Robert M. Coward

Prostate‐specific antigen changes and prostate cancer in hypogonadal men treated with testosterone replacement therapy

To retrospectively review hypogonadal men receiving testosterone replacement therapy (TRT), and evaluate the changes in prostate‐specific antigen (PSA) levels over an extended period, and thus evaluate the occurrence of prostate cancer, as a primary concern in treating late‐onset hypogonadism (LOH) is the potential increased risk of prostate cancer; we also recorded the cardiovascular effects of TRT.

Anabolic steroid induced hypogonadism in young men.

PURPOSE The use of anabolic androgenic steroids has not been traditionally discussed in mainstream medicine. With the increased diagnosis of hypogonadism a heterogeneous population of men is now being evaluated. In this larger patient population the existence of anabolic steroid induced hypogonadism, whether transient or permanent, should now be considered. MATERIALS AND METHODS We performed an initial retrospective database analysis of all 6,033 patients who sought treatment for hypogonadism from 2005 to 2010. An anonymous survey was subsequently distributed in 2012 to established patients undergoing testosterone replacement therapy. RESULTS Profound hypogonadism, defined as testosterone 50 ng/dl or less, was identified in 97 men (1.6%) in the large retrospective cohort initially reviewed. The most common etiology was prior anabolic androgenic steroid exposure, which was identified in 42 men (43%). Because of this surprising data, we performed an anonymous followup survey of our current hypogonadal population of 382 men with a mean±SD age of 49.2±13.0 years. This identified 80 patients (20.9%) with a mean age of 40.4±8.4 years who had prior anabolic androgenic steroid exposure. Hypogonadal men younger than 50 years were greater than 10 times more likely to have prior anabolic androgenic steroid exposure than men older than 50 years (OR 10.16, 95% CI 4.90-21.08). Prior anabolic androgenic steroid use significantly correlated negatively with education level (ρ=-0.160, p=0.002) and number of children (ρ=-0.281, p<0.0001). CONCLUSIONS Prior anabolic androgenic steroid use is common in young men who seek treatment for symptomatic hypogonadism and anabolic steroid induced hypogonadism is the most common etiology of profound hypogonadism. These findings suggest that it is necessary to refocus the approach to evaluation and treatment paradigms in young hypogonadal men.

Tadalafil in the treatment of erectile dysfunction

The treatment for erectile dysfunction (ED) was revolutionized with the development of phosphodiesterase type 5 (PDE5) inhibitors. Tadalafil (Cialis®; Eli Lilly and Company, Indianapolis, IN, USA) is the newest and most versatile PDE5 inhibitor in the clinical armamentarium for the treatment of ED. Its most unique characteristic is its long half-life of 17.5 hours, which lends itself to a longer therapeutic window with on-demand dosing and effective steady-state plasma concentrations with once-daily dosing. Clinical trials have proven its safety and efficacy with both dosing strategies for all severities and etiologies of ED, including difficult-to-treat ED. This thorough review will discuss ED, the physiology of penile erection and the role of PDE5, and all aspects of tadalafil, from its development, through its pharmacology, to its latest clinical studies and indications.

The effects of advanced paternal age on fertility

Modern societal pressures and expectations over the past several decades have resulted in the tendency for couples to delay conception. While women experience a notable decrease in oocyte production in their late thirties, the effect of age on spermatogenesis is less well described. While there are no known limits to the age at which men can father children, the effects of advanced paternal age are incompletely understood. This review summarizes the current state of knowledge regarding advanced paternal age and its implications on semen quality, reproductive success and offspring health. This review will serve as a guide to physicians in counseling men about the decision to delay paternity and the risks involved with conception later in life.

