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1.
PeerJ ; 11: e14770, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36721778

RESUMO

Background: Hypoxic and cold environments have been shown to improve the function and performance of athletes. However, it is unclear whether the combination of subalpine conditions and cold temperatures may have a greater effect. The present study aims to investigate the effects of 6 weeks of training in a sub-plateau cold environment on the physical function and athletic ability of elite parallel giant slalom snowboard athletes. Methods: Nine elite athletes (four males and five females) participated in the study. The athletes underwent 6 weeks of high intensity ski-specific technical training (150 min/session, six times/week) and medium-intensity physical training (120 min/session, six times/week) prior to the Beijing 2021 Winter Olympic Games test competition. The physiological and biochemical parameters were collected from elbow venous blood samples after each 2-week session to assess the athletes' physical functional status. The athletes' athletic ability was evaluated by measuring their maximal oxygen uptake, Wingate 30 s anaerobic capacity, 30 m sprint run, and race performance. Measurements were taken before and after participating in the training program for six weeks. The repeated measure ANOVA was used to test the overall differences of blood physiological and biochemical indicators. For indicators with significant time main effects, post-hoc tests were conducted using the least significant difference (LSD) method. The paired-samples t-test was used to analyze changes in athletic ability indicators before and after training. Results: (1) There was a significant overall time effect for red blood cells (RBC) and white blood cells (WBC) in males; there was also a significant effect on the percentage of lymphocytes (LY%), serum testosterone (T), and testosterone to cortisol ratio (T/C) in females (p < 0.001 - 0.015, η p 2 = 0 . 81 - 0 . 99 ). In addition, a significant time effect was also found for blood urea(BU), serum creatine kinase (CK), and serum cortisol levels in both male and female athletes (p = 0.001 - 0.029, η p 2 = 0 . 52 - 0 . 95 ). (2) BU and CK levels in males and LY% in females were all significantly higher at week 6 (p = 0.001 - 0.038), while WBC in males was significantly lower (p = 0.030). T and T/C were significantly lower in females at week 2 compared to pre-training (p = 0.007, 0.008, respectively), while cortisol (C) was significantly higher in males and females at weeks 2 and 4 (p (male) = 0.015, 0.004, respectively; p (female) = 0.024, 0.030, respectively). (3) There was a noticeable increase in relative maximal oxygen uptake, Wingate 30 s relative average anaerobic power, 30 m sprint run performance, and race performance in comparison to the pre-training measurements (p < 0.001 - 0.027). Conclusions: Six weeks of sub-plateau cold environment training may improve physical functioning and promote aerobic and anaerobic capacity for parallel giant slalom snowboard athletes. Furthermore, male athletes had a greater improvement of physical functioning and athletic ability when trained in sub-plateau cold environments.


Assuntos
Desempenho Atlético , Temperatura Baixa , Condicionamento Físico Humano , Feminino , Humanos , Masculino , Atletas , Hidrocortisona , Oxigênio , Esportes , Testosterona , Esportes na Neve
2.
Biol Res ; 56(1): 2, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36653814

RESUMO

BACKGROUND: The testes are highly susceptible to the adverse effects of chemotherapy and radiation at all stages of life. Exposure to these threats mainly occurs during cancer treatment and as an occupational hazard in radiation centers. The present study investigated the regenerative ability of adipose-derived mesenchymal stem cells (ADMSCs) against the adverse effects of cisplatin on the structure and function of the testes. METHODS: New Zealand white rabbits (N = 15) were divided into three groups of five: a negative control group (no treatment), a cisplatin group (single dose of cisplatin into each testis followed three days later by a PBS injection), and a cisplatin + ADMSCs group (cisplatin injection followed three days later by an ADMSC injection). On day 45 post-treatment, serum testosterone levels were evaluated, and the testes and epididymis were collected for histology, oxidative stress examination, and epididymal sperm analysis. RESULTS: Cisplatin caused damage to the testicular tissue and decreased serum testosterone levels, epididymal sperm counts, and oxidants. An antioxidant imbalance was detected due to increasing malondialdehyde (MDA) and reduced glutathione (GSH) levels in testicular tissue. The ADMSC-treated group displayed a moderate epididymal sperm count, adequate antioxidant protection, suitable hormone levels, and enhanced testicular tissue morphology. CONCLUSIONS: ADMSCs treatment repaired damaged testicular tissue, enhanced biochemical parameters, and modified pathological changes caused by cisplatin.


