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1.
Eur J Endocrinol ; 183(5): 529-536, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33071222

RESUMO

Objective: Transgender individuals sometimes report a lack of physical change during hormone treatment, such as alterations in muscle tone or fat distribution. Identifying characteristics of this subgroup could be a step toward individualizing hormone therapy in transgender individuals. Therefore, we study the variation of changes in body composition and characteristics associated with a lack of change. Design and methods: Body composition measures were recorded in 323 transmen and 288 transwomen at every visit from the start of hormone therapy to a maximum of 24 months follow-up. Absence of change was defined as transmen with a decrease in lean body mass or transwomen with a decrease in fat percentage. Results: A lack of change at 24 months was observed in 19 of 94 (20.2%) transmen and in 9 of 96 (9.4%) transwomen. The risk of not achieving change in body composition was related to lower testosterone levels and less suppression of LH in transmen (OR: 0.67, 95% CI: 0.48-0.94 per SD increase in testosterone and OR: 1.36, 95% CI: 1.01-1.83 per SD increase in LH). Conclusions: There is a large variation in body composition changes during hormone therapy, with a substantial proportion of individuals with no measurable effects. In transmen, serum testosterone and LH were associated with a lack of change, but serum hormone levels were not associated with body composition changes in transwomen. The results provide a rationale for individualizing hormone therapy in transmen, by considering individual effects rather than solely relying on a standardized dosage of hormone therapy.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Androgênios/uso terapêutico , Composição Corporal , Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Testosterona/uso terapêutico , Pessoas Transgênero , Adulto , Distribuição da Gordura Corporal , Acetato de Ciproterona/uso terapêutico , Relação Dose-Resposta a Droga , Impedância Elétrica , Estradiol/sangue , Feminino , Humanos , Hormônio Luteinizante/sangue , Masculino , Medicina de Precisão , Procedimentos de Readequação Sexual/métodos , Testosterona/análogos & derivados , Testosterona/sangue , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
2.
Medicine (Baltimore) ; 99(36): e22085, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899084

RESUMO

RATIONALE: Testicular tumors represent 1% to 1.5% of all tumors in men. Those derived from Leydig cells are rare and account for 1% of testicular tumors. Leydig tumor cells can produce steroid hormones such as estrogen, progesterone and testosterone. The amount and type of hormones secreted by these tumors may produce complicated clinical characteristics in these patients. PATIENT CONCERNS: Here, we report a patient with azoospermia, a testicular Leydig cell tumor (LCT), and elevated plasma testosterone levels. We describe the diagnostic and therapeutic experience of this case, and our follow-up of the patient's clinical indicators and fertility status. DIAGNOSIS: The patient was diagnosed with azoospermia and a testicular LCT. INTERVENTIONS: The patient underwent testicular tumor removal and long-term follow-up. OUTCOMES: After 4 months of follow-up, the patient's semen examination index significantly improved and his wife became naturally pregnant. At 4 months of gestation, the fetus was delivered because of a ruptured amniotic cavity. Twenty-six months after tumor removal, the patient's sex hormone levels had completely returned to normal and spermatogenic function had partially recovered, but there was no natural pregnancy with his partner. CONCLUSION: For LCTs, testis sparing surgery may provide a safe and feasible option to restore spermatogenic function, although longer-term follow-up is required. Drug assistance may be required to maintain spermatogenic function and achieve fertility, and further research is required.


Assuntos
Azoospermia/complicações , Tumor de Células de Leydig/complicações , Neoplasias Testiculares/complicações , Adulto , Humanos , Tumor de Células de Leydig/patologia , Tumor de Células de Leydig/cirurgia , Masculino , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia , Testosterona/sangue
3.
Ecotoxicol Environ Saf ; 203: 111053, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888615

RESUMO

Vinclozolin is a common dicarboximide fungicide used to protect crops from diseases. It is also an endocrine disruptor and is thought to be related to abnormalities of the reproductive tract. However, its mechanism of inducing abnormalities of the male reproductive tract is still unclear. The purpose of this study was to study the effect of gestational vinclozolin exposure on the development of rat fetal Leydig cells. Female pregnant Sprague-Dawley rats were exposed to vinclozolin (0, 25, 50, and 100 mg/kg body weight/day) by gavage from gestational day 14-21. Vinclozolin dose-dependently reduced serum testosterone levels at doses of 50 and 100 mg/kg and the anogenital distance at 100 mg/kg. RNA-seq, qPCR, and Western blotting showed that vinclozolin down-regulated the expression of Nr5a1, Sox9, Lhcgr, Cyp11a1, Hsd3b1, Hsd17b3, Amh, Pdgfa, and Dhh and their encoded proteins. Vinclozolin reduced the number of NR2F2-positive stem Leydig cells at a dose of 100 mg/kg and enhanced autophagy in the testes. In conclusion, vinclozolin disrupts reproductive tract development and testis development in male fetal rats via several pathways.


