Low Serum Testosterone Levels Research Articles

Bone mineral density in adults growth hormone deficiency with different ages of onset: a real-world retrospective study.

Bone mineral density (BMD) impairment is one of the critical factors for long-term quality of life in adults growth hormone deficiency (AGHD). This study aims to investigate the annual changes in BMD in AGHD patients with different ages of onset and to identify predicting factors that influence BMD. AGHD patients (n = 160) with available data for 4 years follow-up from a major tertiary medical center in China were retrospectively included (110 [68.8%] childhood-onset, 119 [74.4%] male). BMD of the axial bone (including total hip, neck of femur, and L1-4) derived from dual X-ray absorptiometry and final height were investigated at the first visit, 12 months, 24 months, 36 months, and 48 months thereafter. Low BMD was defined as Z-score ≤ -2. The prevalence of low BMD was 30.0% at baseline and 12.5% at 4 years of follow-up. The CO AGHD group presented a significantly lower BMD than the AO AGHD group at the baseline (P = 0.009). In contrast, the CO AGHD group had significantly greater median annual BMD change than the AO AGHD group (0.044 vs. -0.0003 g/cm2/year in L1-4, P < 0.001), indicating a significant difference in the overall BMD trend between CO and AO groups. Childhood-onset (odds ratio [OR] 0.326, P = 0.012), low serum testosterone (OR 0.847; P = 0.004) and FT4 (OR 0.595; P = 0.039) level were independent risk factors for BMD loss. The annual changes of BMD show a different pattern in AGHD patients with varying ages of onset. Patients with CO AGHD have a lower bone mass, and in general, appropriate replacement therapy is necessary for long-term bone health in AGHD patients.

Di-(2-ethylhexyl) phthalate exposure induces premature testicular senescence by disrupting mitochondrial respiratory chain through STAT5B-mitoSTAT3 in Leydig cell.

Di-(2-ethylhexyl) phthalate (DEHP), a prevalent plasticizer, is known to have endocrine-disrupting effects on males and cause reproductive toxicity. There were causal effects of DEHP on testosterone levels in the real world by Mendelian randomization analysis. Exposure to DEHP during the preadult stage might lead to premature testicular senescence, but the mechanisms responsible for this have yet to be determined. In this study, we administered DEHP (300mg/kg/day) to male C57BL/6 mice from postnatal days 21 to 49. The mice were kept for 6months without DEHP. RNA sequencing was conducted on testicular tissue at PNM6. The results indicated that DEHP hindered testicular development, lowered serum testosterone levels in male mice, and induced premature testicular senescence. TM3 Leydig cells were exposed to 300μM of mono(2-ethylhexyl) phthalate (MEHP), the bioactive metabolite of DEHP, for 72h. The results also found that DEHP/MEHP induced senescence in vivo and in vitro. The mitochondrial respiratory chain was disrupted in Leydig cells. The expression and stability of STAT5B were elevated by MEHP treatment in TM3 cells. Furthermore, p-ERK1/2 was significantly decreased by STAT5B, and mitochondria-STAT3 (p-STAT3 ser727) was significantly decreased due to the decrease of p-ERK1/2. Additionally, the senescence level of TM3 cells was decreased and treated with 5mM NAC for 1h after MEHP treatment. In conclusion, these findings provided a novel mechanistic understanding of Leydig cells by disrupting the mitochondrial respiratory chain through STAT5B-mitoSTAT3.

(277) A Symbol of Masculinity: Is there a Correlation Between Men's Lower Body and Serum Testosterone Levels?

