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AIM: To investigate the effects of exogenous testosterone treatment on the choroidal parameters in patients with androgen deficiency. METHODS: Right eyes of 24 patients with androgen deficiency and 31 healthy volunteers were included in the study. The eyes were scanned for subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), choroid-stromal area (C-SA), choroid-luminal area (C-LA), choroid-stromal to luminal area ratio (CSLR), and the choroidal parameters within central 1500 µm of the macula (CVI1500, C-LA1500, C-SA1500, and CSLR1500) by enhanced-depth imaging optical coherence tomography (EDI-OCT) at baseline, 6th and 18th weeks of the exogenous testosterone treatment. RESULTS: The mean SFCT values of the androgen deficient groups and healthy controls were 307.7±27.0 and 303.2±37.2 µm (P=0.8). However, CVI, C-SA, CSLR, CVI1500, C-LA1500, and CSLR1500 were significantly different between the groups (all P<0.01). At the 6th week visit after exogenous testosterone treatment, SFCT, CVI, C-LA, and C-SA were significantly decreased, and these parameters returned to baseline levels at the 18th-week visit (all P>0.05). However, CVI1500 and LA1500 significantly increased at the end of the follow-up period (P<0.001). CONCLUSION: CVI is lower in androgen-deficient patients than in healthy subjects. The alterations in the choroid during the testosterone peak are transient in the treatment of patients with androgen deficiency. However, the increase in CVI within the central 1500 µm of the macula persists even after 4mo.
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Purpose: To evaluate the association of Life's Essential 8 (LE8) and its subscales with male biochemical androgen deficiency (MBAD) and total testosterone based on the data from the national health and nutrition examination survey (NHANES) database. Methods: Data of males aged 20 years or older from NHANES of 2013-2016 were extracted. LE8 score was calculated based on American Heart Association definitions. Total testosterone (TT) values were measured in NHANES using precise isotope dilution liquid chromatography. MBAD was defined as serum TT of <300 ng/dL. Univariate and multivariable analyses were conducted. Propensity score matching (PSM) and weighted regression after matching were added as sensitivity analyses. The generalized additive model, smooth curve fitting, and the recursive algorithm were used to determine the potential inflection points. Piecewise regression models with log-likelihood ratio test were used to quantify nonlinear effects. Results: A total of 3094 participants who were males and aged 20 years or above were included. Out of them, 805 males were diagnosed with MBAD. After adjusting the confounders in the multivariable model, LE8 was independently associated with MBAD (OR 0.96, P < 0.001) and TT (ß 2.7, P < 0.001). The association remained robust even after PSM. The non-linear relationship of LE8 behaviors score with MBAD and TT was revealed. Conclusion: LE8 was an independent protective factor of MBAD and a feasible approach to promote male endocrine sexual function.
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Encuestas Nutricionales , Testosterona , Humanos , Masculino , Adulto , Testosterona/sangre , Testosterona/deficiencia , Persona de Mediana Edad , Adulto Joven , Andrógenos/sangre , Andrógenos/deficiencia , Anciano , Hipogonadismo/epidemiología , Hipogonadismo/sangreRESUMEN
Testosterone therapy for men with hypogonadism due to identifiable hypothalamic-pituitary-testicular (HPT) pathology is uncontroversial. However, the risks and benefits of testosterone for men with clinical features of hypogonadism in the absence of identifiable HPT axis pathology have been uncertain. Recent landmark placebo-controlled trials assessed the benefits and risks of testosterone therapy (≤3 years) for middle-aged and older men with symptoms and possible signs of hypogonadism or end-organ androgen deficiency, low or low-normal serum testosterone concentrations, but no HPT pathology: Testosterone therapy (1) had modest-but clinically significant-benefits on average self-reported energy and mood, sexual function, and satisfaction; (2) in conjunction with a lifestyle programme, reversed or reduced incident type 2 diabetes mellitus (T2D) in men at high risk of or newly diagnosed with T2D; (3) modestly improved objectively assessed muscle strength and timed walking distance; (4) increased bone density and strength, but did not reduce falls or typical osteoporotic fractures and surprisingly increased the risk of fractures typically attributable to trauma; and (5) did not significantly increase the risk of myocardial infarction, stroke, or prostate cancer. These landmark trials help to inform clinical decision-making about testosterone therapy for men.
