Faculty Bibliography

Introduction. Men with hypogonadism exhibit decreased serum testosterone levels and may experience a constellation of clinical symptoms, including decrease in muscle mass, loss of sexual desire, impotence, and infertility. While previous studies have shown that implantation of extended release testosterone pellets can provide therapeutic levels of testosterone over several months, additional data are needed to establish this approach as the standard of care for male hypogonadism. Aim. To evaluate the safety and efficacy of testosterone pellets over 6 months as a treatment for male hypogonadism in a clinical practice setting. Methods. A phase IV, single center, open-label study designed to assess the safety and efficacy of subcutaneous insertion of 8 to 12 testosterone 75 mg pellets (450 mg to 900 mg), during a single implantation procedure in hypogonadal men. Subjects who successfully completed the protocol were allowed to enroll in an extension study that included another implantation and 6 months of follow-up. Main Outcome Measures. Safety was determined by investigator-reported adverse events, changes in vital signs, physical exam findings, and laboratory tests. Efficacy was based on serum laboratory tests, physical exams, implantation site evaluations, and vital signs. Secondary objectives were to assess patient preference for testosterone pellets and to maintain optimal total testosterone. Results. Mean testosterone significantly increased and luteinizing hormone (LH) levels significantly decreased from pre-implantation values at weeks 1, 4, and 12, and had returned to pre-implantation levels by week 24. Prostate-specific antigen levels remained unchanged for the duration of the study. Improvements in several symptoms of hypogonadism were determined with multiple questionnaires. Implanted testosterone pellets were generally well tolerated. Conclusion. Implanted testosterone pellets can normalize testosterone and LH levels and improve symptoms for at least 3 months and up to 6 months in men with hypogonadism, and should be considered as a therapeutic option for hypogonadal men. Kaminetsky JC, Moclair B, Hemani M, and Sand M. A phase IV prospective evaluation of the safety and efficacy of extended release testosterone pellets for the treatment of male hypogonadism. J Sex Med **;**:**-**

The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate

PURPOSE: We explored the impact of once daily tadalafil on urodynamic measures in men with lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia via invasive and noninvasive urodynamic studies. MATERIALS AND METHODS: We conducted a multicenter, randomized, double blind, placebo controlled clinical trial comparing once daily tadalafil 20 mg vs placebo during 12 weeks in men with lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia with or without bladder outlet obstruction. Invasive and noninvasive urodynamics, International Prostate Symptom Score and general safety were assessed. The primary study end point was change in detrusor pressure at maximum urinary flow rate. RESULTS: Urodynamic measures remained largely unchanged during the study with no statistically significant or clinically adverse difference between tadalafil and placebo in change in detrusor pressure at maximum urinary flow rate (mean difference between treatments -2.2 cm H(2)O, p = 0.33) or any other urodynamic parameter assessed including maximum urinary flow rate, maximum detrusor pressure, bladder outlet obstruction index or bladder capacity (all measures p > or = 0.13). Treatment with tadalafil resulted in significant improvements in International Prostate Symptom Score (mean difference between treatments -4.2, p < 0.001). Tadalafil was generally well tolerated with the majority of adverse events being mild to moderate in severity and few patients discontinuing due to adverse events (tadalafil 2.0%, placebo 1.0%). CONCLUSIONS: Treatment with tadalafil once daily for lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia showed no negative impact on bladder function as measured by detrusor pressure at maximum urinary flow rate or on any other urodynamic parameter assessed. Nonetheless men receiving tadalafil reported significant improvements in International Prostate Symptom Score with an adverse events profile similar to other recent studies of tadalafil for lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia

