Changes In Testosterone Levels Research Articles

A phase 2 randomized open-label study of oral darolutamide monotherapy vs. androgen deprivation therapy in men with hormone-naive prostate cancer (EORTC-GUCG 1532).

160 Background: Darolutamide is androgen-receptor (AR) inhibitor with low blood–brain barrier penetration and limited potential for clinically relevant drug–drug interactions. Darolutamide has been shown to increase overall survival in combination with androgen deprivation therapy (ADT) in patients with newly diagnosed metastatic hormone sensitive prostate cancer (PC) and, in combination with docetaxel, in men with non-metastatic castration resistant PC. This phase 2 study assessed the efficacy and safety of DARO as a monotherapy without ADT in patients with non-castrate testosterone (T) levels (≥230 ng/dL). Methods: This was a 24-wk, open-label, randomized study of patients with hormone-naïve, histologically confirmed prostate cancer (all stages, with a max of 4 metastatic lesions) requiring hormonal treatment, an ECOG PS score of 0, and a life expectancy >1 y. All patients received DARO 600 mg bid or commercially available LHRH analogue. The primary endpoint is PSA response defined as a ≥ 80% decline at week 24 relative to baseline, in the DARO study arm. The ADT arm is used as an internal control. Secondary endpoints included changes in T levels, safety/tolerability, and quality of life. Results: Among 61 men enrolled, the median (range) age was 72 y (53-86y); 49.2% had metastases; 14.8% and 62.3% had undergone prostatectomy or radiotherapy before study entry. The median (range) of PSA at baseline was 8.9 ng/mL (2.2-333.8). In the DARO arm, the evaluable population with available PSA values at baseline and week 24 consisted of 21 patients. The PSA response rate (>80% PSA decline at wk 24) was 100%, with a median (range) decrease of -99.6% (-94.3, -100) at wk 24 in the DARO arm. Serum T levels increased by a median (range) of 43.4% (5.7-144.0) at wk 24, compared with baseline. In the DARO arm, 45.2% of men reported drug-related AEs (mostly Grade 1 or 2). Most frequent treatment-emergent AEs included gynaecomastia (19.4%), fatigue (12.9%), and hot flush (12.9%). 3.1% of men experienced SAEs, none of which were drug related. HR-QoL measures and ADT arm results will be presented as internal reference. Conclusions: DARO monotherapy (600 mg bid) was associated with significant PSA response in nearly all men with hormone-naïve prostate cancer. Testosterone level changes and most common AEs (gynecomastica, fatigue and hot flush) were consistent with potent AR inhibition. Clinical trial information: NCT02972060 .

Correlation Analysis between Hypogonadal Symptoms and Changes in Body Composition and Physical Fitness after Testosterone Treatment in Men with Testosterone Deficiency.

This study analyzed changes in body composition and physical fitness in men with testosterone deficiency (TD) after testosterone treatment (TT) and examined the correlations of body composition and physical fitness with serum testosterone levels and hypogonadal symptoms. Seventy patients with TD were divided into control (group I, n=23) and experimental (group II, n=47) groups. Patients in the experimental group were administered intramuscular testosterone enanthate (250 mg) for six months. The aging males symptom scale (AMS) score, international prostate symptom score (IPSS), body mass index, waist circumference, and serum laboratory values were measured at baseline and at the end of the study. Bioelectrical impedance analysis was used to assess the patients' body composition. Seven types of basic exercise tests were used to evaluate the patients' physical fitness. After six months, there were no significant differences in group I, while group II had significantly improved IPSS and AMS scores; increased hemoglobin, hematocrit, prostate-specific antigen, and testosterone levels and skeletal muscle mass; and waist circumference, and body fat mass. All elements of the physical fitness test were significantly improved in group II, with the exceptions of flexibility and endurance. Decreased waist circumference was correlated with changes in testosterone levels in group II, and the IPSS, cardiorespiratory fitness, and agility were correlated with improved hypogonadal symptoms. TT improved the hypogonadal and lower urinary tract symptoms in patients with TD and improved body composition, physical fitness, and metabolic syndrome parameters. Increased testosterone and improved hypogonadal symptoms were correlated with a decrease in waist circumference and an improvement in cardiorespiratory fitness and agility. As such, when implementing TT, we should consider whether these areas may be improved, as this can help to predict the effect.

Probiotic and prebiotic supplementation ameliorates chronic restraint stress-induced male reproductive dysfunction.

