Oral Testosterone Undecanoate Research Articles

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.

Newer formulations of oral testosterone undecanoate: development and liver side effects.

Testosterone deficiency is a clinical disorder due to either failure of the testes to produce testosterone or failure of the hypothalamus or pituitary to produce sufficient gonadotropins. Previous formulations of oral testosterone therapy, particularly methyltestosterone, have been associated with adverse liver effects. Many different routes of testosterone delivery have been developed, each with their own administrative benefits and challenges. Newer formulations of oral testosterone undecanoate (TU) provide a convenient administration option, although their use has been limited by hepatotoxicity concerns based on older methyltestosterone data, and prescribing physicians may still be concerned about adverse liver effects. In this review, we discuss the history of oral testosterone development, clarify the mechanism of action of oral TU, and describe the relevant liver safety findings. Relevant literature was allocated to present a review on the history of oral TU development and the mechanism of action of oral TU. We pooled data from individual studies of oral TU products to present a safety summary. Overall, safety results from studies of the newer formulations of oral TU showed that increased liver function test values are not generally associated with oral TU formulations and that no clinically significant liver toxicities were noted in clinical trials of oral TU. Continued research into the safety of oral TU will contribute to a better understanding of the potential risks in patients receiving this therapy, an outcome that highlights the importance of providing patient education and reassurance regarding oral TU safety.

Safety, efficacy, and pharmacokinetics of oral testosterone undecanoate in males with hypogonadism.

Testosterone deficiency results from insufficient testosterone production. Testosterone therapy may require dose titration to reach eugonadal serum testosterone concentrations. The primary objective was the efficacy of oral testosterone undecanoate (TLANDO; Antares Pharma Inc.) in male patients with documented hypogonadism. Secondary objectives included a comparison of oral testosterone undecanoate safety and quality-of-life assessments to 1.62% topical testosterone gel (AndroGel 1.62%; AbbVie). In this phase 3 study, 315 patients were randomized 2:1 to oral testosterone undecanoate or 1.62% topical testosterone gel (NCT02081300). Patients received 225mg oral testosterone undecanoate twice daily, and doses were adjusted by 75mg/dose at weeks 4 and 8 based on average serum total testosterone concentration and maximum observed serum concentration. The primary endpoint was the proportion of patients receiving oral testosterone undecanoate with serum total testosterone concentration within the eugonadal reference range (300-1140ng/dL). Secondary endpoints included the proportion of patients with maximum serum total testosterone concentrations within predetermined limits, safety parameters, and quality-of-life endpoints including the Short Form-36v2 Health Survey, Psychosexual Daily Questionnaire, and International Prostate Symptom Score. Overall mean±SD baseline testosterone was 205.7±71.6ng/dL. For patients receiving oral testosterone undecanoate, 87.4% demonstrated a 24-h average serum total testosterone concentration within the reference range following titration. Oral testosterone undecanoate demonstrated a nominal statistically significantly greater mean change from baseline than 1.62% topical testosterone gel for Short Form-36v2 Health Survey measures of mental health (2.91vs. -0.10; p=0.035), and mental component summary (3.82vs. 0.55; p=0.009); and Psychosexual Daily Questionnaire measure of weekly negative mood (-0.57vs. -0.20; p=0.021). Safety endpoints were comparable between therapies. No deaths or treatment-related serious adverse events were reported. Male patients with hypogonadism receiving oral testosterone undecanoate 225mg twice daily demonstrated improvements in libido and sexual frequency. Serum testosterone concentrations were within the reference range in 87% of patients without dose titration.

Efficacy of oral testosterone undecanoate in children with androgen insensitivity syndrome

