Treatment Of Hypogonadism Research Articles

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

<i>Introduction</i>: 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. <i>Objectives: </i>Evaluate the results of male hypogonadism treatment of testosterone replacement therapy or varicocele surgery. <i>Material and methods: </i>conducted a cross-sectional descriptive study in 111 men with symptoms of hypogonadism from January 2022 to the end of 2023. <i>Result: </i>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<0.001). <i>Conclusion: </i>Testosterone replacement therapy for hypogonadism without varicocele is the gold standard, and microsurgical treatment for hypogonadism with varicocele is the most effective.

Experience in the treatment of patients with androgenic deficiency and comorbidity pathology

Background. Age-related involution of the male reproductive system, known as testosterone deficiency syndrome, andropause, androgen deficiency in the aging male, or partial androgen deficiency in the aging male, causes clinical manifestations that impair quality of life and increase the risk of mortality, especially from cardiovascular disease. In Russia, the problem of hypodiagnosis of androgen deficiency remains up-to-date, with a low frequency of prescription of replacement therapy. Aim. At assessing the effectiveness of testosterone in the rehabilitation of patients with hypogonadism and cardiovascular pathology. Materials and methods. It involved 36 men aged 25–75 years with various cardiological pathologies. Results. As a result of the study, testosterone as a form of a transdermal gel is effective at doses of 50 mg/day. Three-month use of testosterone gel increases the level of testosterone to 2.9 nmol/l (p0.05). Conclusion. Thus, testosterone may play a key role in the treatment of hypogonadism and related cardiovascular diseases, although its safety and feasibility remain a matter of debate.

EP354 - Acute pancreatitis – an unusual cause

Abstract Introduction Drugs are responsible for only 0.1%-2% of acute pancreatitis. Whilst the link between some drugs and pancreatitis is well-established, (steroids, azathioprine), we found only one previous case-report linking testosterone replacement therapy (TRT) to pancreatitis. We report a case of acute pancreatitis secondary to TRT. Case Report A 55-year-old man presented with history of upper abdominal pain. He denied alcohol/illicit drug use, no recent infection/changes to medication. His amylase was raised; CT scan confirmed acute pancreatitis. When interrogating his past medical history for a cause, we learned of his bilateral orchidectomy, radiotherapy and chemotherapy for seminoma in 1993, following which, he was on Testogel. He was managed conservatively, with success. Discussion Although drug-related causes of pancreatitis are uncommon, management is easy with identification/cessation of the causative agent. Therefore, a detailed medical history (including exposure to toxins and medication changes) is important. In our patient, an extensive surgical, medical and social history, CT and bloods excluded other main causes of acute pancreatitis i.e. alcohol, gallstones/infection, hypertriglyceridemia, toxins and trauma. The WHO database of “drugs suspected to cause pancreatitis” includes evidence from published literature, mostly case reports. Testosterone does not feature amongst the 525 drugs mentioned. Conclusion Our anecdotal evidence may provide a possible link between TRT and pancreatitis, however further research is needed to ascertain a definite causality. Reporting such potential links is important due to increased TRT use recently as treatment for female-to-male sex transition and young adults for performance enhancement, as well as remaining the primary treatment for hypogonadism.

Testosterone supplementation and stroke in young adults: a review of the literature.

Testosterone supplementation has increased in recent years for both treatment of hypogonadism and recreational use. Strokes in young adults have similarly increased with a larger proportion of patients in this age group having a stroke due to early onset of cardiovascular risk factors or unrelated to conventional risks. Hormonal treatments are associated with increased stroke risk amongst women, with some studies indicating an increase in stroke risk as high as 40% when compared to non-users. However, less is known about male sex hormones and risks associated with increased stroke. Limited data evaluates the relationship between testosterone supplementation and stroke in young adults. In this review, we analyze the literature and plausible underlying pathophysiological mechanisms associated with increased risks in patients using exogenous testosterone. Furthermore, we highlight the gaps in research about safety and long-term effects on young patients.

Effect of selective androgen receptor modulator RAD140 on prostate and testosterone levels in Wistar strain rats with bilateral orchidectomy