Undergoing varicocele repair before assisted reproduction improves pregnancy rate and live birth rate in azoospermic and oligospermic men with a varicocele: a systematic review and meta-analysis

OBJECTIVE To evaluate how varicocele repair (VR) impacts pregnancy (PRs) and live birth rates in infertile couples undergoing assisted reproduction wherein the male partner has oligospermia or azoospermia and a history of varicocele. DESIGN Systematic review and meta-analysis. SETTING Not applicable. PATIENT(S) Azoospermic and oligospermic males with varicoceles and in couples undergoing assisted reproductive technology (ART) with IUI, IVF, or testicular sperm extraction (TESE) with IVF and intracytoplasmic sperm injection (ICSI). INTERVENTION(S) Measurement of PRs, live birth, and sperm extraction rates. MAIN OUTCOME MEASURE(S) Odds ratios for the impact of VR on PRs, live birth, and sperm extraction rates for couples undergoing ART. RESULT(S) Seven articles involving a total of 1,241 patients were included. Meta-analysis showed that VR improved live birth rates for the oligospermic (odds ratio [OR] = 1.699) and combined oligospermic/azoospermic groups (OR = 1.761). Pregnancy rates were higher in the azoospermic group (OR = 2.336) and combined oligospermic/azoospermic groups (OR = 1.760). Live birth rates were higher for patients undergoing IUI after VR (OR = 8.360). Sperm retrieval rates were higher in persistently azoospermic men after VR (OR = 2.509). CONCLUSION(S) Oligospermic and azoospermic patients with clinical varicocele who undergo VR experience improved live birth rates and PRs with IVF or IVF/ICSI. For persistently azoospermic men after VR requiring TESE for IVF/ICSI, VR improves sperm retrieval rates. Therefore, VR should be considered to have substantial benefits for couples with a clinical varicocele even if oligospermia or azoospermia persists after repair and ART is required.

Feasibility and Outcomes of Robotic-assisted Laparoscopic Radical Cystectomy for Bladder Cancer in Older Patients

OBJECTIVES To report our maturing experience with robotic radical cystectomy as applied to an older patient population with regard to perioperative measures and pathologic outcomes. A robotic approach to radical cystectomy for bladder cancer have recently been described, but its application in an older patient population, which is often the case in bladder cancer and cystectomy, has not yet been assessed. METHODS A total of 119 patients underwent robotic cystectomy and extracorporeal urinary diversion at our institution from January 2006 through October 2009 for clinically localized bladder cancer. Owing to the patient selection early in the present series, the first 20 cases were excluded. The clinical characteristics, operative outcomes, and pathologic results of the consecutive cases were categorized by age (younger, <70 years vs older, age ≥70 years). RESULTS The outcomes of the 61 younger and 38 older patients, including 7 patients >80 years old, were assessed. The younger versus older patients had a lower American Society of Anesthesiologists score (2.6 vs 3.0; P < .001), greater body mass index (28.2 vs 26.1; P = .008), and longer operating room time (4.8 vs 4.4 hours; P = .015). No differences were observed between the 2 groups in blood loss, time to discharge, or complication rate. Also, no significant differences were found in the surgical pathologic findings, including the organ-confined rate (62% vs 71%) and lymph node yield (19.5 vs 18.1). CONCLUSIONS Older patients do not appear to have any significant differences or compromises with regard to the perioperative and pathologic outcomes after robotic radical cystectomy. Thus, robotic radical cystectomy appears to be an appropriate surgical option for older patients.

The evidence for seasonal variations of testosterone in men

Ample evidence exists to support the concept of diurnal variations in testosterone levels; however, substantiation for seasonal fluctuations is sparse and inconsistent. Since circadian disparities exist, laboratory screening for hypogonadism has traditionally been conducted using serum testosterone levels obtained in the early morning. Should circannual variability of testosterone be confirmed, it would make the monitoring of testosterone levels more difficult while forcing the development of seasonal reference standards to allow for comparison. Moreover, decisions to begin treatment and adjustment of practice patterns would likely follow. This review thoroughly explores all of the available evidence concerning seasonal variations in testosterone levels. The impacts of melatonin, vitamin D, sleep-wake cycles, light exposure, physical activity, BMI, and waist circumference are also discussed. Current research suggests that while some evidence exists to support the notion of seasonal testosterone variations, the discussed inconsistencies preclude the incorporation of this concept into current clinical standards.

