Serum Testosterone Research Articles

Microdissection testicular sperm extraction outcomes in azoospermic patients post-orchidopexy surgery: A systematic review and meta-analysis.

Cryptorchidism is a common cause of male infertility, often necessitating microdissection testicular sperm extraction (m-TESE) for sperm retrieval post-surgery. However, uncertainties persist regarding m-TESE outcomes and influencing factors following cryptorchidism surgery. A systematic review and meta-analysis were conducted to evaluate sperm retrieval rates (SRR) among patients undergoing m-TESE after cryptorchidism surgery. Factors including age at orchidopexy, age at m-TESE, type of cryptorchidism, serum hormone levels, testicular volume, and interval from surgery to m-TESE were analyzed for their impact on SRR.Nine studies encompassing 935 patients were included. The overall SRR was 57% (95% confidence interval [CI] 51% to 63%). Compared to patients with negative sperm retrieval (SR-), patients with positive sperm retrieval (SR+) underwent m-TESE at an older age (1.81 years; 95% CI 1.17 to 2.45) and orchidopexy at a younger age (-3.35 years; 95% CI -6.34 to -0.36). Different types of cryptorchidism (including high scrotal, inguinal canal, intra-abdominal) significantly influenced SRR (P<0.05). Serum testosterone, follicle-stimulating hormone, luteinizing hormone levels and testicular volume showed no significant correlation with SRR (P>0.05). Furthermore, SR- patients typically experienced shorter intervals from orchidopexy to m-TESE compared to SR+ patients (34.09 months; 95% CI 0.40 to 67.77). Earlier orchidopexy and much later m-TESE procedures, as well as undescended testis closer to the scrotum, increase the likelihood of successful sperm retrieval. Orchidopexy for cryptorchidism should be done as early as possible, whether it is performed before 18 months of age or detected at a much older age. In patients with undetected cryptorchidism and azoospermia after puberty, m-TESE should not be performed immediately after orchidopexy, the optimal interval from orchidopexy to m-TESE still requires further study.

The effect of chemotherapy regimens in male germ cell tumors on the development of primary hypogonadism.

Male germ cell tumors (GCT) have excellent survival. Long-term sequelae in cancer survivors are an evolving field. We evaluated the risk of patients with GCT to develop primary hypogonadism and adherence to guideline-recommended therapy in a real-world cohort. Monocentric study at a tertiary cancer centre to evaluate treated GCT-patients (2001-2019). Post therapeutic male endocrine function, International Index of Erectile Function (IIEF)-5 and The aging males' symptoms rating scale (AMS) questionnaires were assessed. The overall response rates were low, with 44 of 402 contacted patients participating in the study. From these, 32(73%) underwent blood analysis, 42(95%) answered the IIEF-5 and 43(98%) the AMS. Latent hypogonadism (serum testosterone 8-12 nmol/l) was found in n = 9 (28%) and manifest hypogonadism (testosterone < 8 nmol/l) in n = 8 (25%). 50% (n = 21) indicated erectile dysfunction on IIEF-5 (cut off ≤ 21 pts.) and 62.8% (n = 27) reported symptomatic affection on AMS (cut off ≥ 27 pts.). Majority of tested patients revealed different degrees of hypogonadism. Standard instruments were able to detect gonadal damage in > 50%, which underscored the clinical need to evaluate endocrine function in cancer survivors. We further indicated the difficulties of today's research and provided starting points to assess barriers for study participations.