Assuntos
Azoospermia , Células-Tronco Mesenquimais , Masculino , Animais , Coelhos , Humanos , Testículo/metabolismo , Cisplatino/efeitos adversos , Antioxidantes/farmacologia , Azoospermia/induzido quimicamente , Azoospermia/metabolismo , Azoospermia/patologia , Sêmen , Espermatozoides/metabolismo , Espermatozoides/patologia , Estresse Oxidativo , Testosterona/farmacologia
3.
Iran J Med Sci ; 48(1): 77-84, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36688188

RESUMO

Background: Azoospermia is a risk factor for infertility affecting approximately 1% of the male population. Genetic factors are associated with non-obstructive azoospermia (NOA). Pygo2 and PRDM9 genes are involved in the spermatogenesis process. The present study aimed to assess the association of single nucleotide polymorphism (SNP) in the Pygo2 (rs61758740 and rs61758741) and PRDM9 (rs2973631 and rs1874165) genes with idiopathic azoospermia (IA). Methods: A cross-sectional study was conducted from October 2018 to August 2019 at Rooya Infertility Centre (Qom, Iran). A total of 100 infertile patients with NOA and 100 men with normal fertility were enrolled in the study. Tetra-primer amplification refractory mutation system-PCR method was used to detect SNPs rs61758740, rs61758741, and rs2973631. The restriction fragment length polymorphism method was used for SNP rs1874165. In addition, luteinizing, follicle-stimulating, and testosterone hormone levels were measured. Results: The results showed a significant increase in luteinizing and follicle-stimulating hormone levels in the patient group (P<0.001), but a non-significant difference in testosterone levels in both groups. SNP rs61758740 (T>C) was associated with the increased risk of azoospermia (OR: 2.359, 95% Cl: 1.192-4.666, P=0.012). SNP rs2973631 showed a significant difference in genotype frequency between the patient and control groups in the dominant, recessive, and codominant models. However, in the case of SNP rs1874165, the difference was significant in the dominant, codominant, and overdominant models. Conclusion: There is an association between azoospermia and SNPs in Pygo2 and PRDM9 genes in Iranian infertile male patients with IA. SNPs can be considered a risk factor for male infertility. It should be noted that this article was published in preprint form on the website of europepmc (https://europepmc.org/article/ppr/ppr416800).


Assuntos
Azoospermia , Humanos , Masculino , Azoospermia/epidemiologia , Azoospermia/genética , Irã (Geográfico)/epidemiologia , Polimorfismo de Nucleotídeo Único/genética , Estudos Transversais , Testosterona , Peptídeos e Proteínas de Sinalização Intracelular/genética , Histona-Lisina N-Metiltransferase/genética
4.
Reprod Biol Endocrinol ; 21(1): 10, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36703143

RESUMO

BACKGROUND: Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce gastrointestinal side effects. OBJECTIVE: Inositols have long been debated as a potential alternative for metformin in treating PCOS. Therefore, the present systematic review aimed to evaluate the efficacy and safety of inositols in treating PCOS. METHODS: The present systematic search was performed in CENTRAL, MEDLINE, and Embase from the inception until October 20th, 2021. Eligible randomized controlled trials (RCTs) included women diagnosed with PCOS and compared any inositols with metformin or placebo. Our primary outcome was cycle normalization, whereas secondary outcomes were body mass index (BMI), parameters of carbohydrate metabolism and clinical and laboratory hyperandrogenism. Results are reported as risk ratios or mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: Twenty-six RCTs were identified, including data of 1691 patients (806 inositol, 311 with placebo, and 509 metformin groups). In patients treated with inositols, the risk (CI: 1.13; 2.85) of having a regular menstrual cycle was found by 1.79 higher than in the case of placebo. Moreover, the inositols showed non-inferiority compared to metformin in this outcome. In the case of BMI (MD = -0.45; CI: -0.89; -0.02), free testosterone (MD = -0,41, CI: -0.69; -0.13), total testosterone (MD = -20.39, CI: -40.12; -0.66), androstenedione (MD = -0.69, CI: -1,16; -0.22), glucose (MD = -3.14; CI: -5.75; -0.54) levels and AUC insulin (MD = -2081.05, CI: -2745.32; -1416.78) inositol treatment induced greater decrease compared to placebo. Inositol increased sex-hormone-binding globulin significantly compared to placebo (MD = 32.06, CI:1.27; 62.85). CONCLUSION: Inositol is an effective and safe treatment in PCOS. Moreover, inositols showed non-inferiority in most outcomes compared to the gold standard treatment; metformin. TRIAL REGISTRATION: PROSPERO registration number: CRD42021283275.


Assuntos
Insulinas , Metformina , Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/complicações , Inositol/uso terapêutico , Hipoglicemiantes/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Metformina/efeitos adversos , Testosterona/efeitos adversos , Insulinas/uso terapêutico
5.
Talanta ; 255: 124218, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36603442

