Testosterone Replacement Research Articles

Unlocking Testosterone Production by Biotransformation: Engineering a Fungal Model of Aspergillus nidulans Strain Deficient in Steroid 11α-Hydroxylase Activity and Expressing 17β-Hydroxysteroid Dehydrogenase Enzyme as Proof of Concept

Testosterone holds significant medical and economic importance, with the global market for testosterone replacement therapies valued at approximately USD 1.9 billion in 2023. This hormone is essential for the development and maintenance of male sexual characteristics as well as bone and muscle health. It plays a key role in conditions such as hypogonadism, muscle disorders, and andropause. However, the industrial production of testosterone often involves complex chemical processes that result in low yields, high costs, and environmental damage. Microbial biotransformation of steroids presents an eco-friendly alternative to traditional chemical synthesis. A knockout strain of Aspergillus nidulans deficient in steroid 11α-hydroxylase activity was developed, rendering it incapable of hydroxylating androstenedione, progesterone, and testosterone. In these strains, two newly identified CYP450 enzymes, CYP68L1 from A. nidulans and CYP68L8 from Aspergillus ochraceus, were expressed to confirm their roles as steroid 11α-hydroxylases of androstenedione, progesterone, and testosterone. The availability of these 11α-hydroxylases represents significant progress toward achieving efficient single-step steroid fermentation. Furthermore, the A. nidulans knockout strain serves as an effective model for studying the conversion of androstenedione to testosterone upon the expression of the enzyme 17β-hydroxysteroid dehydrogenase, due to its inability to hydroxylate testosterone.

Androgen receptor CAG repeat polymorphism might be a possible cause of familial constitutional delay of growth and puberty.

Induction of puberty in boys with constitutional delay of growth and puberty (CDGP) through a short course of low-dose testosterone therapy indicates the critical interaction between testosterone and the androgen receptor (AR) during the activation and maturation of the hypothalamic-pituitary-gonadal axis at puberty onset. Previous studies have shown an inverse relationship between the CAG repeat length and the transactivation function or expression level of the AR gene. We aimed to investigate whether the AR CAG repeat polymorphism has any implications on pubertal delay. Thirty-three male patients with CDGP were enrolled in the study group, while 53 age-matched healthy individuals who had entered puberty on time were included in the control group. The CAG repeat length was determined through direct DNA sequencing analysis. The median chronological age of boys with CDGP was 14.2 (14.1-14.6) years, compared to 14.2 (13.65-14.8) years for healthy subjects (p = 0.5). In the CDGP group, 22 (66.7%) children had a family history of the condition. There was no significant difference between the groups in terms of AR CAG repeat length (median AR CAG repeat length: 21 (20-24.5) and 20 (20-24), respectively, p = 0.1). However, in boys with CDGP with a similar family history (n = 22), a significantly longer AR CAG repeat length was found compared to the control group (n = 53) (median AR CAG repeat length: 22 (20-25) and 20 (20-24), respectively, p = 0.03). The median AR CAG repeat length in boys without a family history was 21 (20-22) triplets. Although boys with a family history had a slightly longer AR CAG repeat length than those without, the difference was not statistically significant (p = 0.07). Additionally, no significant differences were observed between boys with non-familial CDGP and control subjects (p = 0.8). Furthermore, no significant differences in anthropometric characteristics or hormonal parameters were found when patients with CDGP were categorized by AR CAG repeat length quartiles. This is the first study to investigate the role of AR CAG polymorphism in the etiopathogenesis of CDGP. Our findings suggest that the AR CAG repeat length may be associated with familial CDGP.

Effects of Testosterone Replacement Therapy on Metabolic Syndrome in Male Patients-Systematic Review.

Metabolic syndrome (MS) comprises several symptoms or disorders that significantly increase the risk of developing atherosclerosis and type 2 diabetes. This study aims to determine the direct impact of testosterone therapy on the components of MS; although excluding type 2 diabetes cases. The authors conducted a systematic literature search of PubMed, Scopus, and Cochrane databases without date limits, using keywords such as "testosterone therapy", "metabolic syndrome" and "men". The studies included in our review focused on the effects of testosterone replacement therapy (TRT) in male patients with MS, yet rejecting individuals where type 2 diabetes constituted the only diagnosis. A meta-analysis was performed using PQStat v1.8.6 software. The overall effect size (mean difference) was calculated using a random effects model. Our meta-analysis indicates that testosterone therapy leads to improvement in the components of MS. Significant reductions were observed in waist circumference (WC) (95% CI: -0.709 to 0.094; p = 0.011), as well as in triglycerides (TG) (95% CI: -0.474 to 0.120; p = 0.039). These findings support the potential therapeutic benefits of testosterone treatment in managing MS. However, further research is vital to explore the long-term effects and the safety of this therapy in patients with metabolic syndrome.

