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Background: Aging often leads to changes in hormone levels, particularly testosterone, which is thought to significantly affect bone health in older males., Objective: This study aimed to explore the link between testosterone levels and bone mineral density in men aged 60 and above., Methods: Data from the National Health and Nutrition Examination Survey 2013-2014 were used. Weighted multivariable linear regression models were employed to study the association between testosterone and bone mineral density. Furthermore, a weighted generalized additive model and smooth curve fitting were used to address potential nonlinear patterns in the data., Results: The analysis included 621 elderly men. After accounting for various factors, the study uncovered a Inverted U-shaped correlation between testosterone levels and femoral neck density. Notably, a turning point was identified at the testosterone level of 406.4 ng/dL. Further examination, using different models, showed that testosterone levels in the third quartile (group Q3) were positively linked to bone density. However, contrasting trends were observed in the first (group Q1) and fourth quartiles (group Q4), where testosterone levels displayed a negative relationship with bone density., Conclusion: The results indicate a complex interplay between testosterone levels and bone mineral density in elderly men. The U-shaped trend suggests that both low and high testosterone levels could negatively impact bone health. These findings highlight the importance of maintaining testosterone levels within an optimal range to preserve bone health in aging men., Competing Interests: Declarations Ethics approval and consent to participate The survey protocol received ethical clearance from the Ethics Review Board of the National Center for Health Statistics. Prior to their participation in the study, every individual participant provided their written informed consent, ensuring adherence to ethical principles. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Context: Hierarchical clustering (HC) identifies subtypes of polycystic ovary syndrome (PCOS)., Objective: This work aimed to identify clinically significant subtypes in a PCOS cohort diagnosed with the Rotterdam criteria and to further characterize the distinct subtypes., Methods: Clustering was performed using the variables body mass index (BMI), luteinizing hormone (LH), follicle-stimulating hormone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), testosterone, insulin, and glucose. Subtype characterization was performed by analyzing the variables estradiol, androstenedione, dehydroepiandrosterone, cortisol, anti-Müllerian hormone (AMH), total follicle count (TFC), lipid profile, and blood pressure. Study participants were girls and women who attended our university hospital for reproductive endocrinology screening between February 1993 and February 2021. In total, 2502 female participants of European ancestry, aged 13 to 45 years with PCOS (according to the Rotterdam criteria), were included. A subset of these (n = 1067) fulfilled the National Institutes of Health criteria (ovulatory dysfunction and hyperandrogenism). Main outcome measures included the identification of distinct PCOS subtypes using cluster analysis. Additional clinical variables associated with these subtypes were assessed., Results: Metabolic, reproductive, and background PCOS subtypes were identified. In addition to high LH and SHBG levels, the reproductive subtype had the highest TFC and levels of AMH (all P < .001). In addition to high BMI and insulin levels, the metabolic subtype had higher low-density lipoprotein levels and higher systolic and diastolic blood pressure (all P < .001). The background subtype had lower androstenedione levels and features of the other 2 subtypes., Conclusion: Reproductive and metabolic traits not used for subtyping differed significantly in the subtypes. These findings suggest that the subtypes capture distinct PCOS causal pathways., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: The anogenital distance (AGD) is considered a postnatal readout of early fetal androgen action. Little is known of prenatal AGD and how it correlates with AGD postnatally., Objective: We present longitudinal measurements of fetal and infant AGD. We evaluate the impact of testosterone and dihydrotestosterone at minipuberty on AGD and penile size., Methods: We performed secondary analyses of an observational, prospective pregnancy and birth cohort, COPANA (2020-2022), at Copenhagen University Hospital-Rigshospitalet, enrolling 685 healthy, singleton pregnant women, of whom 657 attended third trimester ultrasound and 589 infants completed follow-up. Fetal AGD was measured at third semester ultrasound (gestational week 29-34), and infant AGD, penile width, stretched penile length, and circulating testosterone and dihydrotestosterone (LC-MS/MS) were assessed at the minipuberty clinical examination (approximately 3.5 months postpartum)., Results: AGD was available in 650/657 fetuses (310 boys) and 588/589 infants (287 boys). Boys had longer fetal and infant AGD than girls; fetal AGDas: mean (SD) 21.4 mm (±3.5), fetal AGDaf: 12.8 mm (±2.3), P < .001, infant AGDas: 32.0 mm (±5.6) and infant AGDaf: 15.8 (±3.3), P < .001. Fetal AGD correlated with infant AGD in boys and girls (Spearman r = .275, P < .001 and r = .189, P = .001 respectively), but not with circulating testosterone or dihydrotestosterone at minipuberty. Penile size correlated positively with circulating androgen levels at minipuberty: stretched penile length vs testosterone: r = .235, P < .001., Conclusion: AGD is sexually dimorphic already in the third trimester. Fetal and infant AGD correlate. AGD is associated with body size but not circulating androgen levels at minipuberty. These findings suggest that fetal and infant AGD reflect androgen action during early fetal development., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Context: Trinucleotide repeats in the androgen receptor have been proposed to influence testosterone signaling in men, but the clinical relevance of these trinucleotide repeats remains controversial., Objective: To examine how androgen receptor trinucleotide repeat lengths affect androgen-related traits and disease risks and whether they influence the clinical importance of circulating testosterone levels., Methods: We quantified CAG and GGC repeat lengths in the androgen receptor (AR) gene of European-ancestry male participants in the UK Biobank from whole-genome and whole-exome sequence data using ExpansionHunter and tested associations with androgen-related traits and diseases. We also examined whether the associations between testosterone levels and these outcomes were affected by adjustment for the repeat lengths., Results: We successfully quantified the repeat lengths from whole-genome and/or whole-exome sequence data in 181 217 males. Both repeat lengths were shown to be positively associated with circulating total testosterone level and bone mineral density, whereas CAG repeat length was negatively associated with male-pattern baldness, but their effects were relatively small and were not associated with most of the other outcomes. Circulating total testosterone level was associated with various outcomes, but this relationship was not affected by adjustment for the repeat lengths., Conclusion: In this large-scale study, we found that longer CAG and GGC repeats in the AR gene influence androgen resistance, elevate circulating testosterone level via a feedback loop, and play a role in some androgen-targeted tissues. Generally, however, circulating testosterone level is a more important determinant of androgen action in males than repeat lengths., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: Testosterone therapy has been variably associated with increased thrombotic risk but investigations of global coagulation in this setting are lacking., Objective: This work aimed to compare global coagulation of hypogonadal men before (T0) and 6 months after (T1) starting testosterone replacement therapy (TRT), and healthy controls (HCs)., Methods: An observational prospective cohort study was conducted at 2 tertiary endocrinological ambulatory care centers. Patients included 38 men with hypogonadism (mean age 55 years, SD 13) and 38 age-matched HCs. Thrombin generation assay (TGA) was performed at T0 and T1 in hypogonadal men and in HCs. TGA is an in vitro procedure based on the continuous registration of thrombin generation and decay under conditions mimicking the process that occurs in vivo. The following TGA parameters were recorded: lag time; thrombin-peak concentration; time-to-reach peak, velocity index, and endogenous thrombin potential (ETP), the latter representing the total amount of thrombin generated under the driving forces of procoagulants opposed by the anticoagulants. Protein C, antithrombin, factor (F) VIII, and fibrinogen were assessed., Results: No changes in TGA parameters were observed between T0 and T1. Hypogonadal men displayed significantly higher ETP, fibrinogen, and significantly lower antithrombin levels both at T0 and T1 compared to HCs. Thrombin peak of hypogonadal men was significantly higher than HCs at T0 but not at T1. ETP and antithrombin were correlated with testosterone levels., Conclusion: Hypogonadal men display a procoagulant imbalance detected by increased thrombin generation. Short-term TRT does not worsen global coagulation, suggesting that the treatment can be safely prescribed to men diagnosed with hypogonadism., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Psoriasis, a chronic inflammatory skin disease, is associated with systemic complications that extend beyond cutaneous lesions, including cardiovascular risks and sexual dysfunction. Erectile dysfunction (ED) is notably more prevalent in male psoriasis patients, likely driven by both systemic inflammation and psychological stress. Adalimumab (ADA), a tumor necrosis factor-alpha (TNF-α) inhibitor, has been shown to effectively reduce psoriasis severity, but its effects on sexual and reproductive health remain underexplored. This study investigates the impact of ADA on erectile function, sperm parameters, and hormonal profiles in male psoriasis patients. This six-month prospective observational study included 33 biologic-naïve male patients aged 18-50 years with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] > 10). Patients received ADA according to standard clinical protocols. Erectile function was assessed using the International Index of Erectile Function (IIEF-5). Sperm parameters, including ejaculate volume, sperm concentration, total sperm count, motility, vitality, and morphology, were analyzed following World Health Organization (WHO) 2010 criteria. Hormonal profiles (testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and prolactin) were measured via standardized assays. Statistical analyses were performed using paired t-tests or Wilcoxon signed-rank tests, with p-values < 0.05 considered significant. ADA significantly improved erectile function, as the mean IIEF-5 score increased from 21.3 ± 2.2 to 22.2 ± 1.9 (p = 0.03). The percentage of patients with ED decreased from 51.5% at baseline to 36.4% post-treatment (p < 0.001). Progressive sperm motility and vitality showed statistically significant improvement post-treatment (p = 0.02 and p = 0.04, respectively), while other sperm parameters remained unchanged. Total testosterone levels significantly increased from 3.4 ± 0.4 ng/ml to 3.5 ± 0.4 ng/ml (p = 0.02), while LH, FSH, estradiol, and prolactin levels showed no significant changes. The anti-inflammatory properties of adalimumab, through the inhibition of TNF-α, not only reduce psoriasis severity but also appear to exert positive effects on male sexual and reproductive health. Our study demonstrated significant improvements in erectile function, sperm motility, vitality, and testosterone levels in male psoriasis patients after adalimumab therapy. These findings suggest that beyond its role in controlling psoriatic skin lesions, adalimumab may help mitigate the systemic inflammatory burden that contributes to sexual dysfunction and impaired spermatogenesis. Future long-term studies are essential to further explore the sustained impact of TNF-α inhibition on male fertility and reproductive outcomes., Competing Interests: Declarations Consent of publication This paper is submitted with consent and knowledge of all co-authors. Informed consent All patients supplied consent with the awareness that this information might. be made publicly available, according to the consent for the publication of recognized patient. data or other identifying material that was received by the authors and included at the time of article submission to the journal. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Sex differences exist in type 2 diabetes (T2D), and androgens have been implicated in the etiology of T2D in a sex-specific manner. We therefore aimed to investigate whether androgens play a role in explaining sex differences in glucose homeostasis and incidence of T2D., Methods: We used observational data from the German population-based KORA F4 study (n = 1975, mean age: 54 years, 41% women) and its follow-up examination KORA FF4 (median follow-up 6.5 years, n = 1412). T2D was determined through self-reporting and confirmed by contacting the physicians and/or reviewing the medical charts. Multivariable linear and logistic regression models were employed to explore associations. Mediation analyses were performed to assess direct effects (DE) and indirect effects (IE), and the mediating role of androgens (total testosterone (TT), dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAs)) in the association between sex (women vs. men) and glucose- and insulin-related traits (cross-sectional analysis) and incidence of T2D (longitudinal analysis)., Results: After adjustment for confounders, (model 1: adjusted for age; model 2: model 1 + smoking + alcohol consumption + physical activity), women had lower levels of TT, DHEAs, fasting glucose levels, fasting insulin levels, 2 h-glucose levels and HOMA-IR, compared to men. An inverse association was observed for TT and glucose- and insulin-related traits in men, while a positive association was observed for TT and fasting glucose levels in women. We found a mediatory role of TT on the association of sex with fasting glucose levels (IE: β = 3.08, 95% CI: 2.04, 4.30), fasting insulin levels (IE: β = 0.39, 95% CI:0.30, 0.47), 2 h-glucose levels (IE: β = 12.77, 95% CI: 9.01, 16.03) and HOMA-IR (IE: β = 0.41, 95% CI: 0.33, 0.50). Also, the inconsistent mediatory role of TT was seen on the association of sex with incidence of T2D (DE: 0.12, 95% CI: 0.06, 0.20 and IE: OR = 7.60, 95% CI: 3.43, 24.54). The opposing DE and IE estimates suggest that the association between sex and either glucose homeostasis or the incidence of T2D may differ when TT is considered as a potential mediator, with higher TT levels being beneficial for glucose metabolism or incidence of T2D in men, while in women, detrimental. No mediatory role was observed for either DHEA or DHEAs on glucose homeostasis or the incidence of T2D., Conclusions: The dimorphic mediatory role of TT highlights its complex role in metabolic health, contributing differently to the glucose dysregulation and risk of T2D in men and women., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval All study participants have provided written informed consent. The study was approved by the Ethics Committees of the Bavarian Chamber of Physicians (Ethical Approval Number 06068) adhering to the declaration of Helsinki. Informed consent Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s).)

