Safety Of Testosterone Replacement Therapy Research Articles

Investigating the basis of sexual dysfunction during late-onset hypogonadism.

Late-onset hypogonadism (LOH) is the term used to describe the decline in serum testosterone levels associated with increasing age in men above 40 years. A number of symptoms are attributed to LOH, but the most common association is that of sexual dysfunction. LOH has recently come under greater scrutiny with the widespread use of testosterone therapy, and concerns regarding the efficacy and safety of testosterone replacement therapy have been raised. In particular, the cardiovascular safety and the beneficial effects of testosterone replacement therapy on general health have been questioned. This review will give an overview of the current evidence for the relationship of LOH and male sexual dysfunction.

The efficacy and adverse events of testosterone replacement therapy in hypogonadal men: A systematic review and meta-analysis of randomized, placebo-controlled trials.

The efficacy and safety of testosterone replacement therapy (TRT) in hypogonadal men remain incompletely understood. To conduct a systematic review and meta-analysis of randomized clinical trials (RCT) to determine the effects of TRT on patient-important outcomes and adverse events in hypogonadal men. We searched Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, Ovid Cochrane Central Register of Controlled Trials, and Scopus from inception to March 2th, 2017. RCTs that assessed the efficacy and adverse events of TRT of at least 12 weeks compared with placebo in adult men with hypogonadism, defined by morning testosterone ≤300 ng/dL and at least one symptom or sign of hypogonadism. Reviewers working independently and in duplicate assessed the quality of the trials and collected data on patient characteristics, interventions, and outcomes. We found 11 publications, reporting on 4 eligible trials (including 1,779 patients) at low risk of bias. Compared to placebo, TRT was associated with a small but significant increase in sexual desire or libido [standardized mean difference (SMD): 0.17, 95% CI 0.01, 0.34] (n=1383), erectile function [SMD: 0.16, 95% CI 0.06, 0.27] (n=1344), and sexual satisfaction [SMD: 0.16, 95% CI 0.01, 0.31] (n=676), but had no effect on energy or mood. TRT was associated with an increased risk of developing erythrocytosis [relative risk: 8.14, 95% CI: 1.87, 35.40] (n=1579) compared to placebo, but had no significant effect on lower urinary tract symptoms (LUTS). In hypogonadal men TRT improves sexual desire, erectile function, and sexual satisfaction, however it increases the risk of erythrocytosis.

102 Influence of Genetic Variation in the Androgen Receptor on the Risk of Cardiovascular Disease in Aging Men

Controversy still exists regarding the effect of hypogonadism on cardiovascular (CV) health and the safety of testosterone replacement therapy (TRT). We hypothesized that differences in androgen sensitivity, a function of the number of trinucleotide repeats on the androgen receptor (AR) gene, may result in greater reactivity to age-related testosterone changes and increased risk of CV disease. Participants were men from the Vietnam Era Twin Study of Aging (N=696). Mean age was 56.4 years (range:51-60). Average waking, salivary free-testosterone level was acquired on 3 non-consecutive days. Low testosterone (low-T) was defined as being ≥ 1 SD below the mean. The AR gene CAG repeat length was derived using polymerase chain reaction (PCR) fragment analysis and Sanger sequencing. Average repeat length was 22 (range:8-37). CV disease was assessed by self-report and medication data. We tested the interaction between low testosterone (low-T) and CAG repeat length while controlling for age, ethnicity, smoking status, BMI, hypertension, diabetes, and the correlated nature of the twin data.

Association of Testosterone Replacement With Cardiovascular Outcomes Among Men With Androgen Deficiency

