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1.
Anticancer Res ; 41(9): 4443-4446, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475067

RESUMO

BACKGROUND: Androgen deprivation therapy (ADT) is one of the most effective treatments for advanced prostate cancer (PCa). However, it has been reported that the use of ADT is significantly associated with an increased risk of acute kidney injury (AKI) among patients with newly diagnosed non-metastatic PCa. We investigated changes in renal function that occurred in Japanese patients with PCa after ADT was discontinued. PATIENTS AND METHODS: Among 121 patients who underwent prostate biopsies, were pathologically diagnosed with PCa, and received ADT for ≥6 months at our Institution between 2009 and 2014, 60 patients who underwent radiotherapy for stage B or C PCa were eligible for inclusion in this retrospective study. Renal function was assessed using the estimated glomerular filtration rate (eGFR) before treatment and at 1, 3, 6, 9, and 12 months after the initiation of ADT and the rate of change in the eGFR (ΔeGFR) during ADT and after the discontinuation of ADT was investigated. We divided patients into two groups: Group 1 received ADT for 6 months, and group 2 received ADT for 12 months. Age; ΔeGFR; prostate-specific antigen, testosterone and hemoglobin levels; clinical stage; Gleason score; comorbidities; body mass index; heart rate; and the cardiothoracic ratio were analyzed. RESULTS: A total of 60 patients (group 1: n=23, group 2: n=37) were analyzed. The Gleason score of group 2 was higher than that of group 1 (p=0.0011). Regarding clinical stage, group 1 had more patients with stage B disease, and group 2 had more with stage C (p<0.0001). The eGFR decreased with the duration of ADT treatment. At 12 months, renal function had started to recover in group 1, while it had continued to decrease in group 2. CONCLUSION: Discontinuation of ADT tended to result in improvements in renal function. Furthermore, this study indicated that renal dysfunction caused by 6 months of ADT is transient. Normalization of the serum testosterone level seen after the discontinuation of ADT may be associated with improvements in renal function. Thus, intermittent ADT may be a useful treatment for PCa, as it would help to preserve renal function.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Rim/fisiopatologia , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Humanos , Japão , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Testosterona/sangue , Fatores de Tempo , Suspensão de Tratamento
2.
Medicine (Baltimore) ; 100(34): e27072, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449505

RESUMO

ABSTRACT: In patients with coronavirus disease 2019 (COVID-19), men are more severely affected than women. Multiple studies suggest that androgens might play a role in this difference in disease severity. Our objective was to assess the association between sex hormone levels and mortality in patients with severe COVID-19.We selected patients from the Amsterdam University Medical Centers COVID-19 Biobank, in which patients admitted to hospital in March and April 2020, with reverse transcription-polymerase chain reaction proven severe acute respiratory syndrome-coronavirus-2 infection, were prospectively included. Specifically, we included postmenopausal women (>55 years) and age-matched men, with a mortality of 50% in each group. Residual plasma samples were used to measure testosterone, estradiol, sex hormone binding globulin (SHBG), and albumin. We investigated the association of the levels of these hormones with mortality in men and women.We included 16 women and 24 men in March and April 2020 of whom 7 (44%) and 13 (54%), respectively, died. Median age was 69 years (interquartile range [IQR] 64-75). In men, both total and free testosterone was significantly lower in deceased patients (median testosterone 0.8 nmol/L [IQR 0.4-1.9] in deceased patients vs 3.2 nmol/L [IQR 2.1-7.5] in survivors; P < .001, and median free testosterone 33.2 pmol/L [IQR 15.3-52.2] in deceased patients vs 90.3 pmol/L [IQR 49.1-209.7] in survivors; P = .002). SHBG levels were significantly lower in both men and women who died (18.5 nmol/L [IQR 11.3-24.3] in deceased patients vs 34.0 nmol/L [IQR 25.0-48.0] in survivors; P < .001). No difference in estradiol levels was found between deceased and surviving patients.Low SHBG levels were associated with mortality rate in patients with COVID-19, and low total and free testosterone levels were associated with mortality in men. The role of testosterone and SHBG and potential of hormone replacement therapy needs further exploration in COVID-19.


Assuntos
COVID-19/sangue , COVID-19/epidemiologia , Hormônios Esteroides Gonadais/análise , Idoso , Albuminas/análise , COVID-19/mortalidade , Comorbidade , Grupos de Populações Continentais , Estradiol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue
3.
Expert Opin Drug Metab Toxicol ; 17(9): 1149-1156, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34372746

