Decline In Testosterone Levels Research Articles

Association between comorbidities and longitudinal changes in total testosterone among men from the Baltimore Longitudinal Study of Aging.

Previous cross-sectional and longitudinal studies have described decreasing testosterone levels with age in men, without consideration of acquired comorbidities in aging males. We evaluated the longitudinal association between age and testosterone levels as well as the impact of several comorbidities on this relationship using multivariate panel regression analysis. Participants were selected from the Baltimore Longitudinal Study of Aging. Data were obtained on the presence of several comorbidities and total testosterone level during each follow-up visit. A multivariate panel regression analysis was performed to determine the impact of age on testosterone level while controlling for individual comorbidities. The primary outcomes were strength of association between age and various comorbidities, and testosterone level. A total of 625 men were included in this study, with a mean age of 65years and a mean testosterone level of 463ng/dL. On multivariable-adjusted panel regression analysis, age was not significantly associated with testosterone decline, while anemia, diabetes mellitus, heart failure, obesity, peripheral artery disease, and stroke were inversely associated with total testosterone level. We report no association between cancer and total testosterone. This study indicates that a decline in testosterone levels over time may be due to the presence of various comorbidities, which affects the medical management of hypogonadism in aging men. The strengths of this study include the standardized acquisition of testosterone tests and uniform collection of variables, while limitations include the lack of follow-up data from 205 patients and the limited racial/ethnic diversity in the cohort. In this large longitudinal study, we found that when adjusted for the presence of concomitant comorbidities, age does not predict a significant decline in testosterone level. With the overall increase in life expectancy and the simultaneous rise in the incidence of comorbidities such as diabetes and dyslipidemia, our findings may help optimize screening and treatment for late-onset hypogonadism in patients with multiple comorbidities.

Misadventures in Toxicology: Concentration Matters for Testosterone-Induced Neurotoxicity.

Testosterone is the predominant androgen in men and has important physiological functions. Due to declining testosterone levels from a variety of causes, testosterone replacement therapy (TRT) is increasingly utilized, while testosterone is also abused for aesthetic and performance-enhancing purposes. It has been increasingly speculated that aside from more well-established side effects, testosterone may cause neurological damage. However, the in vitro data utilized to support such claims is limited due to the high concentrations used, lack of consideration of tissue distribution, and species differences in sensitivity to testosterone. In most cases, the concentrations studied in vitro are unlikely to be reached in the human brain. Observational data in humans concerning the potential for deleterious changes in brain structure and function are limited by their inherent design as well as significant potential confounders. More research is needed as the currently available data are limited; however, what is available provides rather weak evidence to suggest that testosterone use or abuse has neurotoxic potential in humans.

Ameliorating effect of blueberry consumption on energy drink-induced testicular damage in rats: histological and immunohistochemical study

BackgroundEnergy drinks prevent fatigue and increase physical and cognitive performance; however, they also inflict toxic effects on the body. Blueberry (BB) possesses antioxidant and anti-inflammatory properties. The present study aimed to assess the possible the therapeutic effects of BB on testicular damage in adult male Wistar albino rats induced by administering the energy drink Code Red.ResultsThirty adult rats were used in the study, divided into five groups; Group 1 (Control), where rats were fed on distilled water and basal rodent diet only. The other four groups received different energy drink Code Red doses for 8 weeks and BB supplementation for another 6 weeks. Administration of low and high doses of Code Red induced a decline in serum levels of testosterone and antioxidant enzymes like superoxide dismutase (SOD), and glutathione (GSH), while malondialdehyde (MDA) was significantly increased relative to controls. A low dose of Code Red led to sporadic and scattered appearance of seminiferous tubules with loss of spermatogenic germ cells and marked degeneration of interstitial cells. A high dose of Cod Red exhibited increased degenerative changes in the tubules with highly congested thick vessels in the interstitial tissue. Also, testis from rats consuming either low or high doses of Code Red showed increased caspase-3 immunostaining in seminiferous tubules with early degeneration features. However, the deleterious effect of the administration of Code Red was remarkably ameliorated with the supplementation of BB. A reversal in the mutilative effect of Code Red was observed where with BB supplementation, the histopathology of the testis displayed recovery of most of the seminiferous tubules to normal structure. BB administration in both groups also showed negative or mild immunostaining for caspase-3.ConclusionsOral exposure of rats to Code Red produced noticeable testicular damage, especially in high doses, probably due to increased oxidative stress and inflammation. Blueberry administration exhibited therapeutic effects through its anti-inflammatory and antioxidative properties.