Controversy exists regarding the safety of testosterone replacement therapy (TRT) following recent reports of an increased risk of adverse cardiovascular events. To investigate the association between TRT and cardiovascular outcomes in men with androgen deficiency. A retrospective cohort study was conducted within an integrated health care delivery system. Men at least 40 years old with evidence of androgen deficiency either by a coded diagnosis and/or a morning serum total testosterone level of less than 300 ng/dL were included. The eligibility window was January 1, 1999, to December 31, 2010, with follow-up through December 31, 2012. Any prescribed TRT given by injection, orally, or topically. The primary outcome was a composite of cardiovascular end points that included acute myocardial infarction (AMI), coronary revascularization, unstable angina, stroke, transient ischemic attack (TIA), and sudden cardiac death (SCD). Multivariable Cox proportional hazards models were used to investigate the association between TRT and cardiovascular outcomes. An inverse probability of treatment weight, propensity score methodology, was used to balance baseline characteristics. The cohorts consisted of 8808 men (19.8%) ever dispensed testosterone (ever-TRT) (mean age, 58.4 years; 1.4% with prior cardiovascular events) and 35 527 men (80.2%) never dispensed testosterone (never-TRT) (mean age, 59.8 years; 2.0% with prior cardiovascular events). Median follow was 3.2 years (interquartile range [IQR], 1.7-6.6 years) in the never-TRT group vs 4.2 (IQR, 2.1-7.8) years in the ever-TRT group. The rates of the composite cardiovascular end point were 23.9 vs 16.9 per 1000 person-years in the never-TRT and ever-TRT groups, respectively. The adjusted hazard ratio (HR) for the composite cardiovascular end point in the ever-TRT group was 0.67 (95% CI, 0.62-0.73. Similar results were seen when the outcome was restricted to combined stroke events (stroke and TIA) (HR, 0.72; 95% CI, 0.62-0.84) and combined cardiac events (AMI, SCD, unstable angina, revascularization procedures) (HR, 0.66; 95% CI, 0.60-0.72). Among men with androgen deficiency, dispensed testosterone prescriptions were associated with a lower risk of cardiovascular outcomes over a median follow-up of 3.4 years.

Bulbocavernosus muscle area as a novel marker for hypogonadism

ObjectiveLate-onset hypogonadism, or androgen deficiency in the aging male, is a significant cause of morbidity in older men. Many men in the low normal or equivocal range for low testosterone level exhibit signs and symptoms of hypogonadism. Serum testosterone is an imperfect maker for hypogonadism as symptoms vary greatly within the low to low normal range in addition to variations among testosterone assays. Perineal ultrasound can be effectively used to examine the bulbocavernosus muscle (BCM), an androgenized tissue that may be impacted by androgen receptor activity. MethodsThis study was a retrospective analysis of men who underwent perineal ultrasound for hypogonadism. The ultrasound data were used to calculate the area of the BCM and correlate it with indices of hypogonadismin symptomatic men including free and total testosterone and dual-energy X-ray absorptiometry (DEXA). ResultsThe results demonstrate that there is a significant correlation between total and free testosterone and BCM area in hypogonadal patients. Comparison between BCM area and total testosterone showed R2 = 0.061 and p = 0.0187 and comparison between BCM area and free testosterone showed R2 = 0.0957 and p = 0.0034. In addition, low BCM was also correlated with DEXA results showing osteoporosis and osteopenia (R2 = 0.2239, p = 0.0027). ConclusionThere has been recent controversy over the safety of testosterone replacement therapy. This might be particularly important in men with hypogonadal symptoms but a low normal testosterone level. Our study investigated the use of perineal ultrasound to measure BCM as a surrogate marker for poor androgenized men presenting with hypogonadism.

Testosterone treatment is not associated with increased risk of adverse cardiovascular events: results from the Registry of Hypogonadism in Men (RHYME).

The aim of this study was to assess cardiovascular (CV) safety of testosterone replacement therapy (TRT) in a large, diverse cohort of European men with hypogonadism (HG). The Registry of Hypogonadism in Men (RHYME) was designed as a multi-national, longitudinal disease registry of men diagnosed with hypogonadism (HG) at 25 clinical sites in six European countries. Data collection included a complete medical history, physical examination, blood sampling and patient questionnaires at multiple study visits over 2-3years. Independent adjudication was performed on all mortalities and CV outcomes. Of 999 patients enrolled with clinically diagnosed HG, 750 (75%) initiated some form of TRT. Registry participants, including both treated and untreated patients, contributed 23900 person-months (99.6% of the targeted) follow-up time. A total of 55 reported CV events occurred in 41 patients. Overall, five patients died of CV-related causes (3 on TRT, 2 untreated) and none of the deaths were adjudicated as treatment-related. The overall CV incidence rate was 1522 per 100000 person-years. CV event rates for men receiving TRT were not statistically different from untreated men (P=.70). Regardless of treatment assignment, CV event rates were higher in older men and in those with increased CV risk factors or a prior history of CV events. Age and prior CV history, not TRT use, were predictors of new-onset CV events in this multi-national, prospective hypogonadism registry.

