Testosterone Undecanoate Research Articles

MP45-06 SHOULD WE TREAT TESTOSTERONE DEFICIENCY IN PATIENTS WHO DO NOT HAVE SYMPTOMS?

INTRODUCTION AND OBJECTIVE: Testosterone replacement therapy (TRT) is effective for treating the symptoms and ameliorating the metabolic consequences of hypogonadism. TRT improves muscle mass, bone mineral density, mood, and sexual performance. However, a significant number of patients have low serum levels of testosterone without any subjective symptoms or complaints. We evaluated the suitability of TRT for patients with non-symptomatic late-onset hypogonadism. METHODS: Seventy patients whose initial serum levels of testosterone were < 300 ng/dL without any symptoms or complaints were consecutively enrolled and followed for 30 weeks. All patients received 1,000 mg parenteral testosterone undecanoate on day 1, followed by additional injections on weeks 6, 18, and 30. Serological tests (for total testosterone, lipid profile, glucose, and prostate-specific antigen [PSA]) were performed and Body Mass Index (BMI), International Index of Erectile Function (IIEF) score, International Prostate Symptom Score (IPSS), the Aging Males’ Symptoms (AMS) questionnaire, and the Global Assessment Questionnaire (GAQ) were performed at baseline and at the end of the study. RESULTS: Mean patient age was 56.2 ± 10.5 years. The total IIEF score increased from 44.9 ± 12.9 at baseline to 54.8 ± 13.0 on week 30 (p < 0.001). The AMS score improved from 37.9 ± 11.5 at baseline to 24.6 ± 13.2 on week 30 (p < 0.001). Baseline and 30-week total testosterone levels were 272.2 ± 48.2 and 598.2 ± 52.5 ng/dL, respectively (p < 0.0001). No significant changes were detected in the IPSS, lipid profiles, glucose, BMI, or PSA level. The percentage of patients reporting improvement in the GAQ was 58.6%. Improvements in the sexual desire domain of the IIEF, sexual subscale of the AMS, and change in total testosterone (>300 ng/dL) were significantly correlated with a positive GAQ response. The majority of adverse events were mild, reversible, and of short duration. CONCLUSIONS: Although a patient may not complain of any subjective symptoms at the initial visit, TRT can be considered in patients with low testosterone levels and decreased sexual desire and function. It is postulated that patients with low testosterone levels may not recognize their symptoms. Thus, more specific screening is needed for such patients. Source of Funding: None

Occurrence of Pulmonary Oil Microembolism After Testosterone Undecanoate Injection: A Postmarketing Safety Analysis

BackgroundThe Aveed Risk Evaluation and Mitigation Strategy program was instituted because of potential risk of pulmonary oil microembolism (POME) and/or anaphylaxis after intramuscular injection of Aveed (testosterone undecanoate), indicated for treatment of adult male patients with congenital or acquired primary hypogonadism or hypogonadotropic hypogonadism.AimTo analyze the reporting rate of POME associated with testosterone undecanoate administration (750 mg/3 mL) during postmarketing surveillance.MethodsThe Endo Pharmaceuticals Inc database was searched for POME reports occurring from testosterone undecanoate approval on March 5, 2014, through June 30, 2018. Each case was reviewed and adjudicated by a drug safety physician to confirm the reported event had predefined clinical characteristics consistent with POME.OutcomesAnnual rate and clinical features of spontaneously reported POME cases were characterized.ResultsDuring the 4.3-year period, 90,092 doses of intramuscular testosterone undecanoate were distributed via an Aveed Risk Evaluation and Mitigation Strategy program to health-care professionals for patient treatment. Of 633 individual case safety reports in the Endo Pharmaceuticals Inc safety database, 28 spontaneously reported adverse events were classified as POME, for a yearly spontaneously reported adverse event per-injection rate of <0.1%. Most (21/22) events resolved, and of those with a resolution time reported, most (13/17) resolved in ≤30 minutes. More than 60% (13/21) of patients required no medical intervention (ie, the POME event resolved spontaneously). One fatality was reported 18 months after a documented POME event and appeared unrelated to the reported testosterone undecanoate injection or subsequent injections after the POME event. In 3 out of 4 POME cases with symptoms serious enough to require an emergency room visit, issues with injection technique or dosing were identified as a potential contributing factor.Clinical ImplicationsInjection technique and proper product usage are key elements in the prevention of POME events.Strengths & LimitationsThe reported rate of POME events was determined from a real-world clinical practice patient population; however, postmarketing safety data typically are underreported and retrospective in nature.ConclusionPOME events appear to be rare, with resolution occurring quickly without medical intervention in most cases.Pastuszak AW, Hu Y, Freid JD. Occurrence of Pulmonary Oil Microembolism After Testosterone Undecanoate Injection: A Postmarketing Safety Analysis. Sex Med 2020;8:237–242.

