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1.
Aging Male ; 25(1): 65-71, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35243960

RESUMO

OBJECTIVE: To investigate whether routine assessment of free testosterone improves the diagnostic accuracy of functional hypogonadism. METHODS: Total and free testosterone (calculated on SHBG levels) were determined in 188 patients with sexual symptoms and 184 with infertility. RESULTS: Hypogonadism (calculated free testosterone <63 pg/ml) was found in 47/188 (25.0%) patients with sexual symptoms and in 21/184 (11.4%) with infertility. Total testosterone determination misdiagnosed hypogonadism in 8.4% (12/143) of men with sexual symptoms and in 2% (3/152) with infertility. In subjects with borderline total testosterone, only 24.7% (19/77) had hypogonadism confirmed by free testosterone levels. Free testosterone levels significantly correlated with age, haematocrit, gonadotropins, gynecomastia, BMI, and number of co-morbidities, whereas total testosterone associated only with the latter two. Furthermore, age, haematocrit, BMI, and the presence of erectile dysfunction and of low libido were significantly different between men with normal and low free testosterone, whereas only BMI and low libido were significantly different between patients with normal and low total testosterone. CONCLUSION: Routine assessment of free testosterone allows a more accurate diagnosis of functional hypogonadism, especially in men with sexual symptoms. Free testosterone levels associate with clinical and biochemical parameters of androgen deficiency better than total testosterone levels.


Assuntos
Disfunção Erétil , Eunuquismo , Hipogonadismo , Disfunção Erétil/complicações , Eunuquismo/complicações , Humanos , Hipogonadismo/complicações , Libido , Masculino , Testosterona
2.
Aging Male ; 25(1): 72-87, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35291927

RESUMO

BACKGROUND: Pathogenesis and endothelial function in subclinical hypogonadism (SCH) remain unclear. Undercarboxylated osteocalcin (ucOC) participates in atherosclerosis and reproduction. We explored the underlying mechanisms and interplay of endothelial dysfunction, unOC and reproductive hormones in SCH and primary late-onset hypogonadism (LOH). METHODS: In the SCH, LOH, and healthy eugonadal male groups, we measured serum unOC, calculated luteinizing hormone/testosterone (LH/T), LH.T product, and estradiol/T (E/T) as indicators of impaired Leydig cells, androgen sensitivity index (ASI), and aromatase activity, respectively (LH set-point regulators), and assessed flow-mediated dilation of the brachial artery (FMD%), carotid-intima media thickness (CIMT), and aortic stiffness (AS). RESULTS: ↑LH/T, ↑ASI, ↓aromatase activity, normal T, follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) levels, ↑unOC, and enhanced atherosclerotic markers (↓FMD%, ↑CIMT, ↑AS) are characteristics of SCH. Testosterone was positively correlated with FMD% in SCH. The independent predictors were: SHBG and LH for FMD% and CIMT, respectively, and LH/T, ucOC, FSH, estradiol, and E/T ratio for AS in the LOH group; and LH for FMD% & AS and LH and LH/T for CIMT in all study subjects. CONCLUSIONS: SCH is a distinct clinical entity characterized by impaired androgen sensitivity and aromatase activity, compensatory elevated unOC, endothelial dysfunction, and anti-atherogenic role of testosterone.


Assuntos
Eunuquismo , Hipogonadismo , Espessura Intima-Media Carotídea , Humanos , Masculino , Osteocalcina , Testosterona
3.
Andrology ; 10(4): 669-676, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34994093

RESUMO

BACKGROUND: Male hypogonadism (testosterone level < 300 ng/dl) is a clinical syndrome that results from failure of the testis to produce physiological levels of testosterone. Most marketed testosterone replacement therapy products often require multiple dose adjustment clinic visits to achieve the desired, eugonadal testosterone levels. OBJECTIVE: To evaluate the efficacy and safety of a novel oral testosterone undecanoate therapy for the treatment of hypogonadism. MATERIAL AND METHODS: Ninety-five (N = 95) hypogonadal men were enrolled in this open-label, single-arm, multicenter study in the United States (NCT03242590). Subjects received 225 mg of oral testosterone undecanoate (TLANDO) twice a day for 24 days without dose adjustment. Primary efficacy was percentages of subjects who achieved mean 24-h testosterone levels within the eugonadal range and secondary efficacies were evaluated based on the upper limit of lab normal range of testosterone concentration. RESULTS: Subjects enrolled were on average age of 56 years, with about 17% of subjects older than 65 years. The mean body mass index was 32.8 kg/m2 . The baseline mean total testosterone values were below the normal range (202 ± 74 ng/dl). Post-treatment with 450 mg testosterone undecanoate daily dose without dose adjustment, 80% of subjects (95% confidence interval of 72%-88%) achieved a testosterone Cavg in the normal range and restored testosterone levels to mean testosterone Cavg of 476 ± 184 ng/dl at steady state. Testosterone restoration was comparable to other approved testosterone replacement therapy products. TLANDO was well tolerated with no deaths, no drug-related serious adverse events, and no hepatic adverse events. DISCUSSION AND CONCLUSIONS: TLANDO restored testosterone levels to the normal range in the majority of hypogonadal males. This new oral testosterone replacement therapy can provide an option for no-titration oral testosterone replacement therapy. This therapy has the potential to improve patient compliance in testosterone replacement therapy.