Objective: To investigate the efficacy and safety of oral testosterone therapy in individuals diagnosed with androgen insensitivity syndrome (AIS). Methods: A self-controlled study design was utilized, focusing on individuals with AIS who were genetically diagnosed at the Department of Endocrinology, Genetics, and Metabolism of Beijing Children's Hospital between 2009 and 2021. These patients underwent treatment involving the administration of testosterone. The primary observed indexes include the measurement of penis length, which should meet the minimal surgical standard (penis length≥2.5 cm) or greater than or equal to -2.5 s (lower limit of normal). Secondary observed indexes include penile length standard deviation score (PL-SDS), an increase in penis longitude (ΔPL), medication dosage, the course of therapy, and safety indicators, among others. There were 4 courses of treatment. After each course, patients were evaluated to determine whether termination of treatment was appropriate. Patients who exhibited inadequate post-treatment penile length growth were advised to continue with further treatment. The statistical methodology included t-test, and a Wilcoxon rank sum test to describe efficacy and safety. The patients were followed up until 2023. Results: The study comprised a total of 51 individuals with AIS, comprising 33 males and 18 females (gender of registered permanent residence). Among these patients, 10 were diagnosed with complete androgen insensitivity syndrome (CAIS) and 41 were diagnosed with partial androgen insensitive syndrome (PAIS). There were 2 children with CAIS were diagnosed by doctors and prescribed testosterone undecanoate, but the children did not really take medicine.The penile length of CAIS patients could not be measured (penile length<0.5 cm) before and after treatment. For PAIS patients, baseline penile length and PL-SDS were (2.3±0.6) cm and -3.7±1.3, respectively. The measurements for penile length and PL-SDS after each treatment course were recorded as follows: (2.7±0.8), (2.8±0.6), (2.6±0.4), (2.6±0.4) cm and -2.8±1.6, 2.5±1.6, 2.9±1.2, -3.2±0.9, respectively. Both penile length and PL-SDS interventions showed statistically significant gains when compared to the baseline performance of the 4 courses (t=4.05、3.56、2.55、2.23 and 3.88、3.50、2.50、2.19, all P<0.05). Before treatment, 13 PAIS patients (32%) reached 2.5 cm and seven (17%) reached greater than or equal to -2.5 s. Following the initial, subsequent, third, and fourth therapeutic interventions, 18 cases (44%), 24 cases (59%), 25 cases (61%), and 26 cases (63%) reached 2.5 cm, respectively. Additionally, A total of 12 cases (29%), 15 cases (37%), 20 cases (49%), and 21 cases (51%), respectively, were found to reach greater than or equal to -2.5 s. The study involved the longitudinal monitoring of patients with the highest recorded age being 13.7 years. The weight, height, body mass index, bone age/age, cholesterol, hemoglobin and so on were all within the normal range and the difference were not statistically significant (all P>0.05). All 49 patients were no abnormalities in blood electrolyte, liver and kidney function and thyroid function and no changes in precocious puberty, pubic hair growth, aggressive behavior, vulvar skin darkening, diarrhea or other conditions. Conclusions: Testosterone undecanote in children with CAIS was no effective. The initial course of treatment for patients with PAIS demonstrates observable enhancements in penile length and PL-SDS. For patients with inadequate penile length growth, continued treatment in subsequent courses (such as the second, third, and fourth courses) is recommended toenhance outcomes gradually. Testosterone undecanoate was safe and effective for the majority of individuals with PAIS patients, with few adverse effects and good treatment tolerance.

Comparison of analytical approaches for the detection of oral testosterone undecanoate administration in men.

For antidoping laboratories, the determination of an illicit testosterone (T) administration in urine samples remains a difficult process as it requires the determination of the exogenous origin by carbon isotope ratios (CIRs) of testosterone and its metabolites. As a complement to the urinary analysis, targeting testosterone esters (e.g. testosterone undecanoate [TU]) in serum samples by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) could represent a simpler approach compared with isotope ratio mass spectrometry (IRMS). These two approaches both lead to the direct detection of the administration of exogenous T but with a difference in effort and complexity of the analysis. To compare the detection window obtained with the two strategies, serum and the corresponding urine samples collected from an administration study with oral TU were analysed. Results showed that, at all timepoints where the intact TU was detected in serum, the CIRs of urinary steroids were also not in agreement with an endogenous origin. IRMS analysis required more effort but resulted in slightly longer detection windows than the ester analysis. Finally, this comparison study showed that, in the presence of a suspicious urinary steroid profile, the LC-MS/MS steroid esters analysis in the corresponding serum samples can be very helpful. If steroid esters are not detected, the IRMS analysis can then be conducted on the urine sample afterwards. Overall, the combination of matrices might facilitate the detection of prohibited T administration in sports, especially for athletes with naturally low T/E ratios.

A phase III, single-arm, 6-month trial of a wide-dose range oral testosterone undecanoate product.

Oral testosterone undecanoate (TU) formulations may provide effective, safe, and easily titratable testosterone replacement therapy. Demonstrate efficacy and safety of a novel oral TU formulation. An open-label, single-arm, multi-center trial treated 155 hypogonadal men for 180 days. Treatment began at 200 mg TU twice daily with meals; doses were titrated over two 28-day cycles to between 100 and 800 mg TU daily, measuring average testosterone (T Cavg) after 90 days. Ambulatory blood pressure monitoring (ABPM) occurred at baseline, 120, and 180 days. Titrations used a randomized blood sample taken 3-, 4-, or 5-h post-morning dose. Outcomes used sodium fluoride/ethylenediaminetetraacetate plasma testosterone (T) values; serum results were also reported. Blood pressure (ABPM and in-clinic) was evaluated for change from baseline. After titration, 87.8% of KYZATREX™ treated participants (worse-case scenario) and 96.1% of 90-day completers achieved eugonadal mean plasma T values. Serum T Cavg was 452 ng/dL and maximum T concentrations (T Cmax) met all FDA criteria. Participant eugonadal percentages were comparable across subgroups for age, weight, and body mass index. Diet had no effect on participant eugonadal percentages. KYZATREX was well tolerated, with no drug-related serious adverse events (SAE) and one adverse drug reaction (hypertension) observed in 2% or more of participants. Systolic ambulatory blood pressure increased 1.7 mmHg (95% confidence interval: 0.3-3.1). At baseline, 36% of 155 participants were receiving anti-hypertensive medication and 22% were diabetic. No dose increases occurred in existing anti-hypertensive medication; five participants (3.2%) started anti-hypertensive medication. KYZATREX provided safe and effective testosterone levels within the normal range in hypogonadal male study participants. URL: https://clinicaltrials.gov/ unique identifier NCT04467697, conducted under NCT03198728. Post-completion, clinicaltrials.gov requested creation of the separate NCT04467697 identifier. All subjects were recruited under NCT03198728.