Spectrophotometric and chromatographic strategies for exploring of the nanostructure pharmaceutical formulations which contains testosterone undecanoate

The nanostructure pharmaceutical formulations (NPF) which contains testosterone undecanoate (TU) been used in life science as parent compound delivery systems for therapeutic, but and been used to enhance the performance in sport, so it is a significant substance for public health and nutritional supplements. In most Pharmacopoeias testosterone is described as an ester of some lower acids (often propionate). The aim of this study is to determine purity of the parent compound by chromatography and absorption spectrum in the frame of middle infrared. Chemical structure of undecanoate was prepared and used in order to achieve a better absorption. This is explained by increased lipophilicity of undecanoate. Due to its lipophilic character, TU is soluble in non–polar solvents but shows a satisfactory solubility in absolute ethanol. Based on the molecular structure, a moderate absorption in the frame of UV with a maximum absorption at a not too high wave-length can be predicted. Maximum absorption occurs in a spectral region in which usual ingredients do not present significant interference.

Quantification of endogenous steroid sulfates and glucuronides in human urine after intramuscular administration of testosterone esters

For an effective detection of doping with pseudo-endogenous anabolic steroids, the urinary steroid profile is of high value. In this work, the aim was to investigate steroid metabolism disruption after exogenous intramuscular administration of different testosterone esters. The investigation focused on both sulfo – and glucoro conjugated androgens. A single intramuscular injection of either 1000 mg testosterone undecanoate (Nebido®) or a mixture of 30 mg testosterone propionate, 60 mg testosterone phenylpropionate, 60 mg testosterone isocaproate, and 100 mg testosterone decanoate (Sustanone®), was given to six healthy volunteers. Urine was collected throughout a testing period of 60 days. A LC-MS method was developed and validated for the analysis of eight conjugated steroids in their intact form. The results show that urinary changes in both sulfo – and glucuro conjugated steroid levels are prominent after the injection of testosterone esters. A promising potential marker for the intake of exogenous testosterone is the combined ratio of epitestosterone sulfate/epitestosterone glucuronide to testosterone sulfate/testosterone glucuronide ((ES/EG)/(TS/TG)) as a complementary biomarker for testosterone abuse. This represents a new piece of evidence to detect testosterone doping, representing a new approach and being independent from the metabolic connections of the markers in the steroid passport.

Validation of an ultra-sensitive detection method for steroid esters in plasma for doping analysis using positive chemical ionization GC-MS/MS

The standard approach to detect misuse with testosterone in sport is based on the determination and evaluation of the urinary steroid profile followed by the confirmation of atypical profiles using isotope ratio mass spectrometry. The detection capacity of these methods can be attenuated by confounding factors or testosterone preparations with endogenous isotopic fingerprints. An alternative detection method for misuse of an endogenous steroid in sports is the direct detection of the administered steroid ester present in most preparations. Thus unambiguous proof for doping misuse can be delivered. In this work, the sensitivity of gas chromatography coupled to a triple quadrupole with chemical ionization (GC-CI-MS/MS) is applied to detect trace levels of 10 testosterone and 2 nandrolone esters in plasma for in human doping analysis. The detection method was developed employing a liquid-liquid extraction and HPLC cleanup step before analysis on the GC-CI-MS/MS. The quantitative method was validated in a linear range of 100–2000 pg/ml and proved to be selective, reproducible and very sensitive with limits of detection as low as to 10 pg/ml. A clinical study with the administration of testosterone undecanoate in 3 volunteers was carried out and the compound was detectable up to 86 days after administration.

