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Introduction and Objectives: Chronic obstructive pulmonary disease (COPD) frequently coexists with other comorbidities, including hypogonadism. However, the association between COPD severity and hypogonadism remains controversial. This study aimed to evaluate this association and compare the clinical characteristics of hypogonadal and eugonadal COPD patients., Materials and Methods: A cross-sectional study including men with stable COPD was performed. Hypogonadism was diagnosed based on the presence of symptoms, according to the Androgen Deficiency in Aging Males questionnaire, and a total testosterone deficit (<300ng/dL). COPD severity was classified according to the Spanish COPD guideline risk classification. A multivariate logistic regression analysis was performed in order to evaluate the relationship between COPD severity and hypogonadism., Results: 134 subjects were recruited. The prevalence of hypogonadism was higher in severe COPD than in mild COPD, with a prevalence ratio of 1.8 (p=0.007). An increased odds of hypogonadism was observed in severe COPD subjects (OR 2.60, 95% CI 1.23-5.48, p=0.012) independent of age, body mass index, cardiovascular disease, and chronic renal failure. Hypogonadal COPD patients exhibited lower percentage levels of FVC and FEV 1 and a higher degree of dyspnea than compared to eugonadal COPD patients., Conclusion: Patients with severe COPD had a higher prevalence of hypogonadism compared to those with mild COPD. Additionally, severe COPD was identified as an independent risk factor for hypogonadism. These findings suggest that hypogonadism should be evaluated in patients with COPD, particularly in those with severe disease., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Aims: To compare the effects of semaglutide and testosterone replacement therapy (TRT) on semen quality and parameters of functional hypogonadism (FH) in men with type 2 diabetes mellitus and obesity., Materials and Methods: We designed a randomised open-label trial in 25 men with type 2 diabetes (aged 50 [46-60] years, BMI 35.9 [32.8-38.7] kg/m 2 ) and FH randomised to semaglutide (SEMA) 1 mg/week or intramuscular testosterone undecanoate (TRT) 1000 mg/10-12 weeks for 24 weeks. Semen analysis and parameters of FH were measured at baseline and after 24 weeks of treatment. Participants completed questionnaires of the International Index of Erectile Function-15 (IIEF-15) and the Aging Symptoms in Men (AMS)., Results: The quality of baseline sperm parameters of our study cohort was poor, below the 5th percentile of reference values. In the SEMA group, there was a significant increase in morphologically normal sperm from baseline to the end of the study (2% [2; 3.5] vs. 4% [2; 5.5]; p = 0.012), whereas sperm concentration and total number decreased significantly in the TRT group. Compared to TRT, the SEMA group had a significantly higher number of morphologically normal sperm, sperm concentration and total number. Both groups experienced an increase in total testosterone and improvement in the AMS score, whereas the IIEF-15 score significantly improved only in the TRT group., Conclusion: Semaglutide markedly improved sperm morphology, total testosterone levels and symptoms of hypogonadism. These findings highlight semaglutide's potential as a therapeutic approach for men with obesity-related FH who desire fertility., Clinical Trial Registration Number: NCT06489457, www., Clinicaltrials: gov., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

The study of the relationship between depression and functional hypogonadism in men is an interesting and difficult task. The purpose of the presented review was to identify the problem of functional male hypogonadism, to show a complex multi-stage neurohumoral mechanism of regulation of its potential to influence the affective sphere and to address the influence of pharmacotherapy on the formation of sexual disorders in men. The primary search for literature data was conducted using PubMed (Medline), PsycINFO and Cochrane CENTRAL, e-library.ru, databases using the keywords «hypogonadism», «depression», «testosterone», «antidepressants», «antipsychotics». As a result, 63 sources of information were selected and analyzed. Among the selected papers, there were 2 meta-analyses, 12 reviews and 42 comparative studies, including longitudinal, cross-sectional and controlled studies, 7 practical manuals. Based on the data obtained, it is possible to draw conclusions about the relationship between depression and functional hypogonadism as well as about the possibility of pathogenetic mechanisms of depression to cause changes in the state of the hypothalamic-pituitary-gonadal axis, leading to hypogonadism and vice versa, the ability of hypogonadism to form and enhance depressive symptoms. The concept of the mechanisms of regulation of steroidogenesis can allow the development of alternative methods of therapy and augmentation of depressive disorders, minimization of the number of sexual dysfunctions of psychopharmacotherapy. Further large-scale studies are needed for an in-depth study of this topic and the resolution of a number of contradictions.

Purpose: The aim of this project was to characterize the incidence of men's health disorders, specifically focusing on the incidence of erectile dysfunction (ED) and testosterone deficiency (TD) in a large, nationwide study of testicular cancer (TC) survivors treated in a centralized health care system., Materials and Methods: We conducted a retrospective cohort study of US veterans diagnosed with TC from 1990 to 2021. These veterans were compared with an age-matched and race-matched control group of US veterans without a diagnosis of TC. ED and TD were defined by the presence of diagnosis codes or at least a 6-month prescription for medications treating these conditions or both. Time was measured from the date of TC diagnosis (for patients with TC and matched TC patient date for the corresponding noncancer controls). Impact of chemotherapy among TC survivors on ED and TD was evaluated using multivariable Cox regression models., Results: The cohort included 1754 patients with TC compared with 7117 noncancer controls, with a mean age at diagnosis of 42 years. Patients with TC were significantly more likely than controls to experience ED (hazard ratio, 2.97; 95% CI, 2.68-3.28; P < .001) and TD (hazard ratio, 6.71; 95% CI, 5.78-7.81; P < .001). However, within the TC group, there was no significant difference in the incidence of ED and TD when stratified by receipt of chemotherapy ( P = .9 and P = .066, respectively)., Conclusions: Men's health disorders arise commonly in the lives of TC survivors. It is important for treating physicians to identify these and conduct sexual health assessments as part of survivorship care.

Introduction: 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.

Purpose: Although several reviews have evaluated the use of PDE5 inhibitors (PDE5i) for treating erectile dysfunction (ED), their specific use in middle-aged and old patients has not been fully evaluated. Given that elderly patients with ED often have a complex combination of systemic and sexual health risk factors, the safety and efficacy of PDE5i in such a context are hereby reviewed., Materials and Methods: A thorough examination of existing literature has been conducted on PubMed., Results: PDE5i has good safety and efficacy, but the situation is more complex for patients with hypogonadism than those with normal testosterone levels, with reduced responsiveness to PDE5i. In this case, combination therapy with testosterone is recommended, safe and effective., Conclusions: Eliminating or reducing reversible risk factors and controlling or slowing the development of irreversible factors is an important foundation for using PDE5i to treat ED in all patients, especially middle-aged and elderly ones.

Objective: To assess the association between varicocele and hypogonadism, or erectile dysfunction., Methods: We searched MEDLINE, EMBASE, LILACS, CENTRAL, and other sources. We included cohort, case-control, and cross-sectional studies. The primary outcome was the association between varicocele and hypogonadism, or erectile dysfunction, and the secondary outcome included semen analysis. We assessed the risk of bias with the Newcastle-Ottawa Scale. We performed statistical analysis in Review Manager 5.3 and reported information about the Odds Ratio (OR) with a 95% confidence interval. We produced a forest plot for the primary outcome., Results: We included ten studies in qualitative analysis and six studies in quantitative analysis. Most of the cross-sectional studies showed a low risk of bias, not so for the two case-control studies, which represented a high risk of bias. Most of the reports described a correlation between having varicocele and presenting low testosterone levels: the meta-analysis showed that there is a significant association between varicocele and hypogonadism (OR 3.27 95% CI 1.23 to 8.68). Regarding varicocele and erectile, only one study showed a significant difference in erectile function in comparison to varicocele patients and men without varicocele., Conclusion: There is an association between varicocele presence and hypogonadism, although more studies are needed. Besides, not much is reported about an association between varicocele and erectile dysfunction, but impairment can occur through hormone disturbances., (Copyright © 2024 AEU. Published by Elsevier España, S.L.U. All rights reserved.)

This study aims to assess the effectiveness of pulsed gonadotropin-releasing hormone (GnRH) micropump replacement therapy in the treatment of hypogonadotropic hypogonadism (HH) caused by primary empty sella (PES).The efficacy of pulsed GnRH replacement therapy using the micropump was evaluated in a middle-aged male patient with HH who had experienced the loss of his only child. Relevant literature was also consulted to compare the differences between pulse GnRH treatment and conventional treatment in terms of the development of secondary sexual characteristics, sex hormone levels, sperm production rate, and sperm activity rate in male patient with HH.In this report, a 45-year-old male diagnosed with HH and PES presented with fatigue and decreased libido. The main characteristics included decreased follicle stimulating hormone (FSH) levels of 0.03 mIU/mL, luteinizing hormone (LH) levels of 0.02 mIU/mL, and testosterone (T) levels of 0.72 nmol/L. Magnetic resonance imaging (MRI) revealed an empty sella. Semen analysis showed a small number of normal sperm with reduced motility. During treatment with the micropump pulse GnRH, the patient experienced no side effects and showed improvements in fatigue, reduced libido, sexual urge, anxiety, and feelings of inferiority. LH, FSH, and T levels returned to normal, while sperm activity rate increased to 79.9%. Ultimately, the patient's spouse achieved a natural pregnancy.Pulsed gonadotropin delivery using the micropump demonstrates good efficacy and tolerability, and aligns more closely with the physiological rhythm of GnRH secretion in the human body., Competing Interests: Declarations. Ethics Approval and Consent to Participate: Informed consent was obtained from the patients in the study. This study was approved by the Medical Ethics Committee of The Second Affiliated Hospital of Army Medical University. Consent for Publication: Written informed consent for the publication of his clinical details and clinical images was obtained from the patient. A copy of the consent form is available for review by the Editor of this journal. Competing Interests: There were no conflicts of interest to declare., (© 2024. The Author(s).)

