Normal Testosterone Levels Research Articles

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

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

7291 From Vaginal Bleeding to Genetic Complexity: McCune Albright Syndrome in a Toddler; Emphasizing Atypical Manifestations, Diagnostic Challenges, and Comprehensive Management

Abstract Disclosure: A.G. Martinez Sanchez: None. N. Fernandez: None. C.L. Bustamante Escobar: None. Background: McCune Albright Syndrome (MAS) is a rare genetic disorder characterized by a triad of peripheral precocious puberty, irregular café-au-lait spots, and bone fibrous dysplasia. It is often caused by post-zygotic somatic mutations in the GNAS1 gene. We present a case of a patient initially presenting with precocious puberty, whose diagnostic journey revealed MAS with atypical manifestations. Presentation: A 23-month-old girl was brought to the emergency department after her mother noticed vaginal bleeding during a diaper change; denied any trauma, fever, rash, or dysuria. Patient developed accelerated growth about six months earlier, followed by pubic hair three months prior and bilateral thelarche two weeks before presentation. The patient had no exposure to endocrine disruptors. The physical examination revealed a well-developed child, in the 92nd percentile for weight and 97th for height. Additionally, breast buds, fine hair on the labia, and minimal blood at the vaginal introitus, with no apparent signs of trauma. Initial laboratory findings showed prepubertal LH and FSH levels, elevated estradiol 120 pg/ml (prepubertal range <10) and advanced bone age (4.2 years). Normal levels of testosterone, 17-hydroxyprogesterone, and DHEA sulfate. Pelvic ultrasound demonstrated an enlarged uterus (5.6 x 1.8 x 2.4 cm) and a large cystic lesion (4.4 cm) on the right ovary. During a follow-up at the endocrinology department one week later, a meticulous examination identified an irregular café-au-lait spot measuring about 2cm over the occipital right side of her scalp. Further tests, including GnRH stimulation test, tumor markers (LDH, b-HCG, CEA, and Ca19-9), brain MRI and bone scan, yielded normal findings. Given the presentation consistent with Peripheral precocious puberty, Letrozole was initiated at 1.25 mg daily. Three months later, her growth velocity remained accelerated. However, there was a decrease in both breast tissue and uterus size (4.2 x 1.2 x 1.7 cm), and the ovarian cyst was resolved. Genetic testing in blood indicated no mutations. To conduct a thorough assessment, the insulin-like growth factor (IGF-1) level was measured and found to be 200 ng/mL (normal range 56-144 ng/mL). Unfortunately, obtaining prolactin levels was challenging due to difficult intravenous (IV) access. Conclusion: This case reveals the complexity of MAS in precocious puberty, emphasizing atypical features that add complexity to the diagnosis. Identifying an irregular café-au-lait spot served as a diagnostic indicator, revealing the diverse clinical presentations. The challenges of relying solely on genetic testing for diagnosis are evident due to the mosaic nature and tissue-specific distribution of the mutation, as highlighted by the absence of mutations in this patient. Long-term management requires ongoing monitoring and a multidisciplinary approach for optimal patient outcomes. Presentation: 6/1/2024