Restraint stress (RS) can induce male reproductive deficits by activating the hypothalamic-pituitary-adrenal (HPA) axis and causing oxidative stress. Previous studies have shown that probiotics can alleviate neurological and metabolic disorders induced by stress. However, the effects of probiotics on RS-induced reproductive deficits have not been fully elucidated. This study aimed to investigate whether Lactobacillus rhamnosus NCDC-610 (Probiotic-1) and Lactobacillus fermentum NCDC-400 (Probiotic-2) with prebiotic (fructooligosaccharides (FOS)) could prevent RS-induced reproductive deficits. C57BL6/J mice were subjected to RS for four hours daily before oral administration of probiotics (4 × 109 CFU per mice) either separately or concurrently with FOS. The results showed that oral administration of Probiotic-1 and Probiotic-2 protected against RS-induced sperm deficits, including sperm count, motility, morphology, and histopathology of testes, and improved intestinal health. Furthermore, Probiotic-1 and Probiotic-2 prevented RS-induced changes in testosterone levels by up-regulating the expressions of steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage enzyme (P450scc), and 17β-hydroxysteroid dehydrogenase (17βHSD) in the testes. Additionally, Probiotic-1 and Probiotic-2 increased the activities of catalase and superoxide dismutase and reduced the fold change of interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-α), indicating a protective effect against RS-induced oxidative stress. Oral administration of Probiotic-1 and Probiotic-2, either separately or concurrently with FOS (probiotic dose of 4 × 109 CFU per mice and prebiotic 5% w/v), prevented RS-induced activation of the HPA axis and improved male fertility. These findings suggest that L. rhamnosus NCDC-610 and L. fermentum NCDC-400 are safe and effective probiotics for mitigating stress-induced male reproductive deficits.

Association of lipid accumulation products with testosterone deficiency in adult American men: A cross-sectional study.

Testosterone deficiency and changes in testosterone levels are important in men's health and may be associated with fat accumulation. In order to investigate the connection between testosterone and fat accumulation in adult males, we employed lipid accumulation product and compared it to triglyceride-glucose and Homeostasis Model Assessment of Insulin Resistance. An intersecting surface research of participators from 2013 to 2014 was carried out using National Health and Nutrition Examination Survey, in addition, participants from 2015 to 2016 were selected. Using multivariate adjusted logistic regression, the connection between lipid accumulation product, testosterone levels, and testosterone insufficiency was investigated, smoothed curve fitting was calculated to integrate non-linear relationships, and subgroup analysis was performed to identify sensitive populations. After removing all potential confounders, testosterone levels in 1651 subjects tended to decrease with increasing continuous variable lipid accumulation product (β = -0.49, 95% confidence interval [-0.77, -0.22], p = 0.0005) and adding the chance of testosterone deficiency (odds ratio = 1.01, 95% confidence interval [1.01, 1.01], p < 0.0001). In the lipid accumulation product quartile, testosterone levels decreased the most (β = -77.65, 95% confidence interval [-110.99, -44.31], p < 0.0001) and the risk of testosterone deficiency was highest (odds ratio = 2.76, 95% confidence interval [1.47, 5.20], p = 0.0016). The area under the curve values were 0.718 (95% confidence interval: 0.688-0.750) for lipid accumulation product, 0.723 (95% confidence interval: 0.689-0.756) for Homeostasis Model Assessment of Insulin Resistance, and 0.673 (95% confidence interval: 0.640-0.708) for triglyceride-glucose, with no statistical difference between lipid accumulation product and Homeostasis Model Assessment of Insulin Resistance comparisons. The cut-off value of lipid accumulation product ≥52.408 predicted testosterone deficiency with good sensitivity and specificity. Higher lipid accumulation product was linked to a higher incidence of testosterone loss and inadequate, especially in hypertensive and non-smoker. Lipid accumulation product is a better predictor of testosterone deficiency than triglyceride-glucose and does not differ significantly from the Homeostasis Model Assessment of Insulin Resistance phase.

The effect of Nateglinide and Octreotide on follicular morphology and free radical scavenging system in letrazole-induced rat model of PCOS.