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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Results of recent studies suggest that high levels of endogenous testosterone decrease the risk of diabetes. Testosterone therapy may delay the transition from prediabetes to diabetes and accelerate healing of diabetic foot ulcers in hypogonadal men. We investigated whether testosterone therapy in this population decreases the occurrence of diabetic foot complications within 1 and 5 years of diabetes diagnosis., Methods: Optum's deidentified Clinformatics Data Mart database was searched for male patients with diabetes. Associations between testosterone therapy and the occurrence of ulceration or the use of wound care were explored in the entire population and in those with and without hypogonadism using both bivariate and multivariate analyses., Results: Contrary to the hypotheses, testosterone therapy seems to confer increased risk of diabetic foot complications. In hypogonadal men with at least 1 year of follow-up after diabetes diagnosis, any use of testosterone therapy increased the odds of wound care utilization by a factor of 1.10 (95% confidence interval, 1.03-1.17), and the odds of ulceration by a factor of 1.13 (95% confidence interval, 1.03-1.24). Similar results are seen in all men, both with and without hypogonadism. Further exploration reveals that hypogonadism also increases the risk of wounds among people with diabetes with care utilization in the entire population., Conclusions: Further research is needed to elucidate the mechanisms by which hypogonadism and testosterone therapy impact diabetic foot complications, and whether these mechanisms are mediated by vascular or neurologic factors.

We sought to understand the relationship between hypogonadism and testosterone replacement therapy (TRT) in hypogonadal men on the risk of developing localized and metastatic prostate cancer. We used the Merative MarketScan database of commercial claims encounters to identify men diagnosed with hypogonadism. These men were matched to eugonadal men who served as controls. Multivariate negative binomial regression analysis of prostate cancer diagnoses, hypogonadism, and TRT in hypogonadal men adjusting for various known confounding factors was used to understand the impact of hypogonadism and TRT on prostate cancer risk. We identified 3,222,904 men who met inclusion criteria, of which 50% were diagnosed with hypogonadism (1,611,452) and each were matched to a control (1,611,452). The incidence of prostate cancer was 2.16%, 1.55%, and 1.99% in eugonadal controls, hypogonadal men on TRT, and hypogonadal men without TRT, respectively (p < 0.001). Untreated hypogonadism was independently associated with a decreased risk of localized prostate cancer (IRR 0.46, 95% CI 0.43-0.50, p < 0.001) compared to eugonadal controls. Hypogonadal men on TRT also had a significantly decreased risk of localized prostate cancer (IRR 0.49, 95% CI 0.45-0.53, p < 0.001). Furthermore, hypogonadal men on TRT (IRR 0.21, 95% CI 0.19-0.24, p < 0.001) or without TRT (IRR 0.20, 95% CI 0.18-0.22, p < 0.001) both had significantly decreased risk of metastatic prostate cancer, respectively. Our population-based analysis suggests that untreated hypogonadism in men is associated with a 50% decreased incidence of localized prostate cancer and an 80% decreased incidence of metastatic prostate cancer. TRT in hypogonadal men was also associated with a decreased risk of subsequent prostate cancer. Further research is needed to better understand the relationship between hypogonadism and TRT in hypogonadal men on the risk of subsequent prostate cancer., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Leprosy affects various organs in addition to skin, eyes, and peripheral nerves. Testicular involvement in leprosy patients is common and causes disturbance in endocrine function of the testis and results in hypogonadism. Hypogonadism is frequently undiagnosed and underreported., Objective: This study aimed to assess hypogonadism and associated factors among leprosy patients at Alert Comprehensive Specialized Hospital, Ethiopia., Methods: A cross-sectional study design was used in which consecutive 146 male leprosy patients aged between 18 to 65 years attending outpatient follow-up at leprosy outpatient clinic were included. Data was gathered both from patient charts and through patients' interviews. Androgen deficiency symptoms were assessed by androgen deficiency in the aging male questionnaire, and 5ml of blood samples were taken from study participants and serum total testosterone, LH, and FSH were analyzed by Electrochemiluminescence method. Statistical correlation was assessed by Spearman correlation. A multivariable binary logistic regression model was used to identify the independent factors associated with hypogonadism and P-value <0.05 was used to declare statistical significance., Results: The prevalence of hypogonadism was 39 (26.7%). Out of this, 34 (87.2%) had primary hypogonadism, whereas 5 (12.8%) had secondary hypogonadism. Total testosterone was inversely correlated with Body mass index (r = -0.37, p = 0.002), Luteinizing hormone (r = -0.43, p <0.001), and Follicular stimulating hormone (r = -0.42, p< 0.001). However, Total testosterone was not significantly correlated with age (r = -0.019, p = 0.81). BMI [AOR = 1.32, 95%CI (1.16-1.51)] and grade-II disability [AOR = 3.80, 95%CI (1.23-11.64)] were identified as independent risk factors for hypogonadism., Conclusion: Nearly one-fourth of male leprosy patients had hypogonadism. Overweight and grade-II disability were independent risk factors for hypogonadism., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Urgie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Obesity-induced hypogonadism (OIH) is a prevalent, but often neglected condition in men, which aggravates the metabolic complications of overweight. While hypothalamic suppression of Kiss1-encoded kisspeptin has been suggested to contribute to OIH, the molecular mechanisms for such repression in obesity, and the therapeutic implications thereof, remain unknown., Methods: A combination of bioinformatic, expression and functional analyses was implemented, assessing the role of the evolutionary-conserved miRNAs, miR-137 and miR-325, in mediating obesity-induced suppression of hypothalamic kisspeptin, as putative mechanism of central hypogonadism and metabolic comorbidities. The implications of such miR-137/325-kisspeptin interplay for therapeutic intervention in obesity were also explored using preclinical OIH models., Results: MiR-137/325 repressed human KISS1 3'-UTR in-vitro and inhibited hypothalamic kisspeptin content in male rats, while miR-137/325 expression was up-regulated, and Kiss1/kisspeptin decreased, in the medio-basal hypothalamus of obese rats. Selective over-expression of miR-137 in Kiss1 neurons reduced Kiss1/ kisspeptin and partially replicated reproductive and metabolic alterations of OIH in lean mice. Conversely, interference of the repressive actions of miR-137/325 selectively on Kiss1 3'-UTR in vivo, using target-site blockers (TSB), enhanced kisspeptin content and reversed central hypogonadism in obese rats, together with improvement of glucose intolerance, insulin resistance and cardiovascular and inflammatory markers, despite persistent exposure to obesogenic diet. Reversal of OIH by TSB miR-137/325 was more effective than chronic kisspeptin or testosterone treatments in obese rats., Conclusions: Our data disclose that the miR-137/325-Kisspeptin repressive interaction is a major player in the pathogenesis of obesity-induced hypogonadism and a putative druggable target for improved management of this condition and its metabolic comorbidities in men suffering obesity., Significance Statement: Up to half of the men suffering obesity display also central hypogonadism, an often neglected complication of overweight that can aggravate the clinical course of obesity and its complications. The mechanisms for such obesity-induced hypogonadism remain poorly defined. We show here that the evolutionary conserved miR137/miR325 tandem centrally mediates obesity-induced hypogonadism via repression of the reproductive-stimulatory signal, kisspeptin; this may represent an amenable druggable target for improved management of hypogonadism and other metabolic complications of obesity., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose in relation to the contents of this work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: There is no competing interest.

Background: Isolated hypogonadotropic hypogonadism is a heterogeneous clinical entity. There is a growing list of molecular defects that are associated with hypogonadotropic hypogonadism (HH). TCF12, a recently identified molecular defect, causes craniosynostosis and is suggested to be used as a biomarker for prognosis in various cancer types. Recently, TCF12 variants were shown in a cohort with HH., Case Presentation: A 15.3 years old female patient was referred to the endocrinology clinic for obesity. She had been gaining weight from mid-childhood. She had her first epileptic seizure at the age of 15.1 years and mildly elevated thyroid autoantibodies were detected during evaluation for etiology of seizures. She had not experienced menarche yet. She was operated for left strabismus at the age of 7 years. School performance was poor and she was receiving special education. Tanner stage of breast was 1 and pubic hair was 3. The endocrine workup revealed hypogonadotropic hypogonadism. Also, the Sniffin' Sticks test detected anosmia. Thyroid ultrasonography was performed due to the mildly elevated thyroid autoantibodies, and thyroid nodules with punctate calcifications were detected. Total thyroidectomy and central lymph node dissection were performed regarding the cytological findings of the nodules and multicentric papillary thyroid carcinoma with no lymph node metastasis was detected on pathology specimens. Regarding the phenotypic features of the patients, whole exome sequencing was performed and heterozygous deletion of exon 1 and exon 6-8 in TCF12 was detected., Conclusion: Haploinsufficiency of TCF12 causes anosmic HH. Probably due to the incomplete penetrance and variable expressivity of the disease, patients could display variable phenotypic features such as intellectual disability, developmental delay, and craniosynostosis. Further description of new cases with TCF12 variations could enhance our understanding of craniosynostosis and its potential link to Kallmann syndrome associated with this gene., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Celik, Sezer, Genel, Savas-Erdeve, Karaman and Cetinkaya.)