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Hipogonadismo , Testosterona , Humanos , Masculino , Testosterona/uso terapéutico , Testosterona/sangre , Hipogonadismo/tratamiento farmacológico , Hipogonadismo/sangre , Anciano , Terapia de Reemplazo de Hormonas/métodos , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Andrógenos/uso terapéuticoRESUMEN
AIM: To study the frequency of hypogonadism (HG) in men with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) and to evaluate the impact of HG on the course of RA and and concomitant diseases. MATERIALS AND METHODS: A single-stage continuous study included 170 men with RA, 57 men with AS and 85 men with PsA, who were hospitalized at the Nasonova Research Institute of Rheumatology. Patients were assessed for total testosterone (ТS) levels and subsequently divided into subgroups with normal (>12 nmol/l) and reduced levels. An intergroup comparison was carried out on the main indicators used in clinical rheumatological practice to assess the stage, activity and other medical and demographic characteristics of rheumatic disease, as well as on concomitant conditions. The second stage of the study involved a pairwise intergroup comparison among patients with HG with RA, AS and PsA. RESULTS: The incidence of ТS deficiency among patients with RA was 24.1%, among patients with AS - 17.5%, and with PsA - 31.8%. In patients with RA, HG was associated with a significantly higher mean body mass index, higher fasting blood glucose and uric acid, higher erythrocyte sedimentation rate and anemia. Patients with AS with HG had significantly lower hemoglobin levels and more frequent anemia, as well as higher levels of C-reactive protein and erythrocyte sedimentation rate. In PsA, older age was observed in the androgen deficiency group, as well as higher body mass index and fasting glucose levels; obesity was more common. An intergroup comparison of quantitative and qualitative indicators between patients with androgen deficiency in all three rheumatic diseases (RDs) did not reveal significant differences in the average concentrations of ТS, luteinizing hormone, sex hormone binding globulin, experience of RD, laboratory markers of inflammatory activity, as well as glucose and uric acid. A similar incidence of diabetes mellitus, obesity and anemia was noted for all three nosologies. CONCLUSION: ТS levels and the presence of HG were not associated with the stage and activity of RD, but ТS deficiency was accompanied by higher laboratory indicators of inflammatory activity, lower hemoglobin values, and metabolic disorders. Patients with HG, regardless of nosology, had similar levels of sex hormones and indicators reflecting RD and concomitant conditions.
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Artritis Psoriásica , Artritis Reumatoide , Hipogonadismo , Testosterona , Humanos , Masculino , Hipogonadismo/epidemiología , Hipogonadismo/sangre , Hipogonadismo/diagnóstico , Persona de Mediana Edad , Testosterona/sangre , Artritis Psoriásica/epidemiología , Artritis Psoriásica/complicaciones , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/sangre , Adulto , Artritis Reumatoide/epidemiología , Artritis Reumatoide/complicaciones , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Espondilitis Anquilosante/epidemiología , Espondilitis Anquilosante/complicaciones , Espondilitis Anquilosante/diagnóstico , Espondilitis Anquilosante/sangre , Espondilitis Anquilosante/fisiopatología , Federación de Rusia/epidemiología , Incidencia , Sedimentación SanguíneaRESUMEN
Testosterone is integral to men's sexual and overall health, but there is a gradual decline in the ageing male. The topical administration of testosterone is a valuable option as a supplement (replacement) therapy to alleviate hypogonadal symptoms. The clinical efficacy of a compounded testosterone 5% topical gel was assessed retrospectively in a male patient in his seventies by evaluating the laboratory testing of the serum total testosterone and the results of a validated androgen deficiency questionnaire. After treatment, the patient's hypogonadal symptoms improved and the serum total testosterone level achieved was considered clinically optimal. The skin permeation of the testosterone topical gel (biological testing) was evaluated in vitro using the Franz finite dose model and human cadaver skin, and it is shown that testosterone can penetrate into and through ex vivo human skin. Testosterone therapy is often prescribed for extended periods, and consequently, it is crucial to determine the beyond-use date of the compounded formulations. The analytical testing involved a valid, stability-indicating assay method for compounded testosterone 0.5% and 20% topical gels. This multidisciplinary study shows evidence supporting topically applied testosterone's clinical efficacy and the compounded formulations' extended stability. Personalized, topical testosterone therapy is a promising alternative in current therapeutics for hypogonadal patients.