Assuntos
Eunuquismo , Hipogonadismo , Eunuquismo/tratamento farmacológico , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Hipogonadismo/tratamento farmacológico , Hipogonadismo/etiologia , Masculino , Pessoa de Meia-Idade , Testosterona/uso terapêutico , Congêneres da Testosterona
4.
Andrology ; 10(4): 625-641, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35064779

RESUMO

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


Assuntos
Eunuquismo , Hipogonadismo , Disfunções Sexuais Fisiológicas , Terapia de Reposição Hormonal , Humanos , Hipogonadismo/diagnóstico , Hipogonadismo/tratamento farmacológico , Masculino , Qualidade de Vida , Testosterona/uso terapêutico
5.
Eur J Endocrinol ; 185(3): D1-D9, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34260411

RESUMO

Clinicians commonly encounter middle-aged and older men who present with functional hypogonadism, that is, with clinical features compatible with androgen deficiency and lowered serum testosterone, but without evidence of organic hypothalamic-pituitary-testicular axis pathology. Whether, and when, testosterone therapy should be offered to such men remains uncertain and controversial, in part due to the lack of definitive evidence regarding long-term patient-important health outcomes with testosterone treatment. In this debate, we address this controversy and provide two opposing points of view on the role of testosterone treatment in older men with functional hypogonadism.


Assuntos
Eunuquismo/tratamento farmacológico , Terapia de Reposição Hormonal , Testosterona/uso terapêutico , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
6.
J Endocrinol Invest ; 44(12): 2785-2797, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33970435

RESUMO

PURPOSE: Organic conditions underlying secondary hypogonadism (SH) may be ascertained by magnetic resonance imaging (MRI) of the hypothalamic-pituitary region that could not be systematically proposed to each patient. Based upon limited evidence, the Endocrine Society (ES) guidelines suggest total testosterone (T) < 5.2 nmol/L to identify patients eligible for MRI. The study aims to identify markers and their best threshold value predicting pathological MRI findings in men with SH. METHODS: A consecutive series of 609 men seeking medical care for sexual dysfunction and with SH (total T < 10.5 nmol/L and LH ≤ 9.4 U/L) was retrospectively evaluated. An independent cohort of 50 men with SH was used as validation sample. 126 men in the exploratory sample and the whole validation sample underwent MRI. RESULTS: In the exploratory sample, patients with pathological MRI findings (n = 46) had significantly lower total T, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prostate specific antigen (PSA) than men with normal MRI (n = 80). Receiver Operating Characteristics analysis showed that total T, LH, FSH and PSA are accurate in identifying men with pathologic MRI (accuracy: 0.62-0.68, all p < 0.05). The Youden index was used to detect the value with the best performance, corresponding to total T 6.1 nmol/L, LH 1.9 U/L, FSH 4.2 U/L and PSA 0.58 ng/mL. In the validation cohort, only total T ≤ 6.1 nmol/L and LH ≤ 1.9 U/L were confirmed as significant predictors of pathologic MRI. CONCLUSION: In men with SH, total T ≤ 6.1 nmol/L or LH ≤ 1.9 U/L should arise the suspect of hypothalamus/pituitary structural abnormalities, deserving MRI evaluation.


Assuntos
Eunuquismo , Hormônio Foliculoestimulante , Hipotálamo , Hormônio Luteinizante , Imageamento por Ressonância Magnética/métodos , Hipófise , Disfunções Sexuais Fisiológicas , Testosterona , Definição da Elegibilidade , Eunuquismo/sangue , Eunuquismo/complicações , Eunuquismo/diagnóstico , Hormônio Foliculoestimulante/análise , Hormônio Foliculoestimulante/sangue , Humanos , Hipotálamo/anormalidades , Hipotálamo/diagnóstico por imagem , Itália/epidemiologia , Hormônio Luteinizante/análise , Hormônio Luteinizante/sangue , Masculino , Pessoa de Meia-Idade , Hipófise/anormalidades , Hipófise/diagnóstico por imagem , Disfunções Sexuais Fisiológicas/diagnóstico , Disfunções Sexuais Fisiológicas/epidemiologia , Disfunções Sexuais Fisiológicas/etiologia , Testosterona/análise , Testosterona/sangue
7.
Minerva Endocrinol (Torino) ; 46(3): 252-261, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-32969626