Bassa statura non sindromica e ritardo puberale: non solo ritardo costituzionale di crescita e pubertà

A 14-year-old boy with suspected constitutional delay of growth and puberty (CDGP) presented with short stature, absence of secondary sex characteristics, bone age delayed by one year and family history of CDGP in his mother. The external genitalia were normal. Re-evaluated at the age of 17 years and 7 months (as he missed several visits), he presented with a short near-final height (bone age consistent with chronological age) below the target height, signs of progressed virilization, but insufficient testicular volume. The prevalence of nonsyndromic 46,XX testicular disorder is estimated at 1:20,000 males. In 80% of cases the condition is due to the presence of the SRY gene on the X chromosome, resulting from abnormal paternal meiosis. It is characterized by short stature, hypergonadotropic hypogonadism and sterility. The need for routine screening of gonadal cancer is still a matter of debate. Treatment of this condition consists of testos-terone replacement from the pubertal age. Psychological support should also be warranted since the communication of the diagnosis. The case suggests that non-syndromic 46,XX testicular disorder should be considered when evaluating a boy with hypogonadism and short stature, especially in patients with suspected CDGP who have progressive virilization and advancement of bone age, despite no increase in testicular volume.

Diagnostic utility of testosterone priming prior to dynamic tests to differentiate constitutional delay in puberty from isolated hypogonadotropic hypogonadism in boys

BackgroundDifferentiation between isolated hypogonadotropic hypogonadism (IHH) and constitutional delay in puberty (CDP) throughout adolescence can be challenging for doctors. This study examines the withdrawal effects of short-term, low-dose testosterone treatment (testosterone priming) on the ability of dynamic testing to distinguish between CDP and IHH based on activation of the hypothalamo-pituitary–testicular axis.MethodsA case–control study included 20 boys with delayed puberty (group A) and 20 patients with IHH (group B). Both groups underwent Triptorelin and human chorionic gonadotropin (hCG) stimulation tests before and 2 months after testosterone injections (100 mg) intramuscularly every 4 weekly for 3 months.ResultsThe triptorelin-stimulated 4-h LH with a cutoff of 2.4 IU/L and the hCG-stimulated testosterone with a cutoff of 1.160 ng/mL had sensitivities of 65% each, and specificities of 90% and 95%, respectively, to diagnose CDP. After testosterone withdrawal, the cut-off values for 4-h LH were 8.850 IU/L and 3.190 ng/mL for hCG-stimulated testosterone. Basal inhibin B > 88.25 pg/ml was found to be a differentiating factor in diagnosing CDP after testosterone withdrawal.Conclusionsfollowing the withdrawal of testosterone therapy, Inhibin B levels or 4-h stimulated LH are the most effective discriminant assays to distinguish CDP from IHH.

Semaglutide improved sperm morphology in obese men with type 2 diabetes mellitus and functional hypogonadism.

To compare the effects of semaglutide and testosterone replacement therapy (TRT) on semen quality and parameters of functional hypogonadism (FH) in men with type 2 diabetes mellitus and obesity. We designed a randomised open-label trial in 25 men with type 2 diabetes (aged 50 [46-60] years, BMI 35.9 [32.8-38.7] kg/m2) and FH randomised to semaglutide (SEMA) 1 mg/week or intramuscular testosterone undecanoate (TRT) 1000 mg/10-12 weeks for 24 weeks. Semen analysis and parameters of FH were measured at baseline and after 24 weeks of treatment. Participants completed questionnaires of the International Index of Erectile Function-15 (IIEF-15) and the Aging Symptoms in Men (AMS). The quality of baseline sperm parameters of our study cohort was poor, below the 5th percentile of reference values. In the SEMA group, there was a significant increase in morphologically normal sperm from baseline to the end of the study (2% [2; 3.5] vs. 4% [2; 5.5]; p = 0.012), whereas sperm concentration and total number decreased significantly in the TRT group. Compared to TRT, the SEMA group had a significantly higher number of morphologically normal sperm, sperm concentration and total number. Both groups experienced an increase in total testosterone and improvement in the AMS score, whereas the IIEF-15 score significantly improved only in the TRT group. Semaglutide markedly improved sperm morphology, total testosterone levels and symptoms of hypogonadism. These findings highlight semaglutide's potential as a therapeutic approach for men with obesity-related FH who desire fertility. NCT06489457, www. gov.

