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1.
Lancet Diabetes Endocrinol ; 9(1): 32-45, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33338415

RESUMO

BACKGROUND: Men who are overweight or obese frequently have low serum testosterone concentrations, which are associated with increased risk of type 2 diabetes. We aimed to determine whether testosterone treatment prevents progression to or reverses early type 2 diabetes, beyond the effects of a community-based lifestyle programme. METHODS: T4DM was a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial done at six Australian tertiary care centres. Men aged 50-74 years, with a waist circumference of 95 cm or higher, a serum testosterone concentration of 14·0 nmol/L or lower but without pathological hypogonadism, and impaired glucose tolerance (oral glucose tolerance test [OGTT] 2-h glucose 7·8-11·0 mmol/L) or newly diagnosed type 2 diabetes (provided OGTT 2-h glucose ≤15·0 mmol/L) were enrolled in a lifestyle programme and randomly assigned (1:1) to receive an intramuscular injection of testosterone undecanoate (1000 mg) or placebo at baseline, 6 weeks, and then every 3 months for 2 years. Randomisation was done centrally, including stratification by centre, age group, waist circumference, 2-h OGTT glucose, smoking, and first-degree family history of type 2 diabetes. The primary outcomes at 2 years were type 2 diabetes (2-h OGTT glucose ≥11·1 mmol/L) and mean change from baseline in 2-h OGTT glucose, assessed by intention to treat. For safety assessment, we did a masked monitoring of haematocrit and prostate-specific antigen, and analysed prespecified serious adverse events. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000287831. FINDINGS: Between Feb 5, 2013, and Feb 27, 2017, of 19 022 men who were pre-screened, 1007 (5%) were randomly assigned to the placebo (n=503) and testosterone (n=504) groups. At 2 years, 2-h glucose of 11·1 mmol/L or higher on OGTT was reported in 87 (21%) of 413 participants with available data in the placebo group and 55 (12%) of 443 participants in the testosterone group (relative risk 0·59, 95% CI 0·43 to 0·80; p=0·0007). The mean change from baseline 2-h glucose was -0·95 mmol/L (SD 2·78) in the placebo group and -1·70 mmol/L (SD 2·47) in the testosterone group (mean difference -0·75 mmol/L, -1·10 to -0·40; p<0·0001). The treatment effect was independent of baseline serum testosterone. A safety trigger for haematocrit greater than 54% occurred in six (1%) of 484 participants in the placebo group and 106 (22%) of 491 participants in the testosterone group, and a trigger for an increase of 0·75 µg/mL or more in prostate-specific antigen occurred in 87 (19%) of 468 participants in the placebo group and 109 (23%) of 480 participants in the testosterone group. Prespecified serious adverse events occurred in 37 (7·4%, 95% CI 5·4 to 10·0) of 503 patients in the placebo group and 55 (10·9%, 8·5 to 13·9) of 504 patients in the testosterone group. There were two deaths in each group. INTERPRETATION: Testosterone treatment for 2 years reduced the proportion of participants with type 2 diabetes beyond the effects of a lifestyle programme. Increases in haematocrit might be treatment limiting. Longer-term durability, safety, and cardiovascular effects of the intervention remain to be further investigated. FUNDING: Australian National Health and Medical Research Council, Bayer, Eli Lilly, University of Adelaide, and WW (formerly Weight Watchers).


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/prevenção & controle , Estado Pré-Diabético/tratamento farmacológico , Testosterona/uso terapêutico , Idoso , Austrália , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Progressão da Doença , Método Duplo-Cego , Intolerância à Glucose/sangue , Intolerância à Glucose/tratamento farmacológico , Intolerância à Glucose/patologia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Placebos , Estado Pré-Diabético/sangue , Estado Pré-Diabético/patologia , Indução de Remissão , Comportamento de Redução do Risco , Testosterona/efeitos adversos , Resultado do Tratamento
2.
J Toxicol Sci ; 45(8): 435-447, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32741896

