Martin Kathrins

The Relationship Between Testosterone-Replacement Therapy and Lower Urinary Tract Symptoms: A Systematic Review

OBJECTIVE To systematically review prospective trials evaluating the clinical effects of testosterone-replacement therapy on lower urinary tract symptoms and prostate volume. MATERIALS AND METHODS We performed a literature review through PubMed, Embase, and Cochrane Library from 1994 to 2015 for prospective trials of hypogonadal men with benign prostatic hyperplasia or lower urinary tract symptoms treated with testosterone-replacement therapy. We evaluated the abstracts for outcomes related to International Prostate Symptom Score, prostate volume, and urodynamic parameters. RESULTS An original cohort of 3079 abstracts was reviewed. Thirty-five trials were selected for inclusion. The majority of trials reviewed found no significant prostate growth due to testosterone-replacement therapy. Studies of men with baseline mild lower urinary tract symptoms demonstrated either no change or an improvement in symptoms after treatment. There was a lack of relevant urodynamic studies. Trials of men with the metabolic syndrome demonstrated uniform improvement in lower urinary tract symptoms. Forty-six percent of all the trials identified included exclusion criteria for baseline severe-range lower urinary tract symptoms or other signs of obstructive lower urinary tract symptoms. CONCLUSION The current literature demonstrates scant support for a causative relationship between testosterone-replacement therapy, de novo or worsening lower urinary tract symptoms, and prostate volume. Furthermore, our review found an absence of high quality evidence that would support guideline recommendations that testosterone-replacement therapy is relatively contraindicated in men with severe-range lower urinary tract symptoms. Future clinical trials with more inclusive voiding criteria are needed.

Renal mass size: concordance between pathology and radiology.

Purpose of review Treatment selection of renal masses is informed largely by size. Furthermore, decisions regarding active surveillance involve closely monitoring growth kinetics. It is, therefore, important to understand the accuracy behind radiographic size as compared with pathologic. Recent findings A large number of studies indicate computed tomography (CT) imaging overestimates pathologic size, albeit by a small amount. Smaller masses tend to be overestimated, but larger masses underestimated. Clear cell renal cell carcinoma masses are more likely to be overestimated. CT, ultrasound and MRI have similar concordance with pathologic size. Summary The differences between radiographic and pathologic size are small. Findings show good efficacy across CT, MRI and ultrasound. This may reduce reliance on CT imaging alone in the future.

Low levels of serum testosterone in middle-aged men impact pathological features of prostate cancer

Background Serum testosterone deficiency increases with aging. Age is also a major risk factor for prostate cancer (PrCa) and PCa tumors are more frequently diagnosed among men >65 years old. We evaluated the relationship between preoperative serum testosterone and clinical/ pathological features of PrCa in middle-aged and elderly patients. Methods A total of 605 PrCa patients who underwent robotic-assisted radical prostatectomy between September 2010 and January 2013 at the University of Pennsylvania, and who had serum testosterone levels measured using Elecsys Testosterone II Immunoassay were included in this IRB-approved protocol. Androgen deficiency was determined as serum free testosterone (FT) <47 pg/ml and total testosterone (TT) <193 ng/dl. Demographic, clinical and tumor characteristics of men with low vs. normal TT or FT were compared using t-test or chi-square tests. Logistic regression was used to determine associations of clinical and pathological variables with FT or TT levels. Results Among middle-aged men (45–64 years; n = 367), those with low FT and low TT had, on average, a higher BMI (29.7 vs. 27.4, P < 0.01; and 32.2 vs. 27.6; P < 0.01, respectively) and higher proportion of Gleason 8–10 PrCa (13.3% vs. 4.8%, P = 0.011; and 19.2% vs. 5.1%, P = 0.012) compared to men with normal FT and normal TT values. Patients with low FT had also higher number of positive cores on biopsy (3.9 vs. 3.1 P = 0.019) and greater tumor volume (7.9 ml vs. 6.1 ml, P = 0.045) compared to those with normal FT. Among men ≥65 years (n = 135) there was no difference in prostatectomy specimens of PrCa between patients with low or normal FT or TT. Conclusion Among men aged 45–64 years low serum pretreatment FT and TT predicted more aggressive features of PrCa in prostatectomy specimens. In middle-aged patients low testosterone levels measured pre-operatively may indicate more aggressive disease parameters.

