Testosterone Concentrations Research Articles

Obesity is associated with hyperandrogenemia in a nationally-representative sample of U.S. girls aged 6-18 years.

Studies have associated obesity with peri-pubertal hyperandrogenemia. However, these studies were performed in academic centers and could have been influenced by selection bias. To investigate if free testosterone levels are elevated in peri-pubertal girls with obesity. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2013-2016 databases. 1,299 girls aged 6-18 years residing in U.S. Mean free testosterone concentration (calculated from total testosterone and sex hormone-binding globulin). Among girls aged 6-9 years, mean (95% CI) free testosterone was 0.33 pg/ml (0.28-0.38) in healthy weight girls vs. 0.86 pg/ml (0.67-1.05) in girls with obesity. Among girls aged 10-14 years, free testosterone was 2.29 pg/ml (2.05-2.53) in healthy weight girls vs. 4.10 pg/ml (3.60-4.60) in girls with obesity. Among girls aged 15-18 years, free testosterone was 3.33 pg/ml (2.96-3.70) in healthy weight girls and 5.64 pg/ml (4.93-6.36) in girls with obesity. Girls with obesity in all age groups had higher free testosterone levels compared to healthy weight girls. In each age group, the 95% CIs for free testosterone did not overlap between healthy weight vs. obesity subgroups. A multiple regression model accounted for 42% of the variance in free testosterone (R2=0.42), and both weight and age categories were independent predictors of free testosterone (p<0.0001 for each). In a nationally-representative sample of U.S. girls, obesity is associated with elevated free testosterone, suggesting an important relationship between obesity and peri-pubertal hyperandrogenemia.

Integrated stress response mediates HSP70 to inhibit testosterone synthesis in aging testicular Leydig cells

The integrated stress response (ISR) is implicated in age-related diseases, while the molecular chaperone heat shock protein 70 (HSP70) can facilitate proper protein folding. However, the regulatory mechanism of ISR in insufficient testosterone synthesis of aging Leydig cells (LCs) remains unclear. This study aims to elucidate the regulatory role of ISR in inadequate testosterone synthesis of aging LCs. We observed a positive correlation between testosterone and HSP70 levels, which were found to be decreased in elderly men. ISR was detected in testicular tissue from old mice. The expression of testosterone synthesis related protein and the content of testosterone decreased in testicular tissue of old mice. Conversely, inhibition of the integrated stress response in testicular tissue led to an increase in steroid synthase expression among old mice. Furthermore, inhibiting ISR specifically within aging LCs resulted in enhanced protein translation efficiency and increased expression levels of new HSP70 and steroidogenic acute regulatory protein (StAR). These findings suggest that ISR occurrence within aging LCs affects StAR protein expression through regulation of HSP70-mediated translation, consequently impairing testosterone synthesis.

Effectiveness of Acupuncture for Infertility in Patients with Polycystic Ovary Syndrome: A Systematic Review and Network Meta-Analysis.

This study employs a network meta-analysis method to investigate the clinical effectiveness of acupuncture in patients with polycystic ovary syndrome (PCOS) experiencing infertility. Prospective randomized controlled trials (RCTs) of clomiphene citrate (CC) and letrozole (LE) combined with acupuncture in PCOS infertility patients were identified through computerized searches in databases including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and Chongqing VIP Database. The search period was set from inception until August 1, 2023, with no language restrictions. Two researchers screened articles, extracted data, and independently assessed the risk of bias in eligible trials. Data were analyzed and visualized using the R software gemtc package. With patients with medication treatment only set as controls, a meta-analysis was performed to investigate the difference in the pregnancy outcomes of the PCOS patients following medication amalgamated with different acupuncture treatments, namely, manual acupuncture (MA), electroacupuncture (EA), and warm acupuncture (WA). The serum concentrations of follicle-stimulating hormone (FSH) did not exhibit significant changes following acupuncture treatments. Notably, acupuncture-based medication treatment significantly reduced serum levels of luteinizing hormone (LH) and elevated the testosterone (T) concentrations of patients when compared to medication treatment alone. Patients also showed significantly escalated serum estradiol (E2) levels after receiving CC integrated with acupuncture than those given monotherapy of CC. The combined regimen of medication and acupuncture appeared to improve the pregnancy outcomes compared to the monotherapy of medication, as evidenced by the significantly increased success rate of pregnancy. Furthermore, the treatment combination of CC plus WA and LE plus MA yielded the highest probability of achieving the best pregnancy outcomes. For PCOS infertility patients, acupuncture, as a complementary treatment to CC and LE, holds advantages in improving reproductive hormone levels and enhancing pregnancy success rates. The highest probability of achieving the best pregnancy outcomes is associated with the treatment combination of CC with WA and LE with MA.