A survey of Canadian urologists' opinions and prescribing patterns of testosterone replacement therapy in men on active surveillance for low-risk prostate cancer.

Attitudes regarding the safety of testosterone replacement therapy (TRT) in hypogonadal men with prostate cancer (PCa) have changed over the past few years with the emergence of case studies suggesting a low risk of cancer progression and a better understanding of the interaction of different levels of androgen with prostate cellular metabolism. This new view has the potential to change clinical practice. Active members of the Canadian Urological Association were surveyed about their opinions on the safety of TRT in men with low-risk PCa, as well as their current prescribing habits. Of 57 responding urologists, 86% actively prescribe TRT in men with testosterone deficiency syndrome (TDS), 93% are involved in the treatment of men with PCa, and 95% offer active surveillance as a management option for low-grade/low-stage disease. Furthermore, 65% stated that they would offer TRT to men with TDS who were on active surveillance for PCa and 63% believed that TRT did not increase the risk of progression of PCa in these men. In terms of treatment methods, 96% believed TRT was safe for men who have undergone radical prostatectomy, while a smaller number felt it was safe for patients who have undergone brachytherapy (86%) or external beam radiation (84%). Despite these figures, only 35% of the surveyed physicians had ever offered TRT for men on active surveillance and only 42% actually had men in their practice who were taking testosterone while on active surveillance. The discrepancy between urologists' beliefs about the safety of TRT and their clinical practice patterns may be due to multiple factors, such as hesitation in recommending treatment in real-life practice, low numbers of eligible patients, absence of screening for testosterone deficiency in patients on active surveillance, and patient preference or fears. Furthermore, the difference in perceived safety in men treated by radical prostatectomy vs. radiation therapy suggests that some urologists are concerned that the radiated gland remaining in-situ may be "reactivated" by TRT. The results from this survey will be used as the basis of developing a national Canadian registry of men with low-grade/stage PCa who are receiving TRT while on active surveillance.

Current Literature Review.

Current Literature Review.

Efficacy and safety of testosterone replacement therapy in men with hypogonadism: A meta-analysis study of placebo-controlled trials.

The purpose of the present meta-analysis was to evaluate the efficacy and safety of testosterone replacement therapy in men with hypogonadism. A search was conducted for appropriate randomized controlled trials and the data from 16 trials were pooled. The intended primary outcome of the present study was to determine the efficacy and safety of testosterone replacement therapy. The current data demonstrated that scores for Aging Male Symptoms (AMS) were significantly reduced following testosterone replacement therapy, with a mean decrease in AMS score of 1.52 [95% confidence interval (CI), 0.72 to 2.32; P=0.0002]. Testosterone replacement therapy increased lean body mass [mean difference (MD), 1.22; 95% CI, 0.33 to 2.11; P=0.007], reduced fat mass in a non-significantly manner (MD, −0.85; 95% CI, −1.74 to 0.04; P=0.06) and significantly reduced total cholesterol (MD, −0.16; 95% CI, −0.29 to −0.03; P=0.01). No significant differences were identified in body weight (MD, 0.09; 95% CI, −1.13 to 1.31; P=0.89), body mass index (MD, 0.10; 95% CI, −0.62 to 0.82; P=0.78) or bone mineral density (MD, −0.01; 95% CI, −0.03 to 0.02; P=0.60). Average prostate volume increased (MD, 1.58; 95% CI, 0.6 to 2.56; P=0.002) following testosterone replacement therapy, but the levels of prostate-specific antigen (PSA) (MD, 0.10; 95% CI, −0.03 to 0.22; P=0.14) and the International Prostate Symptom Scores (MD, 0.01; 95% CI, −0.37 to 0.39; P=0.96) did not change. In conclusion, testosterone replacement therapy improves quality of life, increases lean body mass, significantly decreases total cholesterol, and is well-tolerated and safe for men with hypogonadism who are exhibiting PSA levels of <4 ng/ml.

