Reduced Testosterone Levels Research Articles

Effects of vancomycin linoleic acid nanoparticles on male reproductive indices of Sprague–Dawley rats

The management of bacterial infections, especially trains of methicillin-resistant Staphylococcus aureus observe in health care settings, has markedly improved with the introduction of established drugs but using newer nano-based formulations. This study investigates the effects of vancomycin-linoleic acid nanoparticles on testicular tissue in an experimental animal model. Twenty-five adult male Sprague–Dawley rats maintained at the Animal House of the Biomedical Resources Unit were assigned to five groups namely E – solid lipid nanoparticles; F – vancomycin solid lipid nanoparticle; G – linoleic acid nanoparticle; H – vancomycin linoleic acid; and A – control. Perturbations in seminal fluid parameters showed a reduced sperm count in groups F & G which was statistically significant (p < .05) but motility and morphology were not significant when compared to controls (A). Reduced testosterone levels were found in groups E, F and H but were not statistically significant (p > .05). There was also increased luteinizing hormone (LH) and decreased in follicular stimulating hormone (FSH) levels was statistically significant (p < .05). Hypoplasia, tubular atrophy and shrinkage were observed in histologic sections of the treated groups with basement membrane thickening. Vancomycin solid lipid nanoparticle and its constituents SLN and LA disrupted testicular morphometry and the hormonal milieu sufficient to potentially induce altered reproductive function.

Hyperlipidic Diet-induced Obesity Increased Proliferative Signals- AR, ERK1/2- on Mice Prostate, Which can be Restored through Physical Training

Aims: To evaluate the effects of hyperlipidic diet on the mouse prostate and also investigate if physical exercise is able to restore such effects.&#x0D; Methodology: Adult male Swiss mice were fed with a balanced (ND) or hyperlipidic diet (45% saturated fat, HD) for 16 weeks. Half were submitted to a sedentary (NDS and HDS) or exercise routine (swimming- NDE and HDE) for 8 weeks. Then, the prostate was analyzed by immunoreactions (proliferating cell nuclear antigen- PCNA, androgen receptor- AR, and estrogen receptor-ERβ), western blotting (ERK 1/2), and caspase-3 activity.&#x0D; Results: We found that saturated fat uptake promoted 16% weight gain, increased fat-mass and hyperglycaemia, as well as reduced testosterone levels. In addition, HD atrophied prostate secretory epithelium and stimulated cell proliferation through higher expression of AR and activation of ERK signaling. Additionally, saturated fat reduced prostatic ERβ content. Physical exercise per se promoted an anabolic effect by increasing testosterone and stimulating cell proliferation in the prostate of sedentary animals. Finally, exercise was able to restore the proliferative signals caused by the hyperlipidic diet on prostate.&#x0D; Conclusion: We suggest that the combination of hyperlipidic diet and sedentary lifestyle could negatively affected some prostate stimulating pathways that could trigger proliferative diseases in mice and physical exercise may be an interesting strategy to reverse such effects.

Reproductive Dysfunctions in Males with Type 2 Diabetes Mellitus: An Updated Review

Deterioration in reproductive functions is one of the most serious complications of Type 2 diabetes mellitus (T2DM). Neuropathy, angiopathy, oxidative stress, and psychological deviation are the important causative factors in developing reproductive dysfunctions in diabetes. In males, the principal complications are erectile dysfunction (ED), ejaculatory disorders, and functional hypogonadism. Low serum testosterone is frequently observed in males with T2DM but the neuroendocrine pathophysiology is yet to be defined; this reduction in testosterone levels decreases libido. Evaluation of testosterone levels of male diabetic patients with hypogonadism symptoms is recommended. Hypogonadal males with diabetes might benefit from testosterone replacement therapy. However, there is a need for adequately powered long-term studies in this context. Impairment in sexual function is a common complication in males with diabetes. The pathophysiology of sexual dysfunction in diabetes is multifactorial. Males with diabetes have a &gt;3-fold increase in the risk of ED compared to their nondiabetic counterparts. Phosphodiesterase type 5 inhibitors should be considered as first-line therapy in males with T2DM and ED. Nearly 50% of male diabetic patients presented some degree of subfertility or infertility. Alterations in sperm parameters and hormone levels can contribute to diabetes-related male infertility. Endocrinologists, diabetologists, and physicians should address sexual complaints of their patients since these problems can significantly impair their quality of life.