Beyond T-Trials, T4DM and TRAVERSE: the next large testosterone randomized controlled trial.

Lower testosterone concentrations have been associated with poorer health outcomes in ageing men, but proving causality and demonstrating potential for therapeutic benefit requires randomized clinical trials (RCTs). This review discusses recent observational findings and results of major testosterone RCTs, to explore the need for another, larger trial. Evidence of Leydig cell impairment emerges in men above the age of 70 years. Lower testosterone is associated with diabetes risk, and also risk of incident dementia. An individual participant data meta-analysis found that below thresholds of testosterone of 7.4 nmol/L and 5.3 nmol/l respectively, risks of all-cause mortality and cardiovascular deaths in men increased. Testosterone for the Prevention of Type 2 Diabetes Mellitus (T4DM), a multicentre RCT, showed that testosterone treatment prevented or reverted type 2 diabetes in men at high risk. Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE), a cardiovascular safety trial, demonstrated cardiovascular and prostate safety of testosterone treatment in men with or at risk of cardiovascular disease. T4DM confirmed findings from the Testosterone Trials (T-Trials) that testosterone improved sexual function, and bone microarchitecture and density. However, in TRAVERSE, testosterone-treated men had a higher risk of clinical bone fractures, but not major osteoporotic fractures. Men with disorders of the hypothalamic-pituitary-testicular (HPT) axis causing androgen deficiency warrant consideration for testosterone therapy. In men with an intact HPT axis, testosterone treatment is a pharmacological intervention which requires justification from high quality RCT data. Currently, there is insufficient evidence to justify wider use of testosterone for prevention of cardiometabolic disease. However, there is scope for another large testosterone RCT to investigate whether testosterone treatment might, in older men, extend disability-free survival.

Effect of a plant extract of fenugreek (Trigonella foenum-graecum) on testosterone in blood plasma and saliva in a double blind randomized controlled intervention study.

Many aging men experience reduced energy and libido related to non-optimal testosterone levels. We conducted a randomized double-blind trial with TrigozimR fenugreek extract to assess impact on plasma and saliva testosterone, and some subjective effects. 95 men (40-80y) completed a 12-week intervention, taking 3 tablets daily with 0 mg (placebo; n = 22), 600 mg (n = 21), 1200 mg (n = 25) and1800 mg (n = 27) fenugreek extract and essential nutrients. Samples were collected at weeks 0, 2, 6, and 12. Participants answered a pre- and post-intervention questionnaire on lifestyle and libido. We measured total testosterone (HPLC-MS/MS) and sex hormone binding globulin (ELISA), calculated free testosterone index (FTI), and measured saliva testosterone. Plasma total testosterone and FTI increased after any dose of TrigozimR vs. baseline (13.0%, p = 1.0x10-4 and 16.3%, p = 6.2x10-6), but not vs. placebo (9.0%, p = 0.122 and 11.3% p = 0.059). 1800 mg TrigozimR resulted in 12.2% increased FTI (p = 0.025). Saliva testosterone concentration increased after any dose of TrigozimR vs. baseline (31.1%, p = 2.3x10-4) and vs. placebo (37.2%, p = 0.042). 1800 mg TrigozimR for 12 weeks resulted in 19.6% (p = 0.006) increased saliva testosterone. Compliance was confirmed by enhanced plasma concentration of 25-hydroxy vitamin D3. We observed no subjective effects or side-effects of TrigozimR. TrigozimR increased saliva and plasma testosterone concentration during intervention but only for saliva vs. placebo. Saliva may be preferred for measuring free testosterone due to no protein-bound testosterone.

