Increased Serum Testosterone Levels Research Articles

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

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

The association between testosterone, estradiol, estrogen sulfotransferase and idiopathic pulmonary fibrosis: a bidirectional mendelian randomization study

BackgroundThe causal relationships between testosterone, estradiol, estrogen sulfotransferase, and idiopathic pulmonary fibrosis (IPF) are not well understood. This study employs a bidirectional two-sample Mendelian Randomization (MR) approach to explore these associations.MethodsAll genetic data utilized in our study were obtained from the IEU Open GWAS project. For the MR analysis, we employed the inverse variance weighted (IVW), MR-Egger, and weighted median methods to assess the causal relationships. We also conducted a multivariate MR (MVMR) analysis, with adjustments made for smoking. To ensure the robustness of our findings, sensitivity analyses were conducted using Cochran’s Q test, MR-Egger regression, the MR-PRESSO global test, and the leave-one-out method.ResultsGenetically predicted increases in serum testosterone levels by one standard deviation were associated with a 58.7% decrease in the risk of developing IPF (OR = 0.413, PIVW=0.029, 95% CI = 0.187 ∼ 0.912), while an increase in serum estrogen sulfotransferase by one standard deviation was associated with a 32.4% increase in risk (OR = 1.324, PIVW=0.006, 95% CI = 1.083 ∼ 1.618). No causal relationship was found between estradiol (OR = 1.094, PIVW=0.735, 95% CI = 0.650 ∼ 1.841) and the risk of IPF. Reverse MR analysis did not reveal any causal relationship between IPF and testosterone (OR = 1.001, PIVW=0.51, 95% CI = 0.998 ∼ 1.004), estradiol (OR = 1.001, PIVW=0.958, 95% CI = 0.982 ∼ 1.019), or estrogen sulfotransferase (OR = 0.975, PIVW=0.251, 95% CI = 0.933 ∼ 1.018). The MVMR analysis demonstrated that the association between testosterone (OR = 0.442, P = 0.037, 95% CI = 0.205 ∼ 0.953) and estrogen sulfotransferase (OR = 1.314, P = 0.001, 95% CI = 1.118 ∼ 1.545) and the risk of IPF persisted even after adjusting for smoking.ConclusionsIncreased serum levels of testosterone are associated with a reduced risk of IPF, while increased levels of serum estrogen sulfotransferase are associated with an increased risk. No causal relationship was found between estradiol and the development of IPF. No causal relationship was identified between IPF and testosterone, estradiol, or estrogen sulfotransferase.

Transcriptome and proteomic analysis reveal the protective mechanism of acupuncture on reproductive function in mice with asthenospermia

Acupuncture is an integral component of complementary and alternative medicine that has been reported to enhance sperm motility, improve semen quality, and consequently augment male fertility. However, the precise mechanisms of action and the underlying molecular pathways remain unclear. In the present study, we aimed to elucidate the potential mechanisms through which acupuncture improves reproductive function in a mouse model of cyclophosphamide-induced asthenozoospermia. We collected sperm from the epididymis for semen analysis, collected serum to determine gonadotropin and oxidative stress marker levels, conducted histological examination of testicular tissue using hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and observed mitochondrial morphology using transmission electron microscopy (TEM). We also assessed oxidative stress levels and total iron content in testicular tissue and validated the proteomic and transcriptomic analysis results of testicular tissue using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR), protein imprinting analysis, and immunohistochemistry (IHC). Our results indicate that acupuncture enhances sperm quality in asthenozoospermic mice; increases serum testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels; and attenuates oxidative damage, iron accumulation, and mitochondrial injury in mouse testicular tissues. Through protein and transcriptomic analyses, we identified 21 key genes, of which cytochrome b-245 heavy chain (CYBB), glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 1 (ACSL1), and ferritin mitochondria (FTMT) were closely associated with ferroptosis. RT-qPCR, protein imprinting, and immunofluorescence (IF) analyses collectively indicated that acupuncture reduced ACSL1 and CYBB expression, and increased GPX4 and FTMT expression. Overall, the ferroptosis pathway associated with ACSL1/CYBB/FTMT/GPX4 represents a potential strategy through which acupuncture can improve the reproductive function in asthenozoospermic mice.

