RESUMO
OBJECTIVE: We evaluated change (Δ) in AMSS in men with adult-onset testosterone deficiency (TD) on/not on testosterone undecanoate (TU) by analysing a registry of men with adult-onset TD. METHODS: Analyses were performed using non-parametric statistics to determine ΔAMSS at 6-12 monthly intervals in men on/not on TU and movement in AMSS. Factors predicting ΔAMSS were established via linear/multiple regression. RESULTS: TU was significantly associated with lower AMSS values compared with that at baseline/prior assessment during the initial 42 months treatment; 259 of the 260 men showed improvement. In the 361 men not on TU, AMSS values increased during 60 months of follow-up compared with that at baseline/prior assessment; improvement after 60 months was evident in 1 man, whilst AMSS remained the same or worsened in 213 and 147 men, respectively. In men on TU, baseline AMSS was inversely associated with ΔAMSS (R2 = 0.97), with no other factors reaching significance. Baseline AMSS, age, serum total testosterone (TT), waist circumference (WC), and diastolic blood pressure (BP) were associated with ΔAMSS in men not on TU. DISCUSSION: We show that TU was associated with lower AMSS in men with adult-onset TD whilst non-treatment led to increased values. Baseline AMSS values inversely predicted ΔAMSS in both groups.
Assuntos
Testosterona , Humanos , Masculino , Testosterona/deficiência , Testosterona/sangue , Testosterona/análogos & derivados , Testosterona/uso terapêutico , Testosterona/administração & dosagem , Pessoa de Meia-Idade , Idoso , Terapia de Reposição Hormonal/métodos , Adulto , Hipogonadismo/tratamento farmacológico , Hipogonadismo/sangue , Sistema de Registros , Envelhecimento/fisiologiaRESUMO
OBJECTIVES: We describe studies determining the association between testosterone therapy (TTh) and mortality. MATERIALS & METHODS: We used a registry database of 737 men with adult-onset testosterone deficiency defined as presenting with low serum total testosterone (TT) levels ≤12.1 nmol/L and associated symptoms over a near 10-year follow-up. We compared associations between testosterone undecanoate (TU), cardio-metabolic risk factors and mortality using non-parametric statistics followed by separate Cox regression models to determine if any association between TU and morality was independent of age and cardio-metabolic risk factors. Finally, the association between TU and mortality was studied in men stratified by cardio-metabolic risk. RESULTS: During a median follow-up interquartile range (IQR) of 114 (84-132) months, 94 of the 737 men died. TU (ref: non-treatment) was associated with mortality; hazard ratio = 0.23, 95% confidence intervals = 0.14-0.40. Cox's regression models showed the above association to be independent of baseline age, waist circumference, hemoglobin A1c, lipids, blood pressure, smoking, and type 2 diabetes. These variables remained associated with mortality. We finally stratified the men by the high-risk baseline variables and established that the association between mortality and TU was only evident in men at higher risk. A possible explanation could lie with the "law of initial value," where greater improvements are evident following treatment in patients with worse baseline values. CONCLUSIONS: This study with long follow-up confirms that TTh is associated with lower mortality in men with adult-onset TD. This association was evident only in men with greater cardio-metabolic risk factors who demonstrated greater benefit.