Patient Satisfaction with Oral Testosterone Undecanoate in Men Who Received Prior Testosterone Therapy: An Open-Label, Single-Center Clinical Trial.

To evaluate patient satisfaction and symptom control in hypogonadal men transitioning from other testosterone therapies to oral testosterone undecanoate (TU). In this open-label clinical trial, men aged 18 to 75 years with hypogonadism were switched to oral TU after a sufficient washout of previous testosterone therapies. Treatment satisfaction and symptom control were primarily measured using the 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) and quantitative androgen deficiency in aging males (qADAM) questionnaires, respectively. Secondary outcomes included changes in serum testosterone (T), estradiol (E2), hematocrit (HCT), and prostate-specific antigen (PSA) levels. Forty-one men participated, with significant improvements in all TSQM-9 scores observed over 6 months. Symptom control as measured by qADAM remained consistent. There was a significant increase in serum T and E2 levels, but HCT and PSA levels remained stable. Switching to oral TU from other testosterone therapies is associated with increased patient satisfaction and stable hypogonadal symptom control.

FRI431 Erythrocytosis Associated With Oral Testosterone Replacement

Abstract Disclosure: A.A. Engel: None. J.L. Sarvaideo: None. Background: A growing prevalence in male hypogonadism has led to increased interest in the most common adverse event, erythrocytosis. Defined by hematocrit (HCT) &amp;gt; 49-51%, the incidence varies depending on the testosterone formulation.3 The formulations with the lowest risk of erythrocytosis are intranasal testosterone (0-2%) and oral testosterone (0.03%).3 A phase 3 clinical trial of testosterone undecanoate (Jatenzo) reported 4.8% patients experienced an increase in hematocrit, although not severe enough to warrant therapy discontinuation.2 We present a case of erythrocytosis with oral testosterone undecanoate that prompted a change in therapy. Clinical Case: Our patient is a 55-year-old male with secondary hypogonadism potentially related to obesity (BMI 37 kg/m²). AM total testosterone (TT) 151 (348-1197 ng/dL), free testosterone 4.6 pg/mL (6.8-21.5 pg/mL) and LH 3.8 mIU/mL. Labs confirmed. Secondary work-up negative. HCT 43.6% prior to any therapy. Patient treated with injectable testosterone. Despite decreasing to testosterone cypionate 80 mg weekly his HCT increased to 52.7% with a TT of 544 ng/dL. He was switched to oral testosterone undecanoate 237 mg twice daily given presumably lower risk of erythrocytosis. However, HCT increased to 55.1% and TT to 1542 ng/dL. Patient donated blood and oral testosterone dose decreased to 158 mg twice daily with starting HCT 48.9%, but this increased to 53.7%. TT 522 ng/dL. Therapy stopped with improvement of HCT to 45.8%-48.9%, TT 192 ng/dL, and SHBG 20 g/dL. Erythropoietin remained normal. Patient does not smoke cigarettes nor has OSA. Conclusion: We present a case of oral testosterone undecanoate complicated by persistent erythrocytosis despite dose reduction. Testing for contributing etiology was unrevealing. Oral testosterone replacement is considered the formulation least likely to cause erythrocytosis. Certain patient characteristics like OSA, advanced age, obesity, type II diabetes mellitus and an elevated HCT &amp;gt; 50% can predict the likelihood of erythrocytosis although its specific etiology is unclear.3 Proposed mechanisms include elevation in dihydrotestosterone, erythropoietin stimulation, suppression of hepcidin and relation to androgen receptor CAG repeat length.1 Providers should be aware of the possibility of erythrocytosis on oral testosterone. Further research is needed to determine predictive characteristics for erythrocytosis and etiology. Reference: 1. Aghazadeh, M, et al. Elevated dihydrotestosterone is associated with testosterone induced erythrocytosis. J Urol. 2015; 194(1): 160-165. 2. Swerdloff, S, et al. A new oral testosterone undecanoate formulation restores testosterone to normal concentrations in hypogonadal men. J Clin Endocrinol Metab. 2020; 105)8): 1-17. 3. White, J, et al. Testosterone therapy and secondary erythrocytosis. IJIR: Your Sexual Medicine Journal. 2022; 34: 693-697. Presentation: Friday, June 16, 2023