Assuntos
Disruptores Endócrinos/toxicidade , Fungicidas Industriais/toxicidade , Organogênese/efeitos dos fármacos , Oxazóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Testículo/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Masculino , Gravidez , Ratos , Ratos Sprague-Dawley , Testículo/embriologia , Testículo/patologia , Testosterona/sangue
4.
Medicine (Baltimore) ; 99(33): e21639, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872027

RESUMO

INTRODUCTION: Anabolic steroids are commonly used by athletes, body builders, and young adults to improve muscle strength. Deleterious effects of anabolic steroids on physical health are well-established. Psychiatric aspects are of particular importance and include psychosis, delirium, mania, depression, and aggression. We describe the case of a young gentleman who was managed as a case of androgenic steroid induced delirium. PATIENT CONCERN: A 33-year-old gentleman presented with increased aggression, hostility, and destructive impulses. He was a regular user of testosterone propionate, testosterone cyprionate and trenbolone acetate up to 200 mg daily in injectable form. His mental status examination showed labile effect, flight of ideas and persecutory delusions. Physical examination was positive for atrophic testes. Laboratory results showed a decreased plasma testosterone level of 9.59 nmol/l (10.4-37.4 nmol/l). Sex Hormone Binding Globulin was 23.8 nmol/l (18.3-54.1 nmol/l) and bioavailable testosterone was 5.110 nmol/l (4.36-14.30 nmol/l). DIAGNOSIS: He was diagnosed as a case of anabolic steroids induced delirium. INTERVENTIONS AND OUTCOME: Patient was treated with regular haloperidol and quetiapine after which his sensorium, speech and behavior improved. He was discharged on haloperidol 7.5 mg and quetiapine 700 mg daily. CONCLUSION: The purpose of this case report is to emphasize on the neuropsychiatric effects and management of anabolic steroids manifested by delirium, increased aggression, hostility, and destructive impulses.


Assuntos
Delírio/induzido quimicamente , Congêneres da Testosterona/efeitos adversos , Adulto , Agressão/efeitos dos fármacos , Antipsicóticos/administração & dosagem , Delírio/tratamento farmacológico , Haloperidol/administração & dosagem , Humanos , Masculino , Fumarato de Quetiapina/administração & dosagem , Testosterona/sangue , Congêneres da Testosterona/administração & dosagem
5.
PLoS One ; 15(8): e0237315, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866153

RESUMO

The decision to allocate time and energy to find multiple sexual partners or raise children is a fundamental reproductive trade-off. The Strategic Pluralism Hypothesis argues that human reproductive strategies are facultatively calibrated towards either investing in mating or parenting (or a mixture), according to the expression of features dependent on the individual's condition. This study seeks to test predictions derived from this hypothesis in a sample of 242 young men (M ± SD = 22.12 ± 3.08) from Chile's 5th Region (33Ö¯ south latitude). Specifically, two predictions were considered that raise questions about the relationship between traits related to physical and psychological attractiveness (fluctuating facial asymmetry and self-perception of attractiveness) and competitive skills (baseline testosterone and self-perception of fighting ability) with short-term reproductive strategies. Our results indicate that psychological features related to the self-perception of physical attractiveness are related to short-term reproductive strategies. However, no evidence was found that fluctuating facial asymmetry, basal levels of testosterone and self-perception of fighting ability were related to short-term reproductive strategies. These results support the existing evidence of the importance of physical attractiveness in calibrating men's reproductive strategies but cast doubts about the role of fluctuating facial asymmetry. They also suggest that traits related to physical attractiveness, in comparison to competitive capabilities, play a more important role in calibrating men's short-term reproductive strategies.