Effects of short-term oral letrozole on fresh semen parameters, endocrine balance, and prostate gland dimensions in domestic dogs

BackgroundAromatase inhibitors improve male fertility by modifying the hormonal control of spermatogenesis. The present study aimed to investigate the effects of oral administration of letrozole on testosterone and estradiol concentrations and their ratios in blood serum, seminal plasma, prostatic fluid, sperm quality in fresh semen, and prostate gland dimensions. Seven adult male intact mixed-breed dogs were selected. The animals received letrozole (72 µg/kg, PO) daily for four weeks. Blood samplings and semen collections were carried out on days 0 (control), 14 (treatment), 28 (treatment), and 42 (post-treatment).ResultsOur results showed that letrozole administration resulted in a 4.3 fold significant increase in serum, seminal plasma, and prostatic fluid testosterone levels after 14 days. This remained high until the end of the study. Serum and prostatic fluid estradiol levels did not change significantly over the study period. However, the seminal plasma estradiol level showed a significant increase on day 14. The estradiol: testosterone ratio was significantly reduced on day 14 in serum, seminal plasma, and prostatic fluid samples. Letrozole significantly improved the ejaculated spermatozoa viability and concentration after 28 days of oral administration. However, the sperm plasma membrane functional integrity and kinematic parameters were not significantly affected by the treatment. Transabdominal ultrasound examination revealed a significant increase in the height, width, and volume of the prostate gland after 28 days of treatment.ConclusionsAccording to the present research, oral administration of letrozole for 28 days affects local and systemic sex hormone balance leading to an improvement of the ejaculated canine spermatozoa viability and concentration concurrent with an increase in the prostate gland dimensions.

Photoperiodism, testosterone and adult neurogenesis in canaries (Serinus canaria).

Domestic strains of canaries (Serinus canaria) variably respond to photoperiod changes and apparently stay in breeding state for extended periods. Fife Fancy canaries are supposed to be similar to the native species living at 27-39° north where photoperiod significantly changes across the year. Our birds showed reproductive cycles when exposed to light regimes mimicking the annual cycle of photoperiod. However after 6 months in short days (SD: 8L:16D), males developed large testes, as observed by X-ray tomography, and intense singing. Switching to long days (LD: 16L:8D) did not further increase song rate nor testes size but increased song duration, number of syllables per song, and trill occurrence frequency. No sign of regression was observed after 12 weeks in LD but return to SD produced a rapid decrease in testes size and singing activity below values in birds maintained throughout in SD. Fife Fancy thus does not seem to develop absolute but only relative refractoriness. The relatively high singing activity expressed by SD-photosensitive males does not seem to depend on high testosterone (T) concentrations. Singing did not correlate with plasma testosterone (T). Treatment with ATD + Flutamide only marginally decreased song rate and did not affect song quality nor song control nuclei volume. These birds are either supersensitive to low T levels or their reproductive physiology is activated by other mechanisms. Neurogenesis is increased by T and by LD but the function of new neurons incorporated in HVC is poorly understood. We developed a procedure based on X-ray focal irradiation to deplete neural progenitors adjacent to HVC and study the functional consequences. The decrease in neurogenesis increased the variability of T-induced songs in females and decreased their bandwidth. Neurogenesis in HVC thus plays a role in song production and X-ray focal irradiation represents an excellent tool to analyze adult neurogenesis.