Malignancy in disorders of sex development

Disorders of sex development (DSD) represent a spectrum of conditions in which chromosomal, gonadal, or anatomic sex are atypical and affect 1 in 4,500–5,000 live births. The diagnosis of DSD raises concerns of tumor risk and treatment as well as future fertility preservation. We review the current understanding of the types of gonadal tumors that arise in DSD patients as well as possible markers and treatment. The goal is to inform the members of the DSD team (urologist, endocrinologist, geneticist, psychologist) of the latest findings regarding malignancy in DSD. PubMed® and Google ScholarTM literature searches were performed of current and past peer-reviewed literature on DSD (intersex) regarding gonadal development and tumor formation/treatment. Relevant reviews and original research articles were examined, including cited references, and a synopsis of the data was generated. DSD patients are at increased risk for the development of testicular carcinoma in-situ (CIS) and germ cell tumors (GCT), including seminoma, non-seminoma, juvenile granulosa cell, gonadoblastoma, and dysgerminoma. Cancer risk factors include Y-chromosomal material and gonadal position, especially for streak gonads. The 46 XX DSD patients [congenital adrenal hyperplasia (CAH)] with no genetic Y-chromosomal material are not at higher risk of cancer. Post-pubertal complete androgen insensitivity syndrome (AIS) patients remain prone to tumor development if the testes remain in the abdomen. Estimates of the risk of GCT in partial AIS for untreated undescended testes may be as high as 50%. The cancer risk of scrotal testes in partial AIS is unknown. CIS occurs almost exclusively in patients with hypovirilization, most notably in AIS. Persistent Mullerian Duct Syndrome (PMDS) confers the usual cancer risk associated with cryptorchidism, but also a possible tumor risk of the Mullerian remnant. Several markers are under investigation for tumor evaluation in the DSD population beyond hCG and AFP (Oct3/4, TSPY, WT-1). The management of patients with DSD is complex and evaluation of tumor risk is aided by advances in genotyping for Y-chromosomal material not evident in traditional karyotyping. More complete genetic screening for DSD patients should increasingly become the standard of care. Developments in pathologic diagnosis will further challenge our traditional understanding of the oncologic management and surveillance of these patients. Future studies utilizing more advanced histologic examination of gonads will improve our understanding of the true incidences of malignancy in this diverse population.

Impact of testosterone replacement therapy on thromboembolism, heart disease and obstructive sleep apnoea in men

To assess the association of testosterone replacement therapy (TRT) with thromboembolism, cardiovascular disease (stroke, coronary artery disease and heart failure) and obstructive sleep apnoea (OSA).

MP91-04 ADVERSE EFFECTS OF TESTOSTERONE REPLACEMENT THERAPY FOR MEN, A MATCHED COHORT STUDY

INTRODUCTION AND OBJECTIVES: To evaluate role of lowintensity shock wave therapy (LI-SWT) in penile rehabilitation (PR) post nerve sparing radical cysto-prostatectomy (NS-RCP). METHODS: Eighty seven sexually active men with muscle invasive bladder cancer were enrolled in this prospective study. After bilateral NS-RCP with orthotopic diversion (W-Pouch) by a single expert surgeon between January 2015 & October 2016, patients were randomized into 3 groups (29 patients/group). SWL Group received 12 sessions of penile LI-SWT (2/week for 3 weeks, then 3 weeks free of treatment, then 2/week for another 3 weeks). Phosphodiesterase type-5 inhibitors (PDE5i) Group received oral PDE5i of 50 mg /day for 6 months. Control Group was followed up only without any therapy. Patients were assessed before surgery and at 1 (FU1), 3 (FU2), 6 (FU3) and 9-month (FU4) post operatively. Effectiveness was assessed by IIEF-15 questionnaire and erection hardness score (EHS). RESULTS: Mean age was 54.1 5.9 years with mean followup period 15.9 4.2 months. There were no statistically significant differences regarding preoperative patients demographic data & tumor criteria. At FU1; All patients have insufficient erection for vaginal penetration. EHS < 2; with decrease of preoperative IIEF-EF mean score from 28 to 6.6. In SWL group; At FU2; 17/29 patients regained potency which is maintained in 15 only at FU3&4. However; 6 of remaining 12 patients regained & maintained potency at FU3&4. Statistical evaluation showed significant increase in IIEF-EF score from 6.6 at FU1 to 23 at FU2, 24 at FU3 and 24.5 at FU4 ( P <0.001). In PDE5i group; At FU2; 16/29 patients regained & maintained potency at FU3&4. However; 7 of remaining 13 patients regained & maintained potency at FU3&4. Statistical evaluation showed significant increase in IIEF-EF score from 6.6 at FU1 to 22.8 at FU2, 24 at FU3 and 24.7 at FU4 (P <0.001). In Control group; At FU2; 12/29 patients regained & maintained potency at FU3&4. However; 6 of remaining 17 patients regained & maintained potency at FU3&4. Statistical evaluation showed no significant difference in potency recovery rates at FU2 & FU3,4 among the groups ( P 1⁄4 0.14 & P 1⁄4 0.24 respectively). Potency recovery rates at FU2 were 58.6% vs 55.2% vs 41.4% in SWL, PDE5i and Control group, respectively. While potency recovery rates at FU3,4 were 72.4% vs 79.3% vs 62.1% in SWL, PDE5i and Control group, respectively. CONCLUSIONS: LI-SWT is safe and as effective as oral PDE5i in PR post NS-RCP. A large-scale study is required to determine the value of this treatment modality in ED post NS-RCP.