Alsevirone-NF Reduces Serum Testosterone and Inhibits Prostate Cancer Xenograft Growth in Balb/c Nude Mice

Background: The goal of this study was to evaluate the anticancer and testosteroneinhibitory effects of 2‘-[(E) androst-5-en-17-ylidene]methyl-4‘,5‘-dihydro-1‘,3‘-oxazole-3β-oleate (Alsevirone-NF). Materials and Methods: PC-3, DU-145, LnCap and 22rv1 prostate cancer cell lines were used for MTT assay. 22rv1 subcutaneous cancer xenografts in Balb/c nude mice were used for in vivo efficacy experiments. Testosterone level was determined after repeated administration of Abiraterone 20, 100 or 200 mg/kg vs Alsevirone-NF 5, 25 or 50 mg/kg daily for 14 days. Results: Alsevirone-NF induced more significant cytotoxicity against PC3, 22rv1 and DU-145 cell lines compared to Abiraterone or Alsevirone-treated control: IC50 7.1 vs 20.6 vs 29.1 μg/ml, 7.7 vs 20.0 vs 12.7 μg/ml, 3.8 vs 43.4 vs 8.5 μg/ml, respectively. IC50 in LnCap cells was almost equal for all three studied agents, 29.2 vs 26.2 vs 30.2 μg/ml for Abiraterone, Alsevirone and Alsevirone-NF. In gonadectomized mice, significant reduction of testosterone level was observed in mice receiving Alsevirone-NF in a maximum single dose of 50 mg/kg (cumulative dose 700 mg/kg): 0.2 nmol/l vs 0.57 nmol/l in control group and 0.83 nmol/l in Abiraterone group, single dose 100 mg/kg. Statistically significant anticancer effect in vivo was obtained on day 11 after the start of treatment: Abiraterone T/C = 27% (p&lt;0.05), Alsevirone-NF single dose 1200 mg/kg Т/С = 45% (p&lt;0.05). Conclusion: Alsevirone-NF exhibited higher cytotoxic activity, comparable anticancer effect in 22rv1-bearing Balb/c nude mice and provided a more significant reduction of testosterone level in gonadectomized mice in direct comparison against Abiraterone.

Examining the association between serum free fatty acids and blood levels of testosterone

Multiple studies have uncovered the effects that ingested fat has on human blood levels of testosterone. Yet, few reports have discussed the effect of circulating serum free fatty acids (FFAs). The present study aimed to explore the relationship between serum free fatty acids and blood levels of testosterone. In total, 5719 adults were pooled from the database of the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2012. Based on multivariable-linear regression models, we employed a total of 30 FFAs to interpret the relationship of FFAs with blood levels of testosterone. Two models with covariate adjustments were designated for further evaluation and analysis. Capric acid [β=-0.014, 95% confidence interval (CI)=-0.023, -0.004, P=0.005], myristic acid (β=-0.001, 95% CI=-0.001, 0.000, P≤0.001), pentadecanoic acid (β=-0.013, 95% CI=-0.018, -0.008, P≤0.001), margaric acid (β=-0.011, 95% CI=-0.017, -0.005, P≤0.001) and alpha-linolenic acid (β=-0.001, 95% CI=-0.002, 0.000, P=0.004) in the fully adjusted model were significantly negatively correlated with the testosterone level inh obese men. In the fully adjusted model for the female analysis, myristic acid, pentadecanoic acid, palmitic acid, margaric acid, stearic acid, myristoleic acid, oleic acid, nervonic acid and alpha-linolenic acid were found significantly associated with the testosterone level. Our findings indicate a significant negative correlation between serum FFAs and blood levels of testosterone. Furthermore, we reveal the essentiality of serum FFAs and their potential effects on the reduction of testosterone levels.