(393) Pooled Safety Analysis of Ten Clinical Studies Evaluating Fixed-Dose Oral Testosterone Undecanoate in Male Patients With Testosterone Deficiency

Abstract Introduction Oral testosterone undecanoate (TU) was approved outside the United States 50 years ago and is currently used in several countries for the treatment of men with testosterone deficiency. The efficacy of prior oral TU is limited by a short half-life, requiring frequent dosing and administration with meals. A novel formulation of fixed-dose TU is now indicated for the treatment of testosterone deficiency (FDA approved March 2022). In a phase 3 study (NCT03242590: 1021-16-002) evaluating the efficacy and safety of fixed-dose oral TU 225 mg twice daily in adult men with testosterone deficiency, oral TU was well tolerated and restored testosterone levels to eugonadal ranges in most patients. Objective The objective of this pooled analysis of ten clinical studies (LPCN 1021-09-001, S361.1.001, M12-778, M13-298, 1021-14-001, LPCN 1021-16-002, LPCN 1021-16-003, LPCN 1021-13-001, LPCN 1021-18-001, LPCN 1021-18-003) was to further evaluate the safety of fixed-dose TU administered to adult men with testosterone deficiency. Methods This pooled analysis included men with testosterone deficiency who were enrolled or randomized in one of ten clinical studies and received at least one dose of study drug, which included fixed-dose TU, dose-adjusted TU, or topical testosterone gel. Data from separate studies were allocated to defined treatment groups, and these data were pooled to present a safety summary of patients treated with fixed-dose TU. Treatment groups were defined as follows: all fixed-dose TU patients, active control patients (dose-adjusted TU or topical testosterone gel), and placebo patients. Participants in a crossover study of various fixed-dose TU doses were counted once overall for analysis, and data relating to the highest dose were used. Results Overall, 777 patients were included in this pooled analysis: 654 received fixed-dose TU, 104 received topical testosterone gel, 34 received dose-adjusted TU, and 18 received placebo. Baseline characteristics are available on Table 1. Among 654 patients who received fixed-dose TU, 549 (83.9%) patients completed their respective study, and 15 (2.3%) patients discontinued because of an AE. The most frequently occurring treatment-emergent related adverse events (AEs) for patients treated with fixed-dose TU included headache (10 [1.5]), hematocrit increase (8 [1.2]), and acne (6 [0.9]) (Table 2). Three (0.5%) patients receiving fixed-dose TU experienced a blood pressure increase and 13 (2.0%) exhibited hypertension. No patients receiving fixed-dose TU experienced an increase in hepatic enzymes. The mean change from baseline (SD) in hematocrit (HCT) for patients receiving fixed-dose TU was 0.003% (0.029); three patients receiving fixed-dose TU discontinued because of HCT &amp;gt;54%. No patients in this pooled analysis experienced a serious AE (SAE) related to study treatment, and no deaths occurred. Conclusions In this pooled analysis of ten clinical studies in male patients with testosterone deficiency, fixed-dose TU was well tolerated with no hepatic adverse events, no drug-related SAEs, and no deaths. Disclosure Yes, this is sponsored by industry/sponsor: Halozyme (previously Antares) Clarification Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Halozyme (previously Antares)

(067) Oral Testosterone, Is It Ready for Prime Time? A Meta-analysis of Safety and Efficacy in Men with Testosterone Deficiency

Abstract Introduction The prescription rates of testosterone replacement therapy (TRT) have tripled within recent decades. Recently, two novel oral testosterone undecanoate (TU) options have obtained FDA approval and are now commercially available. We present the first meta-analysis analyzing the safety and efficacy of oral TRT in patients with testosterone deficiency (TD). Objective To evaluate the safety and efficacy of TU in the treatment of TD Methods Pair-wise meta-analyses were performed including randomized, placebo-controlled trials investigating the use of TU. Studies were included for analysis if participants received oral TRT or placebo for a period greater than one month and if adverse effects (AE) or changes in serum total testosterone (TT) were recorded. Results Nine studies including a total of 606 patients recorded changes in TT. When separated by population, studies including only men with TD saw improved TT (mean change 1.25 ng/mL, 95% CI: 0.22 to 2.29, I2: 0%). Eight studies including a total of 849 patients recorded rates of AE. There was no statistically significant change in the risk of AE in patients receiving oral TRT compared to placebo (log risk ratio -0.03, 95% CI: -0.08 to 0.03, I2: 0%) [Figure 1]. Conclusions When separated by inclusion criteria, studies examining men with TD tended to report improved TT levels following treatment with TU compared to placebo. In studies examining the safety of oral TRT, its use was not associated with increased rates of AE when compared with placebo. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Antares Pharma; Clarus Therapeutics; Coloplast; Cynosure; Promescent; Sprout; Viome.