Abstract Introduction While a robust lower body and strong lower body strength are regarded as symbols of masculinity, the actual relationship with testosterone is not clear. Previous studies have shown a significant correlation between serum testosterone levels and body fat components, but not with skeletal muscle mass. Objective This study aimed to determine if there is any correlation between male lower body strength, lower body size, and testosterone. Methods Serum testosterone levels, waist circumference, weight and BMI measurement, Body composition tests (skeletal muscle mass, body fat mass, body fat percentage, abdominal fat percentage, visceral fat percentage), and physical fitness tests (cardiorespiratory, flexibility, endurance, strength, agility, power, balance) were conducted in 95 men (aged over 40) who visited the hospital for erectile dysfunction. For understanding the lower body size, the circumference of the thigh and calf was measured, and to measure lower body strength, the muscle strength of the knee joint was measured using an isokinetic dynamometer. Patients with serum testosterone levels below 250ng/dL were defined as group I, and those with levels above 350ng/dL were classified as group II. Differences in body composition, physical fitness, adjusted calf and thigh circumference (by weight), and bilateral knee extension and flexion strength (adjusted by weight) were verified using an independent t-test. Pearson's Chi-square test was used to check for differences in lifestyle habits and underlying diseases, and a simple correlation test was conducted to understand the association between serum testosterone levels and lower body size and strength. Results Age did not significantly differ between the groups. Group I had a significantly higher proportion of alcohol consumption and number of underlying diseases. In body composition, Group I had a significant increase in weight, BMI, and waist circumference compared to Group II. The body fat percentage, abdominal fat percentage, and visceral fat percentage were also significantly higher in Group I than in Group II. In physical fitness, cardiorespiratory function, agility, power, and balance showed significantly better results in Group II than in Group I. The comparison of thigh circumference adjusted by weight showed that Group II was significantly larger than Group I, but there was no difference in calf circumference adjusted by weight. Both left and right knee extension strength showed significantly better power in Group II than in Group I, while there was no difference in flexion strength between the two groups. The simple correlation test showed a significant positive correlation between the adjusted values of thigh and calf circumference and serum testosterone levels, and the calf/thigh circumference value showed a significant negative correlation with serum testosterone levels. Left and right knee extension strength also showed a significant positive correlation with serum testosterone levels. Conclusions The circumference of a male's lower body, particularly the thigh, showed a correlation with serum testosterone levels, and in terms of lower body strength, knee extension strength showed a correlation with serum testosterone levels. A robust thigh and strong lower body strength were found to be closely related to testosterone, a symbol of masculinity. Disclosure No.

Prenatal exposure to Di(2-ethylhexyl) phthalate and high-fat diet synergistically disrupts gonadal function in male mice†.

Prenatal exposure to Di (2-ethylhexyl) phthalate (DEHP) impairs the reproductive system and causes fertility defects in male offspring. Additionally, high-fat (HF) diet is a risk factor for reproductive disorders in males. In this study, we tested the hypothesis that prenatal exposure to a physiologically relevant dose of DEHP in conjunction with HF diet synergistically impacts reproductive function and fertility in male offspring. Female mice were fed a control or HF diet 7days prior to mating and until their litters were weaned on postnatal day 21. Pregnant dams were exposed to DEHP or vehicle from gestational day 10.5 until birth. The male offspring's gross phenotype, sperm quality, serum hormonal levels, testicular histopathology, and testicular gene expression pattern were analyzed. Male mice born to dams exposed to DEHP + HF had smaller testes, epididymides, and shorter anogenital distance compared with those exposed to HF or DEHP alone. DEHP + HF mice had lower sperm concentration and motility compared with DEHP mice. Moreover, DEHP + HF mice had more apoptotic germ cells, fewer Leydig cells, and lower serum testosterone levels than DEHP mice. Furthermore, testicular mRNA expression of Dnmt1 and Dnmt3a was two to eight-fold higher than in DEHP mice by qPCR, suggesting that maternal HF diet and prenatal DEHP exposure additively impact gonadal function by altering the degree of DNA methylation in the testis. These results suggest that the combined exposure to DEHP and high-fat synergistically impairs reproductive function in male offspring, greater than exposure to DEHP or HF dietalone.

(084) Low Serum Testosterone is Associated with an Increased Risk of First-time Nephrolithiasis in Men Without Testosterone Replacement Therapy

