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1.
J Mol Neurosci ; 69(1): 83-93, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31114953

RESUMO

We investigated the early onset of molecular changes in the hippocampus of orchidectomy (ODX)-induced androgen-deficient rats. Transcript levels of the genes associated with loss of synaptic plasticity (Bdnf, Syn, GluN1, α7-nAChR, and M1-mAChR), formation of neurofibrillary tangles (Tau4 and Tau3), and amyloid plaques (App, Adam10, and Bace1), in the hippocampus of rats at 0, 1, 3, 6, and 9 days after ODX (D0, D1, D3, D6 and D9, respectively) were determined. Primarily, the sudden loss of androgen, as confirmed by the decreased serum testosterone levels and accessory sex organ weights, induced a chronological reduction in Syn (at D1), and increase in GluN1 (at D3), α7-nAChR, and M1-mAChR (at D6) and a decrease in Bdnf (at D9) transcript levels. Tau4 and Tau3 mRNA levels were increased at D6 and D9, respectively. No changes in App, Adam10, and Bace1 mRNA levels were detected within the 9-day study period. To confirm those changes were caused by androgen deprivation and not increasing age, the mRNA expression levels of those genes in 9-day orchidectomized rats (ODX-D9) were compared with age-matched intact rats. All changes of mRNA expression levels of the ODX-D9 rats were aligned with the D9 rats, except for GluN1 that was decreased in the ODX-D9 rats. Moreover, the total and phosphorylated tau protein levels were increased in the ODX-D9 rats. These results denote that androgen deficiency induces the early onset of neurodegeneration, while the loss of synaptic plasticity together with the formation of neurofibrillary tangles could be used as markers for neurodegenerative prediction.


Assuntos
Androgênios/deficiência , Hipocampo/metabolismo , Transcriptoma , Fatores Etários , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/crescimento & desenvolvimento , Masculino , Plasticidade Neuronal , Orquiectomia/efeitos adversos , Proteínas Qa-SNARE/genética , Proteínas Qa-SNARE/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Muscarínicos/genética , Receptores Muscarínicos/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/genética , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo
2.
Wiad Lek ; 72(3): 357-361, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31050980

RESUMO

OBJECTIVE: Introduction: Considering significant gap of convincing knowledge in the field of cardiovascular effects of prolactin and its role as a stress hormone in men precise investigations of these peculiarities has become necessary. The aim of this study was to find out the relationship of prolactin concentration with parameters of arterial stiffness in hypertensive men with low testosterone. PATIENTS AND METHODS: Materials and methods: In total 83 men were examined including 27 apparently healthy individuals as the control group. Physical examination, ABPM, non-invasive evaluation of arterial stiffness and central hemodynamics parameters, answering AMS questionnaire, evaluation of total testosterone and prolactin levels using ELISA were performed. RESULTS: Results: Initially 56 hypertensive patients were divided into 2 groups with regard to their total testosterone level: group 1 included 31 hypogonadal men, group 2 - 25 male patients who had their testosterone concentrations within the normal range. Prolactin levels appeared to be significantly higher in hypertensive men with lower testosterone, they had more unfavorable parameters of arterial stiffness and the difference between 1 and 2 group in terms of central aoSBP and aoPWV became statistically significant. Prolactin concentration was not related with RWTT and index Aix% 75, a significant correlation was observed between prolactin and aoPWV. A strong correlation was found between prolactin concentration and psychological symptoms in AMS. CONCLUSION: Conclusion: Our study suggests the positive association of prolactin concentration with psychological domain of andropause symptoms and worse parameters of arterial stiffness among hypertensive men with androgen deficiency.


Assuntos
Androgênios/deficiência , Hipertensão , Prolactina , Hemodinâmica , Humanos , Masculino , Valores de Referência , Testosterona
3.
Panminerva Med ; 61(2): 152-163, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30990285