The role of hormonal changes in adaptation disorders of young systems in the course of community-acquired pneumonia

Community-acquired pneumoniae are considered as life-threatening infectious diseases and are one of the main causes of morbidity, hospitalization, and mortality. The main goal is to study and assess the role of the hormone imbalance in the adaptation disorders of young organism during the community-acquired pneumonia. To achieve the goals of the research 296 male patients with pneumonia, aged 18-21, were examined. The control group consisted of 63 practically healthy male individuals of the same age. Besides standard examinations, the levels of cortisol, testosterone, prolactin, thyroid stimulating hormone, triiodothyronine, thyroxine, antithyroglobulin and anti-thyroid-peroxidase were determined in the blood serum. The analysis shows that the level of prolactin in all research groups tends to increase; the level of testosterone in all the groups tends to decrease; the level of cortisol in the 18-19 age group tends to decrease; in the 20-21 age group this indicator increases, but it remains below the level of the indicator of the control group. The impact of unfavorable factors of military service, the neuropsychological and physical overstrain, the change in the diet and rations, army-specific conditions, and the unusual situation for some individuals lead to an overstrain and exhaustion of the protective adaptation reactions of the organism, manifested also by hormonal shifts. In the conditions of community-acquired pneumonia, the adaptation process of the organism was accompanied by a similar phasal endocrine shifts, manifested by marginal hyperprolactinemia, a decline in testosterone levels, with no increase in the levels of cortisol detected, regardless of the fact that community-acquired pneumonia was a stress factor for the organism. The main pathogen of the community-acquired pneumonia among the military was mycoplasma pneumoniae and chlamydophila pneumoniae. The course of the pneumonia cases was clinically atypical and rapid, swiftly complicating with hemorrhagic alveolitis. In some cases, the clinical course of the illness lagged behind the findings by X-ray imaging examination results.

The role of hormonal changes in adaptation disorders of young systems in the course of community-acquired pneumonia

Community-acquired pneumoniae are considered as life-threatening infectious diseases and are one of the main causes of morbidity, hospitalization, and mortality. The main goal is to study and assess the role of the hormone imbalance in the adaptation disorders of young organism during the community-acquired pneumonia. To achieve the goals of the research 296 male patients with pneumonia, aged 18-21, were examined. The control group consisted of 63 practically healthy male individuals of the same age. Besides standard examinations, the levels of cortisol, testosterone, prolactin, thyroid stimulating hormone, triiodothyronine, thyroxine, antithyroglobulin and anti-thyroid-peroxidase were determined in the blood serum. The analysis shows that the level of prolactin in all research groups tends to increase; the level of testosterone in all the groups tends to decrease; the level of cortisol in the 18-19 age group tends to decrease; in the 20-21 age group this indicator increases, but it remains below the level of the indicator of the control group. The impact of unfavorable factors of military service, the neuropsychological and physical overstrain, the change in the diet and rations, army-specific conditions, and the unusual situation for some individuals lead to an overstrain and exhaustion of the protective adaptation reactions of the organism, manifested also by hormonal shifts. In the conditions of community-acquired pneumonia, the adaptation process of the organism was accompanied by a similar phasal endocrine shifts, manifested by marginal hyperprolactinemia, a decline in testosterone levels, with no increase in the levels of cortisol detected, regardless of the fact that community-acquired pneumonia was a stress factor for the organism. The main pathogen of the community-acquired pneumonia among the military was mycoplasma pneumoniae and chlamydophila pneumoniae. The course of the pneumonia cases was clinically atypical and rapid, swiftly complicating with hemorrhagic alveolitis. In some cases, the clinical course of the illness lagged behind the findings by X-ray imaging examination results.

