Testosterone Therapy In Hypogonadal Men Research Articles

Testosterone treatment improves liver function and reduces cardiovascular risk: A long-term prospective study

ABSTRACT Objectives: To report the association between testosterone treatment in hypogonadal men with hepatic steatosis, non-alcoholic fatty liver disease and cardiovascular disease (CVD). Methods: A prospective study was conducted to assess the physiological and functional performance of the long-term effects of testosterone undecanoate treatment on hepatic steatosis in 496 hypogonadal men. Two groups were studied, the treatment group (T-group) of 312 patients treated with TU 1000 mg every 12 weeks and followed for 8 years, and an untreated control group (C-group) of 184 patients. We evaluated liver functions and Fatty Liver Index (FLI) according to Mayo Clinic parameters and guidelines. Results: The T-group showed a decrease in the FLI (from a mean [SD] of 83.70 [12.15] to 67.12 [19.21]), bilirubin (from a mean [SD] of 1.69 [4.21] to 1.31 [1.91] mg/dL), triglycerides (from a mean [SD] of 254.87 [92.99] to 213.37 [66.91] mg/dL), and gamma-glutamyl-transferase (from a mean [SD] of 39.45 [11.51] to 29.11 [7.68] U/L) over the duration of the study. Other parameters were also reduced in the T-group such as body mass index (from a mean [SD] of 31.59 [4.51] to 29.50 [3.84] kg/m2) and waist circumference (from a mean [SD] of 107.51 [9.95] to 101.86 [9.28] cm). A total of 25 deaths (7.8%) were recorded in the T-group, among them, 11 (44%) were related to CVD. While in the C-group 28 deaths (15.2%) were recorded and all the reported deaths (100%) were related to CVD. Conclusions: The findings suggest that long-term testosterone therapy in hypogonadal men improves liver function. While, the physiological and functional improvements in the liver may be associated with a decrease in CVD-related mortality. Abbreviations ALT: alanine transaminase; AR: androgen receptor; AST: aspartate transaminase; BMI: body mass index; CVD: cardiovascular disease; FLI: Fatty Liver Index; γ-GT: gamma-glutamyl-transferase; MetS: metabolic syndrome; LDL: low-density lipoprotein; NAFLD: non-alcoholic fatty liver disease; RCT: randomised controlled trial; T2DM: type II diabetes mellitus; TT: total testosterone; TTh: testosterone therapy; TU: testosterone undecanoate; WC: waist circumference

Erythrocytosis in a Large Cohort of Trans Men Using Testosterone: A Long Term Follow up Study on Prevalence, Determinants, and the Effect of Years of Exposure

Background: Erythrocytosis is a known side effect of testosterone therapy in hypogonadal men and can increase the risk of thromboembolic events. Erythrocytosis is also seen in trans men (birth-assigned female, male gender identity) receiving testosterone therapy. Currently there are no clinical guidelines for the management of this problem in trans men. Specific aims: 1. To study the prevalence and determinants in the development of erythrocytosis in trans men using testosterone. 2. To study the association between duration of testosterone treatment and hematocrit levels. Methods: A 20 year follow-up study in adult trans men who started testosterone, and had monitoring of hematocrit levels at our center (n=1073). Results: Erythrocytosis (defined as hematocrit levels of >0.50 l/l twice) occurred in 11% of trans men. Multilevel analyses showed former or current smoking (OR 2.2, 95%CI 1.6-3.3), testosterone administration as long-acting intramuscular injection (OR 2.9, 95% CI 1.7-5.0), a higher age at initiation of hormone therapy (up to OR 5.9, 95% CI 2.8-12.3) for people above 40 compared to <18), higher BMI (>30 g/m2 compared to 18.5-25 kg/m2) (OR 3.7, 95% CI 2.2-6.2) and a medical history for chronic pulmonary diseases, sleep apnea or polycythemia vera (OR 2.5, 95% CI 1.4-4.4) as determinants that increased the risk of high hematocrit levels. In the first year of testosterone therapy hematocrit levels increased most: from 0.39 l/l at baseline to 0.45 l/l after 1 year. Although there was only a slight continuation of this increase in the following 20 years (0.45 at 1 year and 0.46 at 20 years), the probability of developing erythrocytosis still increased (10% after 1 year, 38% after 20 years). Conclusion: Erythrocytosis frequently occurs in trans men using testosterone. The biggest increase in hematocrit was seen in the first year, but also after the first years there is a substantial number of people that present with hematocrit >0.50. Because smoking, obesity and use of injection as dosage form are associated with a higher risk for erythrocytosis, a reasonable first step in the care for transmen with erythrocytosis while on testosterone is to advise them to quit smoking and to switch to a transdermal administration type and if BMI is high, to lose weight.