Study Type - Therapy (RCT) Level of Evidence 1b OBJECTIVE To determine, by post hoc analysis, the effects of tadalafil (a long-acting phosphodiesterase 5 inhibitor) on peak urinary flow (Q(max)), bladder capacity, voiding efficiency and the obstructive symptoms of benign prostatic hyperplasia (BPH) in men with lower urinary tract symptoms secondary to BPH (BPH-LUTS), compared with placebo. PATIENTS AND METHODS After a 4-week placebo run-in period, 1058 men with BPH-LUTS were randomly allocated to receive once daily treatment with placebo or tadalafil (2.5, 5, 10, or 20 mg) for 12 weeks. Uroflowmetry, postvoid residual volume (PVR), and BPH symptom score measurements were assessed throughout the trial. RESULTS Increases in Q(max) were numerically greater for tadalafil (2.5, 5, 10, and 20 mg with percentage changes of 15%, 16%, 17%, 22%, respectively) vs placebo (12%), but did not reach statistical significance. Age, baseline Q(max), erectile dysfunction history, sexual activity, and previous alpha-blocker therapy significantly influenced the Q(max) response. Tadalafil was not associated with significant changes in PVR. Tadalafil had its greatest effects on bladder capacity and voiding efficiency in men with a Q(max) of <10 mL/s at baseline, but these changes were not significantly different from placebo responses. Tadalafil treatment significantly improved the IPSS obstructive subscores (tadalafil 2.5, 5, 10, 20 mg with percentage changes of 24%, 31%, 33%, 33%, respectively) vs placebo (13%). CONCLUSIONS Once daily tadalafil did not significantly change Q(max) or voiding efficiency compared with placebo in men with BPH-LUTS, although there were dose-dependent improvements. No subgroups were identified where tadalafil or placebo treatment had a deleterious effect on Q(max). Despite these minimal changes in uroflowmetric measures, tadalafil was associated with clinically meaningful and statistically significant improvements in the obstructive symptoms of BPH

Hypogonadism has a number of important clinical consequences related to androgen deficiency and impaired spermatogenesis. The cause of this condition is multifactorial and can result from hypothalamic, pituitary or gonadal dysfunction as well as factors that affect hormonal signaling along the hypothalamic-pituitary-gonadal axis. While testosterone replacement is the most common treatment, it can paradoxically lead to infertility, and may be a less physiologic therapy for patients with secondary hypogonadism due to pituitary dysfunction. Clomiphene citrate, and its derivatives, may allow for restoration of gonadal function by restoring physiologic pituitary function in a subset of patients with hypogonadism

ABSTRACT Introduction. The validated Quality of Erection Questionnaire (QEQ) evaluates satisfaction with erection quality. Aim. To collate QEQ data, including correlations between QEQ outcomes and outcomes assessing emotional well-being, treatment satisfaction, and erection hardness after sildenafil citrate treatment. Methods. In four trials, men older than 18 years and with erectile dysfunction, a stable sexual partner, and no recent phosphodiesterase type 5 inhibitor use were randomized to double-blind flexible-dose sildenafil or placebo (1:1 ratio) for 6 or 10 weeks (two trials), fixed-dose 50 mg, 100 mg, and placebo (1:1:1 ratio) for 8 weeks (one trial), and 50 mg and 100 mg (1:1 ratio) for 4 weeks after 4 weeks of single-blind sildenafil 50 mg. Exclusion criteria included recent significant cardiovascular disease, use of nitrates, nitric oxide donors, cytochrome P450 3A4 inhibitors, or other erectile dysfunction treatment, and sildenafil hypersensitivity or previous severe or serious treatment-related adverse event. Main Outcomes Measures. Scores on the QEQ, QEQ Question 5 (satisfaction with erection hardness), the Self-Esteem and Relationship Questionnaire, and the Erectile Dysfunction Inventory of Treatment Satisfaction; the percentage of occasions with Erection Hardness Score 3 (EHS 3, hard enough for penetration but not completely hard) and/or EHS 4 (completely hard and fully rigid); and Pearson correlation coefficients. Results. 1,296 men (18-80 years) were randomized. Except for the percentage of occasions with EHS 3, all outcomes improved in men treated with sildenafil and correlated positively with the change in QEQ scores in all trials. Conclusions. Satisfaction with the quality of erections, which is easily monitored with the QEQ, correlated positively with measures of emotional well-being and treatment satisfaction and with the change in percentage of erections that were completely hard and fully rigid, but not with the change in percentage of erections that were hard enough for penetration but not completely hard. Kaminetsky JC, Depko AJ, Stroberg P, Buvat J, Tseng L-J, and Stecher VJ. In men with erectile dysfunction, satisfaction with quality of erections correlates with erection hardness, treatment satisfaction, and emotional well-being. J Sex Med **;**:**-**