Effects of Intrahypothalamic Administration of microRNA Inhibitors and Mimetics on Blood Plasma Biomarkers in the Rat Aging.

The effect of let-7a-5p, miR-9a-3p, miR-132-3p, miR-218a-5p microRNA inhibitors and mimetics, when administered into the dorsomedial nucleus of the hypothalamus (DMN), on the markers of age-related changes in blood plasma in 3-month-old and 24-month-old male rats was studied. In the 24-month-old control rats, the content of C-reactive protein (CRP) increased, and the level of myoglobin decreased compared to the 3-month-old animals. After te administration of miRNA inhibitors, the level of CRP significantly increased, and the content of myoglobin decreased, and after the administration of miRNA mimetics, opposite changes were observed. We found no significant differences in the content of somatotropic hormone and testosterone between the control and experimental groups, as well as between the 3-month-old and 24-month-old animals.

Improving the Determination of Carbon Isotope Ratios of Endogenous Steroids Found in Human Serum.

The determination of serum concentrations of testosterone (T) and 4-androstenedione (A4) was implemented into the steroidal module of the Athlete Biological Passport in 2023. Monitoring T, A4, and the ratio of T/A4 in a longitudinal manner enables the detection of the misuse of low-dose T administrations especially in female athletes, whereas urinary markers of the steroid profile may not be influenced significantly. In contrast to the urinary steroid profile, knowledge on confounding factors regarding serum concentrations of T and A4 is yet comparably scarce, and corroborating exogenous sources of the target analytes by isotope ratio mass spectrometry (IRMS) is desirable. In a recent study, it was demonstrated that carbon isotope ratios (CIRs) of serum steroids can be determined if analyte concentrations permit. The therein-employed method utilized 2D-GC/IRMS, and only a limited number of potential endogenous reference compounds were available. The here-presented approach uses complementary analyte purification strategies, addressing previous limitations. A high-performance liquid chromatography cleanup was developed and fully validated for serum steroids in order to enable all doping control laboratories to potentially implement this method alongside existing protocols for urinary steroids. Besides the already-investigated endogenous steroids cholesterol, dehydroepiandrosterone sulfate, androsterone sulfate, and epiandrosterone sulfate, two additional steroids were included in the test menu, namely, pregnenolone sulfate and 5-androstene-3β,17β-diol sulfate. Serum steroid concentrations down to 25 ng/mL were found to allow robust CIR determinations, and a reference population encompassing 124 male and female athlete samples was investigated to enable the calculation of population-based thresholds for all relevant steroid combinations.

26 Trace minerals to improve bull fertility

Abstract Bull fertility is paramount for reproductive success in cow-calf production systems and there are a variety of factors that influence bull fertility. Trace mineral requirements and recommendations have been established for growing and finishing steers, as well as lactating and pregnant cows, yet no specific requirements have been established for young or mature beef bulls. Nonetheless, trace minerals have been shown to have an important role in sexual maturation and semen quality of ruminants. Research performed in rams indicates that zinc deficiency results in reduced testicular development, decreased testicular concentrations of testosterone, and impaired development of seminiferous tubules. Deficiency of Zn has also been reported to negatively impact male fertility in humans, where men diagnosed with infertility responded positively to Zn supplementation. In growing bulls, diets with greater concentrations of organic forms of Zn, Cu, and Mn, tended to result in earlier attainment of puberty compared with control diets containing inorganic minerals. Furthermore, greater liver concentrations of Zn have been negatively correlated with sperm acrosomal damage in growing bulls, based on flow cytometry analyses. More recent research indicates that the use of hydroxichloride-based trace minerals results in greater liver concentrations of Zn and Cu compared with sulfate sources. While evidence indicates that trace mineral status has an important role in bull fertility, further research is required to better understand the contributions of trace minerals to semen quality. In addition, investigating the impact of trace mineral sources with greater bioavailability on semen quality may result in the development of practical recommendations that optimize bull fertility.