Testosterone Replacement Therapy in the Treatment of Depression.

Depression is a common disorder that affects millions globally and is linked to reduced quality of life and mortality. Its pathophysiology is complex and there are several forms of treatment proposed in the literature with differing side effect profiles. Many patients do not respond to treatment which warrants augmentation with other treatments and the investigation of novel treatments. One of these treatments includes testosterone therapy which evidence suggests might improve depressed mood in older patients with low levels of testosterone and helps restore physical impairments caused by age-related hormonal changes. The objective of this review is to synthesize information regarding clinical depression, its treatment options, and the efficacy and safety of testosterone treatment for the treatment of depression. This review utilized comprehensive secondary and tertiary data analysis across many academic databases and published work pertaining to the topic of interest. Within some subpopulations such as men with dysthymic disorder, treatment resistant depression, or low testosterone levels, testosterone administration yielded positive results in the treatment of depression. Additionally, rodent models have shown that administering testosterone to gonadectomized male animals reduces symptoms of depression. Conversely, some studies have found no difference in depressive symptoms after treatment with testosterone when compared with placebo. It was also noted that over administration of testosterone is associated with multiple adverse effects and complications. The current evidence provides mixed conclusions on the effectiveness of testosterone therapy for treating depression. More research is needed in adult men to see if declining testosterone levels directly influence the development of depression.

IMPACT OF COMORBIDITIES ON MALE TESTOSTERONE LEVELS WITH AGE: RESULTS FROM THE BALTIMORE LONGITUDINAL AGING STUDY

To evaluate the longitudinal impact of additive comorbidity burden on testosterone levels in aging males. We hypothesized that age alone in the absence of comorbidities would not predict a significant decline in testosterone level, but development of comorbidities would lead to testosterone decline with aging.

Lower urinary tract symptoms following discontinuation of long-term non-medical use of testosterone preparations

Introduction. The aging process in men is accompanied by a progressive decrease in the level of serum testosterone (Tc). In addition to chronological aging, various factors contribute to the decline in testosterone levels. One of such factors contributing to the decrease in endogenous Tc and the development of secondary hypogonadism is the long-term use of testosterone preparations (TPs) used for non-medical purposes.Objective. To assess the nature of lower urinary tract symptoms following discontinuation of long-term non-medical use of testosterone preparations.Materials and methods. A clinical and statistical analysis of examination results in 31 men aged 22 – 46 years who received TPs for non-medical purposes while visiting gyms and subsequently turned to urologist with complaints of lower urinary tract symptoms (LUTS) was carried out. The study used the International Prostatic Symptom Score (IPSS) questionnaire, laboratory and instrumental examinations: general urine examination, general blood examination, prostate secretion microscopy, evaluation of serum total Tc, follicle-stimulating and luteinizing hormones, prolactin, estradiol, prostate ultrasound and bladder ultrasound, uroflowmetryResults. When assessing LUTS, the prevalence of irritative symptoms was noted. The level of serum total Tc in 13 (41.9%) men was in the range of 8 – 11 nmol/l, in 18 (58.1%) men it was below 8 nmol/l. In addition, most patients (77.4%) had areas of reduced blood flow in the prostate, and 67.7% had prostate fibrosis.Conclusion. Discontinuation of the use of long-term non-medical TPs can lead to the development of secondary hypogonadism and LUTS, which in most cases are irritative. In the treatment of these patients, an interdisciplinary rehabilitation program should be developed.

Chronic And Acute Effect Of Training And Competition On Hormone Levels In Amateur Masters Cyclists