(394) Effects of Age, Body Mass Index (BMI) and Diabetic Status on Testosterone Levels, Testosterone Dosing and Safety in Hypogonadal Men Treated with an Oral Testosterone Undecanoate (JATENZO)

Abstract Introduction A novel oral testosterone replacement therapy (TRT), testosterone undecanoate (TU, JATENZO) has been shown in 1- and 2-year studies to have durable efficacy and safety. Hypogonadal men are heterogeneous with respect to age, body mass index (BMI), and diabetic status. These factors have been shown to affect the hypothalamic-pituitary-gonadal axis. Objective The purpose of this study is to investigate the role of baseline age, BMI, and diabetic status on change in T levels, final TU dose, and safety. Methods Hypogonadal men, ages 18 – 65 y/o, were recruited into a randomized, open-label, multicenter, dose-titration trial. 222 subjects were randomized to BID TU (n = 166) or testosterone gel (n = 56). Subjects had dose adjustments based on plasma T levels (Cavg). Safety was assessed by standard clinical measures. Post hoc safety, efficacy, and dosing analyses were conducted on subjects who were stratified by age, BMI, and diabetes status. The age groups were &amp;lt;= 44 y/o, 45 – 54 y/o, and =&amp;gt; 55 y/o; the BMI groups were &amp;lt; 30 kg/m^2, 30 – 35 kg/m^2, and &amp;gt; 35 kg/m^2; and the subjects were grouped as non-diabetic, pre-diabetic, or diabetic. Results Overall, serum total T Cavg for the oral TU group was 489 ± 12.6 ng/dL (mean ± SE). For all groups, the mean total T was in the eugonadal range. Age, BMI, or diabetes status did not affect key efficacy variables, such as total T or calculated free T, nor key safety variables, such as hematocrit, PSA, liver transaminases, systolic BP, diastolic BP, HDL-C, or LDL-C. There were no differences in the final TU dose among the age categories. In contrast, the final TU dose was significantly different among BMI categories (p=0.0003), and the diabetic status (p &amp;lt; 0.0001). The higher BMI groups need a significantly higher oral TU dose. Those in the pre-diabetic or diabetic groups needed a significantly higher dose than the non-diabetic group. Because the pre-diabetic and diabetic groups had significantly higher BMI, it is difficult to determine if it was diabetes status or BMI that influenced the final dose [baseline BMI: non-diabetic 30.5 ± 0.52 (mean ± SEM), pre-diabetic 32.7 ± 0.54 (p = 0.003 vs the non-diabetic group), diabetic 32.5 ± 0.56 (p = 0.0175 vs the non-diabetic group)]. BMI had a greater effect on the final dose in the non-diabetic group, and its effect appeared to decrease in the pre-diabetic and diabetic groups. See figure for the final mean doses. Although the final total T values were in the eugonadal range, there was also a significantly smaller change from baseline in total T comparing non-diabetics to diabetics (p=0.0042). Conclusions Regardless of age, BMI, or diabetes status, eugonadal total T levels were achieved in men administered oral TU. Age did not influence the final dose. In contrast, BMI and diabetes status influenced the final dose. Patient characteristics (BMI and diabetic status) may guide dosing of testosterone replacement with oral testosterone undecanoate to optimize T levels. Disclosure Yes, this is sponsored by industry/sponsor: Clarus Therapeutics Clarification Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Clarus Therapeutics.

MP79-01 PATIENT SATISFACTION WITH ORAL TESTOSTERONE UNDECANOATE IN TESTOSTERONE-DEFICIENT MEN WITH PREVIOUS TESTOSTERONE THERAPY: AN OPEN-LABEL, SINGLE-CENTER, PHASE IV CLINICAL TRIAL