Abstract Introduction Serum testosterone levels in men have declined on a population level since 1999. Although the role of testosterone in nephrolithiasis is unclear, men are twice as likely as women to develop kidney stones. Some studies posit high testosterone levels as a lithogenic factor, but a recent study showed an inverse relationship between testosterone levels and kidney stones, suggesting that low testosterone may increase the risk of kidney stones in men over 40. The relationship between low testosterone in men and kidney stone risk remains unclear. Objective To determine the association of low serum testosterone levels with the development of incident kidney stones in men without a history of testosterone therapy (TTh). Methods Using TriNetX, a tool that de-identifies and aggregates electronic health record data from tens of millions of patients, we used the TriNetX Research Network to examine men aged ≥18 with a known testosterone level. Men with a history of nephrolithiasis before testosterone measurement and a history of TTh at any point in their life were excluded as both are known to increase the risk of subsequent kidney stones. Men were divided into a low testosterone group (&amp;lt;300 ng/dL) and a normal testosterone group (300-1000 ng/dL). Demographic and clinical characteristics, including comorbidities and medications, were compared using descriptive statistics for all patients. To address potential confounders, we used propensity score matching based on demographic and clinical characteristics (Table 1). We used 1:1 greedy nearest-neighbor matching with a caliper of 0.1 pooled standard deviations of the propensity score. A standardized mean difference of less than 0.1 indicated successful matching. Our outcome of interest was all-time risk of developing an initial kidney stone in men aged ≥18 following a laboratory-confirmed low testosterone. Subgroup analyses was performed on age cohorts. Survival analysis was performed using a log-rank test and Cox proportional hazards regression. All analyses were performed on the TriNetX platform without natural language processing. Results 445,682 men ≥18 with low testosterone were included. The number of men before matching (Table 1) and in each age subgroup after matching is seen in table 2. The percentage of men that developed a diagnosis of nephrolithiasis increased with age regardless of testosterone level (Table 2). In men ≥18, low testosterone was associated with higher risk of incident nephrolithiasis (HR 1.14, 1.11-1.17). Men with low testosterone aged 34-44 (HR 1.28, 1.18-1.40) had the highest risk of nephrolithiasis. Low testosterone was not associated with an increased risk of nephrolithiasis in men aged 18-24 (Figure 1). Conclusions In investigating the association of low testosterone with kidney stones in men without a history of kidney stones or TTh, we found that low serum testosterone is associated with a higher risk of a first-time encounter diagnosis of nephrolithiasis in men greater than 25 years of age compared to men with normal testosterone levels. Men aged 33-44 with low serum testosterone had the highest risk of nephrolithiasis. Future work will investigate the risk of kidney stone recurrence in men with low serum testosterone levels. Disclosure No.

(248) Evaluation of Androgen Receptor Signaling and Saturation in Erectile Dysfunction

Abstract Introduction Testosterone (T) is a steroid hormone responsible for the development and maintenance of male secondary sex characteristics. T exerts this physiologic function throughout by binding to the androgen receptor (AR). It is unclear how AR function varies as a function of serum T. Objective We hypothesized that there is a saturation value for the AR above which excess serum T does not lead to increased binding or downstream signaling. This study evaluated whether varied serum T levels were associated with AR signaling in the penile tissue of men with erectile dysfunction (ED). Methods The mean age of participants was 61 (IQR 8.5) years. The mean serum T level was 300.2 (IQR 231.3). The results of the western blot showed that HO and PDE-5 signaling was decreased in men with serum T less than 200 ng/dL compared to those with serum T above 200, while AR and iNOS expression was decreased in men with serum T less than 300 ng/dL compared to those with serum T above 300. Results Within a wide range of serum T values, AR signaling was similar in penile tissue above 200-300 ng/dL. These findings provide a possible explanation for why PDE5 inhibitors are most effective in men with serum testosterone levels greater than 200 ng/dL, as our western blot results indicate that PDE-5 signaling is diminished in men with lower serum testosterone levels. This suggests that maintaining eugonadal levels of serum androgens is essential for optimal functioning of PDE-5 inhibitors. Conclusions Our findings suggest that there is a limit to the effect of serum testosterone levels on AR signaling, as the downstream activity appears to plateau beyond a certain point of receptor activation. Disclosure No.

Lower pretreatment serum testosterone level predicts poor prognosis in the patients with metastatic hormone-sensitive prostate cancer undergoing androgen deprivation therapy.

This study aimed to reveal the association between pretreatment serum testosterone levels and prognosis in patients with metastatic hormone-sensitive prostate cancer treated with androgen deprivation therapy. A total of 91 patients were included in this retrospective study. Clinical data were obtained through chart review. Multivariate cox proportional hazards analyses addressed the impact of variables on castration-resistant prostate cancer-free and overall survivals. During a median follow-up of 41.7months, 61 (67%) and 49 (54%) patients developed castration-resistant prostate cancer and died, respectively. The median castration-resistant prostate cancer-free and overall survivals were 15.5 and 59.9months, respectively. The cutoff value for discriminating between low- and high-testosterone levels was determined as 450ng/dl by calculating the receiver operating characteristic curve. Patients in the low-testosterone group (n=37) had a significantly higher body mass index, worse comorbidities represented by the higher Charlson comorbidity index and higher serum lactate dehydrogenase levels, than those in the high-testosterone group (n=54). Castration-resistant prostate cancer free and overall survivals were significantly shorter in the low-testosterone group than in the high-testosterone group (P=0.021 and P<0.001, respectively). Multivariate analysis identified testosterone level of <450ng/dl as an independent factor predicting development of castration-resistant prostate cancer (hazard ratio 2.28, P=0.007), along with high-volume disease and Gleason score 9-10. Similarly, testosterone level of <450ng/dl was independently associated with shorter overall survival (hazard ratio 2.84, P=0.006), along with higher Charlson comorbidity index, visceral metastasis and higher alkaline phosphatase level. Lower baseline serum testosterone levels predict poor prognosis in patients with metastatic hormone-sensitive prostate cancer.