AB004. Contemporary perspectives on testosterone replacement therapy (TRT)

The hormone testosterone (T) is responsible for the normal growth and development of male sex organs, and maintenance of secondary sex characteristics. T is the primary androgenic hormone, and its production and secretion are the end products of a series of hormonal interactions and feedback regulatory mechanisms. Testosterone deficiency (TD) occurs when the testes fail to produce normal levels of T. Primary, or hypergonadotropic, hypogonadism is recognized as testicular failure; T levels are low, and pituitary gonadotropins are elevated. In secondary, or hypogonadotropic hypogonadism, there is an inadequate secretion of pituitary gonadotropins, and, in addition to low serum T levels, luteinizing hormone (LH) and follicle stimulating hormone (FSH) are low or low-normal. The role of T in cardiovascular (CV) disease in men is currently a hotly debated topic. Two recent studies suggest that hypogonadal men undergoing testosterone replacement therapy (TRT) have a higher incidence of CV morbidity and mortality. However, the preponderance of TRT studies conducted over the past 3 decades has demonstrated neutral or lower incidences of CV events. Perhaps the decreased risk with TRT can be attributed to the modification and improvement of CV risk factors. The FDA Advisory Committee convened a meeting on Sep 17, 2014 to further assess TRT and correctly opined that, “with regards to the risk of CV events, the evidence linking TRT to an increased risk of heart attack, stroke, and death was inconclusive.” They also suggested that the appropriate population for TRT be identified and that studies to better determine the risks of major CV events in men receiving TRT be conducted. Despite the results of the 800-elderly-man, NIH-sponsored, 5-year T-Trial to be published in the latter part of 2015, there is still a need for longer and larger randomized, placebo-controlled trials to provide more definitive and reassuring data regarding the efficacy and safety of TRT in symptomatic hypogonadal men.

MP51-14 CONTEMPORARY PRESCRIBING PATTERNS OF TESTOSTERONE REPLACEMENT THERAPY IN HYPOGONADAL PATIENTS WITH A HISTORY OF PROSTATE CANCER

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Evaluation II1 Apr 2015MP51-14 CONTEMPORARY PRESCRIBING PATTERNS OF TESTOSTERONE REPLACEMENT THERAPY IN HYPOGONADAL PATIENTS WITH A HISTORY OF PROSTATE CANCER Victor Lizarraga and Mohit Khera Victor LizarragaVictor Lizarraga More articles by this author and Mohit KheraMohit Khera More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1751AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The safety of testosterone replacement therapy in the setting of patients with both hypogonadism and a history of prostate cancer is currently under debate. Recent evidence suggests that the theoretical risks are not being realized. As our understanding of the risks of testosterone replacement therapy in the setting of prostate cancer is in transition, it is unknown if the practice patterns are changing regarding testosterone the replacement therapy in patients with known prostate cancer. We polled a cohort of practicing urologists to identify the current state of practice in regards to offering testosterone replacement therapy in patients with a history of prostate cancer. METHODS An electronic survey was sent to the membership of the Sexual Medicine Society of North America with questions focused on use of testosterone replacement therapy in patient with hypogonadism and a history of treated or current prostate cancer. RESULTS Fifty seven responses were obtained from attending urologists. 62% of these reported being fellowship trained, most commonly in the fields of andrology or infertility. 94% of these urologists prescribed testosterone to patients with a history of prostate cancer. The majority offered testosterone to patients who had been treated for prostate cancer in the past, 100% for patients post prostatectomy and 92% for patients after external beam radiotherapy. 51% of urologists offered testosterone to patients with no definitive treatment in the past for prostate cancer. One half of these urologists offered testosterone to patients on active surveillance. Informed consent was documented before starting testosterone replacement by 72% of urologist. Follow up for these patients was done most regularly every 3-6 months. CONCLUSIONS Regarding this cohort of urologists, testosterone replacement therapy was regularly offered to patients with a known history of prostate cancer. There is a paucity of published data regarding the use of testosterone in this setting, however practice patterns indicate that there is an interest in offering testosterone therapy to this group of patients. Further study is required to identify the ideal treatment and follow up protocols for these patients. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e625 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Victor Lizarraga More articles by this author Mohit Khera More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Review of health risks of low testosterone and testosterone administration