Assuntos
Terapia de Reposição Hormonal , Testosterona , Humanos , Masculino , Testosterona/uso terapêutico , Testosterona/sangue , Testosterona/deficiência , Testosterona/análogos & derivados , Pessoa de Meia-Idade , Terapia de Reposição Hormonal/efeitos adversos , Idoso , Adulto , Sistema de Registros , Fatores de RiscoRESUMO
BACKGROUND: Salmonella enterica serotype Typhi (S Typhi) is a major public health problem in low-income and middle-income countries. We aimed to investigate the effectiveness and impact of the typhoid conjugate vaccine Typbar-TCV against S Typhi among children in an outbreak setting of extensively drug-resistant (XDR) S Typhi in Pakistan. METHODS: This cohort study was done from Feb 21, 2018, to Dec 31, 2019. A census survey of all households located in the Qasimabad and Latifabad subdistricts of Hyderabad, Pakistan, was done at baseline, and 174â005 households were registered in the census. The Typbar-TCV immunisation campaign was initiated at temporary vaccination centres and 207â000 children aged 6 months to 10 years were vaccinated from Feb 21, 2018, to Dec 31, 2018. Social mobilisers informed parents about the vaccination process. Vaccination records were maintained electronically and linked with the household census surveys. Active surveillance for suspected and blood-culture-confirmed S Typhi was established in hospitals, clinics, and laboratories to assess the following outcomes: cases of suspected typhoid fever, culture-confirmed S Typhi, and antimicrobial resistance. An age-stratified cohort of 1100 vaccinated children was randomly selected from the vaccination registry, tested for Vi-IgG antibodies (data not reported), and followed up fortnightly (via telephone calls or household visits) until Dec 31, 2019, for ascertainment of outcomes during the study period. 20â847 vaccinated and unvaccinated children were randomly selected from the census registry as a quality control cohort and followed up from Oct 1 to Dec 31, 2019, for ascertainment of outcomes. Vaccine effectiveness against suspected, culture-confirmed, and XDR S Typhi was calculated. FINDINGS: 23â407 children from the census registry and surveillance system were included in the vaccine effectiveness analysis. 13â436 (57·4%) children were vaccinated, 12â214 (52·2%) were male, and 10â168 (43·4%) were aged 6-59 months. 5378 (23·0%) of 23â407 children had suspected S Typhi, among whom 775 (14·4%) had culture-confirmed S Typhi and 361 (68·6%) of 526 had XDR S Typhi. Vaccine effectiveness was 55% (95% CI 52-57) against suspected S Typhi (regardless of culture confirmation), 95% (93-96) against culture-confirmed S Typhi, and 97% (95-98) against XDR S Typhi. INTERPRETATION: Typbar-TCV is effective in protecting children against S Typhi infection in an outbreak setting, and was able, with moderate deployment, to curtail a major XDR S Typhi outbreak in a densely populated setting. The vaccine shows efficacy against S Typhi irrespective of antimicrobial resistance. FUNDING: Bill & Melinda Gates Foundation.
Assuntos
Surtos de Doenças/prevenção & controle , Farmacorresistência Bacteriana , Salmonella enterica/genética , Febre Tifoide/prevenção & controle , Vacinas Tíficas-Paratíficas/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Programas de Imunização , Lactente , Masculino , Paquistão/epidemiologia , Salmonella enterica/efeitos dos fármacos , Salmonella enterica/isolamento & purificação , Sorogrupo , Febre Tifoide/epidemiologia , Febre Tifoide/microbiologia , Vacinas Conjugadas/imunologiaRESUMO
OBJECTIVES: We aimed to evaluate the association of testosterone deficiency with inflammation and how long-term testosterone therapy affects inflammation biomarkers over time. METHODS: We conducted a 2-component study. First, we conducted a cross-sectional study using the recently released 2015-2016 National Health and Nutrition Examination Survey (NHANES) data to examine the association between testosterone deficiency and inflammation biomarkers including high sensitivity C-reactive protein (hsCRP), liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the US general population. Then we conducted a longitudinal study to investigate the longitudinal effect of testosterone therapy on inflammation biomarkers and the risk of cardiovascular events, using data from 776 hypogonadal men based on a registry study in Germany with up to 11 years' follow-up. RESULTS: The adjusted odds ratios (ORs) describing the associations between testosterone deficiency and hsCRP ≥ 3mg/L, ALT > 40U/L, and AST > 40U/L were 1.81 (P-value < 0.001), 1.46 (P-value = 0.009), and 0.99 (P-value = 0.971), respectively. In the control group, CRP, ALT, and AST levels increased by 0.003 (95%CI: -0.001, 0.007) mg/L, 0.157 U/L (95%CI: 0.145, 0.170), and 0.147 (95%CI: 0.136, 0.159) U/L per month, while in the treatment group, CRP, ALT, and AST levels decreased by 0.05 (95%CI: -0.055, -0.046) mg/L, 0.142 U/L (95%CI: -0.154, -0.130), and 0.148 (95%CI: -0.158, -0.137) U/L per month. CONCLUSION: Testosterone deficiency was associated with an increased level of inflammation; long-term testosterone therapy alleviated inflammation among hypogonadal men, which may contribute to the reduced cardiovascular risk. Future large trials are warranted to confirm our observational study findings.