Precocious Puberty in Boys with NR0B1 Variants

Precocious puberty (PP) requires appropriate management to prevent short adult height, psychosocial issues, and other adverse outcomes. Genetic diagnosis potentially improves the management of PP. Pathogenic NR0B1 variants, which typically cause X-linked adrenal hypoplasia congenita, can also affect gonadal function. While boys with NR0B1 variants usually exhibit hypogonadotropic hypogonadism during adolescence, previous reports have suggested that minipuberty, a physiological transient activation of the hypothalamic–pituitary–gonadal axis during infancy, occurs in these patients and can persist beyond a typical duration. In rare cases, NR0B1 variants cause PP. PP associated with NR0B1 variants has unique features such as early onset and high serum testosterone levels that are often disproportionate to testicular size. Three underlying mechanisms have been proposed for the association between PP and NR0B1 variants: (1) adrenocorticotropic hormone (ACTH)-dependent, (2) gonadotropin-dependent, and (3) ACTH- and gonadotropin-independent mechanisms. The factors contributing to PP vary among cases. Determining the underlying mechanisms is crucial for adopting appropriate therapeutic strategies to control PP. However, as the detailed molecular networks mediating these mechanisms are largely unclear, further research is needed to pave the way for a more effective and personalized management of patients with PP associated with NR0B1 variants.

Long-term effects of sub-chronic exposure to L-NAME on reproductive system of male rats.

Nω-nitro-l-arginine methyl ester (L-NAME) has been utilized as a nitric oxide synthase antagonist for many years in both basic and clinical research settings to assess its therapeutic potential. Though a number of studies have shown the effect of L-NAME on testicular function, the information regarding the reversibility of these effects upon L-NAME withdrawal is limited. In the present study, male rats (68-80days old) divided randomly into three groups received different doses of L-NAME, i.e. 20mg/kg bw (L20) and 10mg/kg bw (L10) in drinking water, and drinking water only (control) through oral gavage daily for three weeks. The rats were monitored for and sacrificed after 60days of L-NAME treatment termination. The animals had a significantly higher (p < 0.01) mean blood pressure compared to control. Aberrant histological changes were observed in the testes of L-NAME-treated rats. A significant reduction (p < 0.05) in the sperm count and an increase in abnormal sperm morphology (p < 0.05) was observed in L-NAME treated rats. Moreover, the spermatogenic cycle was found to be altered in L-NAME treated rats. No change was observed in serum estradiol levels, while serum testosterone levels were significantly increased (p < 0.05) in L10 and L20 animals. The intra-testicular testosterone was increased significantly (p < 0.01) in L20 animals. A significant decrease (p < 0.05) in superoxide dismutase activity was observed in L20 animals. The sub-chronic exposure to L-NAME resulted in higher mean arterial blood pressure and long-term testicular tissue damage, affecting sperm quality and spermatogenesis.

Resveratrol improves follicular development in PCOS rats by inhibiting the inflammatory response and pyroptosis of granulosa cells.

Chronic inflammation is a key characteristic of polycystic ovary syndrome (PCOS) and is associated with follicular dysplasia in PCOS. PCOS patients treated with 1000mg resveratrol (RES) daily for 3months showed significant improvement in menstrual cycle regularity compared to the placebo group. This investigation explores potential impact of RES on a rat model of PCOS. Sprague-Dawley (SD) rats were subjected to a 30-day letrozole/high-fat diet interventions for PCOS model establishment, followed by RES intervention (20mg/kg/d) for an additional 30days. RES intervention mitigated obesity, estrous cycle irregularities, and ovulation disorders while decreasing serum testosterone and lipopolysaccharide (LPS) levels in PCOS rats. Concurrently, inflammatory markers (TNF-α, NLPR3, IL-6,) and pyroptosis-related markers (GSDMD, cleaved-Caspase-1, IL-1β, IL-18) were downregulated. Additionally, KGN cells (a human granulosa-like cell line) were treated with LPS and RES for in vitro assays. It was observed that RES (15μM) significantly reduced ROS production and downregulated inflammatory cytokine expression in LPS-intervened KGN cells. Additionally, RES downregulated the expression levels of pyroptosis-related factors (GSDMD and cleaved-Caspase-1) and attenuated IL-18 and IL-1β secretion in LPS-induced KGN cells. Furthermore, RES intervention improved the pyroptosis-associated morphology of KGN cells after LPS treatment. In conclusion, RES may restore follicular development in PCOS rats by inhibiting inflammation and NLRP3/GSDMD/Caspase-1-mediated pyroptosis of ovarian granulosa cells, providing new insights into potential therapeutic approaches for PCOS.

Age and sex effects of a validated LC-MS/MS method for the simultaneous quantification of testosterone, allopregnanolone, and its isomers in human serum.