RESUMO

Anti-doping rule violations related to the abuse of endogenous anabolic androgenic steroids can be currently discovered by the urinary steroidal module of Athlete Biological Passport. Since this powerful tool is still subjected to some limitations due to various confounding factors altering the steroid profile, alternative strategies have been constantly proposed. Among these, the measurement of blood concentrations of endogenous steroid hormones by LC-MS is currently of increasing interest in anti-doping, bringing significant advantages for the detection of testosterone abuse in females and in individuals with deletion of UGT2B17 enzyme. Although various research groups have made significant efforts in method development, there is currently no accepted or harmonized anti-doping method for quantitative analysis of the various testosterone doping markers in blood. In this study we present a UHPLC-MS/MS method for the quantification of major circulating steroid hormones together with an extended panel of glucuro- and sulpho-conjugated phase II metabolites of androgens. Chromatographic setup was optimized by comparing the performance of three different C18 stationary phases and by the careful selection of mobile phases with the aim of separating all the target steroids, including numerous isomeric/isobaric compounds. MS parameters were fine-tuned to obtain the sensitivity needed for measuring the target analytes, that show specific serum concentrations ranging from low pg/mL for less abundant compounds to µg/mL for sulpho-conjugated steroids. Finally, sample preparation protocol was developed for the extraction of steroid hormones from 200 µL of serum and the performance was evaluated in terms of extraction recovery and matrix effect. The final method was then applied to authentic serum samples collected from healthy volunteers (40 males and 40 females) at the Blood Bank of the City of Health and Science University Hospital of Turin. The analysis of these samples allowed to obtain results on serum concentrations of the targeted steroids, with particular emphasis on previously undiscovered phase II metabolites, such as the isomers of 5-androstane-3,17-diol glucuronide. This preliminary application also enabled measuring dihydrotestosterone sulphate in male samples, efficiently separating this analyte from its isomer, epiandrosterone sulphate, which circulates in blood at high concentrations. The promising results of this study are encouraging for the measurement of blood steroid profile markers in serum and plasma samples for Athlete Biological Passport purposes.


Assuntos
Doping nos Esportes , Espectrometria de Massas em Tandem , Feminino , Humanos , Masculino , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Esteroides , Testosterona , Androgênios , Detecção do Abuso de Substâncias/métodos
6.
PLoS Med ; 20(1): e1003988, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36595504

RESUMO

BACKGROUND: Prostate cancer (PrCa) is the second most prevalent malignancy in men worldwide. Observational studies have linked the use of low-density lipoprotein cholesterol (LDL-c) lowering therapies with reduced risk of PrCa, which may potentially be attributable to confounding factors. In this study, we performed a drug target Mendelian randomisation (MR) analysis to evaluate the association of genetically proxied inhibition of LDL-c-lowering drug targets on risk of PrCa. METHODS AND FINDINGS: Single-nucleotide polymorphisms (SNPs) associated with LDL-c (P < 5 × 10-8) from the Global Lipids Genetics Consortium genome-wide association study (GWAS) (N = 1,320,016) and located in and around the HMGCR, NPC1L1, and PCSK9 genes were used to proxy the therapeutic inhibition of these targets. Summary-level data regarding the risk of total, advanced, and early-onset PrCa were obtained from the PRACTICAL consortium. Validation analyses were performed using genetic instruments from an LDL-c GWAS conducted on male UK Biobank participants of European ancestry (N = 201,678), as well as instruments selected based on liver-derived gene expression and circulation plasma levels of targets. We also investigated whether putative mediators may play a role in findings for traits previously implicated in PrCa risk (i.e., lipoprotein a (Lp(a)), body mass index (BMI), and testosterone). Applying two-sample MR using the inverse-variance weighted approach provided strong evidence supporting an effect of genetically proxied inhibition of PCSK9 (equivalent to a standard deviation (SD) reduction in LDL-c) on lower risk of total PrCa (odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.76 to 0.96, P = 9.15 × 10-3) and early-onset PrCa (OR = 0.70, 95% CI = 0.52 to 0.95, P = 0.023). Genetically proxied HMGCR inhibition provided a similar central effect estimate on PrCa risk, although with a wider 95% CI (OR = 0.83, 95% CI = 0.62 to 1.13, P = 0.244), whereas genetically proxied NPC1L1 inhibition had an effect on higher PrCa risk with a 95% CI that likewise included the null (OR = 1.34, 95% CI = 0.87 to 2.04, P = 0.180). Analyses using male-stratified instruments provided consistent results. Secondary MR analyses supported a genetically proxied effect of liver-specific PCSK9 expression (OR = 0.90 per SD reduction in PCSK9 expression, 95% CI = 0.86 to 0.95, P = 5.50 × 10-5) and circulating plasma levels of PCSK9 (OR = 0.93 per SD reduction in PCSK9 protein levels, 95% CI = 0.87 to 0.997, P = 0.04) on PrCa risk. Colocalization analyses identified strong evidence (posterior probability (PPA) = 81.3%) of a shared genetic variant (rs553741) between liver-derived PCSK9 expression and PrCa risk, whereas weak evidence was found for HMGCR (PPA = 0.33%) and NPC1L1 expression (PPA = 0.38%). Moreover, genetically proxied PCSK9 inhibition was strongly associated with Lp(a) levels (Beta = -0.08, 95% CI = -0.12 to -0.05, P = 1.00 × 10-5), but not BMI or testosterone, indicating a possible role for Lp(a) in the biological mechanism underlying the association between PCSK9 and PrCa. Notably, we emphasise that our estimates are based on a lifelong exposure that makes direct comparisons with trial results challenging. CONCLUSIONS: Our study supports a strong association between genetically proxied inhibition of PCSK9 and a lower risk of total and early-onset PrCa, potentially through an alternative mechanism other than the on-target effect on LDL-c. Further evidence from clinical studies is needed to confirm this finding as well as the putative mediatory role of Lp(a).