Perinatal Exposure to Methoxychlor Affects Reproductive Function and Sexual Behavior in Mice.

Numerous chemicals derived from human activity are now disseminated in the environment where their exert estrogenic endocrine disrupting effects, and therefore represent major health concerns. The present study explored whether Methoxychlor (MXC), an insecticide with xenoestrogens activities, given during the perinatal period (from gestational day 11 to postnatal day 8) and at an environmentally dose [20 μg/kg (body weight)/day], would affect reproductive physiology and sexual behavior of the offspring in mice. While MXC exposure did not induce any differences in the weight gain of animals from birth to 4 months of age, a clear difference (although in opposite direction according to the sexes) was observed on the anogenital distance between intact and exposed animals. A similar effect was also observed on preputial separation and vaginal opening, which reflects, respectively, in males and females, puberty occurrence. The advanced puberty observed in females was associated with an enhanced expression of kisspeptin cells in the anteroventral periventricular region of the medial preoptic area. Exposure to MXC did not induce in adult females changes in the estrous cycle or in the weight of the female reproductive tract. By contrast, males showed reduced weight of the epididymis and seminiferous vesicles associated with reduced testosterone levels and seminiferous tubule diameter. We also showed that both males and females showed deficits in mate preference tests. As a whole, our results show that MXC impacts reproductive outcomes.

Effect of green coffee supplementation on androgens level in women with polycystic ovary syndrome: A Randomized Clinical Trial

The present study was aimed at determining the effect of green coffee supplementation on androgens level in women with Poly-Cystic Ovary Syndrome (PCOS) through double-blind Randomized Clinical Trial (RCT). Each patient (n = 17) in the treatment group received one green coffee capsule (400 mg) and the control group (n = 17) received one placebo for six weeks. Then, the levels of free testosterone, dihydrotestosterone, and androstenedione; lipid profile; glycemia and insulinemia indices; and anthropometric indices before and after the intervention were determined and compared. The results showed green coffee supplements reduced testosterone level (P = 0.038). There was no significant difference in general characteristics of the participants, including education, occupational status, age of illness, and metformin usage. At the beginning and the end of the study, there was a significant decrease in triglyceride (P = 0.007) and total cholesterol level (P = 0.035) in the green coffee group in comparison with the placebo group. However, no significant difference in anthropometric data including weight, Body Mass Index (BMI), waist circumference, and waist-to-hip ratio was observed. Moreover, no significant difference was observed in fasting blood glucose, insulin levels, insulin resistance index, LDL, HDL, dihydrotestosterone, and androstenedione. The results of the clinical trial showed that supplementation of 400 mg green coffee a day for six weeks significantly reduced free testosterone, triglyceride, and cholesterol levels. Therefore, green coffee might help to improve Poly-Cystic Ovary Syndrome (PCOS).

Borderline-low testosterone levels are associated with lower left ventricular wall thickness in firefighters: An exploratory analysis.