Despite the great relevance of the neurosteroid allopregnanolone and related isomers to various health conditions, quantification typically involves immunoassay, which suffers from serious issues with cross-reactivity of closely related molecules. This article describes the development and partial validation of a liquid chromatography coupled with tandem mass spectrometry assay for the simultaneous quantification of allopregnanolone, pregnanolone, isopregnanolone, epi-allopregnanolone, and testosterone in the human serum of healthy males and females aged 5-85 years. 1-amino-4-methylpiperazine (AMP) was used as a derivatisation reagent to enhance the ionisation signal. Linearity was calculated at 0.99 with a lower limit of quantification of 10.08 pg/mL for allopregnanolone, along with a linearity of 0.98 and a lower limit of quantification of 42.32 pg/mL for testosterone. Application of the method showed sex and age effects across the lifespan for both allopregnanolone and testosterone, whereas a comparative immunoassay for allopregnanolone was not able to detect differences in the same samples. Our partial validation of this method should provide a new tool for researchers to discover the role of allopregnanolone and its isomers in human health, and how it compares to testosterone and sex hormones.

Post-pubertal management of undescended testes from the malignancy risk point of view: a systematic review

Background Undescended testes (UDT) is a condition where one or both testes is absent in the scrotum. The general age recommendation in which the treatment should be performed is before 18 months old due to the infertility risk and malignancy in later life. In post-pubertal UDT, the current guideline recommends orchiectomy; however, the strength rating of this recommendation is weak. Therefore, this study aimed to provide a systematic review of post-pubertal UDT treatment, focusing on the malignancy risk point of view. Methods A systematic search was performed using PubMed, Wiley Online Library and the Cochrane Library up to 5 March 2023. Any study with either post-pubertal orchiectomy or orchidopexy in patients with UDT and reporting the testicular malignancy was included. The exclusion criteria were studies with lack of information of UDT correction time, no history of correction and the full text wasn’t available. The data collected were the occurrence of testicular malignancy in post-pubertal UDT patients corrected with any method. Quality and bias assessment was assessed with Newcastle-Ottawa scale and Joanna Briggs Institute tools. Results Seven articles (three case reports and four observational studies) were reviewed with a total of 42 patients who underwent post-pubertal correction of either unilateral or bilateral UDT. The correction age ranged from 13 to 34 years old, with follow-up of 48.7–252 months. Among those who developed malignancies, the most common were seminoma, teratoma and carcinoma in situ of the testes. In addition, this study was able to propose an algorithm for post-pubertal UDT treatment strategy. Conclusions The scarce resource was the main limitation of this study. Nevertheless, this review showed that post-pubertal UDT management should be tailored individually. Several factors that should be considered include the condition of the contralateral descended testis, UDT location, serum testosterone level, patient’s age, comorbidities, and interest in fertility.

Hyperandrogenism after menopause: diagnostic evaluation

Excessive androgen levels in women after menopause often result from an imbalance in ovarian steroid secretion: a rapid decline in estrogen secretion associated with a slow decrease in androgen secretion, compounded by a physiological decrease in sex hormone-binding globulin. Hyperandrogenism is associated with a higher risk of cardiovascular events and gynecological neoplasms, also impacting the emotional well-being of affected women. Therefore, the aim of these guidelines is to guide the clinical physician in the appropriate clinical and biochemical evaluation of hyperandrogenism after menopause, thus optimizing therapeutic outcomes. The most frequent consultation in this stage of life is facial hirsutism associated with hair loss. If the onset of signs is abrupt, severe, associated with virilization and accompanied by serum testosterone levels in the male range, it is necessary to rule out a tumoral origin. A thorough medical history guides the diagnosis. Determination of total testosterone using reliable methods and imaging studies are valid tools to assist when doubts arise in the differential diagnosis.

Clinical and Biochemical Outcomes in Transgender Individuals Undergoing Hormone Therapy: Protocol for a Systematic Review.

