Effects Of Testosterone Undecanoate Research Articles

Effect of Testosterone Undecanoate on Sexual Functions, Glycaemic Parameters, and Cardiovascular Risk Factors in Hpogonadal Men with Type 2 Diabetes Mellitus.

To study the effect of testosterone undecanoate on sexual functions, glycaemic parameters, and cardiovascular (CV) risk factors in hypogonadal men with type 2 diabetes mellitus (T2DM). It was an open label, single-arm interventional study where testosterone undecanoate (TU) was used in 105 T2DM males aged 30-60 years with hypogonadism. The effect of TU on sexual functions was assessed using the Aging Male Symptoms (AMS) Scale and the International Index of Erectile Function-5 (IIEF-5) Questionnaire. The effect on glycaemic parameters, cardiovascular risk factors (lipids, high-sensitivity C-reactive protein [hsCRP] and carotid intima media thickness [CIMT]) were assessed over a period of 54 weeks of TU therapy. Prevalence of hypogonadism in T2DM patients was 19.1%, of which 74.1% had functional hypogonadism. AMS and IIEF-5 scores showed negative and positive correlation, respectively, with baseline serum testosterone levels. The AMS score showed a significant reduction of 5.8% and IIEF-5 score improved by 31.5% at 54 weeks of TU therapy. Glycosylated hemoglobin (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), and lipids such as total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TG) were significantly reduced by 0.6%, 10.9%, 6.28%, 9.04%, and 6.77%, respectively, at 54 weeks. CIMT was significantly reduced by 2.57% at 54 weeks, whereas no significant change observed with hsCRP. TU is an effective treatment modality for hypogonadal men with T2DM, and it has beneficial effects on sexual functions, glycaemic parameters, and CV risk factors.

Effects of testosterone undecanoate on performance during multi-stressor military operations: A trial protocol for the Optimizing Performance for Soldiers II study

BackgroundPreviously, young males administered 200 mg/week of testosterone enanthate during 28 days of energy deficit (EDef) gained lean mass and lost less total mass than controls (Optimizing Performance for Soldiers I study, OPS I). Despite that benefit, physical performance deteriorated similarly in both groups. However, some experimental limitations may have precluded detection of performance benefits, as performance measures employed lacked military relevance, and the EDef employed did not elicit the magnitude of stress typically experienced by Soldiers conducting operations. Additionally, the testosterone administered required weekly injections, elicited supra-physiological concentrations, and marked suppression of endogenous testosterone upon cessation. Therefore, this follow-on study will address those limitations and examine testosterone's efficacy for preserving Solder performance during strenuous operations. MethodsIn OPS II, 32 males will participate in a randomized, placebo-controlled, double-blind trial. After baseline testing, participants will be administered either testosterone undecanoate (750 mg) or placebo before completing four consecutive, 5-day cycles simulating a multi-stressor, sustained military operation (SUSOPS). SUSOPS will consist of two low-stress days (1000 kcal/day exercise-induced EDef; 8 h/night sleep), followed by three high-stress days (3000 kcal/day and 4 h/night). A 23-day recovery period will follow SUSOPS. Military relevant physical performance is the primary outcome. Secondary outcomes include 4-comparment body composition, muscle and whole-body protein turnover, intramuscular mechanisms, biochemistries, and cognitive function/mood. ConclusionsOPS II will determine if testosterone undecanoate safely enhances performance, while attenuating muscle and total mass loss, without impairing cognitive function, during and in recovery from SUSOPS. Trial RegistrationClinicalTrials.gov Identifier: NCT04120363.

Effects of Testosterone Undecanoate vs Placebo on Intrahepatic Fat Content in Obese Men With T2DM and Hypogonadism

Effects of Testosterone Undecanoate vs Placebo on Intrahepatic Fat Content in Obese Men With T2DM and Hypogonadism

Effects of Testosterone on the Functional Activity of P-Glycoprotein

The effects of testosterone undecanoate on the functional activity of P-glycoprotein (ABCB1 protein) were studied in male Chinchilla rabbits. Testosterone was given as single intramuscular doses of 12 or 24 mg/kg. The functional activity of P-glycoprotein was determined in terms of the pharmacokinetics of its marker substrate - fexofenadine - on days 7, 14, and 21 after hormone administration. Administration of testosterone at a dose of 12 mg/kg (n = 7) increased the C max of fexofenadine on days 7 and 14 and AUC 0-t on day 14 and decreased total clearance on day 14. Use of testosterone at a dose of 24 mg/kg (n = 7) led to increases in the C max of fexofenadine on day 7 and AUC 0-t on days 7, 14, and 21 and decreased total clearance on days 7 and 14. These changes in the pharmacokinetics of fexofenadine provide evidence of decreases in the functional activity of Pgp on the background of testosterone administration. Correlational relationships were found between measures of the pharmacokinetics of fexofenadine and serum testosterone levels.