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Cyclophosphamide (CP) is a widely used chemotherapeutic drug and immunosuppressant in the clinic, and the hypoandrogenism caused by CP is receiving more attention. Some studies found that ferroptosis is a new mechanism of cell death closely related to chemotherapeutic drugs and plays a key role in regulating reproductive injuries. The purpose of this study is to explore ferroptosis' role in testicular Leydig cell dysfunction and molecular mechanisms relating to it. In this study, the level of ferroptosis in the mouse model of testicular Leydig cell dysfunction induced by CP was significantly increased and further affected testosterone synthesis. The ferroptosis inhibitors ferrostatin-1 (Fer-1) and iron chelator deferoxamine (DFO) can improve injury induced by CP. The results of immunohistochemistry showed that Fer-1 and DFO could improve the structural disorder of seminiferous tubules and the decrease of the number of Leydig cells in testicular tissue induced by CP. Immunofluorescence and western blot confirmed that Fer-1 and DFO could improve the expression of key enzymes in testosterone synthesis. The activation of SMAD family member 2 (Smad2)/cyclin-dependent kinase inhibitor 1A (Cdkn1a) pathway can improve the ferroptosis of Leydig cells induced by CP and protect the function of Leydig cells. By inhibiting the Smad2/Cdkn1a signal pathway, CP can regulate ferroptosis, resulting in testicular Leydig cell dysfunction. In this study, CP-induced hypoandrogenism is explained theoretically and a potential therapeutic strategy is provided.
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Ciclofosfamida , Ferroptosis , Células Intersticiales del Testículo , Proteína Smad2 , Animales , Masculino , Ratones , Ciclohexilaminas/farmacología , Ciclofosfamida/toxicidad , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/metabolismo , Fenilendiaminas/farmacología , Transducción de Señal/efectos de los fármacos , Proteína Smad2/metabolismo , Testículo/efectos de los fármacos , Testículo/metabolismo , Testículo/patologíaRESUMEN
Women with hypopituitarism have various degrees of androgen deficiency, which is marked among those with combined hypogonadotrophic hypogonadism and secondary adrenal insufficiency. The consequences of androgen deficiency and the effects of androgen replacement therapy have not been fully elucidated. While an impact of androgen deficiency on outcomes such as bone mineral density, quality of life, and sexual function is plausible, the available evidence is limited. There is currently no consensus on the definition of androgen deficiency in women and it is still controversial whether androgen substitution should be used in women with hypopituitarism and coexisting androgen deficiency. Some studies suggest beneficial clinical effects of androgen replacement but data on long-term benefits and risk are not available. Transdermal testosterone replacement therapy in hypopituitary women has shown some positive effects on bone metabolism and body composition. Studies of treatment with oral dehydroepiandrosterone have yielded mixed results, with some studies suggesting improvements in quality of life and sexual function. Further research is required to elucidate the impact of androgen deficiency and its replacement treatment on long-term outcomes in women with hypopituitarism. The lack of transdermal androgens for replacement in this patient population and limited outcome data limit its use. A cautious and personalized treatment approach in the clinical management of androgen deficiency in women with hypopituitarism is recommended while awaiting more efficacy and safety data.
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Andrógenos , Terapia de Reemplazo de Hormonas , Hipopituitarismo , Humanos , Andrógenos/deficiencia , Andrógenos/uso terapéutico , Andrógenos/administración & dosificación , Femenino , Hipopituitarismo/tratamiento farmacológico , Terapia de Reemplazo de Hormonas/métodos , Hipogonadismo/tratamiento farmacológico , Testosterona/deficiencia , Testosterona/uso terapéutico , Testosterona/administración & dosificación , Calidad de VidaRESUMEN
INTRODUCTION: Previous work has demonstrated a deficiency in urology resident education when it comes to andrology and male infertility. We analyzed the top 100 most frequently cited and influential articles published on testosterone deficiency and its associated therapy, allowing trainees and clinicians to review and understand the characteristics of impactful literature for self-directed learning purposes. METHODS: The ISI Web of Knowledge database was used to find articles on testosterone deficiency, hypogonadism, and replacement therapies. Relevant, peer-reviewed, English articles were included. Article details, including title, citation count, publication year, and more, were gathered. Articles were classified based on content (e.g. clinical outcomes, anatomy, and trends) using defined criteria. RESULTS: The top 300 most cited were reviewed with 100 included. The most cited article had 774 citations, averaging 234 in the top 100. Publication years had peaks in 2003-2004 and 2006-2007. The US led in publications (56), followed by England (16), Germany (14), and Italy (13). Common affiliations included US Department of Veteran Affairs, Veterans Health Administration, RIC Research Education Clinical Center, and University of California System. Articles were categorized as LOE 2 (47), LOE 1 (22), and LOE 5 (21). Articles focused on clinical outcomes (71.7%), anatomy/biomechanics/physiology (14.1%), clinical guidelines (8.1%), and screening (4%). The "Journal of Clinical Endocrinology & Metabolism" published 26 of the top 100 cited articles. CONCLUSIONS: This analysis highlights influential articles regarding testosterone deficiency and management. The discussed articles have significant clinical and therapeutic implications for the practicing urologist which may bolster deficits in current resident education.