The popularity of amateur masters cyclists (AMC) regularly engaging in high intensity training and competition is increasing. Limited data exist on hormonal changes in AMC during intense training and long races. While some studies demonstrate the beneficial effects of lifelong exercise, others suggest that intense exercise can lead to hypogonadism in men. PURPOSE: To examine hormone levels at baseline (BL) and post competition (PC) during a multistage cycling race in highly trained male AMC. METHODS: 18 male AMC competing in a multistage mountain bike race volunteered to participate in the study. Six weeks before the race a BL evaluation was conducted including anthropometric data and cardiopulmonary maximal exercise test (CPET), participants also reported their physical activity and training habits in the prior three months. Blood samples for total testosterone (TT), cortisol and IGF1 levels were obtained at BL and one hour PC of 1st and 2nd race stages. Race times and exercise intensity expressed as heart rate zone were recorded for each stage. RESULTS: Mean age was 50 ± 5.6 years, weight 76.9 ± 7.9, % fat mass 18.9 ± 2.5. On CPET participants achieved mean V̇O2max of 50.7 ± 6.5 ml/kg/min, maximal power was 327.5 ± 45 W, respiratory anaerobic threshold was 86% of V̇O2max. The average reported cycling distance was 210 ± 63 km/week. The first and second stages of the race were completed with average times of 5:57 hours (94.2 K with 1158 m elevation) and 5:27 hours (90.2 K with 1204 elevation), respectively. Time spent in high intensity (4-5 zones) was 31% and 21% of racing stages 1 and 2, respectively. BL hormonal profile was within normal range for TT 16.8 ± 5.2 nmol/L (normal range 6.7-25.7); cortisol 281 ± 57 nmol/L (normal ranges 101 - 536) and IGF1 186.8 ± 47.9 ng/ml (normal range:78-210). TT levels PC deceased by 32% after stage 1 and 39%, after stage 2 (p < 0.0001), cortisol levels increased by 62% after stage 1 and 50% after stage 2 (P = 0.002) and IGF1 increased by 15% after stage 1 and 12% after stage 2 (P = 0.004) in comparison to BL levels. CONCLUSIONS: Adoption of long-term physical training in AMC, did not reduce TT levels to below normal levels. The race resulted in an acute increase in serum cortisol and IGF levels and a decline in testosterone levels.

Non-invasive approach for sterilization in male dogs using therapeutic ultrasound

The objective of this study was to evaluate the efficacy of noninvasive technique of sterilization in male dogs using therapeutic ultrasound. Twelve male dogs were randomly divided into two equal groups subjected to therapeutic ultrasound application with frequenciesl MHz (group B) and 3MHz (group B) performed on days 0, 2, 4, 6 and 8, for 5 minutes in animals of both groups. Sterilization by therapeutic ultrasound application was confirmed by atrophy of testes grossly and by testicular histopathology microscopically. It was concluded that the therapeutic ultrasound sterilization technique is satisfactory in dogs as sufficient testicular degeneration, considerable decline in testosterone levels and azoospermia was evident during post-therapeutic period. Treatment with therapeutic ultrasound with frequency of 1 MHz had better results than 3 MHz.

Testosterone, Depression, and Cognitive Impairment in Men: an Attempt at Practical Analysis

Cognitive impairment (CI) accompanies the aging process and is manifested by difficulties with memorization, learning, concentration and decision-making, which greatly complicates the daily life of the suffering subject. In addition, medical care and social adaptation of these patients are costly and put a significant strain on the health care system. According to a forecast by G. Corona’s group, the number of people with CIs will increase significantly in the coming years, reaching 131.5 million by 2030. To date, a significant amount of researches has been conducted to uncover the mechanisms of development and risk factors of CI in order to develop effective prevention and treatment programs. Age-related decline in testosterone levels are among the potentially modified risk factors of СI. The objective: to analyze the role of testosterone in pathogenesis of cognitive impairment and depression and the possibilities of testosterone therapy to correct them. Materials and methods. Evidence was collected from the study publications and meta-analyzes exploring the role of testosterone in pathogenesis, prevention and correction of cognitive impairment and depression over the past five years and preliminary analysis of data from our own study involving 547 men with hormonal disorders. Results. Cerebral vessels are the target for the direct (via androgen receptors) and indirect (via influence on cardiovascular risk factors) action of androgens. The testosterone insufficiency is associated with both metabolic and cardiovascular disorders (hypertension, diabetes, hyperlipidemia, obesity), as well as depression and CI. Serum-free-testosterone and free testosterone index are the most sensitive biomarkers of testosterone insufficiency in patients with depression and CI. The corrective effect of testosterone therapy (TT) on depression and CI depends on their severity and levels of androgens: a clinically and statistically significant effect was registered in mild disorders with androgen deficiency. The findings of the meta-analysis do not support the use of TT for improving attention, memory (working, verbal, visual), executive function, speech, visual-motor and visual-spatial abilities in subjects with eugonadism and hypogonadism. According to preliminary analysis of the results of our study, the nature of psycho-emotional disorders is determined by the sexual constitution (SC): weak type of SC (feminine men) is associated with the higher incidence of anxiety, the strong type of SC – with propensity for depression, the middle type of SC – with aggression. Thus, testosterone, estrogens, vasopressin, and adrenaline levels should be measured in patient with aggression. Conclusions. Despite the importance of androgens for mood and cognitive functions, and their synchronous decline during the aging process, the place of TT in the prevention/ correction of whole spectrum of CIs is still unclear. It is obvious now that TT can be justified in patients with mild disorders and proven androgen signal attenuation, but in most cases has no independent meaning. Further studies to find optimal TT indications and regimes are mandatory.