Androgenic effects of the aqueous extract of Pycnanthus angolensis (Welw.) Warb. (Myristicaceae) wood in hemicastrated male Wistar rats

Background: Androgen deficiency is the most common disorder of reproductive function and can lead to male sexual disorders. Objective: This study was designed to evaluate the androgenic effects of Pycnanthus angolensis (Welw.) Warb in hemicastrated rats. Materials and methods: Forty-two male rats were divided into 6 groups of 7 rats each, including a group of uncastrated rats that received distilled water (10 ml/kg); a group of castrated rats that received 10 ml/kg of distilled water; a group of castrated rats that received testosterone enanthate (3 mg/kg BW) per week intramuscularly; and 3 groups of castrated rats that received 43, 86 and 172 mg/kg of the aqueous extract of Pycnanthus angolensis, respectively. After 14 days of oral treatment, the rats were killed by decapitation. The blood was collected and the androgen-dependent organs were collected for histological sectioning, and biochemical analysis. The tail of the epididymis was used to assess sperm quality. Results: Treatment with the aqueous extract at doses of 43 and 86 mg/kg, significantly improved the sexual behavior of castrated rats, with increases of 25.92% and 22.74% intromissions frequency, and 67.06% and 56.46% mount frequency, compared to those in the castrated rats which did not receive any treatment. The extract also enhanced sperm quality in castrated rats. Both doses also significantly increased serum testosterone levels with rates of 45.07% and 49.00%, respectively; compared to those in the negative control group. Conclusion: In view of the aforesaid results, Pycnanthus angolensis (Welw.) Warb could be considered as a promising natural agent in hypogonadism management. Keywords: Androgen, hypogonadism, castrated male rats, unilateral castration, Pycnanthus angolensis (Welw.) Warb

Poster 149: Supplemental Testosterone Increases Risk of Reoperation after Total Shoulder Arthroplasty

Objectives: Periprosthetic joint infections (PJIs) are devastating complications after total shoulder arthroplasty (TSA). While it has been shown that increased serum testosterone levels may increase the concentration of skin flora, it is unknown how this correlates clinically with the risk of infection/reoperation. Therefore, we sought to evaluate if supplemental testosterone increases the risk of infection and reoperation after TSA. Methods: We retrospectively reviewed 448 males who underwent TSA between January 1, 2017 and December 31, 2021 who were prescribed supplemental testosterone within 1 year prior to TSA using a commercial claims database. These patients were matched 1:5 to 2240 patients who were not prescribed supplemental testosterone based on year of TSA, age, geographical region, inpatient or outpatient TSA, and comorbidities within 30 days preoperatively including hypertension, hyperlipidemia, diabetes, obesity, smoking, alcohol abuse, and Charleson Comorbidity Index (CCI) using Mahalanobis nearest neighbor matching. Univariable and multivariable analyses were performed. Significance was set at p < 0.05. Results: Patients prescribed supplemental testosterone were younger (mean = 60.5 versus 61.3 years old, p = 0.04), but otherwise demographics were similar between cohorts (Table 1). Mean follow-up was 1.5 years. At 2 years postoperatively, patients prescribed testosterone had a higher cumulative incidence for reoperation for infection at 2.0% compared to 0.9% for those who were not prescribed testosterone (p = 0.04). Multivariable analysis demonstrated that preoperative supplemental testosterone (OR = 2.6, 95% CI = 1.03-6.6, p=0.04), diabetes (OR = 2.9, 95% CI = 1.1-7.9, p=0.04), and alcohol abuse (OR = 11.4, 95% CI=2.2-60.1, p = 0.004) were risk factors for reoperation for infection (Table 2). At 2 years postoperatively, patients prescribed testosterone had a higher cumulative incidence for overall reoperation at 9.6% compared to 4.0% for those who were not prescribed testosterone (p < 0.001). Multivariable analysis showed that supplemental testosterone was found to be risk factor for overall reoperation (OR = 2.1, 95% CI = 1.3-3.2, p = 0.001) (Table 3). Conclusions: Patients prescribed supplemental testosterone had a higher risk of all cause reoperation and reoperation for infection after TSA. Further research is needed to understand the mechanism by how testosterone increases the risk of reoperation after TSA.