7778 Factors Predicting Recovery of Hypogonadism in Men with Prolactinoma Treated with Dopamine Agonists

Abstract Disclosure: S. Constantinescu: None. O. Alexopoulou: None. D.M. Maiter: None. Introduction: Recovery of hypogonadism is an important objective of dopamine agonist (DA) treatment in men with prolactinoma. However, the extent, timeline, and predictive factors of gonadotrope axis recovery are still unclear. Methods: We report data from a large cohort of 89 men with prolactinoma, looking at the evolution of testosterone levels after 6 and 12 months of treatment with DA. We excluded patients with peripheral hypogonadism, surgical treatment performed less than 12 months after onset of DA treatment, and patients with small tumors (≤ 5 mm and prolactin ≤ 50 µg/l) who did not achieve tumor shrinkage during treatment. We defined low testosterone as a morning value < 10 nmol/l. Patients who had started testosterone supplementation were considered as having persistent hypogonadism. Results: Among the 89 men (mean age ± SD: 44 ± 14 years; 65/89 with a macroprolactinoma), 14 (16%) had normal initial testosterone levels (NT) and 75 (84%) had low testosterone at diagnosis (LT). Compared to LT, NT patients had significantly lower PRL (median 53 µg/l versus 490 µg/l, p=0.009) and smaller tumors (median 6.5 mm versus 21.2 mm, p=0.013). In the NT group, after 6 (n=11) and 12 months (n=10), testosterone rose from a median of 13.4 to 16.6 (p=0.266) and 17.9 nmol/l (p=0.012), respectively. In LT patients, after 6 (n=56) and 12 months (n=42), testosterone rose significantly from a median of 5.8 to 10.7 (p<0.001) and 12.5 nmol/l (p<0.001).In the LT group, 45% (32/71) had recovered eugonadism at 6 months and 57% (40/70) at 12 months. These proportions rose to 61% (22/36) and 67% (n=26/39) at 6 and 12 months when prolactin concentrations were normalized. Factors associated with persistent hypogonadism after one year were chiasmal compression at diagnosis (p=0.05), cavernous sinus invasion (p=0.042), cystic tumoral component (p=0.038), a greater tumoral diameter (mean 25 mm vs 15 mm, p<0.01), lower testosterone concentrations at diagnosis (mean 3.6 nmol/l vs 6.8 nmol/l, p<0.001) and at 6 months (mean 6.0 nmol/l vs 13.0 nmol/l, p<0.03), and higher prolactin levels at one year (median 17.15 µg/l vs 8.4 µg/l, p=0.064). Testosterone < 6.7 nmol/l at 6 months predicted the long-term persistence of hypogonadism with 72% sensitivity and 92% specificity. Conclusion: The sensitivity of the gonadotrope axis to high prolactin levels is highly variable in men with prolactinoma and 16% of them retain normal testosterone concentrations. However, this finding does not exclude partial inhibition of the gonadotrope axis that will improve with DA treatment. In patients with low testosterone levels, the recovery rate of hypogonadism is 45% at 6 months and 57% at 12 months, increasing to 67% if prolactin is normalized. Testosterone supplementation could be started early in patients with large, invasive, cystic and/or compressive tumors, with a testosterone concentration lower than 6.7 nmol/L after 6 months of treatment. Presentation: 6/3/2024

Association of Obesity, Inflammation, and Hypogonadism: A Cross-Sectional Study in Males Under 60 Years of Age.

Background Obesity is a significant global health issue closely associated with numerous metabolic disorders, including hypogonadism. Male obesity-related secondary hypogonadism (MOSH) is characterized by reduced testosterone levels, leading to various health complications. The bidirectional relationship between obesity and hypogonadism creates a vicious cycle, with obesity exacerbating hypogonadism and hypogonadism contributing to further obesity. Chronic inflammation, indicated by elevated C-reactive protein (CRP) levels, plays a crucial role in this interplay. The primary aim of this study is to investigate the role of obesity as an isolated factor contributing to hypogonadism. Materials and methods This observational, cross-sectional study was conducted from September 2022 to July 2024 at Dr. D.Y. Patil Medical College and Hospitals in Pune, India. A total of 80 male participants, all under 60 years of age with a BMI greater than 25 kg/m², were included in the study and classified as overweight or obese according to WHO criteria. Exclusion criteria included diabetes, age over 60 years, a BMI less than 25 kg/m², any testicular pathologies, and significant risk factors. After obtaining informed consent, participants underwent thorough clinical examinations and laboratory investigations. Patients who met the criteria were included in the study, with measurements taken for central obesity (waist circumference (WC) and waist-hip ratio (WHR)) and BMI. CRP levels were measured as an inflammatory marker indicative of chronic disease states. Statistical analyses, including correlation and regression analyses, were performed using SPSS software, version 22 (IBM SPSS Statistics, Version 22). Statistical significance was set at p < 0.05. Results The majority of participants fell within the 50-59 age group, with a mean age of 45.95 years. The study found strong positive correlations between BMI (r = 0.76), WC (r = 0.81), and WHR (r = 0.78) with CRP levels, indicating that central obesity is closely linked to systemic inflammation. Additionally, there were significant negative correlations between free testosterone and these anthropometric measures: BMI (r = -0.65), WC (r = -0.70), and WHR (r = -0.67), suggesting that increased adiposity is associated with lower testosterone levels. The strongest negative correlation observed was between CRP and free testosterone (r = -0.82), highlighting the impact of chronic inflammation on hypogonadism. Regression analysis further confirmed that CRP was a significant predictor of free testosterone levels (R-squared = 0.674), emphasizing the crucial role of inflammation in the pathophysiology of hypogonadism in obese individuals. Conclusion This study underscores the intricate relationship between obesity, chronic inflammation, and hypogonadism in men. The bidirectional nature of this relationship suggests that managing obesity and reducing systemic inflammation could potentially alleviate hypogonadism. Interventions focusing on weight loss, improving insulin sensitivity, and anti-inflammatory treatments may thus hold promise in restoring normal testosterone levels in obese men. Understanding and addressing the impact of obesity on male reproductive health is crucial, given the rising prevalence of obesity worldwide. Future research should explore therapeutic avenues and further elucidate the underlying mechanisms of this complex interplay.