Incidence of breakthrough bleeding in transgender and gender-diverse individuals on long-term testosterone

BackgroundLittle is known about maintenance of amenorrhea in transgender and gender diverse individuals with uteri using long-term testosterone gender-affirming hormone therapy. Emerging data describes breakthrough bleeding in adolescents on long-term testosterone, as well as in adults seeking gender affirming hysterectomy. More studies are needed to better understand breakthrough bleeding patterns in transgender and gender diverse individuals on testosterone with uteri, including the frequency, timing, and etiology, and how these may differ in adults compared to younger populations. ObjectivesThe primary aim of this study was to characterize the incidence and patterns of breakthrough bleeding in a cohort of transgender and gender diverse individuals who had been on testosterone for greater than 12 months and had uteri in situ. Secondary aims included identifying the time to first bleed for those who experienced breakthrough bleeding as well as risk factors associated with breakthrough bleeding on testosterone. Study DesignThis was an IRB approved, single tertiary center, retrospective chart review of transgender and gender diverse individuals who had been on testosterone for at least one year. A primary survival analysis looking at the incidence of bleeding was combined with descriptive analyses and evaluation of factors associated with bleeding. ResultsOf the 279 patients included in the analysis, the median age of testosterone initiation was 22 years (IQR 19-41), with the median follow-up time 34 months (range 12-278). The absolute proportion of individuals who ever experienced breakthrough bleeding on testosterone was 34% (n=96, 95% CI [29, 40]). Patients who experienced breakthrough bleeding initiated testosterone at a younger age (20.5 vs 22.0 years, p=0.04), had lower mean serum testosterone levels (389.14 vs 512.7 ng/dL, p=0.001), were more likely to have a mean testosterone level <320ng/dL (52% vs 48% , p=.001), and had higher mean estradiol levels (62% vs 49%, p=0.003). Survival analyses estimated a breakthrough bleeding incidence rate of 0.09 per year (95% CI [.07-1.0]). While 58 people underwent a hysterectomy during the follow-up period, 64% of the cohort who maintained a uterus eventually experienced breakthrough bleeding. The median time to the initial bleeding episode was 22 (IQR 12-201) months after testosterone initiation. Conclusion(s)These results suggest a substantial fraction of transgender and gender diverse individuals using testosterone will experience at least one episode of breakthrough bleeding, even after their initial year using testosterone. We recommend that clinicians counsel all patients that breakthrough bleeding is a common occurrence, even after the first year on testosterone.

Interplay between hippocampal TACR3 and systemic testosterone in regulating anxiety-associated synaptic plasticity.

Tachykinin receptor 3 (TACR3) is a member of the tachykinin receptor family and falls within the rhodopsin subfamily. As a G protein-coupled receptor, it responds to neurokinin B (NKB), its high-affinity ligand. Dysfunctional TACR3 has been associated with pubertal failure and anxiety, yet the mechanisms underlying this remain unclear. Hence, we have investigated the relationship between TACR3 expression, anxiety, sex hormones, and synaptic plasticity in a rat model, which indicated that severe anxiety is linked to dampened TACR3 expression in the ventral hippocampus. TACR3 expression in female rats fluctuates during the estrous cycle, reflecting sensitivity to sex hormones. Indeed, in males, sexual development is associated with a substantial increase in hippocampal TACR3 expression, coinciding with elevated serum testosterone and a significant reduction in anxiety. TACR3 is predominantly expressed in the cell membrane, including the presynaptic compartment, and its modulation significantly influences synaptic activity. Inhibition of TACR3 activity provokes hyperactivation of CaMKII and enhanced AMPA receptor phosphorylation, associated with an increase in spine density. Using a multielectrode array, stronger cross-correlation of firing was evident among neurons following TACR3 inhibition, indicating enhanced connectivity. Deficient TACR3 activity in rats led to lower serum testosterone levels, as well as increased spine density and impaired long-term potentiation (LTP) in the dentate gyrus. Remarkably, aberrant expression of functional TACR3 in spines results in spine shrinkage and pruning, while expression of defective TACR3 increases spine density, size, and the magnitude of cross-correlation. The firing pattern in response to LTP induction was inadequate in neurons expressing defective TACR3, which could be rectified by treatment with testosterone. In conclusion, our study provides valuable insights into the intricate interplay between TACR3, sex hormones, anxiety, and synaptic plasticity. These findings highlight potential targets for therapeutic interventions to alleviate anxiety in individuals with TACR3 dysfunction and the implications of TACR3 in anxiety-related neural changes provide an avenue for future research in the field.