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., Competing Interests: Competing interests CD has advisory roles for Janssen and IPSEN and has received travel compensation from Janssen, IPSEN and BayerB.H. has had advisory roles for ABX, AAA/Novartis, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen R&D, Lightpoint Medical, Inc., and Pfizer; has received research funding from Astellas, Bristol Myers Squibb, AAA/Novartis, German Research Foundation, Janssen R&D, and Pfizer; and has received compensation for travel from Astellas, AstraZeneca, Bayer and Janssen R&D. A.H, MGvB, AI, MN, UK, LP declare no conflicts of interest.VG: receiving grant support, lecture fees, consulting fees, and travel support from AstraZeneca, BMS, Ipsen, and Pfizer, consulting fees and travel support from Bayer, grant support, lecture fees, and consulting fees from MSD, consulting fees from Roche, Eli Lilly, Onkowissen, and EUSA Pharma, consulting fees and lecture fees from Janssen– Cilag, PharmaMar, Merck Serono, and Eisai, lecture fees from Asklepios Clinic, Diakonie Clinic, Dortmund Hospital, andClinic of Oldenburg, and grant support and consulting fees from Novartis. Ethical approval This study protocol was reviewed and approved by the local ethics committee of University Duisburg-Essen (21-9860-BO) and conducted in accordance with the ethical standards of the Declaration of Helsinki. The participants provided informed written consent before participating in the study., (© 2024. The Author(s).)

The purpose of this study was to determine the effects of resistance training (RT) alongside creatine-hydrochloride (Cr-HCl) or creatine monohydrate (CrM) supplementation on anabolic/catabolic hormones, strength, and body composition. Forty participants with an age range of 18-25 years were randomly divided into four groups (n=10): RT+Cr-HCl (0.03 g.kg-1 of body mass), RT+CrM-loading phase (CrM-LP) (0.3 g.kg-1 of body mass for five days (loading) and 0.03 g.kg-1 body mass for 51 days (maintenance)), RT+CrM-without loading phase (CrM-WLP) (0.03 g.kg-1 body mass), and RT+placebo (PL). The participants consumed supplements and performed RT with an intensity of 70-85 % 1RM for eight weeks. Before and after the training and supplementation period, strength (1RM), body composition (percent body fat (PBF), skeletal muscle mass (SMM), muscular cross-sectional area (MCSA)) and serum levels of testosterone, growth hormone (GH), insulin-like growth factor-1 (IGF-1), cortisol, adrenocorticotropic hormone (ACTH), follistatin and myostatin were measured. The results showed that in the supplementation groups, strength, arm and thigh MCSA, and SMM significantly increased, and PBF significantly decreased (P

Aims: Many studies demonstrated reproductive damage in men residing in plains who are exposed to hypoxia at high altitudes. However, little is known about mechanisms between male reproductive impairment and hypobaric hypoxia. Hypoxia is one of the reasons for the imbalance of cellular redox system. Ferroptosis, involved in many pathophysiological progresses, is an oxidative damage-related, iron-dependent regulated cell death, which needs exogenous inducer. In our study, we explored the mechanism between hypoxia and male reproductive dysfunction., Materials and Methods: Here, we established animal model simulating hypobaric hypoxia at an altitude of 5000 m and used ELISA, WB, qPCR, flow cytometry and etc. to obtain different results., Key Findings: The results demonstrated decrease of plasma testosterone (T) and free testosterone (FT) levels under hypoxia, meanwhile there's decline in sperm counts and sperm motility, coupled with increase in sperm malformation rates. Flow cytometry confirmed significant reduction in Leydig cell numbers. Prussian blue staining showed iron depositions in interstitial testis. Features of ferroptosis such as increased MDA (malondialdehyde) levels, reduced solute carrier family 7 member 11 (SLC7A11, xCT) and glutathione peroxidase 4 (GPX4) expression were observed in testis after hypoxic exposure. Further in vitro experiments, we observed that hypoxia suppressed xCT-GPX4 pathway and enhanced cellular ROS accumulation to lead Leydig cell proliferation activity decline., Significance: Our findings firstly indicated that hypoxia leads to male reproductive dysfunction via inducing Leydig cell ferroptosis. This discovery may offer a potential intervention target for addressing male reproductive injuries under hypoxic conditions., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Brucellosis in dromedary camel bulls leads to either temporary or permanent loss of fertility. Camel brucellosis is associated with both orchitis and epididymitis. However, the clinical signs of camel brucellosis are not clear as those in cattle. Therefore, this study aimed to diagnose camel brucellosis based on a serological screening using Rose Bengal plate test (RBPT) followed by competitive ELISA. To understand the impact of brucellosis on camel bull fertility, this study aimed to examine the semen characteristics, evaluate the testicular histopathology, examine hormonal profile, antioxidants and acute phase proteins (APP). A total of 150 mature bulls were used in this study. Blood samples were collected for serological, hormonal, and biochemical analysis. This study revealed that 6.6% and 7.3% of the examined bulls were Brucella-seropositive using RBPT and competitive ELISA, respectively. The Brucella-seropositive dromedary bulls showed poor semen quality, pathological changes orchitis, and lower testosterone. Moreover, our findings showed a higher cortisol level, and significant impairments in the measured APP and antioxidants in Brucella-seropositive bulls. In conclusion, the Brucella-seropositive dromedary bulls showed lower fertility due to poor semen quality and lower testosterone levels. Such lower fertility is likely mediated by high cortisol levels, and impaired APP and antioxidants' defense response., Competing Interests: Declarations Competing interests The authors declare no competing interests. Consent to participate Not applicable. This study did not involve human subjects., (© 2024. The Author(s).)