RESUMO

INTRODUCTION: The concept of subclinical or compensated male hypogonadism (SHG), characterized by increased gonadotropins and normal testosterone levels is emerging. However, its real clinical significance is still conflicting. The aim of the present study was to summarize and discuss the available evidence related to the possible definition of SHG and the possible advantages of testosterone replacement therapy (TRT). EVIDENCE ACQUISITION: A comprehensive systematic Medline, Embase and Cochrane search was performed. Publications from January 1, 1969 up to February 29, 2020 were included. The search was restricted to English-language articles and studies of human participants. EVIDENCE SYNTHESIS: Two main clinical forms of SHG can be described. The first identifies young patients who have a positive medical history for testis damage occurring before puberty onset. The second form can occur as a consequence of an age-dependent decline of T. Whereas the former can be the consequence of several congenital or acquired diseases, also possible causes of primary hypogonadism, the real significance of the latter is still debatable. Available evidence indicates that age-related SHG is quite a common phenomenon, occurring in 9.4% of aging men from the general population. Cross-sectional and longitudinal data have documented that it is associated with poor health and can be a sign of forthcoming increased cardiovascular mortality and morbidity. CONCLUSIONS: Although available evidence suggests that in aging populations SHG can be considered a particular condition associated with an increased CV risk, it is still unknown if treatment with T can improve any outcomes in these subjects. Hence, further interventional studies are advisable to better understand the characteristics of SHG and the possible advantages of an early TRT.


Assuntos
Eunuquismo , Hipogonadismo , Estudos Transversais , Terapia de Reposição Hormonal , Humanos , Hipogonadismo/tratamento farmacológico , Masculino , Testosterona/uso terapêutico
8.
Am J Med ; 134(1): 84-94.e6, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32926849

RESUMO

BACKGROUND: Injury causes significant morbidity and mortality that is sometimes attributed to testosterone and violence. We hypothesized that prescribed testosterone might be associated with the subsequent risk of serious injury. METHODS: We conducted a self-matched individual-patient exposure-crossover analysis comparing injury risks before and after initiation of testosterone. We selected adults treated with testosterone in Ontario, Canada, from October 1, 2012, to October 1, 2017 (enrollment) and continued until October 1, 2018 (follow-up). The primary outcome was defined as an acute traumatic event that required emergency medical care. RESULTS: A total of 64,386 patients were treated with testosterone of whom 89% were men with a median age of 52 years. We identified 34,439 serious injuries during the baseline interval before starting testosterone (584 per month) and 7349 serious injuries during the subsequent interval after starting testosterone (565 per month). Rates of injuries were substantially above the population norm in both intervals with no significant increased risk after starting testosterone (relative risk = 1.00; 95% confidence interval: 0.96-1.04, P = 0.850). The unchanged risk extended to diverse patients, was observed for different formulations and applied to all injury mechanisms. In contrast, testosterone treatment was associated with a 48% increased risk of a thromboembolic event (relative risk = 1.48; 95% confidence interval: 1.25-1.74, P < 0.001). CONCLUSIONS: Testosterone treatment was associated with a substantial baseline risk of serious injury that did not increase further after starting therapy. Physicians prescribing testosterone could consider basic safety reminders to mitigate injury risks.


Assuntos
Eunuquismo/tratamento farmacológico , Testosterona/efeitos adversos , Adulto , Androgênios/efeitos adversos , Androgênios/uso terapêutico , Eunuquismo/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Risco , Testosterona/uso terapêutico
9.
Ann Endocrinol (Paris) ; 82(3-4): 132-133, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32171470