Monitoring of various clinical outcomes and parameters, such as lipid levels, is recommended in transgender individuals undergoing hormone therapies. However, comprehensive data to inform these recommendations is scarce. This study aims to conduct a systematic review and meta-analysis to synthesize evidence from existing literature on the effect of exogenous hormone therapy on clinical and biochemical outcomes for transgender adolescents and adults. We will search multiple electronic databases and will include prospective and retrospective observational studies with and without a control group. The study population will include transgender individuals undergoing hormone therapy with testosterone or estrogen. Comparisons will include age-matched, cisgender individuals and changes from baseline. Primary outcomes include changes in or the development of abnormal lipid parameters. Secondary outcomes include BMI, weight, height, and blood pressure for age, serum testosterone or estrogen levels, and development of disease including hypertension, diabetes, fatty liver disease, obesity, adverse cardiac events, as well as all-cause mortality. The meta-analysis will pool the studies where applicable, and meta-regressions will be conducted to evaluate effect modifiers. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach will be used to evaluate the overall certainty of evidence. We will summarize the selection of the eligible studies using a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart. The results will be presented in a table summarizing the evidence. Data collection is ongoing, and the paper is expected to be published in Spring 2025. This systematic review will summarize and evaluate the evidence of the clinical and biochemical outcomes associated with hormone therapies for transgender individuals. PROSPERO CRD42024483138; https://tinyurl.com/yc4sfvnb. PRR1-10.2196/57931.

Responses in organs, sperm, steroid hormones and CYP450 enzyme in male mice treated by quinestrol only or in conjunction with clarithromycin

Pest rodents persistently undermine crop yields and food security. Fertility control could be a viable alternative for managing rodent populations. This study investigates the antifertility effects of various concentrations of clarithromycin combined with 1.0 mg/kg quinestrol on male rodents to determine an effective contraceptive dose that minimizes quinestrol usage, addressing key concerns such as potential environmental residue, which may impact ecological balance, and poor palatability, which could reduce ingestion and limit the sterilant’s effectiveness. Male mice were divided into five groups and administered different doses of clarithromycin or clarithromycin and quinestrol for three consecutive days, while the control group received sunflower seed oil only. After seven days, organ weights, reproductive organ weights, sperm density, serum hormone levels, and CYP3A4 content in small intestinal and liver tissues were measured to assess persistent effects. Compared with the control group, all treatment groups had significant reductions in epididymal weight, seminal vesicle weight, and serum T and LH levels. Higher concentrations of clarithromycin (2 mg/kg and 10 mg/kg) significantly impacted reproductive metrics, including sperm density, organ weights, and serum LH and testosterone levels, though complete sterilization was not achieved, with more than 60 million cauda epididymal spermatozoa remaining. However, the combination demonstrated potential as an effective strategy for male fertility control. The combination of 2.0 mg/kg clarithromycin and quinestrol can mitigate organ enlargement seen with quinestrol alone. This combination also decreased total enzyme content, thereby diminishing quinestrol’s induction of CYP3A4, which may increase the sterilization effectiveness of the treatment.

Structure-guided design and evaluation of CRM197-scaffolded vaccine targeting GnRH for animal immunocastration

Immunocastration is a humane alternative to surgical castration for controlling population and estrous behaviors in animals. Gonadotropin-releasing hormone (GnRH), the pivotal initiating hormone of the hormonal cascade in mammals, is the optimal target for immunocastration vaccine development. Cognate antigen-mediated cross-linking of B cell receptors (BCRs) is a strong activation signal for B cells and is facilitated by repetitive surface organizations of antigens. In this study, we describe the structure-guided design of highly immunogenic chimeric proteins with variant numbers of GnRH peptide insertion by epitope grafting. Linear B-cell epitopes of cross-reacting material 197 (CRM197) were replaced with multiple copies of GnRH peptide, and the inserts were displayed on the surface of the designs while maintaining the overall folding of CRM197. Among the seven designs, TCG13, which carries 13 copies of GnRH peptide, was the most immunogenic, and its immunocastration efficacy was evaluated in male mice. Vaccination with the BFA03-adjuvanted TCG13 induced potent humoral immunity and reduced the serum testosterone concentration in mice. It could significantly decrease sperm quality and severely impair gonadal function and fertility. These results demonstrate that CRM197 holds great value as a scaffold for epitope presentation in peptide-based vaccine development and supports TCG13 as a promising vaccine candidate for animal immunocastration.Key points• Provide a feasible way to design chimeric immunogen targeting GnRH by epitope grafting.• CRM197 can accommodate the insertion of multiple copies of heterologous epitope peptides.• Administration with the most immunogenic design led to effective immunocastration in male mice.