You have accessJournal of UrologyCME1 Apr 2023MP79-01 PATIENT SATISFACTION WITH ORAL TESTOSTERONE UNDECANOATE IN TESTOSTERONE-DEFICIENT MEN WITH PREVIOUS TESTOSTERONE THERAPY: AN OPEN-LABEL, SINGLE-CENTER, PHASE IV CLINICAL TRIAL Marco-Jose Rivero, Rohit Reddy, Akhil Muthigi, and Ranjith Ramasamy Marco-Jose RiveroMarco-Jose Rivero More articles by this author , Rohit ReddyRohit Reddy More articles by this author , Akhil MuthigiAkhil Muthigi More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003356.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Testosterone therapy (TTh) is available in multiple modalities. Oral formulations, previously unavailable in the United States due to variable bioavailability, are convenient, easy to use, and free of painful injections. Testosterone undecanoate (TU) is a recently approved oral testosterone capsule that provides a uniform response in patients with testosterone deficiency. In this study, we evaluated patient satisfaction with TU in men with a recent history of alternative TTh. METHODS: Patients between 18 and 65 years of age with a diagnosis of testosterone deficiency were recruited. Testosterone deficiency (TD) was defined as two measurements of serum total testosterone below 300 ng/dL combined with one or more characteristic clinical symptoms. Patients were required to have received previous TTh and completed an adequate washout period prior to starting TU. The primary outcomes were patient satisfaction, measured by the Treatment Satisfaction Questionnaire for Medication (TSQM-9); and TD symptom control, measured by the quantitative Androgen Deficiency in Aging Males (qADAM) questionnaire at 3- and 6-month intervals. Routine blood tests were also performed at each time point. RESULTS: Of the 43 patients recruited into the study, 47% had previously received subdermal pellets, 40% intramuscular injections, and 12% intranasal gels. After the appropriate washout period, serum total testosterone levels increased from a baseline mean of 193.4 ng/dL to 747.9 ng/dL at 1 month, 500.6 ng/dL at 3 months, and 692.2 ng/dL at 6 months of treatment with TU. Mean global satisfaction measured by TSQM-9 progressed from 64.1 with previous TTh to 80.2 at 3 months (p=0.011) and 88.8 at 6 months (p<0.001) of treatment with TU. Similar 6-month changes were observed for TSQM-9 measures of effectiveness (p<0.001) and convenience (p<0.001). Mean TD symptom control measured by qADAM at 6 months (35.0) was statistically unchanged from baseline (36.8, p=0.154). No significant changes were noted in hematocrit, prostate-specific antigen, or estradiol throughout the study period. CONCLUSIONS: TU provides patient satisfaction and TD symptom control that is noninferior compared to other forms of TTh. In addition, TU increases serum total testosterone to reference range (300–1000 ng/dL) in >90% of men without a difference in side effect profile over 6 months of treatment. Source of Funding: This project was funded by an investigator-initiated grant provided by Clarus Therapeutics © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1141 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Marco-Jose Rivero More articles by this author Rohit Reddy More articles by this author Akhil Muthigi More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF downloadLoading ...

Safety Aspects and Rational Use of Testosterone Undecanoate in the Treatment of Testosterone Deficiency: Clinical Insights.

Testosterone deficiency is diagnosed by a serum total testosterone level below 300 ng/dL in combination with symptoms such as decreased energy and libido. These symptoms can be ameliorated by restoring serum testosterone to the physiologic range with testosterone therapy (TT). There are numerous forms of testosterone therapy, such as injectable, transdermal, nasal, and subcutaneous applications. There are also multiple formulations of injection, such as testosterone cypionate, testosterone enanthate, and testosterone undecanoate. Testosterone undecanoate (TU) is a long-acting ester formulation of testosterone that can be provided in an injectable or oral form. Oral testosterone undecanoate is marketed as Andriol, Jatenzo, Tlando, and Kyzatrex. Oral TU provides a convenient option for many patients, which may increase compliance with TT. Injectable testosterone undecanoate is marketed as Aveed and Nebido. Injectable TT remains the most cost-effective therapeutic option and is appropriate for most patients as an initial therapy. This review describes the pharmacokinetics of these testosterone undecanoate products and provides a guide for prescribers using these medications. While many forms of testosterone are appropriate for TT, a patient-centered discussion focused on goals of care should best guide physician prescription of these medications.

Sifrim-Hitz-Weiss/CHD4-related syndrome: A new case report.

Sifrim-Hitz-Weiss/CHD4-related syndrome: A new case report.

Effects of Oral Testosterone Undecanoate (Kyzatrex) Versus Testosterone Gel (Androgel) on Long-Term (to 12 Months) Blood Pressure Levels

Purpose: Oral and injectable testosterone replacement therapies have been reported to increase blood pressure (BP) in hypogonadal men. Less is known about the effects of topical testosterone formulations on BP. Materials and Methods: We studied the effects of a new oral testosterone undecanoate (TU) (Kyzatrex™) and a topical testosterone gel (Androgel™) on BP and heart rate, in a 2:1 randomized trial of men with hypogonadism. Digital BPs and clinical assessments were obtained at baseline and at 90, 180 and 365 days. Results: There were 314 men randomized (mean age 49.7 years, 82% white, and 35% with treated hypertension). The mean changes from baseline in systolic BP were 2.2 mmHg (95% confidence interval [CI] 0.6–3.7) on the oral TU and 3.1 mmHg (95% CI 1.0–5.1) on the topical testosterone at 90 days. Similar findings were seen after 180 and 365 days. Heart rate increased by 4.3 and 2.7 beats/min at 90 days on oral and topical testosterone, respectively. For those men with treated hypertension, changes in systolic BP in the oral TU group were higher compared with those without hypertension, whereas those on topical testosterone had similar increases in systolic BP regardless of hypertension status. Outlier analyses for systolic BP at 90 days demonstrated a higher proportions of subjects with increases of 5 and 10 mmHg postbaseline on topical testosterone gel versus this oral TU. Conclusions: These data demonstrate that the overall effects of the oral TU on BP were comparable with a topical testosterone. In men without hypertension, the oral TU induced smaller changes in BP compared with topical testosterone. Clinical Trial Registration (https://www.clinicaltrials.gov/): NCT04467697.