RESUMO

The imbalance of testosterone to estradiol ratio has been related to the development of prostate diseases. Although rat models of prostate diseases induced by endocrine-disrupting chemicals (EDCs) and/or hormone exposure are commonly used to analyze gene expression profiles in the prostate, most studies utilize a single endpoint. In this study, microarray analysis was used for gene expression profiling in rat prostate tissue after exposure to EDCs and sex hormones over multiple time points (prepubertal through adulthood). We used dorsolateral prostate tissues from Sprague-Dawley rats (male offspring) and postnatally administered estradiol benzoate (EB) on postnatal days (PNDs) 1, 3, and 5, followed by treatment with additional hormones [estradiol (E) and testosterone (T)] on PNDs 90-200, as described by Ho et al. Microarray analysis was performed for gene expression profiling in the dorsolateral prostate, and the results were validated via qRT-PCR. The genes in cytokine-cytokine receptor interaction, cell adhesion molecules, and chemokines were upregulated in the EB+T+E group on PNDs 145 and 200. Moreover, early-stage downregulation of anti-inflammatory gene: bone morphogenetic protein 7 gene was observed. These findings suggest that exposure to EB, T, and E activates multiple pathways and simultaneously downregulates anti-inflammatory genes. Interestingly, these genes are reportedly expressed in prostate cancer tissues/cell lines. Further studies are required to elucidate the mechanism, including analyses using human prostate tissues.


Assuntos
Disruptores Endócrinos/toxicidade , Estradiol/análogos & derivados , Estradiol/toxicidade , Perfilação da Expressão Gênica/métodos , Expressão Gênica , Próstata/metabolismo , Puberdade , Testosterona/toxicidade , Transcriptoma , Fatores Etários , Animais , Proteína Morfogenética Óssea 7/genética , Proteína Morfogenética Óssea 7/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Quimiocinas/genética , Quimiocinas/metabolismo , Disruptores Endócrinos/efeitos adversos , Estradiol/efeitos adversos , Inflamação/genética , Masculino , Análise em Microsséries , Ratos Sprague-Dawley , Receptores de Citocinas/genética , Receptores de Citocinas/metabolismo , Testosterona/efeitos adversos
4.
Internist (Berl) ; 61(6): 549-557, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-32377774

RESUMO

Testosterone is a natural hormone which is essential to maintaining physical and emotional wellbeing in men, regardless of age. Male hypogonadism is an endocrine condition of testosterone deficiency with the potential to cause multiple morbidities and psychosocial problems. The condition can be of primary (testicular), secondary (hypothalamic-pituitary) or so-called functional origin (as a result of inflammatory conditions, obesity or chronic illness). Testosterone deficiency can cause symptoms of a sexual nature, foster metabolic dysfunction and impair physical abilities as well as cause osteopenia/osteoporosis and anemia. Testosterone replacement therapy should not be initiated in the case of desired paternity, unclear processes of the prostate or mammary gland and high hematocrit. Diagnosis and treatment as well as monitoring of hypogonadism treatment are clearly regulated by international guidelines and replacement therapy is proven to be effective in ameliorating the above-mentioned symptoms when performed according to these guidelines. In functional hypogonadism, which is most often, but not exclusively, found in older men, treatment of the underlying condition/co-morbidity is mandatory prior to starting testosterone substitution.


Assuntos
Androgênios/uso terapêutico , Terapia de Reposição Hormonal , Hipogonadismo/tratamento farmacológico , Osteoporose/prevenção & controle , Testosterona/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Androgênios/administração & dosagem , Disfunção Erétil/etiologia , Humanos , Hipogonadismo/diagnóstico , Hipogonadismo/etiologia , Masculino , Obesidade , Osteoporose/etiologia , Testosterona/administração & dosagem , Testosterona/efeitos adversos
5.
Am J Surg Pathol ; 44(8): 1040-1049, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32282346