Assuntos
Beleza , Comportamento de Escolha , Reprodução/fisiologia , Autoimagem , Comportamento Sexual/psicologia , Adolescente , Adulto , Chile , Comportamento Competitivo/fisiologia , Humanos , Parceiros Sexuais/psicologia , Inquéritos e Questionários/estatística & dados numéricos , Testosterona/sangue , Testosterona/fisiologia , Adulto Jovem
7.
Nat Rev Endocrinol ; 16(9): 519-533, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32620937

RESUMO

Reproductive function adjusts in response to environmental conditions in order to optimize success. In humans, this plasticity includes age of pubertal onset, hormone levels and age at menopause. These reproductive characteristics vary across populations with distinct lifestyles and following specific childhood events, and point to a role for the early-life environment in shaping adult reproductive trajectories. Epigenetic mechanisms respond to external signals, exert long-term effects on gene expression and have been shown in animal and cellular studies to regulate normal reproductive function, strongly implicating their role in these adaptations. Moreover, human cohort data have revealed differential DNA methylation signatures in proxy tissues that are associated with reproductive phenotypic variation, although the cause-effect relationships are difficult to discern, calling for additional complementary approaches to establish functionality. In this Review, we summarize how adult reproductive function can be shaped by childhood events. We discuss why the influence of the childhood environment on adult reproductive function is an important consideration in understanding how reproduction is regulated and necessitates consideration by clinicians treating women with diverse life histories. The resolution of the molecular mechanisms responsible for human reproductive plasticity could also lead to new approaches for intervention by targeting these epigenetic modifications.


Assuntos
Adaptação Fisiológica/genética , Meio Ambiente , Epigênese Genética/fisiologia , Reprodução/genética , Envelhecimento , Animais , Metilação de DNA , Feminino , Fertilidade , Desenvolvimento Fetal , Humanos , Estilo de Vida , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Fenótipo , Gravidez , Progesterona/sangue , Puberdade/genética , Reprodução/fisiologia , Testosterona/sangue , Migrantes
8.
Toxicol Lett ; 332: 213-221, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32693021

RESUMO

Di-n-hexyl phthalate (DNHP) is commonly used as a plasticizer. However, whether DNHP influences Leydig cell development during puberty remains unexplored. In this study, DNHP (0, 10, 100, and 1000 mg/kg) was administered via gavage to 35-day-old male Sprague-Dawley rats for 21 days. Serum levels of testosterone, luteinizing hormone, follicle-stimulating hormone, Leydig cell number, the expression of Leydig and Sertoli cell genes and proteins were investigated. DNHP significantly increased serum testosterone levels at 10 mg/kg but lowered its level at 1000 mg/kg. DNHP significantly increased luteinizing hormone levels at 1000 mg/kg without affecting follicle-stimulating hormone levels. DNHP increased Leydig cell number at all doses but down-regulated the expression of Lhcgr, Hsd3b1, Hsd17b3, and Hsd11b1 in Leydig cell per se at 1000 mg/kg. DNHP elevated phosphorylation of ERK1/2 and GSK-3ß at 10 mg/kg but decreased SIRT1 and PGC-1α levels at 1000 mg/kg. In conclusion, DNHP exposure causes Leydig cell hyperplasia possibly via stimulating phosphorylation of ERK1/2 and GSK-3ß signaling pathways.


Assuntos
Células Intersticiais do Testículo/efeitos dos fármacos , Ácidos Ftálicos/toxicidade , Plastificantes/toxicidade , Animais , Tamanho Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/efeitos dos fármacos , Hiperplasia , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/ultraestrutura , Hormônio Luteinizante/sangue , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Fosforilação , Ratos , Ratos Sprague-Dawley , Maturidade Sexual , Transdução de Sinais/efeitos dos fármacos , Testosterona/sangue
9.
Rev Int Androl ; 18(3): 117-123, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32660697