Background: 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., Objective: 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., Methods: 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., Results: 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., Conclusions: This systematic review will summarize and evaluate the evidence of the clinical and biochemical outcomes associated with hormone therapies for transgender individuals., Trial Registration: PROSPERO CRD42024483138; https://tinyurl.com/yc4sfvnb., International Registered Report Identifier (irrid): PRR1-10.2196/57931., (©Emily Sattora, Karen Teelin, Christopher Prendergast, Abigail Smith, James Evans, Aamer Imdad. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 12.11.2024.)

Dog overpopulation and stray dogs are global issues that are detrimental to public health and animal welfare. Thus, the goal of the current study was to provide alternatives for surgical castration. Therefore, calcium chloride was employed in this study, which might be an option for castration. Ten dogs were divided into two groups of five: a calcium chloride-treated group and a control group. The treated group received a single bilateral intratesticular injection of 1 ml of sterile saline containing calcium chloride dihydrate (CaCl2•2 H2O) at a dose of 20 mg/kg per testicle. While the control group was treated with 1 ml of sterile saline solution, Semen and blood collection, as well as Doppler ultrasonography, were routinely carried out every week on days 0, 7, 14, 21, and 28 in order to evaluate the impact of the injection on semen parameters and testicular blood flow. The testicular volume and echogenicity in the CaCl2-treated group were significantly (P < 0.001) lower in weeks 2 through 4 than in the control group. Furthermore, in canine semen, CaCl2 dramatically decreased the amount, motility, and viability of sperm. When compared to vehicle-control animals, azoospermia was seen 2 weeks after the injection and persisted for the end of the study. The testes of all dogs were surgically removed at 30 days post-injection, and testes were put in 10% neutral buffered formalin for tissue processing. When compared to the control group, the average weight of testes in the chemical groups was dramatically reduced. Significant decreases in spermatogenic processes, necrosis, and degeneration of seminiferous tubules packed with necrotic debris, and fibrosed interstitial tissue, necrosed and calcified Sertoli, and Leydig cells were seen 30 days after CaCl2 injection. There was a significant decrease in testosterone levels compared to day 0 before CaCl2 injection and the control group. From weeks 1 through 4, there was a substantial decrease in both peak systolic velocity (PSV) and end-diastolic velocity (EDV) values (P < 0.001) following a single intratesticular injection of CaCl2. The resistance index (RI) and pulsatility index (PI) showed the opposite tendency. Based on the histopathological and semen evaluations in this investigation, the study concludes that a single intratesticular injection of CaCl2 appears to be a practical and generally applicable approach for chemical sterilization of dogs., Competing Interests: Declarations Ethics approval and consent to participate All procedures on animals were approved by the Institutional Animal Care and Use Committee at the Faculty of Veterinary Medicine Cairo University with a number: Vet CU18042024892.All methods were carried out in accordance with relevant guidelines and regulations. All methods are reported in accordance with ARRIVE guidelines Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Kisspeptin is a major regulator of gonadotropin secretion in pigs. Previously, CRISPR/Cas9 knockout of KISS1 was used to develop a mosaic parental line of pigs to generate offspring that would not need castration due to loss of kisspeptin. The current goal was to characterize growth and reproductive development of F1 pigs from this parental line. Body weights, gonadotropin concentrations and gonadal development were measured from birth through development (boars to 220 days of age, n = 42; gilts to 160 days of age, n = 36). Testosterone, skatole, and androstenone were also measured in boars. Blood samples were collected by jugular venipuncture for quantification of serum hormones, gonadal tissues were collected for gross morphology and histology, and a fat biopsy was collected (boars) for skatole and androstenone analysis. Body weight did not differ with genotype. There were no differences between KISS1+/+ and heterozygote KISS1+/- animals for most parameters measured. Gonadotropin concentrations were reduced in KISS1-/- boars and gilts compared with KISS1+/+ and KISS1+/- animals (P < 0.05). Concentrations of testosterone in serum and both androstenone and skatole in adipose were less in KISS1-/- boars than in KISS1+/+ and KISS1+/- boars (P < 0.05). Hypogonadism was present in all KISS1-/- gilts and boars. These data indicate that knocking out KISS1 causes hypogonadotropic hypogonadism but does not negatively affect growth in pigs. Only one KISS1 allele is needed for normal gonadotropin secretion and gonadal development, and accumulation of compounds in adipose leading to boar taint., (Published by Oxford University Press on behalf of Society for the Study of Reproduction 2024.)

There are limited data on the effects of a high-fructose diet on the female reproductive system. Although metformin has some functional effects on female fertility, its reproductive outcome on high fructose diet-induced metabolic syndrome is unclear. The aim of the present study is to evaluate the impact of a high fructose diet on histomorphological and molecular parameters of the reproductive organs and vaginal microbiota as well as the treatment potential of metformin. Wistar albino rats were used in the study. The metabolic syndrome model was induced by a high-fructose diet in rats for 15 weeks. Metformin was orally administered once a day for the last 6 weeks. The high-fructose diet increased blood glucose, triglycerides, insulin, and ovarian testosterone levels; however, it reduced ovarian aromatase levels and follicle numbers and caused uterine inflammation. The high-fructose diet-induced molecular abnormalities on ovarian tissue were demonstrated by the downregulation of ovarian insulin signaling pathway proteins and dysregulation of ovarian mitogenic and apoptotic pathway proteins. A high-fructose diet caused vaginal dysbiosis, metformin increased probiotic bacteria in the vaginal microbiota. Our results revealed that metformin improves ovarian impairments by modulating hormonal balance, insulin level, mapk, and apoptotic signaling molecules, as well as regulating the vaginal microbiota., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Testosterone deficiency can cause abnormal lipid metabolism in men, leading to hyperlipidemia. We identified the testosterone-degrading bacterium Pseudomonas nitroreducens in the fecal samples of male patients with hyperlipidemia. Gastric administration of P. nitroreducens in mice led to testosterone deficiency and elevated blood lipid levels. Whole-genome sequencing of P. nitroreducens revealed the presence of 3/17β-hydroxysteroid dehydrogenase (3/17β-HSD), a gene responsible for testosterone degradation, which is also associated with hyperlipidemia. Microbiota analysis of fecal samples collected from 158 patients with hyperlipidemia and 151 controls revealed that the relative abundance of P. nitroreducens and 3/17β-HSD in the fecal samples of patients with hyperlipidemia was significantly higher than that in controls. These results suggest that P. nitroreducens and 3/17β-HSD may be related to the onset of testosterone deficiency-induced hyperlipidemia. Therefore, treatments targeted at eradicating testosterone-degrading bacteria are a potential future option for patients with testosterone-induced hyperlipidemia and should thus be studied further., (© 2024. The Author(s).)

Polycystic ovary syndrome (PCOS) is the most complex and common reproductive endocrine disease among reproductive age women. This study aimed to investigate the effects of vitamin D (Vit.D) in a PCOS mouse model induced by low dose DHEA and high-fat diet. Prepubertal female mice were divided into 4 groups randomly: control, PCOS, PCOS with low dose Vit.D(LDVD), and PCOS with high dose Vit.D(HDVD) groups (n = 10 per group). PCOS mice were administrated with high-fat diet and subcutaneous injection with 6 mg/kg/day dehydroepiandrosterone throughout the study. After the first 30 days, 1,25(OH)2D3 was intend to be administered by intraperitoneal injection for 40 consecutive days, 1.3 µg/kg/week in LDVD group, and 13 µg/kg /week in HDVD group. However, the mice in HDVD group appeared to be fatigue and anorexic after the Vit.D injections, then all died within two weeks. The body weights and testosterone levels in PCOS group were significantly higher than those in the control and LDVD groups (P < 0.001). The total cholesterol levels in the control group were lower than those in PCOS and LDVD groups (P < 0.001). Further, the ratio of liver to body weight was different among groups (P < 0.001). Our data illustrates that Vit.D has therapeutic effects on obesity and hyperandrogenemia in PCOS mouse model induced by low dose DHEA and high-fat diet. However, over dose of Vit.D is toxic. Further researches are needed to elucidate the mechanisms., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Objective: B-type natriuretic peptide (BNP) is a neurohormone primarily secreted from cardiac ventricles in reaction to increased volume and pressure. The plasma level of BNP is used to measure the mechanical function of the heart and the risk of developing chronic obstructive pulmonary disease (COPD). Alpha-1 antitrypsin (AAT) is a glycoprotein that acts as an inhibitor of serine proteases and plays a crucial role in protecting the lungs against potential harm. AAT deficiency also causes COPD. The data on the prevalence of BNP and AAT in African Americans (AA) are limited and inconsistent. No previous studies have investigated whether any association exists between BNP and AAT. We collected fasting blood samples from 114 AA subjects who provided informed consent. The plasma levels of the biomarkers were measured using ELISA., Results: Our findings revealed a significant negative correlation between AAT and BNP (r=-0.266, p = 0.01) as well as between AAT and TNF-α (r=-0.242, p = 0.01). Sex hormones (estrogen and testosterone) have a significant relationship with the levels of AAT and BNP. Increasing the AAT and reducing the levels of inflammation can lower the levels of BNP, which in turn could help lower the risk of heart disease in the AA population., (© 2024. The Author(s).)