Testosterone Therapy Effects on Bone Mass and Turnover in Hypogonadal Men with Type 2 Diabetes.

Male hypogonadism is associated with low bone mineral density (BMD) and increased fragility fracture risk. Patients with type 2 diabetes (T2D) have relatively higher BMD, but greater fracture risk. Evaluate the skeletal response to testosterone therapy in hypogonadal men with T2D compared with hypogonadal men without T2D. Single arm, open-label clinical trial (NCT01378299) involving 105 men (40-74 years old), with average morning testosterone <300 ng/dL. Subjects were injected intramuscularly with testosterone cypionate (200 mg) every 2 weeks for 18 months. Testosterone and estradiol were assessed by liquid chromatography/mass spectrometry; serum C-terminal telopeptide of type I collagen (CTX), osteocalcin and sclerostin by enzyme-linked immunosorbent assay; glycated hemoglobin (HbA1c) by high-performance liquid chromatography, areal BMD (aBMD) and body composition by dual-energy x-ray absorptiometry; tibial volumetric BMD (vBMD) and bone geometry by peripheral quantitative computed tomography. Among our population of hypogonadal men, 49 had T2D and 56 were non-T2D. After 18 months of testosterone therapy, there were no differences in circulating testosterone and estradiol between the groups. Hypogonadal men with T2D had increased osteocalcin, reflecting increased osteoblast activity, compared with non-T2D men (P < .01). T2D men increased lumbar spine aBMD (P < .05), total area at 38% tibia (P < .01) and periosteal and endosteal circumferences at the same site (P < .01 for both). T2D men had reduced tibial vBMD (P < .01), but preserved bone mineral content (P = .01). Changes in HbA1c or body composition were similar between the 2 groups. Testosterone therapy results in greater improvements in the skeletal health of hypogonadal men with T2D than their nondiabetic counterparts.

Design and Conduct of a Real-World Single-Center Registry Study on Testosterone Therapy of Men with Hypogonadism

Aims: Despite the prevalence of hypogonadism (testosterone deficiency [TD]) and widespread use of testosterone therapy (TTh), the effectiveness and safety of long-term testosterone use remains highly contested. Over the past 15 years, we have conducted a registry study of men with TD with a focus on several health outcomes associated with TTh. Design: Observational patient disease registry study. Materials and Methods: Noninterventional disease registry with prospective longitudinal data on a large sample of adult hypogonadal men (n = 858) who were treated in a single Urology Clinic. The registry evaluates men with symptomatic TD during a urological exam of patients who have not been previously treated with TTh. There were no inclusion/exclusion criteria. All hormone assays are carried out in a single laboratory. Standard-of-care treatment of each patient is the sole responsibility of the attending clinician. The registry data consist of comprehensive medical records and questionnaire data collected during patient visits. The registry has a dedicated statistician to ensure adequate statistical analyses of all outcome measures assessed. Main Outcome Measures: We measured the following parameters: height, weight, waist circumference, hemoglobin, hematocrit, fasting glucose, glycated hemoglobin, insulin, systolic and diastolic blood pressure, heart rate, lipids (total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides), highly sensitive C-reactive protein, and total testosterone (T). We assessed quality of life, erectile and urinary function. Clinical parameters were measured two to four times a year. Data are analyzed in regular intervals. Results: As of 2019, 858 men have been enrolled, of whom 85 patients exhibited primary hypogonadism, and the remaining 773 exhibited secondary or functional hypogonadism. Findings from this registry study on the benefit of TTh on anthropometric parameters, cardiometabolic function, diabetes, and prostate health have been reported. Conclusions: This registry study has provided real-world clinical evidence and produced new important findings regarding the effectiveness and safety of long-term TTh in hypogonadal men.

Controversies in Testosterone Therapy.