PMON267 Comparison Between Single Time Point Testing and 24-Hour Average Concentration of Total Testosterone in Hypogonadal Men Treated with an Oral Testosterone Undecanoate Softgel (JATENZO®)

Abstract In 2019, a novel, first-in-class testosterone (T) replacement therapy (TRT), oral testosterone undecanoate (TU) was approved by the U.S. FDA for the treatment of male hypogonadism. During clinical trials, dose adjustments were based on 24-hr average T concentration (Cavg) because single T measurements were considered less accurate. Subsequent, concordance analyses for this oral TU product have shown that a single total T value 6-hrs after the morning oral TU dose best corresponds to Cavg. Nonetheless, a conversion factor for T values obtained at other post-dose time points would be useful for healthcare providers (HCPs) and ease potential scheduling challenges for patients. Consequently, the relationship between other T sampling time points and Cavg was examined to determine if a reliable conversion factor could be derived to help HCPs monitor a patient's serum T concentration at times other than 6-hrs after oral TU administration. Hypogonadal men, age 18–65 y/o, were recruited into a randomized, open-label, multicenter, dose-titration trial. Overall, 166 men were randomized into the oral TU arm. Dose titration was based on Cavg calculated from serial pharmacokinetic (PK) samples. There were three pre-designated PK visits, to individualize the appropriate TU dose and to achieve a eugonadal T Cavg by the final study visit. Ratios between different timepoints and Cavg were determined for PK samples following morning drug administration. Overall, 87.3% (95% CI: 81.3%, 92.0%) of hypogonadal men had a final Cavg in the eugonadal range, with a mean serum total T = 488.7 ± 154.5 ng/dL (16.95 ± 5.37 nmol/L). Pooled values from all PK days demonstrated a linear relationship between T concentrations at 4, 6, and 9-hrs and Cavg (p &amp;lt; 0.0001). Visit and time of sampling interaction were not statistically significant (p &amp;gt;&amp;gt; 0.50), indicating consistency in results among PK visits and among sampling timepoints. A factor was derived to enable conversion of T values assessed at a time other than 6-hrs (post oral TU dose) into a close approximation of Cavg: 1/[1.870–0.14×(hours after AM dose)]. Therefore, a sample drawn at 4-hrs after the morning oral TU dose would be multiplied by 0.75; while one drawn at 8-hrs would be multiplied by 1.33. Hence, T Cavg can be approximated after morning JATENZO administration if a blood sample cannot be collected precisely 6-hrs thereafter. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

A comprehensive UHPLC-MS/MS method for the analysis of endogenous and exogenous steroids in serum for anti-doping purposes.

In the context of steroid analyses, the use of blood could represent a valuable complement to urine. While the blood steroid profile is currently being established to aid unveiling testosterone (T) doping, this matrix is also well suited for detection of exogenous anabolic steroids and steroid esters. In this study, a method to determine a simplified blood steroid profile in combination with the direct detection of exogenous anabolic steroids and steroid esters using just one serum aliquot was developed to obtain a comprehensive analytical workflow. Following the first chromatographic analysis of endogenous and exogenous steroids, samples were derivatised with Girard's reagent T (GT) to improve the ionisation of steroid esters and re-injected. The quantitative performance for T, androstenedione (A4) and 5α-dihydrotestosterone (DHT) was evaluated and the method was validated for qualitative analysis of exogenous analogues with estimated limits of detection (LOD) between 50 and 500 pg/ml. To demonstrate the applicability of the method, samples collected from a clinical study with an oral administration of testosterone undecanoate (TU) to 19 male volunteers were then analysed. The individual serum steroid profiles with the endogenous markers T, A4 and DHT were established as well as the concentrations of TU. TU was detected in all 19 volunteers up to 24 h, while DHT represented the most promising biomarker in endogenous steroid profile for the detection of oral TU administration. These results showed that the selected approach to combine exogenous and endogenous steroid analysis has the potential to strengthen T doping detection in the future.