Several studies have reported an increasing occurrence of poly- and perfluorinated alkyl substances (PFASs) in Arctic wildlife tissues, raising concerns due to their resistance to degradation. While some research has explored PFAS's physiological effects on birds, their impact on reproductive functions, particularly sperm quality, remains underexplored. This study aims to assess (1) potential association between PFAS concentrations in blood and sperm quality in black-legged kittiwakes ( Rissa tridactyla ), focusing on the percentage of abnormal spermatozoa, sperm velocity, percentage of sperm motility, and morphology; and (2) examine the association of plasma levels of testosterone, corticosterone, and luteinizing hormone with both PFAS concentrations and sperm quality parameters to assess possible endocrine disrupting pathways. Our findings reveal a positive correlation between the concentration of longer-chain perfluoroalkyl carboxylates (PFCA; C11-C14) in blood and the percentage of abnormal sperm in kittiwakes. Additionally, we observed that two other PFAS (i.e., PFOSlin and PFNA), distinct from those associated with sperm abnormalities, were positively correlated with the stress hormone corticosterone. These findings emphasize the potentially harmful substance-specific effects of long-chain PFCAs on seabirds and the need for further research into the impact of pollutants on sperm quality as a potential additional detrimental effect on birds.

Human chorionic gonadotropin (hCG) is widely used to treat reproductive dysfunction by enhancing testicular blood flow and stimulating hormonal activity. This study investigates the seasonal variations in the response to hCG treatment in male dogs, focusing on its effects on testicular blood flow and plasma concentrations of testosterone and oestrogen. Conducted across different seasons (spring, summer, fall and winter), the study utilised colour Doppler ultrasonography to measure testicular haemodynamics and analysed hormonal levels at multiple time points post-hCG injection. The findings revealed that the response to hCG is modulated by seasonal factors, with significant variations in both blood flow and hormone levels. A significant negative relationship was indicated between testicular blood flow and testosterone levels, particularly during spring and summer. These results suggest that seasonality should be considered when administering hCG for reproductive treatments in canines., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Minipuberty is the second phase of physiological activation of the reproductive axis, playing a role in the postnatal development of sexual organs. The course of female minipuberty was found to be affected by low maternal vitamin D status and hypothyroidism during pregnancy. The aim of the current study was to assess the hormonal profile and the size of sexual organs in daughters of mothers with gestational diabetes mellitus. The study included three matched groups of infant girls: daughters of healthy women without metabolic disorders during pregnancy (group 1), daughters of women with poorly controlled gestational diabetes mellitus (group 2), and daughters of women with gestational diabetes mellitus adequately controlled during pregnancy (group 3). Urinary levels of gonadotropins, salivary levels of estradiol, testosterone, DHEA-S and progesterone, ovarian volume, uterine length and breast diameter were measured from postnatal month 1 to postnatal month 18. Concentrations of FSH, LH and estradiol were higher, while concentration of progesterone was lower in group 2 than in the remaining groups. There were no between-group differences in concentrations of testosterone and DHEA-S. Levels of LH, FSH, estradiol and progesterone correlated with maternal whole-blood levels of glycated hemoglobin. Group 2 was also characterized by the longest detection periods for LH and estradiol. Ovarian volume, uterine length and breast diameter were greater in group 1 than in the remaining two groups. Over the entire observation period, there were no differences in hormone levels and sizes of the sexual organs between groups 1 and 3. The obtained results suggest that poorly controlled, but not well controlled, gestational diabetes mellitus affects the course of female minipuberty.

The neonatal increase in circulating luteinizing hormone (LH) is crucial for testicular development. In male pigs, blood LH levels start to increase approximately 1 week after birth and return to basal level by 5-6 weeks of age. This study tested the hypothesis that neonatal treatment with a combination of estrogens and androgens suppresses LH secretion and thereby inhibits testicular development. On Day 1 after birth, piglets received a slow-release implant containing estradiol (E 2 , 8-40 mg) and trenbolone acetate (TBA, 40-200 mg) or remained intact. At 4 weeks of age, mean serum LH concentrations were ∼ 7 ng/mL in untreated males, whereas pigs with implants had serum LH concentrations < 1 ng/mL. Despite this reduction, LH was still detected in the pituitary glands of treated pigs. Interestingly, neonatal castration also lowered circulating LH, highlighting the importance of testis physiology in the early establishment of the reproductive axis. The higher dose (20 mg E2 + 100 mg TBA) inhibited testis function more effectively, as evidenced by lower circulating testosterone concentrations compared to intact pigs. Furthermore, E2 + TBA treatment had a lasting impact on testicular growth, resulting in smaller testes at 26 weeks of age and the presence of immature Leydig cells. Overall, neonatal E2 + TBA treatment suppressed the postnatal LH rise and testicular growth until market age, offering a potential non-surgical alternative to castration in male pigs., Competing Interests: Declaration of Competing Interest CheMyong Jay Ko is the founder and CEO of Epivara, Inc. ChanJin Park, Sandra Soto-Heras, Lindsey Reinacher, Katie Chai, and Sherry Zhou are employed by Epivara. Po-Ching Lin, Ji-Eun Oh, Mary Bunnell, Rex A. Hess, and Luiz Renato de França have no conflict of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

There are known sex differences in cardiorespiratory fitness (CRF). Little is known about the impact of pubertal blockade with a gonadotropin-releasing hormone agonist (GnRHa) followed by hormone therapy on CRF for transgender adolescents. We aimed to 1 ) determine the effect of GnRHa monotherapy on CRF and mitochondrial function and associations with metabolomic profiles and 2 ) evaluate changes after 1 and 12 mo of testosterone therapy among transgender adolescents. Participants assigned female at birth ( n = 19, baseline age of 15.0 ± 1.0 yr) from two groups: GnRHa + ( n = 8) and GnRHa - ( n = 11) were examined at baseline and 1- and 12-mo post-testosterone therapy in a longitudinal observational study to assess cardiorespiratory fitness, mitochondrial respiration, and metabolic profile. Fasted morning labs included assessment of metabolomics and peripheral blood mononuclear cell mitochondrial respiration and degree of mitochondrial coupling (respiratory control ratio, RCR). A graded cycle ergometer test was performed. Baseline differences were evaluated between groups. Changes were compared with mixed linear regression models evaluating time (baseline, 1 mo, and 12 mo), group (GnRHa treatment yes/no), and their interaction. At baseline GnRHa + individuals had higher relative V̇o 2peak (30.1 ± 4.83 vs. 25.24 ± 4.47 mL/kg/min, P = 0.042) than GnRHa - individuals. In regression models, GnRHa + individuals had a significant increase in peak watts ( P = 0.011) and total exercise time ( P = 0.005) after 12 mo of testosterone ( P = 0.012) but not GnRHa - individuals. GnRHa + individuals have significantly higher RCR under carbohydrate ( P = 0.0007) and lipid ( P = 0.0002) conditions than GnRHa + individuals. Pretreatment with GnRHa positively influences peak CRF and mitochondrial respiration in adolescent transgender males undergoing testosterone therapy. NEW & NOTEWORTHY This study demonstrates differences in exercise capacity and mitochondrial respiration at baseline based on whether or not individuals had feminizing puberty blocked. Individuals who had puberty blocked had greater improvements in cardiopulmonary exercise testing parameters after 12 mo of testosterone than those who went through feminizing puberty.

The effects of androgens on women's bone health are not fully understood. Mendelian randomization (MR) studies using sex-combined data suggest that sex hormone-binding globulin (SHBG) and bioavailable testosterone (BioT) causally affect bone traits. Given significant sex differences in hormone regulation and effects, female-specific MR studies are necessary. In the current study, we explored the causal relationships of SHBG, BioT, and total testosterone (TT) with forearm fracture (FAFx) risk in women using two-sample MR analyses. We utilized a unique female-specific FAFx outcome dataset from three European biobanks (UFO, HUNT, Estonian Biobank) comprising 111,351 women and 8823 FAFx cases, along with female-specific genetic instruments of SHBG, BioT, and TT identified in the UK Biobank. We also assessed bone mineral density (BMD) at the forearm (FA), femoral neck (FN), and lumbar spine (LS) using female-specific GWAS data from the GEFOS consortium. High SHBG (odds ratio per standard deviation increase (OR/SD): 1.53, 95% confidence intervals (CIs): 1.34-1.75), low BioT (OR/SD: 0.77, 0.71-0.84) and low TT (OR/SD 0.90, 0.83-0.98) were causally associated with increased FAFx risk. BioT was positively, and SHBG inversely, causally associated with especially FA-BMD, but also LS-BMD and FN-BMD, while TT was only significantly positively associated with FA-BMD and LS-BMD. We propose that endogenous androgens and SHBG are important for women's bone health at distal trabecular-rich bone sites such as the distal forearm and may serve as predictors for FAFx risk., (© 2024. The Author(s).)