RESUMO

OBJECTIVE: The main objective of this revision is to summarize the current existing evidence of the potential adverse effects of SARS-CoV-2 on the male reproductive system and provide the recommendations of the Asociación Española de Andrología, Medicina Sexual y Reproductiva (ASESA) concerning the implications of COVID-19 infection in the management of male infertilty patients and testicular endocrine dysfunction. METHODS: A comprehensive systematic literature search of the databases of PubMed, Web of Science, Embase, Medline, Cochrane and MedRxiv, was carried out. RESULTS: The presence of orchitis as a potential complication of the infection by SARS-CoV-2 has not yet been confirmed. One study reported that 19% of males with COVID-19 infection had scrotal symptoms suggestive of viral orchitis which could not be confirmed. It is possible that the virus, rather than infecting the testes directly, may induce a secondary autoimmune response leading to autoimmune orchitis. COVID-19 has been associated with coagulation disorders and thus the orchitis could be the result of segmental vasculitis. Existing data concerning the presence of the virus in semen are contradictory. Only one study reported the presence of RNA in 15.8% of patients with COVID-19. However, the presence of nucleic acid or antigen in semen is not synonyms of viral replication capacity and infectivity. It has been reported an increase in serum levels of LH in males with COVID-19 and a significant reduction in the T/LH and FSH/LH ratios, consistent with subclinical hypogonadism. CONCLUSIONS: The findings of recent reports related to the potential effects of COVID-19 infection on the male reproductive system are based on poorly designed, small sample size studies that provide inconclusive, contradictory results. Since there still exists a theoretical possibility of testicular damage and male infertilty as a result of the infection by COVID-19, males of reproductive age should be evaluated for gonadal function and semen analysis. With regard to the sexual transmission of the virus, there is not sufficient evidence to recommend asymptomatic couples to abstein from having sex in order to protect themselves from being infected by the virus. Additional studies are needed to understand the long-term effects of SARS-CoV-2 on male reproductive function, including male fertility potential and endocrine testicular function.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pandemias , Pneumonia Viral/complicações , Saúde Reprodutiva , Saúde Sexual , Adulto , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Hormônio Foliculoestimulante/sangue , Humanos , Hipogonadismo/sangue , Hipogonadismo/etiologia , Imunoglobulina G/análise , Leucócitos , Hormônio Luteinizante/sangue , Masculino , Orquite/etiologia , Orquite/virologia , Próstata/virologia , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sêmen/virologia , Preservação do Sêmen , Espanha , Testículo/imunologia , Testículo/patologia , Testículo/virologia , Testosterona/sangue , Vasculite/etiologia , Adulto Jovem
10.
DNA Cell Biol ; 39(8): 1458-1466, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32513025

RESUMO

Polycystic ovary syndrome (PCOS) is a multifactorial disorder characterized by irregular menstrual problems, hyperandrogenism, and presence of polycystic ovaries. Till date, molecular mechanism underlying PCOS remains elusive. Recently mitochondrial displacement loop (D-loop) variants have been identified to be novel players in the pathogenesis of PCOS. At present, rare variants, besides common variants, are also the focus of research as it is believed to make essential contribution to the risk of complex diseases. However, rare and low hetroplasmic variants in mitochondrial D-loop are still not investigated in PCOS women. Furthermore, variants in light-strand origin of DNA replication (OriL) of mitochondrial DNA (mtDNA) have not been explored in PCOS. Hence, in this study, we investigated rare to common mitochondrial D-loop and OriL region variants obtained using mtDNA next-generation sequencing in women with PCOS. Furthermore, we also assessed mtDNA copy number, a biomarker of mitochondrial dysfunction (MD) in women with PCOS, as the variants in mtDNA are known to be associated with low mtDNA copy number in PCOS women. A total of 67 D-loop variants including 6 novel variants were identified in 30 PCOS women. Among 67 variants, 29 variants were reported in PCOS women. A single variant, 5746A was found in OriL region in two PCOS women. Both transition and transversion variants were found but transition variants occur at very high frequency compared with transversions (82.35% vs. 17.64%, respectively). As transition variants in mtDNA are known to arise because of polymerase γ errors, occurrence of high transition rates indicates that most mutation arises because of defect in replication errors that causes mtDNA damage leading to MD. Furthermore, mtDNA copy number was found to be low in women with PCOS compared with healthy control women suggesting that MD may be the contributing factor in the pathogenesis of PCOS.


Assuntos
Variações do Número de Cópias de DNA/genética , DNA Mitocondrial/genética , Mitocôndrias/genética , Síndrome do Ovário Policístico/genética , Adolescente , Adulto , Replicação do DNA/genética , DNA Mitocondrial/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Mitocôndrias/patologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/patologia , Testosterona/sangue , Tireotropina/sangue , Adulto Jovem
11.
PLoS One ; 15(6): e0234131, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32502216