RESUMO

Varicoceles exert deleterious effect on testicular function. The condition has been associated with male infertility, testicular hypotrophy and pain. These comprises the common indications for varicocele repair currently. Significant improvement in semen parameters and pregnancy outcomes had been suggested by reports decades ago. However, selection of the best candidates remains an issue since not all patients respond positively to treatment. Consensus has been reached in recent decade after the publication of a series of meta-analyses. Significant improvement in pregnancy outcomes were reported in patients with clinical varicocele and abnormal semen parameters. Varicocelectomy in adolescents with testicular hypotrophy was supported by the positive implication on catch-up growth and semen parameters. However, little is known about the treatment effect of adolescence varicocelectomy on long term fertility and paternity rate. Recent studies on outcome of varicocele repair for pain consistently demonstrated a resolution rate of approximately 90% and support varicocele-associated pain as an indication for surgery. Alternate indications for varicocele repair have been proposed in recent decade. Despite the encouraging preliminary data, most studies were uncontrolled retrospective series. Although varicocelectomy may not obviate the need for assisted reproductive techniques in patients with non-obstructive azoospermia, it potentially increases sperm retrieval rate. The significant increase in serum testosterone after varicocelectomy in patients with androgen deficiency may open an alternative treatment for hypogonadism. The adjunctive role of varicocelectomy before assisted reproduction and the significant decrease in sperm DNA fragmentation after varicocele repair deserve further well-designed controlled studies.


Assuntos
Varicocele/cirurgia , Adolescente , Androgênios/deficiência , Azoospermia/complicações , Fragmentação do DNA , Humanos , Infertilidade Masculina/etiologia , Infertilidade Masculina/cirurgia , Masculino , Estresse Oxidativo , Técnicas de Reprodução Assistida , Testículo/patologia , Procedimentos Cirúrgicos Urogenitais , Varicocele/fisiopatologia
4.
Magy Onkol ; 63(1): 33-39, 2019 Mar 19.
Artigo em Húngaro | MEDLINE | ID: mdl-30889619

RESUMO

During the last decades androgen deprivation therapy (ADT) was the standard treatment of prostate cancers. Survival of metastatic patients is 4 years if they receive ADT, but in case of poor prognosis survival rate is under 3 years. Since 2014 two prospective phase III studies have proven the survival advantage of early docetaxel therapy, administered together with ADT, for metastatic hormone-sensitive prostate cancer patients. Its advantage was even more considerable in case of high-volume metastatic cases. In two other studies the benefit of abiraterone-prednisone therapy combined with ADT was proven in comparison with ADT itself in case of newly diagnosed, metastatic, high-risk, hormone-naïve patients. One prospective study has proven the survival benefit of ADT administered together with radiotherapy of the prostate in case of low volume metastatic diseases. In our analysis we demonstrate these clinical studies and try to answer the contradictory questions about the occasionally overlapping therapeutic options.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Androgênios/deficiência , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Androgênios/metabolismo , Docetaxel/uso terapêutico , Humanos , Masculino , Estudos Prospectivos , Taxa de Sobrevida
5.
Histol Histopathol ; 34(9): 1025-1036, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30912572

RESUMO

The high incidence of prostatic diseases, including malignant tumors, makes the understanding of prostate biology very important. Androgen deprivation, blockade by orchiectomy, or chemical castration causes prostate and tumor shrinkage. The gene networks involved in a cell type-specific fashion are rather unknown. This work was undertaken to identify genes with annotated function in transcription regulation that might define transitions in gene expression. A total of 15 potential regulatory genes were identified. Validation by qRT-PCR showed that Zfp703 and Arid1a exhibit expression maxima at day 1; Ash2l, Nelf, Pbx3, Eya2 at day 4; Dmrt2 at day 5 and Lbh and Sox1 at day 7 after castration. Using immunohistochemistry, we further determined that PBX3 was found in both stromal and epithelial cells, whereas ARID1A and NELF were restricted to the epithelium, and DMRT2 and EYA2 were exclusively found in the stroma. Though the proteins ZFP703 and ASH2l were not found in any experimental condition, their mRNAs were located by in situ hybridization in both epithelium and stroma. In conclusion, androgen deprivation triggers the expression of temporally regulated gene sets in both epithelial and stromal cells. These gene subsets will help establish the regulatory gene expression programs orchestrating the castration-induced remodeling of the prostate gland, and represent putative targets to increase the efficacy of androgen-deprivation to induce epithelial (and cancer) cell death.


