieve a decrease in cIMT. The increase in APN correlated positively with FT (r = 0.320, p = 0.013) and inversely with cIMT (r = −0.283, p = 0.028). FT inversely correlated with cIMT (r = −0.269, p = 0.038). In conclusion, men without MOSH or with MOSH resolution showed a high increase in APN after weight loss with beneficial effects on cIMT. Those without MOSH resolution failed to attain these effects. [ABSTRACT FROM AUTHOR]

Abstract Background Hypogonadism associated with cancer is reported to cause cachexia and a variety of physical and psychological symptoms. This study aims to evaluate whether androgen replacement therapy can improve cancer‐related symptoms in male advanced cancer patients. Methods An investigator‐initiated, prospective, and randomized controlled study was conducted. Patients with low serum testosterone levels (total or free testosterone levels were

The coronavirus disease 2019 (COVID-19) outbreak constitutes an unparalleled socioeconomic burden on the global scale. In critically ill COVID-19 patients, the disease manifests as a state of hyper inflammation causing the ‘cytokine storm’, which leads to various pulmonary, cardiovascular, and spurious manifestations. One such reported sequelae of COVID-19 is sexual dysfunction in males even after recovery from the disease. Various mechanisms have been proposed regarding the erectile dysfunction a patient suffers after COVID-19. Most important is the hypothesis of endothelial dysregulation, subclinical hypogonadism, psychosocial misery, and pulmonary impairment contributing to erectile dysfunction. Assessment of testicular function and hormonal axis is needed to assess the novel association of COVID-19 with sexual and reproductive health issues in males.