RESUMO

Prostatic-type differentiation in the lower female genital tract is encountered rarely and its causes and clinical associations are not well established. Within the vagina, reports to date have invariably described ectopic prostatic-type differentiation as restricted to the lamina propria. We recently encountered a patient receiving testosterone for gender dysphoria whose vaginectomy specimen showed a prostatic glandular proliferation within the surface epithelium. To elucidate its potential association with androgen exposure, we sought similar lesions, resected over a 26-year period, from patients with exogenous or endogenous androgen excess. Thirteen cases were identified, involving the vagina (n=12) and exocervix (n=1). The most common clinical context was gender dysphoria with long-term testosterone therapy; the lesion was present in 7 of 8 gender-dysphoric patients examined. Four other patients had congenital disorders of sexual development associated with endogenous androgen excess (congenital adrenal hyperplasia, 46,XY disorder of sexual development, and ovotesticular disorder of sexual development). Two had no known exposure to androgen excess. Immunohistochemically, glands stained for NKX3.1 (100% of cases), androgen receptor (100%), CK7 (92%), and prostate-specific antigen (69%). Follow-up (median duration, 11 mo) showed no masses or neoplasia. We propose the designation "androgen-associated prostatic metaplasia" for this form of prostate tissue with distinctive clinical, histologic and immunohistochemical features. It is novel and previously unrecognized within the vagina. It is strikingly prevalent among patients undergoing gender-affirming surgery, an increasingly common procedure. Recognition is important to distinguish it from other potentially neoplastic glandular lesions and facilitate accrual of more follow-up data to better understand its natural history.


Assuntos
Diferenciação Celular , Coristoma/patologia , Células Epiteliais/patologia , Próstata , Doenças do Colo do Útero/patologia , Doenças Vaginais/patologia , Adolescente , Adulto , Androgênios/administração & dosagem , Androgênios/efeitos adversos , Diferenciação Celular/efeitos dos fármacos , Criança , Coristoma/induzido quimicamente , Células Epiteliais/efeitos dos fármacos , Feminino , Disforia de Gênero/tratamento farmacológico , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Masculino , Metaplasia , Fatores de Risco , Testosterona/administração & dosagem , Testosterona/efeitos adversos , Transexualidade/tratamento farmacológico , Doenças do Colo do Útero/induzido quimicamente , Doenças Vaginais/induzido quimicamente , Adulto Jovem
6.
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
7.
Artigo em Inglês | MEDLINE | ID: mdl-32197832

RESUMO

This chapter discusses the mechanisms of action of hormonal male contraception, which suppresses the hypothalamic-pituitary-testis axis. When the intratesticular concentration of testosterone is subsequently suppressed to adequately low concentrations, spermatogenesis is arrested. Androgens are a necessary hormonal male contraceptive component because they not only suppress the hypothalamic-pituitary-testis axis, but also provide the male hormone necessary to maintain peripheral androgen functions. Past studies using testosterone alone and testosterone combined with progestins demonstrated contraceptive efficacy in the female partner at rates similar to combined hormonal female methods. Newer hormonal male contraceptive formulations and the alternative routes of administration are discussed, along with potential barriers, challenges, and opportunities for hormonal male contraceptive development. Novel methods that are safe, effective, reversible, user-friendly, and coitus-independent are intrinsic to equitably meet the various needs and limitations of an increasingly diverse population.


Assuntos
Androgênios , Anticoncepcionais Masculinos , Serviços de Planejamento Familiar/tendências , Vasectomia/métodos , Anticoncepção , Anticoncepcionais Masculinos/efeitos adversos , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , Espermatogênese/fisiologia , Testículo/fisiologia , Testosterona/efeitos adversos
10.
Am J Clin Pathol ; 154(1): 33-37, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32134468

RESUMO

OBJECTIVES: To evaluate therapeutic phlebotomy (TP) requests for testosterone replacement therapy (TRT) and to highlight the impact to a blood center (BC) or service that provides TP for individuals on TRT. METHODS: Review of TP requests for individuals on TRT at our BC over a 3-year period from 2014 through 2016, as well as the total number of TP collections. RESULTS: Total TPs during 2014, 2015, and 2016 were 475, 500, and 569, respectively. Annual TP collections for patients on TRT were 193, 212, and 239, respectively. TRT patients with TP orders increased 71.4% during this period. After discontinuation of TP services for TRT at our BC, 32% continued to donate as volunteer blood donors at our BC. CONCLUSIONS: Our BC observed increased TP requests for patients on TRT from 2014 through 2016. Our findings suggest that individuals on TRT may be presenting to BCs as volunteer blood donors to avoid charges for TP.