RESUMO

BACKGROUND: Male hypogonadism, arising from a range of etiologies including androgen-deprivation therapies (ADTs), has been reported as a risk factor for acquired long-QT syndrome (aLQTS) and torsades de pointes (TdP). A full description of the clinical features of aLQTS associated with ADT and of underlying mechanisms is lacking. METHODS: We searched the international pharmacovigilance database VigiBase for men (n=6 560 565 individual case safety reports) presenting with aLQTS, TdP, or sudden death associated with ADT. In cardiomyocytes derived from induced pluripotent stem cells from men, we studied electrophysiological effects of ADT and dihydrotestosterone. RESULTS: Among subjects receiving ADT in VigiBase, we identified 184 cases of aLQTS (n=168) and/or TdP (n=68; 11% fatal), and 99 with sudden death. Of the 10 ADT drugs examined, 7 had a disproportional association (reporting odds ratio=1.4-4.7; P<0.05) with aLQTS, TdP, or sudden death. The minimum and median times to sudden death were 0.25 and 92 days, respectively. The androgen receptor antagonist enzalutamide was associated with more deaths (5430/31 896 [17%]; P<0.0001) than other ADT used for prostate cancer (4208/52 089 [8.1%]). In induced pluripotent stem cells, acute and chronic enzalutamide (25µM) significantly prolonged action potential durations (action potential duration at 90% when paced at 0.5Hz; 429.7±27.1 (control) versus 982.4±33.2 (acute, P<0.001) and 1062.3±28.9ms (chronic; P<0.001), and generated afterdepolarizations and/or triggered activity in drug-treated cells (11/20 acutely and 8/15 chronically). Enzalutamide acutely and chronically inhibited delayed rectifier potassium current, and chronically enhanced late sodium current. Dihydrotestosterone (30nM) reversed enzalutamide electrophysiological effects on induced pluripotent stem cells. CONCLUSION: QT prolongation and TdP are a risk in men receiving enzalutamide and other ADTs. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03193138.


Assuntos
Di-Hidrotestosterona/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Função Ventricular/efeitos dos fármacos , Androgênios/farmacologia , Androgênios/uso terapêutico , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Células Cultivadas , Bases de Dados Factuais , Morte Súbita Cardíaca/epidemiologia , Di-Hidrotestosterona/uso terapêutico , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Eunuquismo/tratamento farmacológico , Eunuquismo/epidemiologia , Eunuquismo/fisiopatologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/fisiologia , Internacionalidade , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/epidemiologia , Síndrome do QT Longo/patologia , Síndrome do QT Longo/fisiopatologia , Masculino , Potenciais da Membrana/efeitos dos fármacos , Miócitos Cardíacos/patologia , Farmacovigilância , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/epidemiologia , Torsades de Pointes/patologia , Torsades de Pointes/fisiopatologia
10.
World J Urol ; 39(9): 3223-3229, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33034733

RESUMO

PURPOSE: Testosterone replacement therapy (TRT) remains controversial in men with treated prostate cancer. We assessed its safety and functional impacts in patients after definitive surgical treatment with robotic-assisted radical prostatectomy (RARP). METHODS: We performed a retrospective analysis of 1303 patients who underwent RARP during the years 2006-2019. We identified men with symptoms of andropause and low serum testosterone who received TRT post-RARP; then we divided the cohort into two groups accordingly for comparison. Biochemical recurrence (BCR) was the primary endpoint. Secondary endpoints included functional outcomes. Predictors of BCR, including the effect of TRT on BCR, were evaluated using univariable and multivariable logistic regression. RESULTS: Among the forty-seven men who received TRT, the mean age was 60.83 years with a median follow-up of 48 months. Three (6.4%) and 157 (12.56%) patients experienced BCR in TRT and non-TRT groups, respectively. Baseline characteristics were similar between both groups except for higher mean BMI in the TRT group (p = 0.03). In the multivariate analysis (MVA), higher pre-RARP prostate-specific antigen (PSA) (p = 0.043), higher International Society of Urological Pathology score (p < 0.001), seminal vesical invasion (p = 0.018) and positive surgical margin (p < 0.001) were predictors of BCR. However, TRT was not (p = 0.389). In addition, there was a significant change in the Sexual Health Inventory for Men (p = 0.022), and serum testosterone level (p < 0.001) before and 6 months after initiation of TRT. CONCLUSION: Our findings suggest that TRT, in well-selected, closely followed, symptomatic men post-RARP is an oncologically safe and functionally effective treatment in prostate cancer patients post-RARP.


Assuntos
Eunuquismo/tratamento farmacológico , Terapia de Reposição Hormonal , Complicações Pós-Operatórias/tratamento farmacológico , Prostatectomia , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Testosterona/uso terapêutico , Idoso , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia/métodos , Estudos Retrospectivos , Testosterona/efeitos adversos , Resultado do Tratamento
11.
Nutrients ; 13(1)2020 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-33375244