BACKGROUND Selective androgen receptor modulators (SARMs) have been investigated as a potential treatment for hypogonadism, a condition characterized by low testosterone levels in men. The idea is to provide therapeutic benefits similar to traditional testosterone replacement therapy. However, research in this area is still in its early stages, and more extensive studies are needed to establish the efficacy of SARM. This study aimed to determine the impact of SARM RAD140 on testosterone levels, fibromuscular stroma, and prostate mass in rats undergoing bilateral orchidectomy. METHODS This was an in vivo study using posttest-only control group design in rats (Rattus norvegicus). The positive and negative control groups consisted of rats with and without bilateral orchidectomy, respectively. The treatment groups were rats given SARM RAD140 with and without orchidectomy. Testosterone levels, histopathology, and prostate mass were examined at the end of week 6, and the quantitative data were analyzed using one-way ANOVA. RESULTS This study found no difference in prostate mass (0.598 [0.05] g versus 0.590 [0.07] g, p = 0.984), fibromuscular stroma ratio (0.483 [0.094] versus 0.463 [0.057], p = 0.984), and testosterone level (0.006 [0.005] ng/dl versus 0.014 [0.004] ng/dl, p = 0.098) compared to positive control with orchidectomy and SARM RAD140 administration 6 weeks after treatment. CONCLUSIONS There were no differences in testosterone levels, prostate mass, or the ratio of fibromuscular stroma to epithelium area in rats undergoing bilateral orchidectomy and placebo surgery with the administration of SARM RAD140.

P-063 Effect of varicocelectomy on serum testosterone levels of hypogonadal men above 40 years of age

Abstract Study question Can varicocelectomy be indicated for the treatment of hypogonadism in men above 40 years of age? Summary answer Varicocelectomy improves serum testosterone (T) levels in men with preoperative hypogonadism. This improvement can be anticipated in men above the age of 40 years. What is known already Varicocele ligation is a common intervention used to restore male fertility potential and enhance conception rates. Few studies reported a favorable effect for varicocelectomy on serum T levels stirring some scientists to indicate treatment for men with late onset hypogonadism. Nonetheless, data is still scarce for such a recommendation highlighting the importance of this work Study design, size, duration The charts of 1696 patients who underwent microsurgical subinguinal varicocelectomy for clinically palpable disease between 2011-2023 were retrospectively reviewed. Patients with available pre- and post-operative serum hormone levels were included in the study while those receiving any form of androgen replacement or induction treatment or with known secondary causes of hypogonadism were excluded. Participants/materials, setting, methods Medical charts were reviewed to collect demographic and clinical data. Patients were classified into 2 groups according to preoperative T levels: hypogonadism group (serum T < 10.4 nmol/L) (n = 226) and eugonadal group (serum T ≥ 10.4 nmol/L) (n = 1469). The hypogonadism group was subclassified according to age into less (n = 161) or ≥ (n=66) 40 years of age. Changes in hormone levels were analyzed using Wilcoxon Signed Ranked. A p value <0.05 was considered significant. Main results and the role of chance The patients mean age was 33.6 ± 8.5 years. Their mean BMI was 27.2 ± 5.8 Kg/m2, mean left testis size was 13.4 ± 3.5 cm3 and right testis size 14.4 ± 4.5 cm3. The maximum left and right vein diameters was 3.9 ± 1.3 mm and 2.46 ± 0.73 mm. Unilateral and bilateral microsurgical varicocelectomy were performed in 82% and 18% of cases, respectively. Post-operatively, no significant changes were observed in hormone levels in comparison to preoperative values in the eugonadal group. However, patients with preoperative hypogonadism had significant increase in serum T (7.7±2.2 vs 11.7±6.6, p < 0.001) and E2 (72.5±31.3 vs 94.8±42, p < 0.001) levels following the intervention. These significant improvements were observed in both men < 40 years of age (p < 0.001 for both T and E2) and ≥ 40 years of age (T: p = 0.027, E2: p = 0.024). Limitations, reasons for caution Results were obtained from a retrospective chart review. The majority of these patients performed surgery for fertility reasons and data regarding hypogonadism symptoms is lacking. Wider implications of the findings Results of this study further confirm that an increase in serum testosterone is likely to be anticipated in patients undergoing varicocelectomy who have low serum testosterone levels pre-operatively Trial registration number not applicable

Diagnosis and treatment of hypogonadism in men seeking to preserve fertility - what are the options?

Male hypogonadism is a clinical syndrome that results in low testosterone levels and frequently leads to infertility. The syndrome occurs due to disruption at one or more levels of the hypothalamic-pituitary-gonadal axis. Testosterone replacement therapy (TRT) is the most common treatment utilised for male hypogonadism. However, long-acting forms of TRT leads to infertility and so is inappropriate for patients wishing to conceive. For patients who wish to remain fertile, nasal TRT, clomiphene citrate, exogenous gonadotropins, gonadotropin releasing hormone and aromatase inhibitors have been used as alternative treatment options with different degrees of success. A review of the literature was performed to identify the safety and efficacy of alternative treatment options. Gonadotropin releasing hormone can successfully induce spermatogenesis but is impractical to administer. Likewise, aromatase inhibitors have limited use due to inducing osteopenia. Nasal TRT may be a good treatment option for these patients, but its efficacy has so far only been demonstrated in small sample sizes. However, clomiphene citrate and exogenous gonadotropins are safe, offer good symptom control and can successfully induce fertility in hypogonadism patients.