Patient Satisfaction with Testosterone Replacement Therapies: The Reasons Behind the Choices

INTRODUCTION Testosterone replacement therapy (TRT) for male hypogonadism is rapidly gaining popularity and acceptance. Options include gels, injections, and implantable subcutaneous pellets. AIMS The aim of this study was to determine rates of patient satisfaction and reasons for patient preferences in hypogonadal men on TRT. METHODS An anonymous, prospective survey was distributed to men presenting for TRT at an academic urology clinic. The survey was organized into multiple domains including patient satisfaction and treatment motivation. MAIN OUTCOME MEASURES Patient satisfaction responses obtained via anonymous survey. RESULTS Average patient age was 49 ± 0.7 years (n = 382). Injectable testosterone was chosen by 53%, gel-based regimens by 31%, and pellets by 17%. Overall, 70% of patients were satisfied with their TRT and 14% reported dissatisfaction. Satisfaction rates were similar between gels (68%), injections (73%), and implantable pellets (70%). Doctor recommendation was the sole significant reason for patients preferring gel-based TRT (66% vs. 37% injection users vs. 31% pellet users). Injectable TRT was favored because of lower cost (35% vs. 21% gel users vs. 19% pellet users). Pellets were favored for ease of use (64% vs. 44% injection users vs. 43% gel users) and convenience (58% vs. 26% injection users vs. 19% gel users). Pellets had increased rates of satisfaction within the first 12 months. Improvements in concentration and mood occurred at higher percentages in satisfied patients. CONCLUSIONS Patients are satisfied with TRT. Lower costs are important to patients on injections. Convenience and ease of use are central in choosing pellet therapy. Men on TRT should be questioned about mood and concentration because these factors exhibited the greatest improvements in satisfied patients.

Testosterone deficiency in the aging male

Treatment for hypogonadism is on the rise, particularly in the aging population. Yet treatment in this population represents a unique challenge to clinicians. The physiology of normal aging is complex and often shares the same, often vague, symptoms of hypogonadism. In older men, a highly prevalent burden of comorbid medical conditions and polypharmacy complicates the differentiation of signs and symptoms of hypogonadism from those of normal aging, yet this differentiation is essential to the diagnosis of hypogonadism. Even in older patients with unequivocally symptomatic hypogonadism, the clinician must navigate the potential benefits and risks of treatment that are not clearly defined in older men. More recently, a greater awareness of the potential risks associated with treatment in older men, particularly in regard to cardiovascular risk and mortality, have been appreciated with recent changes in the US Food and Drug Administration recommendations for use of testosterone in aging men. The aim of this review is to provide a framework for the clinician evaluating testosterone deficiency in older men in order to identify correctly and treat clinically significant hypogonadism in this unique population while minimizing treatment-associated harm.

Impact of the 2012 American Urological Association Vasectomy Guidelines on Post-Vasectomy Outcomes

PURPOSE The 2012 American Urological Association (AUA) vasectomy guidelines recommend the finding of rare nonmotile sperm, representing 100,000 or fewer nonmotile sperm per ml, as a metric of post-vasectomy success. At our institution success was previously defined as 2 sequential azoospermic centrifuged semen pellets. The criteria change of including rare nonmotile sperm as a success end point may simplify post-vasectomy followup and decrease the number of post-vasectomy semen analyses required to assure occlusive success. MATERIALS AND METHODS In the context of the new 2012 guidelines we retrospectively reviewed and analyzed the records of 972 of the 1,740 vasectomies (55.9%) performed between January 2000 and June 2012 after which at least 1 post-vasectomy semen analysis was done. RESULTS A total of 1,919 post-vasectomy semen analyses were obtained from 972 patients with a mean ± SE age of 39.7 ± 0.2 years. Occlusive success was evident in 337 azoospermic men (36.4%), while 514 (52.9%) underwent 2 or more post-vasectomy semen analyses and 458 (47.1%) returned for a single post-vasectomy semen analysis but were lost to followup. Of these noncompliant patients 76.0% were azoospermic, 19.7% had rare nonmotile sperm, 1.5% had greater than 100,000 nonmotile sperm per ml and 2.8% had motile sperm. Three patients underwent repeat vasectomy for persistent rare nonmotile sperm. If the criteria defined by the 2012 guidelines had been used to monitor these men, the occlusive success rate would have improved to 97.6% (949 patients) (p <0.05). Repeat vasectomies as well as 896 subsequent post-vasectomy semen analyses would have been avoided. CONCLUSIONS The AUA vasectomy guidelines provide clear, evidence-based criteria for vasectomy success. The guidelines simplify followup protocols, improve patient compliance and help avoid unnecessary post-vasectomy semen analyses and repeat vasectomies.