RESUMO

BACKGROUND: Low plasma testosterone, either spontaneous or as a result of androgen deprivation therapy for prostate cancer, is associated with an increased risk of cardiovascular events. The underlying mechanism in humans is not understood. Experimental studies in mice have shown that castration facilitates atherogenesis and may increase signs of plaque vulnerability. Pigs used for translational atherosclerosis research have frequently been castrated for practical or commercial reasons, but the effect of castration on atherosclerosis has never been systematically evaluated in pigs. OBJECTIVE: To study the effect of castration on atherosclerotic plaque burden and type in genetically modified minipigs with hypercholesterolemia. METHODS: Newborn male Yucatan minipigs with transgenic overexpression of a human gain-of-function mutant of proprotein convertase subtilisin/kexin type 9 were randomized to undergo orchiectomy (n = 8) or serve as controls (n = 6). Minipigs were started on high-fat diet at 3 months of age and the amount and composition of atherosclerotic lesions were analyzed at 12 months of age. Plasma lipid profiles and behavioral parameters were also assessed. RESULTS: Plasma lipids were slightly affected to a more atherogenic profile by orchiectomy, but atherosclerotic lesion size was unaltered in the LAD, thoracic aorta, abdominal aorta, and iliac arteries. The distribution of lesion types (xanthomas, pathological intimal thickening and fibroatheromas) were also not statistically different between groups in any of the examined vascular territories. The abdominal aorta developed the most advanced stages of disease with reproducible fibroatheroma formation, and here it was found that the area of necrotic core was significantly increased in orchiectomized pigs compared with controls. Orchiectomy also reduced aggressive behavior. CONCLUSIONS: Castration does not alter the burden of atherosclerosis in hypercholesterolemic Yucatan minipigs, but may increase necrotic core area in fibroatheromas.


Assuntos
Aterosclerose/patologia , Hipercolesterolemia/patologia , Animais , Animais Geneticamente Modificados , Aorta/patologia , Aterosclerose/complicações , Dieta Hiperlipídica , Modelos Animais de Doenças , Humanos , Hipercolesterolemia/complicações , Hipercolesterolemia/genética , Artéria Ilíaca/patologia , Lipídeos/sangue , Masculino , Necrose , Orquiectomia , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo , Suínos , Porco Miniatura , Testosterona/sangue
12.
Toxicol Appl Pharmacol ; 401: 115077, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32479917

RESUMO

Triclocarban (TCC) is an antimicrobial compound, widely used in personal care products, such as soaps, toothpaste, and shampoo. This agent is incompletely removed by wastewater treatment and represents an environmental contaminant. Studies show that TCC has been associated with some endocrine disruptions. In vitro, TCC demonstrated potent androgen-augmenting activity and aromatase inhibition. In this sense, exposure during critical periods of development (gestation and lactation) could lead to some adverse health outcomes in offspring. Therefore, the present study evaluated if maternal exposure to three different doses of TCC could interfere in the reproductive parameters of male offspring. Pregnant female Wistar rats were separated into four groups: vehicle Control (CTR); TCC 0.3 mg/kg (TCC 0.3); TCC 1.5 mg/kg (TCC 1.5); TCC 3.0 mg/kg (TCC 3.0). Dams were treated daily by oral gavage from gestational day 0 to lactational day 21. The males were evaluated in different timepoint: infancy (PND 21), puberty (PND 50) and adult life (PND 90-120). The histomorphometric analysis of testis and testosterone level were assessed on PND 21, 50, 120; sexual behavior and sperm parameters at adulthood. In the TCC 3.0 group, a decrease in the testis interstitial volume and an increase in testosterone levels were observed on PND 21. Moreover, there was a decrease in the diameter of the seminiferous tubules on PND 50, and a decrease in sexual competency in adulthood. These results suggest that exposure to a human relevant dose of TCC may interfere with reproduction and could have implications for human health.


Assuntos
Anti-Infecciosos Locais/toxicidade , Carbanilidas/toxicidade , Lactação/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Reprodução/efeitos dos fármacos , Comportamento Sexual Animal/efeitos dos fármacos , Fatores Etários , Animais , Feminino , Lactação/fisiologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/patologia , Ratos , Ratos Wistar , Reprodução/fisiologia , Comportamento Sexual Animal/fisiologia , Testículo/efeitos dos fármacos , Testículo/patologia , Testosterona/sangue
13.
Gene ; 754: 144850, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32505844