Lower Serum Estradiol Levels in Assigned Female at Birth Transgender People with Initiation of Testosterone Therapy: Results from the European Network for the Investigation of Gender Incongruence.

Purpose: Concerns have been raised about undesired estrogenic effects in assigned female at birth (AFAB) transgender people on testosterone therapy. How serum estradiol levels change after initiation of testosterone therapy and if these levels should be monitored remain unclear. Methods: This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence. Serum levels of sex steroids were assessed in 746 AFAB transgender people during a 3-year follow-up period, starting at the initiation of hormone treatment. Results: Estradiol levels decreased from median [P25-P75] 45.6 [24.0-102.2] pg/mL to 36.5 [25.0-46.2] pg/mL over 3 years (p < 0.001); a change was already noticeable during the first 3 months (mean -17.1 pg/mL, 95% confidence interval -23.8 to -10.6, p < 0.001). Serum estradiol levels were lower in people without endogenous estradiol production from ovarian source (contraceptive users or post hystero-oophorectomy) at baseline and after 3 months, compared with people with endogenous estradiol production. Using long-acting testosterone undecanoate injections resulted in a more prominent decrease in serum estradiol values over 12 months, compared with short-acting mixed testosterone esters (p < 0.001) or testosterone gel (p = 0.001). Changes in serum estradiol were positively correlated to changes in luteinizing hormone (ρ = 0.107, p < 0.001) and negatively correlated to changes in follicle-stimulating hormone levels (ρ = -0.167, p < 0.001) and body mass index (ρ = -0.082, p < 0.001). Conclusion: Testosterone administration in AFAB transgender people resulted in decreasing serum estradiol levels. Our results suggest that testosterone therapy leads to central suppression of estradiol production, with partial restitution due to aromatization.

Effect of herbal extract Eurycoma longifolia (Physta\xae) on female reproductive hormones and bone biochemical markers: an ovariectomised rat model study

BackgroundEach year 1.5 million women experience menopause when menstrual cycles cease resulting from the loss of ovarian function and oestrogen deprivation, a hormone that helps prevent bone loss. This study investigated the effects of Physta®, a standardized herbal extract of Eurycoma longifolia Jack (PEL), on hormonal balance and parameters associated with hormonal imbalance, namely body and uterus weight and bone biochemical markers relevant in menopausal symptoms.MethodsForty-eight Sprague Dawley rats were randomly divided into six groups of eight rats each: (A) Sham operated; control (B) Untreated (ovariectomised (OVX) with vehicle), (C) PEL 100 (OVX + 100 mg/kg body weight (bw)), (D) PEL 300 (OVX + 300 mg/kg bw), (E) PEL 500 (OVX + 500 mg/kg bw) and (F) Positive control, testosterone undecanoate (TU) (OVX+ 10 mg/kg bw). Group A and B received daily oral administrations of the vehicle, Group C-E received daily oral administration of PEL and Group F received testosterone undecanoate intramuscularly weekly. At the end of 8 weeks, serum calcium, phosphate, bone alkaline phosphatase (BALP), osteocalcin, follicle stimulating hormone (FSH), luteinising hormone (LH), oestrogen, progesterone and testosterone were measured, then the animals were sacrificed and uterus was isolated, while weight was recorded in all experimental groups.ResultsTreatment of OVX rats with PEL at a dose of 500 mg/kg showed decreased serum FSH (P < 0.001, 4.25 ± 0.22 mIU/ml) and LH (NS, 4.07 ± 0.12 mIU/ml), while there was a significant increase in progesterone (P < 0.05, 2.48 ± 0.08 ng/ml) and oestrogen (P < 0.05, 11.02 ± 0.13 pg/ml) levels when compared to untreated group. PEL treatment at doses of 100 mg/kg, 300 mg/kg and 500 mg/kg showed a non-significant but increasing trend in serum calcium, phosphate, bone alkaline phosphate and testosterone levels. Ovariectomy resulted in a significant reduction (P < 0.001, 238.81 ± 5.39 mg) in uterus weight in the ovariectomised rats, which was alleviated in all PEL treated ovariectomised rats with an increasing trend of uterine weight.ConclusionThe results suggest that PEL could be protective and beneficial for the management of reproductive hormone and bone markers. Therefore, it could be used to address hormonal imbalances and symptoms associated with menopause.