The influence of correction of carbohydrate metabolism and body weight on endogenous testosterone production in men with type 2 diabetes mellitus, obesity and hypogonadism

Male hypogonadism and type 2 diabetes mellitus (T2DM) are often combined and aggravate each other. Considering the pathogenetic relationship with the components of the metabolic syndrome (hyperglycemia, insulin resistance, obesity) and the potential reversibility of testosterone deficiency, as well as the wariness of doctors and patients regarding testosterone replacement therapy, it is interesting to study the effect of various methods for correcting carbohydrate metabolism and obesity on endogenous testosterone production. When analyzing the effect of lifestyle correction, drug therapy for T2DM and obesity, as well as metabolic surgery on testosterone production, encouraging results were obtained with regard to methods that provide, first of all, significant reduction in body weight (medications from the group of glucagon-like peptide-1 receptor agonists and bariatric surgery). As for other classes of new antidiabetic drugs, it is likely that all of them may have direct or indirect beneficial effects on male sexual function, mainly by reducing glucotoxicity and inflammation. However, this hypothesis requires studies on large samples of patients. In addition, there is still no convincing data on the significance of correction of carbohydrate metabolism, regardless of weight loss, in relation to endogenous testosterone production, and there is also no data on the degree of improvement in glycemic control required for a clinically significant increase in serum testosterone levels.

Apilarnil ameliorates Bisphenol A-induced testicular toxicity in adult male rats via improving antioxidant potency and PCNA expression

Apilarnil, a bee-derived product originating from drone larvae, offers a range of advantageous properties for both humans and animals. It functions as an antioxidant, provides neuroprotection, boosts fertility, and has antiviral capabilities. Additionally, it is a provider of androgenic hormones. These beneficial functions are supported by its chemical composition, which comprises mineral salts, vitamins, carbs, lipids, hormones, and amino acids. The current study aimed to evaluate the ameliorative effect of apilarnil against Bisphenol A (BPA)-induced testicular toxicity in male adult rats. Forty-eight Wistar albino rats were randomly classified into six groups. The first, second, and third received olive oil, BPA at a dose of 50 mg/kg body weight (bwt), and apilarnil at a dose of 0.6 g/kg bwt, respectively. The fourth, fifth, and sixth groups received apilarnil with, before, or after BPA administration, respectively. Phytochemical analysis using included linear ion trap-ultra-performance liquid chromatography-tandem mass spectrometry (LTQ-UPLC-MS/MS) and global natural products social molecular networking (GNPS) revealed the presence of lysine, 10-hydroxy-(E)-2-dodecenoic acid, apigenin7-glucoside, testosterone, progesterone, and campesterol. BPA administration decreased serum level of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, glutathione (GSH) concentration, total sperm count, motility, and vitality. Additionally, BPA increased sperm abnormalities, malondialdehyde concentration (MDA), and decreased proliferating cell nuclear antigen (PCNA) expression. The treatment with apilarnil ameliorated BPA reproductive toxicity in rats which was indicated by increased serum testosterone levels, normalized serum levels of FSH and LH, and concentration of MDA and GSH activity. Moreover, apilarnil improved sperm count, motility, morphology, and PCNA expression. Apilarnil was found to enhance reproductive hormones, MDA levels, antioxidant activity, and PCNA expression

Tle6 deficiency in male mice led to abnormal sperm morphology and reduced sperm motility.