Perfluorooctanoic acid (PFOA), which is widely used during the manufacturing of fluoropolymer coatings and polytetrafluoroethylene, is now a widespread pollutant in the environment and within the human body. This study used zebrafish, an aquatic model species, to investigate how low levels of chronic PFOA exposure affect the reproductive system. The results of the experiments in which zebrafish were exposed to 414 ng/L or 4140 ng/L for 60 days showed a variety of adverse effects on testicular tissue and sperm, including dose-dependent changes in plasma estradiol and testosterone levels, various sperm malformations, decreased sperm motility and concentration, and PFOA-induced oxidative stress and testicular damage with increased rates of apoptosis. In addition, offspring of the zebrafish that had been exposed to PFOA were characterized by increased malformation and mortality. Subsequent transcriptional analyses of the male gonads revealed the significant activation of oxidative stress bioprocesses and immuno-inflammatory signaling pathways, along with the dysregulation of reproductive bioprocesses. In conclusion, low-level chronic exposure to PFOA affects both the reproductive performance of adults and the development of offspring; the mechanisms for these adverse effects involve alterations in several molecular pathways that may be involved in PFOA-induced oxidative stress and reproductive abnormalities. The presented data can be used to assess the ecotoxicity of PFOA to the male reproductive system at environmentally-relevant concentrations., Competing Interests: Declaration of competing interest The authors declare the absence of any perceived financial conflicts or personal relationships that might appear to influence the findings presented in this document., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Present investigations were undertaken to record the vulnerability of testis to nickel oxide nano and microparticles in Wistar rat with special reference to their preferred bioaccumulation, consequent generation of reactive species, reciprocal influence on testosterone synthesis, DNA damage in spermatids and histopathological changes. Suitable numbers of rats were gavaged NiONPs or NiOMPs (5 mg/kg b.w.each) for 15 and 30 days. Testes en bloc were removed and processed for the estimation of selected parameters. Results showed that rat testes could accumulate nickel in an exposure time dependent manner. Generation of malondialdehyde, a denominator of ROS, increased significantly in the testes of NiONPs treated rats. Moreover, serum testosterone values also increased in NiONPs treated rats. Higher DNA damage in sperms was also recorded. Nano and microparticles of nickel, both could induce specific dose and time dependent lesions in the testis of rat. Histopathological results revealed degeneration of germinal epithelium and spermatocytes; hypertrophy of seminiferous tubules and necrosis. SEM results also indicated specific morphological changes in cellular components of tubules. This study suggests that testis is also vulnerable to the adverse effects of NiONPs alike liver and kidney. Both micro and nanoparticles of nickel elicited differential effects in a dose and exposure time dependent manner. However, NiONPs induced greater overall toxicity than NiOMPs. The results are expected to be helpful in determining the human reproductive health risks, associated with environmental/ occupational exposure to nanoparticles of nickel., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Aim: Endometrial changes in Japanese transgender men (TGM) on testosterone use remain elucidated. This study aims to present TGM with endometrial cancer and insights from a literature review of similar cases. Furthermore, we investigated the correlation between endometrial cancer and severe obesity in TGM who underwent gender-affirming surgery., Methods: Between July 2020 and April 2023, two groups were assessed: 2 TGM with endometrial cancer and 43 TGM without cancer who underwent gender-affirming surgery. A literature review for TGM with endometrial cancer was conducted. Clinical data were retrospectively collected, and histopathological evaluation of female genital organs was performed., Results: Two TGM with endometrial cancer and an additional four similar cases were identified through a literature search. These TGM had severe obesity (body mass index [BMI] ≥30 kg/m 2 ) and long-term testosterone use, indicating a possible link between endometrial cancer and these factors. Subsequently, we investigated the 43 TGM without cancer. We revealed 30% with obesity (BMI ≥25), only three cases of severe obesity (BMI ≥30), and a significant correlation between testosterone use duration and BMI in TGM without cancer. Histological examination revealed focal proliferative endometrium in 51% of cases and polycystic ovarian changes in 77%., Conclusions: Our observations suggest a potential link between severe obesity, prolonged testosterone use, and endometrial cancer in transgender men. Histological changes in the female genital tract highlighted frequent focal proliferative endometrium, even under testosterone therapy. Further research should focus on larger, multi-institutional studies to confirm these findings and establish endometrial cancer screening for Japanese TGM., (© 2024 Japan Society of Obstetrics and Gynecology.)

Polycystic ovary syndrome (PCOS) is the most common endocrine-related reproductive disorder in women of reproductive age, accompanied by both the impairment of female fecundity and a risk of metabolic disorders. PCOS is emphasized as a worldwide concern due to its unknown etiology and lack of specific medications. The current study aimed to evaluate the effects of L-tartaric acid, an abundantly occurring compound in fruits, on the histostereological and hormonal changes caused by PCOS. Forty adult Sprague Dawley rats were randomly divided into four groups including controls (no intervention), Tartaric acid (40mg/Kg/day from day 21 onwards for 39 days), PCOS (21 days letrozole and then normal saline orally for 39 days), and PCOS + Tartaric acid. After treatments, the ovarian histostereological analysis as well as the level of reproductive hormones including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, progesterone, and testosterone was measured. PCOS caused a significant decrease in the number of unilaminar, multilaminar, antral, and graafian follicles and increased follicular atresia (p-value < 0.001). Moreover, the weight and volume of ovarian tissue and related structures including cortex, medulla, and cysts increased significantly (p-value < 0.0001). However, corpus luteum volume was significantly decreased (p-value < 0.001). Although significant differences were found in some parameters with the control group (p-value < 0.05), the administration of tartaric acid restored the pathological effects of PCOS on the ovarian histostructure. Furthermore, tartaric acid improved the serum levels of LH, estradiol, progesterone, and testosterone (p-value < 0.05). The obtained findings may suggest tartaric acid as a novel strategy for PCOS management, although further studies are necessary., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Background: Steroid hormones (SH) during pregnancy are associated with the development of gestational diabetes mellitus (GDM). Early and mid-Down syndrome screening is used to assess the risk of Down syndrome in the fetus. It is unclear whether changes in SH during this period can be used as an early predictor of GDM., Methods: This study was a multicenter, longitudinal cohort study. GDM is diagnosed by an oral glucose tolerance test (OGTT) between 24 and 28 weeks of gestation. We measured SH levels at early and mid-Down syndrome screening, respectively. Based on the SH changes, logistic regression analysis was used to construct a prediction model for GDM. Finally, evaluated the model's predictive performance by creating a receiver operating characteristic curve (ROC) and performing external validation., Results: This study enrolled 193 pregnant women (discovery cohort, n = 157; validation cohort, n = 36). SH changes occur dynamically after pregnancy. At early Down syndrome screening, only cortisol (F) (p < 0.05, 95 % CI 4780.95-46083.68) was elevated in GDM. At mid-Down syndrome screening, free testosterone (FT) (p < 0.01, 95 % CI 0.10-0.55) and estradiol (E2) (p < 0.05, 95 % CI 203.55-1784.78) were also significantly elevated. There were significant differences in the rates of change in E2 (Fold change (FC) = 1.3425, p = 0.0072), albumin (ALB) (FC=1.5759, p = 0.0117), and dihydrotestosterone (DHT) (FC=-2.1234, p = 0.0165) between GDM and no-GDM. Stepwise logistic regression analysis resulted in the best predictive model, including six variables (Δweight, ΔF, Δcortisone (E), ΔE2, Δprogesterone (P), ΔDHT). The area under the curve for this model was 0.791, and for the external validation cohort, it was 0.799., Conclusions: A GDM prediction model can be constructed using SH measures during early and mid-Down syndrome screening., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to evaluate the repeated oral administration of α-terpineol in juvenile Wistar rats over a 70-day period. The objective was to assess the potential systemic and reproductive toxicity of α-terpineol when administered by gavage at doses of 75, 150, and 300 mg/kg/day to juvenile Wistar rats for 70 days from postnatal day 24. The control group received corn oil for 70 days. During the study, various parameters were evaluated, including clinical signs, body weight, food intake, neurobehavioral observations, haematology, serum biochemistry, organ weights, steroidogenic gene expression, and histopathological examination. No toxicity-related changes were observed in body weight, food intake, neurobehavioral observations, or steroidogenic gene expression. However, sperm evaluation revealed a complete absence of sperm and delayed sexual maturation. Total cholesterol was significantly elevated in both sexes, and serum testosterone was reduced at the 150 and 300 mg/kg doses. Microscopic examination showed severe pathological changes in the testes, epididymis, liver, and kidneys of both males and females. After the 14-day recovery period, total cholesterol levels returned to the normal range, but no recovery was observed in the other organs. The no-observed-adverse-effect level was 75 mg/kg/day for male rats based on the histopathological findings in the testes, liver, and kidneys, and for female rats based on the kidney and liver histopathology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract: An enduring debate in research revolves around the association between elevated endogenous testosterone levels and prostate cancer. This systematic review is intended to assess the present understanding of the role of endogenous testosterone in the diagnosis and treatment of low- and intermediate-risk prostate cancer. Our search strategy was the following: (endogenous testosterone) AND (((low risk) OR (intermediate risk)) AND ((diagnosis) OR (treatment))) AND (prostate cancer); that was applied to PubMed, Web of Science, and Scopus databases to identify pertinent articles. Two investigators performed an independent selection following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The preliminary investigation detected 105 records, and 81 records remained after eliminating duplicates. Following the review of titles and abstracts, 71 articles were excluded. A comprehensive examination of the full text was conducted for 10 articles, excluding 3 of them. After revising the references of eligible articles, other 3 articles were included. We finally identified 10 suitable studies, including three main topics: (1) association between endogenous testosterone and European Association of Urology (EAU) risk classes; (2) association between endogenous testosterone density and the tumor load; and (3) association of endogenous testosterone with tumor upgrading and tumor upstaging. Actual literature about the impact of endogenous testosterone on low- and intermediate-risk prostate cancer is not numerous, but appears to be still conflicting. More investigations are needed to increase the consistency of the literature's results., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