RESUMO

PURPOSE: To compare the pharmacokinetics, pharmacodynamics and safety of the new prolonged-release leuprorelin acetate microspheres for injection (3.75 mg) with the reference product Enantone® (3.75 mg). METHOD: 48 healthy male volunteers were enrolled and randomly received a single 3.75 mg dose of the test drug or Enantone®. RESULTS: There were no significant differences in Cmax, AUC0-t and AUC0-48 between the test group and reference group (P > 0.05). The 90% confidence intervals of the two groups were 87.49%~112.74%, 97.15%~154.25%, and 80.85%~109.01%, respectively. Twenty-eight days after administration, both groups reached 100.0% castration level; there was no difference in the time from administration to reaching castration level between the two groups (P > 0.05); However, the difference between the two groups in the duration of castration level was statistically significant (P < 0.05). There were no major or serious adverse events, and the severity was mild to moderate. CONCLUSION: The pharmacokinetic characteristics of leuprorelin in two groups were consistent. The two groups exhibited similar inhibitory effects on testosterone and more subjects in the test group maintained a longer castration time than those in the reference group.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Leuprolida/administração & dosagem , Testosterona/sangue , Adulto , Antineoplásicos Hormonais/farmacocinética , Antineoplásicos Hormonais/farmacologia , Área Sob a Curva , Preparações de Ação Retardada , Humanos , Injeções , Leuprolida/farmacocinética , Leuprolida/farmacologia , Masculino , Microesferas , Método Simples-Cego , Fatores de Tempo , Adulto Jovem
4.
Nutrients ; 13(8)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34444711

RESUMO

Cardiovascular disease (CVD) is a major contributor to the global burden of disease. Berberine, a long-standing, widely used, traditional Chinese medicine, is thought to have beneficial effects on CVD risk factors and in women with polycystic ovary syndrome. The mechanisms and effects, specifically in men, possibly via testosterone, have not been examined previously. To assess the effect of berberine on CVD risk factors and any potential pathway via testosterone in men, we conducted a randomized, double-blind, placebo-controlled, parallel trial in Hong Kong. In total, 84 eligible Chinese men with hyperlipidemia were randomized to berberine (500 mg orally, twice a day) or placebo for 12 weeks. CVD risk factors (lipids, thromboxane A2, blood pressure, body mass index and waist-hip ratio) and testosterone were assessed at baseline, and 8 and 12 weeks after intervention. We compared changes in CVD risk factors and testosterone after 12 weeks of intervention using analysis of variance, and after 8 and 12 weeks using generalized estimating equations (GEE). Of the 84 men randomized, 80 men completed the trial. Men randomized to berberine had larger reductions in total cholesterol (-0.39 mmol/L, 95% confidence interval (CI) -0.70 to -0.08) and high-density lipoprotein cholesterol (-0.07 mmol/L, 95% CI -0.13 to -0.01) after 12 weeks. Considering changes after 8 and 12 weeks together, berberine lowered total cholesterol and possibly low-density lipoprotein-cholesterol (LDL-c), and possibly increased testosterone. Changes in triglycerides, thromboxane A2, blood pressure, body mass index and waist-hip ratio after the intervention did not differ between the berberine and placebo groups. No serious adverse event was reported. Berberine is a promising treatment for lowering cholesterol. Berberine did not lower testosterone but instead may increase testosterone in men, suggesting sex-specific effects of berberine. Exploring other pathways and assessing sex differences would be worthwhile, with relevance to drug repositioning and healthcare.


Assuntos
Berberina/uso terapêutico , Colesterol/sangue , Fatores de Risco de Doenças Cardíacas , Adulto , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/uso terapêutico , Berberina/administração & dosagem , Berberina/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Método Duplo-Cego , Humanos , Hiperlipidemias/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Testosterona/sangue , Tromboxano A2/sangue , Triglicerídeos/sangue , Relação Cintura-Quadril
5.
Medicine (Baltimore) ; 100(31): e26521, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397795

RESUMO

ABSTRACT: The influencing factors of gestational diabetes mellitus (GDM) in the polycystic ovary syndrome (PCOS) patients remain unclear, we aimed to investigate the risk factors of GDM in patients with PCOS, to provide reliable evidence for the prevention and treatment of GDM in PCOS patients.PCOS patients treated in our hospital from January 1, 2019 to October 31, 2020 were included. The personal and clinical treatment details of GDM and no GDM patients were analyzed. Logistic regressions were performed to analyze the factors influencing the occurrence of GDM.A total of 196 PCOS patients were included, the incidence of GDM in patients with PCOS was 23.98%. There were significant differences in the age, body mass index, insulin resistance index, fasting insulin, testosterone, androstenedione, and sex hormone-binding protein between GDM and no GDM patients with PCOS (all P < .05), and no significant differences in the family history of GDM, the history of adverse pregnancy, and multiple pregnancies were found (all P > .05). Age ≥30 years (odds ratio (OR) 2.418, 95% confidence interval (CI) 1.181-3.784), body mass index ≥24 kg/m2 (OR 1.973, 95%CI 1.266-3.121), insulin resistance index ≥22.69 (OR 2.491, 95%CI 1.193-4.043), fasting insulin ≥22.71 mIU/L (OR 2.508, 95%CI 1.166-5.057), testosterone ≥2.85 nmol/L (OR 1.821, 95%CI 1.104-2.762), androstenedione ≥6.63 nmol/L (OR 1.954, 95%CI 1.262-2.844), sex hormone-binding protein <64.22 nmol/L (OR 1.497, 95%CI 1.028-2.016) were the independent risk factors of GDM in patients with PCOS (all P < .05). The incidence of preeclampsia, premature delivery, premature rupture of membranes, polyhydramnios, and postpartum hemorrhage in the GDM group was significantly higher than that of the no-GDM group (all P < .05). There was no significant difference in the incidence of oligohydramnios between the 2 groups (P = .057).The incidence of GDM in PCOS patients is high, and the measures targeted at the risk factors are needed to reduce the occurrence of GDM in patients with PCOS.