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Bibliometría , Internado y Residencia , Mejoramiento de la Calidad , Testosterona , Urología , Humanos , Testosterona/deficiencia , Urología/educación , Masculino , Investigación BiomédicaRESUMEN
Background Hypogonadism is a condition in which the body's ability to produce sex hormones is reduced. Androgen deficiency and hypothyroidism are similar in many symptoms, and the coexistence of the two conditions is common. The aim of this study is to explore the prevalence of hypogonadism symptoms in male patients diagnosed with primary hypothyroidism. Methods This cross-sectional study was conducted at â¯King Abdulaziz Medical City â¯in Riyadh, â¯Saudi Arabia, with a sample size of 120 adult male patients with primary hypothyroidism. Data collection primarily relied on one instrument, namely, theâ¯Androgen Deficiencyâ¯in Aging Males (ADAM) questionnaire, which was translated into Arabic and validated by previous researchers. Results A total of 120 adult males with hypothyroidism completed the ADAM questionnaire. Out of the 120 patients, 67.5% had a positive screen for hypogonadism. Among patients who had hypogonadism symptoms on the questionnaire, 81% had a BMI above 25, 69% were older than 40, and 65% were smokers. Conclusion Hypogonadism symptoms are common in male patients with primary hypothyroidism. Among patients with primary hypothyroidism, increasing age and being overweight added to the likelihood of having hypogonadism symptoms.
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Testosterone (T), the principal androgen secreted by the testes, plays an essential role in male health. Male hypogonadism is diagnosed based on a combination of associated clinical signs and symptoms and laboratory confirmation of low circulating T levels. In this review, we have highlighted factors, both biological and analytical, that introduce variation into the measurement of serum T concentrations in men; these need to be considered when requesting T levels and interpreting results. There is an ongoing need for analytical standardisation of T assays and harmonisation of pre- and post-analytical laboratory practices, particularly in relation to the laboratory reference intervals provided to clinicians. Further, there is a need to share with service users the most up-to-date and evidence-based action thresholds for serum T as recommended in the literature. Estimation of free testosterone may be helpful. Causes of secondary hypogonadism should be considered. A comprehensive approach is required in the management of male hypogonadism, including lifestyle modification as well as medication where appropriate. The goal of treatment is the resolution of symptoms as well as the optimisation of metabolic, cardiovascular, and bone health. The advice of an endocrinologist should be sought when there is doubt about the cause and appropriate management of the hypogonadism.
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Background: Klinefelter Syndrome (KS) is a sex chromosomal syndrome usually with an extra X chromosome (47, XXY) in males, which has various phenotype (mosaicism 47, XXY/46, XY, or more chromosomes 48, XXXY, 49, XXXXY) and clinical features, including eunuchoid body proportions, abnormally long legs and arm span, gynecomastia, ynecomastia, absent or decreased facial and pubic hair, small hyalinized testes, small penis, below-normal verbal intelligence quotient, and learning difficulties. At present, there are no studies on the correlation between the clinical characteristics of patients with KS and the ultrastructural changes of intracellular organelles in testicular tissue in China. Case presentation: Here we report the ultrastructure manifestation of the testis tissues in a KS patient with hypogonadism and androgen deficiency, to find a relationship between ultrastructural changes of organelles and spermatogenic dysfunction, clinical features, timing of surgery and metabolic abnormalities. It has been shown that the spermatocytes are absent and the ultrastructure of Sertoli cells and Leydig cells is obviously abnormal, which may lead to spermatogenic dysfunction, androgen deficiency, impaired glucose tolerance (IGT), and abdominal fat accumulation. Conclusions: Based on the European Academy of Andrology (EAA) Gudilines on Klinefelter Syndrome, this study conducted a retrospective study on the diagnosis and treatment of one adult patient with KS, aiming to provide a standardized diagnosis and treatment for patients with KS. This study is also highly concerned with the correlation between the ultrastructural changes of target organs and clinical symptoms.