The Effects of Testosterone Replacement Therapy in Adult Men with Metabolic Dysfunction associated Steatotic Liver Disease: A Systematic Review and Meta-analysis.

Sex steroids modulate metabolic-dysfunction associated steatotic liver disease (MASLD) pathobiology. We hypothesized that testosterone therapy (TT) modulates progression of MASLD, and performed a systematic review to evaluate the efficacy of TT on liver steatosis and fibrosis. We searched PubMed and Embase from inception until November 2023. We screened 1489 studies and identified 9 eligible studies. We assessed risk of bias for randomized trials using RoB-2 "Cochrane risk of bias tool for randomized trials", non-randomized studies using ROBINS-I tool "Risk of Bias in Non-randomized Studies-of Interventions", and Murad's Tool for single-arm studies. We pooled estimates using RevMan 5. 3 randomized controlled trials (RCTs), 4 non-randomized studies, and 2 single-arm studies were identified. The population of interest comprised men with MASLD. TT was administered at varying doses, routes, and frequencies, with follow-up ranging 12-weeks to 8-years. Liver fibrosis and steatosis were assessed using liver biopsy in 3 studies, CT/MRI in 5, and serum scores in 2. All studies provided evidence of reduction in liver steatosis with TT compared to no TT. In addition, the LiFT (RCT) trial demonstrated a resolution of MASLD / MASH and a regression in liver fibrosis. TT led to decrease in liver enzymes. Studies were heterogenous in terms of population characteristics, treatment modalities, endpoints, and follow-up. Adverse events were comparable between the 2 groups. TT is a promising treatment option for men with MASLD and low testosterone. It may improve liver steatosis and reduce liver fibrosis. Large, double-blinded randomized placebo-controlled trials are needed.

Prescription Testosterone is Associated with an Increased Risk of Anterior Cruciate Ligament Injury

To characterize the relationship between testosterone replacement therapy (TRT) and anterior cruciate ligament (ACL) injuries. A retrospective cohort study using a large insurance database was conducted. Patients who were prescribed TRT for at least 3 months were matched with controls who were not prescribed TRT. Rates of ACL tears were compared between the cohorts. Multiple subgroups were created based on age (<25 years, 25-35, 36-45, 46-55, 56-65, and 65+). Multivariable logistic regressions were performed to determine the association of TRT with ACL tears while accounting for demographic variables and comorbidities. After matching, there were 160,839 patients in both the TRT cohort and control cohort. The incidence of ACL injuries was 17.8 per 10,000 person-years (95% CI: 16.4-19.2) for patients who were prescribed TRT and 4.9 per 10,000 person-years (95% CI: 4.1-5.7) for controls (p<0.001). Within 2 years of filling a testosterone prescription for at least 3 months, 572 (0.35%) patients experienced an ACL injury compared to only 157 (0.10%) controls during the same follow-up period (OR: 2.77; 95% CI: 2.26-3.42, p<0.001). When stratified by age, all groups except the <25 years of age group demonstrated significantly higher rate of ACL tears (OR 3.91-12.3, p<0.001-0.009). When separated by sex, males on TRT were 3.13 (95% CI: 2.50-3.93, p<0.001) times more likely while females on TRT were 1.94 (95% CI: 1.13-3.41, p=0.018) times more likely to experience an ACL injury compared to controls. This study found that patients prescribed at least three months of TRT had a significantly higher incidence of ACL injuries compared to controls within a two-year follow-up period. Level III, retrospective comparative study.

Association of testosterone replacement therapy with atrial fibrillation and acute kidney injury.