RESUMO

The androgens testosterone and dihydrotestosterone (DHT) are essential for a variety of systemic functions in mature males. Alteration of these hormones results in late-onset hypogonadism (LOH) and benign prostate hyperplasia (BPH). The fruit bodies of fungi of the genus Cordyceps have been regarded as folk medicine or health food with tonic and antifatigue effects. The extract from the fruit body of Cordyceps militaris parasitizing Samia cynthia ricini (CM) was evaluated as a novel-candidate natural product for ameliorating male andropause symptoms. To explore the effects of CM on LOH and BPH, CM was applied to rat models and cultured testicular cells and prostate cells. The concentrations of androgens in the serum and culture media were determined by ELISA. Expression of steroidogenic enzymes and androgen-related genes was evaluated by qPCR, and prostatic cell proliferation was assessed with the cell-viability assay. CM maintained the serum levels of testosterone and DHT, but inhibited testosterone-induced prostate hypertrophy. CM also increased the secretion of testosterone and DHT by primary testicular cells, with no changes in the mRNA expression of steroidogenic enzymes, but decreased the growth of prostatic cell lines. Our data suggest that CM could improve both LOH and BPH in males.


Assuntos
Cordyceps , Carpóforos/química , Hiperplasia Prostática/tratamento farmacológico , Testosterona/metabolismo , Testosterona/farmacologia , Aminoácidos/análise , Animais , Células Cultivadas , Meios de Cultivo Condicionados/química , Di-Hidrotestosterona/análise , Di-Hidrotestosterona/metabolismo , Eunuquismo/tratamento farmacológico , Masculino , Orquiectomia , Próstata/efeitos dos fármacos , Próstata/metabolismo , Ratos , Ratos Wistar , Açúcares/análise , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testosterona/análise , Trealose
12.
Andrology ; 8(6): 1614-1627, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32737921

RESUMO

BACKGROUND: Low testosterone (T) level is considered a marker of poor cardiovascular health. Ten years ago, the Testosterone in Older Men with Mobility Limitations (TOM) trial was discontinued due to a higher number of adverse events in men receiving T compared with placebo. Since then, several studies have investigated the risks of T replacement therapy (TRT) in late-onset hypogonadism (LOH). OBJECTIVE: To review the mechanism by which TRT could damage the cardiovascular system. MATERIALS AND METHODS: Comprehensive literature search of recent clinical and experimental studies. RESULTS: The mechanisms of T-mediated coronary vasodilation were reviewed with emphasis on calcium-activated and ATP-sensitive potassium ion channels. We showed how T regulates endothelial nitric oxide synthase (eNOS) and phosphoinositide 3-kinase/protein kinase B/eNOS signaling pathways in vessel walls and its direct effects on cardiomyocytes via ß1-adrenergic and ryanodine receptors and provided data on myocardial infarction and heart failure. Vascular smooth muscle senescence could be explained by the modulation of growth factors, matrix metalloproteinase-2, and angiotensin II by T. Furthermore, leukocyte trafficking, facilitated by changes in TNF-α, could explain some of the effects of T on atheromatous plaques. Conflicting data on prothrombotic risk linked to platelet aggregation inhibition via NO-triggered arachidonate synthesis or increased aggregability due to enhanced thromboxane A in human platelets provide evidence regarding the hypotheses on plaque maturation and rupture risk. The effects of T on cardiac electrophysiology and oxygen delivery were also reviewed. DISCUSSION: The effects of TRT on the cardiovascular system are complex. Although molecular studies suggest a potential benefit, several clinical observations reveal neutral or occasionally detrimental effects, mostly due to confounding factors. CONCLUSIONS: Attempts to demonstrate that TRT damages the cardiovascular system via systematic analysis of the putative mechanisms led to the contradiction of the initial hypothesis. Current evidence indicates that TRT is safe once other comorbidities are addressed.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/efeitos dos fármacos , Eunuquismo/tratamento farmacológico , Terapia de Reposição Hormonal , Testosterona/uso terapêutico , Animais , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Comorbidade , Eunuquismo/sangue , Eunuquismo/epidemiologia , Eunuquismo/fisiopatologia , Fatores de Risco de Doenças Cardíacas , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Medição de Risco , Testosterona/efeitos adversos , Testosterona/sangue , Testosterona/deficiência , Resultado do Tratamento
13.
Mol Cell Endocrinol ; 516: 110945, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32707080

RESUMO

Hypogonadism is more frequent among men with common metabolic diseases, notably obesity and type 2 diabetes. Indeed, endocrine disruption caused by metabolic diseases can trigger the onset of hypogonadism, although the underlying molecular mechanisms are not entirely understood. Metabolic diseases are closely related to unhealthy lifestyle choices, such as dietary habits and sedentarism. Therefore, hypogonadism is part of a pathological triad gathering unhealthy lifestyle, metabolic disease and genetic background. Additionally, hypogonadism harbors the potential to aggravate underlying metabolic disorders, further sustaining the mechanisms leading to disease. To what extent does lifestyle intervention in men suffering from these metabolic disorders can prevent, improve or reverse hypogonadism, is still controversial. Moreover, recent evidence suggests that the metabolic status of the father is related to the risk of inter and transgenerational inheritance of hypogonadism. In this review, we will address the proposed mechanisms of disease, as well as currently available interventions for hypogonadism.