#120 : Effect of Aromatase Inhibitor, Letrozole on Semen Parameters in Eugonadotropic Hypoandrogenic Men with Oligozoospermia

Background and Aims: Some men with severely defective sperm production commonly have excess aromatase activity, reflected by low serum testosterone and relatively elevated estradiol level. Elevated levels of estrogen lead to feedback inhibition of the hypothalamic-pituitary-gonadal axis, and the end result is a decrease in LH necessary for the production of testosterone and FSH to optimize sperm production. The aim of the study was to evaluate the effect of aromatase inhibitor, letrozole on the semen parameters of infertile male having oligozoospermia, low serum testosterone level and testosterone to estradiol ratio &lt; 10. Method: This prospective study was conducted in the Department of Reproductive Endocrinology and Infertility at Bangabandhu Sheikh Mujib medical University, Dhaka, Bangladesh during the period from May 2019 to April 2020. The sample size was 30 sub fertile men with oligozoospermia (&lt;-10 million/ml), low serum testosterone level (&lt;300 ng/dl), and low testosterone to estradiol ratio (&lt;10). All patients were treated with letrozole 2.5 mg daily for 4 months. At the end of the 4 months semen analysis was performed. Statistical analysis was carried out by using IBM Statistical Package for Social Sciences version 25 for windows. Results: The sperm concentration, sperm motility and total motile sperm count significantly increased after letrozole treatment. The side effects were mild and well tolerated. Conclusion: This study suggests that some men with oligozoospermia low serum testosterone levels and normal gonadotropin concentration may have a treatable endocrinopathy. Letrozole may be used to improve sperm parameters in infertile men with low serum testosterone to estradiol ratio.

Alpha-lipoic acid protects against hyperlipidemia-induced testicular damage in premature rats

This study was designed to investigate the effect of hypercholesterolemia on the reproductive performance of premature male rats and to evaluate the influence of alpha lipoic acid (ALA) in conserving their fecundity. Sixty rats were randomly assigned to one of three groups. The control group (CG n=20 rats), cholesterol feeding group 1 (CFG1 n=20 rats) were fed 1.5% cholesterol with diet for one month, and cholesterol feeding group 2 (CFG2 n= 20 rats) were fed 1.5% cholesterol with diet + ALA 100 mg/kg body weight supplied by water for one month. The results revealed that compared to CG and CFG2, CFG1's body weight increased significantly. After consuming cholesterol for one month, CFG1's lipid profile revealed a substantial rise in blood cholesterol and triglycerides when compared to CG and the group that consumed ALA CFG2. In comparison to CGF1 and CG, the results of the sperm parameters in CGF2 demonstrated a large rise in sperm count with sperm live percentage and a considerable decrease in sperm abnormality %. Rats from CFG1 had significantly lower serum testosterone levels than rats from CFG2 and CG, according to the hormonal profile. We conclude that the significance of alpha lipoic acid (ALA) in preserving fertility ALA is a strong antioxidant that may preserve the parameters of the sperm of hyperlipidemic preterm rats, which may improve the capacity of hyperlipidemic rats to conceive.

Low Testosterone Levels Predict Sarcopenia Showing an Effect on Prognosis in Patients with Cirrhosis: A Retrospective Study

Background: Sarcopenia and low serum testosterone levels are both associated with increased mortality in patients with advanced liver disease. Sarcopenia is a major stumbling block of liver cirrhosis and adversely affects other outcome variables. Objective: The aim of this study is to compare testosterone levels between sarcopenia and non-sarcopenia cirrhosis patients, to compare serum testosterone levels with cirrhosis severity (Child-Pugh Score), evaluate the correlation between serum testosterone levels and L3 SMI Index (Sarcopenia), the correlation between serum testosterone levels with other prognostic markers of cirrhosis (MELD score). Method: An observational study of 131 prospectively collected liver cirrhosis patients, who met the inclusion and exclusion criteria, was conducted in the Department of Gastroenterology, National Institute of Medical Sciences and Research, NIMS University, Jaipur, Rajasthan, India, be-tween August 2019 and July 2021. Spearman’s correlation coefficient was used to evaluate the correlation between testosterone levels and L3 SMI. Results: The mean testosterone level in sarcopenia patients was significantly lowered compared to non-sarcopenia patients (152.05 ± 90.48 vs. 364.28 ± 73.55; p = 0.05). The mean testosterone level was highest in Child A than in Child B and lowest in Child C, which was statistically significant (383.50 ± 54.41 vs. 225.06 ± 58.43 vs. 83.38 ± 25.49, p = 0.05). There was a significantly positive correlation between serum testosterone levels and L3 SMI index by MRI (r = 0.619 and p-value &lt;0.000). There was a significant negative correlation between the MELD score and serum testosterone levels. Conclusion: Serum testosterone levels were significantly lower in sarcopenic as compared to non-sarcopenic patients. Serum testosterone levels progressively decreased as liver disease severity increased. There was a significant positive correlation between serum testosterone levels and L3-SMI Index (Sarcopenia).