Secondary analyses of the Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) trial revealed significantly higher rates of new-onset atrial fibrillation (AF) and acute kidney injury (AKI) in the testosterone replacement therapy (TRT) cohort. To validate the secondary findings of the TRAVERSE trial. We utilized the TriNetX Research Network to identify a cohort of men ages 45-80years old who met similar inclusion criteria to the TRAVERSE trial. We compared hypogonadal men (testosterone 100-300ng/dL) who had a prescription for topical testosterone therapy and men who did not. Propensity score matching was used to match patient populations. Kaplan Meier survival analysis was used to determine the relative risk of new-onset AF and AKI within 3years. New-onset AF and AKI within 3years. There were 2134 men included in each cohort after propensity score matching. Men on TRT had significantly lower testosterone (T) at the time of diagnosis compared to men not prescribed TRT (207 ± 66ng/dL vs 246 ± 140ng/dL, P< 0.001). Kaplan-Meier survival analysis showed a significantly increased risk of AKI among men on TRT (RR 1.53, 95% CI 1.07-2.18). However, TRT was not associated with a significantly increased risk of new-onset AF (RR 1.48, 95% CI 0.93-2.37). Hypogonadal men with underlying cardiovascular risk factors or pre-existing cardiovascular disease who receive TRT may be at increased risk of AKI after starting therapy. We evaluated a large global research database and utilized similar inclusion and exclusion to the TRAVERSE trial. However, our results are limited by the retrospective study design and reliance on documented claims data. Similar to the TRAVERSE trial, our study demonstrated an increased risk of AKI among men on TRT, but did not find increased risk of AF. However, further studies are required to validate these results.

Testosterone replacement therapy and possible side effects

The substitution of testosterone is basic andrological treatment. Beside the "when and how," knowledge of possible side effects is mandatory. Therefore, we highlight the effects of testosterone replacement therapy on bones, cardiac function, sexuality, gynacomatia, fertility, and contraception, but also areas of concern regarding prostate carcinoma and testosterone replacement therapy.

The Relationship Between Exogenous Testosterone Use and Risk for Primary Anterior Cruciate Ligament Rupture.

In the United States, testosterone therapy has markedly increased in recent years. Currently, there is a paucity of evidence evaluating the risk of ligamentous injuries in patients taking testosterone replacement therapy (TRT). The purpose of this study was to quantify the association between TRT and the incidence of anterior cruciate ligament (ACL) injuries and the subsequent risk of ACL reconstruction (ACLR) failure. It was hypothesized that individuals receiving TRT would demonstrate an increased risk for index ACL injury and ACL rerupture. Cohort study; Level of evidence, 3. This is a retrospective cohort study utilizing the PearlDiver database. Records were queried between 2011 and 2020 for patients aged 18 to 59 years who filled a testosterone prescription. A matched control group based on age, sex, Charlson Comorbidity Index, tobacco use, diabetes, and hypothyroidism consisted of patients aged 18 to 59 years who had never filled a prescription for exogenous testosterone. International Classification of Diseases, 9th and 10th Revisions and Current Procedural Terminology (CPT) codes were utilized to identify patients with ACL injuries and those undergoing reconstruction. Multivariable logistic regression was used to compare rates of ACL injury at 6 months, 1 year, and 2 years after initiating TRT. ACLR failure was also examined at 1-year intervals for 5 years for individuals filling a TRT prescription. A total of 851,816 patients were enrolled, with 425,908 patients in the TRT and control groups, respectively. The TRT cohort was significantly more likely to experience an ACL tear during 6-month (OR, 2.66; 95% CI, 2.17-3.26), 1-year (OR, 2.46; 95% CI, 2.11-2.86), and 2-year (OR, 2.22; 95% CI, 1.98-2.48) periods. The rate of reconstruction failure did not differ between the 2 cohorts at up to 5 years of follow-up (P > .05). Patients receiving TRT were significantly more likely to sustain a primary ACL rupture but were not at a statistically significant increased risk of reconstruction failure.

P032 Does testosterone replacement therapy affect the incidence of prostate cancer? A systematic review

P032 Does testosterone replacement therapy affect the incidence of prostate cancer? A systematic review

Differences in cardiorespiratory fitness by gonadotropin-releasing hormone agonist treatment before and after testosterone in transgender adolescents.

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 V̇o2peak (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.