(381) Infertility, Erectile Dysfunction, and Hypogonadism Medications in the NFL: A Comprehensive Analysis of the Substance Abuse Policy, Violation Penalties, and Therapeutic Use Exemptions

Abstract Introduction The National Football League (NFL) faces countless challenges in maintaining a fair and competitive playing field while protecting player health. One aspect of concern involves the use of medications to treat infertility, erectile dysfunction (ED), and hypogonadism, which can potentially alter and enhance athletic performance. The NFL's Substance Abuse Policy governs the use of such medications and imposes strict penalties for violations. Several important players have been affected by these rules while attempting treatment for legitimate medical conditions. This project explored the presence of infertility, ED, and hypogonadism treatments among NFL players, assessed the penalties for their misuse, and analyzed the process for obtaining Therapeutic Use Exemptions (TUEs). Objective To provide in-depth analysis of the NFL's Substance Abuse Policy involving medications for infertility, ED, and hypogonadism treatment. Specifically, we evaluated the presence of specific medications in question as compared with the guidelines established by the World Anti-Doping Agency (WADA), examined the penalties associated with misuse, and investigated the procedures for obtaining TUEs. Methods We obtained a copy and conducted a thorough analysis of NFL’s Substance Abuse Policy, focusing on the presence of commonly prescribed medications to treat infertility, ED, and hypogonadism. This was compared to existing WADA guidelines. We then evaluated specific testing procedures and penalties associated with their use. We finally analyzed and delineated the methodology for obtaining a TUE. Results Our analysis of the Substance Abuse Policy revealed 97 prohibited substances encompassing Anabolic/Androgenic Steroids, Protein and Peptide Hormones, Anabolic Agents including Beta-2 Agonists, Anti-Estrogenic Agents, Selective Androgen Receptor Modulators (SARMs). This list was found to be 98% consistent with existing WADA guidelines. Erectile Dysfunction medications were allowed, specifically Viagra, Cialis, and Levitra. Penalties for violating League Policy ranged from fines (calculated using player-specific salary), suspension, bonus forfeiture, and banishment. Regarding TUEs, specifically for hypogonadism, the application process proved to be complex, requiring substantial medical documentation, laboratory testing including FSH, LH, and semen analysis, and expert review. Obtaining a TUE additionally required annual renewal as well as regular serum testing and medical visits. Conclusions The use of medications treating infertility and hypogonadism among NFL players is a valid medical concern. While potential for abuse exists, many players qualify for treatment based on current medical guidelines. The Substance Abuse Policy was comprehensive, including all major infertility and hypogonadism medications while allowing use of common ED medications. Penalties for violations were strict but accompanied by associated review and appeal processes. The TUE system, while complex and time-intensive, provided pathways for players with genuine medical needs to access necessary treatments while maintaining organizational oversight. This study showed the delicate balance maintained by a multi-billion-dollar industry in promoting fair play while simultaneously allowing players to obtain legitimate medical treatments. Further research and collaboration between medical professionals, players, and league officials is needed to further refine this process for future generations. Disclosure No.

Management of Male Fertility in Hypogonadal Patients on Testosterone Replacement Therapy.

Testosterone is crucial in regulating several body functions in men, including metabolic, sexual, and cardiovascular functions, bone and muscle mass, and mental health. Therefore, optimizing testosterone levels in men is an important step to maintaining a healthy body and mind, especially as we age. However, traditional testosterone replacement therapy has been shown to lead to male infertility, caused by negative feedback in the hypothalamic-pituitary-gonadal (HPG) axis. Recent advances in research have led to the discovery of many new methods of administration, which can have more or less suppressive effects on the HPG axis. Also, the usage of ancillary medications instead of or after testosterone administration might help maintain fertility in hypogonadal patients. The goal of this narrative review is to summarize the newest methods for optimizing fertility parameters in patients undergoing treatment for hypogonadism and to provide the necessary information for healthcare providers to make the right treatment choices.

Association between testosterone levels and RigiScan parameters of patients with erectile dysfunction.