Effect of Combined Low Dose Human Gonadotropic Hormone, Follicle Stimulating Hormone, and Testosterone Therapy (LFT Regimen) Versus Conventional High Dose Human Gonadotropic Hormone and Follicle Stimulating Hormone on Spermatogenesis and Biomarkers in Men With Hypogonadotropic Hypogonadism

ObjectiveIn male Congenital hypogonadotropic hypogonadism(CHH), it was observed that lower dose human gonadotropic hormone(hCG) can maintain normal intratesticular testosterone(ITT) levels. We propose this study to compare the Low-Dose hCG, follicle stimulating hormone(FSH), and Testosterone(T) [LFT Regimen] to conventional treatment to induce virilization and fertility. DesignThis open-label randomized pilot study was conducted from June 2020 to December 2021. Subjects and outcome measuresCHH were randomly assigned to either the LFT regimen (Group A)-low-dose hCG (500U thrice per week), FSH(150U thrice per week) and T(100mg biweekly) or conventional therapy(GroupB) with high hCG dose(2000U thrice per week) and the same FSH dose. The hCG dosage was titrated to reduce Anti-mullerian hormone(AMH) by 50% and normalization of plasma T in groups A and B, respectively. The primary objective was to compare the percentage of individuals who achieved spermatogenesis between the two groups. ResultsOut of 30 patients, 23(76·7%) subjects achieved spermatogenesis, and the median time was 12(9-14·9)months. There was no difference in achieving spermatogenesis between the two groups (64·3%vs87·5%,p=0·204), and even the median time for spermatogenesis was similar (15monthsvs12months,p=0·248). Both groups had non-significant median plasma AMH at spermatogenesis,[6·6ng/ml(3·3-9·76) vs 4·41ng/ml(2·3-6·47),p=0·298]. Similarly, the median plasma Inhibin B at spermatogenesis between groups were comparable[152·4pg/ml(101·7-198·0)vs149·1pg/ml(128·7-237·3),p=0·488]. ConclusionsA reasonable approach to induce fertility in male CHH is to initiate combination therapy using FSH, low-dose hCG targeting AMH <6·9 ng/ml, along with T to achieve normal range. Monitoring AMH could serve as a proxy indicator of spermatogenesis.