Testosterone replacement has a beneficial effect on the hemostatic system by altered gene expression of coagulation factors

This study aimed to investigate the effects of testosterone replacement therapy on hemostasis and some procoagulant gene expression in mice. 42 mice were randomly divided into two groups of non-orchiectomized (non-ORX) and orchiectomized (ORX) with three subgroups (n = 7) each, were subcutaneously administered with sesame oil (control), 2 and 20 mg/kg/week testosterone enanthate. Orchiectomized mice were allowed to recover for one week before treatment. On the 7th week of treatment, blood samples were collected for coagulation parameters analysis and measurement of plasma testosterone levels. Moreover, quantitative real-time PCR analysis was performed on liver samples to assess the expression of factor IX, factor X, and prothrombin genes. The results showed that supraphysiological doses (20 mg/kg) of testosterone significantly increased plasma testosterone levels in all groups, while physiological doses (2 mg/kg) only increased testosterone levels in non-ORX animals. Although testosterone administration had no effect on prothrombin time (PT) and activated partial thromboplastin time (aPTT), supraphysiological doses reduced bleeding time and clotting time. Furthermore, platelet count increased in a dose-dependent manner with testosterone enanthate treatment. The expression of coagulation factors was also decreased with supraphysiological doses of testosterone. In conclusion, testosterone had significant effects on primary hemostasis and common coagulation pathway, including increased platelet number and aggregation, decreased clotting time, and altered gene expression of coagulation factors.

Association of serum testosterone levels with left atrial size, function, and risk of atrial fibrillation in adult men: observational and mendelian randomization analyses

Abstract Background Numerous studies have investigated the association between serum testosterone levels, testosterone replacement therapy (TRT), and cardiovascular risk. However, research examining the relationship between testosterone levels and atrial fibrillation (AF) risk remains limited. We comprehensively analyzed the association between total testosterone (TT) levels, intermediary phenotypes such as left atrium (LA) size and function, and the risk of AF in middle-aged and older men. Methods We utilized data from the UK Biobank, a population-based prospective cohort, focusing on 179,988 White men who had complete serum TT level data and no AF history. Observational associations between TT levels and LA imaging traits, as well as AF risk, were estimated using multivariable regression and time-dependent Cox regression models, treating TT levels as a time-varying variable. Genetic associations were examined by Mendelian randomization (MR), using both UK Biobank and external large consortia genome-wide association study data. Results During the median follow-up of 11.8 years (IQR 10.9–12.5), we observed 13,847 incident AF cases (7.7%). Participants with normal TT levels (≥ 300 ng/dL) showed a 15% reduced risk of AF (HR of 0.85 [95% CI, 0.82–0.89]) compared to those with low TT (&amp;lt; 300 ng/dL). Interestingly, participants undergoing TRT experienced a 51% higher risk of AF (1.51 [1.09–2.07]). Furthermore, each 1-standard deviation increase in TT levels was associated with a reduced AF risk (OR of 0.91 [0.89–0.93]) and an improved LA emptying fraction (1.29 [1.06–1.58]). Applying age-specific cutoff values for low TT levels highlighted a more pronounced AF risk reduction in participants with normal TT. MR analyses supported these observations, suggesting potential causal relationships between TT levels and both LA function and AF risk. Conclusions Our findings suggest that low TT levels are associated with reduced LA function and increased risk of AF, both observationally and genetically, indicating that serum TT could serve as a surrogate marker or even a potential causal mediator in the development of AF.Abstract tableAbstract figure

Effect of 5β-dihydrotestosterone on vasodilator function and on cell proliferation.

Aging is one of the main factors associated with cardiovascular diseases. Androgens exert beneficial effects on the cardiovascular system and testosterone (TES) replacement therapy improves cardiometabolic risk factors. However, TES is contraindicated in patients with prostate cancer due to its proliferative effects on prostatic tumor cells. Additionally, TES and its reduced metabolites 5α- and 5β-dihydrotestosterone (5α-DHT and 5β-DHT) exert vasodilatory effects. Since androgen levels decrease during aging and 5β-DHT lacks genomic effects, this study is focused on analyzing its effect on vasodilator function and the proliferation rate of prostatic tumor and vascular smooth muscle cells. To study the vascular function, mesenteric arteries from aged-orchidectomized Sprague-Dawley rats were used. Mesenteric segments were divided into one control (without treatment) and three groups with the androgens (10 nM, 30 min) to analyze: acetylcholine- and sodium nitroprusside-induced responses and nitric oxide and superoxide anion production. To analyze cell proliferation, the effect of androgens on cell viability was determined. The results showed that 5β-DHT improves vasodilator function in arteries from aged-orchidectomized rats and induces antioxidant action, while the proliferation rate of the androgen-dependent prostatic tumor cells remains unaltered. These results make 5β-DHT a promising therapeutic agent for the treatment of cardiovascular pathologies.