Assuntos
Pró-Proteína Convertase 9 , Neoplasias da Próstata , Humanos , Masculino , Pró-Proteína Convertase 9/genética , Estudo de Associação Genômica Ampla , LDL-Colesterol , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Testosterona , Análise da Randomização Mendeliana
7.
BMJ Case Rep ; 16(1)2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36693705

RESUMO

With an increasing number of patients seeking gender-affirming hormone therapy (GAHT), the clinical impact of testosterone treatments on headache needs to be determined. Our case report looks at the potential effect of testosterone on migraine among transgender patients. We present two transmasculine patients who used masculinising hormone therapy with testosterone. Both patients described their headache as moderate-to-severe pain with features that fulfilled the criteria for chronic migraine without aura. Following GAHT, one patient improved in both frequency and intensity of headache symptoms while the other noted improvement in headache intensity alone. Our report postulates that testosterone therapy may have a positive impact on headaches in individuals participating in GAHT, highlighting the need for further research on the role of testosterone therapy on headache in transmasculine individuals.


Assuntos
Epilepsia , Transtornos de Enxaqueca , Pessoas Transgênero , Humanos , Testosterona/efeitos adversos , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/diagnóstico , Cefaleia/tratamento farmacológico , Epilepsia/tratamento farmacológico
8.
Sci Rep ; 13(1): 380, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36611054

RESUMO

To determine association paths between prenatal androgens and cord blood androgens. The concentrations of T, FT, DHT, DHEA and SHBG in prenatal venous blood and cord blood were measured in 342 pregnant women and their neonates. The association paths between these hormones in prenatal and cord blood were revealed using Pearson correlation, multiple linear regression and path analysis. CB-T, CB-FT and CB-DHT in male neonates were higher than those in female neonates. In male and female neonates, P-FT was lower than CB-FT; however, P-DHT and P-SHBG were higher than CB-DHT and CB-SHBG, respectively. P-DHEA was lower than CB-DHEA in female newborns. In male neonates, there were association paths of P-T → CB-T → CB-FT → CB-DHT, P-T → CB-FT → CB-DHT, P-T → P-FT → CB-FT → CB-DHT, P-T → P-DHT, CB-DHEA → CB-DHT, CB-DHEA → P-DHT, and CB-DHEA → P-DHEA. In female neonates, there were association paths of P-T → CB-T → CB-FT → CB-DHT, P-T → P-FT → CB-FT → CB-DHT, P-T → P-FT → P-DHT, P-T → P-DHT, P-DHEA → P-DHT, CB-DHEA → P-DHEA, and CB-DHEA → CB-FT. There were differences in the T, FT and DHT concentrations in cord blood between male and female neonates and in the FT, DHT, DHEA, and SHBG concentrations between prenatal and cord blood. P-T and P-FT concentrations were positively associated with CB-T and CB-FT concentrations, while CB-DHEA concentration was positively associated with P-DHEA concentration.


Assuntos
Androgênios , Testosterona , Feminino , Masculino , Recém-Nascido , Humanos , Gravidez , Desidroepiandrosterona , Sangue Fetal
9.
In Vivo ; 37(1): 410-416, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36593059

RESUMO

BACKGROUND/AIM: Single-agent tyrosine kinase inhibitors are still prescribed as first-line treatment to a relevant subgroup of patients with metastatic renal cell carcinoma (mRCC). These agents are known to cause disfunction of many endocrine glands (e.g., thyroid). In this two-step trial, we aimed to assess gonadal function among male patients with mRCC treated with sunitinib. PATIENTS AND METHODS: We enrolled a first cross-sectional cohort of pre-treated (>6 months) patients and a subsequent cohort of treatment-naïve patients who were prospectively followed-up. All patients were screened for hypogonadism and received a Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire at study entry and after 6 months of therapy. Patients who were candidates for testosterone replacement therapy (TRT) also received a FACT-G questionnaire at baseline and 3 months after supplementation. RESULTS: Among the 30 enrolled patients, the prevalence of hypogonadism was found to be higher in those receiving sunitinib for a longer period (27.3% at baseline, 41.7% in the first 6 months, and 68.4% after 9 months of therapy). The testosterone level of patients correlated with quality of life (R=0.32). A total of six patients received TRT, with a significant improvement in their global quality of life after the first 3 months of treatment. CONCLUSION: An increasing prevalence of hypogonadism was seen among male patients who received long-term treatment with sunitinib. TRT was associated with relevant improvements in quality of life. These findings corroborate similar published observations and encourage the assessment of gonadal function in male patients with mRCC under treatment with sunitinib.