Long-term testosterone undecanoate replacement therapy: Impact of ethnicity.

Testosterone replacement therapy (TRT) is indicated for symptomatic male hypogonadism. However, the safety and efficacy profiles across different ethnicities for long-term TRT remain unclear. To measure the impact of ethnicity on various biochemical parameters following testosterone undecanoate (TU) replacement. A retrospective analysis of 50 male patients treated with TU from 2006 to 2017 in a large secondary care centre was performed. Changes in total testosterone, PSA, haematocrit, haemoglobin, total cholesterol and low-density lipoprotein (LDL) over eight years of treatment were analysed. Wilcoxon rank sum test was used to assess differences in these parameters between Caucasians and South Asians. Thirty-one Caucasians (age: median (IQR) 55.0years (49.0-68.0); total duration of follow-up 6.1years (2.9-9.3)) and 19 South Asians (age: median (IQR) 52.0years (38.0-69.0); duration of follow-up 6.5years (1.3-8.4)) were treated with TU during the study period. There was no significant difference in total testosterone levels between the two ethnicities. We noted a higher free and bioavailable testosterone in South Asians than Caucasians, albeit within their reference range. PSA was higher in Caucasians than South Asians at two and eight years of TU therapy. After one year of TRT, haematocrit was higher in South Asians than Caucasians at one year, whereas LDL and total cholesterol were significantly higher in Caucasians than South Asians. Caucasians have a tendency towards increased PSA, total cholesterol and LDL compared with South Asians with TU replacement therapy. There is a higher increment of haematocrit in South Asians following one year of TU replacement therapy. All biochemical changes following TRT were within the respective reference ranges suggesting no apparent risk of prostate cancer and venous thromboembolism.

Differential effects of 11 years of long-term injectable testosterone undecanoate therapy on anthropometric and metabolic parameters in hypogonadal men with normal weight, overweight and obesity in comparison with untreated controls: real-world data from a controlled registry study

Background and significanceObesity is a chronic disease, warranting long-term medical intervention. We evaluated effects of testosterone (T) therapy (Th) in men with T deficiency with normal weight, overweight and obesity on anthropometric and metabolic parameters, compared with untreated men.MethodsHypogonadal men (n = 823) with total T ≤ 12.1 nmol/L (age: 60.6 ± 7.0 years) participated in an ongoing registry study. Among these men 474 (57.6%) were obese, 286 (34.8%) overweight and 63 (7.7%) had normal weight. T undecanoate injections were administered to 428 men and 395 remained untreated. Anthropometric and metabolic parameters were measured at least twice a year and changes adjusted for confounding factors to account for baseline differences between groups.ResultsLong-term TTh in hypogonadal men, irrespective of weight at baseline, produced improvements in body weight, waist circumference (WC) and body mass index (BMI). Furthermore, TTh decreased fasting blood glucose and HbA1c and improved lipid profiles. Gradual decreases in blood pressure (systolic and diastolic) and pulse pressure occurred in men treated with T in each group. Marked reductions in mortality and major cardiovascular events were recorded in men receiving TTh.ConclusionsOur findings demonstrate that TTh produces reductions in weight, WC, and BMI. There were 77 (19.5%) deaths in the untreated groups and 23 (5.4%) in the T-groups. Based on these findings we suggest that long-term TTh in overweight and obese hypogonadal men produces progressive and sustained clinically meaningful weight loss and that TTh may contribute to reductions in mortality and incident major adverse cardiovascular events.