Evaluation of Serum Testosterone Level among Diabetic and Non-Diabetic Men Diagnosed with Benign Prostatic Hyperplasia

Background: Type 2 diabetes mellitus (T2DM) and low serum testosterone level had been reported in many studies. Both conditions are endocrinologically related. Many researchers have suggested a causal link claiming that low serum testosterone may be a risk factor for the development of T2DM, while others assert that it may well be a consequence of T2DM and age in the background. Materials and Methods: A total of seventy six (76) men were included in this study. Information from their case-notes were retrieved including biodata, history and physical examination findings, laboratory and imaging results. These information were obtained during their clinic visits and such folders were coded to avoid duplication of information. Variables such as age and body mass index (BMI) were grouped. Patients were also categorized as diabetic and non-diabetic according to their medical history and laboratory results (diabetic when FBG &gt;126mg/dl). Collated data were displayed on SPSS software version 20.0 and analysed. Results: Seventy six patients aged between 41 and 86 years with a mean age of 64.07± 18.84 years were studied. Diabetic group were older (68.39± 7.6 years) than the non-diabetic arm (62.19 ± 8.7 years), however, with lower serum testosterone level (4.45 ±2.7ng/ml) than non-diabetics (5.39 ± 2.17ng/ml). Conclusion: Diabetic men in this study had a lower serum level of testosterone and we suggest a routine laboratory test of this hormone in the elderly to diagnose hypogonadism and prevent its complications.

Prognostic significance of serum testosterone level in patients with castration-resistant prostate cancer treated with cabazitaxel.

Serum testosterone level is a potential prognostic marker for castration-resistant prostate cancer. However, its role as a prognostic marker in cabazitaxel chemotherapy remains unclear. This study aimed to elucidate the clinical significance of serum testosterone levels before cabazitaxel chemotherapy. This single-institution, retrospective study included 47 patients with metastatic castration-resistant prostate cancer (mCRPC) who received cabazitaxel therapy. Serum testosterone levels were measured before the initiation of cabazitaxel therapy. Progression-free survival and overall survival (OS) were not significantly different between patients with high and low serum testosterone levels. Analysis of patients aged <70 years revealed that those with high serum testosterone levels (total testosterone level > 0.055 ng/mL) had significantly longer OS than those with low serum testosterone levels (total testosterone level < 0.055 ng/mL, p = 0.012). Multivariate analysis revealed that low serum testosterone levels (hazard ratio [HR] = 11.874, 95% confidence interval [CI] 2.076-67.953, p = 0.005) and high prostate-specific antigen levels (HR = 18.051, 95% CI 2.462-132.347, p = 0.004) in the pretreatment phase were independent prognostic factors for OS in patients receiving cabazitaxel therapy. Serum testosterone level may be a prognostic marker for cabazitaxel therapy in patients with mCRPC who are younger than 70 years, and high serum testosterone levels may lead to longer survival.

Hyperhomocysteinemia lowers serum testosterone concentration via impairing testosterone production in Leydig cells.

Hyperhomocysteinemia (HHcy) plays a salient role in male infertility. However, whether HHcy interferes with testosterone production remains inconclusive. Here, we reported a lower serum testosterone level in HHcy mice. Single-cell RNA sequencing revealed that genes related to testosterone biosynthesis, together with nuclear receptor subfamily 5 group A member 1 (Nr5a1), a key transcription factor for steroidogenic genes, were downregulated in the Leydig cells (LCs) of HHcy mice. Mechanistically, Hcy lowered trimethylation of histone H3 on lysine 4 (H3K4me3), which was bound on the promoter region of Nr5a1, resulting in downregulation of Nr5a1. Intriguingly, we identified an unknown cell cluster annotated as Macrophage-like Leydig cells (McLCs), expressing both LCs and macrophages markers. In HHcy mice, McLCs were shifted toward pro-inflammatory phenotype and thus promoted inflammatory response in LC. Betaine supplementation rescued the downregulation of NR5A1 and restored the serum testosterone level in HHcy mice. Overall, our study highlights an etiological role of HHcy in LCs dysfunction.