Assuntos
Adaptação Fisiológica/fisiologia , Androgênios/deficiência , Regulação da Expressão Gênica/fisiologia , Próstata/metabolismo , Animais , Masculino , Orquiectomia , Ratos , Ratos Wistar
6.
Am J Ophthalmol ; 197: 136-144, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30268865

RESUMO

PURPOSE: To evaluate the efficacy, safety, and quality of life (QOL) of transdermal androgen in treatment of dry eye patients associated with androgen deficiency. DESIGN: Randomized controlled trial. METHODS: Fifty patients with dry eye from a tertiary eye center in northern Thailand were randomized to receive transdermal androgen (AndroGel; Besins Healthcare, Brussels, Belgium) or placebo for 4 weeks. Main outcome measures were symptoms and signs of dry eye. Serum level of sex hormone and QOL questionnaires were also evaluated at the baseline and after treatment. RESULTS: After 4 weeks, the Ocular Surface Disease Index decreased significantly in the AndroGel group compared to the placebo (-14.36 ± 7.76 vs 0.14 ± 14.60, P < .001). Significant improvements of tear break-up time (7.40 ± 3.37 vs -1.14 ± 1.68 seconds, P < .001), corneal fluorescein staining (-0.62 ± 0.30 vs 0.19 ± 0.37, P < .001), and Schirmer test (6.84 ± 5.10 vs -0.48 ± 2.14 mm, P < .001) were observed in the AndroGel group compared to the placebo. Serum testosterone in female patients significantly increased in the AndroGel group compared to the placebo (P < .001), while no different change was observed in serum testosterone in male subjects and the sex hormone-binding globulin in both groups. In the AndroGel group, 20% of patients had oily skin and 4% had acne. No serious adverse effects were reported. The menopause rating score improved significantly in the AndroGel group compared to the placebo (P < .001), while the aging male symptoms were not different in both groups (P = .589). CONCLUSIONS: Transdermal androgen was effective in relieving symptoms and signs of dry eye as well as improving QOL in aging patients. There were no serious side effects during a short-term treatment.


Assuntos
Androgênios/uso terapêutico , Síndromes do Olho Seco/tratamento farmacológico , Idoso , Androgênios/deficiência , Método Duplo-Cego , Síndromes do Olho Seco/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/uso terapêutico , Qualidade de Vida , Adesivo Transdérmico
7.
Prostate ; 79(2): 183-194, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30298636

RESUMO

BACKGROUND: Serum folate concentrations in the United States have risen since dietary folic acid fortification was first mandated in 1998. Although maternal folic acid offers protection against neural tube defects in conceptuses, its impact on other organ systems and life stages have not been fully examined. Here, we used a mouse model to investigate the impact of a Folic acid (FA) enriched diet on prostate homeostasis and response to androgen deprivation. METHODS: Male mice were fed a control diet (4 mg FA/kg feed) or a folic acid supplemented diet (24 mg FA/kg feed) beginning at conception and continuing through early adulthood, when mice were castrated. RESULTS: We made the surprising observation that dietary FA supplementation confers partial resistance to castration-mediated prostate involution. At 3, 10, and 14 days post-castration, FA enriched diet fed mice had larger prostates as assessed by wet weight, taller prostatic luminal epithelial cells, and more abundant RNAs encoding prostate secretory proteins than castrated control diet fed mice. Diet did not significantly affect prostate weights of intact mice or serum testosterone concentrations of castrated mice. RNA-Seq analysis revealed that the FA enriched diet was associated with a unique prostate gene expression signature, affecting several signaling and metabolic pathways. CONCLUSIONS: Continuous exposure to a FA enriched diet slows prostate involution in response to androgen deprivation. Prostates from FA diet mice have increased secretory gene expression and increased luminal cell heights. The influence of dietary FA supplementation on the prostate response to androgen deprivation raises a future need to consider how dietary folic acid supplementation affects efficacy of androgen-reducing therapies for treating prostate disease.