Assuntos
Hipogonadismo/tratamento farmacológico , Inflamação/sangue , Inflamação/epidemiologia , Infarto do Miocárdio/epidemiologia , Testosterona/metabolismo , Testosterona/farmacologia , Adulto , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Proteína C-Reativa/análise , Estudos Transversais , Alemanha/epidemiologia , Humanos , Fígado/metabolismo , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Sistema de Registros , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
AIMS: To investigate whether testosterone therapy (TTh) in men with hypogonadism and type 2 diabetes mellitus (T2DM) improves glycaemic control and insulin sensitivity, and results in remission of T2DM. MATERIAL AND METHODS: A total of 356 men who had total testosterone levels ≤12.1 nmol/L (350 ng/dL) and symptoms of hypogonadism were included in the study and followed up for 11 years. All patients received standard diabetes treatment and 178 patients additionally received parenteral testosterone undecanoate 1000 mg every 12 weeks following an initial 6-week interval. A control group comprised 178 hypogonadal patients who opted not to receive TTh. RESULTS: Patients with hypogonadism and T2DM treated with testosterone had significant progressive and sustained reductions in fasting glucose, glycated haemoglobin (HbA1c) and fasting insulin over the treatment period. In the control group, fasting glucose, HbA1c and fasting insulin increased. Among the patients treated with testosterone 34.3% achieved remission of their diabetes and 46.6% of patients achieved normal glucose regulation. Of the testosterone-treated group, 83.1% reached the HbA1c target of 47.5 mmol/mol (6.5%) and 90% achieved the HbA1c target of 53.0 mmol/mol (7%). In contrast, no remission of diabetes or reductions in glucose or HbA1c levels were noted in the control group. There were fewer deaths, myocardial infarctions, strokes and diabetic complications in the testosterone-treated group. CONCLUSIONS: Long-term TTh in men with T2DM and hypogonadism improves glycaemic control and insulin resistance. Remission of diabetes occurred in one-third of the patients. TTh is potentially a novel additional therapy for men with T2DM and hypogonadism.
Assuntos
Diabetes Mellitus Tipo 2 , Hipogonadismo , Glicemia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Hipogonadismo/complicações , Hipogonadismo/tratamento farmacológico , Hipogonadismo/epidemiologia , Masculino , Sistema de Registros , Testosterona/análogos & derivadosRESUMO
Pakistan is facing the world's largest outbreak of extensively drug-resistant (XDR) Typhoid. Vaccination campaign for children aged 6 months to 10 years old with Typhoid Conjugate Vaccine (Typbar-TCV®) was conducted in high-risk areas of Hyderabad during 2018. About 207,000 children were vaccinated. Here we report the adverse events following immunization (AEFI) during the campaign. The campaign was carried out using outreach and fixed centre strategy. Community mobilizers visited each household to perform line listing and mobilize parents with age-eligible children. Children were observed for 30 min post-vaccination. Two-pronged strategy was used for ascertainment of AEFI. A 24/7 hotline number was provided to all parents/caretakers (n = 199,861) to report AEFI during 14 days following immunization. An age-stratified (n = 7139 children) were actively followed at days 7 and 14 for the ascertainment of AEFI. All AEFI were examined by three trained medical officers. A structured questionnaire using Brighton collaboration criteria with level 3 diagnostic certainty was used for the recording of AEFI. Data were analysed using Microsoft Excel Office 365. Overall, 499 AEFI (433 in the subset actively followed and 66 self-reported through hotline) were observed. The rate of AEFI was significantly higher among very young children (age group 6 to 12 months) as compared to 2 to 3 years old children (0.54% vs. 0.33% respectively; p-value < 0.001). Fever was the most common AEFI self-reported through the hotline (38/199,861 = 0.02%) and among the subset followed actively for 14 days (206/7139 = 2.89%). Fever was followed by local reactogenicity 10/199,861(0.01%), and 134/7139 (1.88%) through self-reported hotline and active follow-up, respectively. No serious AEFI was observed. Administration of a single dose of Typbar-TCV among children aged 6 months to 10 years old during an outbreak setting of Hyderabad Pakistan was safe.
Assuntos
Febre Tifoide , Vacinas Tíficas-Paratíficas , Sistemas de Notificação de Reações Adversas a Medicamentos , Criança , Pré-Escolar , Surtos de Doenças , Humanos , Imunização , Lactente , Paquistão , Febre Tifoide/epidemiologia , Febre Tifoide/prevenção & controle , Vacinas Tíficas-Paratíficas/efeitos adversos , Vacinação/efeitos adversos , Vacinas ConjugadasRESUMO
Low baseline testosterone level has been associated with the development of risk factors for cardiovascular disease such as insulin resistance and obesity. In addition to the absolute testosterone level, remarkable changes in testosterone level may have an acute effect on cardiovascular disease development and progression, which has been rarely investigated. In this study, we used a clinical dataset of 376 hypogonadal men whose testosterone levels were measured every six months for up to 11 years from a registry study in Germany, and conducted survival analyses to investigate the effect of testosterone changes since the last visit (time-varying) on the risk of cardiovascular events. Given the potential discrepancies in comorbidity conditions among patients with prior cardiovascular events and those without, all the analyses were stratified by patients' prior cardiovascular event status. We found the effects were not different among patients with prior cardiovascular events and those without. Regardless of patients' prior cardiovascular event status, patients with larger testosterone declines (≥3.12 nmol/L, 90th percentile) since the last visit were more likely to experience myocardial infarction. In conclusion, recent pronounced testosterone drop-offs may affect the risk of cardiovascular events among hypogonadal men. Future longitudinal studies are needed to confirm our exploratory study findings.