RESUMO

Obesity is associated with germ cell apoptosis, spermatogenesis arrest, and testicular endocrine suppression. The aim of the present study was to investigate the crosstalk between germ cell apoptosis and cell cycle machinery in sedentary and obese rats after moderate-intensity continuous (MICT), high-intensity continuous (HICT) and High-intensity interval (HIIT) exercise trainings. Male Wistar rats (n = 30) were randomly divided into 5 groups; the control, sedentary high-fat diet (HFD)-received (HFD-sole), MICT, HICT and HIIT-induced HFD-received groups. The serum levels of LDL-C, HDL-C, triglyceride, and testosterone, mRNA and protein levels of Cyclin D1, Cdk4, p21, apoptotic cell number/mm2 of testicular tissue and testicular DNA fragmentation ratio were investigated. The obese animals in HFD-sole group represented a significant (p < 0.05) reduction in serum HDL-C and testosterone levels, Cyclin D1, Cdk4 expressions, and exhibited a remarkable (p < 0.05) increment in LDL-C, triglyceride, p21 expression, apoptotic cell number and DNA fragmentation ratio versus control animals. However, the animals in MICT, HICT, HIIT groups exhibited a significant (p < 0.05) increment in serum HDL-C and testosterone, Cyclin D1 and Cdk4 expressions and showed a significant (p < 0.05) reduction in serum LDL-C and triglyceride, p21 expression, apoptotic cell number and DNA fragmentation versus the HFD-sole group. In conclusion, a crosslink between cell cycle machinery and apoptosis of germ cells was revealed in the testicles of HFD-sole animals, and MICT, HICT and HIIT could ameliorate the obesity-induced impairments, respectively. This effect may be attributed to the effect of exercise training protocols on maintaining Cyclin D1 and Cdk4 and suppressing p21 expression levels in the testicles.


Assuntos
Apoptose , Proteínas de Ciclo Celular/metabolismo , Dieta Hiperlipídica/efeitos adversos , Treinamento Intervalado de Alta Intensidade/métodos , Obesidade/terapia , Condicionamento Físico Animal/métodos , Testículo/metabolismo , Animais , Proteínas de Ciclo Celular/genética , Lipídeos/análise , Masculino , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/patologia , Ratos , Ratos Wistar , Testosterona/sangue
14.
Eur J Endocrinol ; 183(3): 343-355, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32508310

RESUMO

Objective: Retrospective studies suggest that women have more active brown adipose tissue (BAT) than men, but little is known of the effect of fluctuating sex steroids across the menstrual cycle on thermogenesis in women. Design: To characterise the effects of sex and sex steroids on BAT activity we recruited healthy weight men (n = 14) and women at two stages of the menstrual cycle (luteal, n = 9; follicular, n = 11). Methods: Infrared thermography measured supraclavicular temperature to index BAT thermogenesis in response to both cold (immersion of one hand in water at 15°C) and meal (Ensure, 10 kcal/kg body weight) stimuli. Results: Adaptive BAT temperature responses were greater (P < 0.05) in women than men, irrespective of stage of menstrual cycle. Whereas during cold exposure, the increase in BAT temperature was abrogated (P < 0.05) in women during follicular phase compared to men and women during luteal phase. Plasma concentrations of progesterone, 17ß-estradiol, testosterone and cortisol were measured. Regression analyses demonstrated that baseline BAT temperature was positively correlated (P < 0.05) with progesterone levels, but was inversely associated (P < 0.05) with cortisol concentration. Both cold- and meal-induced changes in BAT temperature mildly correlated (P = 0.07; P < 0.05) with 17ß-estradiol levels, but not with testosterone concentrations. Conclusions: Baseline supraclavicular temperature is elevated in women during the luteal phase of the menstrual cycle, which correlated with elevated progesterone concentrations. Women exhibited greater thermogenic responses than men, irrespective of the state of the menstrual cycle, which was associated with plasma levels of 17ß-estradiol. We conclude that sex steroids may regulate BAT thermogenesis in healthy adults.


Assuntos
Tecido Adiposo Marrom/fisiologia , Hormônios Esteroides Gonadais/fisiologia , Caracteres Sexuais , Termogênese/fisiologia , Adulto , Temperatura Corporal/fisiologia , Temperatura Baixa , Estradiol/sangue , Feminino , Fase Folicular/fisiologia , Humanos , Fase Luteal/fisiologia , Masculino , Refeições , Ciclo Menstrual/fisiologia , Estudos Retrospectivos , Testosterona/sangue , Adulto Jovem
15.
Tunis Med ; 98(2): 138-143, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32395803

RESUMO

AIM: To determine the prevalence and the risk factors of hypogonadism in men with chronic renal failure (CRF). METHODS: We conducted a cross sectional analysis in 48 men with CRF. Total testosterone, prolactin, and gonadotropins were measured in all patients. Hypogonadism was defined by a low level (<10 nmol/l) or a low normal level (10-14 nmol/l) of total testosterone. RESULTS: The mean age was 53.31±10.22 years. Renal impairment was mild, moderate, severe and at end stage in 9,14,4 and 21 patients, respectively. Nineteen patients had been undergoing extra-renal purification. The average of total testosterone was 13.44±6.17 nmol/L. It was lower in patients with diabetic nephropathy (p=0.004). Hypogonadism was diagnosed in 22 patients (46 %). In this group, gonadotropins were normal in 21 cases and elevated in only one case. Hyperprolactinemia was retained in six patients. Type 2 diabetes (OR: 3.96; p=0.02) and diabetic nephropathy (OR=4.26; p=0.01) were the only risk factors of hypogonadism in our patients. CONCLUSION: Our results had demonstrated a high prevalence of hypogonadism in males with chronic renal failure. This hormone disorder was associated with type 2 diabetes and diabetic nephropathy.