BackgroundLow endogenous testosterone has been associated with increased cardiovascular risk in men.ObjectivesTo determine the prevalence of low serum testosterone level (TT) in a cohort of male US career firefighters and to examine its relation with left ventricular wall thickness (LVWT).Materials and MethodsWe conducted a cross‐sectional study among 341 career firefighters, (age: 37.5 ± 10.3 years; BMI: 28.9 ± 4.5 kg/m2), who underwent an occupational medical screening examination. TT quartiles were determined, and LVWT distribution among them was plotted. Then, TT values were categorized as low (<264 ng/dL), borderline (264‐399 ng/dL), reference range (400‐916 ng/dL), and high (>916 ng/dL). To further investigate the association of mildly decreased TT on LVWT, we divided the borderline group into borderline‐low (264‐319 ng/dL) and borderline‐high (320‐399 ng/dL) ranges. LVWT values were classified as low LVWT when <0.6 cm. A multivariate model was used to compare LVWT, age, BMI, systolic blood pressure (SBP), and HbA1c among groups by TT values.ResultsThe prevalence of low TT was 10.6% and of borderline was 26.4%, while 58.7% had levels in the reference range. The low‐TT group was older and had higher BMI and SBP as compared to the reference group (P < .01). LVWT values were different among groups (P = .04) and significantly lower in firefighters with borderline‐low TT as compared to the reference group (P < .05). This finding also occurred within obese firefighters (P = .03). The borderline‐low group had a higher adjusted risk for a low LVWT as compared to the reference group [OR: 4.11 (95% CI: 1.79‐9.43)].DiscussionOur findings highlight the possible relationship between a mild reduction in testosterone levels (borderline) and lower LVWT.ConclusionsA high prevalence of subnormal TT levels (low and borderline: 37%) was observed in this relatively homogeneous cohort of career firefighters. Mildly decreased TT levels and lower LVWT might represent a preclinical condition and a window of opportunity for cardiovascular preventive interventions in firefighters.

Effect of Moringa oleifera leaves extract against electromagnetic field impairments on hemoglobin and testes of rat

The present study has revealed the effect of Moringa oleifera leaves extract against electromagnetic field induced impairments. Forty-two adult white Albino male rats, weighting 150-180 g were involved in this study and divided into six equal groups. The first group was the control while the second group was daily supplemented with 200 mg/kg Moringa oleifera leaves extract orally for six days. The third group was exposed to an electromagnetic field of 1.5 mT, 50 Hz for 9 hours. The other three groups were exposed to an electromagnetic field of 1.5 mT, 50 Hz for 9 hours, and received the Moringa oleifera leaves extract in different supplemented ways. Blood samples were collected for the absorption spectrum of hemoglobin molecules analysis and serum total testosterone was studied. Samples of testes were taken for histopathological observations. The results showed that exposure of the animals to the electromagnetic field resulted in changing the absorption spectrum of hemoglobin, a highly significant reduction in testosterone level, and degenerative changes in testes. All these induced changes were decreased in groups treated by Moringa oleifera leaves extract in all ways. So through this study, one can conclude that damages induced by exposure to the electromagnetic field can be decreased by Moringa oleifera leaves extract.

Cardiac biomarkers in patients with prostate cancer and cardiovascular disease receiving gonadotrophin releasing hormone agonist vs antagonist

BackgroundGonadotrophin releasing hormone (GnRH) agonists and antagonists reduce testosterone levels for the treatment of advanced and metastatic prostate cancer. Androgen deprivation therapy (ADT) is associated with increased risk of cardiovascular (CV) events and CV disease (CVD), especially in patients with preexisting CVD treated with GnRH agonists. Here, we investigated the potential relationship between serum levels of the cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NTproBNP), D-dimer, C-reactive protein (CRP), and high-sensitivity troponin (hsTn) and the risk of new CV events in prostate cancer patients with a history of CVD receiving a GnRH agonist or antagonist.MethodsPost-hoc analyses were performed of a phase II randomized study that prospectively assessed CV events in patients with prostate cancer and preexisting CVD, receiving GnRH agonist or antagonist. Cox proportional hazards models were used to determine whether the selected biomarkers had any predictive effect on CV events at baseline and across a 12-month treatment period.ResultsBaseline and disease characteristics of the 80 patients who took part in the study were well balanced between treatment arms. Ischemic heart disease (66%) and myocardial infarction (37%) were the most common prior CVD and the majority (92%) of patients received CV medication. We found that high levels of NTproBNP (p = 0.008), and hsTn (p = 0.004) at baseline were associated with the development of new CV events in the GnRH agonist group but not in the antagonist. In addition, a nonsignificant trend was observed between higher levels of NTproBNP over time and the development of new CV events in the GnRH agonist group.ConclusionsThe use of cardiac biomarkers may be worthy of further study as tools in the prediction of CV risk in prostate cancer patients receiving ADT. Analysis was limited by the small sample size; larger studies are required to validate biomarker use to predict CV events among patients receiving ADT.