Assuntos
Diabetes Gestacional/epidemiologia , Diabetes Gestacional/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Adulto , Fatores Etários , Androstenodiona/sangue , Índice de Massa Corporal , China/epidemiologia , Diabetes Gestacional/etiologia , Jejum/sangue , Feminino , Ruptura Prematura de Membranas Fetais/epidemiologia , Humanos , Incidência , Insulina/sangue , Resistência à Insulina , Síndrome do Ovário Policístico/complicações , Poli-Hidrâmnios/epidemiologia , Hemorragia Pós-Parto/epidemiologia , Pré-Eclâmpsia/epidemiologia , Gravidez , Nascimento Prematuro/epidemiologia , Fatores de Risco , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/sangue , Adulto Jovem
7.
Front Endocrinol (Lausanne) ; 12: 694083, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34226825

RESUMO

Background: Male sex is related to increased COVID-19 severity and fatality although confirmed infections are similarly distributed between men and women. The aim of this retrospective analysis was to investigate the impact of sex hormones on disease progression and immune activation in men with COVID-19. Patients and Methods: We studied for effects of sex hormones on disease severity and immune activation in 377 patients (230 men, 147 women) with PCR-confirmed SARS-CoV-2 infections hospitalized at the Innsbruck University Hospital between February and December 2020. Results: Men had more severe COVID-19 with concomitant higher immune system activation upon hospital admission when compared to women. Men with a severe course of infection had lower serum total testosterone (tT) levels whereas luteinizing hormone (LH) and estradiol (E2) levels were within the normal range. tT deficiency was associated with elevated CRP (rs = - 0.567, p < 0.001), IL-6 levels (rs = - 0.563, p < 0.001), lower cholesterol levels (rs = 0.407, p < 0.001) and an increased morbidity and mortality. Men with tT levels < 100 ng/dL had a more than eighteen-fold higher in-hospital mortality risk (OR 18.243 [95%CI 2.301 - 144.639], p = 0.006) compared to men with tT levels > 230 ng/dL. Moreover, while morbidity and mortality showed a positive correlation with E2 levels at admission, we detected a negative correlation with the tT/E2 ratio upon hospital admission. Conclusion: Hospitalized men with COVID-19 present with rather low testosterone levels linked to more advanced immune activation, severe clinical manifestations translating into an increased risk for ICU admission or death. The underlying mechanisms remain elusive but may include infection driven hypogonadism as well as inflammation mediated cholesterol reduction causing gonadotropin suppression and impaired androgen formation. Finally, in elderly late onset hypogonadism might also contribute to lower testosterone levels.


Assuntos
COVID-19/sangue , COVID-19/diagnóstico , Índice de Gravidade de Doença , Testosterona/sangue , Testosterona/deficiência , Idoso , COVID-19/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Testosterona/imunologia
8.
Gene ; 799: 145847, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34274473

RESUMO

BACKGROUND: Uncontrolled type 1 diabetes mellitus (T1D) impairs reproductive potential of males. Insulin treatment restores metabolic parameters but it is unclear how it protects male reproductive health. Herein, we hypothesized that insulin treatment to T1D rats protects testicular physiology by mediating mechanisms associated with apoptosis and cell cycle. METHODS: Mature male Wistar rats (n = 24) were divided into 3 groups: control, T1D-induced (received 40 mg kg-1 streptozotocin) and insulin-treated T1D (Ins T1D; received 40 mg kg-1 streptozotocin and then treated 0.9 IU/100 gr of insulin for 56 days) (N = 8/group). Expression levels of intrinsic apoptosis pathways regulators (Bcl-2, Bax, Caspase-3 and p53) and core regulators of cell cycle machinery (Cyclin D1, Cdk-4 and p21) were determined in testicular tissue by immunohistochemistry (IHC) and RT-PCR techniques. The percentage of testicular apoptotic cells was evaluated by TUNEL staining. RESULTS: Our data shows that insulin treatment to T1D rats restored (P < 0.05) T1D-induced increased of caspase-3 and p53 expression in testis. Moreover, the testis of T1D rats treated with insulin exhibited increased expression of Cyclin D1 and cdk-4, and a reduced expression of p21 when compared with the expression in testis of T1D rats. Finally, insulin treatment could fairly control T1D-induced apoptosis. Accordingly, treatment of T1D rats with insulin led to a remarkable reduction (p < 0.05) in the percentage of apoptotic cells in the testis. CONCLUSIONS: Insulin treatment is able to restore the network expression of apoptosis and proliferation-related genes caused by T1D in the testis and via this mechanism, preserve the fertility of males.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina/fisiologia , Testículo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Fertilidade , Expressão Gênica/efeitos dos fármacos , Masculino , Substâncias Protetoras/farmacologia , Ratos Wistar , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Testículo/patologia , Testosterona/sangue
9.
Nutrients ; 13(6)2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34203033