Safety, efficacy, and pharmacokinetics of oral testosterone undecanoate in males with hypogonadism.

Testosterone deficiency results from insufficient testosterone production. Testosterone therapy may require dose titration to reach eugonadal serum testosterone concentrations. The primary objective was the efficacy of oral testosterone undecanoate (TLANDO; Antares Pharma Inc.) in male patients with documented hypogonadism. Secondary objectives included a comparison of oral testosterone undecanoate safety and quality-of-life assessments to 1.62% topical testosterone gel (AndroGel 1.62%; AbbVie). In this phase 3 study, 315 patients were randomized 2:1 to oral testosterone undecanoate or 1.62% topical testosterone gel (NCT02081300). Patients received 225mg oral testosterone undecanoate twice daily, and doses were adjusted by 75mg/dose at weeks 4 and 8 based on average serum total testosterone concentration and maximum observed serum concentration. The primary endpoint was the proportion of patients receiving oral testosterone undecanoate with serum total testosterone concentration within the eugonadal reference range (300-1140ng/dL). Secondary endpoints included the proportion of patients with maximum serum total testosterone concentrations within predetermined limits, safety parameters, and quality-of-life endpoints including the Short Form-36v2 Health Survey, Psychosexual Daily Questionnaire, and International Prostate Symptom Score. Overall mean±SD baseline testosterone was 205.7±71.6ng/dL. For patients receiving oral testosterone undecanoate, 87.4% demonstrated a 24-h average serum total testosterone concentration within the reference range following titration. Oral testosterone undecanoate demonstrated a nominal statistically significantly greater mean change from baseline than 1.62% topical testosterone gel for Short Form-36v2 Health Survey measures of mental health (2.91vs. -0.10; p=0.035), and mental component summary (3.82vs. 0.55; p=0.009); and Psychosexual Daily Questionnaire measure of weekly negative mood (-0.57vs. -0.20; p=0.021). Safety endpoints were comparable between therapies. No deaths or treatment-related serious adverse events were reported. Male patients with hypogonadism receiving oral testosterone undecanoate 225mg twice daily demonstrated improvements in libido and sexual frequency. Serum testosterone concentrations were within the reference range in 87% of patients without dose titration.

Testosterone and the prevention of type 2 diabetes mellitus: therapeutic implications from recent trials.

Type 2 diabetes (T2D) is increasing to epidemic proportions and frequently associated with obesity and a low serum testosterone concentration in men. This review valuates recent randomized controlled trials (RCTs) investigating the effect of testosterone treatment on glycemic control and T2D prevention. The 2-year Testosterone for the Prevention of Type 2 diabetes Trial (T4DM) study showed that in men aged 50 years and over with visceral obesity and impaired glucose tolerance, testosterone treatment on the background of a lifestyle intervention reduced T2D risk by 40%. The Testosterone Effects on Atherosclerosis Progression in Aging Men and Testosterone Trials demonstrated modest improvements in insulin sensitivity and body composition. However, the Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men trial found no significant glycemic benefits over 2 years. Recent data from the Diabetes Prevention Program Outcome Study support the cost efficacy and durability of metformin. In men at high risk of T2D, treatment with testosterone prevents the disease; however, there are caveats to its use and other approaches may be more applicable. Differences in trial designs, age groups, and outcome measures contribute to varying results. HbA1C is a suboptimal outcome measure. Future research should explore potential synergies between testosterone and GLP-1 receptor agonists in T2D management, while considering cost-effectiveness.