There is a chronic inflammation in PCOS patients, which is correlated with the pathogenesis of PCOS. IL-18 and IL-18BP are related with some inflammatory diseases, while less explored in PCOS. Whether IL-18BP could be a potential drug of PCOS remains unknown.IL-18 and testosterone levels were evaluated in serum of 10 non-PCOS control patients and 20 PCOS patients. Female C57/BL6 mice were gavaged with letrozole to induce PCOS mouse model and IL-18 level was evaluated in the serum of PCOS mouse model, and IL-18 is intraperitoneally injected in female mice, IL-18BP is intraperitoneally injected in the PCOS mice models. Then the body weights, estrous cycles, reproductive hormones and morphology of ovaries were analyzed. The level of ovarian chronic inflammation, fibrosis and endoplasmic reticulum (ER) stress are evaluated.IL-18 levels are increased in the serum of PCOS patients and PCOS mice models respectively. The serum DHEAS, iWAT weight and adipocyte size were increased in IL-18 group compared to the control group (P < 0.05). In the PCOS mouse model treated with IL-18BP, the body weight and serum LH/FSH ratio was decreased compared to the PCOS group (P < 0.05). The expression levels of inflammatory factors and fibrosis-related genes, the expression level of endoplasmic reticulum stress-related genes, and the ROS positive area of ovarian tissue was decreased (P < 0.05).IL-18 is involved in inducing PCOS phenotypes, while IL-18BP relieves PCOS phenotypes by alleviating ovarian chronic inflammation, fibrosis and ER stress in PCOS mice., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Androgen receptors are expressed in the kidney and serum testosterone is negatively associated with serum phosphate in males, suggesting a role of testosterone in renal phosphate handling. In this cross-sectional study, we examined the association of serum total and free testosterone with acute phosphate and calcium excretion in males in response to an oral phosphate challenge. Thirty-five healthy adult males with normal baseline testosterone levels consumed a 500 mg phosphorus drink and the urinary excretion of minerals, as well as levels of relevant circulating parameters, were assessed at baseline and hourly for 4 h. Serum total testosterone was positively associated with overall phosphate excretion (r = 0.35, p = 0.04) and calcium excretion (r = 0.44, p = 0.00) in response to the challenge. Serum free testosterone was positively associated with post-challenge calcium excretion (r = 0.34, p = 0.048), but significance was not reached for phosphate excretion (r = 0.31, p = 0.07). Serum total and free testosterone were not associated with parathyroid hormone, fibroblast growth factor-23, or vitamin D-key factors implicated in phosphate and calcium regulation. Overall, higher serum total testosterone levels in healthy middle-aged males are associated with a greater capacity to acutely excrete phosphate and calcium after a single oral phosphate challenge, suggesting potential ramifications of testosterone deficiency related to mineral homeostasis., (© 2024 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Introduction: Female hormones and obesity have an impact on women with asthma. We aimed to describe how these components affect asthma inflammatory processes., Methods: Sex hormones [FSH, LH, estradiol (E2), estrone (E1), testosterone and Δ4 androstenedione (A4)] and serum IL1β, IL13, IL17a, IL-5, IL6, TNF-a were measured from 11 to18 pre- and postmenopausal women with asthma., Results: Premenopausal normal weight women revealed higher levels of IL5 and IL17a than obese women on both days of the menstrual cycle (IL5: D1: 6.4 vs 1.4 pg/ml, p  = .036 and D14: 3 vs 1.4 pg/ml, p  = .045 and IL17a: D1: 13.7 pg/ml vs 10.6 pg/ml and D14: 12.4 pg/ml vs 10.6 pg/ml, p  = .009, respectively). In premenopausal women on D1, Δ4 Androstenedione was positively correlated with IL1β ( p  = .016, r  = 0.733), whereas on D14, Estradiol with IL1β ( p  = .009, r = -.768) and TNF-a with Testosterone ( p  = .004, r = -0.816), and Δ4 Androstenedione ( p  = .002, r = -0.841) negatively. In postmenopausal women, TNF-a was negatively associated with FSH ( p  = .004, r = -0.638), but positively with Testosterone ( p  = .025, r  = 0.526) and IL10 also positively with Estradiol ( p  = .007, r  = 0.610)., Conclusion: Obesity shows a protective role in asthma through the suppression of IL5 and IL17. Estrogens seem to inhibit Th1 and Th2 inflammation, while androgens have a dual role with negative and positive correlations with neutrophilic biomarkers.

Introduction: Polycystic ovarian syndrome (PCOS) is the commonest endocrine condition affecting reproductive age women. Many biomarkers may aid assessment and management, however evidence is limited on their utility in clinical practice. We conducted a review of systematic reviews to identify the most useful biomarkers in the clinical management of PCOS., Methods: We searched MEDLINE, EMBASE, CENTRAL and HTA until August 2023 for reviews evaluating biomarkers in PCOS women compared to healthy controls. Methodological quality was assessed using the AMSTAR2 tool. We reported pooled evidence for each biomarker with 95% confidence intervals from the most recent, up-to-date, and best quality review., Results: From 3360 citations, we included 75 systematic reviews (88 biomarkers, 191,792 women). Most reviews (50/75, 67%) were moderate quality, but reported high heterogeneity (66/75, 88%). We identified 63 abnormal biomarkers in women with PCOS versus healthy controls. Of these, 22 core biomarkers could help evaluate the multisystemic impact of PCOS and inform patient management and surveillance: dehydroepiandrosterone, prolactin, sex hormone-binding globulin, total and free testosterone, anti-Mullerian hormone, systolic and diastolic blood pressure, c-reactive protein, fibrinogen, oral glucose tolerance test, homoeostatic model assessment-insulin resistance index, fasting insulin, total cholesterol, triglycerides, lipoprotein(a), HDL, LDL, non-HDL-cholesterol, ferritin, iron, and 25-hydroxy-vitamin D., Conclusion: We identified 22 core biomarkers assessing the multisystemic impact of PCOS and inform its clinical management. Future research is required to establish validated healthcare pathways., (© 2024 The Author(s). Clinical Endocrinology published by John Wiley & Sons Ltd.)

Reproductive deficiency is a major outcome of pesticide exposure sequel to cellular oxidative damage to sex organs. Flavonoid possess potent antioxidant capacities to mitigate pesticide related cellular injury. The present investigation examined the mitigative effect of micronized purified fractions of diosmin and hesperidin on reproductive hormones, sperm parameters, and testicular glycogen in male Wistar rats after sub-chronic Chlorpyriphos (CPF) exposure. Twenty-five male Wistar rats (120-145 g) were randomly allocated five rats per group. Group I (DW) received distilled water (2 ml/kg), Group II (S/oil) received soya oil (2 ml/kg), Group III (DAF) received Daflon at 1000 mg/kg, Group IV (CPF) received Chlorpyriphos (7.74 mg/kg), and Group V (DAF + CPF) received Daflon (1000 mg/kg) followed by CPF (7.74 mg/kg) after 30 min of Daflon. This regimen was administered daily for 60 days. After cervical venesection under light chloroform anesthesia, blood samples were examined for levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Each rat's testicular tissue was quickly cut, collected, and glycogen evaluated. Sperm concentration, motility, morphology, and viability were measured in the right caudal epididymis. Results revealed that the untreated CPF group had significantly lower FSH, LH, testosterone, testicular glycogen, and sperm concentration. Additionally, CPF group sperm characteristics were abnormal compared to other groups. These reproductive hormones, testicular glycogen, and sperm parameters improved in the Daflon-treated groups. Hence, pre-treatment with flavonoid fractions of diosmin and hesperidin mitigated CPF-induced reproductive toxicity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The hypothalamic-pituitary-testicular axis is characterised by the existence of major functional changes from its establishment in fetal life until the end of puberty. The assessment of serum testosterone and gonadotrophins and semen analysis, typically used in the adult male, is not applicable during most of infancy and childhood. On the other hand, the disorders of gonadal axis have different clinical consequences depending on the developmental stage at which the dysfunction is established. This review addresses the approaches to evaluate the hypothalamic-pituitary-testicular axis in the newborn, during childhood and at pubertal age., Design: We focused on the hormonal laboratory and genetic studies as well as on the clinical signs and imaging studies that guide the aetiological diagnosis and the functional status of the gonads., Results: Serum gonadotrophin and testosterone determination is useful in the first 3-6 months after birth and at pubertal age, whereas AMH and inhibin B are useful biomarkers of testis function from birth until the end of puberty. Clinical and imaging signs are helpful to appraise testicular hormone actions during fetal and postnatal life., Conclusions: The interpretation of results derived from the assessment of hypothalamic-pituitary-testicular in paediatric patients requires a comprehensive knowledge of the developmental physiology of the axis to understand its pathophysiology and reach an accurate diagnosis of its disorders., (© 2023 John Wiley & Sons Ltd.)