RESUMO

The Kaliningrad region is known for its specific climate, which can negatively affect the adaptive potential of the body. This manifests in an increased incidence of respiratory diseases and skin conditions. To prevent high morbidity, a plant protein product was included in the diet of first-year university students. This study aimed to assess the effectiveness of this food intervention in preventing the most common diseases among Kaliningrad students. Two groups of university students took part in the food trial. In the control group, catabolic processes prevailed in nutrient metabolism. Disadaptation manifested itself in the metabolism of proteins, vitamins, minerals, hematopoiesis and humoral immunity. Inflammation was indicated by α1- and α2-globulins, a weak immune response, and IgM and IgG. High oxidative stress and low antioxidative ability of blood serum were observed. The plant-based protein product (FP) helped preserve testosterone level and prevent an increase in catabolic reactions. Moreover, it had a positive effect on both red blood cell hematopoiesis (a smaller increase in the average volume of erythrocytes, the same average concentration and content of hemoglobin, an increased relative red cell distribution width (RDW) and white blood cell hematopoiesis (a beneficial effect for the immune system: lymphocytes, the relative content of neutrophils, monocytes, basophils and eosinophils). The stimulation of humoral immunity was evidenced by beta- and gamma-globulins, an active immune response, the level of IgM and IgG, antioxidant protection, reduction of peroxides and an increase in antioxidant activity of blood serum. The 34-week observation showed a 1.7-fold decrease in the incidence of respiratory illnesses and a 5.7-fold decrease in skin and subcutaneous tissue diseases. Acute respiratory infections were reduced 1.8-fold. There were no cases of community-acquired pneumonia in the treatment group, compared with 55.1‰ in the control group. The incidence of respiratory diseases was 3.3-10.6 times lower in the treatment group than in the control group in weeks 6-19. The findings testify to the prophylactic effect of functional food during social adaptation and acclimatization of students.


Assuntos
Alimento Funcional , Proteínas de Vegetais Comestíveis/administração & dosagem , Doenças Respiratórias/prevenção & controle , Dermatopatias/prevenção & controle , Contagem de Células Sanguíneas , Clima , Alimento Funcional/análise , Hematopoese , Humanos , Imunidade Humoral , Micronutrientes/análise , Minerais/sangue , Estresse Oxidativo , Doenças Respiratórias/epidemiologia , Federação Russa , Dermatopatias/epidemiologia , Testosterona/sangue , Vitaminas/sangue
10.
J Fam Pract ; 70(3): 147-149, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-34314340
11.
Urol Int ; 105(9-10): 743-748, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34265771

RESUMO

INTRODUCTION: The coronavirus disease 2019 (COVID-19) is a global pandemic which may affect multiple organs and systems including testes and disrupt the gonadal functions. The current study aimed to evaluate the effect of COVID-19 on the semen parameters and sex-related hormone levels in infertile men. METHODS: The study included 21 patients who were evaluated in Ankara City Hospital, Andrology Clinic, for male infertility and have had the diagnosis of COVID-19. All the patients were evaluated in terms of semen parameters. The follicle-stimulating hormone, luteinizing hormone, and testosterone (T) levels were also evaluated in 8 of the patients. The results were presented through 2 dependent group analyses, based on the data of the patients collected before and after the diagnosis of COVID-19. RESULTS: None of the patients needed to be hospitalized at any time through the course of COVID-19. There was a significant decrease in semen volume, percentage of total motility, percentage of progressive motility, and normal sperm morphology after COVID-19 (3 [1-8] vs. 2.5 [1.5-5], p = 0.005; 48.6 ± 22.1 vs. 34.7 ± 20.7, p = 0.001; 35.1 ± 21.7 vs. 21.8 ± 15.9, p < 0.001; 6 [3-24] vs. 5 [3-18], p = 0.015; respectively). There was also a significant decline in T level of the patients after the diagnosis of COVID-19 (350.1 ± 115.5 vs. 289.8 ± 103.3, p = 0.009). CONCLUSION: COVID-19 may have unfavorable effects on the gonadal functions and may lead to further deterioration of the semen parameters in infertile men, which should be considered through the evaluation for infertility.