Testosterone prescriptions have increased dramatically in recent years, largely because of changes in expert guidelines. Concerns have been raised that testosterone therapy (TTh) may be associated with an increased incidence of conditions such as cardiovascular (CV) disease, thromboembolic events, obstructive sleep apnea (OSA), benign prostatic hyperplasia (BPH), and prostate cancer (PCa) and also may be a beneficial therapy in the management of prediabetes. As such, considerable debate remains regarding which hypogonadal populations are appropriate candidates for TTh. This systematic review aims to affirm or refute, using the most current evidence, the published concerns surrounding TTh and its potential increased risk of conditions such as CV disease, thromboembolic events, OSA, urolithiasis, BPH, and PCa, as well as its role as a potential tool for managing prediabetes. A systematic review of literature surrounding TTh and its impact on increasing risk for the adverse conditions mentioned previously was performed. 62 publications were selected for inclusion based on their relevance to the effects and risks of TTh. Evidence is current through December2019. Evidence demonstrates that positive associations exist between TTh and OSA, erythrocytosis, as well as urolithiasis. TTh may potentially be used to treat hypogonadal men with prediabetes. While low testosterone is positively correlated with adverse CV events, TTh in hypogonadal men either has no effect or decreases such risk. TTh is likely not associated with increased risk of PCa incidence or recurrence. Despite historical beliefs that TTh increases the risk of CV disease, thromboembolic events, BPH, and PCa, recent evidence suggests that TTh conveys less risk than previously perceived. While caution should continue to be exercised, evidence suggests that TTh is a reasonable treatment option in many hypogonadal men who were previously excluded from TTh based on risk factors and prior health histories. Twitchell DK, Pastuszak AW, Khera M. Controversies in Testosterone Therapy. Sex Med Rev 2021;9:149-159.

SUN-083 Hypertension and Hemodynamic Parameters in Men with Hypogonadism Improve Under Long-Term Treatment with Testosterone Undecanoate Injections (TU) Compared to Untreated Hypogonadal Control Patients

Background: The prevalence of hypogonadism in men with hypertension is high and may be related to overweight and obesity. In an ongoing registry study in a single urology practice, we monitored blood pressure and hemodynamic parameters for up to 12 years. Material and Methods: In a registry study of men with hypogonadism in a urological office, 676 of 805 patients (84%) had hypertension defined as systolic blood pressure (SBP) ≥130 and/ or diastolic blood pressure (DBP) ≥85 mmHg according to the harmonized definition of the metabolic syndrome. 376 received testosterone therapy (TTh) with TU 1000 mg/12 weeks following an initial 6-week interval (T-group). 304 had opted against TTh and served as controls (CTRL). 10-year data are reported. 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 and lipids to account for baseline differences between groups. Results: Mean (median) follow-up: T-group 7.7±2.6 (9), CTRL 8.1±2.1 (9) years. Total observation time: T-group 2900, CTRL 2463 years. Baseline age was 58.5±6.8 (T-group) and 63.8±4.8 years (CTRL). In the T-group, 189 men were and 187 were not aware of their hypertension at their first visit to the urologist, in CTRL, 139 and 161, respectively. Antihypertensives were used by 52.7% in T-group and 46.7% in CTRL. All patients were encouraged to improve their lifestyle at baseline. SBP decreased in the T-group by 23.6±0.7mmHg [95% CI: -24.9;-22.3] (p<0.0001) and increased in CTRL by 7.7±0.8mmHg [95% CI: 6.0;9.3] (p<0.0001), estimated adjusted difference between groups: -31.3mmHg [95% CI: -33.7;-28.9] (p<0.0001). DBP decreased in the T-group by 12.8±0.7 mmHg [95% CI: -14.1;-11.4] (p<0.0001) and increased in CTRL by 4.4±0.9 mmHg [95% CI: 2.6;6.1] (p<0.0001), difference between groups: -17.1 mmHg [95% CI: -19.5;-14.7] (p<0.0001). Heart rate decreased in the T-group by 1.6±0.3 bpm [95% CI: -2.3;-1.0] (p<0.0001) and increased in CTRL by 1.2±0 bpm [95% CI: 0.4;2.1] (p<0.005), difference between groups: -2.9 mmHg [95% CI: -4.0;-1.7] (p<0.0001). (p<0.0001). Pulse pressure, a surrogate marker of arterial stiffness, decreased in the T-group by 10.3±0.7 mmHg [95% CI: -11.7;-9.0] (p<0.0001) and increased in CTRL by 2.4±0.9 mmHg [95% CI: 0.7;4.0] (p<0.01), difference between groups: -12.7 mmHg [95% CI: -15.0;-10.4] (p<0.0001). Adverse events: T-group: 15 deaths (4%), no myocardial infarctions (MIs) or strokes. CTRL: 65 deaths (21.7%), 59 MIs (19.7%), 52 strokes (17.3%). Conclusion: Long-term testosterone therapy in hypogonadal men improved blood pressure, heart rate and arterial stiffness. In the untreated control group, all these parameters increased. Considerably less major adverse cardiovascular events occurred in the T-group.

Do Androgens Modulate the Pathophysiological Pathways of Inflammation? Appraising the Contemporary Evidence.