Characteristics of depression treatment in men with testosterone deficiency

BACKGROUND: Treatment of depression in men with testosterone deficiency is particularly challenging because of the overlap between the symptoms of depression itself and those associated with testosterone deficiency, which requires the development of additional diagnostic and therapeutic approaches. AIM: To enhance the effectiveness of comprehensive treatment of depression in men with testosterone deficiency. MATERIALS AND METHODS: The study involved 140 male participants (aged 18–65 years) diagnosed with depressive episodes and recurrent depressive disorder according to the International Classification of Diseases, 10th revision. Patients were divided into the main group (testosterone levels below 12.1 nmol/l) and the control group (normal testosterone levels). The main group (n=90) was further divided into three therapeutic subgroups of 30 patients each: receiving sertraline monotherapy, testosterone monotherapy, and combined sertraline and testosterone treatment. The control group included men with depression and normal testosterone levels (n=50), who received sertraline only. RESULTS: Depression in men in the context of testosterone deficiency has distinct clinical features, both phenomenologically and syndromally. The severity of the depressive syndrome in men with testosterone deficiency is lower (17.0 [16.0; 18.75] points on the HDRS scale) than in patients with normal testosterone levels (19.0 [18.0; 22.0] points on the HDRS scale), and the depressive episode tends to occur later in life (47.0 [42.0; 55.0] years) compared to those with normal levels of testosterone (29.5 [24.25; 40.0] years) and is less likely to be recurrent than in those with normal testosterone levels (29.5 [24.25; 40.0] years). The study of the efficacy and safety of depression therapy in the context of testosterone deficiency shows that a combined approach to the treatment of depression in men with testosterone deficiency has both advantages (considering the specifics of patients by normalizing testosterone levels and erectile function) and disadvantages (relatively higher risk of adverse events) compared to sertraline monotherapy. CONCLUSION: The identified characteristics of the course and treatment of depression in the context of reduced testosterone levels allowed for the development of a more effective therapeutic and diagnostic algorithm.

Increase in Testosterone Levels and Improvement of Clinical Symptoms in Eugonadic men With a Prolactin-secreting Adenoma.

Testosterone concentrations, albeit rarely, may be in the normal range (>3.0 ng/mL) in men with a prolactin-secreting pituitary adenoma (PSPA-nt). The evolution of total, bioavailable testosterone, gonadotropin levels, and that of graded symptoms of testosterone deficiency (TD) are uncertain in these patients. Retrospective case-control longitudinal study at a tertiary referral center. From 287 men, we selected 25 PSPA-nt men undergoing prolactin normalization (<20.0 ng/mL) during the follow-up. Graded symptoms of TD were investigated by structured interviews. Biochemical changes and TD symptoms were compared to those of a matched cohort of 61 men with pituitary neoplasms and normal testosterone levels (PA-nt). Baseline testosterone levels were similar between PSPA-nt and PA-nt subjects. The prevalence of specific and suggestive symptoms of TD was higher in PSPA-nt (20% and 68%) than in PAnt (3.3 and 29.5%; P = .02 and P = .0015, respectively). At the follow-up, total and bioavailable testosterone levels increased in PSPA-nt but not in PA-nt patients (Δ change: 1.28 ± 2.1 vs0.03 ± 1.5 ng/mL, + 0.33 ± 0.55 vs-0.26 ± 0.60 ng/mL; P = .0028 and P = .0088, respectively). LH and FSH levels also increased in PSPA-nt men (P < .05). Specific and suggestive, but not nonspecific symptoms of TD, improved only in PSPA-nt men (P < .05 for both). Baseline testosterone and LH were the strongest predictors of testosterone improvement in PSPA-nt patients. Despite having normal testosterone levels at baseline, patients with PSPA-nt experience a relief of TD symptoms and an improvement of their pituitary-gonadal axis function following prolactin normalization, especially when baseline TT and LH levels are in the low-normal range.

Reproductive Health Assessment and Reports of Fertility Counseling in Pediatric and Adolescent Patients with Sickle Cell Disease After Hematopoietic Cell Transplantation