Testosterone undecanoate effects on behavior and cognitive functions in male swiss albino mice exposed to chronic social defeat

Objective: To examine the impact of exogenous testosterone undecanoate (TU) on chronic stress-induced behavioral changes of sensory contact model in adolescent male Swiss Albino mice. Design: Stress was induced by sensory contact model (SCM) for 12 consecutive days. Defeated mice were randomly assigned to control group (vehicle), testosterone undecanoate (100mg/Kg) (TU 100) or testosterone undecanoate (500mg/Kg) (TU 500) given intramuscular once for 45 days administered 2 hours after the last SCM session. Results: SCM significantly reduced distance traveled, time spent in the center, average speed in the open field test compared to negative control group. In addition, SCM significantly reduced preference index of defeated group in the NOR test, time spent in the open arms in the EPM test, reduced escape time and time in the quadrant in Morris water maze test (MWM) when compared to the negative control group.SCM significantly reduced the mRNA expression of CREB in the hippocampus of defeated group when compared to the negative control group. In the open field test, TU 500 treatment showed a significant increase in both distance traveled and average speed compared to the defeated group, while TU 100 treatment did have an anxiolytic effect indicated by the significantly increased time spent in the center and the significantly reduced time spent in the corner and the significantly reduced immobility time when compared to the defeated group. Both TU 100 and TU 500 did improve the retention memory indicated by the significant increase in the preference index compared to the defeated group in the NOR test. In the EPM test, both TU 100 and TU 500 did show an anxiolytic effect through a significant increase in the time spent in the open arms and a significant reduction in the time spent in the closed arms compared to the defeated group. In MWM, both TU 100 and TU 500 showed a significant improvement in learning memory as indicated by a significant reduction in the escape time and a significant increase in the time spent in the target quadrant on the probe day. Interestingly, TU 500 treatment showed a significant increase in CREB relative mRNA expression in the prefrontal cortex region compared to both defeated and negative control groups. Conclusion: Exogenous testosterone administration ameliorated some age-related neurobehavioral responses after exposure to chronic social defeat; however, more studies are needed to clarify the mechanisms that underlie them.

EFFECT OF A COMBINATION OF DUTASTERIDE AND PARENTERAL TESTOSTERONE UNDECANOATE ON TESTOSTERONE DEFICIENCY SYMPTOMS AND PROSTATE IN PATIENTS WITH TESTOSTERONE DEFICIENCY AND BENIGN PROSTATIC HYPERPLASIA

Background and objective The effect of a combination of testosterone and 5-Alpha reductase inhibitors (5-ARIs) on serum tes-tosterone levels, TD symptoms, and the prostate are not sufficiently established. Therefore, we examined the effects of long-acting parenteral testosterone undecanoate (TU) and dutasteride used in combination for the treatment of BPH patients with TD.&nbsp; Subjects and methods We selected 130 patients with a prostate volume (PV) &gt; 30 g from those diagnosed with TD and had received parenteral TU for 1 year. These patients were assigned to the following two groups: Group I, which comprised patients who received TU injections along with dutasteride, and Group II, which included patients with TU-only treatment. Statistical analyses were performed between the two groups to compare the results of serological tests, symptom questionnaire scores, and PV.&nbsp; Results No significant differences were observed in the baseline characteristics such as mean age, comorbidities, testosterone levels, symptom questionnaire scores between the two groups. There were no significant differences in the testosterone levels or the change in testosterone levels after treatment between the two groups. The PV was significantly increased in Group II and significantly decreased in Group I. Both groups showed a significant increase in the total scores and all subscale scores of the IIEF and AMS after treatment. Group II had a significantly higher total IIEF score than Group I and a significantly lower score in the sexual function subscale of the AMS after treatment. Conclusions The combination of TU and dutasteride considerably improved serum testosterone levels, alleviated TD symptoms, and effectively reduced PV in patients with TD and BPH. However, compared with the TU-only treatment, the combination was less effective in improving symptoms related to sexual function. Therefore, dutasteride should be used with caution when treating BPH patients with TD, who mainly complain of sexual dysfunction.