Assuntos
COVID-19/virologia , Infertilidade Masculina/patologia , SARS-CoV-2/patogenicidade , Análise do Sêmen , Espermatozoides/patologia , Adulto , COVID-19/diagnóstico , Fertilidade , Hormônio Foliculoestimulante Humano/sangue , Interações Hospedeiro-Patógeno , Humanos , Infertilidade Masculina/sangue , Infertilidade Masculina/virologia , Hormônio Luteinizante/sangue , Masculino , Estudos Retrospectivos , Fatores de Risco , Espermatozoides/virologia , Centros de Atenção Terciária , Testosterona/sangue , Turquia , Adulto Jovem
12.
Aging (Albany NY) ; 13(12): 16229-16247, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34139672

RESUMO

Brain mitochondrial dysfunction and reduced testosterone levels are common features of aging in men. Although evidence suggests that the two phenomena are interrelated, it is unclear whether testosterone supplementation ameliorates mitochondrial dysfunction in the aging male brain. Here, we show that testosterone supplementation significantly alleviates exploratory behavioral deficits and oxidative damage in the substantia nigra and hippocampus of aging male rats. These effects were consistent with improved mitochondrial function, reflected by testosterone-induced increases in mitochondrial membrane potential (MMP), antioxidant enzyme (GSH-PX, catalase, and Mn-SOD) expression/activity, and mitochondrial respiratory complex activities in both brain regions. Furthermore, elevated PGC-1α, NRF-1, and TFAM expression (suggestive of enhanced mitochondrial biogenesis), increased citrate synthase activity, mtDNA copy number, and ND1, COX1, and ATP6 expression (indicative of increased mitochondrial content), as well as increased PINK1/Parkin and decreased P62 expression (suggesting mitophagy activation), were detected in the substantial nigra and hippocampus of aged male rats after testosterone supplementation. These findings suggest that testosterone supplementation may be a viable approach to ameliorating brain mitochondrial dysfunction and thus prevent or treat cognitive-behavioral deficits and neurodegenerative conditions associated with aging.


Assuntos
Envelhecimento/patologia , Encéfalo/metabolismo , Mitocôndrias/patologia , Testosterona/farmacologia , Envelhecimento/sangue , Animais , Antioxidantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Transporte de Elétrons/efeitos dos fármacos , Comportamento Exploratório/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Proteínas Quinases/metabolismo , Ratos Sprague-Dawley , Substância Negra/metabolismo , Testosterona/sangue , Tirosina 3-Mono-Oxigenase/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
13.
Pan Afr Med J ; 38: 292, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178211

RESUMO

Introduction: there is an association between hypogonadism and obesity, chronic hyperglycaemia, and ageing in men with type 2 diabetes mellitus (T2DM). T2DM is known to be associated with low testosterone. There is a paucity of data on the risk factors of hypogonadism in Nigerian men with T2DM. The objective of this study was to determine the clinical and biochemical correlates of hypogonadism and clinical predictors of low total testosterone levels in men with T2DM. Methods: this was a cross-sectional study consisting of 358 men with T2DM and 179 non-diabetic men (controls). Structured Androgen Deficiency in the Ageing Male questionnaire was administered. Clinical and biochemical parameters were measured. Free testosterone was calculated from albumin, SHBG and total testosterone using Vermeulen´s method. Hypogonadism was defined as fasting TT as < 8 nmol/L with or without symptoms or TT of 8-12 nmol/L with symptoms of androgen deficiency. Low testosterone was defined as serum total testosterone levels ≤ 12 nmol/L. Results: the mean (±SD) total testosterone of men with T2DM and controls were 8.79±3.35 nmol/L and 15.41±3.79 nmol/L respectively (p < 0.001). The risk of hypogonadism was associated with central obesity (Odds ratio [OR] 2.24, 95% confidence interval [CI] 0.38-13.07), systolic hypertension (OR 3.93, 95% CI 0.67-23.10), hyperglycaemia (OR 2.48, 95% CI 0.37-16.46) and hypercholesterolaemia (OR 2.50, 95% CI 0.43-14.61). In a multivariable regression analysis, there was a significant negative correlation between total testosterone and triglycerides (r -1.85, 95% CI -3.58 - 0.12, P = 0.04) and HDL cholesterol (r -1.25, 95% CI -5.95-3.45, P = 0.02). Conclusion: this study shows that in men with T2DM, triglycerides and HDL cholesterol are independent correlates of hypogonadism but not central adiposity, systolic blood pressure and glycaemia. Further large prospective studies are recommended.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Hipogonadismo/etiologia , Obesidade/complicações , Testosterona/sangue , Adulto , Envelhecimento , Glicemia/metabolismo , HDL-Colesterol/sangue , Estudos Transversais , Humanos , Hipogonadismo/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Triglicerídeos/sangue
14.
J Zoo Wildl Med ; 52(2): 721-725, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34130417