Assuntos
Androgênios/deficiência , Ácido Fólico/administração & dosagem , Próstata/efeitos dos fármacos , Androgênios/sangue , Animais , Castração , Suplementos Nutricionais , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Próstata/anatomia & histologia , Próstata/fisiologia , Receptores Androgênicos/biossíntese , Testosterona/sangue
8.
Adv Exp Med Biol ; 1210: 351-378, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31900917

RESUMO

Metastatic or locally advanced prostate cancer (PCa) is typically treated with androgen deprivation therapy (ADT). Initially, PCa responds to the treatment and regresses. However, PCa almost always develops resistance to androgen deprivation and progresses to castrate-resistant prostate cancer (CRPCa), a currently incurable form of PCa. Wnt/ß-Catenin signaling is frequently activated in late stage PCa and contributes to the development of therapy resistance. Although activating mutations in the Wnt/ß-Catenin pathway are not common in primary PCa, this signaling cascade can be activated through other mechanisms in late stage PCa, including cross talk with other signaling pathways, growth factors and cytokines produced by the damaged tumor microenvironment, release of the co-activator ß-Catenin from sequestration after inhibition of androgen receptor (AR) signaling, altered expression of Wnt ligands and factors that modulate the Wnt signaling, and therapy-induced cellular senescence. Research from genetically engineered mouse models indicates that activation of Wnt/ß-Catenin signaling in the prostate is oncogenic, enables castrate-resistant PCa growth, induces an epithelial-to-mesenchymal transition (EMT), promotes neuroendocrine (NE) differentiation, and confers stem cell-like features to PCa cells. These important roles of Wnt/ß-Catenin signaling in PCa progression underscore the need for the development of drugs targeting this pathway to treat therapy-resistant PCa.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Androgênios/deficiência , Androgênios/metabolismo , Animais , Humanos , Masculino , Microambiente Tumoral/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos
10.
Jpn J Clin Oncol ; 48(9): 827-834, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30053039

RESUMO

Background: Prostate cancer (PCa) patients receiving androgen deprivation therapy (ADT) are prone to suffer a series of potential side effects, including metabolic change, declining physical strength and worsening fatigue. Recent studies found that the change of lifestyle interventions can help to alleviate some adverse reactions, but the results were controversial. Therefore, the aim of this review was to comprehensively evaluate the effects of these lifestyle interventions on the side effects on PCa patients who received ADT. Methods: We searched several electronic databases, including ScienceDirect, PubMed, Cochrane library, CNKI and Wanfang database, without language restrictions. Among the literature, such lifestyle interventions as dietary advice, exercise and physical activities were carried out in the way of randomized controlled trials (RCTs) on PCa patients taking ADT. Pooled estimates were performed using fixed-effects or random-effects model. Results: Eleven RCTs involving 905 participants were included in this review. Compared with usual care group, exercise intervention could significantly improve the quality of life (QoL) of PCa patients undergoing ADT (P = 0.05, SMD = 0.17, 95% CI -0.00 to 0.34), but exercise plus dietary advice could not significantly improve the QoL (P = 0.15, SMD = 0.45, 95% CI -0.17 to 1.08). Moreover, lifestyle intervention could significantly change body composition (P = 0.03, SMD = -0.1, 95% CI -0.19 to -0.01). However, there showed no obvious difference in mitigating fatigue and depression (P = 0.46, SMD = 0.11, 95% CI -0.18 to 0.39; P = 0.31, SMD = -0.18, 95% CI -0.54 to 0.17). Conclusions: The results of this meta-analysis from present study indicated that exercise interventions can better improve the QoL and alleviate treatment-related side effects on prostate cancer patients taking ADT, and better therapeutic regimens for PCa patients are likely to emerge in the process.


Assuntos
Androgênios/deficiência , Estilo de Vida , Neoplasias da Próstata/terapia , Composição Corporal , Depressão/etiologia , Exercício , Fadiga/etiologia , Humanos , Masculino , Neoplasias da Próstata/complicações , Qualidade de Vida , Treinamento de Resistência
11.
Nutrients ; 10(7)2018 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-29933617