Conditioning regimens for hematopoietic cell transplant (HCT) in patients with sickle cell disease (SCD) place patients at risk for reproductive health issues. The purpose of this study was to assess reproductive health and reports of fertility counseling in patients with SCD who received a transplant. This was a secondary analysis of gonadal hormone production, future infertility risk assessment, and parent-proxy/patient reports of fertility counseling in SCD transplant recipients who are currently pubertal and were enrolled in the Atlanta sites of the Sickle Cell Transplant Evaluation of Long-term and Late Effects Registry (STELLAR) between May 2017 and October 2023. Clinical information was abstracted from medical records and reproductive health survey data from the STELLAR database. Descriptive statistics were reported as median (interquartile range [IQR]) or percentages. There were 20 females and 12 males in the study population. Females were median (IQR) 19.6 (9.4) years old and males 20.8 (11.4) years old at the time of the study. Transplants most commonly occurred in the decade 2010 to 2019 at 10.7 (4.8) years old for females and 11.1 (4.1) years old for males. Most participants received bone marrow stem cells (95.0% females, 100.0% males) from matched sibling donors (90.0% females, 100.0% males). Participants received one of seven HCT conditioning regimens with cyclophosphamide equivalent doses ranging from 3388 to 9706 mg/m2. The majority of females (90.0%) had diminished ovarian reserve with low anti-Mullerian hormone levels, and 61.1% had premature ovarian insufficiency with two follicle-stimulating hormone levels (FSH) ≥40 mIU/mL post-HCT. All males had normal testosterone levels, but 63.6% had elevated FSH levels suggestive of impaired spermatogenesis post-HCT. Parent proxies (for patients <18 years old) and patients ≥18 years old completed surveys 9.0 years (5.2) and 7.9 years (9.3) since HCT in females and males respectively. Twenty-five percent of parent proxies and 45% of patients reported that they had not been informed by a healthcare provider of the risk of infertility post-transplant. There are high rates of gonadal dysfunction post-HCT, but many parent proxies and patients do not recall being told of the risk for future infertility. More effective methods of education are warranted to ensure SCD patients and their families clearly understand the risk for reproductive health issues post-HCT.

Erectile Dysfunction in Adolescents and Young Adults.

The goal of this paper is to provide a summary of the recent research, evaluation, work-up, and treatment recommendations regarding erectile dysfunction in adolescents and young adults to better equip pediatric urologists to manage patients with this condition. The latest research regarding erectile dysfunction in this population includes organic and psychogenic etiologies, correlations between the COVID-19 pandemic, and online pornography consumption. In our large pediatric urology practice, we found an 31x increase of adolescent males presenting with erectile dysfunction since 2014. The majority of cases are attributed to a psychogenic etiology such as anxiety or depression. It is likely that with stress from anxiety and depression, cortisol levels rise, increasing vascular resistance and leading erectile dysfunction in this population. Most patients want to be reassured of normal testosterone levels, offered cognitive behavioral therapy, and be rehabilitated with tadalafil starting at 5mg p.o. daily until tapered.

Association between sex hormones and erectile dysfunction in men without hypoandrogenism

In addition to testosterone, various endocrine hormones, such as dehydroepiandrosterone sulfate (DHEA-S) and estradiol, may be involved in erectile function. However, the role of these sex hormones in the erectile function of men without hypoandrogenism remains unclear. This cross-sectional study included 398 community-dwelling men without hypoandrogenism. The participants were categorized into the non-ED and ED groups. Multivariable logistic regression analyses were performed to investigate the relationship between ED and serum sex hormone levels, including total testosterone, DHEA-S, estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin. Among the 398 men, 66 (17%) and 332 (83%) were categorized into the non-ED and ED groups, respectively. In the multivariable analyses, serum DHEA-S and estradiol levels were significantly associated with ED (odds ratio [OR]: 0.996, P = 0.030; OR: 1.082, P = 0.002; respectively), whereas serum total testosterone, LH, FSH, and prolactin levels did not demonstrate significant association. After adjusting for age, none of neutrophil-to-lymphocyte ratio, serum plasminogen activator inhibitor-1 levels, and skin advanced glycation end-products levels demonstrated significant correlation with serum DHEA-S and estradiol levels. In conclusion, lower testosterone levels did not affect ED in men with normal testosterone levels, whereas serum DHEA-S and estradiol levels were significantly associated with ED.