RESUMO

Improvac® is a gonadotropin-releasing hormone vaccine developed to reduce "boar taint" in the meat of male domestic pig. The use of Improvac for contraception of zoo and free-living animals has been increasing in recent years. This study reports the use, efficacy, and side effects of Improvac on five male sea lions. Administration of two injections of 600 µg of Improvac (gonadotropin releasing factor analogue-protein conjugate) 4-5 wk apart were delivered to two Patagonian and three California sea lions to reduce testosterone-related aggression, anorexia, and lethargy that occur during the breeding season. Behavior and physical changes were recorded for all individuals, and blood samples were taken from one Patagonian sea lion to measure plasma testosterone concentrations over time. Observations revealed a descension of the testes into the scrotum, orchitis, lameness, anorexia, and lethargy in all individuals for the first 3-5 d after the first administration of the vaccine. Plasma testosterone concentrations rose after the first dose of the vaccine and remained elevated for 1 mo, decreasing after the second injection to undetectable levels. Improvac administration can cause a peak of testosterone and breeding behavior just after the first inoculation, as previously described in swine and elephants, but has not been documented in pinnipeds. None of the treated animals in this study showed breeding behaviors during their normal breeding season (July-September).


Assuntos
Hormônio Liberador de Gonadotropina/imunologia , Leões-Marinhos , Estações do Ano , Comportamento Sexual Animal , Vacinação/veterinária , Vacinas/imunologia , Animais , Animais de Zoológico , Humanos , Imunização/veterinária , Masculino , Testosterona/sangue , Vacinas/administração & dosagem
15.
Ecotoxicol Environ Saf ; 221: 112435, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34171690

RESUMO

The present work was designed to assess the potential ameliorative effect of thymol on the testicular toxicity caused by imidacloprid (IMI) in adult male rats. Forty adult male rats were allocated into four groups; control group was given corn oil, thymol-treated group (30 mg/kg b.wt), IMI-treated group (22.5 mg/kg b.wt), and IMI + thymol-treated group. All administrations were done by gavage every day for duration of 56 days. As a result, the IMI exposure caused a significant decline in the body weight change, reproductive organ weights, sperm functional parameters, and serum level of testosterone, widespread histological alterations, and apoptosis in the testis. Additionally, the IMI-treated rats exhibited a remarkable increment in the serum levels of follicle stimulating hormone and luteinizing hormone. Also, IMI induced testicular oxidative stress, as indicated by elevated malondialdehyde (MDA) levels and a marked decline in the activity of antioxidant enzymes and reduced glutathione (GSH), and total antioxidant capacity (TAC) levels. Moreover, IMI treatment significantly downregulated the mRNA expression of steroidogenic genes and proliferating cell nuclear antigen (PCNA) immunoexpression in the testicular tissue. However, thymol co-administration significantly mitigated the IMI-induced toxic effects. Our findings suggested that IMI acts as a male reproductive toxicant in rats and thymol could be a potential therapeutic option for IMI reprotoxic impacts.


Assuntos
Apoptose/genética , Neonicotinoides/toxicidade , Nitrocompostos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Testículo/efeitos dos fármacos , Timol/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Espermatozoides/efeitos dos fármacos , Testosterona/sangue
16.
Toxicology ; 458: 152836, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34147545

RESUMO

China's clean energy and resources are mainly located in the west and north while electric load center is concentrated in the middle and east. Thus, these resources and energy need to be converted into electrical energy in situ and transported to electric load center through ultra-high voltage direct current (UHVDC) transmissions. China has built 25,000 km UHVDC transmission lines of 800 kV and 1100 kV, near which the impact of electric field on health has attracted public attention. Previous studies showed that time-varying electromagnetic field exposure could disturb testosterone secretion. To study the effect of non-time-varying electric field caused by direct current transmission lines on testosterone synthesis, male ICR mice were continually (24 h/d) exposed to static electric field of 56.3 ± 1.4 kV/m. Results showed that on the 3rd day of exposure and on the 7th day after ceasing the exposure of 28 d, serum testosterone level and testicular oxidative stress indicators didn't change significantly. On the 28th day of exposure, serum testosterone levels, testicular glutathione peroxidase (GSH-Px) activity, the mRNA and protein levels of testicular StAR, PBR, CYP11A1 decreased significantly, and testicular malondialdehyde (MDA) content increased significantly. Meanwhile, electron-dense edges and vacuolation appeared in lipid droplets of Leydig cells. The gap between inner mitochondrial membrane (IMM) and outer mitochondrial membrane (OMM) enlarged, which would cause the swelling of mitochondria, the rupture and deficiency of mitochondrial membranes. Analysis showed that testicular oxidative stress could induce the damage of mitochondrial structure in Leydig cells, which would decrease the rate of cholesterol transport from cytoplasm to mitochondria. Since cholesterol is the necessary precursor of testosterone synthesis, testosterone synthesis was inhibited. The decrease of the mRNA and protein expression levels of StAR and PBR in testes could diminish the cholesterol transported from OMM to IMM. The decrease of the mRNA and protein expression levels of CYP11A1 could reduce the pregnenolone required in testosterone synthesis and inhibit testosterone synthesis consequently.