Objective: POLR3-HLD or 4H leukodystrophy is an autosomal recessive disorder characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, and caused by variants in POLR3A , POLR3B , POLR1C , or POLR3K genes. Neurological and non-neurological clinical features and disease severity vary. While previous studies reference variable cognition, this is the first report of 4H detailing a comprehensive neuropsychological assessment. Method: The current study presents a 20-year-old, English-speaking, right-handed, non-Hispanic White female with 12 years of education with genetically confirmed 4H POLR3B -related leukodystrophy without hormonal replacement treatment. Results: At age 4, developmental delays, ataxia, hearing loss, and abnormal dentition were present. Imaging, endocrinology, and neurologic examinations revealed hypomyelination, reduced cerebellar volume, delayed bone age density, osteopenia, and evidence of adrenarche without signs of true puberty. Neuropsychological assessment at age 20 revealed global cognitive impairment with intellectual, attention, verbal memory retrieval, construction, executive (e.g. processing speed, sustained attention) and math computation deficits, along with behavioral dysregulation. Conclusion: We present the first detailed neuropsychological assessment of a patient with 4H leukodystrophy. The neuropsychological assessment revealed cognitive and behavioral dysexecutive deficits aligning with hypomyelination observed on imaging. Further longitudinal studies are needed to shed light on the neurobehavioral presentation associated with this disorder to assist care providers, patients, and their families.

Purpose: To describe the incidences of hypogonadism, hypertension, and dyslipidaemia in patients with stage 1 seminoma (S1S) testicular cancer (TC) treated with a risk-adapted strategy., Methods: A retrospective analysis from 2000 to 2020 was conducted. Active surveillance (AS), carboplatin one cycle, and carboplatin two cycles were offered according to risk factors. Cumulative incidences and relapse-free survival (RFS) were estimated., Results: Of the 145 patients, 8 (5.4%) were excluded due to bilateral TC or hypogonadism at diagnosis. Median follow-up time was 8.2 years. Eighty-four, 30, and 33 patients were treated with AS, carboplatin one cycle, and carboplatin two cycles, respectively. In the overall population, the 5-year and 10-year cumulative incidences were 1.6% and 5.3% for hypogonadism; 2.0% and 8.6% for hypertension; and 12.4% and 25.1% for dyslipidaemia. No statistically significant differences were found in the incidences among the three adjuvant strategies. Five-year and 10-year RFS were 85.9% and 83.3% for AS; 92.4% and 84.0% for carboplatin one cycle; and 96.7% at both times for carboplatin two cycles., Conclusion: There were no statistically differences in cumulative incidences of hypogonadism, hypertension, and dyslipidaemia in S1S patients treated with a risk-adapted strategy., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Introduction: The associated symptoms of hypogonadism have been reported in patients with various types of cancer. However, the prevalence and significance of hypogonadism among certain hematologic malignancies have not been completely summarized in recent literature., Objective: In this review we aimed to examine the current literature on hypogonadism in patients with hematologic malignancies, with emphasis on leukemias, lymphomas, and multiple myeloma (MM)., Methods: This review included relevant studies published before July 2023 that were retrieved through a search of PubMed using the keywords "hematologic cancer," "hematologic malignancy," blood cancer," "leukemia," "lymphoma," "hypogonadism," "multiple myeloma," and "testosterone.", Results: The search yielded 214 studies, of which 21 met the inclusion criteria. Commonly reported findings were that patients who had received hematopoietic stem cell therapy for acute lymphoblastic leukemia and acute myelogenous leukemia as children had laboratory-confirmed hypogonadism as adults. However, the impact of these diseases on hypogonadal symptoms was variable in these studies.Studies reporting on lymphoma and hypogonadism had mixed results, with some studies finding that the degree of cytotoxic chemotherapy was associated with hypogonadism, while others showed no correlation. Regardless, multiple studies found that hypogonadism secondary to lymphoma treatment and symptoms of hypogonadism had no apparent association.The most comprehensive assessment of the frequency of hypogonadism in an MM cohort found that 74% of 561 MM patients were classified as hypogonadal compared to 33% of patients in a control population. Testosterone supplementation was found to lower interleukin-6 levels, which could potentially help manage some of the adverse effects of MM, including decreased bone mineral density., Conclusion: There is a relationship between hematologic malignancies and hypogonadism, which is likely multifactorial. In this review we established that the most plausible factors are related to the secondary effects of gonadotoxic treatments and/or systemic inflammatory responses to the diseases., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.)

Introduction: Patients with long-term chronic illnesses frequently present with hypogonadism, which is primarily managed through exogenous testosterone. These same patients also experience a high degree of cachexia, a loss of skeletal muscle and adipose tissue., Objective: To perform a contemporary review of the literature to assess the effectiveness of testosterone replacement therapy (TRT) for managing chronic disease-associated cachexia., Methods: We performed a PubMed literature search using MeSH terms to identify studies from 2000 to 2022 on TRT and the following cachexia-related chronic medical diseases: cancer, COPD, HIV/AIDS, and liver cirrhosis., Results: From the literature, 11 primary studies and 1 meta-analysis were selected. Among these studies, 3 evaluated TRT on cancer-associated cachexia, 3 on chronic obstructive pulmonary disease, 4 on HIV and AIDS, and 2 on liver cirrhosis. TRT showed mixed results favoring clinical improvement on each disease., Conclusions: Cachexia is commonly observed in chronic disease states. Its occurrence with hypogonadism, alongside the shared symptoms of these 2 conditions, points toward the management of cachexia through the administration of exogenous testosterone. Robust data in the literature support the use of testosterone in increasing lean body mass, improving energy levels, and enhancing the quality of life for patients with chronic disease. However, the data are variable, and further studies are warranted on the long-term efficacy of TRT in patients with cachexia., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This case report describes a man in his 20s presenting with bilateral crypto-orchidism, micropenis and underdeveloped secondary sexual characteristics. The patient also exhibited hyposmia, eunuchoid stature and gynecomastia. Biochemical investigations revealed low levels of testosterone, luteinising hormone and follicle-stimulating hormone. Hence, he was diagnosed with Kallmann syndrome. Imaging studies showed an absent right kidney and cystic dilatation of the distal ureteric bud, seminal vesicle and absent/hypoplastic ejaculatory duct. The association of hypogonadotropic hypogonadism with Zinner syndrome, a rare condition characterised by renal agenesis, seminal vesicle cyst and ejaculatory duct obstruction, was noted., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© The Author(s) 2024. Published by Oxford University Press.)

(1) Background and objectives : Maturity-onset diabetes of the young (MODY) is a group of diabetes caused by gene defects related to insulin secretion. MODY1, MODY2, and MODY3 are the most common and account for approximately 80% of all cases. Other types are relatively rare. This study describes the clinical, analytical, and genetic characteristics of a patient with MODY10, and diabetic nephropathy, retinopathy, and functional hypogonadism diagnosis. (2) Materials and methods : A clinical case was analyzed and whole exome generation sequencing (WES) was used to detect mutations related to a monogenic variant. (3) Results : A seventeen-year-old male patient, who was diagnosed with apparent type 1 diabetes at the age of eight was started with insulin therapy. He came to the emergency room with glycemic decompensation, facial, and lower limb edema. During his evaluation, he had near-nephrotic range proteinuria of 2902 mg/24 h, a kidney ultrasound showing mild pyelocalyceal dilation, proliferative diabetic retinopathy, and was also diagnosed with functional hypogonadotropic hypogonadism. These comorbidities improved with adequate glycemic control. WES showed missense variant c.94G>A (p.Gly32Ser) in the INS gene, according to Clinvar corresponding to MODY10. It was a "de novo" variant not reported in his parents. (4) Conclusions : Monogenic diabetes (MD) is rare and MODY10 is among the less frequent types. MODY should be suspected in patients with type 1 phenotype with negative autoimmunity even in the absence of a family history of diabetes. To the best of our knowledge, we present here the first patient with these phenotypic traits of MODY10 reported in Latin America.