It is difficult to diagnose hypogonadism because of the lack of objective assessments of erectile dysfunction (ED), which is caused by hypogonadism. To provide a new approach for diagnosing hypogonadism, this study evaluated the efficacy of nocturnal penile tumescence and rigidity (NPTR) testing with RigiScan for patients with ED with and without hypogonadism. From June 2021 to February 2023, 133 patients with ED (62 with hypogonadism and 71 without) underwent NPTR testing at the Department of Andrology. A detailed history of all participants was obtained. All participants also underwent a physical examination, sex hormone testing, and ultrasound examination of the cavernous vessels of the penis. Patient characteristics, sex hormone serum levels, and RigiScan Plus data of NPTR testing of patients with ED were obtained and evaluated. Between the groups, there were no significant differences in age, body mass index, or erectile function score or in the prevalence of smoking, drinking, diabetes, hypertension, and hyperlipidemia. RigiScan data revealed differences in erection episodes per night, average event rigidity, erection durations, and percentage of tumescence greater than baseline, which were significantly lower in the testosterone-deficient group than in the normal testosterone group. The average event rigidity of the tip displayed the largest area under the curve value, with a sensitivity of 67.6%, a specificity of 85.5%, and a cutoff value of 52.50. Our findings may allow appropriate patients to receive testosterone replacement therapy, which has been shown to be an effective treatment for hypogonadism. This is the first study of its kind to perform a comprehensive review of the association between hypogonadism and RigiScan parameters. This study was limited by its small sample size. RigiScan parameters of patients with ED and testosterone deficiency were significantly lower than those of patients with normal testosterone; therefore, RigiScan is useful for the differential diagnosis of patients with ED caused by hypogonadism.

Trazodone associated with Clomiphene a proposal treatment for post finasteride syndrome

Erectile dysfunction caused by medications are probably caused by the disconnection of synaptic circuits responsible for linking libido to erection. For instance, it is well known that sexual dysfunction may occur in patients treated with finasteride, an inhibitor of the enzyme 5alpha-reductase, prescribed for androgenetic alopecia and benign prostatic hyperplasia. Interestingly, sexual dysfunction persists after drug discontinuation. Clomiphene citrate is a selective estrogen receptor modulator that has been used for the treatment of hypogonadism in men. It acts centrally to increase secretion of luteinizing hormone. Trazodone is a multifunctional drug with hypnotic actions at low doses due to blockade of 5-HT2A receptors, as well as H1 histamine receptors and α1 adrenergic receptors, therefore this drug can cause severe priapism and in many cases causing penile necrosis or permanent loss of erectile function. Therefore, we propose that trazodone and clomiphene can restore libido synaptic circuits, thus these associated drugs can be a treatment for post-finasteride syndrome.

Impact of testosterone levels and testosterone replacement ther-apy on men’s health

Various studies have shown that testosterone levels heavily impact many areas of a man’s health. Low serum testosterone (and, by analogy, late onset hypogonadism) may be responsible for such conditions as type 2 diabetes, obesity in abdominal area, and most of all, heightened cardiovascular risk (CV). Among other outcomes researchers have pointed out metabolic syndrome and dyslipidemia, as well as increased risk of anxiety disorders and major depressive disorder. There have also been reports of testosterone’s influence on fertility, bone mineral density and the development of polycythemia. All of these effects can be linked to the increased levels of inflammatory markers caused by low testosterone and lead to higher risk of premature death. Overly high testosterone, however, has been proven to have a notable influence on men’s personality, as well as other psychological and social traits, both in endogenously elevated testosterone level, and in patients with history of anabolic- androgenic steroid use. The last decade’s research of testosterone’s impact on the organism has brought contradictory results. Therefore, examination and understanding of the influence of its abnormal levels proves important to not only guarantee the best quality of hypogonadism treatment, but also to efficiently prevent any side effects or complications associated with testosterone use.

Male-specific consequences of obesity - functional hypogonadism and fertility disorders.

Obesity is currently one of the most serious public health problems which affects up to 30-40% of the population, and its prevalence is higher in men than in women. Complications of obesity include atherosclerosis, cardiovascular diseases, and type 2 diabetes mellitus, but it also has a negative impact on the hormonal system and fertility. The hormonal consequences of excess body fat in men are functional hypogonadism, which not only causes clinical symptoms of testosterone deficiency, but is also a risk factor for obesity (a vicious circle mechanism). Reduced fertility in obese men may be a consequence of functional hypogonadotropic hypogonadism (decreased gonadotropins and testosterone secretion, reduced libido, and erectile dysfunction), but other mechanisms associated with excess adipose tissue, like hyperinsulinaemia, hyperleptinaemia, chronic inflammation, and oxidative stress also play an important role. Therefore, in obese men deterioration of semen parameters (sperm concentration, motility, and morphology) and reduced fertility are observed, also concerning the effectiveness of assisted reproductive techniques. Reducing the mass of adipose tissue causes an increase in testosterone concentrations and has a beneficial effect on semen parameters. Functional hypogonadism in obese men should be diagnosed only after exclusion of organic causes of hypogonadism. Lifestyle changes, including physical exercise and low-caloric diet, and optimization of comorbidities, are still first line of treatment. In some patients, if such treatment is ineffective, pharmacotherapy or bariatric surgery may be considered. Testosterone replacement therapy is contraindicated in obese men with functional hypogonadism, especially in those who desire fertility. Selective oestrogen receptor modulators and aromatase inhibitors improve sperm quality but are not recommended for the treatment of hypogonadism in obese men. GLP-1 analogues appear to be effective and safe in the treatment of low testosterone and infertility in obese men and may be the main method of pharmacotherapy in the future.