Hypogonadism is prevalent in older men and testosterone replacement therapy (TRT) for older hypogonadal men is a promising therapy. However, a number of important clinical concerns over TRT safety remain unsolved due to a lack of large-scale randomized clinical trials directly comparing the health risks of untreated hypogonadism vs long-term use of TRT. Meta-analyses of clinical trials of TRT as of 2010 have identified three major adverse events resulting from TRT: polycythemia, an increase in prostate-related events, and a slight reduction in serum high-density lipoprotein cholesterol. There are other purported health risks but their incidence can be neither confirmed nor denied based on the small number of subjects that have been studied to date. Furthermore, subsequent literature is equivocal with regard to the safety and utility of TRT and this topic has been subject to contentious debate. Since January 2014, the United States Food and Drug Administration has released two official announcements regarding the safety of TRT and clinical monitoring the risks in TRT users. Additionally, the health risks related to the clinical presentation of low or declining testosterone levels not been resolved in the current literature. Because TRT is prescribed in the context of putative risks resulting from reduced testosterone levels, we reviewed the epidemiology and reported risks of low testosterone levels. We also highlight the current information about TRT utilization, the risks most often claimed to be associated with TRT, and current or emerging alternatives to TRT.

Evaluation for Testosterone Deficiency.

There has been a recent increase in the number of Operators presenting to clinics for evaluation of possible low testosterone. In response, USASOC recently released an Androgen Deficiency Clinical Practice Guideline (CPG) to help guide providers through the initial evaluation and treatment of patients. The diagnosis of hypogonadism is based on consistent signs and symptoms of androgen deficiency and unequivocally low serum testosterone (below 300 ng/dL). Testosterone levels can change for a variety of reasons and an adequate evaluation requires multiple laboratory tests over a period of time. If a diagnosis of hypogonadism is confirmed, differentiating between primary and secondary hypogonadism can help guide further care. Testosterone replacement therapy options are available, but careful monitoring for side-effects is required. Controversy still exists surrounding the safety of testosterone replacement therapy, and referral to endocrinology should strongly be considered before initiating treatment.

The impact of drug reimbursement policy on rates of testosterone replacement therapy among older men.

BackgroundDespite a lack of data describing the long-term efficacy and safety of testosterone replacement therapy (TRT), prescribing of testosterone to older men has increased with the availability of topical formulations. The magnitude of this increase and the impact of formulary restrictions on testosterone prescribing are poorly characterized.MethodsWe conducted a time series analysis using the linked health administrative records of men aged 66 years or older in Ontario, Canada between January 1, 1997 and March 31, 2012. We used interventional autoregressive integrated moving average models to examine the impact of a restrictive drug reimbursement policy on testosterone prescribing and examined the demographic profile of men initiating testosterone in the final 2 years of the study period.ResultsA total of 28,477 men were dispensed testosterone over the study period. Overall testosterone prescribing declined 27.9% in the 6 months following the implementation of the restriction policy (9.5 to 6.9 men per 1000 eligible; p<0.01). However, the overall decrease was temporary and testosterone use exceeded pre-policy levels by the end of the study period (11.0 men per 1000 eligible), largely driven by prescriptions for topical testosterone (4.8 men per 1000 eligible). Only 6.3% of men who initiated testosterone had a documented diagnosis of hypogonadism, the main criteria for TRT reimbursement according to the new policy.ConclusionGovernment-imposed restrictions did not influence long-term prescribing of testosterone to older men. By 2012, approximately 1 in every 90 men aged 66 or older was being treated with TRT, most with topical formulations.