In Experimental Dilated Cardiomyopathy Heart Failure and Survival Are Adversely Affected by a Lack of Sexual Interactions.

Nearly one in three people in the U.S. will develop heart failure (HF), characterized by fluid retention (edema) in the lungs and elsewhere. This leads to difficult breathing, deterioration of physical capacity, restriction of normal activities and death. There is little data about the safety and effects of sexual interactions in patients with HF. We tested whether a lack of sexual interactions affected pathophysiological outcomes in a pre-clinical mouse model of dilated cardiomyopathy that recapitulates the progressive stages of human HF. Male mice were randomly given access to, or deprived from, sexual interactions with female mice, which were confirmed by videography and generation of offspring. Cohousing with access to sexual interactions markedly prolonged survival, while cohousing without access to sexual activity did not. Sexual interactions improved systolic function, reduced HF-associated edema, altered transcription of heart contractile protein genes and decreased plasma testosterone levels. To determine whether testosterone levels contributed to survival, testosterone levels were experimentally reduced. Reduction of testosterone levels significantly prolonged survival. Taken together, in mice with dilated cardiomyopathy, sexual activity altered cardiac contractile gene transcription, improved systolic function, reduced edema and prolonged survival which may be in part due to lower testosterone levels.

Depressive symptoms are not associated with long-term integrated testosterone concentrations in hair

Objectives The association between depressive symptomatology and endogenous testosterone levels is inconclusive. Large inter- and intra-individual testosterone differences suggest point measurements from saliva or serum to be inadequate to map basal testosterone concentrations highlighting the potential for long-term integrated testosterone levels from hair. Methods Using data from a prospective cohort study, a total of 578 participants (74% female) provided complete data on depressive symptomatology, clinical features, and hair samples for quantification of testosterone concentrations at baseline. Available data of three annual follow-up examinations were used for longitudinal analyses. Results Correlation analysis showed in both, men and women, hair testosterone across all the four time points not to be significantly related to depressive symptoms. Examined clinical features were not associated with testosterone levels, except for having a current diagnosis of a psychological disorder, which was associated with reduced testosterone levels in men, but not in women. Acceptable model fit for an autoregressive cross-lagged panel analysis emerged only for the female subsample suggesting inverse cross-relations for the prediction of testosterone by depressive symptomatology and vice versa. Conclusions Findings from this study add to the literature by showing no association between long-term integrated testosterone in hair and depressive symptomatology in men and women.

Changes in Beck Depression Inventory scores in prostate cancer patients undergoing androgen deprivation therapy or prostatectomy.

ObjectivesAndrogen deprivation therapy (ADT) has seen increasing use as a prostate cancer treatment in recent years and has proven medically effective in numerous contexts. The treatment, however, is associated with a host of side effects including depression. Managing the psychological wellbeing of prostate cancer patients is important for maximizing their survival outcomes. Thus, this study aimed to evaluate depressive symptomatology in patients with androgen deprivation therapy (ADT) compared with that in patients who underwent prostatectomy and to explore the factors that affect depressive symptoms, which might occur during ADT.MethodsOne hundred and seven patients undergoing ADT (ADT group) and prostatectomy (Operation group) were enrolled. Adjustments were made for differences in characteristics between groups using a propensity score model with stabilized weights before treatment. Depressive symptoms between groups were compared using the Beck Depression Inventory (BDI) before treatment and six months after treatment initiation. To identify factors affecting depressive symptoms during ADT, multivariate regression analysis was performed on the mean change in BDI score, age, body mass index, testosterone level, prostate-specific antigen level, the international index of erectile function (IIEF), and the Gleason score.ResultsThe BDI score significantly increased in the ADT group compared to the operation group six months after treatment initiation (p < 0.001). Multivariate regression analysis revealed that before ADT, the BDI score was higher by 0.446 according to the IIEF. During ADT, the BDI score increased by 1.579 according to changes in BMI (p = 0.021) and decreased by 0.01 according to changes in testosterone levels (p = 0.034).ConclusionDepressive symptoms can be exacerbated in prostate cancer patients undergoing ADT. Efforts are needed to diagnose and treat depression appropriately, especially if depressive symptoms change in ADT patients with a high IIEF score before ADT, or reduced testosterone levels or increased BMI during ADT.