A-056 Data Driven Approach to Ensure Accurate Total Testosterone Results in Consumer Initiated, Home-collected Capillary Samples

Abstract Background Home-collected direct access testing (DAT) has become increasingly attractive as telehealth utilization advances. With DAT, consumers initiate their lab order and have access to clinical consulting staff. Steroid hormone concentrations are uniquely positioned for DAT due to their inherent stability and non-acute indications. Total testosterone (TT) is used to screen for or monitor treatment of hypogonadism. Once diagnosed, testosterone is administered by intramuscular or subcutaneous injection or via transdermal patch or topical gel. TT in adult men is typically between 200 and 900 ng/dL. However, in our DAT lab we were encountering a significant percentage of samples with supraphysiological TT concentrations (>1500 ng/dL). The objective of this study was to design a quality assurance workflow to differentiate whether the supraphysiological results were accurate or erroneous. Methods TT was measured using the Roche Cobas e801 immunoassay; basic assay parameters were verified per general CAP guidelines (precision, accuracy, linearity, method comparison, interferences, carryover, dilution). Additional validation experiments were performed to verify that capillary plasma was an acceptable sample type (n = 30 paired capillary/venous samples) and to determine if extreme summer temperature fluctuations would influence stability (n = 46 participants; samples subjected to temperature cycling for 72 h before re-evaluation). Self-collected capillary samples received for clinical testing with a TT concentration >1500 ng/dL were run on a 1:5 dilution (extending the clinical reportable range to 7500 ng/dL) and the sample was reflexed to luteinizing hormone (LH) and follicle stimulating hormone (FSH). Reference intervals in adult men for LH and FSH are 1.7–8.6 mIU/mL and 1.4–13.0 mIU/mL, respectively. When available, clinical notes were reviewed for additional information on exogenous hormone usage. Results All general assay parameters were within acceptable metrics. TT concentrations between capillary and venous samples had an average absolute bias of −9.2 ng/dL or −3.8% (n = 30; range = <20–823 ng/dL; y = 0.954x + 1.915; R = 0.995). Baseline and post-summer temperature cycling TT concentrations had an average absolute bias of −8.1ng/dL or −3.4% (n = 46; range = <20–716 ng/dL; y = 0.934x + 7.728; R = 0.999). Samples (n = 506) with a TT concentration >1500 ng/dL were reflexed to TT dilution and LH/FSH. Most (n = 413; 82%) had undetectable (<0.3 mIU/mL) LH/FSH and a mean TT concentration of 3356 ng/dL (SD = 1972). For 18.6% (n = 77) of this subset, we had medication information; 68 were using injectable testosterone. Elevated TT was likely a true result caused by overuse of anabolic steroids. A smaller subset of samples (n = 21) had detectable LH/FSH with mean concentration/SD of 6.1/5.2 mIU/mL for LH, 5.3/5.4 mIU/mL for FSH, and TT >7500 ng/dL. Medication notes were available for 5 of these samples and indicated that the TT results were likely caused by topical contamination (false positive). A final subset (n = 40) had detectable LH/FSH and TT between 1500 and 7500 ng/dL. These samples could not be binned into simple categories and instead were sent to the lab director for review. Conclusion Self-collected capillary specimens are acceptable for TT measurements. A quality assurance reflex to LH/FSH can support or refute the validity of supraphysiological results in a consumer initiated/DAT population.

Contemporary treatment options for male hypogonadism

Introduction
 Male hypogonadism is a disease in which testicular function is impaired. Its symptoms are due to testosterone deficiency and most of them show low specificity. These include reduced libido, erectile dysfunction and mood disorders, among others. The biochemical indicator of hypogonadism is a testosterone concentration below 350 ng/ml (12nmol/L), according to the European Association of Urology (EAU). The increased incidence of hypogonadism is associated with aging and the presence of comorbidities such as type II diabetes and obesity. Men with testosterone deficiency have an increased risk of cardiovascular disease and premature death.
 Goals
 Summary of current reports on the diagnosis and treatment of hypogonadism. An overview of the advantages and disadvantages of the different types of formulations used in testosterone replacement therapy.
 MethodsReview of literature available in PubMed and Google Scholar databases.
 Conclusions
 The medical interview, physical examination and ancillary tests help to classify hypogonadism appropriately. Measuring the concentration of gonadotropins, helps diversify primary from secondary hypogonadism. Testosterone replacement therapy (TRT) uses formulations that have varying release profiles, route of administration and drug formulation. The choice of testosterone product should involve age, lifestyle, and individual preferences of the patient.