Infertility affects over 15% of the global population, and genetic mutations are a substantial cause of infertility. Recent studies have focused on the subcortical maternal complex and its role in early embryonic development. TLE6, a core protein in the subcortical maternal complex, is crucial for female fertility; however, its role in male germ cells remains poorly understood. In this study, we generated a novel Tle6 knockout mouse model using CRISPR-Cas9 to examine the impact of Tle6 mutations on male fertility. Tle6 knockout males exhibited a reduced total sperm count compared to wild-type mice, with a marked decrease in highly motile sperm. Histological observation of Tle6 +/- mouse testes showed no apparent structural changes, though impaired sperm maturation was observed. Immunofluorescence staining showed that TLE6 localizes to the midpiece of sperm. It was also confirmed that the expression of Tle6 is reduced in Tle6 +/- male mice. In addition, Tle6 +/- mice exhibited a significant increase in serum testosterone levels compared to wild-type mice. Changes in the expression of genes related to sperm function were also observed in the testes of Tle6 knockout mice. These findings suggest that TLE6 is involved in sperm production and function, and that mutations in TLE6 may impair the production of functional sperm in humans, potentially leading to infertility.

Efecto del extracto de Boswellia serrata sobre el daño testicular inducido por Metotrexato

This study aimed to determine the effect of Boswellia serrata extract on Methotrexate– induced testicular damage by evaluating antioxidant system, reproductive organ weights, some spermatological parametres and serum Testesterone levels. For this purpose, 40 Sprague Dawley rats were divided into 4 groups. 1. Control Group (n=10): No treatment was given for 10 days. 2. B. serrata Group (n=10): B. serrata was given by gavage at a dose of 500 mg·kg-1 for 10 days. 3. Methotrexate Group (n=10): Methotrexate was given intraperitoneally as a single dose of 20 mg·kg-1. 4. Methotrexate + B. serrata Group (n=10): After methotrexate was given intraperitoneally as a single dose of 20 mg·kg-1, 500 mg·kg-1 B. serrata was given by gavage for 10 days. It was determined that B. serrata significantly increased serum Testosterone levels (P<0.001), testicular GSH levels (P<0.001), motility of sperm (P<0.001), concentration of sperm (P<0.001), absolute ventral prostate (P<0.001) and absolute seminal vesicles (P<0.05) organ weight in Methotrexate + B. serrata group. The decrease in testicular MDA levels (P>0.05) and the increase in GSH–Px enzyme activity of testes (P>0.05) and final body weight (P>0.05) were not significant in Methotrexate + B. serrata group compared to the Methotrexate group. In conclusion, the negative effects of Methotrexate on the male reproductive system can be reduced by administering B. serrata extract.

Evaluation of <i>Abrus precatorius</i> on reproductive function of male Wistar rat

Background: In recent times, attention has been shifted from synthetic drugs to the use of medicinal plants and this has greatly improved reproductive functions. Abrus precatorious plant has different parts which are used as diverse sources of naturally occurring chemicals that have a variety of therapeutic effects on the body. However, in this present study, we consolidated the reproductive property of Abrus precatorius in paroxetine-induced male reproductive dysfunction. Methods: Twenty four (24) male rats were divided into four (4) groups each containing six animals was used for this experiment following paroxetine-induced erectile dysfunction. Group one, received 1ml of distilled water, Group two received 20mg/kg of Paroxetine and 50mg/kg of sildenafil, Group three received 20mg/kg of Paroxetine and 300mg/kg of A. precatorius extract, Group four received 20mg/kg of Paroxetine and 900mg/kg of A. precatorius extract for 21 days. Results: Results from the studies reveal that there was significant decrease in the sperm motility of the rats administered with Abrus precatorius when compared with control. Interestingly, the high dose extract increased the serum testosterone levels significantly while the low dose extract significantly reduce the level of testosterone when compared with the control. Histological examination of the testes of treated rats displayed noticeable atrophy, which was characterized by disruption of the seminiferous epithelium and reduction in cell population of the Leydig cells. Conclusion: It appears that very high dose of Abrus precatorius may induce infertility by increasing serum testosterone levels.