Unveiling the mechanisms of reproductive toxicity induced by full life-cycle exposure to environmentally relevant concentrations of tris(2-chloroethyl) phosphate in male zebrafish

Tris (2-chloroethyl) phosphate (TCEP), a commonly used organophosphate flame retardant, has garnered considerable concern owing to its pervasive presence in the environment and its toxic effects on living organisms. The perpetuation of populations and species hinges on successful reproduction, yet research into the mechanisms underlying reproductive toxicity remains scant, particularly in aquatic species. In this work, zebrafish embryos were exposed to TCEP (0, 0.8, 4, 20, and 100 µg/L) for 120 days until sexual maturation, and multiple reproductive endpoints were investigated in male zebrafish. Our results showed that the body weight, body length, and gonadal-somatic index (GSI) were remarkably decreased in all TCEP treatment groups (except GSI in the 0.8 µg/L TCEP-treated group). Long-term exposure to TCEP led to reduced reproductive capacity of male zebrafish, as evidenced by decreased fertilization. Histological observation gave an indication of delayed testicular development and inhibited spermatogenesis under TCEP stress. The content of testosterone (T) was significantly elevated in all TCEP treatment group, whereas 17 β-estradiol (E2) levels remained stable. Transcriptome analysis revealed a lot of downregulated genes involved in steroid hormone biosynthesis, energy metabolism, and sperm motility, which might account for the imbalance of steroid hormone levels, retarded spermatogenesis and declined fertilization success. Overall, these findings offered a thorough understanding of the mechanisms underlying the male reproductive toxicity caused by TCEP, highlight the risk of TCEP on reproductive health of fish.

Physiological Anti-Müllerian Hormone Concentrations in Male and Female Dogs and Cats before and around Puberty.

In recent years several studies established the diagnostic value of anti-Müllerian hormone (AMH) in companion animals. However, less is known about physiological AMH concentrations in young individuals highlighting the necessity to apply the diagnostic findings to this group. The aim of this study was to determine the AMH values of healthy male and female dogs between the age of 8 and 48 weeks, tomcats under 8 weeks and up to 48 weeks of age and queens between 2 to 12 weeks of age. In total, 96 blood samples were collected. Anti-Müllerian hormone was measured in all samples and testosterone was measured in the oldest age group of the males in both species. The hormones were analyzed using a human based chemiluminescence immune assay. Overall, AMH concentrations were higher in males than in females (p < 0.001). According to the AMH concentration there was no difference in males, but queens had significant higher AMH concentrations than bitches (p < 0.001). AMH remained high in males up to week 24 and decreased significantly thereafter (tomcats: p = 0.015; male dogs: p = 0.013), which correlated with an increase in testosterone levels for male dogs only. In bitches, AMH remained below the detection limit until the week 16 and slightly increased subsequently. In queens, AMH was detectable from the beginning with a significant increase in the older age group (p = 0.003). Half of the cats in the older age group even approached the chemiluminescence immune assay's upper limit. The results show that female cats secrete AMH much earlier than female dogs in which AMH secretion begins just shortly before the start of the puberty. In the male animals, the decrease in AMH concentration around puberty was similar in dogs and cats, but a correlation with the increase of testosterone was only observed in dogs. Further research is required to determine the origin of the high AMH concentrations in female kittens and the lack of correlation between testosterone and AMH concentrations in male kittens.

Association between low total serum testosterone and body mass index in Australian survivors of testicular cancer: a retrospective analysis