Assuntos
Androgênios/efeitos adversos , Flebotomia/métodos , Policitemia/induzido quimicamente , Policitemia/terapia , Testosterona/efeitos adversos , Adulto , Doadores de Sangue , Humanos , Masculino , Pessoa de Meia-Idade , Policitemia/sangue
11.
Rev. Hosp. Ital. B. Aires (2004) ; 40(1): 34-38, mar. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1102292

RESUMO

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)


There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)


Assuntos
Humanos , Feminino , Idoso , Testosterona/uso terapêutico , Pós-Menopausa/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Fenitoína/efeitos adversos , Placebos/administração & dosagem , Psicotrópicos/efeitos adversos , Tamoxifeno/efeitos adversos , Testosterona/administração & dosagem , Testosterona/análise , Testosterona/efeitos adversos , Testosterona/farmacologia , Fármacos Cardiovasculares/efeitos adversos , Indometacina/efeitos adversos , Hormônio Liberador de Gonadotropina/efeitos adversos , Pós-Menopausa/fisiologia , Ensaios Clínicos Controlados como Assunto , Antagonistas Colinérgicos/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/terapia , Danazol/efeitos adversos , Consenso , Inibidores da Aromatase/efeitos adversos , Uso Off-Label , Inibidores do Fator Xa/efeitos adversos , Anfetaminas/efeitos adversos , Antagonistas dos Receptores Histamínicos/efeitos adversos , Antagonistas de Androgênios/efeitos adversos , Androgênios/fisiologia , Cetoconazol/efeitos adversos , Entorpecentes/efeitos adversos
12.
Int J Mol Sci ; 21(4)2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32093293

RESUMO

We investigated the metabolite changes of Morus roots (MRs) according to different cultivar families (Simheung, Daesim, Cheong-il, Sangchon, Daeseong, Suhong, Suwon, and Igsu) using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to understand the relationship between different cultivars and metabolite changes. Data were analyzed by partial least squares discriminant analysis (PLS-DA), and samples were successfully separated in PLS-DA scores. Eight metabolites in the electrospray ionization (ESI)-positive mode and 16 metabolites in the ESI-negative mode contributed to the separation in PLS-DA. Our data suggest that comparative analysis of MR metabolites according to different cultivars is useful to better understand the relationship between the different cultivars and metabolite changes. Furthermore, we analyzed the MRs for their ability to improve benign prostatic hyperplasia (BPH). LNCaP cells were used to evaluate the prostate-specific antigen (PSA) inhibitory activity of MRs, and, amongst them, the extract with the highest activity was selected. Igsu demonstrated the highest inhibition effect of prostate-specific antigen (PSA) expression among the MR cultivars. Igsu was also evaluated by administration in a testosterone-induced benign prostatic hyperplasia model in Sprague-Dawley rats. Igsu was shown to ameliorate BPH as evidenced by the prostate index, expression of androgen receptor (AR) signaling-related protein, growth factors, cell proliferation-related proteins, apoptosis-related proteins, mitogen-activated protein kinase (MAPK) signaling proteins, and histological analysis. Hence, this study strongly suggests that Igsu may have a beneficial effect of on BPH.