(524) Adolescent Varicocelectomy: Long-term Follow-up of Clinical Outcomes and Patient Satisfaction

Abstract Introduction Worldwide 10–15% of male adolescents have a varicocele, which is the most common surgically correctable cause of male subfertility. In young adult men, varicocele can be associated with smaller testis volume and abnormal semen parameters. However, there is still controversy in whether surgical repair has better long-term outcomes than just active surveillance. Objective To evaluate satisfaction, symptoms improvement, hypogonadism, and paternity in patients who underwent varicocelectomy when they were adolescents. Methods We performed a retrospective chart review of adolescents undergoing varicocelectomy from 2011-2021. Inclusion criteria were having primary varicocele, having 12-21 years at time of surgery, having had the varicocelectomy >1-year ago, ≥1 postoperative visits, and having answered the questionnaire. Exclusion criteria were having a diagnosis of secondary varicocele (renal malignancy or venous abnormality) and incomplete records. Data about clinical, surgical, and postoperative outcomes were gathered. Patients were contacted by phone and were asked about orchialgia, paternity, varicocele recurrence, diagnosis and treatment for hypogonadism, and satisfaction after surgery. Descriptive analysis and paired t-test were used, statistical significance was assessed at p<0.05. Results From a total of 50 patients meeting the inclusion criteria, we were able to contact 23 patients. The mean age at varicocele diagnosis was 17.43±2.52 years. Varicocele was grade 3 in 16 (69.6%) patients and left-sided in 17 (73.9%) patients. Eight (34.8%) patients had a preoperative testicular ultrasound, that in 2(25%) patients showed testicular volume discrepancy >20%. At the physical exam, 6(26.1%) patients were found to have asymmetric testicles. Overall, 2(8.7%) patients had a previous varicocele repair and 7(30.4%) had a preoperative abnormal semen analysis. Mean age at surgery was 18.78±2.02 years. Microscopic varicocelectomy was performed in 22 (95.7%) patients, mainly in the left-side (78.3%). Pre- and postoperative FSH and T levels were done in 10 patients, without any significant difference after surgery (p=0.074 and p=0.069, respectively). Pre- and postoperative semen analysis were performed in 12 patients and showed a significant improvement in motility after varicocelectomy (p=0.022). Mean follow-up after surgery was 1.42±1.40 months. The questionnaire was performed in a mean of 3.43±2.55 months after varicocelectomy and the mean age of the responders was 22.3±3.11 years. Orchialgia persisted in 7 patients (30.4%), predominately in the left side (71.4%). None of the patients had been diagnosed with varicocele recurrence nor had required a surgical reintervention. Twenty-one (86.9%) patients were not actively trying to achieve a natural conception nor had been involved in a pregnancy after varicocelectomy. Two patients (8.7%), with a preoperative abnormal semen analysis, were able to conceive. None of the patients referred to have hypogonadism nor being under testosterone therapy. The majority of patients (86.9%) referred to be satisfied with the postoperative results. Conclusions Our results suggested that long-term outcomes of varicocelectomy in adolescents would show high patient satisfaction, low rate of recurrence, no association with hypogonadism, and a significant persistence of testicular pain. Although male fertility after varicocelectomy demonstrated promising results, a longer follow-up assessment should be done when patients are actively trying to conceive, to have a more representative sample size. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus, Boston Scientific, Endo Pharmaceuticals and Coloplast

(070) Testosterone Therapy in Men with Klinefelter Syndrome: Analysis of a Global Federated Research Network

Abstract Introduction Klinefelter syndrome (KS) is a genetic condition in which a male is born with an extra X-chromosome and is one of the on-label indications for testosterone replacement therapy (TRT). The prevalence of testosterone deficiency in men with KS is difficult to predict and not well described in the literature. Furthermore, there is no previous literature detailing the rates of TRT prescription in men diagnosed with KS. Objective We aimed to determine the rates of hypogonadism and prescription of TRT in men with KS using a large, federated research database. We hypothesized that men with KS are undertreated for testosterone deficiency with TRT due to a combination of factors including a poor understanding of hypogonadism in this population and neurocognitive issues leading to delay in seeking treatment for hypogonadism. Methods We queried TriNetX, a large, multicenter electronic health record database, to identify all men with a diagnosis of Klinefelter syndrome (ICD-10-CM Q98.4) excluding men with prescription of TRT prior to diagnosis of KS or a diagnosis of KS more than 20 years ago. Descriptive analysis on associated comorbidities and demographic characteristics was performed. We then filtered the initial cohort to find men who received a laboratory measurement of testosterone level on the day of diagnosis with KS or later. Prevalence of testosterone deficiency was determined as defined by testosterone level < 300 ng/dl. The primary outcome of the study was prescription of any of the following forms of TRT on the day of diagnosis or later using associated medication codes: testosterone, testosterone 17-phenylpropionate, testosterone enanthate, testosterone cypionate, testosterone undecanoate. Rates of TRT prescription were determined for both the initial cohort and the hypogonadal subgroup. Results There were 5,437 total men with diagnosis of KS. A total of 1,581 men with KS received laboratory measurement of testosterone level, 1,113 (70.4%) of whom were hypogonadal. Mean testosterone level in this group was 354 ng/dL [50 – 658]. Of the 1,113 men found to be hypogonadal, only 657 (59.0%) men were given prescription for TRT. Conclusions This is the first study to evaluate TRT prescribing habits in men with KS. In this large, retrospective study, TRT was under-prescribed in men with KS. Further studies are needed to corroborate these findings and to evaluate the barriers to receiving care in this population. Disclosure No