Assuntos
Carcinoma de Células Renais , Gônadas , Neoplasias Renais , Sunitinibe , Humanos , Masculino , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Estudos Transversais , Gônadas/efeitos dos fármacos , Gônadas/fisiopatologia , Hipogonadismo/epidemiologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Qualidade de Vida , Sunitinibe/efeitos adversos , Testosterona/análise
10.
Cardiovasc Diabetol ; 22(1): 3, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624450

RESUMO

BACKGROUND: Low-density lipoprotein (LDL)-cholesterol is positively associated with cardiovascular disease (CVD) and inversely associated with type 2 diabetes, which could detract from lipid modification. Here, we examined whether lipid traits potentially relevant to CVD aetiology, i.e. apolipoprotein B (apoB), triglycerides (TG) and lipoprotein(a) [Lp(a)] exhibited the same associations. We investigated sex-specifically, including the role of sex hormones, because sex disparities exist in lipid profile and type 2 diabetes. We also replicated where possible. METHODS: We used Mendelian randomization (MR) to examine sex-specific associations of apoB, TG and Lp(a) with type 2 diabetes, HbA1c, fasting insulin, fasting glucose, testosterone and estradiol in the largest relevant sex-specific genome-wide association studies (GWAS) in people of European ancestry and replicated where possible. We also assessed sex-specific associations of liability to type 2 diabetes with apoB, TG and Lp(a). RESULTS: Genetically predicted apoB and Lp(a) had little association with type 2 diabetes or glycemic traits in women or men. Genetically predicted higher TG was associated with higher type 2 diabetes risk [odds ratio (OR) 1.44 per standard deviation (SD), 95% confidence interval (CI) 1.26 to 1.65], HbA1c and fasting insulin specifically in women. Higher TG was associated with lower testosterone in women and higher testosterone in men, but with lower estradiol in men and women. Genetic liability to type 2 diabetes was associated with higher TG in women, and possibly with lower apoB in men. CONCLUSIONS: Lipid traits potentially relevant to CVD aetiology do not exhibit contrasting associations with CVD and type 2 diabetes. However, higher TG is associated with higher type 2 diabetes risk and glycemic traits, which in turn further increases TG specifically in women, possibly driven by sex hormones.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Masculino , Humanos , Feminino , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Triglicerídeos , Apolipoproteínas B , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Insulina , Hormônios Esteroides Gonadais , Testosterona , Estradiol , Fatores de Risco
11.
Dev Cogn Neurosci ; 59: 101194, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36634500

RESUMO

Changes in gonadal hormones during puberty are thought to potentiate adolescents' social re-orientation away from caregivers and towards peers. This study investigated the effect of testosterone on neural processing of emotional (vocal) stimuli by unfamiliar peers vs. parents, in transgender boys receiving exogenous testosterone as a gender-affirming hormone (GAH+) or not (GAH-). During fMRI, youth heard angry and happy vocal expressions spoken by their caregiver and an unfamiliar teenager. Youth also self-reported on closeness with friends and parents. Whole-brain analyses (controlling for age) revealed that GAH+ youth showed blunted neural response to caregivers' angry voices-and heightened response to unfamiliar teenage angry voices-in the anterior cingulate cortex. This pattern was reversed in GAH- youth, who also showed greater response to happy unfamiliar teenager vs. happy caregiver voices in this region. Blunted ACC response to angry caregiver voices-a pattern characteristic of GAH+ youth-was associated with greater relative closeness with friends over parents, which could index more "advanced" social re-orientation. Consistent with models of adolescent neurodevelopment, increases in testosterone during adolescence may shift the valuation of caregiver vs. peer emotional cues in a brain region associated with processing affective information.


Assuntos
Pessoas Transgênero , Voz , Masculino , Humanos , Adolescente , Cuidadores , Testosterona , Emoções/fisiologia , Ira/fisiologia
12.
J Obstet Gynaecol ; 43(1): 2163625, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36689253

RESUMO

Total testosterone (TT), sex hormone-binding globulin (SHBG), dehydroepiandrosterone (DHEA) levels, and cervical length (CL) were investigated in pregnant Egyptian women with polycystic ovary syndrome (PCOS, n = 38), history of miscarriages (RM, n = 40) and without the conditions (HC, n = 40). At week 8, the RM had lower levels of TT (p = 0.000) and free androgen index (FAI) (p = 0.000) and higher SHBG (p = 0.000) and DHEA (p < 0.05) than the PCOS. Compared with the HC, they had elevated SHBG (p < 0.05) and DHEA (p = 0.001) and reduced CL (p = 0.000). TT (p = 0.001) and FAI (p = 0.000) were higher and SHBG (p = 0.000) and CL (p = 0.001) lower in the PCOS than in the HC group. At week 16, TT (p = 0.000) and FAI (p = 0.000) were higher, and SHBG (p = 0.000) and CL (p < 0.05) lower in PCOS than in RM and HC. The PCOS had elevated FAI than the RM (p = 0.000) and HC (p = 0.001) at week 20. The DHEA, SHBG and CL abnormalities in PCOS and RM may compromise pregnancy outcomes.IMPACT STATEMENTWhat is already known on this subject? Hyperandrogenaemia, low sex hormone-binding globulin (SHBG), shortened cervical length (CL) and polycystic ovary syndrome (PCOS) are the most cited risk factors for recurrent miscarriages (RM). However, the published data are inconsistent, perhaps because of the confounding effects of ethnicity and nutritional milieu.What do the results of this study add? The study's findings comprising ethnically and socially homogenous women demonstrate that PCOS and RM are characterised by elevated dehydroepiandrosterone (DHEA) and shortened CL, and PCOS by reduced SHBG. These abnormalities would be expected to have an adverse impact on pregnancy outcomes.What are the implications of these findings for clinical practice and/or further research? Twenty-weeks DHEA and CL values have the potential to predict outcome risk in women with a history of RM and PCOS. Further research on other population groups is required to validate the current study's findings.