The role of testosterone in the pathophysiology of inflammation is of critical clinical importance; however, no universal mechanism(s) has been advanced to explain the complex and interwoven pathways of androgens in the attenuation of the inflammatory processes. PubMed and EMBASE searches were performed, including the following key words: “testosterone”, “androgens”, “inflammatory cytokines”, “inflammatory biomarkers” with focus on clinical studies as well as basic scientific studies in human and animal models. Significant benefits of testosterone therapy in ameliorating or attenuating the symptoms of several chronic inflammatory diseases were reported. Because anti–tumor necrosis factor therapy is the mainstay for the treatment of moderate-to-severe inflammatory bowel disease; including Crohn’s disease and ulcerative colitis, and because testosterone therapy in hypogonadal men with chronic inflammatory conditions reduce tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6, we suggest that testosterone therapy attenuates the inflammatory process and reduces the burden of disease by mechanisms inhibiting inflammatory cytokine expression and function. Mechanistically, androgens regulate the expression and function of inflammatory cytokines, including TNF-α, IL-1β, IL-6, and CRP (C-reactive protein). Here, we suggest that testosterone regulates multiple and overlapping cellular and molecular pathways involving a host of immune cells and biochemical factors that converge to contribute to attenuation of the inflammatory process.

Incidence and severity of prostate cancer (PCa) in 792 hypogonadal men with and without long-term testosterone therapy (TTh): Results from a controlled registry study.

167 Background: There is no evidence that TTh in hypogonadal men increases PCa incidence or severity. A US-Scandinavian group recently found that men receiving TTh had lower risk of aggressive PCa (Loeb S et al., J Clin Oncol 2017; 35:1430-6). Methods: 412 men with testosterone ≤350 ng/dL and symptoms received testosterone undecanoate 1000 mg every 3 months for up to 12 years. 380 hypogonadal men (57-74) opted against TTh. Median follow-up: 9 years. Total observation time covered approximately 6,400 patient-years. Prostate volume (PV) and PSA were measured and digital rectal examination/transrectal ultrasound performed before treatment/observation initiation and then every 3-6 months (T-group) or once or twice per year (CTRL). Biopsies were performed when indicated according to EAU guidelines. Results: In the T-group, 11 men (2.7%) were diagnosed with PCa. In CTRL, 34 (8.9%) were diagnosed with PCa. The incidence per 10,000 years was 33 in the T-group and 108 in CTRL. The mean baseline age of PCa patients was 65.2 years in the T-group and 64.3 in CTRL. All PCa diagnoses in the T-group were made within the first 18 months of treatment initiation. In CTRL, PCa was diagnosed at any time during the observation time. In the T-group, radical prostatectomy was performed in all men. All but 1 patient had a Gleason score (GS) ≤6, and all but 1 a predominant GS of 3. Tumor grade was G2 in all 11 (100%), tumor stage T2a in 7 (64%), T2b in 3 (27%), and T2c in 1 (9%) patient(s). In CTRL, radical prostatectomy was performed in all but 6 patients. GS was &gt; 6 in all 34 patients. 7 men had a GS of 7, 17 a GS of 8, and 10 a GS of 9. 2 men had a predominant Gleason score of 3, 22 had 4, and 10 had 5. Tumor grade was G2 in 6 (17.6%) and G3 in 28 (82.4%) patients, tumor stage T2c in 1 (0.3%), T3a in 3 (8.8%), T3b in 13 (38.2%) and T3c in 17 (50%) patients. In CTRL, biochemical recurrence occurred in 8 (23.5%) patients. These patients received androgen deprivation therapy (ADT). 10 (29.4%) patients died of whom 5 were on ADT. In the T-group, there were no biochemical recurrences or deaths during the observation time. Conclusions: In hypogonadal men, TTh may decrease PCa incidence compared to CTRL. PCa was less severe in the T-group.

Testosterone therapy in hypogonadal men

Testosterone therapy in hypogonadal men

Testosterone therapy in hypogonadal men: a systematic review and network meta-analysis

ObjectiveTo assess the relative effects of individual testosterone products among hypogonadal men.DesignSystematic review and network meta-analysis.MethodsWe searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (25 May 2017) for randomised-controlled trials...

Long-Term Testosterone Therapy Improves Urinary and Sexual Function, and Quality of Life in Men with Hypogonadism: Results from a Propensity Matched Subgroup of a Controlled Registry Study.