Does Exist a Differential Impact of Degarelix Versus LHRH Agonists on Cardiovascular Safety? Evidences From Randomized and Real-World Studies.

The main systemic therapy for the management of hormone-sensitive prostate cancer (PC) is androgen deprivation therapy (ADT), with the use of long-acting luteinizing hormone releasing-hormone (LHRH) agonists considered the main form of ADT used in clinical practice to obtain castration in PC. The concomitant administration of antiandrogens for the first weeks could reduce the incidence of clinical effects related to the testosterone flare-up in the first injection of LHRH. On the contrary, Gonadotropin Rh (GnRH) antagonists produce a rapid decrease of testosterone levels without the initial flare-up, with degarelix commonly used in clinical practice to induce castration in PC patients. Even if no long-term data are reported in terms of survival to define a superiority of GnRH or LHRH, for oncological efficacy and PC control, data from randomized clinical trials and from real-life experiences, suggest a difference in cardiovascular risk of patients starting ADT. The age-related decline in testosterone levels may represent a factor connected to the increase of cardiovascular disease risk, however, the role of ADT in increasing CV events remains controversial. For these reasons, the aim of the paper is to synthesize the difference in cardiovascular risk between LHRH and degarelix in patients undergoing ADT. A difference in cardiovascular risk could be indeed an important parameter in the evaluation of these two forms of castration therapy. The Randomized trials analyzed in this paper sustain a possible protective role for degarelix versus LHRH agonists in reducing the rate of new CV events and interventions in the short-term period. On the contrary, real-word data are contradictory in different national experiences and are strongly conditioned by huge differences between the LHRH agonists group and the degarelix group.

Antioxidant and Anti Infertility Potency of Pomegranate (Punica granatum L.) in γ Irradiated Rats

THIS study aims at examining the radiation protection activity of pomegranate extract against oxidative stress, lipid profile escalation (T. cholesterol and Triglycerides) and infertility (sex hormone profile and sperm abnormalities) progressed in male rats after ionizing irradiation. Rats were divided into four groups, six adult male rats each as follows: 1) control group, 2) pomegranate group treated with a concentration of 22mg pome extract/kg of animal body weight (day after day for two weeks), 3) irradiated group exposed to 5 Gy single dose, and 4) pomegranate and irradiated group treated with the same previous concentration of pomegranate extract before being exposed to a 5 Gy single dose of gamma rays. Measurements in irradiated group recorded disturbances in oxidative stress markers manifested by significant increases in the content of the lipid peroxidation product malondialdehyde (MDA) accompanied by decreases in both glutathione (GSH) contents and superoxide dismutase (SOD) activities. Lipids were also affected by irradiation where significant elevations for both cholesterol and triglycerides were observed. The data obtained for sex hormones levels recorded a significant decline in testosterone level. This decline was associated with abnormalities in sperms (abnormalities of the head, tail and both head & tail). However, the level of FSH and LH recorded significant elevations. Furthermore, in the group of rats that received pome extract before exposure to radiation, the results revealed that pomegranate appear to have a strong ability to cause a significant guard for sex hormones, preventing sperm abnormalities and adjustment of oxidative stress markers & lipid profile.