Assuntos
Aborto Habitual , Síndrome do Ovário Policístico , Gravidez , Feminino , Humanos , Testosterona , Síndrome do Ovário Policístico/epidemiologia , Globulina de Ligação a Hormônio Sexual , Egito , Desidroepiandrosterona
13.
Theriogenology ; 198: 211-216, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36610370

RESUMO

The domestic cat is a highly prolific species; thus, reproductive control is crucial to reducing feral cat overpopulation. This study aimed to assess the effect of a commercially-available GnRH vaccine for swine on suppressing sperm production in male cats. Twelve sexually mature tomcats were randomly divided into two groups. Treated cats (n = 9) received a GnRH vaccine (Improvac, Zoetis Belgium SA, 0.5 mL sc) twice 4 wk apart, and the control group (CON, n = 3) saline solution (0.5 mL sc). Reproductive parameters and blood samples were recorded every 2 wk, from 6 wk before vaccination until 24 wk after the first dose. Day 0 of the study was defined as the day of primary immunization with either the vaccine or saline solution. Serum testosterone concentrations of treated cats dropped to basal levels 6 wk after D0, while CON cats maintained serum testosterone concentrations between normal ranges during the study period. No differences were observed in pretreatment and CON seminal samples. However, a progressive decrease in seminal quality was observed in treated cats from wk 8 until the end of the study. By wk 24, sperm concentration and total sperm count decreased by 90%, motility decreased by 70%, and viability decreased by 60%. Moreover, testicular volume was reduced by 49%, and penile spines showed almost complete atrophy by the end of the study. Although treated cats showed a decrease in the hematocrit, erythrocyte count, and hemoglobin concentration, values were within the reference range for domestic cats. No differences were observed in the other hematological and biochemical parameters evaluated. Our results agree with previous immunocontraception studies in cats, showing that Improvac vaccination effectively reduced sperm quality, testicular volume, and serum testosterone concentration. Further studies should be carried out to define the Improvac long-term effect.


Assuntos
Anticoncepção Imunológica , Vacinas , Gatos , Masculino , Suínos , Animais , Hormônio Liberador de Gonadotropina , Testículo , Anticoncepção Imunológica/veterinária , Solução Salina , Sêmen , Testosterona
14.
Toxicol Appl Pharmacol ; 460: 116374, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36634874

RESUMO

The prevalence of autoimmune diseases has increased worldwide, including in men of reproductive age. Cyclosporine A (CsA) is an immunosuppressive drug commonly used for long periods in the prophylaxis and treatment of autoimmune dysfunction and transplant rejection. Owing to CsA toxicity, most clinical settings use lower CsA doses. Therefore, we evaluated whether a low dose (10 mg/kg) of CsA affects sperm parameters (daily sperm production, motility, morphology, mitochondrial activity, and acrosomal integrity), plasma testosterone levels, and fertility after short-term (10 days) and long-term (50 days) treatments in mice. Short-term CsA treatment partially affected sperm parameters and fertility, as shown by the reduction in sperm hyperactivation and gestational rate 10 days after the interruption of short-term CsA treatment. Long-term CsA treatment impairs sperm count, hyperactivated motility, and acrosomal integrity. This treatment regimen further decreased plasma testosterone concentrations but did not affect reproductive outcomes in mating trials. These outcomes were reversed 50 days after the interruption of long-term CsA treatment. We conclude that a low CsA dose differentially impairs sperm parameters and testicular steroidogenesis in a time-dependent and mostly reversible manner but does not affect male fertility.