Two-Year Analysis of a New Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men: Efficacy, Impact on Psychosexual Function, and Safety

BackgroundLong-term data evaluating the efficacy and safety of oral testosterone undecanoate (oral TU; JATENZO) in adult hypogonadal men provides important information for healthcare professionals who prescribe testosterone replacement therapy (TRT). AimTo determine the efficacy and safety of long-term oral TU therapy, including its impact on total testosterone (T) levels and psychosexual functioning. MethodsHypogonadal men, between 18 and 75 years old, (mean age 56.2; 87.2% white) who completed a 12-month, open-label, multicenter, randomized, active-controlled trial were given the opportunity to enroll in a 12-month extension study. Among the 129 eligible TU-treated subjects, 86 chose this option, and 69 completed 24 months of uninterrupted oral TU therapy. OutcomesThe efficacy of oral TU was documented by measuring total serum T concentrations; sexual function was measured using the Psychosexual Daily Questionnaire (PDQ). For safety, liver function tests, cardiovascular endpoints, and prostate health were measured. ResultsOver 2 years, total serum T concentrations for patients treated with oral TU were in the eugonadal range (300–1,000 ng/dL [10–35 nmol/L]; mean ± SD: 617 ± 427 ng/dL [21 ± 15 nmol/L]) and increased significantly from baseline (P < .0001). For sexual function, mean score changes versus baseline for all PDQ domains at all time points were significantly improved (P < .0011 for all). For the sexual activity and sexual desire components, patient scores were consistently greater than validated thresholds for clinically meaningful change. Typical T-induced safety changes were observed, including a 3–6 mm Hg increase in systolic blood pressure (P < .05); a slight increase in hematocrit (P < .0001) that stayed <48% throughout the study; no clinically significant changes in prostate-specific antigen levels; and decreased high-density lipoprotein cholesterol (-9.8 ± 0.9 mg/dL from baseline; P < .0001). There were no clinically significant changes from baseline in liver function tests. Clinical ImplicationsOver 2 years of treatment, this novel oral TU formulation maintained total T concentrations in mideugonadal ranges, with improvements in sexual function and no clinically significant changes in liver function or other safety concerns previously associated with oral TRT. Strengths & LimitationsThese are the first long-term data to evaluate the efficacy and safety of a novel formulation of oral TU; the comparative long-term safety of oral TU would be strengthened by confirmatory studies versus other TRT formulations. ConclusionOral TU offers a safe and effective long-term treatment option for men with hypogonadism.Honig S, Gittelman M, Kaminetsky J, et al. Two-Year Analysis of a New Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men: Efficacy, Impact on Psychosexual Function, and Safety. J Sex Med 2022;19:1750–1758.

Patient Satisfaction After Switching to Jatenzo (Oral Testosterone Undecanoate): Update on an Open-label, Single-arm Clinical Trial

This is the first study investigating patient satisfaction among men receiving oral testosterone decanoate (TU) who were previously using other forms of testosterone therapy. Oral TU appeared to lead to greater patient satisfaction in comparison to previous modalities and similar improvements in hypogonadal symptoms. TU represents a favorable and viable option for hypogonadal individuals who are unhappy with existing treatment options.

Single-center real-life experience with testosterone treatment in adult men with Prader-Willi syndrome.

Hypogonadism is the most frequent hormonal deficiency in individuals with Prader‐Willi syndrome (PWS). This often necessitates testosterone treatment, but limited data are available to guide testosterone treatment in adult men with PWS. We aimed to evaluate the serum testosterone concentrations and adverse effects of testosterone treatment in individuals with PWS attending a specialist obesity management service. A retrospective audit was undertaken at Austin Health, Melbourne between January 2010 and April 2021. Main outcome measures were testosterone formulation and dose, serum total testosterone concentration, and prevalence of polycythemia and behavioral disturbance. Data were available for eight individuals with median baseline age 19 years (range, 19–42) and BMI 37 kg/m2 (range, 27–71). Six men had obstructive sleep apnea; none were smokers. Baseline testosterone concentration was 1.8 nmol/L (IQR, 1.1–3.3) with hematocrit 0.43. Testosterone formulations were intramuscular testosterone undecanoate (TU) 1000 mg (n = 5), transdermal testosterone gel 50 mg daily (n = 1), and oral TU 80–120 mg daily (n = 2). Median total testosterone concentration was 9.7 nmol/L (IQR, 8.5–14.7). Nine of 25 (36%) hematocrit results in six patients measured >0.50 (range, 0.50–0.56). Intramuscular TU was well tolerated and was the only formulation to achieve serum total testosterone concentrations in the adult male reference range. Worsening behavioral disturbance resulted in treatment discontinuation in one individual. Our experience reinforces the need to regular monitoring of hematocrit in men with PWS treated with testosterone. However, a worsening of behavior problems was uncommon in this series.