To investigate the effects of octreotide and nateglinide on ovarian follicle count, ovarian tissue damage, biochemical parameters and free radical scavenging system in letrazole-induced rat model of PCOS. Forty-two female Sprague-Dawley rats were divided into six groups. Group 1 (Control Group): after localizing the ovaries and the uterine horns, the abdominal wall was closed without any surgical procedure. Group 2 (PCOS Group): PCOS was induced by administrating Letrozole orally for 21 successive days. At the end of 21 days, rats underwent ovarian biopsies. The experimental PCOS model was considered successful in the presence of atretic follicles without granulosa cell stratification. Group 3 (PCOS + Nateglinide Group): Nateglinide was administered by oral dropper for 30 days to the rats in which PCOS model was created. Group 4 (Nateglinid only Group): 30 days of NG was applied to the rats without PCOS. Group 5 (PCOS+Octreotide Group): 0.1 mg/kg/day Octreotide was given intraperitoneally for 4 weeks to the rats in which PCOS model was created. Group 6 (Octreotide only Group): animals without PCOS given 0.1 mg/kg/day Octreotide at the end of the treatment, bilateral oophorectomy was performed and blood samples were collected from all groups. Ovarian tissue was stained immunohistochemically with TLR-4 in addition to conventional staining. In addition to follicle classification, ovarian damage was graded. Serum insulin, FSH and LH, TNF-α, IL-6, SHBG, SOD, IGF-1, MDA and GSH levels were also measured. The cystic and degenerated follicle density of PCOS group was high compared with the other groups. Both cystic and degenerated follicles were significantly reduced in PCOS+NG and PCOS+OC groups compared to PCOS group. There was no difference between the groups in terms of serum LH, FSH and insulin levels (p>0.05). Serum testosterone level was significantly higher in the PCOS group compared to the other groups (p<0.01). Adding OC or NG to PCOS groups did not cause significant changes in testosterone levels. TNF-α and IL-6 levels were high in PCOS group (p<0.03). IGF-1 and MDA levels were higher in PCOS than in other groups (p<0.03, p<0.01 respectively). Adding OC or NG to the treatment normalized IGF-1 and MDA levels. Serum GSH levels were significantly lower in the PCOS group (p<0.05). Adding NG to the treatment increased GSH levels. Both NG and OCT reverses atretic and degenerate follicle damage due to PCOS through TLR-4, antioxidant and anti-inflammatory pathways.

Endoscopic Enucleation of Prostate Could Increase Testosterone Levels in Hypotestosteronemic Patients with Bladder Outlet Obstruction.

We evaluated the impact of endoscopic enucleation of the prostate on testosterone levels in hypotestosteronemic patients with bladder outlet obstruction. We enrolled 294 men with lower urinary tract symptoms (LUTS) who received surgery between January 2019 and December 2020 in simple tertiary centre. The inclusion criteria were as follows: being a male patient aged 45-95 years and having recurrent urinary tract infection, having previously failed medical treatment for LUTS or urine retention, and undergoing bipolar or thulium laser enucleation of the prostate. The preoperative and postoperative data were retrospectively reviewed. This study included 112 men with a mean age of 69.4 years. The mean preoperative and postoperative testosterone levels were 4.8 and 4.98, respectively. Of the patients, 88 (78.6%) received ThuLEP and 24 received BipolEP. We divided the patients into two groups according to preoperative serum testosterone levels: normal-testosterone (≥3 ng/mL) and low-testosterone (&lt;3 ng/mL) groups. A significant change in testosterone levels (p = 0.025) was observed in the low-testosterone group. In contrast, no significant difference in testosterone levels was noted in the normal-testosterone group (p = 0.698). Endoscopic enucleation surgery of the prostate could improve postoperative testosterone levels in hypotestosteronemic patients with bladder outlet obstruction.

Changes in levels of testosterone, insulin sensitivity and metabolic profiles during GnRH therapy: Reciprocity between insulin sensitivity and pituitary responsiveness to GnRH in teenage and young male patients with congenital hypogonadotropic hypogonadism.

A direct evaluation of insulin sensitivity on pituitary response to gonadotropin relasing hormone (GnRH) has not been shown in congenital hypogonadotropic hypogonadism (CHH), despite a growing body of evidence in the association of testosterone concentrations with insulin sensitiviy. The objective of the study was to explore whether increased testosterone concentrations in men with CHH improve insulin sensitivity, or vice versa. A retrospective study at a tertiary centre. Series of male CHH patients were included from Jannuary 2014 to December 2019. Insulin sensitivity indices calculated from oral glucose tolerance test and steroid hormone levels were examined in 52 patients with newly diagnosed CHH and 22 healthy controls. Thirty-two of the 52 CHH patients received pulsatile GnRH therapy with follow-up every 3-6 months. Compared to healthy controls, CHH patients had elevated 2 hpost-load glucose, HbA1c, fasting insulin, HOMA of insulin resistance(HOMA-IR)and decreased Matsuda index and testosterone (p ≤ .01). The median follow-up for patients (n = 32) who received pulsatile GnRH therapy was 13.5 (11.3-24) months (432 person-months in total). GnRH therapy increased testosterone and Matsuda index (p ≤ .0001), whilst decreased platelet count (p = .04), leptin (p = .04), fasting glucose (p = .01)and HOMA-IR (p &lt; .0001) compared with baseline. The median treatment duration first time to reach the lower limit of normal testosterone concentrations of patients with high and low baseline insulin sensitivity was 15 (95% CI:8.1-21.9) and 30 months (21.2-38.8), respectively. Correspondingly, after GnRH therapy, luteinizing hormone responsiveness to GnRH provocative test was more vigorous in patients with high insulin sensitivity than those with low insulin sensitivity [17.0 (9.5-25.9)vs. 8.2 (3.3-13.0), p = .01]. Pulsatile GnRH therapy elevated testosterone levels in male CHH patients, ameliorated impaired insulin sensitivity and attenuated subclinical inflammatory response, increased insulin sensitivity, in turn, may benefit the efficacy of pulsatile GnRH therapy.