RESUMO

Male osteoporosis is associated with higher rates of disability and mortality. Hence the search for suitable intervention and treatment to prevent the degeneration of skeletal health in men is necessary. Eurycoma longifolia (EL), a traditional plant with aphrodisiac potential may be used to treat and prevent male osteoporosis. The skeletal protective effect of quassinoid-rich EL extract, which has a high content of eurycomanone, has not been studied. This study aimed to determine whether EL could prevent skeletal deteriorations in gonadal hormone-deficient male rats. Ninety-six male Sprague⁻Dawley rats were randomly assigned to baseline, sham-operated (Sham), orchidectomised or chemically castrated groups. Chemical castration was achieved via subcutaneous injection of degarelix at 2 mg/kg. The orchidectomised and degarelix-castrated rats were then divided into negative control groups (ORX, DGX), testosterone-treated groups (intramuscular injection at 7 mg/kg weekly) (ORX + TES, DGX + TES), and EL-supplemented groups receiving daily oral gavages at doses of 25 mg/kg (ORX + EL25, DGX + EL25), 50 mg/kg (ORX + EL50, DGX + EL50), and 100 mg/kg (ORX + EL100, DGX + EL100). Following 10 weeks of treatment, the rats were euthanized and their blood and femora were collected. Bone biochemical markers, serum testosterone, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa β-ligand (RANKL) levels and histomorphometric indices were evaluated. Quassinoid-rich EL supplementation was found to reduce degenerative changes of trabecular structure by improving bone volume, trabecular number, and separation. A reduction in the percentage of osteoclast and increase in percentage of osteoblast on bone surface were also seen with EL supplementation. Dynamic histomorphometric analysis showed that the single-labeled surface was significantly decreased while the double-labeled surface was significantly increased with EL supplementations. There was a marginal but significant increase in serum testosterone levels in the ORX + EL25, DGX + EL50, and DGX + EL100 groups compared to their negative control groups. Quassinoid-rich EL extract was effective in reducing skeletal deteriorations in the androgen-deficient osteoporosis rat model.


Assuntos
Remodelação Óssea/efeitos dos fármacos , Eurycoma/química , Osteoporose/tratamento farmacológico , Extratos Vegetais/farmacologia , Quassinas/farmacologia , Androgênios/sangue , Androgênios/deficiência , Animais , Biomarcadores/sangue , Masculino , Orquiectomia , Osteoblastos/efeitos dos fármacos , Osteoporose/sangue , Osteoprotegerina/sangue , Ligante RANK/sangue , Ratos , Ratos Sprague-Dawley , Testosterona/sangue
12.
Nature ; 559(7714): 363-369, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29950727

RESUMO

Patients with prostate cancer frequently show resistance to androgen-deprivation therapy, a condition known as castration-resistant prostate cancer (CRPC). Acquiring a better understanding of the mechanisms that control the development of CRPC remains an unmet clinical need. The well-established dependency of cancer cells on the tumour microenvironment indicates that the microenvironment might control the emergence of CRPC. Here we identify IL-23 produced by myeloid-derived suppressor cells (MDSCs) as a driver of CRPC in mice and patients with CRPC. Mechanistically, IL-23 secreted by MDSCs can activate the androgen receptor pathway in prostate tumour cells, promoting cell survival and proliferation in androgen-deprived conditions. Intra-tumour MDSC infiltration and IL-23 concentration are increased in blood and tumour samples from patients with CRPC. Antibody-mediated inactivation of IL-23 restored sensitivity to androgen-deprivation therapy in mice. Taken together, these results reveal that MDSCs promote CRPC by acting in a non-cell autonomous manner. Treatments that block IL-23 can oppose MDSC-mediated resistance to castration in prostate cancer and synergize with standard therapies.


Assuntos
Interleucina-23/antagonistas & inibidores , Interleucina-23/metabolismo , Células Supressoras Mieloides/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/terapia , Antagonistas de Receptores de Andrógenos/farmacologia , Antagonistas de Receptores de Andrógenos/uso terapêutico , Androgênios/deficiência , Animais , Proliferação de Células , Sobrevivência Celular , Humanos , Interleucina-23/sangue , Interleucina-23/imunologia , Masculino , Camundongos , Células Supressoras Mieloides/citologia , Células Supressoras Mieloides/imunologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Feniltioidantoína/análogos & derivados , Feniltioidantoína/farmacologia , Feniltioidantoína/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/metabolismo , Receptores Androgênicos/metabolismo , Receptores de Interleucina/metabolismo , Transdução de Sinais
13.
Andrologia ; 50(9): e13075, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29952429