Association of Serum Testosterone and Luteinizing Hormone With Blood Pressure and Risk of Cardiovascular Disease in Middle-Aged and Elderly Men.

BackgroundThe age‐related decline in testosterone levels is thought to be of great importance for male aging and cardiovascular diseases. However, data are controversial on whether abnormal sex hormones are linked to the presence of cardiovascular diseases and it is also uncertain how blood pressure modifies the association between testosterone levels and major cardiovascular diseases.Methods and ResultsThis is a multicenter, population‐based, cross‐sectional study of 6296 men conducted between 2013 and 2016. Basic information and clinical symptoms were obtained by questionnaires. Blood pressure and plasma levels of total testosterone, sex hormone–binding globulin, luteinizing hormone, and free testosterone were determined in men in a multistage random, cluster sampling in 6 provinces of China. There were 5786 Chinese men (mean [SD] age 55.0 [10.1] years) included after exclusion criteria were applied; 37.2% (2150) of them were diagnosed with hypertension. Total testosterone, free testosterone, and sex hormone–binding globulin were inversely associated with the prevalence of hypertension. Age >65 years or body mass index ≥24 negatively impacted the inverse correlation between testosterone levels and hypertension, whereas smoking and family history of hypertension strengthened the correlation. In participants with grade 2 hypertension, total testosterone was positively associated with the presence of stroke, and luteinizing hormone was also positively correlated with cardiovascular and cerebrovascular diseases.ConclusionsLower total testosterone could be a promising risk marker for prevalent hypertension. Both low and high levels of testosterone are associated with greater cardiovascular risk. Primary hypogonadism may be a risk marker for major cardiovascular diseases in men with severe hypertension.

Association between testosterone level and coronary artery disease

Background: With increasing age, men experience a gradual decline in testosterone levels. It had long been considered that male sex is a strong risk factor for coronary artery disease (CAD). Aim and Objective: The aim of the study was to evaluate the difference between the Plasma Sex Hormone and the degree of Coronary Artery Stenosis in male patients undergoing Coronary Angiography and in matched controls. Materials and Methods: This study was done at the Department of Physiology, Thanjavur Medical College Tamil Nadu. Participants (n = 80) were recruited from the population in and around Thanjavur. The Institute Ethical Committee approval was obtained for this study. Subjects who met inclusion and exclusion criteria were included in this study as control group: Group A (n = 40) and study group: Group B (n = 40). Informed, written consent was taken from both groups. We studied the Plasma Sex Hormone parameters such as Serum Testosterone level (ng/dL), follicle-stimulating hormone level (mIU/ml), and luteinizing hormone level (mIU/ml) were analyzed by Chemo Luminescence Immunoassay. Before the hormonal assay, the angiogram report was obtained from the cardiologist. Results: The mean testosterone level was 6.837 ± 2.330 for Group A and the mean testosterone level for Group B was 4.967 ± 2.734, for which P = 0.001 (

Gut Environment Changes Due to Androgen Deprivation Therapy in Patients With Prostate Cancer