Cognitive impairment is associated with female sex, low level of education, lack of spousal relationship, and serum testosterone in type 2 diabetes

Abstract Background: Relationship between cognitive impairment, serum testosterone, and body mass index in type 2 diabetes (T2D) is not fully understood. Objectives: To compare cognition between T2D patients and healthy controls. To determine relationship of mild cognitive impairment (MCI) with serum total testosterone and sociodemographic factors. Materials and Methods: The study was a cross-sectional case-control study. About 17 male and female T2D patients and healthy controls were randomly selected. Montreal cognitive assessment-basic (MoCA-B) was used to assess cognition; anthropometric indices were measured using standard protocols, while total testosterone was assayed from serum using competitive ELISA kits. Results: The mean age of the T2D patients and healthy controls was 51.62 and 66.76 years, respectively. About 82.35% of the T2D patients had MCI compared to 58.82% of the healthy controls. MCI was associated with female sex (P = 0.033), lack of spousal relationship (P = 0.016), low level of education (P = 0.014), and normal or high level of total testosterone (P = 0.010). Conclusion: Proportion of MCI in T2D patients is high and is associated with female sex, lack of spousal relationship, low level of education, and normal or high testosterone level.

Anemia and testosterone deficiency risk: insights from NHANES data analysis and a Mendelian randomization analysis

Background Previous research has shown that testosterone deficiency (TD) increases the risk of anemia, but it is unclear whether anemia affects testosterone levels. This study investigated the influence of anemia on testosterone levels. Methods Utilizing data from six NHANES cycles, including demographic, testosterone levels, and hemoglobin concentrations, we employed multivariable-adjusted logistic regression to investigate the relationship between anemia and testosterone levels. Moreover, a two-sample Mendelian randomization (MR) study employing genome-wide association study (GWAS) data examined the causal relationship. Kaplan–Meier survival estimation was used to compared the overall survival (OS) of anemic and nonanemic patients with low testosterone and normal testosterone levels. Results The inclusion of 21,786 participants (2318 with anemia and19,468 without anemia) revealed that nonanemic patients exhibited higher testosterone levels than did anemic patients (β = 22.616, 95% CI: 3.873–41.359, p = 0.01807). MR analysis confirmed anemia as a cause of TD (OR = 1.045, 95% CI: 1.020–1.071, p < 0.001). Anemic males with low testosterone had reduced OS compared to those with normal levels (p < 0.001). Conclusions Anemia emerged as a potential risk factor for TD, highlighting a bidirectional relationship between these conditions. Additional prospective investigations are essential for the validation and reinforcement of our findings.

Response of Male Reproductive System Against Ionizing Radiation and Available Radio-protective Agents: Cellular and Molecular Insight.

The reproductive organ, housing spermatogonial stem cells (SSCs), undergoes ongoing division impacted by the irradiation dosage and exposure duration. Within the male reproductive organ, germ stem cells (spermatogonia) and somatic cells (Sertoli and Leydig cells) are present. Lower doses of ionizing (>4-6 Gy) and non-ionizing radiation (radiofrequency and microwave range 900 MHz - 2.45 GHz) may cause sperm-related issues, while higher doses (15 Gy) may affect Leydig cells and testosterone production. Response to radiation varies with age and pubescence. Spermatogonial stem cells, crucial for regenerating the spermatogenic lineage, express molecular markers like Estrogen receptor, FSH (Follicular Stimulating Hormone) receptor, TLR-4 (Toll-like Receptor-4), TLR-5 (Toll-like Receptor-5), FGF2 (Fibroblast Growth Factor-2), KIT (Receptor Tyrosine Kinase), AT-1 (Angiotensin II Type-1 Receptor), LXRs-γ (Liver X Receptor-γ), TNF-β (Tumor Necrosis Factor-β), and PCNA (Proliferating Cell Nuclear Antigen), influencing stem cell activity in testes. This study aimed to review the various available radioprotective agents and their efficacy in targeting the male reproductive system from the available literature. Various radioprotective herbal/synthetic/microbial/metallic extracts/formulations/ drugs [Septilin, Silymarin, Organic Turmeric, Oestrogen, Melatonin, Febuxostat, SQGD (Semiquinone glucoside derivative), Rapamycin, Entolimod, Zinc, Selenium, etc.] have been investigated up to exposure, but owing to effectiveness issues, they are unable to fulfil the aim to the fullest of restoring male fertility and normal testosterone levels during such eventuality. Further study is needed to optimize these tactics and fill knowledge gaps. Also, the effective components of herbal, synthetic drugs, etc., should be isolated and tested up to clinical levels, paving the way for successful radioprotection and radiomitigation strategies in the male reproductive system.