RESUMO

We investigated whether low androgen levels affected erectile function by regulating the expressions of intermediate-conductance Ca2+ -activated K+ channel (IKca) and small-conductance Ca2+ -activated K+ channel 3 (SKca3) in corpus cavernous of rats. Thirty-six healthy male SD rats were randomly divided into the 4-week control group, 4-week castration group, 4-week androgen replacement after castration group, 8-week control group, 8-week castration group and 8-week androgen replacement after castration group, respectively. The rats in the androgen replacement groups were subcutaneously injected with testosterone (3 mg/kg) every other day after castration. After 4 and 8 weeks, maximum intracavernous pressure/mean arterial pressure (ICPmax /MAP) was measured. Expressions of IKca, SKca3, endothelial nitric oxide synthase (eNOS) and P-eNOS in penile corpus cavernosum were detected. ICPmax /MAP decreased significantly in the castration groups as compared to the control groups and the androgen replacement groups (p < 0.01). mRNA expressions of IKca and SKca3 decreased significantly in the castration groups as compared to the control groups and androgen replacement groups (p < 0.01). Protein expressions of eNOS, P-eNOS, IKca and SKca3 in the castration groups were significantly reduced as compared to the control groups and androgen replacement groups (p < 0.01). Under low androgen levels, ICPmax /MAP can be reduced by down-regulating the expressions of SKca3 and IKca, inhibiting P-eNOS/eNOS and reducing eNOS bioactivity.


Assuntos
Androgênios/deficiência , Disfunção Erétil/etiologia , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Pênis/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo , Animais , Pressão Sanguínea , Disfunção Erétil/metabolismo , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Testosterona/sangue
14.
PLoS One ; 13(5): e0197252, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29795595

RESUMO

PURPOSE: Intermittent androgen deprivation therapy is an effective treatment for metastatic prostate cancer. However, no study to date has evaluated the long-term outcomes of this treatment among patients with prostate cancer after radical prostatectomy. We retrospectively examined the treatment outcomes of patients with prostate-specific antigen recurrence who underwent radical prostatectomy at our department. MATERIALS AND METHODS: Of the 690 patients who underwent radical prostatectomy for local prostate cancer between 1988 and 2011, 129 patients who received androgen deprivation therapy for prostate-specific antigen recurrence were included in this study. Patient characteristics, luteinizing hormone-releasing hormone agonist administration, and outcomes were compared between the intermittent androgen deprivation group (n = 66) and the continuous androgen deprivation therapy group (n = 63). The non-recurrence and overall survival rates were compared between groups. RESULTS: Thirty-six patients (27.9%) experienced recurrence after luteinizing hormone-releasing hormone agonist administration. The 5-year non-recurrence rate and 10-year overall survival rate were higher in the intermittent group (92.9%) than in the continuous group (92.9 vs 57.9%, P < 0.001; and 95.9% vs 84.3%, P = 0.047, respectively). Furthermore, 63 patients (48.8%) showed a PSA nadir of less than 0.01 ng/mL after initiation of luteinizing hormone-releasing hormone agonist; among these patients, the non-recurrence rate was significantly higher in the intermittent androgen deprivation group (P = 0.003). CONCLUSIONS: Intermittent androgen deprivation therapy for prostate specific antigen recurrence after radical prostatectomy contributed to improvement of the non-recurrence rate and overall survival, and can be considered an effective therapy for better prognosis.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Hormônio Liberador de Gonadotropina/agonistas , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Idoso , Androgênios/deficiência , Humanos , Masculino , Prostatectomia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
15.
Urologiia ; (1): 92-95, 2018 Mar.
Artigo em Russo | MEDLINE | ID: mdl-29634140