(073) The Effects of Intranasal Testosterone (Natesto™) for Treatment of Hypogonadism on Maintenance of Spermatogenesis: Demographic Data from a Single-Institution, Prospective, Non-blinded Study

Abstract Introduction Testosterone therapy (TTh) is becoming increasingly common among men of reproductive age in the United States. An estimated 3 million men are on TTh; however, exogenous testosterone use can disrupt the hypothalamic-pituitary-gonadal axis, leading to reduced spermatogenesis and infertility. The spontaneous recovery of spermatogenesis after cessation of TTh is possible, but may take months to years and can lead the patient to experience hypogonadal symptoms. Recent preliminary results have suggested that a 4.5% intranasal testosterone gel (Natesto™) may offer the potential to offset these symptoms and re-establish eugonadal levels of circulating testosterone. It has also been shown that men on Natesto™ maintain follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels and total motile sperm count within the normal range. This prospective, non-blinded study seeks to confirm the role of Natesto™ to alleviate hypogonadal symptoms in men on gonadotropin therapy for restoration of spermatogenesis. Objective To determine if Natesto™ can alleviate hypogonadal symptoms while preserving the recovery of spermatogenesis. The primary objective of this study is to examine changes in total motile sperm count at baseline, 14 weeks, and 26 weeks. Secondary outcomes include changes in LH, FSH, testosterone, estrogen, and quality of life measurements at these time intervals. Methods IRB approval was obtained for this study. Male patients between 18 and 64 years of age with a diagnosis of testosterone-induced hypo-spermatogenesis were recruited from a tertiary referral male infertility clinic between December 2021 and June 2022. Patients ceased intramuscular testosterone therapy and initiated gonadotropin therapy with FSH 75IU and hCG 3000IU every other day as well as 4.5% testosterone gel (Natesto™) three times daily. Patients were evaluated at baseline, 14 weeks, and 26 weeks. Clinic visits consisted of a hormone profile with total testosterone, estradiol, FSH, LH, questionnaires (IIEF, SF36, and ADAM) as well as a semen analysis. Results A total of 9 patients who met inclusion criteria were identified and elected to take part in the study. Four of the patients obtained baseline intake questionnaires, bloodwork, and a semen analysis with at least 1 additional follow-up visit. Five patients are pending initial follow-up. Patient intake demographic data included a median age of 35, LH of 3.15, FSH of 3.2, testosterone 260ng/dl, IIEF 20, SF-36 energy/fatigue score of 42.5%, and ADAM of 5.5. Four patients had complete gonadotropin suppression, and 6 were azoospermic. Interval semen analyses revealed total motile sperm count increases from 17.9 to 25 million and 9.7 to 10.9 million, with 2 patients demonstrating persistent azoospermia. Mean testosterone increased by 297.5ng/dl. No patients reported adverse events. Conclusions Preliminary results are limited and suggest that men undergoing cessation of testosterone therapy for restoration of spermatogenesis have decreased sexual and overall function scores. Continuation of this study, with recruitment of a larger sample size, will provide important, novel data regarding the effect of Natesto™ therapy on the hypogonadal symptoms seen in men during TTh cessation for spermatogenesis restoration. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Endo Pharmaceuticals

(395) Our Experience with Subcutaneous Injection of Non-Proprietary Testosterone Cypionate as a Novel Approach for Hypogonadism