Assuntos
Eunuquismo/etiologia , Estilo de Vida , Doenças Metabólicas/complicações , Eunuquismo/patologia , Humanos , Masculino
14.
Andrology ; 8(6): 1705-1711, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32558292

RESUMO

INTRODUCTION AND OBJECTIVES: Adult patients with Klinefelter syndrome (KS) may present with testicular volume loss and a decrease in circulating testosterone (T) levels. However, the actual rate of hypogonadism in adult KS men is unknown. We aimed to (a) assess the prevalence of different forms of hypogonadism in a cohort of KS patients with non-obstructive azoospermia (NOA); and (b) investigate potential preoperative predictor of positive sperm retrieval (SR) at surgery in the same cohort of men. METHODS: Complete data from 103 KS men with NOA who underwent testicular sperm extraction (TESE) between 2008 and 2019 at five centers were analyzed. Comorbidities were scored with the Charlson Comorbidity Index (CCI). Patients were categorized into four groups of hypogonadism as follows: eugonadism [normal total T (tT) (≥3.03 ng/mL) and normal luteinizing hormone (LH) (≤9.4 mUI/mL)], secondary hypogonadism [low tT (≤3.03 ng/mL) and low/normal LH (≤9.4 mUI/mL)], primary hypogonadism [low tT (≤3.03 ng/mL) and elevated LH (≥9.4 mUI/mL)], and compensated hypogonadism [normal tT (≥3.03 ng/mL) and elevated LH (≥9.4 mUI/mL)]. Descriptive statistics tested the association between clinical characteristics and laboratory values among the four groups. RESULTS: Median (IQR) patients age was 32 (24, 37) years. Baseline follicle-stimulating hormone and tT levels were 29.5 (19.9, 40.9) mUI/mL and 3.8 (2.5, 11.0) ng/mL, respectively. Eugonadism, primary hypogonadism, and compensated hypogonadism were found in 16 (15.6%), 34 (33.0%), and 53 (51.4%) men, respectively. No patients had secondary hypogonadism. Positive SR rate at TESE was 21.4% (22 patients); of 22, 15 (68.2%) patients underwent assisted reproductive technology and five (22.7%) ended in live birth children. Patients' age, BMI, CCI, FSH levels, and positive SR rates were comparable among hypogonadism groups. No preoperative parameters were associated with positive SR at logistic regressions analysis. CONCLUSIONS: Findings from this cross-sectional study showed that 15.6% of adult KS men have normal tT values at presentation in the real-life setting. Most KS patients presented with either compensated or primary hypogonadism. Sperm retrieval rates were not associated with different forms of hypogonadism.


Assuntos
Azoospermia/terapia , Eunuquismo/epidemiologia , Síndrome de Klinefelter/epidemiologia , Recuperação Espermática , Adulto , Azoospermia/diagnóstico , Azoospermia/epidemiologia , Azoospermia/fisiopatologia , Comorbidade , Estudos Transversais , Eunuquismo/diagnóstico , Fertilidade , Humanos , Itália/epidemiologia , Síndrome de Klinefelter/diagnóstico , Masculino , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Espanha/epidemiologia , Adulto Jovem
16.
Andrology ; 8(6): 1628-1641, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32593233

RESUMO

BACKGROUND: Late-onset hypogonadism (LOH) is a syndrome characterized by clinical and biochemical evidence of low testosterone levels with advancing age. In recent years, several guidelines, position statements and other recommendations have become available. It is unclear whether similar indications are reported in these documents. OBJECTIVE: To review similarities and differences among available documents on the management of hypogonadism, with a special focus on LOH. MATERIALS AND METHODS: PubMed, Google and international societies websites were searched on March 2020 for documents published in the last 10 years on the management of hypogonadism and LOH. RESULTS: Nine documents were found, each developed by: (a) the American Urological Association; (b) the British Society for Sexual Medicine; (c) the Canadian Medical Association; (d) the Endocrine Society; (e) the Endocrine Society of Australia; (f) the European Academy of Andrology; (g) the European Association of Urology; (h) the International Consultation for Sexual Medicine; and (i) the International Society for the Study of Aging Male. DISCUSSION: Despite similar principles, differences were found both for the diagnostic workup and follow-up. Particularly, discrepancies were reported both for total and free testosterone levels for diagnosis and for total testosterone for monitoring. CONCLUSION: Available documents differ in terms of specific recommendations for the management of hypogonadism and LOH. Given the relevant clinical implications of adequate management of these disorders, future guidelines should report more consistent measures to be adopted in clinical practice.