Introduction: Hypogonadism is associated with frailty, lower health-related quality of life, decreased muscle mass, and premature mortality, which may predispose patients to poor postoperative outcomes. We aimed to determine the prevalence of hypogonadism in men undergoing radical cystectomy (RC) and whether hypogonadism and frailty are associated with adverse postoperative outcomes., Materials and Methods: The IBM MarketScan database was used to identify men who underwent RC between 2012 and 2021. Frailty was determined using published Hospital Frailty Risk Score ranges. Patients were considered to have hypogonadism if diagnosed within 5 years prior to RC. Length of stay (LOS), complications, emergency department (ED) visits and inpatient readmissions were compared. Sub-group analysis of men with hypogonadism was performed to determine the effect of testosterone replacement therapy (TRT) on clinical outcomes., Results: Among 3,727 men who underwent RC, 226 (6.1%) had a diagnosis of hypogonadism. Overall, 565 (15.2%) men were low-risk frailty, 2,214 (59.4%) intermediate-risk frailty, and 948 (25.4%) were high-risk frailty, and men with hypogonadism were significantly more frail compared to men without hypogonadism (P = 0.027). There was no significant difference in LOS, complications, or rate of ED visits and inpatient readmissions between cohorts (P > 0.05). However, high-risk frailty was associated with an increased risk of 90-day ED visit (HR 1.19, 95%CI 1.00-1.41, P = 0.049) and 90-day readmission (HR 1.60, 95%CI 1.29-1.97, P < 0.001) after RC. Among men with hypogonadism, 58 (25.7%) were on TRT. There was no significant difference in frailty, LOS, complications, or 90-day ED visits or 90-day inpatient readmissions between patient with hypogonadism prescribed TRT and those without TRT., Conclusions: These findings suggest that hypogonadism and preoperative frailty may be important to evaluate prior to undergoing RC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Testosterone replacement therapy (TRT) is an indicated treatment of several medical conditions including late-onset hypogonadism, congenital syndromes, and gender affirmation hormonal therapy. Increasing population age, medical benefits, and public awareness of TRT have resulted in increased prevalence of its utilization. However, TRT is not without concern for adverse risks including venous thromboembolic complications, cardiovascular events, and prostate issues. In the field of orthopaedic surgery, research is beginning to delineate the complex relationship between TRT and the development of orthopaedic conditions and potential effects on surgical interventions and outcomes. In this review, we discuss current literature surrounding TRT and subsequent development of osteoarthritis, incidence of total joint arthroplasty, musculotendinous pathology, postoperative infection risk, improvements in postoperative rehabilitation metrics, enhancement of osseous healing, and increased bone-implant integration. The authors suggest future areas of investigation that may provide guidance on how surgeons can mitigate adverse risks while optimizing benefits of TRT in the orthopaedic patient., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Research Question: Can a novel classification system of the infertile male - 'APHRODITE' (Addressing male Patients with Hypogonadism and/or infeRtility Owing to altereD, Idiopathic TEsticular function) - stratify different subgroups of male infertility to help scientists to design clinical trials on the hormonal treatment of male infertility, and clinicians to counsel and treat the endocrinological imbalances in men and, ultimately, increase the chances of natural and assisted conception?, Design: A collaboration between andrologists, reproductive urologists and gynaecologists, with specialization in reproductive medicine and expertise in male infertility, led to the development of the APHRODITE criteria through an iterative consensus process based on clinical patient descriptions and the results of routine laboratory tests, including semen analysis and hormonal testing., Results: Five patient groups were delineated according to the APHRODITE criteria; (1) Hypogonadotrophic hypogonadism (acquired and congenital); (2) Idiopathic male infertility with lowered semen analysis parameters, normal serum FSH and normal serum total testosterone concentrations; (3) A hypogonadal state with lowered semen analysis parameters, normal FSH and reduced total testosterone concentrations; (4) Lowered semen analysis parameters, elevated FSH concentrations and reduced or normal total testosterone concentrations; and (5) Unexplained male infertility in the context of unexplained couple infertility., Conclusion: The APHRODITE criteria offer a novel and standardized patient stratification system for male infertility independent of aetiology and/or altered spermatogenesis, facilitating communication among clinicians, researchers and patients to improve reproductive outcomes following hormonal therapy. APHRODITE is proposed as a basis for future trials of the hormonal treatment of male infertility., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Importance: The effect of testosterone replacement therapy (TRT) in men with hypogonadism on the risk of progression from prediabetes to diabetes or of inducing glycemic remission in those with diabetes is unknown., Objective: To evaluate the efficacy of TRT in preventing progression from prediabetes to diabetes in men with hypogonadism who had prediabetes and in inducing glycemic remission in those with diabetes., Design, Setting, and Participants: This nested substudy, an intention-to-treat analysis, within a placebo-controlled randomized clinical trial (Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men [TRAVERSE]) was conducted at 316 trial sites in the US. Participants included men aged 45 to 80 years with hypogonadism and prediabetes or diabetes who were enrolled in TRAVERSE between May 23, 2018, and February 1, 2022., Intervention: Participants were randomized 1:1 to receive 1.62% testosterone gel or placebo gel until study completion., Main Outcomes and Measures: The primary end point was the risk of progression from prediabetes to diabetes, analyzed using repeated-measures log-binomial regression. The secondary end point was the risk of glycemic remission (hemoglobin A1c level <6.5% [to convert to proportion of total hemoglobin, multiply by 0.01] or 2 fasting glucose measurements <126 mg/dL [to convert to mmol/L, multiply by 0.0555] without diabetes medication) in men who had diabetes., Results: Of 5204 randomized participants, 1175 with prediabetes (mean [SD] age, 63.8 [8.1] years) and 3880 with diabetes (mean [SD] age, 63.2 [7.8] years) were included in this study. Mean (SD) hemoglobin A1c level in men with prediabetes was 5.8% (0.4%). Risk of progression to diabetes did not differ significantly between testosterone and placebo groups: 4 of 598 (0.7%) vs 8 of 562 (1.4%) at 6 months, 45 of 575 (7.8%) vs 57 of 533 (10.7%) at 12 months, 50 of 494 (10.1%) vs 67 of 460 (14.6%) at 24 months, 46 of 359 (12.8%) vs 52 of 330 (15.8%) at 36 months, and 22 of 164 (13.4%) vs 19 of 121 (15.7%) at 48 months (omnibus test P = .49). The proportions of participants with diabetes who experienced glycemic remission and the changes in glucose and hemoglobin A1c levels were similar in testosterone- and placebo-treated men with prediabetes or diabetes., Conclusions and Relevance: In men with hypogonadism and prediabetes, the incidence of progression from prediabetes to diabetes did not differ significantly between testosterone- and placebo-treated men. Testosterone replacement therapy did not improve glycemic control in men with hypogonadism and prediabetes or diabetes. These findings suggest that TRT alone should not be used as a therapeutic intervention to prevent or treat diabetes in men with hypogonadism., Trial Registration: ClinicalTrials.gov Identifier: NCT03518034.