EFFECT OF A COMBINATION OF OMEGA-3 AND ORAL TESTOSTERONE UNDECANOATE ON SERUM TESTOSTERONE LEVELS IN PATIENTS WITH TESTOSTERONE DEFICIENCY

Background and Objective Oral testosterone undecanoate (TU) is taken up by the intestinal lymphatic system. Thus, the dietary lipid content affects TU absorption. This study aimed to investigate the effect of combined omega-3 fatty acids (OMG3) and oral TU on serum testosterone levels in patients with testosterone deficiency (TD). Material and Methods Sixty consecutive patients with symptomatic TD and low serum total testosterone (TT) levels were enrolled and divided randomly into group 1, oral TU 80 mg twice daily for 30 days, and group 2, OMG3 and oral TU 80 mg twice daily for 30 days. Serum TT concentrations and male function scales were evaluated at baseline and 7 days and 1 month post-treatment. Dietary habits were investigated, and caloric and lipid intakes were measured during the treatment periods. Results The groups did not differ in terms of mean age, body mass index, comorbidities, initial serum TT concentrations, and IIEF/AMS scores. After 7 days and 1 month of treatment, serum TT concentrations were only significantly increased in group 2. The degree of increase in TT was higher in group 2 than in group 1 at 7 days and 1 month, although the difference was only significant at 1 month. Both groups exhibited significant improvements in IIEF and AMS scores at 1 month, with no significant inter-group difference. A diet diary study revealed that 23.3% and 20% of both groups did not eat breakfast and both groups consumed <12 g of lipids and <500 Kcals, without significance differences. Conclusion We observed a significant increase in serum TT concentration after 1 month of treatment with the combination of OMG3 and oral TU, compared to with oral TU monotherapy. Therefore, the combination of OMG3 and oral TU can be considered for the treatment of TD in Korean patients with irregular breakfast habits.

Anabolic androgenic steroids exert a selective remodeling of the plasma lipidome that mirrors the decrease of the de novo lipogenesis in the liver

IntroductionThe abuse of anabolic androgenic steroids (AASs) is a source of public concern because of their adverse effects. Supratherapeutic doses of AASs are known to be hepatotoxic and regulate the lipoproteins in plasma by modifying the metabolism of lipids in the liver, which is associated with metabolic diseases. However, the effect of AASs on the profile of lipids in plasma is unknown.ObjectivesTo describe the changes in the plasma lipidome exerted by AASs and to discuss these changes in the light of previous research about AASs and de novo lipogenesis in the liver.MethodsWe treated male Wistar rats with supratherapeutic doses of nandrolone decanoate and testosterone undecanoate. Subsequently, we isolated the blood plasma and performed lipidomics analysis by liquid chromatography-high resolution mass spectrometry.ResultsLipid profiling revealed a decrease of sphingolipids and glycerolipids with palmitic, palmitoleic, stearic, and oleic acids. In addition, lipid profiling revealed an increase in free fatty acids and glycerophospholipids with odd-numbered chain fatty acids and/or arachidonic acid.ConclusionThe lipid profile presented herein reports the imprint of AASs on the plasma lipidome, which mirrors the downregulation of de novo lipogenesis in the liver. In a broader perspective, this profile will help to understand the influence of androgens on the lipid metabolism in future studies of diseases with dysregulated lipogenesis (e.g. type 2 diabetes, fatty liver disease, and hepatocellular carcinoma).

316 Paradigm Shifting Beneficial Effects of TLANDO (Oral Testosterone) on Liver

Oral Testosterone, methyltestosterone (e.g., Testred), was approved in 1941 and indicated as a testosterone replacement therapy (TRT) in males with a deficiency or absence of endogenous testosterone. Its prolonged use has been severely limited because of the development of liver disease, such as peliosis hepatis, hepatic neoplasms, hepatocellular carcinoma cholestatic hepatitis, and jaundice.There are significant overlapped co-morbidities between male hypogonadism and non-alcoholic fatty liver disease (NAFLD): obesity, hypertension, type 2 diabetes, and metabolic syndrome. TLANDO, a novel oral TRT containing Testosterone Undecanoate (TU) lymphatically delivered, is currently under regulatory review for marketing approval. To evaluate the effect of TLANDO on liver safety in prolonged use and to assess beneficial effects of TLANDO in hypogonadal patients with fatty liver disease. To evaluate liver safety of TLANDO (oral TRT) in chronic use, a 52-week, multi-center, open-labelled, active controlled (topical T) study was performed in hypogonadal men (N=315) in the SOAR trial (NCT02081300). Serum liver enzymes were measured at each visit (7 visits through 52 weeks) and analyzed. To assess liver beneficial effects of TLANDO, a 16-week open-label, multi-center, single arm study was performed in the Liver Fat Study (LFS: NCT03868059) with TLANDO (225mg BID fixed dose) in hypogonadal subjects (N=36). Liver fat % was measured by the Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) technique.