Beneficial effects of oral antioxidant supplementation on semen quality parameters, reproductive hormones, and sperm DNA integrity in men with idiopathic oligoasthenoteratozoospermia.

Recently, oral antioxidants in combined forms have been used to treat men with idiopathic infertility. This study aimed to evaluate the effects of treatment with vitamin C, vitamin E, selenium, zinc, arginine, L-carnitine, and coenzyme Q10 on sperm quality parameters, DNA integrity, reproductive hormones, and pregnancy rates in men with infertility and idiopathic oligoasthenoteratozoospermia (OAT). A prospective study was conducted on 420 men with infertility and idiopathic OAT who took an oral supplement of antioxidant SP-Power tablets twice daily for 6 months. Semen quality, reproductive hormones, and the DNA fragmentation index (DFI) were evaluated at baseline and at 3 and 6 months after supplementation, using the World Health Organization 2021 guidelines. No significant difference was observed in volume or the percentage of typical morphology during treatment. A significant improvement in sperm concentration was observed after supplementation (8.67±1.41, 12.17±1.91, and 19.01±0.86 at baseline, 3, and 6 months respectively, p<0.01). The total motility, progressive motility, and total motile sperm count also increased significantly (p<0.01), whereas the DFI decreased after 6 months. There was an increase in normal FSH levels and testosterone levels after 6 months of supplementation of antioxidant SP-Power but these differences were not statistically significant (p=not significant and p=0.06, respectively). Supplementation with SP-Power tablets improved sperm quality parameters, sperm DFI, some reproductive hormones, and pregnancy rates in men with infertility and idiopathic OAT, which could be attributed to the supplement's synergistic antioxidant action. Further studies are needed to determine the effects of supplementation on oxidative stress markers.

(135) Systematic Review on the Association of Peyronie’s Disease Development and Severity to Testosterone Level: Do we Have Enough Data?

Abstract Introduction Exact pathophysiology of Peyronie's disease (PD) are still poorly known with the combination of tissue ischemia to predefined hereditary variables. Due to the anti-inflammatory factors and ability to regulate collagen metabolism and wound healing, androgens have been the subject of several clinical research studying their role in the onset and severity of PD. Objective The aim of this study is to investigate the relationship between testosterone level to the development and severity of PD. Methods A systematic search on PubMed, Scopus, and Embase was conducted on April 4th, 2023 using the keywords of testosterone, hypogonadism, and Peyronie’s disease. All studies that compare the testosterone levels of the patients with or without PD or evaluate the association of PD severity were considered. Each included studies are evaluated for its quality and risk of bias. Results Eleven studies comprising 1.106 patients with PD and 507 control were included. Three of the four studies examining the association of testosterone level to PD development found that testosterone/DHEA-s levels were lower in the PD group compared to the control. In addition, four of seven studies found that the severity or degree of penile curvature among patients with PD has lower testosterone levels. On contrary, only two of six studies support the correlation of testosterone level to penile plaque diameter. In two studies that confirmed the correlation of penile plaque and degree of curvature to testosterone levels, they also found that PD patients with normal or higher testosterone levels responds better to medical treatment. Conclusions Contemporary literature on the correlation between PD and testosterone levels shows conflicting results. Although around half of the studies support its possible correlation to penile curvature severity, no definitive conclusion can be made. Further research is warranted to seek the impact of low testosterone level to PD and whether it needs to be routinely evaluated in clinical practice. Disclosure No.

Serum total testosterone is associated with phosphate and calcium excretion in response to oral phosphate loading in healthy middle-aged males.

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 500mg 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.

Adult-type granulosa cell tumor associated with elevated luteinizing hormone: Two rare case reports.