Introduction: Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system and is widely recognized as a disease primarily affecting women. The relationship between MS and hypogonadism is complex and not fully understood, with recent evidence showing that hypogonadism may have a significant impact on the quality of life and disease progression of patients with MS., Objectives: This review aims to provide an overview of the current knowledge regarding the relationship between MS and hypogonadism, including the mechanisms underlying this relationship; the effects of hypogonadism on patients with MS; and the potential benefits and drawbacks of testosterone replacement therapy for patients with MS and hypogonadism., Methods: This scientific review analyzed 19 articles that investigated the potential relationship among MS, testosterone levels, and hypogonadism. The articles were published between November 2008 and March 2022 and were identified through a comprehensive search of the PubMed database. The search terms used included "multiple sclerosis," "testosterone," "hypogonadism," and "MS and testosterone levels.", Results: Of the 19 articles reviewed, 11 described a positive correlation between low testosterone levels and dysfunction within the hypothalamic-pituitary-gonadal axis in individuals with MS. These findings suggest that low testosterone levels may contribute to dysfunction within the hypothalamus-pituitary-gonadal axis, which plays a crucial role in regulating testosterone production. The results also showed a relationship between sexual dysfunction and low testosterone levels, as well as a positive correlative relationship between these factors., Conclusion: The reviewed articles indicate a complex relationship among MS, testosterone levels, and the hypothalamic-pituitary-gonadal axis, with low testosterone levels potentially contributing to dysfunction in this axis and to sexual dysfunction. Further research is needed to better understand the effects of testosterone therapy on MS and sexual dysfunction in patients with MS., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Men with Klinefelter syndrome (KS) develop hypergonadotropic hypogonadism, are in need of testosterone replacement therapy (TRT), and present with a more than 4-fold increased risk of thrombosis. TRT in KS has the potential to modify thrombotic risk, but data are scarce., Aim: To assess effects of 18 months of TRT on hemostasis in KS and identify genes associated with the prothrombotic phenotype., Methods: Untreated and TRT-treated men with KS were included at baseline and matched to healthy controls. TRT was initiated in untreated KS and all groups were reassessed after 18 months of follow-up. Thrombin generation was evaluated with or without thrombomodulin, and fibrin clot lysis was evaluated by turbidity measurements. RNA expression was assessed in blood, fat, and muscle tissue of patients with TRT-treated KS and controls., Results: Thrombin generation with thrombomodulin was slightly increased in untreated KS, but overall KS was not associated with a hypercoagulable state. KS presented with fibrinolytic impairment associated with higher body fat and higher levels of fibrinogen. Eighteen months of TRT in KS was associated with a reduction in body fat and fibrinogen, attenuating the prothrombotic profile. The expression of ENPP4 was higher in men with KS and served as a key player among a group of genes associated with impaired fibrinolysis., Conclusion: KS is associated with a specific expression profile contributing to fibrinolytic impairment and increased thrombotic risk in the patients. TRT in patients with KS has the potential for alleviating the prothrombotic phenotype, in particular by reducing body fat and fibrinogen., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Childhood cancer survivors are at risk for hypogonadism. The impact of hypogonadism on neurocognitive impairment and emotional distress in the non-cancer population has been shown; however, the relationship among the childhood cancer survivor population is unknown. We aimed to evaluate the contribution of hypogonadism to neurocognitive impairment and emotional distress among survivors., Design: Cross-sectional study using retrospective cohort., Methods: In total, 3628 survivors who completed standard neurocognitive tests (six domains: processing speed, memory, executive function, attention, academics, and global cognition) and self-reported emotional distress were included in our study. Participants were stratified by sex and gonadal status. Outcomes were compared between hypogonadal and eugonadal groups by multivariable analysis, adjusting for established predictors, and mediation analyses to determine the direct/indirect effects of hypogonadism on outcomes., Results: The hypogonadal group exhibited a higher prevalence of neurocognitive impairment across domains, but no difference in emotional distress. Hypogonadal females exhibited higher relative risk (1.7, 95% CI, 1.2-2.5) for impaired visual processing speed, compared to eugonadal females after adjusting for cancer-related variables. In mediation models, hypogonadism had a significant direct (P < .01) and indirect (from P < .01) impact on impairment in visual processing speed among females. Males demonstrated direct (P = .03) and indirect (P = .04) impact of hypogonadism on motor processing speed., Conclusion: Processing speed may be the most vulnerable neurocognitive domain associated with hypogonadism in survivors, while other domains were mainly impacted by cancer-related variables. Our findings support the need for further evaluation of the impact of sex hormone replacement therapy on neurocognitive function., Competing Interests: Conflict of interest: None of the authors have any conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: With the increase in obesity epidemic among Asians, it is necessary to evaluate the impact of obesity on this population. Low testosterone levels are known to be associated with obesity. This is the 1st study from Asia to evaluate incidence and magnitude of hypotestosteronemia in young adults with BMI more than 32.5 kg/m 2 defined as moderate to severe obesity in Asians., Materials and Methods: One hundred thirty-four male patients with BMI more than 32.5 kg/m 2 , between 18 and 30 years old who visited a single bariatric facility between 2017 and 2020, were evaluated with BMI, total and free testosterone levels and clinical features of gynecomastia, hypogonadism, and thinning of pubic and armpit hair. Statistical analysis was performed using SPSS, Spearman's correlation coefficient, and ANOVA test., Results: 60.4% of patients (84/134) had low testosterone levels (< 300 ng/dl) and 23.9% (32/134) had levels between 300 and 400 ng/dl. 89.6% patients (120/134 had gynecomastia, 60.4% (81/134) had thinning of pubic and arm pit hair, and 62.7% (84/134) had hypogonadism. Testosterone levels showed a decreasing trend with increasing BMI, but it was not statistically significant., Conclusion: Obesity is one of the important etiologies of hypotestosteronemia and its manifestations in young adults. The actual incidence may be significantly higher than what is reported in the literature. High-quality research is required to address questions of diagnosis and best treatment options., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Testosterone is crucial in regulating several body functions in men, including metabolic, sexual, and cardiovascular functions, bone and muscle mass, and mental health. Therefore, optimizing testosterone levels in men is an important step to maintaining a healthy body and mind, especially as we age. However, traditional testosterone replacement therapy has been shown to lead to male infertility, caused by negative feedback in the hypothalamic-pituitary-gonadal (HPG) axis. Recent advances in research have led to the discovery of many new methods of administration, which can have more or less suppressive effects on the HPG axis. Also, the usage of ancillary medications instead of or after testosterone administration might help maintain fertility in hypogonadal patients. The goal of this narrative review is to summarize the newest methods for optimizing fertility parameters in patients undergoing treatment for hypogonadism and to provide the necessary information for healthcare providers to make the right treatment choices.

Objectives: To explore the role of conventional X-ray imaging in detecting vertebral fractures (VFs) in patients with acromegaly, both at diagnosis of disease and at the last clinical visit. The risk factors for VFs were also evaluated., Design and Methods: A retrospective cohort study was conducted on 60 consecutive patients with acromegaly, in a tertiary referral centre. Thoracolumbar spine radiography (X-spine) was performed at the last clinical visit during the follow-up in order to detect VFs. Routine chest radiograph, performed as a part of the general evaluation at diagnosis of acromegaly, were retrospectively analysed to screen for baseline VFs., Results: At diagnosis of acromegaly, chest X-ray revealed that 10 (17%) patients had VFs. Of the 50 patients without VFs at diagnosis of acromegaly, 33 (66%) remained unfractured at the last clinical visit (median [IQR] time, 144 [96-192] months after the diagnosis of acromegaly), whereas 17 (34%) had VFs. Overall, 22 patients (37%) had novel VFs detected on X-spine including five patients with previous VFs. Risk factor for incident VFs was the presence of hypogonadism at diagnosis of acromegaly (p = 0.016)., Conclusions: In acromegaly patients, conventional X-rays can detect vertebral fractures early at diagnosis of acromegaly. They can also reveal incident VFs, which may occur several years later even in patients without VFs at diagnosis, above all in relation to hypogonadism., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Background: Clinical data regarding hypogonadism in very old men with multimorbidity are rare. Hypogonadism can contribute to osteoporosis, anemia and sarcopenia and is therefore a relevant problem for geriatric patients., Methods: A total of 167 men aged 65-96 years (mean 81 ± 7 years) admitted to an acute geriatric ward were included in a cross-sectional study. Body composition derived from dual-energy X‑ray absorptiometry, bone mineral density, handgrip strength, multimorbidity, polypharmacy and laboratory values were obtained from the routine electronic clinical patient file., Results: Hypogonadism was present in 62% (n = 104) of the study participants, of whom 83% showed clinical manifestation of hypogonadism (hypogonadism in combination with anemia, sarcopenia and/or low T‑score). The subgroups showed a distribution of 52% primary and 48% secondary hypogonadism. Compared to the eugonadal patients, hypogonadal patients had reduced handgrip strength (p = 0.031) and lower hemoglobin levels (p = 0.043), even after adjustment for age, body mass index and glomerular filtration rate., Conclusion: Hypogonadism is common in geriatric patients. If chronic anemia, sarcopenia, or osteoporosis are diagnosed, testosterone levels should be determined in geriatric settings., (© 2023. The Author(s).)