Glycyrrhizin alleviated cisplatin-induced testicular injury by inhibiting the oxidative, apoptotic, hormonal, and histological alterations.

To evaluate the potential contribution of glycyrrhizin (GLZ) to mitigate the testicular toxicity linked to cisplatin (CIS) intoxication. 40 mature male Wistar albino rats (Rattus norvegicus albinus) were randomly divided into 4 equal groups (n = 10) for 60 days: the control group, CIS-treated group (single dose of 7 mg/kg, IP), GLZ-treated group (25 mg/kg, PO), and GLZ plus CIS-treated group. Blood and testis samples were examined using biochemical, histological, and immunohistochemical techniques. Semen samples were also obtained, and any abnormalities were reported. Serum follicle-stimulating hormone, luteinizing hormone, and testosterone levels were all markedly reduced by CIS. Oxidative stress and a significant reduction in levels of the antioxidant enzymes glutathione peroxidase, superoxide dismutase, and catalase were linked to CIS. Immunohistochemically, CIS showed diffuse, significantly positive immunolocalizations against the anti-caspase 3 antibody, indicating widespread apoptosis within the testicular parenchyma. Histopathologically, CIS showed diffuse coagulative necrosis of spermatogenic cells, necrotic Sertoli cells, intertubular edema, and Leydig cell hyperplasia. Moreover, CIS revealed a noteworthy increase in sperm abnormalities. Pre-coadministration and posttreatment with GLZ mitigated the majority of these detrimental consequences, and serum levels of antioxidant enzymes, luteinizing hormone, follicle-stimulating hormone, and testosterone were significantly elevated. Glycyrrhizin has been proven to be a strong antioxidant as well as antiapoptotic and cytoprotective against CIS testicular damage. The described model is a tool to evaluate the testicular protective impact of GLZ.

Acrylamide-induced hypothalamic-pituitary-gonadal axis disruption in rats: Androgenic protective roles of apigenin by restoring testicular steroidogenesis through upregulation of 17β-HSD, CYP11A1 and CYP17A1

Acrylamide (ARL) exposure induces significant toxicity to the hypothalamic-pituitary-gonadal (HPG) axis, leading to detrimental effects on behavior, neuroendocrine functions, steroidogensis, oxidative stress, inflammation, hormonal balance, sperm quality, and histopathological integrity in rats. This study investigates the protective role of oral apigenin (API; 10 or 20 mg/kg/day for 28 days) against ARL-induced toxicity in the HPG axis of male Wistar rats. Behavioral assessments revealed that ARL exposure impaired motor coordination and balance, as evidenced by increased landing foot splay distance and gait score. ARL-induced toxicity elevated brain Tau protein levels and disrupted hypothalamic GnRH levels, both mitigated by API. ARL triggered oxidative/nitrosative stress, reducing GSH contents and increasing MDA and NO levels in brain and testicular tissues, which were reversed by API. Hormonal imbalance, marked by decreased serum testosterone, FSH, and LH levels, was corrected by API. API enhanced semen quality parameters, with elevation in sperm count concentration and the percentages of both progressive motility and individual motility. It also normalized testicular PS and PC content, enhanced testicular cellular energy and restored seminal amino acid. The repression of testicular steroidogenesis-related enzymes CYP11A1, CYP17A1, and 17β-HSD following ARL exposure was alleviated by API administration. API also mitigated the inflammatory effects of ARL by reducing the expression of p–NF–κB p65 and TNF-α in testicular tissue. Histopathological examinations showed that API reduced neuronal and testicular degeneration, improving spermatogenesis. These findings suggest that API confers significant protective effects against ARL-induced HPG axis toxicity by restoring testicular steroidogenesis through the upregulation of 17β-HSD, CYP11A1, and CYP17A1, potentially due to its antioxidant, anti-inflammatory, and neuroprotective properties.