Assuntos
Ciclosporina , Testosterona , Masculino , Camundongos , Animais , Sêmen , Espermatozoides , Testículo , Motilidade Espermática , Contagem de Espermatozoides
15.
Theriogenology ; 198: 356-360, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36640740

RESUMO

Prostatic hyperplasia (PH) is an androgen-dependent condition associated with increased prostatic size that is common in intact dogs, and similar to the condition in men. In dogs, the increase in prostatic size is most prominent the first years, and after approximately four years (in beagles), a plateau is reached, and further growth is slower. Why the prostate continues to grow more in some individuals is not clear. Most testosterone in the circulation is bound to albumin or sex hormone binding globulin (SHBG) and only a minor part is unbound and biologically active. The binding to SHBG has higher affinity than that to albumin. In addition, SHBG has own biological functions, modifying testosterone action. The aim of the present study was to investigate if there is an association between relative prostatic size and the variables total testosterone concentration, SHBG concentration, an estimation of bioavailable testosterone: the ratio between testosterone and SHBG (free androgen index, FAI), estradiol concentration, the estradiol/testosterone ratio, dog age and dog weight. Hormone concentrations were measured in serum from 79 intact male dogs aged ≥ four years, weighing ≥ five kg. The size of the prostate was estimated using ultrasonography, and relative prostate size, Srel, was calculated as the estimated size related to the normal size for a 4-year-old dog of the same weight. There as a negative correlation between testosterone concentration and age (ρ = -0.27, P = 0.018) and a positive correlation between age and Srel (ρ = 0.27, P = 0.016) and between SHBG and weight (ρ = 0.38, P = 0.001). The FAI was negatively correlated with dog weight (ρ = -0.32, P = 0.004). There were no significant correlations between Srel and SHBG or FAI or between estradiol or estradiol/testosterone and Srel, age or weight. A multiple regression analysis showed significant associations between log Srel and log testosterone concentration, log age and log weight of the dog, with an adjusted R2 of 9.5%. Although the variables total testosterone concentration, age and weight of the dog were all significantly associated with Srel, the coefficient of determination was low, indicating that they only explained a minor part of the prostatic size. The results support the analysis of total testosterone in studies of prostatic growth in the dog.


Assuntos
Doenças do Cão , Hiperplasia Prostática , Masculino , Cães , Animais , Testosterona , Androgênios , Estradiol , Hiperplasia Prostática/veterinária , Próstata
16.
N Engl J Med ; 388(3): 240-250, 2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36652355

RESUMO

BACKGROUND: Limited prospective outcome data exist regarding transgender and nonbinary youth receiving gender-affirming hormones (GAH; testosterone or estradiol). METHODS: We characterized the longitudinal course of psychosocial functioning during the 2 years after GAH initiation in a prospective cohort of transgender and nonbinary youth in the United States. Participants were enrolled in a four-site prospective, observational study of physical and psychosocial outcomes. Participants completed the Transgender Congruence Scale, the Beck Depression Inventory-II, the Revised Children's Manifest Anxiety Scale (Second Edition), and the Positive Affect and Life Satisfaction measures from the NIH (National Institutes of Health) Toolbox Emotion Battery at baseline and at 6, 12, 18, and 24 months after GAH initiation. We used latent growth curve modeling to examine individual trajectories of appearance congruence, depression, anxiety, positive affect, and life satisfaction over a period of 2 years. We also examined how initial levels of and rates of change in appearance congruence correlated with those of each psychosocial outcome. RESULTS: A total of 315 transgender and nonbinary participants 12 to 20 years of age (mean [±SD], 16±1.9) were enrolled in the study. A total of 190 participants (60.3%) were transmasculine (i.e., persons designated female at birth who identify along the masculine spectrum), 185 (58.7%) were non-Latinx or non-Latine White, and 25 (7.9%) had received previous pubertal suppression treatment. During the study period, appearance congruence, positive affect, and life satisfaction increased, and depression and anxiety symptoms decreased. Increases in appearance congruence were associated with concurrent increases in positive affect and life satisfaction and decreases in depression and anxiety symptoms. The most common adverse event was suicidal ideation (in 11 participants [3.5%]); death by suicide occurred in 2 participants. CONCLUSIONS: In this 2-year study involving transgender and nonbinary youth, GAH improved appearance congruence and psychosocial functioning. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.).


Assuntos
Identidade de Gênero , Hormônios Esteroides Gonadais , Funcionamento Psicossocial , Pessoas Transgênero , Adolescente , Criança , Feminino , Humanos , Estudos Prospectivos , Testosterona/uso terapêutico , Pessoas Transgênero/psicologia , Estradiol , Hormônios Esteroides Gonadais/uso terapêutico , Adulto Jovem , Masculino
17.
Molecules ; 28(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36677863

RESUMO

Benign prostatic hyperplasia (BPH) is a chronic disease that affects the quality of life of older males. Sinomenine hydrochloride (SIN) is the major bioactive alkaloid isolated from the roots of the traditional Chinese medicinal plant Sinomenium acutum Rehderett Wilson. We wondered if the SIN administration exerted a regulatory effect on BPH and its potential mechanism of action. Mice with testosterone propionate-induced BPH subjected to bilateral orchiectomy were employed for in vivo experiments. A human BPH cell line (BPH-1) was employed for in vitro experiments. SIN administration inhibited the proliferation of BPH-1 cells (p < 0.05) by regulating the expression of androgen-related proteins (steroid 5-alpha reductase 2 (SRD5A2), androgen receptors, prostate-specific antigen), apoptosis-related proteins (B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax)) and proliferation-related proteins (proliferating cell nuclear antigen (PCNA), mammalian target of rapamycin, inducible nitric oxide synthase) in vitro. SIN administration decreased the prostate-gland weight coefficient (p < 0.05) and improved the histological status of mice suffering from BPH. The regulatory effects of SIN administration on SRD5A2, an apoptosis-related protein (Bcl-2), and proliferation-related proteins (PCNA, matrix metalloproteinase-2) were consistent with in vitro data. SIN exerted a therapeutic effect against BPH probably related to lowering the SRD5A2 level and regulating the balance between the proliferation and apoptosis of cells. Our results provide an important theoretical basis for the development of plant medicines for BPH therapy.