Context: Few long-term randomized trials have evaluated the efficacy of testosterone replacement therapy (TRT) in improving sexual function and hypogonadal symptoms in men with hypogonadism and whether effects are sustained beyond 12 months., Objective: The Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) study evaluated the effect of TRT on major adverse cardiovascular events in middle-aged and older men with hypogonadism. The Sexual Function Study, nested within the parent trial, determined testosterone's efficacy in improving sexual activity, hypogonadal symptoms, libido, and erectile function among men reporting low libido., Methods: Among 5204 men, 45-80 years, with 2 testosterone concentrations <300 ng/dL, hypogonadal symptoms, and cardiovascular disease (CVD) or increased CVD risk enrolled in the TRAVERSE trial, 1161 with low libido were enrolled in the Sexual Function Study (587 randomized to receive 1.62% testosterone gel and 574 to placebo gel for the duration of their participation in the study). Primary outcome was change from baseline in sexual activity score. Secondary outcomes included hypogonadal symptoms, erectile function, and sexual desire., Results: TRT was associated with significantly greater improvement in sexual activity than placebo (estimated mean [95% CI] between-group difference 0.49 [0.19,0.79] and 0.47 [0.11, 0.83] acts per day at 6 and 12 months, respectively; omnibus test P = .011); treatment effect was maintained at 24 months. TRT improved hypogonadal symptoms and sexual desire, but not erectile function, compared with placebo., Conclusion: In middle-aged and older men with hypogonadism and low libido, TRT for 2 years improved sexual activity, hypogonadal symptoms, and sexual desire, but not erectile function., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease, affecting one-fourth of the adult population worldwide. Recent data found an association between MASLD and hypogonadism, but this relation in patients with type 2 diabetes mellitus (T2DM) is still unclear., Objective: To evaluate in men with T2DM the association between total testosterone (TT) and noninvasive indices of hepatic steatosis (Fatty Liver Index [FLI], Hepatic Steatosis Index [HSI], Dallas Steatosis Index [DSI]) and fibrosis (AST to Platelet Ratio Index [APRI], Fibrosis-4 Index [FIB-4]), and their predictive cutoff values in identifying hypogonadism., Methods: Cross-sectional study on 189 men with T2DM, without history of liver diseases and alcoholism, recruited on an outpatient basis. Interventions were andrological evaluation, metabolic parameters, TT, and liver indices. The main outcome measures were comparison of steatosis and fibrosis indices with testosterone levels and presence of hypogonadism. Receiver operating characteristic curves were used to identify cutoff values of liver indices in predicting low testosterone (<12 nmol/L)., Results: FLI, HSI, and DSI were negatively related with TT and were higher in the low-testosterone group than in the normal-testosterone group (FLI: 74.1 [61.4-93.5] vs 56.5 [32.1-78.2], P < .001; HSI: 41.5 [39.2-45.9] vs 40.1 [36.6-43.2], P = .005; DSI: 0.45 [-0.08-+1.04] vs -0.07 [-1.02-+0.58], P < .001). FLI and DSI also correlated with clinical symptoms of hypogonadism. No differences between groups were observed for APRI and FIB-4. FLI ≥63 was the best parameter as predictive index of low TT (sensitivity 73%, specificity 64%)., Conclusion: We found an association between noninvasive indices of steatosis and hypogonadism in patients with T2DM. These indices could be used to direct the patients to andrological evaluation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Testosterone treatment in men with hypogonadism improves bone density and quality, but trials with a sufficiently large sample and a sufficiently long duration to determine the effect of testosterone on the incidence of fractures are needed., Methods: In a subtrial of a double-blind, randomized, placebo-controlled trial that assessed the cardiovascular safety of testosterone treatment in middle-aged and older men with hypogonadism, we examined the risk of clinical fracture in a time-to-event analysis. Eligible men were 45 to 80 years of age with preexisting, or high risk of, cardiovascular disease; one or more symptoms of hypogonadism; and two morning testosterone concentrations of less than 300 ng per deciliter (10.4 nmol per liter), in fasting plasma samples obtained at least 48 hours apart. Participants were randomly assigned to apply a testosterone or placebo gel daily. At every visit, participants were asked if they had had a fracture since the previous visit. If they had, medical records were obtained and adjudicated., Results: The full-analysis population included 5204 participants (2601 in the testosterone group and 2603 in the placebo group). After a median follow-up of 3.19 years, a clinical fracture had occurred in 91 participants (3.50%) in the testosterone group and 64 participants (2.46%) in the placebo group (hazard ratio, 1.43; 95% confidence interval, 1.04 to 1.97). The fracture incidence also appeared to be higher in the testosterone group for all other fracture end points., Conclusions: Among middle-aged and older men with hypogonadism, testosterone treatment did not result in a lower incidence of clinical fracture than placebo. The fracture incidence was numerically higher among men who received testosterone than among those who received placebo. (Funded by AbbVie and others; TRAVERSE ClinicalTrials.gov number, NCT03518034.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: There is insufficient attention to hypogonadism in Chinese males with type 2 diabetes mellitus (T2DM). We evaluated the relationship between Combined obesity- and lipid-related indices [Visceral Adiposity Index (VAI), Chinese Visceral Adiposity Index (CVAI), Triglyceride Glucose Index (TyG) and Lipid Accumulation Product (LAP)] with total testosterone (TT) and analyzed the predictive capability of the respective cut-off values., Methods: We recruited 958 hospitalized male patients with T2DM at the Affiliated Hospital of Qingdao University, collected baseline data and four calculated indices, and obtained their dominance ratio (OR) and corresponding 95% confidence intervals (CI) with TT by multivariate logistic regression. Receiver operating characteristic (ROC) curves were then used to determine cutoff values in predicting hypogonadism (TT< 12 nmol/L), and we also analyzed the combinations between the different indices., Results: VAI, CVAI, TyG, and LAP all have satisfactory predictive capabilities. The test capability (sensitivity and specificity) of all four indices was better or not worse than that of body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) and waist circumference (WC). All four indices were effective predictors of hypogonadism at their respective cutoff values (VAI ≥ 2.284, CVAI ≥ 145.779, TyG ≥ 4.308, and LAP ≥ 59.850). Of these, LAP had the largest area under the curve (AUC, AUC = 0.852, Std. Error = 0.014, 95% CI = 0.818-0.873). However, the predictive capability of the combined indices was not significantly improved over the individual indices., Conclusions: VAI, CVAI, TyG, and LAP are sensitive indices for predicting hypogonadism in Chinese male patients with T2DM. Considering the need for concise and accurate indices in clinical practice, we suggest LAP as a commonly used index., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Wang, Xu, Li and Wang.)

Background: Beta thalassemia is a lifelong disease involving malformed red blood cells (RBC). One of the disease's complications is hypogonadism, in which adults tend to exhibit regression in sexual characteristics, experience sexual dysfunction, and therefore have a lower quality of life. Around 3-10% of the Indonesian population carries the beta-thalassemia gene. This study aimed to see the proportions of hypogonadism in transfusion-dependent thalassemia patients and its contributing factors., Methods: This is a cross-sectional study involving 60 male patients admitted to three Indonesian general hospitals from July 2022 to July 2023. All patients were diagnosed with beta-thalassemia via chromatography hemoglobin analysis. We performed a single-time physical examination and laboratory examinations to determine FSH, LH, and free testosterone levels. The correlation between Hb and sexual hormone levels was analyzed using Spearman's rank correlation coefficient. ROC curve analysis was conducted afterward. All statistical analysis was done in SPSS version 29., Results: 31 out of 60 thalassemia patients had hypogonadism. Pre-transfusion Hb count was found to be linearly correlated with FSH (r = 0.388, p = 0.049), LH (r = 0.338, p = 0.008), and free testosterone (r = 0.255, p = 0.049). ROC analysis indicated that pre-transfusion Hb was viable as a predictor for hypogonadism (AUC = 0.655, 65.5% sensitivity, 67.7% specificity)., Conclusion: We confirmed the role of pre-transfusion Hb count as a potential predictor for hypogonadism due to the tissue hypoxia mechanism and transfusion-related iron overload in TDT patients. Decreased Hb is linearly correlated with FSH, LH, and testosterone levels. Decreased Hb also downregulates these factors.

Background: Testicular cancer (TC) survivors cured with chemotherapy (CT) are prone to develop cardiovascular diseases, as part of an accelerated aging phenotype. A mechanism contributing to these events can be telomere shortening., Patients and Methods: In a prospective cohort of patients with disseminated TC who received cisplatin-based CT, mean absolute leukocyte telomere length (TL) was measured before and 1 year after start of treatment. Cardiovascular risk factors, including development of the metabolic syndrome and hypogonadism, were assessed before and up to 5 years after CT., Results: For the whole group (n = 55), TL did not change 1 year after CT (5.7 (2.2-13.4) vs. 5.8 kb (1.6-19.2), P = 0.335). At baseline, patients with a BMI >30 kg/m 2 (n = 12) had shorter TL (4.9 (2.2-13.4) vs. 6.3 kb (3.1-12.9), P = 0.045), while no age-dependent differences were measured. Patients with TL shortening after 1 year (n = 7) showed a significant increase in diastolic blood pressure (P = 0.007) and triglycerides (P = 0.003), compared to those with unchanged TL. There was no association between telomere shortening after 1 year or short TL at baseline (n = 7+11) and development of metabolic syndrome (25% vs. 21%; P = 0.777), or hypogonadism (38% vs. 17%; P = 0.120) after 5 years., Conclusions: A small subset of TC patients treated with cisplatin-based CT showed telomere shortening 1 year after treatment. This shortening was associated to a rise in diastolic blood pressure and triglycerides, but not to newly developed metabolic syndrome and hypogonadism after 5 years., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JG received research grants from Roche, Siemens, and Abbvie paid to the institution. MD is founder and shareholder of Cleara Biotech and advisor for Oisin Biotechnologies. Cleara Biotech and Oisin Biotechnologies were not involved in the study. All remaining authors have declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In otherwise normal boys with undescended testes, early orchidopexy is recommended to preserve fertility, to decrease the risk of testicular cancer, and to facilitate its detection. Indeed, compared to the general population, the risk of testicular cancer is increased two- to eight-fold in isolated cryptorchidism and usually occurs before the age of 40 years. By contrast, when cryptorchidism is associated with congenital hypogonadotropic hypogonadism, the risk of testicular cancer is unknown., Objective: The aim of this study was to determine the characteristics of testicular cancer when cryptorchidism is associated with congenital hypogonadotropic hypogonadism., Methods: We conducted a PubMed research without date limits including the following key words: hypogonadism, hypogonadotropic hypogonadism, testicular cancer, testicular germ cell tumors, undescended testis, Kallmann syndrome, FSH, AFP (α foeto protein), βHCG., Results: Only 3 patients with testicular cancer and congenital hypogonadotropic hypogonadism have been published in the past 4 decades and two were diagnosed at 50 and 64 years., Conclusion: Gonadotropin deficiency may protect against testicular cancer, and orchidopexy in this context may be deferred., (© 2023 S. Karger AG, Basel.)