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INTRODUCTION: Metabolic syndrome (MetS) is a combination of hormonal, metabolic and clinical disorders. Currently, MetS in men is considered as one of the main risk factors for the development of cardiovascular diseases, insulin resistance, and pathology of the reproductive system. AIM: To study the effect of a complex of folic acid, L-carnitine, vitamin E, zinc and selenium, which are part of the biologically active food supplement "Speroton", on the parameters of carbohydrate and lipid metabolism in men with MetS, especially in the early stages of its development, as well as on erectile function and quality of life of patients. MATERIALS AND METHODS: A total of 64 patients aged 30 to 51 years with MetS of varying severity were included in the study. The main group consisted of 34 patients aged 32 to 51 years (mean age 46.2+/-2.1 years), while in the control group, there were 30 patients aged 30 to 49 years (mean age 45.4+/-3.4 years). The standard therapy in the main group was supplemented by taking the dietary supplement "Speroton" for 3 months. In the control group, patients received only standard therapy for MetS. The results were evaluated after 3 and 6 months from the start of treatment. All patients underwent laboratory evaluation of sex hormones, carbohydrate metabolism and lipid profile. In addition, the concentration of zinc in the spermatozoa was measured, as well as the level of total antioxidant capacity of the sperm. The uroflowmetry, ultrasound of the bladder with the measurement of the postvoid residual, and transrectal ultrasound of the prostate were also performed. RESULTS: An addition of the antioxidant complex "Speroton" to the combination treatment of MetS in the main group allowed to decrease the parameters of oxidative stress by almost two times. By the 6th month of follow-up, the level of insulin improved, which was accompanied by a decrease in the level of HbA1c by 16.3%, suggesting the stabilization of carbohydrate metabolism. A decrease in body mass index by almost 14% (p<0.05) in the main group was found, as well as normalization of the lipid profile. According to the analysis of the erectile function in patients of the main group after 6 months from the beginning of therapy, there was a decrease in the total score to a moderate erectile dysfunction (12.5+/-2.1 points). There was a decrease in storage symptoms and, in part, voiding symptoms in patients in the main group, who received antioxidant therapy. In addition, a positive correlation between the concentration of zinc and the level of total antioxidant capacity in the ejaculate was seen. CONCLUSIONS: Our results suggest the high therapeutic efficiency of dietary supplement "Speroton" as an antioxidant complex for the treatment of patients with MetS of varying severity. The addition of antioxidants "Speroton" to the standard therapy of MetS contributes to the improvement of the sensitivity of insulin receptors, the normalization of carbohydrate and lipid metabolism, endothelial function and blood pressure, which is accompanied by a significant decrease in LUTS severity, as well as an improvement in the erectile function of patients.
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Disfunción Eréctil , Síndrome Metabólico , Humanos , Masculino , Adulto , Persona de Mediana Edad , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/complicaciones , Antioxidantes/uso terapéutico , Disfunción Eréctil/complicaciones , Calidad de Vida , Semen , Lípidos , Carbohidratos , Zinc/uso terapéuticoRESUMEN
Leptin, an adipokine hormone, is a critical regulator of energy homeostasis, appetite, and metabolism. Recent advances have elucidated its role in male fertility. This forum provides an overview of the interplay between leptin, its receptors, and signaling pathways in the context of male fertility, revealing its multifaceted impact on reproductive health.
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Although testosterone replacement in men with classic hypogonadism due to an identified pathology of the hypothalamic-pituitary-testicular axis is uncontroversial, the role of testosterone treatment for men with age-related declines in circulating testosterone is unclear. This is due to the lack of large, long-term testosterone therapy trials assessing definitive clinical endpoints. However, men ≥50 years of age, particularly those who have a body mass index >25 kg/m2 and multiple comorbidities, commonly present with clinical features of androgen deficiency and low serum testosterone concentrations. Clinicians are faced with the question whether to initiate testosterone therapy, a difficult dilemma that entails a benefit-risk analysis with limited evidence from clinical trials. Using a case scenario, we present a practical approach to the clinical assessment and management of such men.