Abstract Introduction Subcutaneous injection of testosterone has been investigated as a method of testosterone replacement therapy (TRT) in hypogonadal men. We have been investigating the use of a non-proprietary subcutaneous (SubQ) injection of testosterone cypionate using a ½ inch 27g needle for replacement to treat hypogonadism. This is an update on our work which includes a larger sample size and longer follow up. Objective To assess the use of non-proprietary SubQ TRT as treatment in hypogonadal men and its effect on HCT, PSA, and patient satisfaction. Methods This study is a retrospective chart review of patients receiving SubQ TRT with a mean follow up length of 9.8 months (range 0-24 months). Patient data was collected prior to initiation of therapy and at subsequent visits. Testosterone, HCT, and PSA were determined through regular blood draws and a patient satisfaction survey was performed over the phone. Univariate analysis and paired t-tests were used to analyze study variables. Results 41 total patients received SubQ TRT. Mean changes in total testosterone level (increased 281.3 + 81.1, p-value=0.0008), hematocrit (increased 1.5 + 1.0), PSA (increased 0.4 + 0.4), SHIM score (increased 3.8 + 1.4, p-value=0.0088) and AUA symptom score (decreased 0.9 + 1.6) were calculated at the patients’ initial visit and most recent follow up while still on SubQ TRT (Table 1). A total of 30 patients had been on various combinations of TRT before switching to SubQ including IM (13), CC (13) Testopel (8), HCG (2) SubQ (2), T gel (1) and Anastrozole (1). Data on the most frequent TRTs is demonstrated in Table 2. Patient satisfaction surveys were completed by 32 patients (78%), with 26 (81.2%) patients reporting overall satisfaction with SubQ TRT versus 45% (9/20) with past forms of TRT. 93.7% (15/16) reported SubQ TRT was both easier and less painful, and 73.6% (14/19) preferred SubQ injections over their previous form of TRT. Reasons for stopping SubQ TRT included unrelated stroke (1), prostate cancer (1), development of scar tissue (1) or bruising (1), ineffective therapy (1), difficulty drawing up the syringe (1), cost (1), and trouble obtaining medication from the pharmacy (1). Conclusions The use of non-proprietary testosterone cypionate SubQ as treatment for hypogonadism results in an elevation in serum total testosterone and improvement on both SHIM and AUA symptom scores at follow up. PSA and HCT rose over the span of treatment, but the rises were not statistically significant, and no patient developed erythrocytosis. Our data demonstrate SubQ TRT is easier and less painful to use and scores higher on overall patient satisfaction compared to other forms of TRT. Disclosure No

MP43-06 TESTOSTERONE THERAPY IN MEN WITH KLINEFELTER SYNDROME: ANALYSIS OF A GLOBAL FEDERATED RESEARCH NETWORK

You have accessJournal of UrologyCME1 Apr 2023MP43-06 TESTOSTERONE THERAPY IN MEN WITH KLINEFELTER SYNDROME: ANALYSIS OF A GLOBAL FEDERATED RESEARCH NETWORK Katherine Campbell, Justin Loloi, Chase Carto, and Ranjith Ramasamy Katherine CampbellKatherine Campbell More articles by this author , Justin LoloiJustin Loloi More articles by this author , Chase CartoChase Carto More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003289.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Klinefelter Syndrome (KS, 47 XXY) represents the most common genetic form of male hypogonadism. Given the degree and prevalence of hypogonadism in these men, it is recommended that patients with KS and testosterone deficiency should be treated with lifelong testosterone supplementation (TRT) that begins at puberty to secure the development of sexual male characteristics and prevent long-term sequelae. Primary hypogonadism (including KS) is an on-label indication for TRT. The objective of this study was to determine the rates of hypogonadism and prescription of TRT in men with KS. We hypothesized that men with KS are under treated for testosterone deficiency with TRT because of the relationship between KS and neurocognitive impairment. METHODS: We queried TriNetX, a large, multicenter electronic health record database, to identify all men with a diagnosis of Klinefelter syndrome (ICD-10-CM Q98.4). We collected data on comorbidities including cognitive impairment, type 2 diabetes mellitus, obesity, hyperlipidemia, hypertension, osteoporosis in addition to demographic characteristics. Prevalence of testosterone deficiency was determined as defined by testosterone level <300 ng/dl. The primary outcome of the study was prescription of any of the following forms of TRT on the day of diagnosis or later. RESULTS: There were 5,437 total men with diagnosis of KS. A total of 1,581 men with KS received laboratory measurement of testosterone level, 1,113 (70.4%) of whom were hypogonadal. Mean testosterone level in this group was 354 ng/dL [50–658]. Of the 1,113 men found to be hypogonadal, only 657 (59.0%) men were given prescription for TRT. CONCLUSIONS: Despite the recent addition of KS as an indication for treatment to the FDA-approved label for TRT, in this large, retrospective study, TRT was under-prescribed in men with KS. Under treatment of hypogonadism in men with KS can lead to long-term consequences such as metabolic syndrome and cognitive impairment. This is the first study to evaluate TRT prescribing patterns in men with KS. Future research is needed to corroborate these findings and to evaluate barriers, especially as related to to receiving care in this population. Source of Funding: This work was supported by NIH Grant R01 DK130991 and Clinician Scientist Development Grant from the ACS to Ranjith Ramasamy © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e603 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Katherine Campbell More articles by this author Justin Loloi More articles by this author Chase Carto More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF downloadLoading ...