Assuntos
Campos Eletromagnéticos , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/efeitos da radiação , Testosterona/biossíntese , Animais , Antioxidantes/metabolismo , Colesterol/metabolismo , Citoplasma/metabolismo , Citoplasma/efeitos da radiação , Glutationa Peroxidase/metabolismo , Células Intersticiais do Testículo/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos ICR , Membranas Mitocondriais/metabolismo , Membranas Mitocondriais/efeitos da radiação , Dilatação Mitocondrial/efeitos da radiação , Estresse Oxidativo/efeitos da radiação , Fosfoproteínas/metabolismo , Testosterona/sangue , Vacúolos/efeitos da radiação , Vacúolos/ultraestrutura
17.
Eur J Endocrinol ; 185(2): 279-288, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34081616

RESUMO

Objective: It has been suggested that adverse early life exposures increase the risk of developing polycystic ovary syndrome (PCOS) in later life. We hypothesized that women born preterm would have more biochemical and clinical signs of PCOS than women born at term. Design: The ESTER Preterm Birth Study participants were born in Northern Finland and identified from the Northern Finland Birth Cohort and the Finnish Medical Birth Register. Altogether, 74 women born very or moderately preterm (<34 gestational weeks, VMPT), 127 born late preterm (at 34-36 weeks, LPT), and 184 born full term (≥37 weeks, controls) were included in the analysis (mean age: 23.2 years). Methods: We measured serum total testosterone and sex hormone-binding globulin (SHBG) and calculated the free androgen index (FAI). PCOS according to the clinical and biochemical signs was defined either as hirsutism and oligoamenorrhea (via questionnaire) or as oligoamenorrhea and elevated testosterone levels (>2.4 nmol/L). Results: Women born VMPT/LPT exhibited 33.0% (8.7, 62.8)/16.4% (-2.0, 38.1) higher testosterone, 28.5% (5.3, 45.9)/24.1% (5.6, 38.9) lower SHBG levels, and 64.6% (19.4, 127.1)/42.5% (11.1, 82.9) higher FAI than controls after adjusting for age and recruitment cohort, maternal BMI, smoking, and pregnancy disorders, parental education, history of hypertension, diabetes, myocardial infarction or stroke, and subject's birth weight s.d. Odds ratios for having PCOS were 1.67 (0.44, 6.23)/3.11 (1.26, 7.70). Conclusions: Women born preterm have a more hyperandrogenic hormonal profile, and those born LPT are approximately three times more likely at risk to have PCOS compared to women born at term.


Assuntos
Biomarcadores , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/epidemiologia , Nascimento Prematuro/epidemiologia , Adulto , Crianças Adultas/estatística & dados numéricos , Androgênios/sangue , Biomarcadores/análise , Biomarcadores/sangue , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Finlândia/epidemiologia , Idade Gestacional , Hirsutismo/sangue , Hirsutismo/diagnóstico , Hirsutismo/epidemiologia , Humanos , Recém-Nascido , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/etiologia , Gravidez , Complicações na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Fatores de Risco , Testosterona/sangue , Adulto Jovem
18.
J Chromatogr A ; 1650: 462228, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34090133

RESUMO

Bioactive 11-oxygenated C19 adrenal-derived steroids (11-oxy C19) are potentially relevant in diverse endocrine and metabolic contexts. We report the development and validation of a liquid chromatography electrospray ionization tandem mass spectrometric method (LC-ESI-MS/MS) for the simultaneous quantification of seven 11-oxy C19 using 200 µL of plasma or serum. Sample preparation involved chemical derivatization using hydroxylamine after liquid-liquid extraction to improve specificity and sensitivity. The method allowed the quantitation of total 11-oxy C19 (free + sulfate and glucuronide conjugates) following enzymatic hydrolysis. This included the abundant precursor 11-hydroxyandrostenedione (11OHA4) and the most potent androgenic derivatives 11-keto-testosterone (11KT) and 11-keto-dihydrotestosterone (11KDHT), their abundant metabolites 11-hydroxyandrosterone (11OHAST) and 11-keto-androsterone (11KAST) potentially feeding back into the pool of potent androgens, in addition to 11-keto-androstenedione (11KA4) and 11-hydroxytestosterone (11OHT). Stable isotopes were used as internal standards, and calibrators and quality controls were prepared in the same matrix as the study samples. Performance was validated against the Food and Drug Administration Criteria. The method was sensitive with lower limit of quantification (LLOQ) values of 10 and 20 pg/mL for free and total 11-oxy C19, respectively. The applicability was demonstrated in men and women adult donors that showed sex-differences. All steroids were quantified well above LLOQ, except 11KDHT that remained undetectable suggesting interfering endogenous molecules present in non-derivatized samples in which a peak was observed. By providing accurate and reliable quantitative data, this method will permit to evaluate how profiling of 11-oxy C19 will be most informative as diagnostic, prognostic and/or theranostic tools.