The association of serum testosterone with dyslipidemia is mediated by obesity: the Henan Rural Cohort Study.

This study aimed to evaluate the relationships of serum testosterone with dyslipidemia and blood lipid levels and test whether obesity mediated these associations by gender in Chinese rural population. A total of 6150 subjects were finally analyzed in this study. Serum testosterone for each subject was detected by liquid chromatography equipped with tandem mass spectrometry. Logistic regression and linear regression were employed to evaluate the associations of serum testosterone with the prevalence of dyslipidemia and blood lipid levels. Mediation analysis was conducted to identify the mediation effects of obesity on the relationship between serum testosterone and dyslipidemia. After adjusting for multiple confounders, per unit change in serum ln-testosterone levels was associated with a decreased prevalent dyslipidemia in men (odds ratio (OR): 0.785, 95% confidence interval (CI) (0.708, 0.871)). Males with the levels of serum testosterone in the third or fourth quartiles had a 49.4% (OR: 0.506, 95% CI 0.398, 0.644) or 67.1% (OR: 0.329, 95% CI 0.253, 0.428) significantly lower odds of prevalence of dyslipidemia. In addition, a onefold increase in ln-testosterone was related to a 0.043mmol/L (95% CI 0.028, 0.059) increase in high-density lipoprotein cholesterol (HDL-C) in men. Results of the mediation analysis suggested that obesity played a partial role in the association of testosterone with dyslipidemia in men. These findings suggested that serum testosterone levels were negatively associated with lipid levels and prevalent dyslipidemia, and obesity mediated the effects of serum testosterone on dyslipidemia in men, implying that obesity prevention should be highlighted to decrease the prevalence of dyslipidemia related to changes in testosterone levels.

Androgens in postmenopausal women

Key content Androgen therapy can improve sexual wellbeing, libido and sexual arousal in postmenopausal women through its effect on the central nervous system. Testosterone levels gradually decline throughout a woman’s lifespan and testosterone therapy may be useful for menopausal women with sexual dysfunction, in whom estrogen therapy alone has been ineffective. Learning objectives To understand the physiology and the potential impact of changes in testosterone levels in postmenopausal women. To be aware of the potential role of androgen therapy in postmenopausal women with low sexual desire causing distress. To review the available evidence behind the use of androgen therapy for female sexual dysfunction in the menopause. Ethical issues More women are spending a greater proportion of their lives in the postmenopausal period, so it is important to gain a greater understanding of the role of testosterone replacement after the menopause in improving sexual dysfunction. Off‐label use of testosterone gels and creams is common; when prescribing these, clinicians must inform women of the potential benefits and risks as well as the fact that long‐term safety data is still lacking.

Acute effects of para-chloroamphetamine on testosterone and markers of apoptosis in seminiferous epithelium of prepubertal male rats

Serotonin is a neurotransmitter that affects the secretion of gonadotropins and testosterone. In prepubertal male rats, serotonin has a stimulating role in testosterone secretion. Here, we used prepubertal male rats to study the effects of para-chloroamphetamine (pCA) on circulating testosterone and gonadotropins and markers of apoptosis in germ cells from day 1 to day 5 post-treatment. The intraperitoneal administration of pCA induced a significant reduction in concentrations of hypothalamic serotonin and circulating testosterone, but gonadotropins were not affected. In the seminiferous epithelium of pCA-treated rats, increased the number of germ cells positive to markers of apoptosis, concomitantly with alterations in morphometry and the presence of multinucleated germ cells. Levels of testosterone were reduced starting from 1 day after pCA was administered. The time window between the administration of the pCA and collection of samples was sufficient to detect changes in testosterone levels, in contrast with a previous work where no changes were found. There was a possible relationship between the reduction of testosterone and an increase in the number of germ cells positive to apoptosis markers. However, the mechanism that links pCA–testosterone–germ cell positive to markers of apoptosis is unknown. Our outcomes support the view that pCA exposure during the prepubertal stage has an acute impact on testosterone levels and affects the structure and physiology of seminiferous epithelium.