Abstract: McFadden, BA, Walker, AJ, Cintineo, HP, Bozzini, BN, Sanders, DJ, Chandler, AJ, and Arent, SM. Sex differences in physiological responses to a National Collegiate Athletic Association Division I soccer season. J Strength Cond Res 38(11): 1891-1899, 2024-Identifying physiological changes that occur in response to workload demands can help to elucidate athlete management and recovery strategies. The purpose of this study was to compare the physical and physiological demands between men and women throughout the course of a collegiate soccer season. Men ( N = 23) and women ( N = 26) soccer players participated in blood draws before preseason (T1) and every 4 weeks thereafter (T2-T4). Workload was determined at all practices and games via heart rate and global positioning satellite monitoring systems. Repeated measures multivariate analysis of variance and linear mixed models were used to assess workload and biomarker responses throughout the season ( p < 0.05). Both teams experienced the highest workloads during the first 4 weeks of the season ( p < 0.05), which was followed by several biomarker perturbations. Sex-by-Time interactions were observed for total cortisol, growth hormone, insulin-like growth factor-1, thyroxine, thyroid-stimulating hormone, vitamin D, and omega 3 fatty acid index ( p < 0.05). Additional Sex effects were observed for free and total testosterone, estrogen, prolactin, sex-hormone binding globulin, creatine kinase, and iron levels ( p < 0.05). Women soccer players experienced further Time effects for free cortisol, iron, ferritin, and percent transferrin saturation ( p < 0.05). Male soccer players experienced additional Time effects for total testosterone, estrogen, creatine kinase, interleukin-6, triiodothyronine, and ferritin ( p < 0.05). Despite similar patterns of change in workloads, differential fluctuations in physiological markers were observed between the sexes. Understanding sex differences in response to comparable workloads may enhance exercise prescriptions for better athlete management plans. Additional strategies to increase iron may be warranted in female athletes., (Copyright © 2024 National Strength and Conditioning Association.)

Abstract: Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive patients who were treated at Beijing Children's Hospital, Capital Medical University (Beijing, China), between January 2016 and October 2023 were retrospectively reviewed. Clinical evaluations, including physical examination, hormone examination, serum tumor marker analysis, abdominal and scrotal ultrasound, chest X-ray, and bone age measurement, were conducted before surgery and at follow-up time points. Surgical approaches were selected according to the individual conditions. Patients with an abnormal hormonal status and suspected of having central precocious puberty were referred to endocrinologists to confirm the diagnosis. Subsequently, gonadotropin-releasing hormone analog therapy was proposed. The mean patient age was 81.3 (range: 40-140) months at the time of the operation. Ten patients had peripheral precocious puberty at admission. All patients had elevated preoperative testosterone levels, whereas tumor marker levels were normal. Testis-sparing surgery was performed in eleven patients, and radical orchiectomy was performed in one patient. The follow-up duration (mean ± standard deviation) was 36.2 ± 25.3 months. Five patients had central precocious puberty, with a mean duration of 3.4 (range: 1-6) months postoperatively. Three patients were receiving gonadotropin-releasing hormone analog therapy, and good suppression of puberty was observed. No risk factors were found for secondary central precocious puberty. There was a high prevalence of central precocious puberty secondary to Leydig cell tumors in our study. Gonadotropin-releasing hormone analog therapy has satisfactory treatment effects. Larger sample sizes and long-term follow-up are needed in future studies., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Purpose: Approximately 25% to 50% of patients with high-risk localized prostate cancer experience biochemical recurrence (BCR) within 2 years of radical prostatectomy. The Apa-RP study (NCT04523207) investigated whether adjuvant apalutamide plus androgen deprivation therapy (ADT) in high-risk patients who have undergone radical prostatectomy improved BCR-free survival., Materials and Methods: Apa-RP was a multicenter, open-label, single-arm, phase 2 study conducted in community urology practices in the US. High-risk patients who had radical prostatectomy received 12 cycles of apalutamide (240 mg daily; 28-day cycles) plus ADT. The primary end point was BCR-free survival. Secondary end points included testosterone recovery (≥150 ng/dL) and safety., Results: One hundred eight patients were enrolled; median age was 66.0 years (range 46.0-77.0 years). Median preoperative PSA and baseline testosterone were 7.6 ng/mL (range 2.2-62.7 ng/mL) and 340.0 ng/dL (range 43.0-939.0 ng/dL), respectively. The BCR-free rate at 24 months (12 months after completion of planned therapy) was 100% (90% CI 93-100). Serum testosterone recovery rate (≥50 and ≥150 ng/dL) 12 months after treatment completion was 96% (95% CI 88-98) and 77% (95% CI 66-85), respectively. Overall, 107 (99%) patients experienced treatment-emergent adverse events, with 24 (22%) experiencing grade 3 to 4 events., Conclusions: In Apa-RP, BCR-free survival was 100% with 77% of patients having testosterone recovery (≥150 ng/dL) within 12 months of actual treatment completion and a manageable safety profile. These results provide proof of concept that treatment intensification with 12 cycles of apalutamide plus ADT could become an option for patients with high-risk localized prostate cancer who have undergone radical prostatectomy., Trial Registration: ClinicalTrials.gov Identifier: NCT04523207.

Orchitis is a frequent inflammatory reproductive disease that causes male infertility and a decline in sperm quality. Gut microbiota can regulate systemic and local inflammation, spermatogenesis and blood-testosterone barrier (BTB). In this study, we investigated correlation between gut microbiota and orchitis by establishing a mouse gut microbiota imbalance model induced by antibiotics (ABX) treatment and orchitis model induced by lipopolysaccharide (LPS) infection. Based on these two models, 16s rRNA sequencing and feces microbiota transplantation (FMT) experiments were combined to examine the function and regulatory mechanisms of the gut microbiota in host defense against orchitis. Compared with control mice, gut microbiota imbalance resulted in increasing inflammatory responses, modulating oxidative stress related enzyme activity, testosterone levels and the permeability of blood testosterone barrier, which are restored after FMT. Subsequently, we tested the relationship between the gut microbiota imbalance and testicular inflammation severity in orchitis. It was found that the ABX and LPS co-treated mice had more severe inflammatory responses, lower testosterone levels and greater permeability of the BTB than the LPS-treated mice, but these changes could be partially recovered by gut microbiota transplantation. In conclusion, these above results proved for the first time that gut microbiota is involved in the pathogenesis of orchitis, which laid a good foundation for the subsequent development of anti-orchitis drugs and probiotic targeting intestinal flora., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Background: After the Coronavirus Disease pandemic, depression became more present, including in adolescents. Escitalopram, a selective serotonin reuptake inhibitor, was approved in 2009 for treatment of the major depressive disorder, both in children and adolescents. The undesirable effects of antidepressants on sexual dysfunction are usually underestimated., Aims: To investigate the effects of chronic mild stress, induced from peripuberty up to adulthood, on male sexual behavior parameters, with or without the escitalopram treatment, using rats as experimental model in a translational study., Materials and Methods: Forty-four peripubertal male rats were distributed into four groups: Sham control, escitalopram, stress, and stress + escitalopram. The chronic mild stress consisted of nine different stressors randomly applied one per day, for 8 weeks (from 41 to 97 days postpartum). Escitalopram therapy by gavage (10 mg/kg) started at 70 days postpartum and lasted for 4 weeks. The male sexual behavior parameters were evaluated at 114 days postpartum. After that, euthanasia was performed for blood and testis collection. Histopathology of the testes and plasmatic testosterone level were carried out., Results: There was a reduction in sexual activity and motivation in rats exposed to the stress protocol, which were treated or not with escitalopram, as well as an increase in the total number of mounts in animals exposed to the stress and treated with escitalopram. The testosterone levels were lower in animals exposed to the stress, which were or not treated with escitalopram (stress and stress + escitalopram). The frequency of histologically normal seminiferous tubule sections was lower in animals that were exposed to the stress and/or received escitalopram (escitalopram, stress, and stress + escitalopram)., Conclusion: Chronic mild stress induced from peripuberty, associated or not to escitalopram treatment, altered the testosterone levels and testicular histoarchitecture and seems to be related to the reduction in male sexual motivation., (© 2024 American Society of Andrology and European Academy of Andrology.)