OBJECTIVES: The purpose of this study was to report on the clinical outcomes of patients treated at our institution for prostate cancer (PCa) who had been previously diagnosed as Human immunodeficiency virus (HIV) positive. METHODS: The authors conducted a retrospective study of 14 PCa/HIV patients who were being treated for PCa with external beam radiotherapy, brachytherapy, or a combination of the two. Each patient's prostate-specific antigen (PSA) level, CD4 count, and viral load were obtained before the initial radiation treatment and at the time of their most recent follow-up. In addition, 13 of 14 patients completed a quality of life survey with a social worker on staff and were examined by their radiation oncologist to assess the complications after treatment. RESULTS: Comparing pretreatment data with the data at last follow-up, only 1 patient's PSA level remained above 1.1 ng/mL. The average CD4 count remained stable, increasing from 523 to 577 cells/mm(3), with the lowest final count at 200 cells/mm(3). Viral load increased in only 2 of 14 patients. There were no unusual rectal, urinary, or sexual complications, and no infections related to treatment. CONCLUSIONS: Based on changes in viral load and CD4 count, radiotherapy does not appear to have a long-term negative effect on the immune system. Treatment complications are consistent with HIV-negative patients, giving no evidence that the subset of PCa/HIV patients should be treated differently from PCa patients without HIV when considering radiation therapy. More investigation will be necessary before reliable mortality and morbidity data can be assessed

Male sexual dysfunction (MSD) is a common disorder associated with a wide range of physical and psychological conditions. Erectile dysfunction, the most commonly studied aspect of MSD, is common and increases with age and with certain comorbid conditions. The pathophysiology of ED and other forms of MSD can be traced to a variety of etiologies, including vascular, hormonal, psychiatric, iatrogenic and potentially neurobiological causes

PURPOSE: We assessed the efficacy and safety of tadalafil dosed once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia. MATERIALS AND METHODS: Following a 4-week, single-blind, placebo run-in 281 men were randomly assigned (1:1) to 5 mg tadalafil for 6 weeks, followed by dose escalation to 20 mg for 6 weeks or 12 weeks of placebo. RESULTS: Tadalafil significantly improved the mean change from baseline in International Prostate Symptom Score at 6 weeks (5 mg tadalafil -2.8 vs placebo -1.2) and at 12 weeks (5/20 mg tadalafil -3.8 vs placebo -1.7). Larger changes were observed with inclusion of the placebo run-in at 12 weeks (5/20 mg tadalafil -7.1 vs placebo -4.5). Significant improvements were also seen in the International Prostate Symptom Score irritative and obstructive domains, the International Prostate Symptom Score quality of life index, a question about urinary symptom improvement and the Benign Prostatic Hyperplasia Impact Index (significant at 12 weeks) vs placebo. International Prostate Symptom Score and International Index of Erectile Function erectile function domain scores significantly improved in the 56% of men with lower urinary tract symptoms/benign prostatic hyperplasia who were sexually active and had erectile dysfunction. Changes in uroflowmetry parameters were similar in the placebo and tadalafil groups. Commonly reported (2% or greater) treatment emergent adverse events were "erection increased," dyspepsia, back pain, headache, nasopharyngitis and upper respiratory tract infection (each 5.1% or less). No change in post-void residual volume was seen with tadalafil treatment. CONCLUSIONS: Tadalafil once daily was well tolerated and demonstrated clinically meaningful and statistically significant symptomatic improvement for lower urinary tract symptoms/benign prostatic hyperplasia. Tadalafil also improved erectile function in men with lower urinary tract symptoms and erectile dysfunction.