Evaluation of androgen receptor markers in erectile dysfunction.

Steroid hormones, such as testosterone, play a crucial role in modulating the development of male internal and external genitalia as well as secondary sex characteristics by binding to the androgen receptor. Once bound, androgen receptor operates as an inducible transcription factor, interacting with a multitude of co-regulators to initiate various downstream signaling pathways. The androgen saturation hypothesis posits that beyond a specific threshold, androgen receptor binding and functionality remain unaltered despite an increase in serum testosterone levels. The objective of this study was to explore the expression of these proteins in penile tissue samples from men with severe erectile dysfunction to enhance our understanding of the influence of serum testosterone on androgen receptor function. Patients undergoing surgical management for high-grade ED at our institution were invited to participate in the study. During inflatable penile prosthesis surgery, corpus cavernosum biopsy was obtained. Protein was extracted from each sample for western blot analysis which was probed with androgen receptor, heme oxygenase, inducible nitric oxide synthase, and phosphodiesterase type 5 antibodies with GAPDH for protein normalization. 12 men agreed to participate in this study. Serum testosterone levels were obtained from all participants on the morning of their surgery. The median testosterone level was 300.15 ng/dL. Our findings revealed a decrease in androgen receptor and inducible nitric oxide synthase expression at serum testosterone levels below 300 ng/dL (p = 0.022, 0.03). Similarly, hemeoxygenase and phosphodiesterase type 5 expression levels were significantly lower at serum T concentrations below 200 ng/dL (p = 0.017, 0.014). These data showed a significant decrease in the expression of proteins downstream of the androgen receptor at lower serum T levels. This suggests a potential correlation between serum T concentration and androgen receptor signaling and supports a potential saturation value between 200 and 300 ng/dL.

Effect of testosterone in young ice-hockey players on hematological, biochemical parameters and the level of physical performance

Ice-hockey combines intense physical activity at high speed with elements of power struggle. Testosterone is the main anabolic hormone, an increase in which during adolescence is associated with faster growth, increased muscle mass, physical strength, and increased overall and aerobic performance. Thus, it is interesting to study the effect of different testosterone levels on metabolic parameters and physical performance of young ice-hockey players.Objective: to compare hematological and biochemical parameters, as well as exercise performance in young ice-hockey players, depending on the testosterone level.Materials and methods: the study included 100 young ice-hockey players aged 15–17 years (average age 15.3 ± 1.1 years). The study group included 25 young ice-hockey players with an increased level of total blood testosterone (> 27.5 nmol/l). The control group included 75 young athletes with normal testosterone levels. All athletes included in the study underwent the PWC 170 test to assess physical performance. Assessment of hematological parameters included hemoglobin (HGB), hematocrit, red blood cell, mean corpuscular volume (MCV), mean concentration hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). β-crosslaps, myoglobin and creatine phosphokinase (CPK) activity were measured to assess the functional state of muscle and bone tissue.Results: A comparative assessment of the CBC in young ice-hockey players did not reveal significant differences depending on the level of serum testosterone level. Tolerance to physical activity in the study groups also did not differ. Young ice-hockey players with increased testosterone levels showed lower β-crosslaps values compared to the control group. The values of other biomarkers of the functional activity of muscle tissue did not depend on the level of testosterone levels.Conclusion: Increased serum testosterone level in the range from 27.5 to 40 nmol/l, detected in young ice-hockey players aged 15–17 years, is not associated with a change in hematological and biochemical parameters. High total testosterone levels do not improve physical performance. It is necessary to continue studies to assess the dynamics of the serum testosterone in young ice-hockey players to clarify the long-term effects of androgens on the metabolic and functional indicators of young athletes. Increasing serum testosterone levels in athletes is subject to wide discussion in the community of sports physicians and endocrinologists.

Dasatinib and quercetin increase testosterone andsperm concentration in mice.