We investigated the effects of long-term testosterone therapy on urinary and sexual function, and quality of life in hypogonadal men. We performed an observational, prospective, cumulative registry study in 656 men with a mean ± SD age of 60.7 ± 7.2 years who had total testosterone 12.1 nmol/l or less and symptoms of hypogonadism. In the testosterone treated group 360 men received parenteral testosterone undecanoate 1,000 mg/12 weeks for up to 10 years. The 296 men who elected against testosterone therapy served as controls. From each group 82 patients were propensity matched by age, waist circumference and body mass index, resulting in 82 matched pairs of 164 men. Data were analyzed and estimated differences between the groups were adjusted for components of metabolic syndrome and quality of life. We found significant decreases in I-PSS (International Prostate Symptom Score) and post-void bladder volume (each p <0.0001) in patients receiving testosterone therapy but not in the untreated group. We recorded a decrease in AMS (Aging Males' Symptoms Scale) in the testosterone treated group but not in the untreated group (p <0.0001). We also recorded significant improvement in the IIEF-EF (International Index of Erectile Function-Erectile Function) domain in the testosterone treated group but not in the untreated group (p <0.0001). The improvement was maintained throughout followup. Long-term testosterone therapy in hypogonadal men resulted in significant improvements in urinary and sexual function, and in quality of life. In untreated hypogonadal men voiding and erectile function deteriorated with continued followup.

Testosterone Therapy Among Prostate Cancer Survivors.

The use of testosterone in men with a history of prostate cancer remains controversial in light of established findings linking androgens to prostate cancer growth. However, hypogonadism significantly affects quality of life and has negative sequelae, and the risks and benefits of testosterone therapy might be worthwhile to consider in all men, even those with a history of high-risk prostate cancer. To discuss the effects of testosterone on the prostate and the use of testosterone therapy in hypogonadal men with a history of prostate cancer. Review of the literature examining the effects of testosterone on the prostate and the efficacy and safety of exogenous testosterone in men with a history of prostate cancer. Summary of effects of exogenous and endogenous testosterone on prostate tissue invitro and invivo, with a focus on effects in men with a history of prostate cancer. Testosterone therapy ameliorates the symptoms of hypogonadism, decreases the risk for its negative sequelae, and can significantly improve quality of life. Recent studies do not support an increased risk for de novo prostate cancer, progression of the disease, or biochemical recurrence in hypogonadal men with a history of non-high-risk prostate cancer treated with testosterone therapy. Evidence supporting the use of testosterone in the setting of high-risk prostate cancer is less clear. Despite the historical reluctance toward the use of testosterone therapy in men with a history of prostate cancer, modern evidence suggests that testosterone replacement is a safe and effective treatment option for hypogonadal men with non-high-risk prostate cancer. Additional work to definitively demonstrate the efficacy and safety of testosterone therapy in men with prostate cancer is needed, and persistent vigilance and surveillance of treated men remains necessary.

MP47-07 PREDIABETES, HYPOGONADISM & ERECTILE DYSFUNCTION: GLYCAEMIC CONTROL IN 109 HYPOGONADAL MEN TREATED WITH TESTOSTERONE UNDECANOATE INJECTIONS (TU) FOR UP TO 8 YEARS: REAL-LIFE DATA FROM REGISTRY STUDIES

You have accessJournal of UrologySexual Function/Dysfunction: Evaluation1 Apr 2016MP47-07 PREDIABETES, HYPOGONADISM & ERECTILE DYSFUNCTION: GLYCAEMIC CONTROL IN 109 HYPOGONADAL MEN TREATED WITH TESTOSTERONE UNDECANOATE INJECTIONS (TU) FOR UP TO 8 YEARS: REAL-LIFE DATA FROM REGISTRY STUDIES Aksam Yassin, Ahmad Haider, Karim Haider, Gheorghe Doros, Abdulmaged Traish, and Farid Saad Aksam YassinAksam Yassin More articles by this author , Ahmad HaiderAhmad Haider More articles by this author , Karim HaiderKarim Haider More articles by this author , Gheorghe DorosGheorghe Doros More articles by this author , Abdulmaged TraishAbdulmaged Traish More articles by this author , and Farid SaadFarid Saad More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.326AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Testosterone therapy (TRT) has been studied in hypogonadal men with type 2 diabetes mellitus (T2DM). However, there is no information on effects of TRT in hypogonadal men with prediabetes. Our aim was to study erectile function in hypogonadal men with prediabetes. METHODS From two registries of hypogonadal men receiving long-term TRT with TU, 109 men with prediabetes, defined as a baseline HbA1c from 5.7 to 6.4%, were analysed. TU was administered in 3-month intervals for up to 8 years. At each or each other visit, questionnaires were applied and anthropometric and metabolic parameters were measured. RESULTS Mean age was 57.37 ± 8.99 years. Total testosterone increased from 8.55 ± 2.14 to trough levels between 16 and 19 nmol/L. Mean IIEF-EF (maximum score: 30) improved from 13.04 ± 6.3 to 22.55 ± 4.74. The improvement was statistically significant for three years and remained statistically significant vs baseline throughout the observation time, and stable compared to previous years. Weight decreased from 96.15 ± 13.05 to 84.14 ± 6.98 kg by -14 ± 0.65%, waist circumference from 103.8 ± 6.88 to 94.32 ± 4.53 cm by -9.62 ± 0.44 cm (p<0.0001 for both). Fasting glucose decreased from 5.43 ± 0.68 to 4.63 ±0.67, change from baseline -0.94 ± 0.11 mmol/L reaching a plateau after 1 year. HbA1c decreased from 5.9 ± 0.21 to 5.38 ± 0.26%, change from baseline -0.59 ± 0.04% with statistical significance compared to the previous year for the first 3 years. The triglyceride:HDL ratio, considered a surrogate parameter of insulin resistance, declined from 5.62 ± 2.61 to 2.6 ± 0.74 (p<0.0001 for all). No patient progressed from prediabetes to T2DM. All but 4 patients′ last HbA1c was <5.7%. 3 patients dropped out, 2 due to relocation to a different city, 1 was lost to follow-up. There were no major adverse cardiovascular events during the full observation time. CONCLUSIONS Hypogonadal men with prediabetes showed clinically meaningful and sustainable weight loss and improvements in glycaemic control upon long-term TU treatment. No patient advanced from prediabetes to T2DM. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e629 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Aksam Yassin More articles by this author Ahmad Haider More articles by this author Karim Haider More articles by this author Gheorghe Doros More articles by this author Abdulmaged Traish More articles by this author Farid Saad More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Testosterone Therapy after Radiation Therapy for Low, Intermediate and High Risk Prostate Cancer