Background: It is estimated that up to 2040 there will be 1,017,712 new cases of prostate cancer worldwide. Androgen deprivation therapy (ADT) is widely used as a treatment option for all disease stages. ADT, and the resulting decline in androgen levels, may indirectly affect gut microbiota. Factors affecting gut microbiota are wide-ranging; however, literature is scare on the effects of ADT on gut microbiota and metabolome profiles in patients with prostate cancer. Methods: This 24-week observational study investigated the relationship between testosterone levels in Japanese patients with prostate cancer undergoing ADT, with changes in gut microbiota. Sequential faecal, and serum blood samples were collected 1 and 2 weeks before ADT, and 1, 4, 12, 24 weeks after ADT. Bacterial 16S rRNA gene-based microbiome analyses, and capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS)-based metabolome analyses were performed. Findings: A total of 23 patients completed the study. The α- and s-diversity of gut microbiota decreased significantly at 24 weeks after ADT (p=0.017, p<0.001, respectively). Relative abundances of Proteobacteria, Gammaproteobacteria, Pseudomonadales, Pseudodmonas, and concentrations of urea, lactate, butyrate, 2-hydroxyisobutyrate and S-adenosylmethionine (SAM) changed significantly after ADT (p<0.05). There was a significant positive correlation between the abundance of Proteobacteria, a known dysbiosis indicator, and the concentration of lactate (R=0.49, p<0.01). Interpretation: The decline in testosterone levels resulted in detrimental changes in gut microbiota. This dysbiosis may contribute to an increase in frailty and an increased risk of adverse outcomes in patients with prostate cancer. Clinical Trial Registration Information: This study was also registered in the UMIN clinical registry (UMI21161). Funding Information: This work was supported in part by JSPS KAKENHI (18H04805 to S.F.), AMED-CREST (JP20gm1010009 to S.F.), JST ERATO (JPMJER1902 to S.F.), the Takeda Science Foundation (to S.F.), the Food Science Institute Foundation (to S.F.), the Programme for the Advancement of Research in Core Projects under Keio University’s Longevity Initiative (to S.F.). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: This study was conducted in accordance with the ethical principles of Declaration of Helsinki. The samples and clinical information used in this study were obtained by written informed consent, and with the approval of the institutional review boards of Juntendo University school of Medicine (Approval number: 14-117).

Low semen quality and adverse histological changes in testes of adult male mice treated with bee venom (Apis mellifera).

Background:Male infertility has been on the rise since the past seven decades. Recently, in Libya, bee venom therapy (BVT) has become a popular method among alternative healthcare practitioners for treating male infertility. However, a literature search did not find any published studies that investigated the use of BVT for infertility treatment.Aim:To investigate the effect of bee venom on the male reproductive status through measurements of semen quality parameters and testicular histological changes in adult male mice.Methods:A total of 48 male mice were randomly divided into three experimental groups (which were subdivided into two subgroups with eight mice each) as follows: control, bee venom sting (BVS), and bee venom injection (BVI). The normal control subgroup mice were not subjected to any treatment, while the vehicle control subgroup mice were injected (i.p.) with 200 μl of 0.9% saline solution. In the BVS-treated subgroups, each mouse was stung by one live bee for five times (BVS-5) or seven times (BVS-7) every third day for 2 or 3 weeks. While each mouse in the BVI-treated subgroups received 23 μg/kg in a dose volume of 200 μl BVIs (i.p.) for five times (BVI-5) or seven times (BVI-7) every third day for 15 or 21 days.Results: The findings of this study showed that repeated bee venom treatment by sting or injection to adult male mice resulted in a significant decline in testosterone levels, sperm count, sperm motility, and a very significant increase in the percentage of abnormal sperm morphology; also, there were harmful testicular histological changes in the structural organization of seminiferous tubules and degenerative changes in the germinal epithelium compared to control group. Conclusion:The results of this study provide evidence for the low semen quality and adverse testicular histological changes in male mice treated with bee venom. Hence, there is a desperate need for educating alternative healthcare practitioners and infertile couples about the harmful effects of BVT on reproductive status.

Comparative immuno-modulatory effects of basil and sesame seed oils against diazinon-induced toxicity in rats; a focus on TNF-α immunolocalization.