RESUMO

AIM: To investigate the impact of fibroblast growth factor 21 (FGF-21) on the severity of androgen deficiency in young and middle-aged men with type 2 diabetes mellitus. MATERIALS AND METHODS: The study comprised 100 men with type 2 diabetes mellitus, cardiovascular multi-morbidity, obesity and androgen deficiency (study group) and 20 healthy men aged 35-50 years. The study group was further divided into two subgroups. Patients of the subgroup 1 received the standard treatment for type 2 diabetes and cardiovascular disease. Patients of the subgroup two were treated with conventional therapy concurrently with testosterone undecanoate. The baseline examination included the following parameters: glycated hemoglobin, total testosterone, prolactin, thyroid stimulating hormone and blood FGF-21. At nine months after the treatment, the blood levels of glycated hemoglobin, FGF21 and testosterone were re-examined. The evaluation of the severity of androgen deficiency was carried out using the ICEF-5 questionnaire and the Aging Males Symptoms scale (AMS). RESULTS: In the study group, the mean FGF-21 level was 2.7 times higher, and the total testosterone level was 2-2.5 times lower than in the control group (p<0.05). A negative correlation was found between the blood levels of FGF-21 and total testosterone (r=-0.41, p<0.05). At nine months post treatment, the subgroup with testosterone undecanoate administered as add-on therapy showed a further decrease in FGF-21 levels and improved androgen deficiency symptoms. DISCUSSION: FGF-21 is one of the markers for type 2 diabetes, cardiovascular multi-morbidity, obesity and androgen deficiency. Given the association of FGF-21 with androgen deficiency, it can be assumed that FGF-21 plays a role in premature aging. Treatment of androgen deficiency as add-on therapy to the standard treatment of this category of patients improves their prognosis and the quality of life. CONCLUSION: Young and middle-aged men with type 2 diabetes should undergo regular screening for androgen deficiency with the purpose of its early diagnosis and timely treatment. The detection of elevated levels of FGF-21 in young and middle-aged men with type 2 diabetes mellitus and cardiovascular multi-morbidity may indicate premature aging and requires preventive measures.


Assuntos
Senilidade Prematura/sangue , Senilidade Prematura/prevenção & controle , Androgênios/deficiência , Diabetes Mellitus Tipo 2/sangue , Fatores de Crescimento de Fibroblastos/sangue , Adulto , Androgênios/sangue , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diagnóstico Precoce , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Testosterona/administração & dosagem , Testosterona/análogos & derivados , Testosterona/uso terapêutico
16.
Prog Urol ; 28(6): 315-321, 2018 May.
Artigo em Francês | MEDLINE | ID: mdl-29650456

RESUMO

INTRODUCTION: Age-related androgenic deficiency (DALA) is a pathology that is increasingly cited in recent publications. The cardiovascular risk of testosterone is debated: present for the FDA, absent for the European Medicines Agency in 2015. Our objective was to analyze the association between androgens and vascular pathologies in adverse reactions reported in pharmacovigilance databases. MATERIAL AND METHOD: We conducted a retrospective case series study of the French and Canadian pharmacovigilance databases for the period 2005-2015. Cases were defined as the association of the occurrence of a cardiovascular event (myocardial infarction or stroke) and the presence of testosterone in the treatment of patients. RESULTS: Of the 10 years analyzed, 12 French cases and 6 Canadian cases (representing 13 MIs and 5 strokes) were recorded in men aged 55 years on average. All were doubtful: differential diagnoses were possible (2.4 confounding conditions on average per patient) and overall cardiovascular risk was high for the majority of cases. CONCLUSION: Our study shows a very low report of cardiovascular effects under testosterone, all doubtful. Pending further studies, it seems reasonable to consider the cardiovascular risk of patients who are candidates for hormone therapy for age-related androgen deficiency. LEVEL OF EVIDENCE: 3.


Assuntos
Androgênios/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Hipogonadismo/tratamento farmacológico , Testosterona/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Androgênios/deficiência , Androgênios/uso terapêutico , Canadá/epidemiologia , Bases de Dados Factuais , Feminino , França/epidemiologia , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Hipogonadismo/complicações , Masculino , Pessoa de Meia-Idade , Farmacovigilância , Estudos Retrospectivos , Fatores de Risco , Testosterona/deficiência , Testosterona/uso terapêutico
17.
Aging Male ; 21(3): 149-157, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29575951

RESUMO

BACKGROUND: The androgen deficiency in the aging male (ADAM) affects physical, sexual, and psychological aspects with characteristics symptoms of middle-aged men. The practice of regular physical activity and physical exercise can attenuate these symptoms. The aim of this randomized clinical trial is to propose a physical exercise protocol based on concurrent training for middle-aged men with ADAM. METHOD: Randomized clinical trial with a 6-month intervention will randomly divided into two groups: experimental group (EG) and control group (CG). Four evaluations will be carried out, (1) pre-intervention; (2) in the first month of intervention; (3) in the third month of intervention; (4) post-intervention, evaluating: physical, psychological, sexual, and hormonal aspects. The intervention protocol with concurrent training will have duration of 6 months; frequency of 3 times weekly, with 60 min per session. The two-way ANOVA test will be used for the inter-group and intra-group comparisons with repeated measurements, and also Sydak's comparison test. CONCLUSION: This protocol was developed with the intent of easing the symptoms of ADAM. In addition, it is believed that the concurrent training protocol could be capable to recover hormonal, physical, psychological, and sexual aspect of middle-aged men with ADAM.