Assuntos
Doenças Cardiovasculares , Hipogonadismo , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Humanos , Hipogonadismo/complicações , Hipogonadismo/epidemiologia , Estudos Longitudinais , Masculino , Fatores de Risco , TestosteronaRESUMO
Objective: The association between erectile dysfunction (ED), hypogonadism, cardiovascular disease, and type 2 diabetes is well documented, but long-term data are limited. The aim of this study is to investigate effects of long-term testosterone therapy (TTh) with testosterone undecanoate in men with hypogonadism and ED.Patients and methods: Observational, prospective registry of 805 hypogonadal men with different degrees of ED, evaluated by the International Index of Erectile Function - Erectile Function Domain. Four hundred and twelve patients underwent TTh, 393 patients served as controls, with an observation period up to 12 years.Results: TTh led to substantial and sustained reduction of ED; improvement in erectile function was significant for each successive year until year 9. This was accompanied by improvements in cardiometabolic risk factors and urinary function throughout the 12-year follow-up period. Benefits of TTh were stronger for patients with moderate/severe ED than for patients with no/minor ED. Incidence of prostate cancer, major adverse cardiovascular events, and mortality were significantly lower in men on TTh compared with untreated men.Conclusion: Long-term TTh for up to 12 years alleviates ED, improves cardiometabolic risk factors, and reduces prostate cancer. Patients must stay on TTh consistently for a long time to achieve maximum benefits of TTh.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Disfunção Erétil/tratamento farmacológico , Hipogonadismo/tratamento farmacológico , Neoplasias da Próstata/prevenção & controle , Testosterona/análogos & derivados , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Estudos Prospectivos , Qualidade de Vida , Sistema de Registros , Testosterona/administração & dosagem , Testosterona/uso terapêuticoRESUMO
Objectives: To investigate whether testosterone replacement therapy (TRT) reduces prostate cancer (PCa) risk via stabilizing serum testosterone (T) levels beyond simply elevating serum T levels and whether TRT reduces PCa risk due to low serum T levels at a young age.Methods: We analyzed data of 776 hypogonadal men from a urology center in Bremerhaven, Germany through 2004-2016 to investigate whether the TRT group has more stable T levels and whether TRT can reduce the risk of PCa due to low serum T levels at an early age. We derived an index, Maximum Decline of T Relative to Baseline (MDRB), to describe the magnitude of T declines and variations over time.Results: We found the TRT group has more stable serum T levels (e.g. smaller drop-offs) during the follow-up period as compared to the non-TRT group, and the mean of MDRB is significantly higher in the untreated group (1.553 nmol/L VS 0.013 nmol/L; p-value < .001). TRT significantly reduces the risk of PCa associated with T deficiency at a young age (p-value = .00087).Conclusions: TRT may reduce PCa risk via maintaining serum T levels within individual's normal range; T surveillance may be needed for males who have low serum T levels at a young age to monitor abnormal variations of T levels and ensure timely treatment when necessary to reduce PCa risk.