The Effect of Prostate Cancer Radiotherapy on Testosterone Level: A Systematic Review and Meta-analysis.

In the current study, a systematic search and meta-analysis were performed to evaluate the effect of prostate cancer radiotherapy on testosterone levels of patients. To illuminate the effect of radiotherapy on the testosterone level of prostate cancer patients, a systematic search was conducted in accordance with the PRISMA guideline in electronic databases of Scopus, Embase, PubMed, Web of Science, and clinical trials up to December 2018 using relevant keywords. Based on a certain set of inclusion and exclusion criteria, 12 eligible studies that had data on the testosterone level following prostate cancer radiotherapy were included in the meta-analysis. According to the various techniques of prostate cancer radiotherapy, the dose values scattered to the testicular tissues ranged from 0.31 to 10 Gy. Combining the findings from 12 studies, it was found that prostate cancer radiotherapy leads to a significant reduction in the testosterone level (Weighted Mean Difference [WMD]: -51.38 ng/dL, 95% CI: -75.86, -26.90, I2=0.0%, P<0.05). Furthermore, subgroup analysis by the patient number showed a significant reduction in the testosterone level at patient number < 50 (WMD: -80.32 ng/dL, 95% CI: -125.10, -35.55, I2= 0.0%) and 50 < patient number < 100 (WMD: -46.99 ng/dL, 95% CI: - 87.15, -6.82, I2= 0.0%). Subgroup analysis based on treatment technique type revealed a significant reduction in testosterone level after conventional radiotherapy (WMD: -56.67, 95% CI: -100.45,-12.88, I2= 34.3%) and IMRT/SBRT technique (WMD: -57.42, 95% CI: -99.39, -15.46, I2= 0.0%) in comparison with the proton therapy (WMD: 0.00, 95% CI: -80.24, 80.24). The findings showed a significant decrease in the testosterone level of prostate cancer patients after radiotherapy compared with pre-treatment levels.

Nutraceutical Effects of Lycopene in Experimental Varicocele: An "In Vivo" Model to Study Male Infertility.

Varicocele is one of the main causes of infertility in men. Oxidative stress and consequently apoptosis activation contribute to varicocele pathogenesis, worsening its prognosis. Natural products, such as lycopene, showed antioxidant and anti-inflammatory effects in several experimental models, also in testes. In this study we investigated lycopene effects in an experimental model of varicocele. Male rats (n = 14) underwent sham operations and were administered with vehicle (n = 7) or with lycopene (n = 7; 1 mg/kg i.p., daily). Another group of animals (n = 14) underwent surgical varicocele. After 28 days, the sham and 7 varicocele animals were euthanized, and both operated and contralateral testes were weighted and processed. The remaining rats were treated with lycopene (1 mg/kg i.p., daily) for 30 days. Varicocele rats showed reduced testosterone levels, testes weight, Bcl-2 mRNA expression, changes in testes structure and increased malondialdehyde levels and BAX gene expression. TUNEL (Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling) assay showed an increased number of apoptotic cells. Treatment with lycopene significantly increased testosterone levels, testes weight, and Bcl-2 mRNA expression, improved tubular structure and decreased malondialdehyde levels, BAX mRNA expression and TUNEL-positive cells. The present results show that lycopene exerts beneficial effects in testes, and suggest that supplementation with the tomato-derived carotenoid might be considered a novel nutraceutical strategy for the treatment of varicocele and male infertility.

Testosterone Levels Are Decreased and Associated with Disease Duration in Male Spinocerebellar Ataxia Type 2 Patients.