Assuntos
Envelhecimento/fisiologia , Androgênios/deficiência , Terapia por Exercício/métodos , Adulto , Envelhecimento/sangue , Androgênios/sangue , Andropausa/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa , Testosterona/sangue
19.
Curr Diabetes Rev ; 14(3): 280-285, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28031016

RESUMO

BACKGROUND: Androgen Deficiency in Aging Male (ADAM) questionnaire is increasingly popular for the evaluation of testosterone deficiency (TD) in Sub-Saharan African men with type 2 diabetes mellitus (T2DM). However, its reliability in this population is unknown. OBJECTIVE: To evaluate the reliability of the ADAM questionnaire for the clinical detection of testosterone deficiency in Sub-Saharan African men with T2DM. METHODS: Total testosterone < 8nmol/L was used as gold standard for diagnosis of TD in a crosssectional survey of 200 males with T2DM aged 30-69 years. Participants also completed the Saint Louis University ADAM questionnaire whereby TD was diagnosed by a "yes" answer to question 1 (reduced libido) or 7 (erectile dysfunction) or any other three questions. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy of the ADAM tool were computed. RESULTS: The mean age of the participants was 58.0 ± 8.8 years. 142 subjects (71.0%) had TD based on the ADAM questionnaire. However, TD was biochemically confirmed in 59 subjects (29.5%). ADAM questionnaire rendered sensitivity of 88.1%, specificity of 44.7%, PPV of 50.0%, NPV of 85.7% and accuracy of 61.4%. Low libido alone had better specificity (75.5%) and accuracy (73.2%) than the entire questionnaire. CONCLUSION: Despite an impressive sensitivity, the low specificity and overall accuracy of the ADAM questionnaire makes it unreliable for the detection of AD in Sub-Saharan African men with type 2 DM. However, presence of a sustained low libido appears to be a reliable pointer to underlying testosterone deficiency requiring biochemical confirmation.


Assuntos
Envelhecimento/sangue , Androgênios/deficiência , Diabetes Mellitus Tipo 2/complicações , Hipogonadismo/diagnóstico , Inquéritos e Questionários/normas , Testosterona/deficiência , Adulto , África ao Sul do Saara , Grupo com Ancestrais do Continente Africano/estatística & dados numéricos , Idoso , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etnologia , Técnicas de Diagnóstico Endócrino/normas , Projetos de Pesquisa Epidemiológica , Humanos , Hipogonadismo/sangue , Hipogonadismo/complicações , Hipogonadismo/etnologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Testosterona/sangue
20.
Mol Cell Endocrinol ; 470: 188-198, 2018 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-29111388

RESUMO

Regionalised interaction of the activins, follistatin and inhibin was investigated in the male reproductive tract of mice lacking the inhibin α-subunit (Inha-/-). Serum and intratesticular activin B, although not activin A and follistatin, were increased in Inha-/- mice at 25 days of age, but all three proteins were elevated at 56 days. None of these proteins were altered within the epididymis and vas deferens at either age. At 25 days, histology of the epididymis and vas deferens was similar to wild-type. At 56 days, the testis contained extensive somatic cell tumours, leading to Leydig cell regression and testosterone deficiency. The epididymis and vas deferens showed epithelial regression and increased prominence of the interstitial stroma. Immunoregulatory and fibrotic gene expression in the epididymis and vas deferens were unchanged. Thus, absence of the inhibin α-subunit has marginal effects on activins in the epididymis and vas deferens, and regression of these tissues is associated with androgen deficiency.


Assuntos
Ativinas/metabolismo , Androgênios/deficiência , Inibinas/genética , Testículo/metabolismo , Testículo/patologia , Ativinas/sangue , Ativinas/genética , Envelhecimento/patologia , Animais , Epididimo/patologia , Folistatina/sangue , Folistatina/genética , Regulação da Expressão Gênica , Inibinas/deficiência , Inibinas/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Fenótipo , Células Estromais/metabolismo , Células Estromais/patologia , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patologia , Ducto Deferente/patologia
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