Exposure to environmental heavy metals may pose a risk factor for developing preeclampsia (PE) modified through intervention. This case-control study aimed to investigate the association between serum heavy metal concentrations and PE in pregnant women and whether hormones served as mediating factors in the impact of heavy metals on PE. From October 2020 to 2022, 160 patients with PE and 160 pregnant women with normal deliveries were recruited at Dongguan Songshan Lake Central Hospital. Serum concentrations of manganese (Mn), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), lead (Pb), β-human chorionic gonadotropin (β-hCG), progesterone (P), estradiol (E2), testosterone (T), cortisol (Cort), and cortisone (Cor) were measured. Logistic, restricted cubic splines, weighted quantile sum and multivariate linear regression models were employed to account for different aspects and explore the relationships among heavy metals, hormones, and PE. Mediation model analysis was performed to assess the role of hormones in mediation. The median concentrations of Mn, E2, and Cort were lower in the PE group than in the control group. The median concentrations of Cu, Zn, β-hCG, and T were higher in the PE than in the control. Mn, E2, and Cort showed negative associations with PE, while Cu, Zn, β-hCG, and T demonstrated positive associations, as determined through logistic regression. Mn, Cu, and Zn displayed linear dose-response relationships with PE. Zn and Cu had high weights in the positive association model of mixed heavy metal exposure with PE. The mediation analysis revealed that serum E2, P, T, Cort, and Cort/Cor might be potential mediators of the association between heavy metals (Mn, Cu, and Zn) and PE., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yudong Pu reports financial support was provided by Songshan Lake Central Hospital. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: To ascertain the adverse health outcomes experienced by those using prescribed testosterone and non-prescribed anabolic-androgenic steroids presenting to general practitioner (GP) clinics., Methods: Retrospective clinical audit from nine GP clinics in major metropolitan areas across three Australian states. Data included demographic and individual characteristics (age, sexuality, body mass index, smoking status and HIV status); performance and image-enhancing drug use (type, reasons for use, patient-reported adverse effects); and blood biochemistry measurements (lipid profiles, liver function tests and red blood cell tests). Adverse health outcomes included evidence of polycythaemia, hypertension, liver abnormalities and hypercholesterolemia., Results: Three hundred men were identified as either using prescribed testosterone (66%; n = 197) or non-prescribed anabolic-androgenic steroids (AAS) (34%; n = 103). Individuals in the prescribed group were more likely to be older (p < 0.001), gay or bisexual (p < 0.001) and living with diagnosed HIV (p < 0.001) compared to individuals in the non-prescribed group. Abnormal liver function, polycythemia and gynecomastia were the top three adverse events experienced. When adjusting for age, sexuality, HIV status and smoking status, those who used non-prescribed AAS were more likely to experience any adverse event (aPR = 1.28; 95% CI 1.01-1.60; p = 0.038), hypertension (aPR = 1.86; 95% CI 1.19-2.91; p = 0.006) and liver abnormalities (aPR = 1.51; 95% CI 1.04-2.20; p = 0.030) compared to those using prescribed testosterone., Discussion and Conclusion: For GPs who have clients who may be using, or who they suspect of using, AAS, these findings highlight the importance of not only exploring a patient's history of the adverse effects they have experienced, but that measuring for these other conditions may provide a more accurate clinical picture., (© 2024 The Author(s). Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Photoperiod is a pivotal factor in affecting testicular function and spermatogenesis in seasonal-breeding animals. Mitophagy is essential for spermatogenesis, but its association with seasonal photoperiods has not been studied extensively. To explore this, we exposed male Brandt's voles (Lasiopodomys brandtii) to long-photoperiod (LP, 16 h/day) and short-photoperiod (SP, 8 h/day) conditions from their embryonic stages. Our results indicated that testis weight, volume, and relative testes weight were all significantly increased in LP compared to SP. Additionally, blood testosterone levels were markedly higher in LP than SP. Histological examination revealed that seminiferous diameter and epithelium thickness were greater in LP, with an increased abundance of germ cell types and cell numbers compared to SP. RT-qPCR analysis showed that mitophagy-promoting genes, such as Pink1, Prkn, Tomm7, Mnf2, Lc3, Optn, Gabarap, and Nbr1 were all upregulated in LP. Fluorescence in situ hybridization indicated that Pink1 expression was present in spermatogonia in SP, while in LP, Pink1 expression extended to almost all germ cell types with significantly higher mean optical density. Prkn expression was found in all germ cell types in both LP and SP, with a significantly higher mean optical density of 10-week-old LP males. Transmission electron microscopy showed normal mitochondrial morphology with clear membranes in SP, while the LP group had reduced cristae in mitochondria and damaged mitochondria undergoing autophagy. This study suggests that mitophagy may be involved in the photoperiodic spermatogenesis in Brandt's voles, providing insights into the role of photoperiod in seasonal reproduction in wild animals., (© 2024 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Increasing fertility rates have become one of the factors that concern all people in the world. Therefore, the study aims to use two mutated strains of probiotics enriched with selenium (PSe40/60/1 and BSe50/20/1) to improve fertility. Thirty Swiss albino male mice were divided into three groups; control, LP + S was given Lactobacillus plantarum PSe40/60/1 plus selenium, and BL + S was given Bifidobacterium longum BSe50/20/1 plus selenium. Free testosterone, LH, and FSH were measured in serum by biochemical analysis. Testicular tissues were examined by histopathological analysis. The count and motility of sperm, and sperm abnormalities were determined by microscopic examination. The method of qRT-PCR was used to detect gene expression of Tspyl1, Hsd3b6, and Star genes. The biochemical results showed that serum content of free testosterone (FT) hormone had significantly increase in the BL + S and LP + S groups compared with control. Levels of LH and FSH hormones were the highest in the BL + S group. The treated groups showed all developmental stages of spermatogenesis, including spermatogenesis, spermatocytes, and seminiferous tubule spermatids, as well as intact Sertoli cells and Leydig cells without changes. When compared to the control group, sperm count and motility increased in the BL + S group, while sperm abnormalities decreased. The expression of Tspyl1 gene in testicular tissues decreased in the LP + S and BL + S groups, while the expression of Star and Hsd3b6 genes was higher in the BL + S group and lower in the LP + S group compared with the control group. Therefore, Bifidobacterium longum BSe50/20/1 enriched with selenium could be useful in enhancing male fertility., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objective: The longitudinal efficacy and clinical utility of Testosterone Therapy (TTh) in ameliorating functional hypogonadism (FH) remain contentious, with long-term data being scarce. To address this lacuna, a comprehensive long-term registry study, stratifying patients across a spectrum of hypogonadal etiologies, offers a robust investigative paradigm., Materials and Methods: This 9-year registry, encompassing 650 patients (equivalent to 4,362 cumulative years of treatment), included 188 patients diagnosed with FH (mean age 42.3 ± 11.3 years) and 462 individuals with classical hypogonadism (CH). The cohort segregated into 266 men with primary hypogonadism (PH, mean age 34.0 ± 11.7 years) and 196 with secondary hypogonadism (SH, mean age 31.9 ± 12.0 years). Uniform treatment across the cohort involved intramuscular administration of testosterone undecanoate (1,000 mg). A comparative analysis was conducted focusing on anthropometric, metabolic, and safety parameters., Results: Serum testosterone levels increased from 6.6 ± 2.4 to 19.3 ± 2.9 nmol/L (p < 0.001). TTh was linked with weight reduction and decreased waist circumference (WC) in both CH and FH cohorts (both p < 0.001). Cox regression and Kaplan-Meier analyses delineated disparities: men with FH demonstrated a higher propensity for losing > 10% body weight and > 5% WC compared to CH (hazard ratio [HR] 1.3 [1.1-1.4], p = 0.008 and HR 1.4 [1.3-1.5], p = 0.001). Increases in hematocrit > 50% were uniform across groups, albeit amelioration of anemia was more pronounced in FH versus CH (p = 0.002). Increments of prostate-specific antigen (PSA) levels were more likely to occur in FH (HR 1.3 [1.1-1.6], p = 0.003). FH patients exhibited pronounced improvements in metabolic parameters and in aging male symptom score (AMS) and IIEF-EF questionnaire scores. These effects were markedly modulated by age and initial weight. Subgroup analysis of age-matched obese patients revealed an accentuated impact of TTh in CH compared to FH., Discussion and Conclusion: The therapeutic outcomes of TTh across distinct hypogonadal populations demonstrate heterogeneous responses, significantly influenced by diagnostic categorization, age, and baseline risk factor profiles., (© 2024 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)