Spinocerebellar ataxia type 2 (SCA2) is a progressive neurodegenerative disorder due to an unstable expansion of a CAG repeat in the ATXN2 gene. Despite clinical and experimental evidence indicating the relevance of the gonadotropic axis to the prognosis and therapeutics for several late-onset neurodegenerative disorders, its functioning and association with disease severity have not been previously explored in SCA2. To assess serum levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), and their clinical relevance in SCA2 patients. A case-control study involving 94 Cuban SCA2 patients and 101 gender- and age-matched healthy controls was conducted. Testosterone, LH, and FSH serum levels were determined by radioimmunoassay or immunoradiometric assay systems. Clinical outcomes included age at onset, disease duration, Scale for the Assessment and Rating of Ataxia (SARA) score, and progression rate. Univariate general linear models were generated. Testosterone, LH, and FSH serum levels were significantly reduced in male SCA2 patients relative to control individuals. On average, there was a 35% reduction in testosterone levels in male patients versus male control individuals. Testosterone levels were associated with disease duration (r = 0.383; p = 0.025) and age at onset (r = 0.414; p = 0.011) in male SCA2 patients, but no association was observed between testosterone and CAG expansion size, SARA score, or progression rate. Testosterone levels might be a biomarker of disease progression in male SCA2 patients. Further studies are needed to explore the effects of low testosterone levels on non-motor symptoms, and to assess the potential of testosterone replacement therapy in male SCA2 patients.

Ameliorative Role of Green Tea and Zinc Oxide Nanoparticles Complex Against Monosodium Glutamate-Induced Testicular Toxicity in Male Rats.

This study was designed to estimate the long-term effects of zinc oxide nanoparticles/green tea (ZnONPs/GTE) complex against monosodium glutamate (MSG). The antioxidant/oxidative status, testosterone levels, DNA damage, and histopathological changes of testis were evaluated. The rats were divided into eight groups that were treated as follows: saline, the lower dosage of MSG (6.0 mg/kg), the higher dosage of MSG (17.5 mg/Kg), GTE, ZnONPs, ZnONPs/GTE and the last two groups were treated with the lower dosage of MSG or the higher dosage of MSG with ZnONPs/GTE complex. The data showed minimal toxicity in testicular tissue after the administration of ZnONPs. The MSG treatment in the adult male rats reduced testosterone levels and disrupted testicular histology, which revealed dose-dependence of MSG. Also, ZnONPs induced testicular dysfunction through the interference of antioxidant/oxidant balance and suppression of testosterone levels as well as induction of cellular damage of testis. The combination of ZnONPs with GTE complex significantly protects against MSG or ZnONPs toxicity by decreasing the DNA damage, oxidative stress, and enhancement of antioxidant as well as histological structure of testis. We could recommend using ZnONPs/GTE complex to reduce the toxicity of ZnONPs and MSG on the testis at the cellular and oxidative stress levels.

Androgen Deprivation Therapy for Prostatic Cancer in Patients With Torsades de Pointes.

BackgroundMen normally have shorter heart rate-corrected QT interval (QTc) than women, at least in part due to accelerating effects of testosterone on ventricular repolarization. Accumulating data suggest that androgen-deprivation therapy (ADT) used for the treatment of prostatic cancer, may increase Torsades de Pointes (TdP) risk by prolonging QTc. However, the evidence for such an association is currently limited to few case reports, in most cases deriving from the analysis of uncontrolled sources such as pharmacovigilance databases.ObjectiveTo better determine the clinical impact of ADT on TdP development, we examined the prevalence of this therapy in a consecutive cohort of 66 TdP patients, prospectively collected over a ~10 years period.Methods and ResultsWe found and described four patients who were under ADT for prostatic cancer when TdP occurred, and in two cases degenerated to cardiac arrest. Notably, in this unselected population, ADTs unexpectedly represented the second most frequently administered QT-prolonging medication in males (4/24, 17%), after amiodarone. Moreover, in the ADT patients, a blood withdrawal was performed within 24 h from TdP/marked QTc prolongation occurrence and circulating concentration of androgens and gonadothropins were measured. As expected, all cases showed markedly reduced testosterone levels (total, free, and available).ConclusionWe provide evidence that a significant proportion of patients developing TdP were under treatment with ADT for prostatic cancer, thus confirming the clinical relevance of previous pharmacovigilance signals. An accurate assessment of the arrhythmic risk profile should be included in the standard of care of prostatic cancer patients before starting ADT.