Limited literature exists regarding the safety of testosterone therapy in men treated for prostate cancer. We present multi-institutional data on testosterone therapy in hypogonadal men with prostate cancer treated with radiation therapy. We retrospectively reviewed the records of hypogonadal men treated with testosterone therapy after radiation therapy for prostate cancer at 4 institutions. Serum testosterone, free testosterone, estradiol, sex hormone-binding globulin, prostate specific antigen, prostate specific antigen velocity and prostate biopsy findings were analyzed. A total of 98 men were treated with radiation therapy. Median age was 70.0 years (range 63.0 to 74.3) at initiation of testosterone therapy. Median baseline testosterone was 209 ng/dl (range 152 to 263) and median baseline prostate specific antigen was 0.08 ng/ml (range 0.00 to 0.33). In the cohort the tumor Gleason score was 5 in 3 men (3.1%), 6 in 44 (44.9%), 7 in 28 (28.6%), 8 in 7 (7.1%) and 9 in 4 (4.1%). Median followup was 40.8 months (range 1.5 to 147). Serum testosterone increased to a median of 420 ng/dl (range 231 to 711) during followup (p <0.001). Overall a nonsignificant increase in mean prostate specific antigen was observed from 0.08 ng/ml at baseline to 0.09 ng/ml (p = 0.05). Among patients at high risk prostate specific antigen increased from 0.10 to 0.36 ng/ml (p = 0.018). Six men (6.1%) met criteria for biochemical recurrence. Testosterone therapy in men following radiation therapy for prostate cancer was associated with a minor increase in serum prostate specific antigen and a low rate of biochemical recurrence.

Incidence of Prostate Cancer in Hypogonadal Men Receiving Testosterone Therapy: Observations from 5-Year Median Followup of 3 Registries

Although there is no evidence that testosterone therapy increases the risk of prostate cancer, there is a paucity of long-term data. We determined whether the incidence of prostate cancer is increased in hypogonadal men receiving long-term testosterone therapy. In 3 parallel, prospective, ongoing, cumulative registry studies 1,023 hypogonadal men received testosterone therapy. Two study cohorts were treated by urologists (since 2004) and 1 was treated at an academic andrology center (since 1996). Patients were treated when total testosterone was 12.1 nmol/l or less (350 ng/dl) and symptoms of hypogonadism were present. Maximum followup was 17 years (1996 to 2013) and median followup was 5 years. Mean baseline patient age in the urological settings was 58 years and in the andrology setting it was 41 years. Patients received testosterone undecanoate injections in 12-week intervals. Pretreatment examination of the prostate and monitoring during treatment were performed. Prostate biopsies were performed according to EAU guidelines. Numbers of positive and negative biopsies were assessed. The incidence of prostate cancer and post-prostatectomy outcomes was studied. A total of 11 patients were diagnosed with prostate cancer in the 2 urology settings at proportions of 2.3% and 1.5%, respectively. The incidence per 10,000 patient-years was 54.4 and 30.7, respectively. No prostate cancer was reported by the andrology center. Limitations are inherent in the registry design without a control group. Testosterone therapy in hypogonadal men does not increase the risk of prostate cancer. If guidelines for testosterone therapy are properly applied, testosterone treatment is safe in hypogonadal men.