BackgroundPrimary hypogonadism is a recognised complication in survivors of testicular cancer. However, secondary hypogonadism can result from other causes that suppress the hypothalamic-pituitary axis, including obesity, high dose glucocorticoids, chronic end organ failure, and diabetes. The aim of this study was to explore low total serum testosterone in Australian survivors of testicular cancer and examine associations with body mass index, age, and prior chemotherapy use.MethodsClinical data including height, weight, diagnosis, treatment, and hormonal evaluations during follow-up were extracted from the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group Chemocog study (2007-2012), accompanied by data from two Australian, high-volume testicular cancer centres included in the iTestis testicular cancer registry (2012-2019). Low testosterone was defined by a serum concentration of testosterone (T) < 10 nmol/L, and was classified as primary by a serum concentration of luteinising hormone (LH) > 8 IU/L, otherwise as secondary.ResultsTwo hundred eighty-five individuals with either stage 1 or advanced testicular cancer were included. Of these, 105 (37%) were treated with orchidectomy and chemotherapy. Forty-nine (17%) met criteria for low testosterone during follow-up: 21 (43%) had primary and 27 (55%) had secondary low testosterone. Survivors of testicular cancer with higher body mass index were more likely to display low testosterone, both primary (p = 0.032) and secondary (p = 0.028). Our data did not show evidence of an association between older age or chemotherapy use and low testosterone in our cohort.ConclusionsLow total serum testosterone was common in survivors of testicular cancer, and associated with a higher body mass index prior to orchidectomy, suggesting that elevated body mass index may contribute to low testosterone in this population, and that body weight, diet, and exercise should be addressed in testicular cancer follow-up.

Rotenone-induced cell apoptosis via endoplasmic reticulum stress and PERK-eIF2α-CHOP signalling pathways in TM3 cells

Rotenone (ROT), a widely used natural pesticide, has an uncertain effect on reproductive toxicity. In this study, we used 20 mice distributed randomly into four groups, with each group receiving ROT doses of 0, 2, 4, and 8 mg/kg/day for 28 days. The results demonstrated that ROT induced significant testicular damage, including impaired spermatogenesis, inhibition of testosterone synthesis, and apoptosis of Leydig cells. Additionally, ROT disrupted the normal ultrastructure of the endoplasmic reticulum (ER) in testicular tissue, leading to ER stress in Leydig cells. To further explore whether ROT-induced apoptosis in Leydig cells is related to ER stress, the mouse Leydig cell line (TM3 cells) was treated with ROT at 0, 250, 500, and 1000 nM. ROT inhibited TM3 cell viability, induced cytotoxicity, and reduced testosterone content in the culture supernatants. Furthermore, ROT treatment triggered apoptosis in TM3 cells by activating ER stress and the PERK-eIF2α-CHOP signalling pathway. Pre-treatment of TM3 cells exposed to ROT with the ER stress inhibitor 4-phenylbutyric acid (4-PBA) alleviated these effects, decreasing apoptosis and preserving testosterone levels. Further intervention with the PERK inhibitor GSK2606414 reduced ROT-induced apoptosis and testosterone reduction by inhibiting PERK activity. In summary, ROT-induced male reproductive toxicity is specifically driven by apoptosis, with the PERK-eIF2α-CHOP signalling pathway activated by ER stress playing a crucial role in the apoptosis of Leydig cells triggered by ROT.

Androgenic Alopecia Is Associated With More Severe Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

To evaluate the possible association between androgenic alopecia (AGA) and lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). A total of 148 patients aged over 45 with LUTS secondary to BPH were prospectively enrolled in this study. According to the Norwood-Hamilton classification, the patients were divided into two groups: AGA (n = 69) and non-AGA (n = 79). In addition, the cases of AGA were categorized as vertex (n = 39) and frontal baldness (n = 30). The International Prostate Symptom Score (IPSS), uroflowmetry parameters, prostate volume, serum total testosterone (TT), and free and total prostate-specific antigen concentrations of all patients were assessed and compared between the groups. Correlations between the AGA grade and other variables were also investigated. The serum TT level (354 ± 97.1 vs. 308.6 ± 73.1 ng/dL, p = 0.01), total IPSS (16.1 ± 8.1 vs. 13.4 ± 7.7, p = 0.04), IPSS storage subscore (IPSS-S) (7.1 ± 3.5 vs. 5.8 ± 3.6, p = 0.03), and number of nocturia episodes (2.5 ± 1.4 vs. 1.8 ± 1.4, p < 0.01) were significantly higher in the AGA group than in the non-AGA group. There were no significant differences in any of the parameters between the patients with vertex and frontal baldness. The AGA grade showed a significant positive correlation with the TT level (r = 0.407, p = 0.003), IPSS-S (r = 0.164, p = 0.04), and number of nocturia episodes (r = 0.203, p = 0.015). This study demonstrated that among patients with LUTS, those with AGA had worse symptoms and higher TT levels compared with those without AGA of similar age. Furthermore, the AGA grade was positively correlated with the TT level and storage symptoms.