The role of leptin and obesity on male infertility.

Several studies suggest a strong association between leptin, obesity, and infertility with respect to the hypothalamic-pituitary-gonadal (HPG) axis, androgen regulation, and sperm production, but the direct mechanistic association between these is still largely unexplored. This review focuses on understanding the association between leptin, obesity, and male infertility. Obesity is linked to fertility dysfunction in both genders. Obesity in men may affect their fertility by impaired spermatogenesis, reduced testosterone levels, erectile dysfunction, and poor libido by putatively targeting the HPG and hypothalamic-pituitary-adrenal axes. Leptin plays key roles in many metabolic functions, including reproduction. High concentrations of leptin have been found in infertile men with disorders affecting the testicular parenchyma, including nonobstructive azoospermia, oligozoospermia, and oligo-astheno-teratozoospermia. Additionally, serum leptin levels have negative associations with serum testosterone levels and sperm parameters and positive associations with serum follicle-stimulating hormone and luteinizing hormone levels and abnormal sperm morphology. Excessive leptin production may be a significant contributor to the development of androgen insufficiency and reduced reproductive function in obese men. Understanding the relation between leptin, obesity, and reproduction may shed light on future targeted treatments for male infertility.

Comparative efficacy of statins, metformin, spironolactone and combined oral contraceptives in reducing testosterone levels in women with polycystic ovary syndrome: a network meta-analysis of randomized clinical trials

BackgroundPolycystic ovary syndrome (PCOS) is an endocrine disorder affecting about 10% of women in reproductive age and associated with a variety of hormonal abnormalities, including hyperandrogenemia and infertility, all of which could lead to PCOS. Statins were previously introduced as a therapeutic option for reducing testosterone levels in women with PCOS, either alone or in combination. The aim of this study is to evaluate the effectiveness of different statins alone or in combination with metformin in reducing testosterone levels in women with PCOS.MethodsMedline, Embase, and clinicaltrials.gov were searched for studies that investigated the efficacy of statins, metformin, spironolactone, or combined oral contraceptives (COCs), individually or in combination, in reducing the testosterone level in patients with PCOS. The search was limited to randomized clinical trials and conducted according to the preferred reporting items for systematic reviews and meta-analyses - extension statement for network meta-analyses (PRISMA-NMA). The quality of included studies was assessed using the Cochrane Collaboration risk of bias (RoB) assessment tool. A frequentist network meta-analysis using random-effects models was used to assess the efficacy in reducing testosterone level and were expressed as odds ratios (OR) and 95% credible interval (95%Crl). All statistical analyses were performed using netmeta Version 1.0 on R statistical package.ResultNine RCTs involving 613 patients were included. Atorvastatin showed greater reduction in testosterone level compared to COC (MD −2.78, 95%CrI −3.60, −1.97), spironolactone plus metformin (MD −2.83, 95%CrI −3.80, −1.87), simvastatin (MD −2.88, 95%CrI −3.85, −1.92), spironolactone (MD −2.90, 95%CI −3.77, −2.02), simvastatin plus metformin (MD −2.93, 95%CrI −3.79, −2.06), metformin (MD −2.97, 95%CrI −3.69, −2.25), lifestyle modification (MD −3.02, 95%CrI −3.87, −2.18), and placebo (MD −3.04, 95%CrI −3.56, −2.53).ConclusionAtorvastatin was found to be more effective than the other management strategies in reducing the total testosterone level for patients with PCOS. Future studies should focus on the optimal dose.