Effects of 5-Year Treatment With Testosterone Undecanoate on Lower Urinary Tract Symptoms in Obese Men With Hypogonadism and Metabolic Syndrome

To investigate the possible effects of testosterone undecanoate (TU) injections in a population of obese (mean age 57) hypogonadal men with lower urinary tract symptoms (LUTS) in a long-term observational study. Twenty obese hypogonadal men with metabolic syndrome were treated with TU injections every 12weeks for 60months; also 20 matched subjects in whom TU was unaccepted or contraindicated were used as controls. LUTS severity and the impact of TU injections were assessed by differences in International Prostate Symptom Score (IPSS), maximum urinary flow (Qmax) rate in milliliters, post-void residual (PVR) volume, and prostate size every 12months in a 5-year controlled study. TU injections did not produce differences in IPSS, Qmax, PVR, and prostate size in both groups. No modification in prostate-specific antigen (PSA) and hematocrit levels was also found between the 2 groups. Interestingly, controls showed increased incidence of prostatitis than TU-treated men (10% vs 30%, P<.01). We showed that 5years of TU treatment did not change IPSS, PVR, Qmax, or prostate size in obese hypogonadal men with metabolic syndrome and moderate LUTS at baseline. Therefore, long-term TU replacement therapy is a safe and effective treatment for reverting hypogonadal features related to metabolic syndrome and does not impact negatively on LUTS and prostate volume.

Editorial Comment

A decade ago, The Institute of Medicine Report on Testosterone and Aging1Liverman C.T. Blazer D.G. Testosterone and Aging: Clinical Research Directions. Institute of Medicine of the National Academies. The National Academy of Sciences. National Academy Press, Washington, D.C.2004Google Scholar indicated that “the potential for testosterone therapy to increase risk for symptomatic prostatic hypertrophy is of major concern… but quantifying these risks will require randomized trials that include large number of men followed for multiple years.” In relation to the development of prostate cancer, the report drew attention to the need for a study including a population of 5000 men followed for 3 to 5 years. The logistic and financial implications of such undertakings are enormous and little progress has occurred since. Most of the information on the effect of testosterone on prostate enlargement is drawn from trials assessing new delivery forms of testosterone, involve a limited number of participants, and typically have insufficient follow-up. Therefore, by default, evidence accumulates through reports such as this one that are controlled and randomized, include credible outcome measures, and a significant follow-up, but still lack sufficient power to provide categorical evidence. Nevertheless, it adds to the growing body of literature reassessing the effect of androgens on the prostate gland.2Fernández-Balsells M.M. Murad M.H. Lane M. et al.Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis.J Clin Endocrinol Metab. 2010; 95: 2060-2075Crossref Scopus (544) Google Scholar The relationship between the prostate and gonadal steroids is complex and incompletely understood. There is corroborated data indicating that serum levels of androgens do not reflect the prostatic microenvironment.3Marks L.S. Mostaghel E.A. Nelson P.S. Prostate tissue androgens: history and current clinical relevance.Urology. 2008; 72: 247-254Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar, 4Page S.T. Lin D.W. Mostaghel E.A. et al.Dihydrotestosterone administration does not increase intraprostatic androgen concentrations or alter prostate androgen action in healthy men: a randomized-controlled trial.J Clin Endocrinol Metab. 2011; 96: 430-437Crossref PubMed Scopus (58) Google Scholar Thus, it is not surprising that this study supports clinical observations made well over a decade ago (references 29 and 30 in the article). However, it is increasingly evident that direct effects of androgens on the prostate are only part of the story. Consequently, this report advances the notion of a causal relationship between hypogonadism and the metabolic syndrome with prostate inflammation and hypertrophy. Although this concept remains speculative, it also has an appealing rationale. Proinflammatory cytokines (tumor necrosis factor-α, C-reactive protein, interleukin-β) have been found to be elevated in patients with hypogonadism, are considered surrogate marker for the metabolic syndrome, and are known to decrease during testosterone therapy.5Corcoran M.P. Meydani M. Lichtenstein A.H. et al.Sex hormone modulation of proinflammatory cytokine and C-reactive protein expression in macrophages from older men and postmenopausal women.J Endocrinol. 2010; 206: 217-224Crossref PubMed Scopus (100) Google Scholar, 6Kalinchenko S.Y. Tishova Y.A. Mskhalaya G.J. et al.Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double-blinded placebo-controlled Moscow study.Clin Endcrinol (Oxf). 2010; 73: 602-612Crossref PubMed Scopus (277) Google Scholar Undoubtedly, these are auspicious areas of research worth pursuing. Effects of 5-Year Treatment With Testosterone Undecanoate on Lower Urinary Tract Symptoms in Obese Men With Hypogonadism and Metabolic SyndromeUrologyVol. 83Issue 1PreviewTo investigate the possible effects of testosterone undecanoate (TU) injections in a population of obese (mean age 57) hypogonadal men with lower urinary tract symptoms (LUTS) in a long-term observational study. Full-Text PDF ReplyUrologyVol. 83Issue 1PreviewThe literature is presently lacking large controlled, long-term studies on the effects of testosterone replacement therapy (TRT) because of economic considerations. There are several small interventional non controlled studies that report similar results,1 but this indeed represents the first controlled, non sponsored, 5-year study investigating the effects of TRT on urinary tract function. While I was designing such a complex study, I had clear in my mind 3 important facts that potentially would not have been harmful to the prostate: first, according to our previous study,2 intramuscular testosterone undecanoate is poorly aromatized into estrogens; second, after TRT, intraprostatic levels of testosterone and its metabolite dihydrotestosterone, are by far lower than plasmatic ones3; third, testosterone withdrawal does not permanently revert hypogonadism as well as body composition changes determined by TRT (data not published) and, thus, it should be continuously administered in hypogonadal men. Full-Text PDF