187 Improvement of Metabolic Syndrome (MetS) Parameters in Men with Hypogonadism With and Without Testosterone Therapy (TTh): Real-Life Evidence from more than 7,000 Patient-Years

We have previously published benefits of testosterone therapy (TTh) on cardiometabolic risk factors over 8 years. To study effectiveness and safety of depot injections of testosterone undecanoate (TU) in a urological setting in comparison to an untreated hypogonadal control group. At time of analysis, 823 men with hypogonadism participated in a registry study established in 2004. 428 men received parenteral TU 1000 mg/12 weeks following an initial 6-week interval (T-group) for up to 11 years, 395 men decided against TTh and served as controls (CTRL). Measurements were performed 1-4 times a year for approximately 7,116 patient-years. Mean changes over time between groups were compared by mixed effects model for repeated measures with random effect for intercept and fixed effects for time, group and their interaction and adjusted for age, weight, waist circumference, fasting glucose, blood pressure, lipids, and quality of life scale AMS to account for baseline differences between groups.

314 Improvement of Urinary Function Improves in Hypogonadal Men Receiving Long-term Treatment with Testosterone Compared to a Hypogonadal Control Group: 7116 Patient-years of Clinical Experience

In the most recent version of the EAU Guidelines on Male Hypogonadism, the contraindication severe LUTS due to BPH has been removed. In an ongoing registry study we monitored urinary function for a maximum of 12 years. We report data from 823 men with symptomatic hypogonadism participating in a registry study started in 2004. 428 men received testosterone undecanoate (TU) injections 1000 mg/12 weeks following an initial 6-week interval (T-group), 395 opted against TTh serving as controls (CTRL). Changes over time between groups were compared by a mixed effects model for repeated measures with a random effect for intercept and fixed effects for time, group and their interaction and adjusted for age, weight, waist circumference, blood pressure, fasting glucose, lipids and quality of life to account for baseline differences between groups. Mean (median) follow-up: T-group 8±3 (9), CTRL 9±2 (10) years. Total observation time: T-group 3594, CTRL 3522 years. Baseline age: 58±7 (T-group) vs. 64±5 years (CTRL).

182 Improved Patient Reported Sexual and Mental Domain Outcomes with Oral Testosterone (TLANDO) Relative to Topical Testosterone in Treated Hypogonadal Men

Male hypogonadism is characterized by symptoms and deficiency in testosterone (total testosterone (TT) levels of <300 ng/dL), a critical hormone for sexual, cognitive, and body function and development. Free testosterone (fT) is testosterone not bound to protein and available to bind to receptors for androgenic action. fT accounts for only 1% to 4% of TT and typically fT < 6 ng/dL also can be considered hypogonadism. TLANDO, an oral Testosterone undecanoate (TU) lymphatically delivered TRT option with non liver-toxicity, currently under regulatory review has demonstrated efficacy with consistent intra and inter-day TT levels in hypogonadal men. Moreover, TLANDO’s proposed fixed (no titration) dose dosing regimen reliably normalized TT levels in more than 80% of the hypogonadal subjects without regard to meal fat content. Multiple clinical studies have demonstrated good gastrointestinal tolerability and good safety profile up to 52-week study duration. The goal of this report is to assess key sexual and mental domain related Patient Reported Outcomes (PRO) following TLANDO (oral TRT) compared to topical TRT in hypogonadal men and examine the role of fT as the key serum marker to assess successful treatment in TRT.

A new oral testosterone undecanoate therapy comes of age for the treatment of hypogonadal men.