Assuntos
Hipogonadismo/epidemiologia , Hipogonadismo/etiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/epidemiologia , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Gonadotropinas/sangue , Humanos , Hipogonadismo/sangue , Hipogonadismo/diagnóstico , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Prolactina/sangue , Fatores de Risco , Testosterona/sangue
16.
Medicine (Baltimore) ; 99(18): e19934, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358364

RESUMO

The aim of the present study is to assess whether the preoperative clinical indicators have an impact on sperm retrieval rate (SRR) in men with idiopathic nonobstructive azoospermia (NOA).We retrospectively studied 241 consecutive men with NOA who underwent microdissection testicular sperm extraction from 2016 to 2019 in the Reproductive Medicine Center, including 154 patients diagnosed with idiopathic NOA. They were grouped according to preoperative indicators, including average testicular volume, follicle-stimulating hormone (FSH), luteinizing hormone, Testosterone (T), and pathology, respectively.The overall SRR was 20.0% (31/155). Men with testicular volume of ≤5 mL had significant higher SRR than men with testes 5 to 10 and ≥10 mL (35.6% vs 12.3%, P = .002; 35.6% vs 16.2, P = .049, respectively). The SRR in men with FSH ≥ 24.8 mIU/mL was significant higher, compared with FSH level of 12.4 to 24.8 mIU/mL (32.6% vs 15.8%, P = .033). Men with Sertoli cell-only had significantly lower SRR than other pathological type (8.1%). Men with an FSH ≥ 24.8 mIU/mL in testicular volume ≤5 mL group had a significantly higher SRR than FSH level of 12.4 to 24.8 mIU/mL in testicular volume of ≤5 to 10 mL group (44.0% vs 11.4%, P = .002). Men with a luteinizing hormone level of 8.6 to 17.2 mIU/mL in testicular volume of 5 to 10 mL group had a poor prognosis, with an SRR of only 6.5%.Severely reduced testicular volume (≤5 mL) and severely increased FSH level (≥24.8 mIU/mL) had the better sperm retrieval outcome, which can be used as independent predictors in men with idiopathic NOA. And a combination of testicular volume and the hormone seemed to be useful in further increase predictive value.


Assuntos
Azoospermia/fisiopatologia , Microdissecção/estatística & dados numéricos , Recuperação Espermática/estatística & dados numéricos , Testículo/fisiopatologia , Adulto , Azoospermia/sangue , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Microdissecção/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Testosterona/sangue , Adulto Jovem
17.
Toxicology ; 441: 152504, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32445656

RESUMO

Manganese (Mn) is essential for animal development and homeostasis. However, anthropogenic activities increase the concentration of Mn in the environment and lead to increased risk of exposure to high doses of the metal. Thus, this study aimed to evaluate the effect of high doses of Mn on the male reproductive system of swiss mice. The 22-day old mice were randomly sorted into four groups and exposed to 0 (control), 15, 30 and 60 mg of MnCl2/kg/day, via daily gavages for 45 days. After the exposure, the mice were euthanized and sperm, hormonal and oxidative stress endpoints were evaluated in the testis, seminal vesicle and hypothalamus. Exposure to Mn promoted weight reduction of androgen-dependent organs, as well as alteration of the levels of fecal androgenic metabolites. Sperm parameters were drastically affected in all treated groups and the antioxidants tested (catalase and glutathione-disulfide reductase activities, and non-protein thiols content) decreased in the testis. However, only a few endpoints were altered in the seminal vesicle. For the hypothalamus, there was a reduction in acetylcholinesterase activity, suggesting a neurotoxic potential of Mn. In conclusion, Mn may affect the hypothalamic-gonadal axis by impairing the development of androgen-dependent organs, testicular redox status and Leydig cell maturation.