Assuntos
Androgênios , Análise Química do Sangue , Cromatografia Líquida , Espectrometria de Massas em Tandem , Adulto , Androgênios/sangue , Androstenodiona/análogos & derivados , Androstenodiona/sangue , Análise Química do Sangue/métodos , Feminino , Glucuronídeos , Humanos , Hidroxitestosteronas/sangue , Limite de Detecção , Masculino , Oxigênio/química , Esteroides/sangue , Testosterona/análogos & derivados , Testosterona/sangue
19.
Hum Genet ; 140(8): 1169-1182, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33963445

RESUMO

Male infertility impacts millions of couples yet, the etiology of primary infertility remains largely unknown. A critical element of successful spermatogenesis is maintenance of genome integrity. Here, we present a genomic study of spermatogenic failure (SPGF). Our initial analysis (n = 176) did not reveal known gene-candidates but identified a potentially significant single-nucleotide variant (SNV) in X-linked germ-cell nuclear antigen (GCNA). Together with a larger follow-up study (n = 2049), 7 likely clinically relevant GCNA variants were identified. GCNA is critical for genome integrity in male meiosis and knockout models exhibit impaired spermatogenesis and infertility. Single-cell RNA-seq and immunohistochemistry confirm human GCNA expression from spermatogonia to elongated spermatids. Five identified SNVs were located in key functional regions, including N-terminal SUMO-interacting motif and C-terminal Spartan-like protease domain. Notably, variant p.Ala115ProfsTer7 results in an early frameshift, while Spartan-like domain missense variants p.Ser659Trp and p.Arg664Cys change conserved residues, likely affecting 3D structure. For variants within GCNA's intrinsically disordered region, we performed computational modeling for consensus motifs. Two SNVs were predicted to impact the structure of these consensus motifs. All identified variants have an extremely low minor allele frequency in the general population and 6 of 7 were not detected in > 5000 biological fathers. Considering evidence from animal models, germ-cell-specific expression, 3D modeling, and computational predictions for SNVs, we propose that identified GCNA variants disrupt structure and function of the respective protein domains, ultimately arresting germ-cell division. To our knowledge, this is the first study implicating GCNA, a key genome integrity factor, in human male infertility.


Assuntos
Azoospermia/congênito , Genes Ligados ao Cromossomo X , Infertilidade Masculina/genética , Mutação , Proteínas Nucleares/genética , Espermatozoides/metabolismo , Adulto , Animais , Azoospermia/diagnóstico , Azoospermia/genética , Azoospermia/metabolismo , Azoospermia/patologia , Sequência de Bases , Estudos de Coortes , Hormônio Foliculoestimulante/sangue , Expressão Gênica , Genoma Humano , Instabilidade Genômica , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/metabolismo , Infertilidade Masculina/patologia , Hormônio Luteinizante/sangue , Masculino , Meiose , Modelos Moleculares , Proteínas Nucleares/deficiência , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Espermatogênese/genética , Espermatozoides/patologia , Testículo/metabolismo , Testículo/patologia , Testosterona/sangue , Sequenciamento Completo do Exoma
20.
Toxicol Appl Pharmacol ; 423: 115568, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33965371

RESUMO

N-methyl pyrrolidone (NMP) is an FDA approved molecule used as an excipient in pharmaceutical industry. Besides having a central role in formulation of drugs, the most important function of any excipient is to guarantee the safety of the medicine during and after its administration. Several studies have shown that exposure to NMP and especially in rats produce a gonadotoxic effect leading to infertility. However, the mechanisms underlying the effect of NMP on male reproduction are unknown. The aim of this study was to assess the reproductive toxicity of NMP in male rats and to elucidate the underlying mechanism. Male Sprague Dawley rats were injected intraperitoneally, twice/ week, at a dose of 108 mg/ 100 g of body weight with NMP. Analysis of reproductive parameters revealed testicular atrophy in NMP treated animals compared to control animals. Germ cell composition within the seminiferous tubules was disturbed and manifested in an increase in number of cells with fragmented DNA. A subsequent decrease in number of spermatocytes and spermatids was observed. Alpha screen assay shows that NMP acts at the concentrations we applied in vivo as a low affinity inhibitor for BRDT (testis specific bromodomain protein). BRDT inhibition is mirrored by a significant decrease in the expression of early stage spermatocyte markers (lmna, aurkc and ccna1), during which BRDT expression predominates. A significant decrease in testosterone levels was also observed. Since NMP interferes with spermatogenesis on various levels, its use in humans must be carefully monitored.


Assuntos
Proteínas Cromossômicas não Histona/antagonistas & inibidores , Proteínas Cromossômicas não Histona/metabolismo , Pirrolidinonas/toxicidade , Espermatogênese/efeitos dos fármacos , Teratógenos/toxicidade , Animais , Relação Dose-Resposta a Droga , Hormônio Foliculoestimulante/sangue , Masculino , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/fisiologia , Ratos , Ratos Sprague-Dawley , Espermatogênese/fisiologia , Testosterona/sangue
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