Assuntos
Morus/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Próstata/metabolismo , Hiperplasia Prostática , Testosterona/efeitos adversos , Animais , Masculino , Extratos Vegetais/química , Próstata/patologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Ratos , Ratos Sprague-Dawley , Testosterona/farmacologia
13.
Sci Rep ; 10(1): 404, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941959

RESUMO

Hyperandrogenemia and metabolic disturbances during postnatal life are strongly linked both to polycystic ovary syndrome and other conditions that arise from prenatal exposure to androgen excess. In an animal model of this condition, we reported that insulin sensitivity (IS) was lower in young female sheep born to testosterone-treated mothers versus sheep born to non-exposed mothers (control). This lower insulin sensitivity remains throughout reproductive life. However, it is unknown whether abnormal postnatal levels of testosterone (T) further decrease IS derived from prenatal exposure to testosterone. Therefore, we assessed the effects of an acute testosterone administration (40 mg) on IS and insulin secretion during an intravenous glucose tolerance test performed at 40 weeks of age (adulthood) in previously ovariectomized sheep at 26 weeks of age (prepuberty), that were either prenatally exposed to testosterone (T-females, n = 6) or not (C-females, n = 6). The incremental area under the curve of insulin was greater in C-females both with or without the acute testosterone treatment (P < 0.05). The ISI-Composite was lower after an acute testosterone treatment, only in T-females. We conclude that prenatal exposure to testosterone disrupts pancreatic insulin secretion in response to glucose and that in this setting further hyperandrogenemia may predispose to lower insulin sensitivity.


Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Resistência à Insulina , Secreção de Insulina/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/patologia , Testosterona/efeitos adversos , Animais , Feminino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ovinos
15.
Curr Diabetes Rev ; 16(3): 189-199, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30073928

RESUMO

BACKGROUND: The current estimated numbers of patients with Type 2 Diabetes (T2D) is believed to be close to 10% of the whole populations of many geographical regions, causing serious concerns over the resulting elevated morbidity and mortality as well as the impact on health care systems around the world. In addition to negatively affecting the quality of life, diabetes is associated with cardiovascular and cerebrovascular complications, indicating that appropriate drug therapy should not only deal with metabolic dysfunction but also protect the vascular system, kidney function and skeletal muscle mass from the effects of the epigenetic changes induced by hyperglycaemia. OBJECTIVE: To provide an insight into the management of hypogonadism associated with T2D, this review focuses on clinical observations related to androgen therapy in qualified diabetic patients, and discusses the lines of evidence for its benefits and risks. The potential interactions of testosterone with medicines used by patients with T2D will also be discussed. CONCLUSION: From recent clinical findings, it became evident that a considerable percentage of patients suffering from T2D manifested low serum testosterone and experienced diminished sexual activity, as well as reduced skeletal muscle mass and lower bone density. Although there are some controversies, Testosterone Replacement Therapy (TRT) for this particular population of patients appears to be beneficial overall only if it is implemented carefully and monitored regularly.


Assuntos
Androgênios/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Hipogonadismo/tratamento farmacológico , Testosterona/uso terapêutico , Androgênios/efeitos adversos , Androgênios/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Interações Medicamentosas , Terapia de Reposição Hormonal/efeitos adversos , Terapia de Reposição Hormonal/métodos , Humanos , Hipoglicemiantes/uso terapêutico , Hipogonadismo/etiologia , Masculino , Qualidade de Vida , Medição de Risco , Testosterona/efeitos adversos , Testosterona/sangue
16.
Anesth Analg ; 130(4): 890-898, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-30896595