Methods for Evaluating the Efficacy of Medical Castration: A Systematic Review.

Measuring serum testosterone determination during medical castration is recommended by prostate cancer (PCa) guidelines to assess its efficacy and define castration resistance. It has been suggested that other biochemical compounds, such as free testosterone or luteinising hormone (LH), could also assess castration efficacy. We aimed to analyse the current evidence for serum biochemical compounds that could be appropriate candidates for evaluating medical castration efficacy. A systematic review was conducted after two investigators independently searched the literature in the PubMed, Cochrane Library, and EMBASE databases published between January 1980 and February 2023. Their searches used the medical subject headings 'prostatic neoplasms', 'testosterone and androgen antagonists', 'gonadotropin-releasing hormone/analogues and derivatives', 'free testosterone', and 'luteinising hormone'. Studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria, and their eligibility was based on the Participants, Intervention, Comparator, and Outcome strategy. The search was limited to original articles published in English. Among the 6599 initially identified titles, 15 original studies analysing the clinical impact of serum testosterone levels in PCa patients undergoing androgen deprivation therapy (ADT) were selected for evidence acquisition. The risk of bias in individual studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. All selected studies used immunoassays to measure serum testosterone, although only methods based on liquid or gas chromatography and mass spectrometry are recommended to measure low testosterone concentrations. The reported series were not uniform in clinical stage, ADT types, and the time or number of serum testosterone measurements. Only some studies found low serum testosterone levels (<20 or <32 ng/dL) associated with greater survival free of biochemical progression and castration resistance. We conclude that little current evidence justifies the measurement of serum testosterone during ADT using no appropriate methods. No reported longitudinal studies have examined the clinical impact of serum testosterone measured using liquid chromatography with tandem mass spectrometry (LC-MSMS), free testosterone, or LH in PCa patients undergoing medical castration. We conclude that well-designed longitudinal studies examining the clinical impact of serum testosterone measured with LC-MSMS, serum-free testosterone, and LH on biochemical progression and castration resistance in PCa patients undergoing neo-adjuvant castration in radiation therapy or continuous castration are needed.

High doses of clethodim-based herbicide GrassOut Max poses reproductive hazard by affecting male reproductive function and early embryogenesis in Swiss albino mice

Clethodim is a widely used and approved class II herbicide, with little information about its impact on the reproductive system. Herein, we investigated the male reproductive toxicity of clethodim using a mouse model. GrassOut Max (26% clethodim-equivalent) or analytical grade clethodim (≥90%) were given orally to male mice for 10 d in varying doses. All parameters were assessed at 35 d post-treatment. Significant decrease in testicular weight, decreased germ cell population, elevated DNA damage in testicular cells and lower serum testosterone level was observed post clethodim based herbicide exposure. Epididymal spermatozoa were characterized with significant decrease in motility, elevated DNA damage, abnormal morphology, chromatin immaturity and, decreased acetylated-lysine of sperm proteins. In the testicular cells of clethodim-based herbicide treated mice, the expression of Erβ and Gper was significantly higher. Proteomic analysis revealed lower metabolic activity, poor sperm-oocyte binding potential and defective mitochondrial electron transport in spermatozoa of clethodim-based herbicide treated mice. Further, fertilizing ability of spermatozoa was compromised and resulted in defective preimplantation embryo development. Together, our data suggest that clethodim exposure risks male reproductive function and early embryogenesis in Swiss albino mice via endocrine disrupting function.

Baseline endogenous serum testosterone levels and all-cause mortality in men with prostate cancer treated by radical radiotherapy: 11-year follow-up data.