Diazinon (DZN), a common organophosphorus insecticide (OPI), has hazardous effect to human and animals with its ubiquitous use. Considering the implication of reactive oxygen species (ROS) in the OPIs toxicity, the present study was aimed to evaluate the ameliorative properties of basil (BO) and sesame (SO) seed oils against the toxic effect of DZN. Forty adult male albino rats were divided into four experimental groups (n = 10 rats/group); control, DZN (10mg/kg b.w/day), DZN + BO (5ml/kg b.w/day), and DZN + SO (8ml/kg b.w/day) groups, treated for a period of 4weeks. DZN-exposed animals showed significant elevation in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) with a significant decline in testosterone level compared with control. On the other hand, DZN + BO and DZN + SO groups revealed significant decreases in ALT, AST, BUN, and Cr with a significant increase in testosterone level when compared with DZN-exposed animals. Oxidative/antioxidant indices revealed significant increases of malondialdehyde (MDA) levels along with significant decreases of superoxide dismutase (SOD), glutathione peroxidase (Gpx), and catalase (CAT) activities among DZN-treated rats compared with control. Distinctly lower levels of MDA and increased activities of SOD, Gpx, and CAT were evident in both DZN + BO and DZN + SO groups when compared with DZN-exposed animals. Inflammatory and immuno-modulatory markers assessment showed a significant increase in TNF-α with a significant decline in IL-10 level in DZN group; meanwhile, both DZN + BO and DZN + SO groups revealed significant declines in levels of TNF-α with significant increases in IL-10. Corresponds immunohistochemistry, the total scores (TS) of TNF-α immunostainings in hepatorenal, testicular, and epididymal tissues of control, DZN + BO and DZN + SO groups were significantly lower than those values of DZN group. Additionally, the examined tissues of DZN + BO group revealed significant lower TS of TNF-α immunostaining compared with DZN + SO group. The overall data suggested that both BO and SO can be efficiently used as preventive herbal compounds against DZN-induced oxidative stress with special reference to their possible antioxidant, anti-inflammatory, and free radical activities. However, BO has more potent protective effect against DZN-induced tissue injury at both immunohistochemical and molecular levels.

IS TESTOSTERONE PROGNOSTIC IN PROSTATE CANCER TREATMENT? THE UROLOGICAL STANDPOINT.

SUMMARYProstate cancer (PC) is known as an androgen-dependent tumor with testosterone as its natural growth factor, its action is mediated by the androgen receptor (AR) important for the biology and progression of PC. During aging a progressive decline in testosterone levels begins, caused by disability of aged Leydig cells to produce testosterone in response to luteinizing hormone. Surgical treatment of PC can influence the hypothalamic-pituitary-gonadal axis with less impact on it compared to patients treated with radiation. Patients with pre-operative low baseline testosterone level had mean Gleason score higher and AR expression was higher; significantly lower testosterone levels were recorded in patients with lymph node metastases. But some data are conflicting, and some results are opposite to those mentioned before. These data show that there is no significant association between all sex hormone in men and lethal PC or total mortality. In patients with metastatic PC, results showed that elevation of baseline androstenedione levels was predictive of prostate-specific antigen (PSA) response; higher baseline androstenedione levels were associated with an improved overall survival. In these patients, the relationship between serum testosterone and PC prognosis varies in different clinical settings and according to androgen deprivation therapy administration.

Sodium Fluoride and Fluoride Contaminated Ground Water Induced Altered Reproductive Performances in Male Rats.

Present study was undertaken to investigate the toxic effect of sodium fluoride (NaF)- and fluoride (F)-contaminated ground water on reproductive performances of male rats. Healthy adult male rats were categorised into three groups, first group of rats were served as control, whereas secondgroup of rats wereorally intubated with NaF (10mg/kgbw/1ml/rat) and third group of rats wereallowed to drink F-contaminated ground water (5mg/L)through drinking water bottles for 52days. Exposure of NaF- and F-contaminated ground water caused significant decline in sperm motility, serum concentration of testosterone, and increase in sperm abnormality compared with controls. Further, significant histological alterations characterized with shrunken seminiferous tubules and degeneration of different stages of spermatogonial cells wereobserved in rats treated with NaF- and F-contaminated ground water. After the confirmation of toxic effect of F, these NaF- and F-contaminated ground water-treated male rats were allowed to mate with proven fertile untreatedfemale rats to study the reproductive performances of male rats. There was a decline in parturition index, fertility index of male and female, gestation index and number of pups delivered in NaF-treated male rats compared with controls. However, gestation index and number of pups delivered were declined in F-contaminated ground water-treated male rats compared with controls. These results clearly indicate that F exposure affected the reproductive performances of male rats. The present study further revealed the fact that F-induced decline in testosterone levels, reduced sperm motility, and loss of spermatogonial cells affected the reproductive performances of male rats.