RESUMO

BACKGROUND: Data on testosterone replacement therapy and cardiovascular outcomes are conflicting, with the Food and Drug Administration requiring prescription testosterone preparations to indicate a possible increased cardiovascular risk. Whether patients on testosterone replacement therapy undergoing cardiac surgery have an increased risk of postoperative in-hospital mortality and cardiovascular events remains unknown. We therefore sought to identify the impact of testosterone replacement on the incidence of a composite of postoperative in-hospital mortality and cardiovascular events in men undergoing cardiac surgery. METHODS: After institutional review board approval, data from male American Society of Anesthesiologists III/IV patients ≥40 years of age who underwent cardiac surgery between May 2005 and March 2017 at the Cleveland Clinic (Cleveland, OH) main campus were included. The primary exposure was preoperative testosterone use. The primary outcome was a collapsed composite of postoperative in-hospital mortality and cardiovascular events, including myocardial infarction, stroke, and pulmonary embolism. The secondary outcome was a collapsed composite of minor cardiovascular events, including postoperative rhythm disturbance requiring permanent device, atrial fibrillation, and deep venous thrombosis. We compared patients who received testosterone and those who did not, using propensity score matching within surgical procedure matches. Moreover, as a sensitivity analysis, we used a multivariable logistic regression model to assess the association between testosterone replacement therapy and major or minor cardiovascular events adjusted for potential baseline and intraoperative confounders by including all eligible patients. RESULTS: Among 20,604 patients who met inclusion and exclusion criteria, 301 patients who used testosterone routinely within 1 month before the surgery were matched to 1505 of 20,303 patients who did not use testosterone. Among the matched cohort, 8 (2.7%) patients in the testosterone group and 45 (3.0%) in the nontestosterone group had ≥1 major cardiovascular adverse event after surgery. The adjusted odds ratio was 0.89 (95% CI, 0.41-1.90; P = .756), comparing testosterone to nontestosterone patients. As for the secondary outcomes, 89 (30%) patients in the testosterone group and 525 (35%) patients in the nontestosterone group had ≥1 minor cardiovascular event. The odds of minor events were not significantly different, with an odds ratio of 0.78 (95% CI, 0.60-1.02; P = .074) comparing testosterone to nontestosterone patients. CONCLUSIONS: Preoperative testosterone is not associated with a statistically significant increased incidence of a composite of postoperative in-hospital mortality and cardiovascular events after cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Doenças Cardiovasculares/epidemiologia , Terapia de Reposição Hormonal/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Testosterona/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Mortalidade Hospitalar , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Pontuação de Propensão , Estudos Prospectivos , Testosterona/uso terapêutico , Resultado do Tratamento
17.
Oxid Med Cell Longev ; 2019: 4748312, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885795

RESUMO

Epidemiologic studies revealed a context between lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and metabolic syndrome. However, molecular mechanisms underlying this relationship are largely unknown. Prostate enlargement and increased prostate smooth muscle tone are important factors in the pathophysiology of LUTS suggestive of BPH. In the present study, we studied effects of the metabolic hormone ghrelin on prostate enlargement in rats with experimentally induced BPH, growth of cultured stromal cells from human prostate (WPMY-1), and smooth muscle contraction of human prostate tissues. Ghrelin (20 nmol/kg daily, p.o., 2 weeks) increased prostate size in rats with testosterone-induced BPH. Microarray identified 114 ghrelin-upregulated genes (2-fold or more) in these prostates, with possible roles in growth, smooth muscle contraction, or metabolism. 12 genes were selected for further analyses. In human prostate tissues, mRNA levels of 11 of them correlated positively with ghrelin receptor (GHSR) expression, but only two with the degree of BPH. Accordingly, no correlation was evident between GHSR expression level and BPH in human prostate tissues. In WPMY-1 cells, the GHRS agonist MK0677 upregulated 11 of the selected genes. MK0677 induced proliferation of WPMY-1 cells, shown by EdU assay, colony formation, proliferation markers, flow cytometry, and viability. In myographic measurements, GHSR agonists enhanced contractions of human prostate strips. Together, ghrelin may aggravate prostate enlargement, stromal cell growth, and prostate smooth muscle contraction in BPH. Ghrelin may deteriorate urethral obstruction independently from BPH, qualifying the ghrelin system as an attractive new target to be tested for LUTS treatment in BPH.