Evaluation of Treatment Results for Male Hypogonadism in Patients with Varicocele and Without Varicocele in Can Tho City

&amp;lt;i&amp;gt;Introduction&amp;lt;/i&amp;gt;: male hypogonadism is defined by the European Association of Urology 2022 as being associated with reduced testicular function, reduced androgen production, and/or impaired sperm production. Male hypogonadism has many causes and accompanying diseases such as diabetes, varicocele, etc. Male hypogonadism hadsymptoms of varicocele and had two treatment options: testosterone replacement therapy or surgical treatment of varicocele. Each method has different advantages and disadvantages, so we research to evaluate each treatment method’s results. &amp;lt;i&amp;gt;Objectives: &amp;lt;/i&amp;gt;Evaluate the results of male hypogonadism treatment of testosterone replacement therapy or varicocele surgery. &amp;lt;i&amp;gt;Material and methods: &amp;lt;/i&amp;gt;conducted a cross-sectional descriptive study in 111 men with symptoms of hypogonadism from January 2022 to the end of 2023. &amp;lt;i&amp;gt;Result: &amp;lt;/i&amp;gt;The average age was 65.2 ± 2.4 years. The Androgen Deficiency in Aging Males (ADAM) questionnaire has the highest rate of 90.99% showing symptoms of decreased erection strength. Hypogonadism is associated with body mass index and diabetes. After treatment, the hypogonadism group with grade III varicocele had the lowest response to treatment. After treatment, total testosterone in blood levels in all treatments increased (p&amp;lt;0.001). &amp;lt;i&amp;gt;Conclusion: &amp;lt;/i&amp;gt;Testosterone replacement therapy for hypogonadism without varicocele is the gold standard, and microsurgical treatment for hypogonadism with varicocele is the most effective.

The Promise and Challenges of Oral Testosterone Therapy

In recent years, the landscape of testosterone replacement therapy (TRT) has evolved significantly, offering new hope for hypogonadal men seeking effective and convenient treatment options. The introduction of oral testosterone undecanoate (TU) marks a pivotal advancement in this field, as highlighted in the comprehensive review by Dr. Julian Borges. This editorial aims to explore the implications of these findings and the future of oral TRT in clinical practice.

Comment on: Low serum testosterone is associated with an increased risk of first-time renal calculi in men without testosterone replacement therapy.

Comment on: Low serum testosterone is associated with an increased risk of first-time renal calculi in men without testosterone replacement therapy.

Gender identity in Klinefelter Syndrome: a patient-centered approach to treatment

Introduction There is increasing evidence that gender dysphoria (GD) is more prevalent in the Klinefelter Syndrome (KS) population than in males in the general population; however, the exact incidence is uncertain. The aim of this study was to further explore the prevalence of gender-related issues, the role that physical characteristics play in gender identity, and the issues surrounding Hormone Replacement Therapy (HRT) in KS. Methods As part of a registered Quality Improvement Project (QIP), one online 23-point questionnaire on KS patient attitudes toward gender identity was shared with members of the Klinefelter Syndrome Association (KSA). In total, 139 anonymous responses were collected between December 2021 and January 2023. The questionnaire was developed with the guidance of multiple clinicians (including gender psychiatrists, urologists, psychosexual medicine specialists, and endocrinologists) and patient Delphi rounds. Data was reviewed and analyzed by 4 independent researchers within the QIP team. Results Only 53% of KS patients responding to this survey fully identified as male and 19% stated that they did not enjoy living as the sex on their birth certificate, with 43% considering changing aspects of their physical appearance to better match their gender. Regarding HRT, 67% of respondents were receiving Testosterone Replacement Therapy (TRT). 63% wanted TRT and 17% wanted estrogen, including 6% of TRT users who would prefer estrogen instead. 36% that were currently receiving TRT did not identify as male, and 3 participants stated that they have GD. Conclusion These results indicate that a significant proportion of KS patients do not fully identify with the male gender and are unhappy living as the sex on their birth certificate. Although TRT worked for most, its use should be discussed carefully with those with gender identity concerns.