Diagnosis and treatment of infertility-related male hormonal dysfunction

Treatment of infertility-related hormonal dysfunction in men requires an understanding of the hormonal basis of spermatogenesis. The best method for accurately determining male androgenization status remains elusive. Treatment of hormonal dysfunction can fall into two categories — empirical and targeted. Empirical therapy refers to experience-based treatment approaches in the absence of an identifiable aetiology. Targeted therapy refers to the correction of a specific underlying hormonal abnormality. However, the tools available for inferring the intratesticular hormonal environment are unreliable. Thus, understanding the limitations of serum hormonal assays is very important for determining male androgen status. Furthermore, bulk seminal parameters are notoriously variable and consequently unreliable for measuring responses to hormonal therapy. In the setting of azoospermia owing to spermatogenic dysfunction, hormonal therapy — relying on truly objective parameters including the return of sperm to the ejaculate or successful surgical sperm retrieval — is a promising treatment. This approach to the treatment of fertility-related hormonal dysfunction in men contrasts with the current state of its counterpart in female reproductive endocrinology. Treatment of male hormonal dysfunction has long emphasized empirical therapy, whereas treatment of the corollary female dysfunction has been directed at specific deficits.

Inactivation of calcium channels in vascular smooth muscle myocytes

Many of the structural domains involved in Ca2+ channel (CACN) inactivation are also involved in determining their sensitivity to antagonist inhibition. We hypothesize that differences in inactivation properties and their structural determinants may suggest candidate domains as targets for the development of novel, selective antagonists. The characteristics of Ca2+ current (ICa) inactivation, steady-state inactivation (SSIN), and recovery from inactivation were studied in freshly dispersed smooth muscle cells from rabbit portal vein (RPV) using whole-cell, voltage-clamp methods. The time course of inactivation could be represented by two time constants. Increasing ICa by increasing [Ca2+]o or with more negative holding potentials decreased both time constants. With Sr2+, Ba2+, or Na+ as the charge carrier, ICa inactivation was also represented by two time constants, both of which were larger than those found with Ca2+. With Ca2+, Sr2+, or Ba2+ as the charge carrier, both time constants had minimum values near the voltage associated with maximum current. When Na+ (140 mM) was the charge carrier, voltages for Imax (−20 mV) or τmin (o mV) did not correspond. SSIN of ICa had a half-maximum voltage of −32±4 mV for Ca2+, −43 mV±5 mV for Sr2+, −41±5 mV for Ba2+, and −68±6 mV for Na+. The slope factor for SSIN per e-fold voltage change was 6.5±0.2 mV for Ca2+, 6.8±0.3 for Sr2+, and 6.6±0.2 for Ba2+, representing four equivalent charges. When Na+ or Li+ was the charge carrier, the slope factor was 13.5±0.7 mV, representing two equivalent charges. For ICa in rat left ventricular (rLV) myocytes, there was no difference in the slope factor of SSIN for Ca2+ and Na+. The rate of recovery of ICa from inactivation varied inversely with recovery voltage and was independent of the charge carrier. These results suggest that inactivation of ICa in PV myocytes possess an intrinsic voltage dependence that is modified by Ca2+. For RPV but not rLV ICa, the charge of the permeating ion confers the voltage-dependency of SSIN.

Implications of Sperm Source on ICSI Outcome: Assessment of TESE and Other Surgical Sperm Retrieval Methods

This chapter addresses the options for sperm origin for couples requiring intracytoplasmic sperm injection (ICSI) for advanced fertility treatment. Sperm from various sources have been shown to have differing properties, which are thought to affect ICSI outcomes. One of these key differences is in the DNA fragmentation index (DFI). It has been postulated that sperm DFI increases during transit through the male genital tract and that this may impact fertilization and pregnancy rates. Sperm may be either ejaculated or surgically retrieved from the testicle, vas deferens, or epididymis. Various retrieval methods exist. In men with azoospermia, epididymal and testicular sperm have been utilized for ICSI with varied results; therefore, a conclusive superior source cannot be identified. In men with cryptozoospermia, ejaculated sperm or surgically retrieved sperm can be used. Comparing testicular and ejaculated sperm, combining all studies no statistically significant difference in pregnancy or fertilization rates have been seen.

Original investigations into the diagnosis and treatment of ejaculatory dysfunction

The method employed is simple, harmless and-above all-not objectionable to patients. In cases such as those described, it is preferable to other therapeutic measures, which are too often both prolonged and useless. -Schellen T. Induction of ejaculation by electrovibration. Fertil Steril 1968;19(4):566-9. Retrograde ejaculation was associated with stricture of the urethra of long standing. A tight stricture may allow passage of urine but not semen, which is more viscid. -Girgis SM, Etriby A, El-Hefnawy H, Kahil S. Aspermia: a survey of 49 cases. Fertil Steril 1968;19(4):580-8.