Effect of testosterone undecanoate on hematological profiles, blood lipid and viscosity and plasma testosterone level in castrated rabbits

The association between testosterone replacement therapy and cardiovascular risk remains controversial. Blood viscosity is a known individual risk factor for cardiovascular disease mortality. The objective of the present study was to investigate the effects of the long-acting injectable testosterone undecanoate (TU) on risk factors of cardiovascular disease. In total, 24 male New Zealand white rabbits (2.5 kg) were randomly divided into 3 groups of 8. Group 1 was used as control. Group 2 was castrated bilaterally and Group 3 was administrated with 6 mg/kg of TU at day 1 and 6 weeks after castration. Whole blood viscosity, total plasma testosterone, hemoglobin (Hb), hematocrit (Hct), fibrinogen (FBN), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were measured at baseline, 6 weeks and 18 weeks. In the control group, whole blood viscosity and FBN were significantly increased at 6 and 18 weeks. Castration significantly increased the levels of TC, TG, HDL-C and LDL-C, but decreased Hct and Hb. In the TU injection group, whole blood viscosity was markedly decreased in all share rates, whereas the FBN level was increased. Hb and Hct showed a tendency for higher concentration at 6 weeks. Long-acting injectable TU provides another reliable treatment option for testosterone replacement therapy. Moreover, the patients may receive additional beneficial effect in lowered whole blood viscosity.

Effectiveness of Testosterone Undecanoate Treatment in Men with Asthenospermia

Objective To assess the effectiveness of testosterone undecanoate on sperm motility and pregnancy incidence in men with asthenospermia. Methods A clinical trial was performed. Fifty men with asthenospermia were included to receive placebo (control group, n=9) or T undecanoate 80 mg/d (study group, n=41). Pregnancy incidence and sperm characteristics after 1, 2 and 3 months of medication and 3 months after the end of the trial were measured. Results Compared with the placebo, T undecanoate treatment produced a satisfactory improvement of seminal motility (F=55.904, P=0.000). In study group, the incidence of pregnancy was 28.2% while the incidence of pregnancy in control group was 11.1%. In study group, 26 patients took T undecanoate for more than 3 months. In the 3 months, semen volume showed no statistical difference (F=1.206, P=0.312) before and after treatment, sperm concentration (F=0.023, P=0.000) and motility a, b, a+b (P=0.000) showed statistical differences. Motility grade a showed significantly higher increment in 2 and 3 months after treatment than 1 month and there was no statistical difference between 2 and 3 months. So did grade b. Conclusions The results indicate that T undecanoate increases seminal motility, leading to a higher incidence of pregnancy in couples with infertility related to asthenoaspermia.

Effects of Testosterone Undecanoate on Cardiovascular Risk Factors and Atherosclerosis in Middle-Aged Men with Late-Onset Hypogonadism and Metabolic Syndrome: Results from a 24-month, Randomized, Double-Blind, Placebo-Controlled Study

Effects of Testosterone Undecanoate on Cardiovascular Risk Factors and Atherosclerosis in Middle-Aged Men with Late-Onset Hypogonadism and Metabolic Syndrome: Results from a 24-month, Randomized, Double-Blind, Placebo-Controlled Study

Effects of Testosterone Undecanoate on Cardiovascular Risk Factors and Atherosclerosis in Middle-Aged Men with Late-Onset Hypogonadism and Metabolic Syndrome: Results from a 24-month, Randomized, Double-Blind, Placebo-Controlled Study