Purpose: Sexual dysfunctions are often experienced by male patients with acromegaly, due to a combination of hypogonadism and other comorbidities, but are a scarcely investigated complication. Erectile dysfunction is also closely related to cardiovascular diseases through endothelial dysfunction. Therefore, this project aimed to assess the prevalence of erectile dysfunction in a population of acromegalic men and evaluate its association with cardio-metabolic disorders, also exploring associations with androgen and estrogen receptor gene polymorphisms., Methods: Sexually active men aged 18-65 with previous diagnosis of acromegaly were recruited. Clinical and laboratory data were retrospectively collected. Each patient also provided a blood sample for AR and ERβ gene polymorphisms analyses and filled out the IIEF-15 questionnaire., Results: Twenty men with previous diagnosis of acromegaly (mean age 48.4 ± 10.0 years) were recruited. 13/20 subjects (65%) had erectile dysfunction, but only four had a concurrent biochemical hypogonadism, with no significant correlation with IIEF-15 scores. Total testosterone negatively correlated with sexual intercourse satisfaction domain (ρ = - 0.595; p = 0.019) and general satisfaction domain (ρ = - 0.651; p = 0.009). IGF-1 levels negatively correlated with biochemical hypogonadism (ρ = - 0.585; p = 0.028). The number of CAG and CA repeats in AR and ERβ receptors genes was not significantly associated with IIEF-15 scores or with GH/IGF-1 levels, but a negative correlation between CA repeats and the presence of cardiomyopathy (ρ = - 0.846; p = 0.002) was present., Conclusions: Men with acromegaly have a high prevalence of erectile dysfunction, but it does not appear to be correlated with treatments, testosterone levels and AR/ER-beta signaling. Nonetheless, a shorter CA polymorphic trait (ERbeta) is associated with the presence of cardiomyopathy. If confirmed, these data may suggest an association between an incorrect hormonal balance and increased cardiovascular risk in acromegaly subjects., (© 2023. The Author(s).)

Context: The T4DM study randomized 1007 men with impaired glucose tolerance or newly diagnosed diabetes to testosterone undecanoate (TU, 1000 mg) or matching placebo (P) injections every 12 weeks for 24 months with a lifestyle program with testosterone (T) treatment reducing diabetes diagnosis by 40%., Background: The long-term effects on new diagnosis of diabetes, cardiovascular and prostate disease, sleep apnea, weight maintenance trajectory and androgen dependence were not yet described., Methods: A follow-up email survey after a median of 5.1 years since last injection obtained 599 (59%) completed surveys (316 T, 283 P), with participants in the follow-up survey compared with nonparticipants in 23 anthropometric and demographic variables., Results: Randomization to was TU associated with stronger belief in study benefits during (64% vs 49%, P < .001) but not after the study (44% vs 40%, P = .07); there is high interest in future studies. At T4DM entry, 25% had sleep apnea with a new diagnosis more frequent on TU (3.0% vs 0.4%, P = .03) during, but not after, the study. Poststudy, resuming prescribed T treatment was more frequent among TU-treated men (6% vs 2.8%, P = .03). Five years after cessation of TU treatment there was no difference in self-reported rates of new diagnosis of diabetes, and prostate or cardiovascular disease, nor change in weight maintenance or weight loss behaviors., Conclusion: We conclude that randomized T treatment for 24 months in men with impaired glucose tolerance or new diabetes but without pathological hypogonadism was associated with higher levels of self-reported benefits and diagnosis of sleep apnea during, but not after, the study as well as more frequent prescribed poststudy T treatment consistent with androgen dependence in some men receiving prolonged injectable TU., (© Commonwealth of Australia, 2023.)

Background: The nucleoside transport capabilities of the human equilibrative nucleoside transporter-3 (hENT3) are disrupted by mutations in SLC29A3 (10q22.2), which are genes for the nucleoside transporter and are the cause of the unusual autosomal recessive disease known as H syndrome. As a result, histiocytic cells invade a number of organs., Case Presentation: A 17-year-old Syrian male was admitted to the internal medicine department with a one-month history of polyuria, polydipsia, general weakness, and pallor. He had a history of progressive bilateral sensorineural hearing loss and failure to gain weight for three years. Physical examination revealed various abnormalities, including scrotal mass, small penis and testicles, absence of pubic and axillary hair, joint abnormalities, short stature, hallux valgus, fibrous protrusion near the navel, and hyperpigmented non-itchy painful skin plaques. Clinical signs along with laboratory test results confirmed hyperglycemia, primary hypogonadism, osteopenia, and growth hormone deficiency. After a review of the relevant medical literature, this patient's presentation of hyperglycemia with hypogonadism, hyperpigmentation, hallux valgus, hearing loss, hematological abnormalities, and short stature suggested the diagnosis of H syndrome. The patient received treatment with insulin and testosterone, leading to a significant improvement in his presenting symptoms., Conclusions: H syndrome is a very rare condition, and the fact that the first case has only recently been reported in Syria serves to emphasize how rare it is. H Syndrome should be suspected if a patient has short stature with signs of hyperglycemia and other endocrine and cutaneous abnormalities. We are reporting this case to increase physicians' awareness of this exceedingly rare and unique syndrome., (© 2023. The Author(s).)

Study Question: Does Cushing's syndrome (CS) differently affect the gonadotrope axis and testicular functions (GA/TF) according to the hypercortisolism intensity and underlying etiology?, Summary Answer: Endogenous cortisol excess caused by CS leads to varying degrees of hypogonadotropic hypogonadism (HH) with more severe GA/TF impairment and altered spermatogenesis in men with intense hypercortisolism associated with paraneoplastic/ectopic adrenocorticotrophic hormone (ACTH) secretion (EAS)., What Is Known Already: CS is very rarely studied in men due to its lower prevalence in men than in women. In a few old reports focusing exclusively on a limited number of men with Cushing's disease (CD), the occurrence of hypogonadism was reported. However, a detailed assessment of the impact of CS on the GA/TF in a significant series of patients has not been performed. Yet, hypogonadism could worsen CS-associated comorbidities such as osteoporosis and myopathy. To date, the full spectrum of GA/TF impairment in men with CS of different etiologies and intensity remains unknown., Study Design, Size, Duration: In this monocentric study, 89 men with CS diagnosed at a tertiary endocrine university center (Bicêtre, Paris Saclay) between January 1990 and July 2021 were evaluated and compared to 40 normal men of similar age., Participants/materials, Setting, Methods: The CS patient cohort of 89 men included 51 with CD, 29 with EAS and 9 with CS of adrenal origin i.e. (ACTH-independent CS (AI-CS)). They all had frank hypercortisolism, with increased 24 h-urinary-free cortisol (24 h-UFC) in two separate samples. A case-control study was performed focusing on pituitary gonadotrope function and testicular sex steroids and peptides. An additional set of six CS men had an evaluation including semen analysis. In a subgroup of 20 men with available data after CS remission, a longitudinal analysis was conducted to assess the reversibility of GA/TF defects., Main Results and the Role of Chance: Compared to controls, men with CS had significantly lower total testosterone (TT), bioavailable TT, and free TT (P < 0.0001). Hypogonadism, defined as serum TT levels <3.0 ng/ml, was present in 83% of men with EAS, in 61% of men with CD, and in 33% of men with AI-CS. Low-normal LH concentrations in the included men with hypercortisolism indicated HH. Serum sex hormone-binding globulin levels were moderately decreased in men with CD (P = 0.01 vs controls). Among the CS men, those with EAS had significantly lower TT, LH, and FSH levels than those with CD or AI-CS. When compared to controls, patients with EAS were the only group exhibiting a significant decrease in both serum FSH (P = 0.002) and the testicular peptides inhibin B (P < 0.0001) and anti-Müllerian hormone (P = 0.003). Serum INSL3 levels were significantly lower in men with CD than in the controls (P = 0.03). Of note, 24 h-UFC and ACTH were inversely and significantly associated with the majority of reproductive hormones including LH, FSH, TT, and inhibin B. Following successful curative therapy, reproductive assessment at a mean of 6.0 ± 4.3 years showed a significant increase in serum TT (P < 0.0001) and plasma LH (P = 0.02) levels, indicating a reversal of HH in 75% of the affected males. Among the six patients with available semen analysis, the two EAS cases exhibited a decrease in Sertoli cell peptides associated with a severe oligozoospermia, which completely normalized following removal of the source of hypercortisolism., Limitations, Reasons for Caution: The potential bias due to the retrospective design is counteracted by the analysis of the largest male CS cohort to date as well as the use of stringent inclusion and exclusion criteria. Due to the low number of patients with semen analysis in this study, further research is needed to unravel the full spectrum of spermatogenesis defects in men with CS., Wider Implications of the Findings: This work reveals the variable spectrum of reproductive impact in men with CS. We demonstrate that GA/TF impairment depends on the intensity of hypercortisolism which in turn is related to the underlying etiology. The causal link between hypercortisolism and GA/TF impairment was attested by its reversibility in most patients after CS remission. The wider implications of our findings lie in the potential generalization to a much commoner entity, iatrogenic CS due to chronic exposure to exogenous glucocorticoids., Study Funding/competing Interest(s): Several research grants were attributed to J.Y.: (i) a grant from Programme Hospitalier de Recherche Clinique (PHRC # P081212 HYPOPROTEO); (ii) a grant from the French Association of Patients with Adrenal Diseases ('Association surrénales'); and (iii) independent Investigator Research Grants from HRA Pharma, Novartis and Recordati Pharma. A SICPA Foundation grant (Lausanne, Switzerland) allowed protected research time for G.E.P. The above sponsors were not involved in any part of the study. The authors have no competing or other conflicts of interest to declare., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Börjeson-Forssman-Lehmann syndrome (BFLS) is an X-linked intellectual disability syndrome caused by variants in the PHF6 gene. We ascertained 19 individuals from 15 families with likely pathogenic or pathogenic PHF6 variants (11 males and 8 females). One family had previously been reported. Six variants were novel. We analysed the clinical and genetic findings in our series and compared them with reported BFLS patients. Affected males had classic features of BFLS including intellectual disability, distinctive facies, large ears, gynaecomastia, hypogonadism and truncal obesity. Carrier female relatives of affected males were unaffected or had only mild symptoms. The phenotype of affected females with de novo variants overlapped with the males but included linear skin hyperpigmentation and a higher frequency of dental, retinal and cortical brain anomalies. Complications observed in our series included keloid scarring, digital fibromas, absent vaginal orifice, neuropathy, umbilical hernias, and talipes. Our analysis highlighted sex-specific differences in PHF6 variant types and locations. Affected males often have missense variants or small in-frame deletions while affected females tend to have truncating variants or large deletions/duplications. Missense variants were found in a minority of affected females and clustered in the highly constrained PHD2 domain of PHF6. We propose recommendations for the evaluation and management of BFLS patients. These results further delineate and extend the genetic and phenotypic spectrum of BFLS., (© 2023. The Author(s).)