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Hipogonadismo , Testosterona , Masculino , Humanos , Hipogonadismo/diagnóstico , Hipogonadismo/tratamiento farmacológico , Testículo , Terapia de Reemplazo de Hormonas , Medición de RiesgoRESUMEN
Recent publications of well-conducted population studies have informed us that the syndromic prevalence of age-related low testosterone, also known as late-onset hypogonadism, is quite low. Several well-conducted trials in middle-aged and older men with age-related decline in testosterone levels have revealed that efficacy of testosterone therapy is modest with improvement in sexual function, mood, volumetric bone density, and anemia. Although select older men might benefit from testosterone therapy, its effect on prostate cancer risk and major adverse cardiovascular events remains unclear. The results of the ongoing TRAVERSE trial will likely provide important insights into these risks.
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Hipogonadismo , Testosterona , Persona de Mediana Edad , Humanos , Masculino , Anciano , Testosterona/uso terapéutico , Envejecimiento , Hipogonadismo/tratamiento farmacológico , Reproducción , Terapia de Reemplazo de Hormonas/efectos adversosRESUMEN
17ß-hydroxysteroid dehydrogenase type 3 (17ß-HSD3) converts Δ4-androstene-3,17-dione (androstenedione) to testosterone. It is expressed almost exclusively in the testes and is essential for appropriate male sexual development. More than 70 mutations in the HSD17B3 gene that cause 17ß-HSD3 deficiency and result in 46,XY Disorders of Sex Development (46,XY DSD) have been reported. This study describes three novel Tunisian cases with mutations in HSD17B3. The first patient is homozygous for the previously reported mutation p.C206X. The inheritance of this mutation seemed to be independent of consanguineous marriage, which can be explained by its high frequency in the Tunisian population. The second patient has a novel splice site mutation in intron 6 at position c.490 -6 T > C. A splicing assay revealed a complete omission of exon 7 in the resulting HSD17B3 mRNA transcript. Skipping of exon 7 in HSD17B3 is predicted to cause a frame shift in exon 8 that affects the catalytic site and results in a truncation in exon 9, leading to an inactive enzyme. The third patient is homozygous for the novel missense mutation p.K202M, representing the first mutation identified in the catalytic tetrad of 17ß-HSD3. Site-directed mutagenesis and enzyme activity measurements revealed a completely abolished 17ß-HSD3 activity of the p.K202M mutant, despite unaffected protein expression, compared to the wild-type enzyme. Furthermore, the present study emphasizes the importance of genetic counselling, detabooization of 46,XY DSD, and a sensitization of the Tunisian population for the risks of consanguineous marriage.
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17-Hidroxiesteroide Deshidrogenasas , Trastorno del Desarrollo Sexual 46,XY , Humanos , Masculino , 17-Hidroxiesteroide Deshidrogenasas/genética , 17-Hidroxiesteroide Deshidrogenasas/metabolismo , Trastorno del Desarrollo Sexual 46,XY/genética , Homocigoto , Mutación , Mutación Missense , TestosteronaRESUMEN
International guidelines suggest to use testosterone therapy (TTh) in hypogonadal men presenting symptoms of testosterone deficiency (TD), even if there is no fixed threshold level of T at which TTh should be started. We aimed to develop and validate a nomogram named TRACE (Testosterone ReplACEment) for predicting the need of TTh in patients with "low-normal" total testosterone levels. The following nomogram variables were used: serum T level; serum LH level; BMI; state of nocturnal erections; metabolic comorbidities; and IPSS total score. The nomogram has been tested by calculating concordance probabilities, as well as assaying the calibration of predicted probability of clinical testosterone deficiency and need for TTh, together with the clinical outcome of the TTh. A cohort of 141 patients was used for the development of the nomogram, while a cohort of 123 patients attending another institution was used to externally validate and calibrate it. Sixty-four patients (45.3%) received TTh. Among them, sixty patients (93.7%) reported a significant clinical improvement after TTh. The nomogram had a concordance index of 0.83 [area under the ROC curve 0.81 (95% CI 0.71-0.83)]. In conclusion, the TRACE nomogram accurately predicted the probability of clinical impairment related to TD, and resulted in a simple and reliable method to use to select hypogonadal patients with not clearly pathological testosterone values who will benefit from TTh.