Adult-type granulosa cell tumors (AGCTs), which account for 2% to 5% of all malignant ovarian tumors, are rare sex cord-stromal tumors that usually secrete excess estrogens, but they can also secrete androgens. We report 2 patients of childbearing age with AGCT who presented with the complaint of abnormal menstruation and elevated luteinizing hormone (LH), and mildly elevated testosterone. The ovarian tumors had hormonal activity. The 2 patients underwent laparoscopic left adnexectomy. The second patient underwent 4 cycles of chemotherapy with paclitaxel and carboplatin as adjuvant treatments. Their postoperative pathology confirmed AGCTs. Also, their menstrual cycle returned to normal, with normal serum LH and testosterone levels. There was no sign of recurrence. The cases suggest that elevated serum LH levels may be a sign of unknown tumors in cases of oligomenorrhea or secondary amenorrhea. It is useful to evaluate the serum levels of inhibin B and anti-Müllerian hormone to improve the early recognition of ovarian granulosa cell tumors.

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

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

Insights From Liquid Chromatography-Mass Spectrometry-Measured Androgens in Indian Women With Polycystic Ovary Syndrome.

Hyperandrogenemia is the defining feature of polycystic ovary syndrome (PCOS). Increasingly androgens are being advocated to be measured through liquid chromatography-mass spectrometry (LC-MS/MS). The role of LC-MS/MS over immunoassay in diagnosis of PCOS has been debated over a long time. We analyzed the role of androgens as measured by LC-MS/MS in diagnosing women with PCOS. We performed a prospective case-control study involving 59 women with PCOS compared with 30 age- and BMI-matched controls. In PCOS phenotypes A-C (hyperandrogenic by definition), 19/47 (40%) had normal testosterone (T) levels but 14/19 (75%) had either elevated androstenedione (A4) or dehydroepiandrosterone. A4 had the highest area under curve (0.89) for diagnosing PCOS followed by T (0.81). Even in the PCOS-D phenotype (sonologic polycystic ovaries + oligomenorrhoea), A4 was significantly higher as compared to controls though still in normal range. A4 had arole in diagnosing hyperandrogenism in women with PCOS. Further studies clarifying the role of androgen profiles in diagnosing PCOS and its cost-effectiveness may be required in the future.

PREVALENCE AND EFFECTS OF PROGRESSIVE OSTEOARTHRITIS ON SEX STEROIDS IN MALE AND FEMALE PATIENTS OF DISTRICT BUNER, KPK PAKISTAN

Osteoarthritis is a major cause of disability in older people; pain is considered one of the most important signs of osteoarthritis, which normally affects the weight-bearing joint, especially the knee joint. The objective of the present study was to find out the prevalence and effects of progressive Osteoarthritis (OA) on sex steroids in male patients of district Buner KP, Pakistan. Data was collected from 294 OA patients (Male, 46.18%; Female, 54.76%) at different hospitals through questionnaires, face-to-face interviews and blood sampling in district Buner. Results showed that the 50 to 60-year age group was mostly affected by OA (29.81%). In the case of females, OA was common in the plain areas, while male patients were in hilly areas. Among 294 patients, housewives (23.46%) and agriculture (18.7%) are more affected by Osteoarthritis. Blood samples were collected from 18 male patients of different age groups and analysed through the ELISA (enzyme-linked immunosorbent Assay) Test. The results obtained from ELISA showed that most of the OA patients have normal testosterone levels, but the two age groups, i.e., 50 to 60 and 60 to 70, have abnormal results of 0.251 ng/ml and 1.89 ng/ml. After analysis of all testosterone test results at different age groups, analysis of variance (ONE WAY ANOVA) results show that SS, MS and F values were 36.30, 7.26 and 9.3, respectively. We concluded that people over 40 are more likely to get OA. Osteoarthritis is more common in women than males, and it is more common in overweight people. Mountainous locations have a higher incidence of males with OA than females. Additionally, there are more females than males in plain terrain. According to our findings, bilateral OA is more typical than unilateral OA. Our research indicates a tenuous connection between OA and male patients' testosterone levels.