Longitudinal studies have demonstrated that male hypogonadism could be considered a surrogate marker of incident cardiovascular disease. To evaluate the effects of parenteral testosterone undecanoate (TU) in outclinic patients with metabolic syndrome (MS) and late-onset hypogonadism (total testosterone (T) at or below 11nmol/L or free T at or below 250pmol/L). This is a randomized, double-blind, double-dummy, placebo-controlled, parallel group, single-center study. Fifty patients (mean age 57±8) were randomized (4:1) to receive TU 1,000mg (every 12 weeks) or placebo (PLB) gel (3-6 g/daily) for 24 months. Homeostasis model assessment index of insulin resistance (HOMA-IR), carotid intima media thickness (CIMT), and high-sensitivity C-reactive protein (hsCRP). At baseline, all patients fulfilled the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) and International Diabetes Federation (IDF) criteria for the definition of MS. An interim analysis conducted at 12 months showed that TU markedly improved HOMA-IR (P < 0.001), CIMT (P < 0.0001), and hsCRP (P<0.001) compared with PLB; thus, all patients were shifted to TU treatment. After 24 months, 35% (P < 0.0001) and 58% (P < 0.001) of patients still presented MS as defined by NCEP-ATPIII and IDF criteria, respectively. Main determinants of changes were reduction in waist circumference (P<0.0001), visceral fat mass (P<0.0001), and improvement in HOMA-IR without changes in body mass index (BMI). TU reduced fasting glucose, waist circumference, and improved surrogate markers of atherosclerosis in hypogonadal men with MS. Resumption and maintenance of T levels in the normal range of young adults determines a remarkable reduction in cardiovascular risk factors clustered in MS without significant hematological and prostate adverse events.

T04-P-04 Effects of Testosterone Undecanoate (TU) administered alone or in combination with letrozole or dutasteride in Female to Male transsexuals (FtM)

Introduction The role of testosterone (T) and its metabolites, diidrotestosterone (DHT) and estradiol (E), on different physiological functions is not completely known. Ovariectomized FtM T treated represent an interesting model to study the effects of T and its metabolites on different physiological functions. In this study, TU 1000 mg (Nebido ® ) was injected in 15 FtM (week 0, 6,18, 30 and 42) alone (n=5; group A) or in combination with dutasteride 5 mg/d (n=5; group B) or letrozole 5 mg/d (n=5; group C). Results Hormone, bone and metabolic parameters at baseline and at week 54 were: TotalT (nmol/L) GROUP A 7.9±6.0, 13.6±2.6, GROUP B 7.1±6.3, 18.4±4.6§, GROUP C 4.8±4.8, 18.2±4.2§, baseline and wk 54 respectively. E (pmol/L) GROUP A 64.4±43.4, 89.6±36.3, GROUP B 41.4±19.4, 76.0±47.4, GROUP C 37.8±23.1, 18.0±0.0* baseline and wk 54 respectively. DHT (nmol/L) GROUP A 1.3±1.2, 2.2±0.9, GROUP B 1.0±0.7, 0.4±0.1*, GROUP C 0.9±0.7, 2.7±1.3 baseline and wk 54 respectively. *= P §= P No significant changes of any parameters occurred except for bone mass density that significantly decreased in group C and lean mass that increased significantly less in group B as compared to group A. TU injections were well tolerated by all subjects. Conclusions This data suggests that TU is an optimal formulation for replacement in FtM that is well accepted and does not cause major problems. The aromatization of TU is important for maintenance of bone density while DHT may have a role in muscle mass maintenance.

Effects of Testosterone Undecanoate as a Male Contraceptive Candidate on Rat Immunological Features

Testosterone undecanoate (TU) is under phase III clinical trial as a hormonal male contraceptive in China. Sex hormones can modulate the immune system. Female hormonal contraceptives may affect SIV/HIV‐1 transmission. To evaluate the safety of TU and to understand whether long‐term use of TU for a male contraceptive affects users' immunological features, adult male rats were treated for a 32‐week TU‐treated phase at the dose of 20 mg TU/kg body weight and a 24‐week recovery phase. The reproductive and immunological parameters of 4–6 rats in each subgroup were examined at the stated time point. The mean sperm count and viability in the treated rats were significantly suppressed (p < 0.01). In the TU‐treated group: the mean blood leukocyte and lymphocyte counts; the proliferation indexes of T cells from peripheral blood mononuclear cells (PBMC) and spleen; and, of B cells from spleen, as well as the mean counts of blood T, NK, and B cells decreased in comparison with those of control group. These decreases were not significant (p > 0.01). Similarly, the mean serum IgM, IgG, and IgA levels and complement activity in TU‐treated rats were lower than those in control group (p > 0.01), and the changes in the antibody levels of the examined genital secretions were not significant (p > 0.01). The changes in the thickness of urethra epithelium, and in secretory component (SC) expression in genitals were not observed in the treated group. These results demonstrated that long‐term supraphysiological TU injection did not obviously affect the examined rat immunological parameters.