Salivary testosterone in male and female youth with and without autism spectrum disorder: considerations of development, sex, and diagnosis

BackgroundPuberty is characterized by significant physical, hormonal, and psychological changes, which may be especially challenging for individuals with autism spectrum disorder (ASD). Although the etiology of ASD remains uncertain, studies suggest imbalances in hormones, such as testosterone, may modulate the autism phenotype. While differences in fetal and postnatal testosterone have been reported, there is limited literature regarding testosterone variations during adolescence in ASD. We investigated morning salivary testosterone levels in youth with ASD and typical development (TD) to explore hypothesized differences, expecting elevated hormonal levels in ASD compared to TD.MethodsYouth with ASD (n = 140) and TD (n = 104), ages 10 to 13 years, were enrolled as part of a longitudinal study on pubertal development. Pubertal stage was determined by gold standard physical examination, and salivary testosterone was collected in the morning immediately upon waking and 30 min after waking and averaged across 3 days. Diagnostic (ASD/TD) and sex (male/female) differences, as well as interactions with age and puberty, were examined using robust linear mixed effect models.ResultsYouth with ASD showed significantly elevated testosterone concentrations compared to same-age TD peers. After the inclusion of natural cubic splines to account for nonlinearity in age, a significant age-by-sex interaction emerged with distinct developmental slopes for males and females. At younger ages, females had higher testosterone, until about 11.5 years of age, when levels began to plateau, while male testosterone concentrations continued to rapidly increase and surpass females. As expected, more advanced pubertal development was associated with elevated testosterone. In contrast, no significant effect of parent-reported social communication symptoms was observed.LimitationsLimitations include an unequal sex distribution, non-representative sample (e.g., cognition and race/ethnicity), and inability to examine afternoon/evening testosterone due to detection limits.ConclusionsTestosterone may play a unique role in the presentation of ASD, especially during periods of dynamic hormonal changes including puberty. Inherent developmental (age, puberty) and sex-based (male, female) factors play a more prominent role in changes in testosterone levels during adolescence. Even so, future research is warranted to determine the differential expression and impact of exposure to excess testosterone during the pubertal transition for youth with ASD.

Effect of High Testosterone Levels on Endothelial Function in Aorta and Erectile Function in Rats.

BackgroundTestosterone is an important hormone for the physical and mental health of men; however testosterone administration has also been suggested to adversely affect the cardiovascular system.AimTo investigate the effects of excessive testosterone administration on vascular endothelial and erectile function in rats.MethodsA total of seventy-five 12-week-old rats were divided into the following groups: Sham, castrated (Cast), castrated with subcutaneous administration of 100 mg/kg/month testosterone (Cast + T1), and castrated with subcutaneous administration of 100 mg/kg/week testosterone (Cast + T4). To observe the changes in testosterone level after the administration, rats were further divided into the following groups: control; T(6.25), wherein the rats were subcutaneously injected with 6.25 mg/kg testosterone; T(25) per week, wherein the rats were subcutaneously injected with 25 mg/kg testosterone per week; and T(100), wherein the rats were subcutaneously injected with 100 mg/kg testosterone per week. The relaxation responses of aorta were measured in these rats using standardized methods, and their erectile function was also evaluated. Statistical analysis of the obtained data was performed using two-way analysis of variance (ANOVA), Tukey-Kramer's multiple comparison test, or Student's t-test.OutcomesAt the end of the study period, endothelial function was evaluated through measurement of isometric tension, while erectile function was assessed using intracavernosal pressure (ICP), mean arterial pressure (MAP), and the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), sirtuin 1 (Sirt1) and vascular endothelial growth factor A.ResultsThe ICP/MAP ratio in the Cast group (0.42 ± 0.04) was significantly lower than that in the Sham group (0.79 ± 0.07). The ICP/MAP ratio in the Cast + T1 group (0.73 ± 0.06) was significantly higher than that in the Cast group (P < .01) and that of the Cast + T4 (0.38 ± 0.01) group was unchanged (P > .05). The T(25) and T(100) groups exhibited significantly lower responses to ACh than the control group at 4 weeks (P < .01). Meanwhile, the ICP/MAP ratios in the T(25) group (0.44 ± 0.07) and T(100) group (0.47 ± 0.03) were significantly lower than that in the control group (0.67 ± 0.05) at stimulation frequencies of 16 Hz (P < .05). The expression of androgen receptor, Sirt1, and eNOS were significantly lower while that of iNOS was higher in the T(25) group compared with the control group (P < .05).Clinical TranslationThe results based on this animal model indicate that extremely high testosterone levels may affect endothelial and erectile function.Strengths and LimitationsWe found that high-dose testosterone administration decreased endothelial function in aorta and erectile function in rats. A major limitation of this study is that the blood concentration may not be representative of that in humans, and further research is needed.ConclusionThe findings suggest that high doses of testosterone may cause endothelial dysfunction in the aorta and erectile dysfunction in rats and that the blood concentration should be monitored after testosterone administration.Kataoka T, Fukamoto A, Hotta Y, et al. Effect of High Testosterone Levels on Endothelial Function in Aorta and Erectile Function in Rats. Sex Med 2022;10:100550.