Assuntos
Terapia de Reposição Hormonal/métodos , Hipogonadismo/tratamento farmacológico , Neoplasias da Próstata/prevenção & controle , Testosterona/uso terapêutico , Adulto , Idoso , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Testosterona/sangue , Testosterona/deficiênciaRESUMO
BACKGROUND: The Aga Khan University clinical microbiology laboratory identified an outbreak of ceftriaxone-resistant Salmonella Typhi in Hyderabad, Pakistan, through antimicrobial resistance surveillance. An outbreak investigation was carried out to identify the risk factors and institute control measures. Here we report the preliminary findings of this outbreak investigation, using data collected from 30 November 2016 to 28 March 2017. METHODS: The design for the investigation was a case-control study that included identification of culture-proven ceftriaxone-resistant S. Typhi cases, suspected cases from the households or neighborhood of the confirmed cases, and enrollment of controls matched by age to identify the risk factors. Data were collected through face-to-face interviews using a structured questionnaire. Blood cultures were obtained from all suspected cases. Drinking water samples from each household of cases and controls were obtained for microbiological testing. Geographic Information System coordinates were obtained for all cases and controls. RESULTS: Only 2 subdistricts of Hyderabad (Latifabad and Qasimabad) were affected. A total of 101 confirmed cases of ceftriaxone-resistant S. Typhi had been reported in 4 months with the first case reported on 30 November 2016. Median age was 48 (interquartile range, 29-84) months. The majority (60% [61/101]) of the cases were 6-60 months old. More than half (56% [57/101]) of the cases were male. About 60% of the cases were admitted to hospital and treated as inpatient. More than half (57/101) of the patients developed complications related to typhoid. CONCLUSIONS: Community awareness was raised regarding chlorination of drinking water and sanitation measures in Hyderabad. These efforts were coordinated with the municipal water and sewage authority established to improve chlorination at processing plants and operationalize fecal sludge treatment plants. Outbreak investigation and control efforts have continued. Immunization of children with typhoid conjugate vaccine within Hyderabad city is planned.
Assuntos
Ceftriaxona/farmacologia , Surtos de Doenças , Salmonella typhi/efeitos dos fármacos , Febre Tifoide/epidemiologia , Febre Tifoide/microbiologia , Vacinas Tíficas-Paratíficas/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Paquistão/epidemiologia , Saneamento , Febre Tifoide/prevenção & controle , Microbiologia da Água , Qualidade da Água , Abastecimento de Água , Adulto JovemRESUMO
BACKGROUND: Pakistan is currently facing the largest outbreak of ceftriaxone-resistant Salmonella enterica serotype Typhi described to date. Here we aimed to report the outbreak investigation done in Hyderabad, Pakistan, and identify disease risk factors. METHODS: We did an age-matched case-control (1:4) study, in which cases of ceftriaxone-resistant S Typhi were identified from active sentinal sites (three hospitals in Hyderabad, Pakistan), community, and laboratory-based surveillance. Ceftriaxone-resistant S Typhi infection (ie, resistance to ampicillin, chloramphenicol, co-trimoxazole, fluoroquinole, and ceftriaxone) was confirmed using blood culture. Healthy participants (controls) were enrolled for the first 200 people (cases) with ceftriaxone-resistant S Typhi. A structured questionnaire was administered to identify exposures 4 weeks before the illness (cases) or enrolment (controls). Cases were included if written informed consent was provided. Four controls were selected from the same community as the corresponding case, matched on age, being healthy at the time of enrolment, and with no febrile illness in the 4 weeks before enrolment. Samples of drinking water from households and community water sources (ie, hand pumps or taps in common areas outside households) were collected for testing. Conditional logistic regression analysis was used to assess the risk factors for ceftriaxone-resistant S Typhi outbreak in Hyderabad. FINDINGS: Between Nov 30, 2016, and Dec 30, 2017, 486 people with ceftriaxone-resistant S Typhi were identified from Hyderabad. Of the 486 cases, 296 (61%) were male and 447 (92%) were aged 15 years or younger. Several factors were significantly associated with acquisition of ceftriaxone-resistant S Typhi, including male sex (adjusted odds ratio [aOR] 1·53, 95% CI 1·06-2·21), eating outside of the house (aOR 1·48, 1·01-2·19), exposure to a patient with S Typhi infection (aOR 3·81, 2·21-6·83), and a history of antimicrobial use (aOR 4·25, 2·53-7·13). Nine (69%) of 13 water samples taken from the households of people with ceftriaxone-resistant S Typhi infection were positive for Escherichia coli, indicating faecal contamination. S Typhi DNA was detected in 12 (22%) of 55 water samples from community water sources. Geospatial mapping showed clustering of cases around sewerage lines. INTERPRETATION: Hyderabad faces the largest reported outbreak of ceftriaxone-resistant S Typhi. The outbreak is suspected to be attributed to the contaminated drinking water, especially the mixing of sewage with drinking water. The risk of ceftriaxone-resistant S Typhi infection is increased among children aged 15 years and younger, male individuals, and those eating outside the house. Vaccination and chlorination of water are recommended for the containment of the outbreak. FUNDING: None.