Assuntos
Grelina/efeitos adversos , Contração Muscular/efeitos dos fármacos , Músculo Liso/fisiopatologia , Próstata/efeitos dos fármacos , Hiperplasia Prostática/induzido quimicamente , Testosterona/efeitos adversos , Animais , Proliferação de Células , Humanos , Masculino , Próstata/patologia , Ratos , Células Estromais
18.
Sci Rep ; 9(1): 19232, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848372

RESUMO

Polycystic ovary syndrome (PCOS) is a major reproductive disorder that is responsible for 80% of anovulatory infertility and that is associated with hyperandrogenemia, increased risk of obesity, and white adipose tissue (WAT) dysfunction. We have previously demonstrated that the combination of chronic testosterone (T) treatment and an obesogenic Western-style diet (WSD) exerts synergistic functional effects on WAT, leading to increased lipid accumulation in visceral adipocytes by an unknown mechanism. In this study, we examined the whole-genome transcriptional response in visceral WAT to T and WSD, alone and in combination. We observed a synergistic effect of T and WSD on gene expression, resulting in upregulation of lipid storage genes concomitant with adipocyte hypertrophy. Because DNA methylation is known to be associated with body fat distribution and the etiology of PCOS, we conducted whole-genome DNA methylation analysis of visceral WAT. While only a fraction of differentially expressed genes also exhibited differential DNA methylation, in silico analysis showed that differentially methylated regions were enriched in transcription factor binding motifs, suggesting a potential gene regulatory role for these regions. In summary, this study demonstrates that hyperandrogenemia alone does not induce global transcriptional and epigenetic response in young female macaques unless combined with an obesogenic diet.


Assuntos
Metilação de DNA , Dieta Ocidental/efeitos adversos , Hiperandrogenismo/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Transcrição Genética , Animais , Feminino , Hiperandrogenismo/induzido quimicamente , Hiperandrogenismo/patologia , Gordura Intra-Abdominal/patologia , Macaca mulatta , Obesidade/induzido quimicamente , Obesidade/patologia , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Testosterona/efeitos adversos , Testosterona/farmacologia
19.
Rev. cuba. endocrinol ; 30(3): e213, sept.-dic. 2019. tab, graf
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1126443

RESUMO

RESUMEN Introducción: El hipogonadismo masculino puede provocar una reducción importante de la calidad de vida. La determinación de testosterona total constituye la opción inicial para el diagnóstico bioquímico del hipogonadismo. Objetivo: Determinar el intervalo de referencia de testosterona total para la población masculina en edad reproductiva del municipio Plaza de la Revolución. Métodos: Se realizó un estudio transversal y descriptivo, en una muestra representativa (n= 143) de la población masculina entre 20 y 40 años de edad, del municipio Plaza de la Revolución. Para el reclutamiento de la muestra se utilizó un método directo. El intervalo de referencia se estableció mediante un método no paramétrico. Se realizó interrogatorio, examen físico, complementarios bioquímicos (glucemia, colesterol, triglicéridos, HDL-c, LDL-c), y hormonales (testosterona total, PRL, FSH y LH). Resultados: El promedio de edad fue de 29,7 años. El índice de masa corporal osciló entre 18,95 y 29,88 kg/m2 (valor medio 24,15). Las medias de las circunferencias de cintura y cadera fueron de 86,62 cm y 99,77 cm respectivamente. El intervalo de referencia de testosterona total calculado para la población masculina del municipio Plaza de la Revolución, fue de 7,69 a 40,52 nmol/L. La mediana para la testosterona total fue de 19,10 nmol/L. Conclusiones: El intervalo de referencia de testosterona total calculado para la población masculina adulta (20 - 40 años) del municipio Plaza de la Revolución difiere del reportado por el fabricante del kit diagnóstico y puede resultar de utilidad en la práctica clínica(AU)