In-utero exposure to real-life environmental chemicals disrupts gene expression within the hypothalamo-pituitary-gonadal axis of prepubertal and adult rams

Environmental chemicals (ECs) have been associated with a broad range of disorders and diseases. Daily exposure to various ECs in the environment, or real-life exposure, has raised significant public health concerns. Utilizing the biosolids-treated pasture (BTP) sheep model, this study demonstrates that in-utero exposure to a real-life EC mixture disrupts hypothalamo-pituitary-gonadal (HPG) axis gene expression and reproductive traits in prepubertal (8-week-old, 8w) and adult (11-month-old) male sheep. Ewes were maintained on either BTP or pastures fertilized with inorganic fertilizer [control (C)] from approximately one month prior to insemination until around parturition. Thereafter, all animals were kept under control conditions. Effects on reproductive parameters including testosterone concentrations and the expression of key genes in the HPG axis were evaluated in eight-week-old and adult male offspring from both C and biosolids-exposed (B) groups. Results showed that, at 8w, relative to C (n = 11), B males (n = 11) had lower body weight, and altered testicular expression of HSD3B1, LHR and HSD17B3, BMP4, ABP, P27kip and CELF1. Principal component analysis (PCA) identified two 8w B subgroups, based on hypothalamic expression of GnRH, ESR1, and AR, and pituitary expression of KISSR. The two subgroups also exhibited different serum testosterone concentrations. The largest biosolids effects were observed in the hypothalamus of adult rams with NKB, ESR1, KISS1, AR, DLK1 and GNRH1 mRNA expression differing between B (n = 10) and C (n = 11) rams. Testicular steroidogenic enzymes CYP11A1 and HSD3B1 mRNA expression also differed between exposure groups. PCA identified two adult B subgroups, with BS1 (n = 6) displaying hypothalamic effects and BS2 (n = 4) both hypothalamic and testicular effects. The subgroups also differed in circulating testosterone concentrations. These findings demonstrate that exposure to a real-life EC mixture may predispose some males to infertility, by disrupting key functional HPG markers before puberty with consequent downstream effects on steroid hormones and spermatogenesis.

Assessment of reproductive, genotoxic, and cytotoxic effects of leachate-contaminated water in male mice

Leachate-contaminated water (LCS) poses significant health risks due to its heavy metal content and altered physicochemical properties. This study examined the physicochemical parameters and heavy metal levels in LCS and assessed its reproductive toxicity, genotoxicity, and cytotoxic effects in exposed mice. Groups of mice (n = 5) were orally administered 100 μL of 30 % and 70 % LCS (v/v) twice daily for 35 days. Drinking water served as a negative control, and cyclophosphamide (Cyp) (20 mg/kg bw) as a positive control. On day 36, the mice were weighed, sacrificed, and their testicular weight, sperm count, sperm morphology, viability, acrosome integrity, and serum testosterone were examined. Oxidative stress in the testes, histopathological changes, and serum markers for liver and kidney function (SGOT, SGPT, and creatinine) were also assessed. Genotoxic effects were evaluated using a micronuclei (MN) assay. Analysis of the leachate showed altered physicochemical parameters and elevated heavy metal levels. Exposure to LCS led to a significant decrease in relative testis weight, sperm count, normal sperm morphology, viability, acrosome integrity, and serum testosterone levels. It also caused a notable increase in MDA levels and a decrease in catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) levels, along with histological changes in the testes of LCS-treated mice compared to controls. Additionally, there was a significant rise in MN formation in RBCs and elevated levels of liver enzymes and creatinine, indicating liver and renal toxicity. Histological alterations in the liver and kidneys were also observed in LCS-exposed mice. These findings suggest that LCS induces reproductive toxicity, genotoxicity, and cytotoxicity in male subjects.