Assuntos
Antibacterianos/farmacologia , Ceftriaxona/farmacologia , Surtos de Doenças , Febre Tifoide/epidemiologia , Febre Tifoide/microbiologia , Resistência beta-Lactâmica , Adolescente , Adulto , Fatores Etários , Estudos de Casos e Controles , Criança , Pré-Escolar , Transmissão de Doença Infecciosa , Água Potável/microbiologia , Feminino , Humanos , Lactente , Paquistão/epidemiologia , Fatores de Risco , Salmonella typhi , Sorogrupo , Fatores Sexuais , Inquéritos e Questionários , Febre Tifoide/transmissão , Adulto JovemRESUMO
Purpose: To analyze data from an observational, prospective, cumulative registry study in 805 hypogonadal men stratified by mild or moderate-to-severe lower urinary tract symptoms (LUTS) according to International Prostate Symptom Score. Materials and Methods: A total of 412 men underwent testosterone therapy (TTh) with injectable testosterone undecanoate, 393 men served as untreated controls. Measures of urinary function, anthropometric and metabolic parameters were performed at least twice per year. Results: Data from 615 men with mild LUTS (253 treated, 362 untreated) and 190 with moderate-to-severe LUTS (159 treated, 31 untreated) were available. During a follow-up period of 8 years a significant improvement of LUTS was noted for all TTh-patients whereas the control-groups showed deterioration or fluctuation around initial values. Despite advancing age, TTh fully prevented worsening of symptoms. In parallel, a considerable improvement of anthropometric parameters, lipids and glycemic control, blood pressure, C-reactive protein, and quality of life was found. Moderate-to-severe LUTS was associated with worse cardiometabolic risk profile at baseline as well as worse cardiovascular outcomes during follow-up in comparison to mild LUTS. Effect size of TTh was more pronounced in men with moderate-to-severe than with mild LUTS. Conclusions: Correcting hypogonadism by TTh is highly effective and safe for improving LUTS in hypogonadal men. TTh may also improve cardiometabolic risk and major adverse cardiovascular events.
Assuntos
Androgênios/uso terapêutico , Hipogonadismo/complicações , Hipogonadismo/tratamento farmacológico , Sintomas do Trato Urinário Inferior/complicações , Testosterona/uso terapêutico , Idoso , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Seguimentos , Hemoglobinas Glicadas/metabolismo , Humanos , Hipogonadismo/fisiopatologia , Lipídeos/sangue , Sintomas do Trato Urinário Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Sistema de Registros , Fatores de Risco , Índice de Gravidade de Doença , Testosterona/sangue , Aumento de Peso , Redução de Peso/efeitos dos fármacosRESUMO
PURPOSE: We investigated the effects of long-term testosterone therapy on urinary and sexual function, and quality of life in hypogonadal men. MATERIALS AND METHODS: We performed an observational, prospective, cumulative registry study in 656 men with a mean ± SD age of 60.7 ± 7.2 years who had total testosterone 12.1 nmol/l or less and symptoms of hypogonadism. In the testosterone treated group 360 men received parenteral testosterone undecanoate 1,000 mg/12 weeks for up to 10 years. The 296 men who elected against testosterone therapy served as controls. From each group 82 patients were propensity matched by age, waist circumference and body mass index, resulting in 82 matched pairs of 164 men. Data were analyzed and estimated differences between the groups were adjusted for components of metabolic syndrome and quality of life. RESULTS: We found significant decreases in I-PSS (International Prostate Symptom Score) and post-void bladder volume (each p <0.0001) in patients receiving testosterone therapy but not in the untreated group. We recorded a decrease in AMS (Aging Males' Symptoms Scale) in the testosterone treated group but not in the untreated group (p <0.0001). We also recorded significant improvement in the IIEF-EF (International Index of Erectile Function-Erectile Function) domain in the testosterone treated group but not in the untreated group (p <0.0001). The improvement was maintained throughout followup. CONCLUSIONS: Long-term testosterone therapy in hypogonadal men resulted in significant improvements in urinary and sexual function, and in quality of life. In untreated hypogonadal men voiding and erectile function deteriorated with continued followup.