Assuntos
Endocrinologia/normas , Eunuquismo/tratamento farmacológico , Terapia de Reposição Hormonal/normas , Guias de Prática Clínica como Assunto/normas , Testosterona/uso terapêutico , Adulto , Idade de Início , Idoso , Biomarcadores/sangue , Consenso , Eunuquismo/sangue , Eunuquismo/diagnóstico , Eunuquismo/fisiopatologia , Medicina Baseada em Evidências/normas , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Testosterona/efeitos adversos , Testosterona/sangue , Testosterona/deficiência , Resultado do Tratamento
17.
Andrology ; 8(6): 1539-1550, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32469467

RESUMO

BACKGROUND: Bone health is underdiagnosed and undermanaged in men. Bone loss occurs in men with hypogonadism and in aging men. Thus, patients with a diagnosis of late-onset hypogonadism (LOH) are at risk of osteoporosis and osteoporotic fractures. OBJECTIVES: To provide an update on research data and clinical implications regarding bone health in men with LOH by reviewing literature articles on this issue. MATERIALS AND METHODS: A thorough search of listed publications in PubMed on bone health in older men with hypogonadism was performed, and other articles derived from these publications were further identified. RESULTS: Late-onset Hypogonadism may be associated with reduced bone mineral density (BMD). In a pathophysiological perspective, the detrimental effects of testosterone (T) deficiency on BMD are partly ascribed to relative estrogen deficiency and both serum T and serum estradiol (E2) need to be above 200 ng/dL and 20 pg/mL to prevent bone loss. The effects of exogenous T on BMD are controversial, but most of the studies confirm that testosterone replacement therapy (TRT) increases BMD and prevents further bone loss in men with hypogonadism. No data are available on TRT and the prevention of fractures. DISCUSSION AND CONCLUSION: In men with documented LOH, a specific clinical workup should be addressed to the diagnosis of osteoporosis in order to program subsequent follow-up and consider specific bone active therapy. TRT should be started according to guidelines of male hypogonadism while keeping in mind that it may also have positive effects also on bone health in men with LOH.


Assuntos
Densidade Óssea , Eunuquismo/metabolismo , Osteoporose/fisiopatologia , Fraturas por Osteoporose/fisiopatologia , Testosterona/deficiência , Idade de Início , Animais , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Eunuquismo/diagnóstico , Eunuquismo/tratamento farmacológico , Eunuquismo/epidemiologia , Terapia de Reposição Hormonal , Humanos , Masculino , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologia , Osteoporose/prevenção & controle , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Prognóstico , Medição de Risco , Fatores de Risco , Testosterona/sangue , Testosterona/uso terapêutico
18.
NeuroRehabilitation ; 46(3): 355-368, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32250330

RESUMO

BACKGROUND: Endocrinopathy, including hypogonadism, is common following traumatic brain injury (TBI). Prior evidence suggests hypogonadism is associated with poorer function. OBJECTIVE: Determine the feasibility, safety, and efficacy of testosterone (T) therapy in hypogonadal men following TBI in acute rehabilitation. DESIGN: Randomized, double blind, placebo-controlled pilot trial. SETTING: Inpatient rehabilitation brain injury unit. PARTICIPANTS: Men ages 18 -65, post moderate to severe TBI receiving inpatient rehabilitation. INTERVENTIONS: Transdermal T gel or placebo. MAIN OUTCOME MEASURES: Revised FIM™ score, strength, adverse events. RESULTS: Of 498 screened, 70 participants were enrolled, and 22 meeting all criteria were randomized into placebo (n = 10) or physiologic T therapy (n = 12). There was no significant difference between groups in rate of improvement on the FIM™ (intercepts t = -0.31, p = 0.7593, or slopes t = 0.61, p = 0.5472). The Treatment group demonstrated the greatest absolute improvement in FIM™ scores and grip strength compared to Placebo or Normal T groups. There was no difference in adverse events between groups. Percentage of time with agitation or aggression was highest in the Placebo group. CONCLUSIONS: Although there were no significant differences in rates of recovery, treatment group subjects showed greater absolute functional and strength improvement compared to the Placebo or Normal T groups.