PI-01 BEST ABSTRACT: EFFECTS OF LONG-TERM TESTOSTERONE THERAPY ON PROSTATE, URINARY AND SEXUAL PARAMETERS IN 300 HYPOGONADAL MEN TREATED FOR UP TO 6 YEARS

You have accessJournal of UrologyPlenary Session I: Best Abstract and Late Breaking Abstracts1 Apr 2014PI-01 BEST ABSTRACT: EFFECTS OF LONG-TERM TESTOSTERONE THERAPY ON PROSTATE, URINARY AND SEXUAL PARAMETERS IN 300 HYPOGONADAL MEN TREATED FOR UP TO 6 YEARS Ahmad Haider, Gheorghe Doros, and Abdulmaged Traish Ahmad HaiderAhmad Haider More articles by this author , Gheorghe DorosGheorghe Doros More articles by this author , and Abdulmaged TraishAbdulmaged Traish More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.807AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There are still concerns regarding safety of testosterone replacement therapy (TRT) for the prostate. We investigated whether long-term TRT with injectable testosterone undecanoate (TU) affected parameters related to prostate, urinary and sexual function. METHODS Prospective, longitudinal, registry study of 300 patients (mean age 57.7 ± 6.76 years), with testosterone levels ≥ 350 ng/dl (12 nmol/L) receiving parenteral TU 1000 mg at baseline, after 6 weeks and thereafter every 12 weeks for up to 72 months (6 years). Prostate volume and residual voiding volume were measured by ultrasound at every or every other visit. IPSS, IIEF-EF and AMS questionnaires were filled in at every visit and blood samples taken to measure PSA. Because prostatic diseases are closely associated with the metabolic syndrome, we also assessed anthropometric and metabolic parameters. RESULTS Testosterone increased from 9.86 ± 1.34 nmol/L to trough levels of 16 to 17 nmol/L for the observation period. Prostate volume increased from 28.34 ± 10.79 to 30.72 ± 14.28 ml (p<0.0001 vs baseline). PSA increased from 1.77 ± 0.97 to 2.0 ± 1.01 ng/ml (p=0.0021 vs baseline). 5/300 patients were diagnosed with prostate cancer (PCa) following elevated PSA (> 4 ng/mL). Tumor stage was pT2a in 4 and pT1b in 1 man, Gleason score 3+3 in 4 and 3+2 in 1 patient, resp. All men underwent radical prostatectomy. The proportion was 1.7% with an incidence of 39.4 per 10.000 patient years. The International Prostate Symptom Score (IPSS) decreased from 6.57 ± 4.21 to 2.58 ± 1.32 (p<0.0001). The residual voiding volume decreased from 46.78 ± 23.58 to 15.85 ± 5.32 ml (p<0.0001). The International Index of Erectile Function Erectile Function Domain (IIEF-EF, maximum score: 30) increased from 20.01 ± 5.06 to 26.11 ± 3.33 (p<0.0001) with a plateau at 36 months. The Aging Males Symptoms scale (AMS) as a measure of quality of life improved from 53.43 ± 10.21 to 17.41 ± 2.36 (p<0.0001). Weight dropped progressively by 16.8 ± 0.41 kg, and waist circumference (WC) by 8.94 ± 0.24. Similarly, improvements in lipid pattern, blood pressure, and glucose homeostasis were observed. CONCLUSIONS The incidence of PCa did not suggest an increased risk of PCa in hypogonadal men on long-term TRT. Long-term treatment with TU did not negatively affect voiding function as measured by IPSS, or residual voiding volume. Erectile function was markedly and sustainably improved. Part of these effects may be a result of parallel reduction in body weight and visceral fat, measured by WC, and other elements of the metabolic syndrome. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e221-e222 Peer Review Report Advertisement Copyright & Permissions© 2014MetricsAuthor Information Ahmad Haider More articles by this author Gheorghe Doros More articles by this author Abdulmaged Traish More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Comprehensive evaluation of androgen replacement therapy in aging Japanese men with late-onset hypogonadism