Low Levels of Cortisol are Associated with HIV infection in Older People: A Hormonal Substudy in the OVER50 Cohort.

People with the human immunodeficiency virus (PWH) who were diagnosed long ago are more prone to age-related conditions and comorbidities than the general population. We hypothesized that older PWH have endocrine abnormalities that may influence the patient's health status. Mean hormonal values across the thyrotropic, somatotropic, corticotropic, and gonadal axis, and percentage of subjects with abnormal values, were compared between PWH aged ≥50 years (n=30) and people without HIV (n=30) (Over50 cohort). Clinical factors were also analyzed as independent variables. PWH had a higher prevalence of comorbidities (36.67% PWH and 20.69% controls had ≥3 comorbidities). Male PWH exhibited lower estradiol levels than male controls (29.75±7.68 pg/mL vs. 35.45±10.04 pg/mL; p=0.0041). Abnormal concentrations of testosterone were found in 35% of male PWH compared to 55% of male controls (mostly above reference values). Cortisol levels were significantly lower among PWH (9.97±4.33 μg/dL vs. 13.56±3.39 μg/dL; p=0.002); 16.6% of PWH exhibited abnormally low levels (<5 μg/dL), compared to 0% of controls, and 3 PWH met criteria for a definitive diagnosis of adrenal insufficiency (<3.6 μg/dL). For the somatotropic axis, growth hormone (GH) levels were significantly lower in male PWH than in controls (p=0.0394). No significant differences were found in relation to the thyroid axis. Hormones are generally similar between the chronic PWH who are receiving ART treatment and the general control population, except for cortisol in both sexes and testosterone and estradiol in men. Some special attention should be given to cortisol in PWH due to a presumably higher risk of adrenal complications.

Effect of Lemon peel extract mediated gold nanoparticles on hematobiochemical and sperm parameter alterations in lead- arsenic induced combined exposure in male rats

Gold was used in the vedic era in India to enhance strength, potency and to combat the aging process in humans. It is one of the few metals which can be used at nano scale due to its resistance to oxidation. Considering the biological activity of gold, the present study was carried out to evaluate the effect of Lemon peel extract gold Nanoparticals (LPGNP) on As + Pb induced reproductive toxicity in rats. In present study twenty-four wistar rats were divided into four groups, group I served as control, group II, III, IV received co-exposure of Sodium Arsenate 13.8mg/kg and Lead acetate 116.4 mg/kg, p.o. daily for 14 days, followed by oral administration of LPGNP @10 and 20 mg/kg, to group III and IV, respectively for 6 weeks. At the end of experiment hematology, reproductive parameters and histopathology of testes was studied. The findings of study revealed significant alteration in hematobiochemical parameters, serum testosterone concentration, sperm motility, total sperm count and sperm viability in rats received As-Pb exposure whereas LPGNP administration caused marked improvement in reproductive parameters. In histopathology of testis, As + Pb caused degenerative changes of seminiferous tubules, and sloughing of spermatogenic cells. In LPGNP treated rats, minimal histopathological alterations were observed in testis. In conclusion LPGNP caused significant improvement in biochemical and sperm parameters and testosterone level in As + Pb induced reproductive toxicity in rats.

The influence of Cola nitida on Testosterone and Progesterone Concentrations in the Overweight Humans under Resting Condition

The influence of Cola nitida on Testosterone and Progesterone Concentrations in the Overweight Humans under Resting Condition