Testosterone 2% Gel Can Normalize Testosterone Concentrations in Men with Low Testosterone Regardless of Body Mass Index

Little is known about the effect of body mass index (BMI) on the efficacy and safety of testosterone therapy in hypogonadal men. A prior noncomparative trial demonstrated that testosterone 2% gel restored testosterone levels in hypogonadal men and was generally well tolerated. This post hoc analysis evaluated the influence of BMI on the pharmacokinetics of testosterone therapy in men with low testosterone. Men (N = 149) aged 18-75 applied testosterone 2% gel to the front and inner thigh once daily for 90 days. Starting dose was 40 mg/day, which could be adjusted at days 14, 35, and 60. Patients were split into categories depending on baseline BMI: Tertile 1 (≤ 29.1 kg/m(2)), Tertile 2 (29.2-32.4 kg/m(2)), and Tertile 3 (>32.4 kg/m(2)). Efficacy end points were average serum total testosterone concentrations over 24 hours and maximum serum testosterone concentrations at day 90. Adverse events were recorded. The efficacy analysis included 129 men with low testosterone (mean age 52.9, 54.0, and 54.2 years for Tertiles 1, 2, and 3, respectively) defined as serum testosterone <250-300 ng/dL. Baseline testosterone levels were comparable across BMI tertiles. After 90 days of treatment with testosterone 2% gel (≥ 40 mg/day), 79.1%, 79.5%, and 73.8% of patients in Tertiles 1, 2, and 3, respectively, achieved serum testosterone concentrations in the physiologic range (i.e., ≥ 300 to ≤ 1,140 ng/dL). The mean average daily dose at day 90 was higher in participants in Tertiles 3 vs. 2 (P = 0.039) and Tertiles 3 vs. 1 (P = 0.010). The gel was generally well tolerated, with skin reactions the most commonly reported adverse event (16.1%; n = 24). In this study, daily application of testosterone 2% gel was effective at returning serum testosterone to physiologic levels in men with low testosterone and high BMI, although required dose was affected by BMI.

Long‐term testosterone therapy in hypogonadal men ameliorates elements of the metabolic syndrome: an observational, long‐term registry study

AimThe goal of this study was to determine if long-term testosterone (T) therapy in men with hypogonadism, henceforth referred to as testosterone deficiency (TD), ameliorates or improves metabolic syndrome (MetS) components.MethodsWe performed a cumulative registry study of 255 men, aged between 33 and 69 years (mean 58.02 ± 6.30) with subnormal plasma total T levels (mean: 9.93 ± 1.38; range: 5.89–12.13 nmol/l) as well as at least mild symptoms of TD assessed by the Aging Males' symptoms scale. All men received treatment with parenteral T undecanoate 1000 mg (Nebido®, Bayer Pharma, Berlin, Germany), administered at baseline and 6 weeks and thereafter every 12 weeks for up to 60 months. Lipids, glucose, liver enzymes and haemoglobin A1c analyses were carried out in a commercial laboratory. Anthropometric measurements were also made throughout the study period.ResultsTestosterone therapy restored physiological T levels and resulted in reductions in total cholesterol (TC) [7.29 ± 1.03 to 4.87 ± 0.29 mmol/l (281.58 ± 39.8 to 188.12 ± 11.31 mg/dl)], low-density lipoprotein cholesterol [4.24 ± 1.07 to 2.84 ± 0.92 mmol/l (163.79 ± 41.44 to 109.84 ± 35.41 mg/dl)], triglycerides [3.14 ± 0.58 to 2.16 ± 0.13 mmol/l (276.16 ± 51.32 to 189.78 ± 11.33 mg/dl)] and increased high-density lipoprotein levels [1.45 ± 0.46 to 1.52 ± 0.45 mmol/l (56.17 ± 17.79 to 58.85 ± 17.51 mg/dl)] (p < 0.0001 for all). There were marked reductions in systolic and diastolic blood pressure, blood glucose, haemoglobin A1c, C-reactive protein (6.29 ± 7.96 to 1.03 ± 1.87 U/l), alanine aminotransferase and aspartate aminotransferase (p < 0.0001 for all).ConclusionsLong-term T therapy, at physiological levels, ameliorates MetS components. These findings strongly suggest that T therapy in hypogonadal men may prove useful in reducing the risk of cardiometabolic diseases.