Assuntos
Genitália Masculina/efeitos dos fármacos , Manganês/toxicidade , Reprodução/efeitos dos fármacos , Androgênios/análise , Animais , Fezes/química , Genitália Masculina/metabolismo , Células Intersticiais do Testículo/efeitos dos fármacos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Motilidade Espermática/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Testosterona/sangue
19.
Int J Sports Med ; 41(10): 646-651, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32455452

RESUMO

We aimed to determine whether basal concentrations of testosterone, cortisol or the ratio testosterone/cortisol were related to sweat Na+ loss, sweat Na+ concentration ([Na+]) and sweat rate during exercise. Twenty-two female elite soccer players participated in the study. Testosterone and cortisol were measured in blood samples before exercise. Sweat samples were collected during a training session (~20°C, ~30% RH, and ~0.55 m/s of wind speed) to measure sweat [Na+]. Sweat rate was determined by considering the difference between post-and pre-body weight, along with the amount of liquid consumed. During exercise, sweat Na+ loss (0.33[0.19] g/h) and sweat rate (0.49[0.20] L/h) were related to basal testosterone concentration (1.4[0.4] pg/mL) (r=0.54; r=0.55, respectively; p<0.05), but not with basal cortisol concentration (119.2[24.2] ng/mL) nor testosterone/cortisol ratio (0.012[0.003]) (p>0.05). However, when Na+ loss was adjusted to sweat rate, no association was found between Na+ loss and testosterone (p>0.05). In addition, no differences were found between players with high vs. low Na+ loss adjusted to sweat loss in menstrual phase or intensity during exercise (p>0.05). In conclusion, these results suggest that in these specific environmental conditions, basal levels of testosterone might increase sweat rate and therefore, the amount of Na+ lost during exercise in elite women soccer players.


Assuntos
Metabolismo Basal , Hidrocortisona/sangue , Futebol/fisiologia , Sódio/metabolismo , Sudorese/fisiologia , Testosterona/sangue , Adulto , Índice de Massa Corporal , Peso Corporal , Feminino , Humanos , Ciclo Menstrual/fisiologia , Equilíbrio Hidroeletrolítico , Adulto Jovem
20.
N Engl J Med ; 382(23): 2187-2196, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32469183

RESUMO

BACKGROUND: Injectable luteinizing hormone-releasing hormone agonists (e.g., leuprolide) are the standard agents for achieving androgen deprivation for prostate cancer despite the initial testosterone surge and delay in therapeutic effect. The efficacy and safety of relugolix, an oral gonadotropin-releasing hormone antagonist, as compared with those of leuprolide are not known. METHODS: In this phase 3 trial, we randomly assigned patients with advanced prostate cancer, in a 2:1 ratio, to receive relugolix (120 mg orally once daily) or leuprolide (injections every 3 months) for 48 weeks. The primary end point was sustained testosterone suppression to castrate levels (<50 ng per deciliter) through 48 weeks. Secondary end points included noninferiority with respect to the primary end point, castrate levels of testosterone on day 4, and profound castrate levels (<20 ng per deciliter) on day 15. Testosterone recovery was evaluated in a subgroup of patients. RESULTS: A total of 622 patients received relugolix and 308 received leuprolide. Of men who received relugolix, 96.7% (95% confidence interval [CI], 94.9 to 97.9) maintained castration through 48 weeks, as compared with 88.8% (95% CI, 84.6 to 91.8) of men receiving leuprolide. The difference of 7.9 percentage points (95% CI, 4.1 to 11.8) showed noninferiority and superiority of relugolix (P<0.001 for superiority). All other key secondary end points showed superiority of relugolix over leuprolide (P<0.001). The percentage of patients with castrate levels of testosterone on day 4 was 56.0% with relugolix and 0% with leuprolide. In the subgroup of 184 patients followed for testosterone recovery, the mean testosterone levels 90 days after treatment discontinuation were 288.4 ng per deciliter in the relugolix group and 58.6 ng per deciliter in the leuprolide group. Among all the patients, the incidence of major adverse cardiovascular events was 2.9% in the relugolix group and 6.2% in the leuprolide group (hazard ratio, 0.46; 95% CI, 0.24 to 0.88). CONCLUSIONS: In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events. (Funded by Myovant Sciences; HERO ClinicalTrials.gov number, NCT03085095.).


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Leuprolida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Pirimidinonas/uso terapêutico , Testosterona/sangue , Adenocarcinoma/sangue , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Injeções Subcutâneas , Leuprolida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/efeitos adversos , Neoplasias da Próstata/sangue , Pirimidinonas/efeitos adversos
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