Objective: This study assessed the efficacy and safety of testosterone replacement therapy (TRT) in aging Japanese men with late-onset hypogonadism (LOH).Methods: This study included 50 (median age: 57.7 years) Japanese men with LOH, who were consecutively enrolled and treated with TRT for at least six months at our institution. We evaluated the following measurements before and after six months of treatment with TRT as follows: blood tests, prostate volume, residual urine volume, self-ratings for International Index of Erectile Function 5 (IIEF-5), International Prostate Symptom Score (IPSS), Self-Rating Depression Scale (SDS), Aging Male Symptom (AMS) and the Medical Outcomes Study 8-item Short-Form health survey (SF-8).Results: Following six months of TRT, the levels of testosterone, red blood cells, hemoglobin and hematocrit were significantly increased from baseline, while total cholesterol level was significantly decreased from baseline. Furthermore, TRT led to a significant increase in IIEF-5 score and a significant decrease in IPSS score. Of 30 men who were diagnosed with depression at baseline, only 11 men (36.7%) were still suffering from depression after TRT, and SDS scores were significantly decreased from baseline at month six. Treatment with TRT led to a significant decrease in all scores of the AMS scale as well as a significant improvement in all scores of the SF-8 survey, with the exception of the bodily pain score.Conclusion: These findings suggest that TRT is an effective and safe treatment for aging Japanese men with LOH. TRT improved depressive symptoms as well as health-related quality of life.

Testosterone replacement therapy does not promote priapism in hypogonadal men with sickle cell disease: 12‐month safety report

Hypogonadism, which is highly prevalent in men with sickle cell disease (SCD), affects quality of life and causes great morbidity. The safety of testosterone replacement therapy (TRT) in SCD in relation to priapism episodes is relatively unknown. Our aim was to monitor the safety of TRT in a cohort of seven hypogonadal men with SCD. Testosterone undecanoate (Nebido) 1 g was administered intramuscularly to adult men with homozygous SCD (Hb SS) having hypogonadism [serum total testosterone ≤12.0 nmol/L (346 ng/dL), reference range 12.5-38.1 nmol/L (360-1098 ng/dL)] for 12 months. Serum total testosterone, haemoglobin, haematocrit, renal and liver function tests, glucose and PSA measurements were done at baseline and 12-month follow-up. Trough serum total testosterone, haemoglobin and haematocrit were measured three monthly. Priapism events and adverse drug events were assessed every 3 months. International Index of Erectile Function (IIEF), Androgen Deficiency in the Ageing Male (ADAM) and World Health Organization Quality of Life (WHOQOL) questionnaires were administered at baseline, 6 and 12 months. Seven men with a mean age of 34.4 years were treated. Median total testosterone increased from 10.6 to 11.2 nmol/L (p = 0.46). Median serum lactate dehydrogenase levels decreased from 1445 to 1143.5 IU/L (p < 0.05), while all other laboratory indices remained stable. Injection site pain was the most frequently reported adverse event, with no increases in painful crises, hypersensitivity or oedema. After TRT, there was no significant increase in priapism frequency. Median questionnaire scores were increased for the IIEF (46-68, p = 0.018), reduced for ADAM (5.0-2.0, p = 0.016) and unchanged for WHOQOL (98-103, p = 0.086). TRT using testosterone undecanoate with eugonadal intent for hypogonadism appears to be safe in men with SCD. This treatment does not appear to promote priapism occurrences and rather it possibly improves sexual function. Future prospective evaluations in larger groups of hypogonadal men with SCD are necessary to confirm these findings.

Abstract 19261: The Association Between Testosterone Replacement Therapy and Adverse Cardiovascular Outcomes in Veterans Undergoing Coronary Angiography