e17003 Background: Low levels of serum testosterone are associated with higher all-cause mortality and cardiovascular mortality in some studies.(PMID: 18040028). But men with low levels of serum testosterone at reduced risk of developing prostate cancer. (PMID: 30077399). In middle-aged and elderly men, single point testosterone measurements have been shown to reliably reflect long term androgen exposure. [PMID: 1548361]. We assessed the interaction of pre-treatment serum testosterone levels and long term all-cause mortality in men with newly diagnosed prostate cancer. Methods: Prostate cancer pts enrolled in an ethics approved, prospective study evaluating a rating scale. Baseline serum testosterone levels were measured before the pts were commenced on androgen deprivation therapy and radical radiotherapy. Patient characteristics: Mean age 68.2yrs (median 69yrs); Age range category &lt; 60yrs:14.9% , 61-70yrs:47.3% and &gt; 71 yrs: 37.8%. Charlson Comorbidity Index (CCI) prevalence at baseline as follows CCI- Low risk : 39.9%; CCI-medium risk : 51.4%; CCI-high risk: 8.8%. PSA median level was 10.85 ug/L. Tumour was localised in a majority of pts- stage T1/T2 in 72% . Pts with M1 disease were not enrolled. Histology grade: Gleeson grade 6 in 7.4% and Gleeson grade 7 in 53.4% . Serum testosterone: Median 11.9 nmol/l; Mean 12.4 (Min-Max 2.6 to 26.7). Cox proportional hazards regression used to analyze the effect of baseline Serum Testosterone on long term overall survival, while controlling for covariates (age, cancer T stage, PSA category, Gleeson Category and Charlson Comorbidity index). Results: Lower levels of serum testosterone at baseline were associated with decreased all-cause mortality. There was no significant correlation between testosterone levels and age in our study sample of relatively elderly population (Pearson Correlation p = 0.362); There was no correlation testosterone levels and PSA levels(P = 0.821); no association between serum Testosterone levels and Gleeson Grade as well as T stage. (F = 0.78 ; P = 0.46 and F = 1.34 ; P = 0.26 respectively). There was also no significant variation in testosterone levels according to Comorbidity categorised by Charlson Comorbidity Index. (F = 1.31 P = 0 .26). Conclusions: Lower Serum testosterone levels were associated with decreased all-cause mortality in this prospectively collected survival data of non-metastatic Prostate cancer patients. [Table: see text]

Sarcopenia in end-stage liver disease and after liver transplantation.

Sarcopenia occurs in 30-70% of patients with end-stage liver disease and is associated with inferior pre- and post-liver transplant outcomes such as prolonged intubation times, long intensive care and hospitalization times, heightened risk of post-transplant infection, reduced health-related quality of life, and increased rates of mortality. The pathogenesis of sarcopenia is multifactorial and involves biochemical disturbances such as hyperammonemia, low serum concentrations of branched-chain amino acids (BCAAs) and low serum levels of testosterone, as well as chronic inflammation, inadequate nutritional status, and physical inactivity. Prompt recognition and accurate assessment of sarcopenia are critical and require imaging, dynamometry, and physical performance testing for the assessment of its subcomponents: muscle mass, muscle strength, and muscle function, respectively. Liver transplantation mostly fails to reverse sarcopenia in sarcopenic patients. In fact, some patients develop de novo sarcopenia after undergoing liver transplantation. The recommended treatment of sarcopenia is multimodal and includes a combination of exercise therapy and complementary nutritional interventions. Additionally, new pharmacological agents (e.g. myostatin inhibitors, testosterone supplements, and ammonia-lowering therapy) are under investigation in preclinical studies. Here, we present a narrative review of the definition, assessment, and management of sarcopenia in patients with end-stage liver disease prior to and after liver transplantation.

Klinefelter syndrome in combination with familial male-limited precocious puberty (clinical case)

The article presents the results of a literature review on Klinefelter syndrome combined with familial male-limited precocious puberty and describes a clinical case. Klinefelter syndrome is a form of male hypogonadism, characterized by the presence of an extra X chromosome, small testes, seminiferous tubule dysgenesis, high levels of gonadotropin, low serum testosterone level, underdeveloped secondary sex characteristics and male infertility. Klinefelter syndrome is characterized by extreme heterogeneity of clinical and genetic manifestations. The prevalence of Klinefelter syndrome is 0.1 to 0.2% in male newborns and increases to 3 to 4% among infertile men and 10 to 12% in patients with azoospermia. Currently, it is not known how to treat patients with mild Klinefelter syndrome that remains undiagnosed or is combined with other genetic pathology, including gonadotropin-independent precocious puberty. This disease is caused by an autosomal dominant inherited activating pathogenic variant of the gene encoding the luteinizing hormone/chorionic gonadotropin receptor, which belongs to the family of G protein-coupled receptors. In men, activation of pathogenic variants of this gene causes excessive secretion of testosterone, which triggers early peripheral (precocious) puberty. Treatment recommendations have been developed in part mainly because of the limited number of reported cases, small sample sizes, and short-term outcomes. The presented clinical case is important in view of the possible risk of developing malignant testicular neoplasms in patients with precocious puberty. Therefore, long-term follow-up during and after puberty is recommended. It is of great importance to take into account the aforementioned clinical manifestations in order to made early diagnosis of this syndrome, offer timely genetic counseling to parents, and rehabilitate these patients physically, psychically and socially.