Testosterone to Estradiol Ratios in Fertile and Subfertile Men: A Large Cohort Analysis

ObjectiveTo validate the established normal testosterone to estradiol ratio and characterize the distribution of testosterone to estradiol ratios in a large cohort of fertile and subfertile men. Materials and MethodsRetrospective review of adult men (≥18 years of age) presenting for fertility evaluation between 2002 and 2021 who underwent evaluation by a reproductive urologist, had two separate semen analyses and had hormonal testing within six months of their index semen analysis. Men were dichotomized into fertile and subfertile groups based on total motile sperm count on two semen analyses. The subfertile cohort included men with a total motile sperm count <20 million on both semen analyses. The main outcome measures were serum testosterone, serum estradiol, and serum testosterone to estradiol ratio. ResultsAmong 816 men, 651 (79.8%) were classified as fertile and 165 (20.2%) as subfertile. Median testosterone (ng/dL) to estradiol (pg/mL) ratios were similar between the groups (14.48 vs 15.00, p=0.5). The 20th percentile testosterone to estradiol ratio for the fertile group was 9.77. ConclusionsThis is the largest study to date characterizing testosterone to estradiol ratios in men presenting for fertility evaluation. We validated the 10/1 ratio that was previously established as the 20th percentile for fertile men. We found no difference in testosterone to estradiol ratios between fertile and subfertile men defined by total motile sperm count, highlighting the need for further investigation to better define the cohort of men with infertility who could benefit from aromatase inhibitor therapy.

Investigating High-risk Factors, Precise Diagnosis, and Treatment of Castration- Resistant Prostate Cancer (CRPC).

The treatment of metastatic castration-resistant prostate cancer (mCRPC) in the actual world currently presents difficulties. In light of this, it is crucial to investigate high-risk factors for the progression of advanced prostate cancer and to identify methods for delaying the onset of CRPC. This study aimed to explore the high-risk factors that impact the progression of prostate cancer and emphasize the significance of precise diagnosis and treatment based on etiological classification in the clinical management of castration-resistant prostate cancer. A retrospective analysis was conducted on 277 newly diagnosed cases of PCa treated with endocrine therapy. A follow-up was done on prostate-specific antigen (PSA) levels and testosterone. Additionally, a prospective analysis was performed on the clinical data of 60 patients with CRPC. Following the principle of "4W1H", 30 patients were included in the precision treatment group for a second biopsy and related tests, while another 30 patients were included in the conventional treatment group. The therapeutic effect and prognosis of the two groups were observed. Distant metastasis (HR = 1.879, 95% CI: 1.311 ~ 2.694, P = 0.001), PSA nadir > 0.2 ng/mL (HR = 1.843, 95% CI: 1.338 ~ 2.540, P = 0.001), testosterone nadir > 20 ng/dL (HR = 1.403, 95% CI: 1.035 ~ 1.904, P = 0.029), and time to testosterone nadir > 6 months (HR = 1.919, 95% CI: 1.364 ~ 2.701, P = 0.001) were risk factors for the progression to CRPC. Patients in the CRPC group were treated with precision therapy and conventional therapy based on their molecular subtyping. The precision treatment group showed a significantly prolonged median PSA progression-free survival compared to the conventional treatment group (16.0 months vs. 13.0 months, P=0.025). The median radiographic progression-free survival was also significantly extended in the precision treatment group compared to the conventional treatment group (21.0 months vs. 16.0 months, P=0.042). Patients with prostate cancer diagnosed with distant metastasis at initial presentation require early intervention. Close monitoring of PSA and serum testosterone changes is necessary during the process of endocrine therapy. After entering the CRPC stage, the etiological classification precision treatment can improve the therapeutic effect and improve the prognosis of patients.

Mitochondrial malfunction-initiated Leydig cell premature senescence partially participates in 1-nitropyrene-evoked downregulation of steroidogenic synthases in testes