Cellular senescence is a defense mechanism to arrest proliferation of damaged cells. The number of senescentcells increases with age in different tissues and contributes to the development of age-related diseases. Old mice treated with senolytics drugs, dasatinib and quercetin (D+Q), have reduced senescent cells burden. The aim of this study was to evaluate the effects of D+Q on testicular function and fertility of male mice. Mice (n = 9/group) received D (5 mg kg-1) and Q (50 mg kg-1) via gavage every moth for three consecutive days from 3 to 8 months of age. At 8 months mice were breed with young non-treated females and euthanized. The treatment of male mice with D+Q increased serum testosterone levels and sperm concentration and decreased abnormal sperm morphology. Sperm motility, seminiferous tubule morphometry, testicular gene expression and fertility were not affected by treatment. There was no effect of D+Q treatment in β-galactosidase activity and in lipofuscin staining in testes. D+Q treatment also did not affect body mass gain and testes mass. In conclusion, D+Q treatment increased serum testosterone levels and sperm concentration and decreased abnormal sperm morphology, however did not affect fertility. Further studies with older mice and different senolytics are necessary to elucidate the effects in the decline of sperm output (quality and quantity) associated with aging.

(300) Impact of Intranasal Testosterone versus Intramuscular Testosterone cypionate on Hematocrit of Hypogonadal Men: Data from an ongoing Phase IV, Open-label, Randomized Clinical Trial.

Abstract Introduction The potential increase in hematocrit and subsequent risk of polycythemia has been regarded as one of the most worrisome adverse effects of testosterone therapy (TT). Recent evidence has shown that the modality of delivery and half-life of each formulation may affect the incidence of these side effects. Therefore, we hypothesized that longer-acting intramuscular testosterone would increase hematocrit to a higher degree than the shorter-acting nasal formulations that can more closely mimic normal physiology. Objective To compare the effects of Intranasal Testosterone (NT) and Intramuscular Testosterone (TC) on hematocrit and serum testosterone levels in testosterone deficient men over 4 months. Methods This Phase IV, randomized, open-label clinical trial was performed on 39 symptomatic, testosterone deficient (TD) men with at least two serum testosterone levels below 300 ng/dL drawn before 10AM. Men were randomized (1:1) to receive either nasal gel three times per day (5.5mg per nostril) and intramuscular TC (200mg) once every two weeks. The primary outcomes were changes in Hematocrit and serum T before and after four months. Secondary outcomes were changes in estradiol (E), PSA and 17-OHP. Data analysis was performed using two-sample and single-sample T tests (Microsoft Excel v.16.60). Results A total of 39 men with testosterone deficiency were randomized to receive either NT (n=15) or TC (n=24). The median participant age was 46 years old with a mean serum T of 237.1 ng/dL and hematocrit of 43.3%. Prevalence of participants who screened positive for OSA on STOP-BANG questionnaire for NT and TC group were 67% and 71%, respectively. Compared to their respective baselines, men in both groups saw significantly increased serum testosterone levels (p 52%) after 4 months was 0% in NT group and 4.2% in TC. Those taking TC saw increases in E (p=0.003) and decreases in 17-OHP (p<0.001) at follow-up, where NT saw no changes. Neither regimen significantly impacted PSA at follow-up. Conclusions Both Intranasal and Intramuscular testosterone regimens are effective in treating hypogonadal men. However, short-acting nasal T does not appear to impact hematocrit levels especially when compared to testosterone cypionate. Those who are at increased risk of developing polycythemia or want to avoid changes in their E or 17-OHP levels may benefit from short-acting T formulations. Disclosure Yes, this is sponsored by industry/sponsor: Acerus Pharmaceuticals Clarification Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus Pharmaceuticals

Effects of sodium valproate monotherapy on reproductive hormonal levels in adult male epileptic patients