Introduction: Osteopathy in patients with acromegaly is characterized by increased prevalence of vertebral fragility fractures (VF). However, the diagnostic criteria for osteoporosis are seldomly met in terms of bone mineral density (BMD), as patients with acromegaly frequently present normal BMD for age and gender., Methodology: We performed a cross-sectional study on 71 patients with acromegaly and 75 patients with hypogonadism. Turnover markers comprised alkaline phosphatase, osteocalcin, the C-terminal telopeptide of type I collagen and total procollagen type-1 amino-terminal propeptide; imaging comprised dual x-ray absorptiometry for BMD, T and Z scores of the lumbar spine, femoral neck and total hip, trabecular bone score (TBS), and x-ray scans of the thoracic and lumbar spine., Results: Vertebral fractures (VF) in subjects with acromegaly were significantly more frequent than in subjects with hypogonadism, with a prevalence of 29.6% compared to 9.3%. Patients with acromegaly had significantly higher BMD at all skeletal sites but lower TBS than hypogonadal subjects. This difference remained statistically significant after grouping patients with acromegaly according to gonadal status and comparing them with patients with hypogonadism. However, presence of hypogonadism in patients with acromegaly did not influence BMD, TBS or VF prevalence. Moreover, patients with active acromegaly did not have significantly different BMD, TBS and VF prevalence compared to patients with controlled disease. Patients with acromegaly with VF had significantly lower BMD at all skeletal sites than those without VF, but no difference in TBS., Conclusions: Vertebral fractures are frequent in acromegaly, and are associated with lower BMD but not with TBS. Patients with acromegaly, regardless of gonadal status, have significantly higher BMD but lower TBS than hypogonadal patients. Moreover, disease activity and hypogonadism do not influence BMD, TBS or VF in acromegaly., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Introduction: Late-onset hypogonadism is the clinical entity characterised by low testosterone concentrations associated with clinical symptoms in the absence of organic disease in ageing men. It has been associated with metabolic syndrome, reduced bone mineral density, and increased cardiovascular morbidity and mortality risk. Although testosterone replacement therapy (TRT) reverses most of these conditions in young hypogonadal men, the risk/benefit ratio of TRT in older men is debatable., Aim: To update the 2015 EMAS statement on TRT in older men with new research on late-onset hypogonadism and TRT., Materials and Methods: Literature review and consensus of expert opinion., Summary Recommendations: TRT should be offered only to symptomatic older men with confirmed low testosterone concentrations after explaining the uncertainties regarding the long-term safety of this treatment. TRT may be offered to men with severe hypogonadism and erectile dysfunction to improve sexual desire, erectile, and orgasmic function. It should also be considered in hypogonadal men with severe insulin resistance or pre-diabetes mellitus. TRT may also be considered, in combination with proven treatment strategies, for osteoporosis, or for selected patients with persistent mild depressive symptoms and/or low self-perceived quality of life, combined with standard medical care for each condition. TRT is contraindicated in hypogonadal men actively seeking fertility treatment. Due to a lack of data, TRT should not be routinely used in older men to improve exercise capacity/physical function, improve cognitive function, or prevent cognitive decline. TRT must be avoided in older, frail men with known breast cancer or untreated prostate cancer and all men who have had myocardial infarction or stroke within the last four months, and those with severe or decompensated heart failure. The quality of evidence regarding patients with previous prostate cancer or cardiovascular disease is too low to draw definitive conclusions. Any limits on duration of use are arbitrary, and treatment should continue for as long as the man feels the benefits outweigh the risks for him, and decisions must be made on an individual basis. Withdrawal should be considered when hypogonadism is reversed after the resolution of underlying disorder. Short-acting transdermal preparations should be preferred for TRT initiation in older men, but injectable forms may be considered subsequently. Older men on TRT should be monitored at 3, 6, and 12 months after initiation and at least yearly thereafter, or earlier and more frequently if indicated. Evaluation should include assessment of the clinical response, and measurement of total testosterone, haematocrit, and prostate-specific antigen (PSA) concentrations. Bone density and/or quality should also be assessed. Obese and overweight patients should be encouraged to undergo lifestyle modifications, including exercise and weight loss, to increase endogenous testosterone., Competing Interests: Declaration of competing interest, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: The study aims to determine whether body mass index (BMI), metabolic syndrome (MS) or its individual components (primary hypertension, type 2 diabetes mellitus and dyslipidemias) are risk factors for common urological diseases., Materials and Methods: Cross-sectional study with data collected on February 28, 2022 from the TriNetX Research Network. Patients were divided in cohorts according to their BMI, presence of MS (BMI > 30 kg/m 2 , type 2 diabetes mellitus, primary hypertension and disorders of lipoprotein metabolism) and its individual components and its association with common urological conditions was determined. For each analysis, odds ratio (OR) with 95% confidence intervals were calculated. Statistical significance was assessed at p  < .05., Results: BMI > 30 kg/m 2 was associated with increased risk of lithiasis, kidney cancer, overactive bladder, male hypogonadism, benign prostatic hyperplasia, and erectile dysfunction ( p  < .05). On the contrary, BMI was inversely associated with ureteral, bladder and prostate cancer ( p  < .05). In all urological diseases, MS was the strongest risk factor, with prostate cancer (OR = 2.53) showing the weakest and male hypogonadism the strongest (OR = 13.00) associations., Conclusions: MS and its individual components were significant risk factors for common urological conditions. Hence holistic approaches with lifestyle modification might prevent common urological disease.Key messagesOverall, metabolic syndrome is the strongest risk factor for all the analysed urological diseases.Abnormally high body mass index can be a risk or protective factor depending on the threshold and urological disease that are being evaluated.Metabolic syndrome and increased BMI should be considered important factors associated to the prevalence of common urological diseases.

Objectives: Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder that is characterized by a segmental dermatomal facial port-wine stain birthmark and is frequently accompanied by ipsilateral brain and eye abnormalities. We present a case of a patient with SWS who exhibited hypogonadotropic hypogonadism, growth hormone (GH) deficiency, and central hypothyroidism at the age of 20 despite the absence of radiographic findings in the pituitary and hypothalamus., Case Presentation: A 20-year-old male with SWS with epilepsy and Klippel-Trenaunay syndrome presents with delayed pubertal development, short stature, and obesity. Upon further examination, he was found to have biochemical and clinical evidence of hypogonadism, hypothyroidism, and GH deficiency. A pituitary MRI displayed no abnormalities of the pituitary or hypothalamus. Treatment with testosterone cypionate and levothyroxine was initiated. Despite successful pubertal induction, IGF-1 levels have remained low and treatment with recombinant human growth hormone (rhGH) is now being considered for metabolic benefits., Conclusions: This case emphasizes the importance of endocrine evaluation and treatment of hormonal deficiencies in patients with SWS despite the absence of radiographic findings., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Context: The melanocortin 3 receptor (MC3R) has recently emerged as a critical regulator of pubertal timing, linear growth, and the acquisition of lean mass in humans and mice. In population-based studies, heterozygous carriers of deleterious variants in MC3R report a later onset of puberty than noncarriers. However, the frequency of such variants in patients who present with clinical disorders of pubertal development is currently unknown., Objective: This work aimed to determine whether deleterious MC3R variants are more frequently found in patients clinically presenting with constitutional delay of growth and puberty (CDGP) or normosmic idiopathic hypogonadotropic hypogonadism (nIHH)., Methods: We examined the sequence of MC3R in 362 adolescents with a clinical diagnosis of CDGP and 657 patients with nIHH, experimentally characterized the signaling properties of all nonsynonymous variants found and compared their frequency to that in 5774 controls from a population-based cohort. Additionally, we established the relative frequency of predicted deleterious variants in individuals with self-reported delayed vs normally timed menarche/voice-breaking in the UK Biobank cohort., Results: MC3R loss-of-function variants were infrequent but overrepresented in patients with CDGP (8/362 [2.2%]; OR = 4.17; P = .001). There was no strong evidence of overrepresentation in patients with nIHH (4/657 [0.6%]; OR = 1.15; P = .779). In 246 328 women from the UK Biobank, predicted deleterious variants were more frequently found in those self-reporting delayed (aged ≥16 years) vs normal age at menarche (OR = 1.66; P = 3.90E-07)., Conclusion: We have found evidence that functionally damaging variants in MC3R are overrepresented in individuals with CDGP but are not a common cause of this phenotype., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)