Serum testosterone (T) in males has been declining during the past decades. The previous reports found that 1-nitropyrene (1-NP) exposure suppressed testicular T synthesis. The purpose of the current study was to further explore whether premature senescence participates in 1-NP-triggered reduction of testicular T synthesis. Adult male mice were orally exposed to 1-NP (0, 100, and 500 μg/kg) daily for 14 days. Serum and testicular T contents were diminished in 1-NP-administered mice. Mitochondria-located steroidogenic synthases, including StAR, CYP11A1, and 3βHSD1, were downregulated in 1-NP-administered mouse testes and MLTC-1 cells. Mechanistically, 1-NP exposure increased acetylation modification of mitochondrial steroidogenic synthases by inhibiting the enzymatic activity of SIRT3, an NAD+-dependent deacetylase. Supplementing NAD+ precursor and Sirt3 overexpression relieved 1-NP-triggered reduction of steroidogenic synthase levels in mouse testes and MLTC-1 cells. By contrast, Sirt3 silencing aggravated 1-NP-evoked acetylation and reduction of steroidogenic synthase levels in MLTC-1 cells. Further experiments demonstrated that 1-NP exposure caused mitochondrial malfunction and premature senescence in mouse testes and MLTC-1 cells. Supplementation with mitochondria-directed antioxidant mitoquinone (MitoQ) prevented 1-NP-evoked Leydig cell premature senescence and downregulation of testicular steroidogenic synthases. These results suggest that mitochondrial malfunction-initiated Leydig cell premature senescence may partially participate in 1-NP-evoked reduction of steroidogenic synthase levels in testes.

The Impact of Chemokine-Like Receptor 1 Gene Knockout on Lipopolysaccharide-Induced Epididymo-Orchitis in Mice.

This comprehensive study delved into the pivotal function of chemokine-like receptor 1 (CMKLR1) in lipopolysaccharide (LPS)-triggered epididymo-orchitis in mice. Upon LPS exposure, wild-type (WT) mice exhibited marked elevations in serum pro-inflammatory markers, including G-CSF, IL-6, and RANTES, along with heightened levels of TNF-α and IL-6 in testicular and epididymal tissues, which accompanied by pronounced structural damage within the testicular tissue and a concurrent decline in serum testosterone, estradiol (E2) levels, and testicular steroid synthetase expression. Remarkably, Cmklr1 gene ablation intensified the pro-inflammatory response in the serum (especially IFN-γ), testes, and epididymis of epididymo-orchitis models. Furthermore, Cmklr1 deficiency uniquely induced structural alterations within the epididymis, which is absent in the WT model. This genetic manipulation also exacerbated the decline in serum testosterone and E2 levels and testicular steroid synthase activity. While chemerin levels were significantly diminished in WT epididymo-orchitis models, Cmklr1 knockout had no discernible effect on chemerin expression in the model. In addition, a noteworthy observation was the elevation of the serum low density lipoprotein/high density lipoprotein (LDL/HDL) ratio in Cmklr1-deficient mice. Collectively, these findings underscore that the lack of chemerin/CMKLR1 signaling axis could potentially worsen the symptoms during LPS-induced epididymo-orchitis, highlighting its potential as a therapeutic target in related pathologies.

Does the hemodialysis program affect the testosterone serum level in patients with end-stage renal disease?

This study aimed to evaluate the effect of high flux membrane hemodialysis on total serum testosterone (TST) levels in male patients with end-stage renal disease (ESRD). The study included 60 male ESRD patients with a mean age of 54.02 ± 13.40years, undergoing a standard hemodialysis program et al. Najah National University Hospital. All patients underwent three weekly sessions of four hours each using high flux membrane hemodialysis. TST and hematocrit (Hct) levels were measured before and after hemodialysis. Patients with prostate cancer, liver insufficiency, prior prostate surgery, or those on androgen therapy were excluded. The study assessed changes in TST and Hct levels and their correlation. Post-dialysis, there was a significant increase in serum testosterone levels from 3.13 ± 1.44ng/ml to 4.17 ± 2.04ng/ml (r = 0.78, p = 0.001). Hematocrit levels also rose significantly from 32.31% ± 3.90% to 35.27% ± 4.89% (r = 0.754, p = 0.001). The percentage change in TST and Hct levels was 35 ± 0.33% and 9 ± 0.1%, respectively, with a correlation between these changes (r = 0.277, p = 0.032). High flux membrane dialysis did not filter testosterone molecules, and the significant increase in TST levels post-dialysis is likely due to hemoconcentration. Since many patients had low or borderline TST levels before dialysis, androgen supplementation may offer clinical benefits.