Aims: to assess the effects of valproate (VPA) on serum levels of testosterone, prolactin, follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol ( E2) in adult male epileptic patients in comparison to healthy controls. Methods: This study was conducted from Oct. 2005 to Aug. 2006. Patients were received from specialist neurology Clinic. Out of 62 patients interviewed only 46 fulfilled the criteria of selection . Apparently healthy 50 subjects were also included in this study as a control group. Blood samples were taken from both patients and controls and assay of testosterone, prolactin ,FSH, LH and E2 were done using radioimmunoassay (RIA) technique. Body mass index (BMI) was calculated using special equation. Results: There was a significantly higher testosterone levels in epileptic male patients on VPA therapy in comparison to healthy controls, with insignificant effect on the levels of prolactin, FSH, LH and E2. The duration of therapy and the dosage of VPA had no effect on the serum levels of the above measured parameters. Conclusion: VPA monotherapy might be associated with significant increase in serum testosterone level with insignificant effects on serum prolactin, FSH, LH and E2 in adult male epileptic patients and the duration of therapy and daily dose have no influence on such effect.

Strategies to Increase Testosterone in Men Seeking Fertility.

Prevalence of testosterone deficiency is increasing in the adolescent and young adult male population. As the average paternal age rises, there is a significant population of men with hypogonadism seeking testosterone therapy wishing to achieve or maintain fertility potential. Identification of potential lifestyle modifications that may improve the testosterone deficiency is one of the initial interventions of the holistic strategy in treatment. This is followed by drug therapy; however, traditional testosterone therapy acts as a contraceptive by suppressing the hypothalamus-pituitary-gonadal (HPG) axis and therefore cannot be used as a treatment strategy. A solution has been the off-label use of selective estrogen receptor modulators, human chorionic gonadotropin (hCG), and anastrozole inhibitors to treat hypogonadal symptoms while increasing intratesticular testosterone, a necessity for spermatogenesis. Recently, a novel therapy, Natesto intranasal testosterone gel, has been shown to increase serum testosterone levels while maintaining semen parameters. This is hypothesized to be because of its short-acting properties having lesser effect on the HPG axis, in contrast to the long-acting properties of traditional testosterone therapy. It is important to differentiate hypogonadal men between those seeking to achieve or maintain fertility status because the drug therapy of choice differs. This can be accomplished by determining the levels of 17-hydroxyprogesterone (17-OHP), because it is a biomarker for intratesticular testosterone. Those with low 17-OHP may wish to initiate treatment with alternative therapies, whereas those with high 17-OHP may trial short-acting testosterone therapies. As the urologist's armamentarium continues to increase, better strategies to increase testosterone levels in men seeking fertility can be achieved.

Prevalence of secondary erythrocytosis in men receiving testosterone therapy: A matched-cohort analysis of intranasal gel, injections, and pellets.

Increased hematocrit (HCT) is a common adverse effect in men on testosterone therapy (TTh). We aimed to uncover differences in HCT changes among men receiving different forms of TTh, namely intranasal gels, intramuscular injections, and subcutaneous pellets. We conducted a single-center, retrospective, matched-cohort study of patients treated for testosterone deficiency (TD) to investigate the effect of three TTh regimens on HCT. We included men who received intranasal testosterone (NT), intramuscular testosterone (TC), or subcutaneous testosterone pellet (TP) regimens between January 2011 and December 2020. We matched treatment cohorts 1:1:1 for age, body mass index (BMI), and history of obstructive sleep apnea. Those taking TTh for less than 16 weeks were excluded. Comparison between groups was performed with U-Mann Whitney test, Student t-test, ANOVA, or Kruskal Wallis test as appropriate. Seventy-eight matched-cohort individuals with testosterone deficiency (TD) received either NT, TC, or TP. The most common TD symptoms prior to initiation of TTh were erectile dysfunction (38%), low libido (22%), and lack of energy (17%). Baseline serum testosterone and HCT were higher in NT (p<0.05) recipients. As expected, all men receiving TTh were found to have increased serum testosterone levels at followup (p<0.001). Relative to their respective baselines, men receiving TC experienced the greatest increase in serum testosterone (240.8 ng/dL to 585.5 ng/dL), followed by NT (230.3 ng/dL to 493.5 ng/dL) and TP (210.8 ng/dL to 360.5 ng/dL) (all p<0.001). TC and TP were associated with significant increases in HCT (4.4% and 1.7%), while NT was associated with a decrease in HCT (-0.8%) at 16-week followup. When controlled for age, BMI, and OSA, men receiving NT experienced decreased HCT compared to TC or TP at 16-week followup. Intranasal testosterone, while able to increase serum testosterone levels to reference range, does not appear to have a significant impact on HCT compared to the longer-acting forms of TTh.