Assuntos
Androgênios/uso terapêutico , Hipogonadismo/tratamento farmacológico , Ereção Peniana/efeitos dos fármacos , Testosterona/análogos & derivados , Micção/efeitos dos fármacos , Idoso , Androgênios/farmacologia , Seguimentos , Humanos , Hipogonadismo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ereção Peniana/fisiologia , Estudos Prospectivos , Qualidade de Vida , Sistema de Registros/estatística & dados numéricos , Testosterona/farmacologia , Testosterona/uso terapêutico , Resultado do Tratamento , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/fisiopatologia , Micção/fisiologiaRESUMO
Background Dutasteride has been successfully used in treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). However, dutasteride inhibits 5α-reductase type 1 and type 2 enzymes and may compromises glucocorticoids and androgen metabolism and alters metabolic function resulting in undesirable metabolic and sexual adverse side effects. Aim The aim of this study was to investigate the long-term adverse effects of dutasteride therapy in men with BPH on: i) blood glucose, ii) glycated hemoglobin (HbA1c), iii) low density lipoprotein-cholesterol (LDL-C); high density lipoprotein-cholesterol (HDL-C) and total cholesterol (TC), iv) testosterone (T), v) liver alanine and aspartate aminotransferases (ALT and AST) and vi) erectile dysfunction (ED). Methods A retrospective registry study, with a cohort of 230 men aged between 47 and 68 years (mean 57.78 ± 4.81) were treated with dutasteride (0.5 mg/day) for LUTS, secondary to BPH. A second cohort of 230 men aged between 52 and 72 years (mean 62.62 ± 4.65) were treated with tamsulosin (0.4 mg). All men were followed up for 36-42 months. At intervals of 3-6 months, and at each visit, plasma glucose, HbA1c, TC, LDL-cholesterol, T levels and liver alanine amino transferase (ALT) and aspartate aminotransferase (AST) were determined. Further patient assessment was made by the International Index of Erectile Function (IIEF-EF) questionnaire, the Aging Male Symptom (AMS) and International Prostate Symptom Scores (IPSS). Results Long-term treatment with dutasteride therapy is associated with significant improvements in LUTS, as assessed by reduction in prostate volume, IPSS and prostate specific antigen (PSA). Long-term dutasteride therapy, however, resulted in increased blood glucose, HbA1c, TC and LDL levels, ALT and AST activities, AMS Score and reduced T levels and worsened ED as assessed by the IIEF-EF scores. No worsening of ED, glucose, HbA1c, ALT, AST, AMS were observed in men treated with tamsulosin. Most importantly, long-term dutasteride therapy resulted in reduction in total T levels, contributing to a state of hypogonadism. Conclusion Our findings suggest that long-term dutasteride therapy produces worsening of ED, reduced T levels and increased glucose, HbA1c and alters lipid profiles, suggesting induced imbalance in metabolic function. We strongly recommend that physicians discuss with their patients these potential serious adverse effects of long-term dutasteride therapy prior to instituting this form of treatment.
Assuntos
Glicemia/efeitos dos fármacos , Disfunção Erétil/diagnóstico , Disfunção Erétil/etiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/complicações , Inibidores de 5-alfa Redutase/efeitos adversos , Inibidores de 5-alfa Redutase/uso terapêutico , Idoso , Biomarcadores , Dutasterida/efeitos adversos , Dutasterida/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/patologia , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: In the absence of large, prospective, placebo-controlled studies of longer duration, substantial evidence regarding the safety and risk of testosterone (T) therapy (TTh) with regard to cardiovascular (CV) outcomes can only be gleaned from observational studies. To date, there are limited studies comparing the effects of long-term TTh in men with hypogonadism who were treated or remained untreated with T, for obvious reasons. We have established a registry to assess the long-term effectiveness and safety of T in men in a urological setting. Here, we sought to compare the effects of T on a host of parameters considered to contribute to CV risk in treated and untreated men with hypogonadism (control group). PATIENTS AND METHODS: Observational, prospective, cumulative registry study in 656 men (age: 60.7 ± 7.2 years) with total T levels ≤12.1 nmol/L and symptoms of hypogonadism. In the treatment group, men (n = 360) received parenteral T undecanoate (TU) 1000 mg/12 weeks following an initial 6-week interval for up to 10 years. Men (n = 296) who had opted against TTh served as controls. Median follow-up in both groups was 7 years. Measurements were taken at least twice a year, and 8-year data were analyzed. Mean changes over time between the 2 groups were compared by means of a mixed-effects model for repeated measures, with a random effect for intercept and fixed effects for time, group, and their interaction. To account for baseline differences between the 2 groups, changes were adjusted for age, weight, waist circumference, fasting glucose, blood pressure, and lipids. RESULTS: There were 2 deaths in the T-treated group, none was related to CV events. There were 21 deaths in the untreated (control) group, 19 of which were related to CV events. The incidence of death in 10 patient-years was 0.1145 in the control group (95% confidence interval [CI]: 0.0746-0.1756; P < .000) and 0.0092 in the T-treated group (95% CI: 0.0023-0.0368; P < .000); the estimated difference between groups was 0.0804 (95% CI: 0.0189-0.3431; P < .001). The estimated reduction in mortality for the T-group was between 66% and 92%. There were also 30 nonfatal strokes and 26 nonfatal myocardial infarctions in the control group and none in the T-treated group. CONCLUSION: Long-term TU was well tolerated with excellent adherence suggesting a high level of patient satisfaction. Mortality related to CV disease was significantly reduced in the T-group.