Background:A novel formulation of oral testosterone undecanoate (TU) was studied in a long- and short-term phase III trial to evaluate safety and efficacy.Methods:Hypogonadal men (age 18–65 years; two morning serum testosterone (T) <300 ng/dl with signs/symptoms) were recruited into a 365 day (trial I) or 105 day (trial II), randomized, multicenter trial. Patients were randomized 1:1 to oral TU (n = 161) or T-gel (n = 160) in trial I, and 3:1 to oral TU, twice daily (BID) JATENZO® (n = 166) or a topical T product [Axiron® (n = 56)] in trial II. Dose adjustments were based on average T concentrations (Cavg). Efficacy was assessed based on T levels, body composition and bone density. Safety was assessed by standard clinical measures.Results:Oral TU efficacy (% of patients with eugonadal T Cavg) was 84% (serum Cavg = 628 ± 343 ng/dl) and 87% (serum T equivalent Cavg ≈ 489 ± 155 ng/dl) in trials I and II, respectively. Oral TU significantly (p <0.0001) improved all Psychosexual Daily Questionnaire parameters in trials I and II. In trial I, lean mass increased 3.2 ± 2.7 kg and fat decreased by 2.4 ± 3.6 kg (both p <0.0001) and bone density improved in hip (+0.012 ± 0.0225 g/cm2) and spine (+0.018 ± 0.0422 g/cm2) after 365 days (both p <0.0001). Oral TU-associated adverse effects were consistent with other T-replacement therapies but oral TU patients experienced a greater number of mild gastrointestinal adverse effects. Oral TU subjects in both studies exhibited an increase in mean systolic blood pressure of about 3–5 mmHg. Oral TU was not associated with liver toxicity nor did it cause an elevation in high-sensitivity C-reactive protein or lipoprotein-associated phospholipase A2 (cardiovascular safety biomarkers) after 365 days of therapy.Conclusion:A new oral TU formulation was safe and effective and represents a significant therapeutic advance for the treatment of appropriate hypogonadal men.

378 Improvement of Erectile Function in Hypogonadal Men Receiving Long-term Treatment with Testosterone Compared to a Hypogonadal Control Group: 7116 Patient-years of Clinical Experience

Testosterone Deficiency was added to the 2018 AUA Guidelines with 31 Statements, with a moderate recommendation in informing patients about improvement of erectile function (EF) under treatment. In an ongoing registry study in a single urology practice, we monitored EF for up to 12 years. We report data from 823 men with symptomatic hypogonadism participating in a registry study started in 2004. 428 men received testosterone undecanoate (TU) injections 1000 mg/12 weeks following an initial 6-week interval (T-group), 395 opted against TTh and served as controls (CTRL). Changes over time between groups were compared by a mixed effects model for repeated measures with a random effect for intercept and fixed effects for time, group and their interaction and adjusted for age, weight, waist circumference, blood pressure, fasting glucose, lipids and quality of life to account for baseline differences between groups. Mean (median) follow-up: T-group 8±3 (9), CTRL 9±2 (10) years. Total observation time: T-group 3594, CTRL 3522 years. Baseline age: 58±7 in T-group, 64±5 years in CTRL.

The Oxidant Effect of Bisphenol A (BPA) Can be Decoupled from its Endocrine Disruptor Property

Bisphenol A (BPA) is an environmental defilement released mainly from polycarbonate plastic and epoxy resins. The main toxicological impact of BPA is its endocrine disruptor activities. Its structural features confer the ability to bind to both estrogen receptor (ER) subtypes. Furthermore, we recently reported that BPA aggravates male reproductive hormones. In addition to its endocrine disruptor properties, we have also reported that BPA possesses oxidant activity which is able to trigger oxidative stress. Several types of research previously reported that oxidative stress may cause hormonal imbalance and vice versa. However, the relation of both the toxicological properties of BPA is poorly understood. In this study, we found that oral testosterone undecanoate treatment in BPA-induced rats does not prevent decreasing serum superoxide dismutase, glutathione peroxidase, and catalase, and increasing serum malondialdehyde. Oral N-acetyl cysteine (NAC) in BPA-induced rats also does not attenuate decreasing total testosterone levels. These results suggest that the oxidant effect and endocrine disruptor property of BPA can be separated and might not interfere with one another. Therefore, future treatment in any pathological condition resulting from BPA exposure has to be carried out with more comprehensive approaches rather than focusing on its endocrine disruptor activity.