ABSTRACT Introduction: Male hypogonadism may cause a significant reduction in the quality of life. The determination of total testosterone constitutes the initial option for the biochemical diagnosis of hypogonadism. Objective: To determine the reference interval of total testosterone for the male population in reproductive age of Plaza de la Revolución municipality. Methods: It was conducted a cross-sectional and descriptive study in a representative sample (n=143) of the male population from 20 to 40 years old of Plaza de la Revolución municipality. For the recruitment of the sample it was used a direct method. The reference interval was established through a non-parametric method. There were conducted interrogations, physical examination, complementary biochemical (blood glucose, cholesterol, triglycerides, HDL-c, LDL-c), and hormonal tests (total testosterone, PRL, FSH and LH). Results: The average age was 29.7 years. The body mass index ranged between 18.95 and 29.88 kg/m2 (mean value of 24.15). The means of the waist and hip circumferences were 86.62 and 99.77 cm, respectively. The reference interval of total testosterone calculated for the male population of Plaza de la Revolución municipality was of 7.69 to 40.52 nmol/L. The mean for total testosterone was 19.10 nmol/L. Conclusions: The reference interval of total testosterone calculated for the adult male population (20 - 40 years old) of Plaza de la Revolución municipality differs from that reported by the manufacturer of the diagnostic kit and it can be useful in clinical practice(AU)


Assuntos
Humanos , Masculino , Adulto , Exame Físico/métodos , Testosterona/efeitos adversos , Hipogonadismo/diagnóstico , Qualidade de Vida , Valores de Referência , Índice de Massa Corporal , Epidemiologia Descritiva , Estudos Transversais
20.
ESC Heart Fail ; 6(6): 1216-1221, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31696666

RESUMO

AIMS: Although preliminary studies have demonstrated safety and effectiveness of single replacement therapy for growth hormone deficiency or testosterone deficiency in heart failure (HF), no data are available regarding the combined treatment with both GH and T in this setting. Thus, the aim of the present hypothesis generating pilot study was to evaluate the effectiveness and safety of multiple hormonal replacement therapies in chronic HF. METHODS AND RESULTS: Five stable HF with reduced ejection fraction patients, with a concomitant diagnosis of growth hormone deficiency and testosterone deficiency, on top of guideline-based HF treatment underwent 1 year of GH replacement therapy by subcutaneous injections of somatotropin at a dose of 0.012 mg/kg every second day. After 12 months, a T replacement treatment was added at a dosage of 1000 mg every 3 months. Each patient underwent a complete M-mode, two-dimensional, and Doppler echocardiographic examination, and an incremental symptom-limited cardiopulmonary exercise test on a bicycle ergometer at baseline (BL), after 1 year of GH treatment (V1), and after 1 year of combined GH + T treatments (V2). One-year of GH treatment resulted in a significant improvement in left ventricular ejection fraction (+5.4%, P < 0.01), New York Heart Association functional class (P < 0.05), and peak oxygen consumption (VO2 peak) (+19.3%, P < 0.01), and in a significant reduction in NT-proBNP levels (-35.1%, P < 0.01). Notably, one additional year of combined GH and T replacement therapy induced a further increase in VO2 peak (+27.7%, final delta change + 52.44%, P < 0.01), as well as a significant improvement in muscular strength, as assessed by handgrip dynamometry (+17.5%, final delta change + 25.8%, P < 0.01). These beneficial effects were paralleled with an improvement of the overall clinical status (as assessed by New York Heart Association class). Of note, neither adverse effects nor cardiovascular events were reported during the follow-up period. CONCLUSIONS: Our preliminary data suggest for the first time that combined replacement therapy with GH and T could be considered safe and therapeutic in HF patients with multiple hormone deficiencies, supporting the hypothesis that multiple hormone deficiencies syndrome can be considered as a novel and promising therapeutic target in HF. Further studies with a more robust design and larger population are needed.


Assuntos
Hormônio do Crescimento , Insuficiência Cardíaca/tratamento farmacológico , Terapia de Reposição Hormonal , Testosterona , Idoso , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento/efeitos adversos , Hormônio do Crescimento/deficiência , Hormônio do Crescimento/uso terapêutico , Humanos , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Projetos Piloto , Volume Sistólico/fisiologia , Testosterona/administração & dosagem , Testosterona/efeitos adversos , Testosterona/deficiência , Testosterona/uso terapêutico
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