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Hipogonadismo/tratamento farmacológico , Testosterona/uso terapêutico , Idoso , Índice de Massa Corporal , Hemoglobinas Glicadas/análise , Humanos , Hipogonadismo/complicações , Lipídeos/sangue , Fígado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Estudos Prospectivos , Sistema de Registros , Acidente Vascular Cerebral/epidemiologiaRESUMO
BACKGROUND/OBJECTIVES: Long-term testosterone therapy (TTh) in men with hypogonadism has been shown to improve all components of the metabolic syndrome. In this study, we investigated the effects of long-term TTh up to 8 years in hypogonadal men with a history of cardiovascular disease (CVD). PATIENTS AND METHODS: In two urological clinics observational registries, we identified 77 hypogonadal men receiving TTh who also had a history of CVD. The effects of TTh on anthropometric and metabolic parameters were investigated for a maximum duration of 8 years. Any occurrence of major adverse cardiovascular events was reported. All men received long-acting injections of testosterone undecanoate at 3-monthly intervals. RESULTS: In 77 hypogonadal men with a history of CVD who received TTh, we observed a significant weight loss and a decrease in waist circumference and body mass index. Mean weight decreased from 114±13 kg to 91±9 kg, change from baseline: -24±1 kg and -20.2%±0.5%. Waist circumference decreased from 112±8 cm to 99±6 cm, change from baseline: -13±0.3 cm. Body mass index decreased from 37±4 to 29±3, change from baseline: -8±0.2 kg/m(2). Cardio-metabolic parameters such as lipid pattern, glycemic control, blood pressure, heart rate, and pulse pressure all improved significantly and sustainably. No patient suffered a major adverse cardiovascular event during the full observation time. CONCLUSION: In men with hypogonadism, TTh appears to be effective in achieving sustained improvements in all cardiometabolic risk factors and may be effective as an add-on measure in the secondary prevention of cardiovascular events in hypogonadal men with a history of CVD.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Terapia de Reposição Hormonal , Hipogonadismo/tratamento farmacológico , Prevenção Secundária/métodos , Testosterona/análogos & derivados , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/fisiopatologia , Alemanha , Nível de Saúde , Frequência Cardíaca/efeitos dos fármacos , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Hipogonadismo/sangue , Hipogonadismo/complicações , Hipogonadismo/diagnóstico , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Recidiva , Sistema de Registros , Testosterona/administração & dosagem , Testosterona/efeitos adversos , Testosterona/sangue , Testosterona/deficiência , Fatores de Tempo , Resultado do Tratamento , Circunferência da Cintura , Redução de Peso/efeitos dos fármacosRESUMO
BACKGROUND: 5α-reductase inhibitors (5α-RIs) (finasteride and dutasteride) have been proven useful in treatment of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH). However, these inhibitors exert undesirable sexual side effects and, in some cases, these effects are persistent. There is considerable disagreement with regard to whether the adverse side effects resolve with continuous treatment. AIM: To investigate the long-term adverse effects of finasteride treatment in men with BPH on erectile function and to compare these adverse effects in men treated with the α1-adrenergic receptor blocker, tamsolusin. METHODS: In this retrospective registry study, a cohort of 470 men aged between 47 and 68 years (mean 57.78±4.81) were treated with finasteride (5 mg/day). A second cohort of 230 men aged between 52 and 72 years (mean 62.62±4.65) were treated with tamsulosin (0.4 mg). All men were followed up for 45 months. At intervals of 3 months and at each visit, plasma testosterone (T) levels and the international index of erectile function (IIEF-EF) questionnaire scores were determined. RESULTS: Long-term treatment with finasteride therapy is associated with worsening of erectile dysfunction (ED) as shown by the significant decrease in the IIEF-EF scores in men treated with finasteride. No worsening of ED was observed in men treated with tamsulosin. The increase in ED due to finasteride did not resolve with continued treatment with finasteride. Most importantly, long-term finasteride therapy resulted in reduction in total T levels, contributing to a state of hypogonadism. On the contrary, no changes in T levels were noted in men treated with tamsolusin. CONCLUSION: Our findings suggest that in men with BPH, long-term finasteride therapy but not tamsulosin results in worsening of ED and reduces total T concentrations. Clinicians are urged to discuss the impact of 5α-RIs therapy on sexual function with their patients before commencing this therapy.