Assuntos
Hiperplasia Prostática , Animais , Humanos , Masculino , Camundongos , Apoptose , Proliferação de Células , Colestenona 5 alfa-Redutase/metabolismo , Metaloproteinase 2 da Matriz , Proteínas de Membrana , Extratos Vegetais/farmacologia , Antígeno Nuclear de Célula em Proliferação , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Qualidade de Vida , Testosterona/farmacologia
18.
Sci Rep ; 13(1): 1721, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36720901

RESUMO

The purpose of this study was to verify whether there is a causal relationship between breast cancer and bone mineral density (BMD). Summary statistics for exposures and outcomes were obtained from corresponding genome-wide association studies. The bidirectional and multivariate mediated Mendelian randomization (MR) analyses were performed. In the bidirectional MR analysis, breast cancer might reduce the BMD of the heel (HE-BMD) (FDR = 1.51 × 10-4) as might its ER+ subtype (FDR = 1.51 × 10-4). From BMD to breast cancer, no significant association was found (FDR > 0.05). The mediating MR analysis showed that Higher free testosterone (FT) only mediated the causal relationship between breast cancer and HE-BMD by 2.9%; both ER+ type and FT were independent factors of HE-BMD (ER+: P = 0.021; FT: P = 6.88 × 10-6). Higher FT could increase the risk of breast cancer (FDR = 1.21 × 10-3) as could total testosterone (TT) (FDR = 5.81 × 10-3). Similarly, higher FT could increase the risk of ER+ subtype (FDR = 2.51 × 10-6) as could TT (FDR = 5.55 × 10-4). These results indicate that BMD is not a risk factor for breast cancer but breast cancer and its ER+ subtype are risk factors for BMD loss. Furthermore, higher FT and TT levels are associated with both an increased incidence of breast cancer and increased bone density.


Assuntos
Densidade Óssea , Neoplasias , Densidade Óssea/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Testosterona
19.
J Cogn Neurosci ; 35(3): 396-420, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36603042

RESUMO

Previous studies have demonstrated that paternal caregiving behaviors are reliant on neural pathways similar to those supporting maternal care. Interestingly, a greater variability exists in parental phenotypes in men than in women among individuals and mammalian species. However, less is known about when or how such variability emerges in men. We investigated the longitudinal changes in the neural, hormonal, and psychological bases of expression of paternal caregiving in humans throughout pregnancy and the first 4 months of the postnatal period. We measured oxytocin and testosterone, paternity-related psychological traits, and neural response to infant-interaction videos using fMRI in first-time fathers and childless men at three time points (early to mid-pregnancy, late pregnancy, and postnatal). We found that paternal-specific brain activity in prefrontal areas distinctly develops during middle-to-late pregnancy and is enhanced in the postnatal period. In addition, among fathers, the timing of the development of prefrontal brain activity was associated with specific parenting phenotypes.


Assuntos
Encéfalo , Pai , Masculino , Lactente , Animais , Humanos , Gravidez , Feminino , Pai/psicologia , Encéfalo/fisiologia , Comportamento Paterno/fisiologia , Comportamento Paterno/psicologia , Testosterona/metabolismo , Poder Familiar/psicologia , Mamíferos/metabolismo
20.
Toxicol Lett ; 375: 69-76, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36610527

RESUMO

The objectives of the study were to simulate low-level Pb exposure scenario in an animal model and to examine reproductive adverse effects. Based on obtained data, we have performed Benchmark dose (BMD)-response modelling. Male Wistar rats were randomized in seven groups (n = 6): one control and six treated with: 0.1, 0.5, 1, 3, 7, and 15 mg Pb/kg body weight, daily for 28 days by oral gavage. The rats were sacrificed and the blood and testes were used for further analysis of testosterone levels in serum, testicular essential metal levels and histological analysis. The Pb treatment led to a dose-dependent decrease of serum testosterone levels with a negative trend (BMDI 0.17-6.13 mg Pb/kg). Increase of Zn (dose-dependent, BMDI 0.004-19.7 mg Pb/kg) and Cu and a decrease of Mn testicular levels were also detected with unscathed histology of the testes. The presented results might be used in further evaluation of the point of departure in human health risk assessment for Pb.


Assuntos
Chumbo , Testículo , Testosterona , Animais , Masculino , Ratos , Benchmarking , Chumbo/administração & dosagem , Chumbo/toxicidade , Ratos Wistar , Testículo/química , Testículo/patologia , Testosterona/sangue , Modelos Animais
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