Assuntos
Androgênios , Lesões Encefálicas Traumáticas , Eunuquismo , Testosterona , Adolescente , Adulto , Idoso , Androgênios/administração & dosagem , Androgênios/efeitos adversos , Androgênios/uso terapêutico , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/fisiopatologia , Lesões Encefálicas Traumáticas/reabilitação , Método Duplo-Cego , Eunuquismo/tratamento farmacológico , Eunuquismo/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Testosterona/administração & dosagem , Testosterona/efeitos adversos , Testosterona/uso terapêutico , Adulto Jovem
19.
Andrology ; 8(6): 1551-1566, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32068334

RESUMO

BACKGROUND: The aim of testosterone replacement therapy (TRT) is to improve symptoms and signs of testosterone deficiency including decreased libido, erectile dysfunction, depressed mood, anaemia, loss of muscle and bone mass, by increasing serum testosterone levels to physiologic range. TRT has been used in the last 70 years, and overtime, numerous preparations and formulations have been developed to improve pharmacokinetics (PKs) and patient compliance. The routes of delivery approved for use in the Western world include buccal, nasal, subdermal, transdermal and intramuscular (IM). OBJECTIVES: The aim of this narrative review was to describe and compare all available and approved testosterone preparations according to pharmacology, PKs and adverse effects. MATERIALS AND METHODS: We have performed an extensive PubMed review of the literature on TRT in clinical practice. Contraindications and monitoring of TRT were analyzed by comparing available guidelines released in the last five years. We provide a review of advantages and disadvantages of different modalities of TRT and how to monitor treatment to minimize the risks. RESULTS: TRT is associated with multiple benefits highly relevant to the patient. However, the recommendations given in different guidelines on TRT are based on data from a limited number of randomized controlled trials (RCTs), as well as non-randomized clinical studies and observational studies. This is the case for the safety of a long-term TRT in late-onset hypogonadism (LOH). No evidence is provided indeed on the effects of TRT on endpoints such as deterioration of heart failure suggesting a cautious approach to T replacement in older men with a history of heart failure. CONCLUSION: Clinicians must consider the unique characteristics of each patient and make the necessary adjustments in the management of LOH in order to provide the safest and most beneficial results.


Assuntos
Eunuquismo/tratamento farmacológico , Terapia de Reposição Hormonal , Testosterona/administração & dosagem , Tomada de Decisão Clínica , Formas de Dosagem , Vias de Administração de Medicamentos , Composição de Medicamentos , Eunuquismo/sangue , Eunuquismo/diagnóstico , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Masculino , Medição de Risco , Fatores de Risco , Testosterona/efeitos adversos , Testosterona/deficiência , Testosterona/farmacocinética , Resultado do Tratamento
20.
Andrology ; 8(6): 1606-1613, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32056383

RESUMO

BACKGROUND: There have always been concerns regarding testosterone replacement therapy and prostate safety because of the central role of testosterone in prostate tissue. Even though there is a body of evidence supporting that the benefits of testosterone replacement therapy outbalance the risks of prostate disease, this matter is still debatable and represents a common concern among testosterone prescribers. OBJECTIVES: The aim of this article was to review the influence of testosterone on prostate pathophysiology and discuss the potential impact of testosterone replacement therapy on the most common prostate pathologies, including benign prostatic hyperplasia and prostate cancer. MATERIALS AND METHODS: We have performed an extensive PubMed review of the literature examining the effects of testosterone replacement therapy on the prostate and its most common affections, especially in terms of safety. RESULTS: Testosterone replacement therapy has been shown to improve components of metabolic syndrome and decrease prostate inflammation, which is related to the worsening of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia. Studies evaluating the link between testosterone replacement therapy and benign prostatic hyperplasia/LUTS have mostly demonstrated no change in symptom scores and even some benefits. There are a significant number of studies demonstrating the safety of testosterone replacement therapy in individuals with late-onset hypogonadism and a history of prostate cancer. The most recently published guidelines have already acknowledged this fact and do not recommend against T treatment in this population, particularly in non-high-risk disease. CONCLUSION: Testosterone replacement therapy could be considered for most men with late-onset hypogonadism regardless of their history of prostate disease. However, a discussion about the risks and benefits of testosterone replacement therapy is always advised, especially in men with prostate cancer. Appropriate monitoring is mandatory.


Assuntos
Eunuquismo/tratamento farmacológico , Terapia de Reposição Hormonal , Próstata/efeitos dos fármacos , Hiperplasia Prostática/fisiopatologia , Neoplasias da Próstata/fisiopatologia , Testosterona/uso terapêutico , Biomarcadores/sangue , Tomada de Decisão Clínica , Eunuquismo/sangue , Eunuquismo/epidemiologia , Eunuquismo/fisiopatologia , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Masculino , Prognóstico , Próstata/metabolismo , Próstata/fisiopatologia , Hiperplasia Prostática/sangue , Hiperplasia Prostática/epidemiologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Medição de Risco , Fatores de Risco , Testosterona/efeitos adversos , Testosterona/sangue , Testosterona/deficiência
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