Comparing of the effects of sesame oil and rapeseed oil versus suet oil and animal butter on the reproductive system of male rats

ABSTRACT Background The aim of this study was to compare the effect of vegetable oils and animal oils on the reproductive system of male rats. Methods This study was a random and observational study conducted on 36 male rats with the age of 6 weeks weighing 200 ± 20 grams. Different groups were fed by sesame oil, suet oil, rapeseed oil and animal butter. The control group was fed by standard food used normally to feed animals in the laboratories. At the end of six weeks, testosterone level changes and weight changes were compared among different groups. Data were analyzed by SPSS-IBM version 16. Result Weight changes among groups did not show a dramatic statistical difference (P = .571 > 0.005). Average weight in control group was 202 and about the male rats fed by 10% of animal butter and by sesame oil were 206.5 and 99, respectively. Weight changes among groups were significant (P value = 0.005 > 0.0004). The average testosterone level in the control group was 2.4. This value in the different groups fed by 10% oils, the maximum was 12.2 and the minimum was 1.35 assigned to animal butter and rapeseed oil, respectively. So we concluded that using 10% of different oils causes an increase in testosterone level (P value = 0.001 > 0.05). The maximum testosterone level was 3.6 in the rapeseed 20% group and lowest 0.45 in the sesame 20% group. Conclusion We found that animal oil-containing diet has no significant harmful effect on male rat reproductive system in comparison with plant oils.

Evaluation of Serum Testosterone Levels Following Three Months of SA3X (Spilanthes acmella) Supplementation.

Introduction: Low testosterone is usually associated with erectile dysfunction (ED). SA3X (Spilanthes acmella) has proven to be effective in alleviating symptoms of ED, which could be due to an alteration in serum testosterone levels. This study was carried out to evaluate the change in testosterone levels in participants with ED supplemented with SA3X for three months.Materials and Methods: A group of 326 sexually active men aged 25-60 years was investigated from November 2021 to May 2022 in Hyderabad. The participants were subjected to supplementation with SA3X capsules for three months, and a follow-up was done at the end of six months with serum testosterone assessment in each visit. The change in testosterone level was assessed using a mixed model repeated measures analysis.Results: A significant increase was observed in the mean serum testosterone levels by the end of the second month (323.91 ± 13.76 ng/dL vs. 309.84 ± 14.11 ng/dL; p=0.03) and third month (332.27 ± 12.85 ng/dL vs. 309.84 ± 14.11 ng/dL; p<0.01) of SA3X therapy. The adjusted mean change in testosterone levels was found to be 22.43 ng/dL at the end of the three-month therapy. It was also observed that the change in testosterone levels was significantly lower in participants having diabetes mellitus, hypercholesterolemia, and a history of substance abuse. However, participants on phosphodiesterase-5 inhibitors had an increased change in testosterone levels.Conclusion: Supplementation with SA3X capsules for three months increases the serum testosterone levels. However, causality cannot be ascertained owing to the longitudinal nature of the study, and further controlled trials are required for the same.

Declining semen quality and polybrominated diphenyl ethers (PBDEs): Review of the literature to support the derivation of a reference dose for a mixture risk assessment.

To support a mixture risk assessment for chemicals that interfere with male reproductive health, we reviewed the literature to identify studies of polybrominated diphenyl ethers (PBDEs) and poor semen quality. Several epidemiological studies have shown associations of PBDE exposures with declining semen quality, non-descending testes and penile malformations. In rodent studies, poor semen quality, changes in testosterone levels and reproductive tissues have been observed. In vitro studies with reporter gene constructs show PBDE congeners as androgen receptor antagonists, and mixture studies in these systems have demonstrated that PBDE congeners act together with other androgen receptor antagonists. These observations led us to attempt the estimation of reference doses for specific PBDE congeners that can be used in a future mixture risk assessment for deteriorations of semen quality. While epidemiological studies provide support for such associations, they were uninformative for derivations of reference doses, due to the incompatibility of dose metrics used in exposure assessments. We therefore based our estimates on animal studies. Using a rigorous confidence rating approach, we found robust evidence that BDE-47 produced reductions in semen quality. We identified only one high confidence study of BDE-99 and accordingly evaluated the strength of evidence as moderate. One high confidence, and several medium confidence experimental studies observed declines in semen quality after BDE-209 exposure. Using established risk assessment procedures, we estimated that BDE-47 exposures below 0.15μg/kg/d are unlikely to lead to reductions in semen quality. The corresponding exposures for BDE-99 and BDE-209 are 0.003μg/kg/d and 1000μg/kg/d. It is planned to use these estimates as reference doses in a mixture risk assessment of deteriorations in semen quality, involving multiple other chemicals also contributing to poor semen quality.