Abstract 5277: Activation of TRPM8 channel suppresses prostate cancer growth and progression

Abstract Prostate cancer (PC) is one of the most prevalent male malignancies and a leading cause of cancer-related deaths in men. While androgen-deprivation therapy is successful in the early stages of PC, tumor cells eventually become resistant to its effects. With a median survival of 18 months, the shift to androgen-independent prostate cancer (AIPC) has a poor prognosis. Mechanisms causing this change have yet to be explained, however mounting evidence implicates the loss of transient receptor potential melastatin 8 (TRPM8) as a significant contributor. The prostate epithelium normally expresses the ionotropic receptor TRPM8. Our team has recently shown that testosterone-induced activation of TRPM8 enhances Ca2+ absorption and causes apoptosis. This prompted us to propose that increased TRPM8 activity on the plasma membrane is cytotoxic to PC cells and that TRPM8 internalization is a crucial step in the pathogenesis of PC. We examined the amounts of TRPM8 mRNA in benign tumor and metastatic PC patient datasets. TRPM8 mRNA is initially elevated in the early stages of PC but is increasingly lost during the progression to AIPC. In addition, male and female TRPM8−/− mice exhibited increased serum testosterone levels, heightened AR activity, and activation of cell cycle, invasion, and adhesion-related effectors. In both AR+ and AR− xenograft models, our research reveals that TRPM8 possesses potent antitumor properties. Given this, investigating the in vivo role of TRPM8 in PC has the potential to significantly enhance patient outcomes by preventing progression to the androgen-independent state. Citation Format: Swapna Asuthkar. Activation of TRPM8 channel suppresses prostate cancer growth and progression. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5277.

Sleep duration and testosterone levels in community older men: results from the West China Health and Aging Trend study.

Sleep duration and testosterone levels in community older men: results from the West China Health and Aging Trend study.

Do the Covid-19 vaccines affect the reproductive parameters of men?—A Northern Saudi experience

The COVID-19 vaccine acceptance is a psychological behavior influenced by many factors, including fear of an adverse effect on the reproductive system. The aim of this study is to assess the COVID-19 vaccines effect on reproductive parameters among the male population of northern Saudi Arabia. We conducted a prospective cohort study among 100 volunteers who received two doses of COVID-19 vaccines. A pre- and post-vaccination blood sample was collected and analyzed for testosterone, prolactin, and follicle-stimulating hormone (FSH). Semen samples were also collected and analyzed. The Wilcoxon signed-rank test was used to compare the values between pre- and post-vaccination. Of the 100 samples analyzed, there was a significant increase in progressive sperm motility after the second dose of vaccination, but the increase was within the physiological limits (pre-55.03 [42.00-61.75] vs. post-57.50 [42.25-63.00], P = 0.008). Similarly, a significant increase in serum testosterone level after the second vaccination dose was observed (pre-380.65 [301.60-485.73] vs. post-410 [318.18-505.35], P = 0.016). These preliminary results show that the COVID-19 vaccines do not have any adverse effect on the reproductive parameters of men. A prospective long-term follow-up study will be necessary on all WHO -approved COVID vaccines to determine their long-term effect on men's reproductive health. The future follow-up study could strengthen our findings and encourage the men who have vaccine hesitancy to take due to fear of its effect on reproductive parameters.