Testosterone therapy in hypogonadal men results in sustained and clinically meaningful weight loss

SummaryWhat is already known about this subjectHypogonadism is associated with increased fat mass and reduced muscle mass, which contributes to obesity and health risks, such as cardiovascular disease.Testosterone treatment of hypogonadal men improves muscle mass and reduces fat mass; however, many of these studies are of short duration.Thus, the long-term effects of testosterone on body anthropometry are not known.What this study addsLong-term testosterone treatment of hypogonadal men, up to 5 years duration, produced marked and significant decrease in body weight, waist circumference and body mass index.Hypogonadism contributes to reduced muscle mass and increased adiposity. Testosterone treatment ameliorates loss of muscle mass and reduces fat accumulation associated with hypogonadism. In this study, we evaluated the long-term effects of normalizing testosterone (T) levels in hypogonadal men on anthropometric parameters. Open-label, single-center, cumulative, prospective registry study of 261 men (32–84 years, mean 59.5 ± 8.4 years, with T levels ≤12 nmol L−1 [mean: 7.7 ± 2.1]). Among the 261 men on T treatment, we followed up on 260 men for at least 2 years, 237 for 3 years, 195 for 4 years and 163 for at least 5 years. Subjects received parenteral T undecanoate 1000 mg every 12 weeks after an initial interval of 6 weeks. Body weight (BW), waist circumference (WC) and body mass index (BMI) were measured at baseline and yearly after treatment with T. BW decreased from 100.1 ± 14.0 kg to 92.5 ± 11.2 kg and WC was reduced from 107.7 ± 10.0 cm to 99.0 ± 9.1 cm. BMI declined from 31.7 ± 4.4 m kg−2 to 29.4 ± 3.4 m kg−2. All parameters examined were statistically significant vs. baseline and vs. the previous year over 5 years, indicating a continuous weight loss (WL) over the full observation period. The mean per cent WL was 3.2 ± 0.3% after 1 year, 5.6 ± 0.3%, after 2 years, 7.5 ± 0.3% after 3 years, 9.1 ± 0.3% after 4 years and 10.5 ± 0.4% after 5 years. The data obtained from this uncontrolled, observational, registry study suggest that raising serum T to normal physiological levels in hypogonadal men produces consistent loss in BW, WC and BMI. These marked improvements were progressive over the 5 years of the study.

Update: Hypogonadotropic Hypogonadism in Type 2 Diabetes and Obesity

Studies over the last few years have clearly established that at least 25% of men with type 2 diabetes have subnormal free testosterone concentrations in association with inappropriately low LH and FSH concentrations. Another 4% have subnormal testosterone concentrations with elevated LH and FSH concentrations. The Endocrine Society, therefore, now recommends the measurement of testosterone in patients with type 2 diabetes on a routine basis. The subnormal testosterone concentrations are not related to glycosylated hemoglobin or duration of diabetes, but are associated with obesity, very high C-reactive protein concentrations, and mild anemia. In addition, subnormal testosterone concentrations in these men are associated with a two to three times elevated risk of cardiovascular events and death in two early studies. Short-term studies of testosterone therapy in hypogonadal men with type 2 diabetes have demonstrated an increase in insulin sensitivity and a decrease in waist circumference. However, the data on the effect of testosterone replacement on glycemic control and cardiovascular risk factors such as cholesterol and C-reactive protein concentrations are inconsistent. As far as sexual function is concerned, testosterone treatment increases libido but does not improve erectile dysfunction and thus, phosphodiesterase inhibitors may be required. Trials of a longer duration are clearly required to definitively establish the benefits and risks of testosterone replacement in patients with type 2 diabetes and low testosterone.

Androgen Receptor Gene CAG Repeat Polymorphism and Effect of Testosterone Therapy in Hypogonadal Men in Korea

Background: As the number of CAG repeats in the androgen receptor (AR) gene increases, transcriptional activities decrease and the effects of testosterone decline. In this study, we evaluated the importance of the CAG repeat polymorphism in regard to the ef fect/safety of testosterone therapy in hypogonadal Korean men. Methods: The number of CAG repeats was determined in 42 hypogonadal men who underwent testosterone therapy for more than 24 months between December 1999 and August 2007. Body mass index, lean body mass, body fat, bone mineral density, type I collagen N-telopeptide (NTx), osteocalcin, lipid profile, hematocrit and PSA levels prior to and after 24 months of testosterone therapy were identified in our medical record review. Results: Twenty-four months of testosterone therapy increased lean body mass, hematocrit, and PSA levels and reduced body fat, NTx, and HDL cholesterol levels. The mean number of CAG repeats in the AR gene was 23 ± 3 (range, 15-29) in hypogonadal Korean men. The number of CAG repeats was not found to be associated with changes in lean body mass, body fat, NTx, HDL cholesterol, hematocrit, or PSA levels during testosterone therapy. Conclusions: No association between the number of CAG repeats in the AR gene and the effect/safety of testosterone therapy was detected in hypogonadal Korean men. (Endocrinol Metab 26:225-231, 2011)