Background: Adverse cardiac events were not demonstrated in randomized controlled trials of testosterone replacement therapy (TRT) in men until 2009 when the Testosterone in Older Men with Mobility Limitations trial was halted due to increased cardiac events in the treatment group. Therefore, the safety of TRT in older men with medical comorbidities is under debate. Methods: We used the VA CART-CL registry to identify all veterans undergoing coronary angiography between 2005 and 2011 who had total testosterone levels ≤ 250 ng/dL measured post-procedure. We derived a propensity-matched (2:1) cohort of patients dispensed TRT to patients not dispensed TRT. Multivariable Cox regression assessed the association between TRT and myocardial infarction (MI) or death treating TRT as a time varying covariate. We also evaluated this association within strata of CAD: no CAD, nonobstructive CAD (&gt;20% stenosis in any vessel), and obstructive CAD (≥ 70% in any vessel or ≥ 50% in the left main). Results: Of the 3,375 veterans who had a total testosterone level ≤ 250, 461 (12%) were initiated on TRT after a mean of 546 days (median 463 days) after coronary angiography. No significant differences were observed in the baseline characteristics of the TRT and non-TRT propensity matched groups including mean age (61), hypertension (89%), diabetes (55%), and mean testosterone level (166). In multivariable analyses, there was a significant interaction between TRT and CAD strata (p=0.04). Among veterans with no CAD or nonobstructive CAD, there was no association between TRT and MI/death (p=0.46 and p=0.3, respectively). Among those with obstructive CAD, TRT was associated with significantly increased risk of MI/death (HR 2.51; 95% CI 1.6 - 3.94). Conclusion: In this cohort of veterans undergoing coronary angiography with low testosterone levels, TRT can be associated with increased risk of MI/death as compared to no TRT. This risk appears to be present in patients with obstructive CAD but not among patients with less severe CAD. These findings may have potential implications for targeting testosterone use among selected patient populations.

SERUM TESTOSTERONE IS ASSOCIATED WITH AGGRESSIVE PROSTATE CANCER IN OLDER MEN: RESULTS FROM THE BALTIMORE LONGITUDINAL STUDY OF AGING

Study Type – Prognosis (inception cohort) Level of Evidence 1b OBJECTIVE To evaluate the relationship between testosterone levels and the development of high-risk prostate cancer, by prospectively examining serum androgen concentrations in a well-studied cohort, as the role of testosterone in prostate cancer progression is debated. PATIENTS AND METHODS The study comprised 781 men in the Baltimore Longitudinal Study of Aging who had sex steroid measurements before a diagnosis of prostate cancer, or at their last visit for those without cancer (no cancer, 636; cancer, not high risk, 109; cancer, high risk, 36). High-risk cancer was defined as death from prostate cancer, a prostate specific antigen (PSA) level of ≥20 ng/mL at diagnosis, or a Gleason score of ≥8. The hazard ratio (HR) of high-risk disease was determined using a Cox proportional hazards regression model with simple updating, and risk rates were stratified by age and tercile for androgens of interest based on the proportional hazards analyses. RESULTS The likelihood of high-risk prostate cancer doubled per unit (0.1) increase in the free testosterone index (FTI) for patients aged >65 years (HR 2.07, 95% confidence interval, CI, 1.01–4.23; P = 0.047); the likelihood for men aged ≤65 years was inversely related to the FTI (HR 0.96, 95% CI 0.35–2.6; P = 0.9). The risk rate per person-years increased from lowest to highest tercile of FTI for the oldest men (age >70 years) but this trend was not apparent among younger men. CONCLUSION Higher levels of serum free testosterone are associated with an increased risk of aggressive prostate cancer among older men. These data highlight the importance of prospective trials to insure the safety of testosterone-replacement therapy.

Androgen Replacement in Men Undergoing Treatment for Prostate Cancer

Hypogonadism is a clinical and biochemical syndrome that may cause significant detriment in the quality of life and adversely affect the function of multiple organ systems. With the increase in life expectancy and prostate cancer (PCa) survival, a significant increase in the number of men with hypogonadism who have undergone presumably curative treatment for PCa is anticipated. To critically review the literature regarding testosterone replacement therapy (TRT) after PCa treatment with curative intent. Review of peer-reviewed literature. There was special focus on the potential implications and safety of TRT in men with hypogonadism who have undergone curative treatment for PCa. English-language relevant publications were identified via electronic medical databases (MEDLINE, EMBASE, and DARE). Despite the wide spread of contraindication of testosterone replacement in men with known or suspected PCa, there is no convincing evidence that the normalization of testosterone serum levels in men with low but no castrate levels is deleterious. In the few available case series describing testosterone replacement after treatment for PCa, no case of clinical or biochemical progression was observed. Although further studies are necessary before definitive conclusions can be drawn, the available evidence suggests that TRT can be cautiously considered in selected hypogonadal men treated with curative intent for PCa and without evidence of active disease.