Catch‐up fat in male adults induces low testosterone and consequently promotes metabolic abnormalities and cognitive impairment

Catch-up fat in adults (CUFA) caused by rapid nutrition promotion after undernutrition plays an important role in the epidemic of insulin resistance (IR)-related diseases in developing societies. Insulin resistance is considered to be closely associated with reduced testosterone levels and cognitive function. However, the effects of CUFA on testosterone levels and cognitive function are unclear in males. To investigate the changes in testosterone levels and cognitive function in CUFA in male humans and rats, and explore their probable relationship and mechanisms in rats. The blood testosterone levels, fasting glucose, and blood insulin (FINS) were measured in subpopulation 1 (27 CUFA individuals, 61 controls without CUFA) aged 40-50 years to show the characteristics of sex hormone levels and the metabolic status in CUFA men. Cognitive Flexibility Inventory was conducted in subpopulation 2 (54 CUFA individuals, 214 controls) over 20 years to investigate the associations between sex hormone levels, cognitive function, and CUFA. Male rats (n = 27) were randomly allocated to the NC group (normal chow controls), RN group (CUFA, refeeding after caloric restriction), and RT group (RN with testosterone intramuscular injected while refeeding). The blood testosterone levels, intraperitoneal insulin tolerance test (IPITT), and FINS were measured, and the attentional set-shifting task test (ASST) for the assessment of cognitive function was performed in these animals. Insulin signaling pathway, N-methyl-d-aspartate receptors subtype 2A (NR2A) and 2B (NR2B) expression levels were determined in the rat cerebral cortex. The total testosterone levels decreased (medium [inter-quartile ranges], 13.43 [9.87-18.96] vs. 15.58 [13.37-24.96], p = 0.036), and HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) elevated (1.61 [1.08-2.33] vs. 1.24 [0.87-1.87], P = 0.037) in CUFA men in subpopulation 1. Additionally, cognitive impairment was observed in CUFA men in subpopulation 2. Moreover, our results indicated decreases in total and free testosterone levels, elevations in visceral lipid accumulation, FINS, HOMA-IR, blood glucose, and the area under the curve after IPITT, increases in the number of trials required to achieve the criterion of the first reversal of discrimination (R1) in ASST, and downregulation of IRS-1 mRNA expression, AKT phosphorylation, and the NR2A and NR2B expression in brain tissue in male CUFA rats. Notably, testosterone supplementation improved visceral lipid accumulation and IR-related metabolic disorders, cognitive dysfunction, decreases in IRS-1 mRNA expression, Akt phosphorylation, and NR2A and NR2B expression in brain tissue in male CUFA rodents. CUFA was characterized by reduced testosterone levels, metabolic abnormalities, and cognitive dysfunction in males, and testosterone supplementation attenuated these changes, as well as the alteration in insulin signaling and NR2A and NR2B expression in male CUFA rodents. Herein, we tentatively put forward that CUFA in males induces low testosterone, consequently promoting metabolic abnormalities and cognitive impairment probably mediated by defects in insulin signaling and NR2A, NR2B pathway in brain tissue.

Impacts of Androgen Abuse and Overtraining on Endocrine Profile in Bodybuilders

Abuse of androgens and overtraining expose bodybuilders to multifactorial stress influences related to endocrine activity. Endocrine responses in 23 bodybuilder athletes were investigated after a strength training period, during which they were taking high doses of androgenic-anabolic steroids. Serum concentrations of TSH, T3, and T4 were unchanged significantly. Serum LH and FSH concentrations decreased dramatically (P&lt;0.05). In addition, low mean concentration of serum testosterone was recorded, with more substantial reduction in participants of elder ages. The multiple regression model used in this analysis supported this inference. On the other hand, a positive association was observed between levels of blood lipids (total cholesterol, triglyceride) and the outcome predictor (mean serum testosterone level). The results also suggested a negative correlation between testosterone level and each of age and HDL level. The current study shows that excessive bodybuilding exercise has an impact on the hypothalamic–pituitary–thyroid (HPT) axis in top-level athletes. Also, simultaneous usage of anabolic steroids induces extreme shifts in the hypothalamic-pituitary–gonadal (HPGA) axis, which is reflected as changes in testosterone level, development of the overtraining syndrome, and adverse influences on hormonal control.

Assessment of hormonal homeostasis in women with abnormal uterine bleeding and chronic stress

The objective: to study the concentration of estradiol, progesterone, follicle-stimulating and luteinizing hormones, testosterone, prolactin and cortisol in women with abnormal uterine bleeding (AUB) and of chronic psycho-emotional stress.Materials and methods. We examined 100 women of reproductive age with AUB and chronic stress (main group) and 50 patients with AUB without chronic stress (comparison group). 30 women without AUB and chronic stress were included in the control group. The AUB diagnosis was made on the basis of order No. 353 of the Ministry of Health of Ukraine dated April 13, 2016. The concentrations of estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin and cortisol were determined in blood serum in all the women in the follicular phase of the menstrual cycle using the ELISA method.Results. In patients with AUB and chronic stress, a significant decrease of estradiol by 37.50% relative to healthy women, FSH – 44.42%, LH – 22.12%, progesterone – 38.23% and a significant increase in prolactin by 41.92% and cortisol – 82.96% were established. In the patients with AUB without chronic stress a significant decrease in estradiol level by 23.95%, FSH by 22.09% and progesterone by 21.91%, and a significant increase in cortisol by 21.55% were found. The concentration of testosterone in the main group and the comparison group, as well as changes in the levels of LH and prolactin in the patients of the comparison group, were insignificant relative to the control group. Conclusions. In women of reproductive age with abnormal uterine bleeding and chronic stress, there is a significant decrease in the concentration of estradiol, progesterone, follicle-stimulating and luteinizing hormones in the blood serum, an increase of prolactin and cortisol, and the absence of significant changes in testosterone level in the follicular phase of the menstrual cycle.

Inter-annual repeatability and age-dependent changes in plasma testosterone levels in a longitudinally monitored free-living passerine bird.

While seasonal trends in testosterone levels are known from cross-cohort studies, data on testosterone inter-annual individual repeatability in wild birds are rare. Also, our understanding of hormonal age-dependent changes in testosterone levels is limited. We assessed plasma testosterone levels in 105 samples originating from 49 repeatedly captured free-living great tits (Parus major) sampled during the nesting to investigate their relative long-term repeatability and within-individual changes. Furthermore, we examined the inter-annual repeatability of condition-related traits (carotenoid- and melanin-based plumage ornamentation, ptilochronological feather growth rate, body mass, and haematological heterophil/lymphocyte ratio) and their relationships to testosterone levels. We show that testosterone levels are inter-annually repeatable in females, with a non-significant pattern in males, both in absolute values and individual ranks (indicating the maintenance of relative status in a population). In males, we found a quadratic dependence of testosterone levels on age, with a peak in midlife. In contrast, female testosterone levels showed no age-dependent trends. The inter-annual repeatability of condition-related traits ranged from zero to moderate and was mostly unrelated to plasma testosterone concentrations. However, males with elevated testosterone had significantly higher carotenoid-pigmented yellow plumage brightness, a trait presumably involved in mating. Showing inter-annual repeatability in testosterone levels, this research opens the way to further understanding the causes of variation in condition-related traits. Based on a longitudinal dataset, this study demonstrates that male plasma testosterone undergoes age-related changes that may regulate resource allocation. Our results thus suggest that, unlike females, male birds undergo hormonal senescence similar to mammals.

The serum levels of testosterone in coronary artery disease patients; relation to NO, eNOS, endothelin-1, and disease severity.

The changes in testosterone level and its correlation with the endothelial nitric oxide systems balance in patients with coronary artery disease (CAD) remains uncertain. Therefore, in our study, we aimed to evaluate the levels of testosterone, endothelin-1 (ET-1), nitric oxide (NO), and endothelial NOS (eNOS) in CAD patients, and control group to find the relationship between these parameters and disease severity. Forty-four patients as CAD group with significant (≥50%) stenosis confirmed by angiography was included in the study, and 40 healthy men were included as the control group. According to the number of vessels obstruction, CAD severity was determined. The serum indicated parameters were assessed to discriminate between patients and controls. It was found that testosterone levels in the CDA group were significantly lower than those of the control group (p<0.05). In addition, the level of ET-1 in the CAD group was higher than that in the control group, but levels of NO and eNOS in observation were significantly lower than those in the control group (p<0.05). The correlation analysis revealed that testosterone was passivity correlated with serum NO levels (r=0.550, p=0.001). The current study reports that serum levels of testosterone are closely related to endothelial NO levels and might be of relevance to the pathogenesis of endothelial dysfunction and disease severity in CAD patients.