Theodore R. Saitz

New insights on premature ejaculation: a review of definition, classification, prevalence and treatment

There are ongoing debates about the definition, classification and prevalence of premature ejaculation (PE). The first evidence-based definition of PE was limited to heterosexual men with lifelong PE who engage in vaginal intercourse. Unfortunately, many patients with the complaint of PE do not meet these criteria. However, these men can be diagnosed as one of the PE subtypes, namely acquired PE, natural variable PE or premature-like ejaculatory dysfunction. Nevertheless, the validity of these subtypes has not yet been supported by evidence. The absence of a universally accepted PE definition and lack of standards for data acquisition have resulted in prevalence studies that have reported conflicting rates. The very high prevalence of 20%-30% is probably due to the vague terminology used in the definitions at the time when such surveys were conducted. Although many men may complain of PE when questioned for a population-based prevalence study, only a few of them will actively seek treatment for their complaint, even though most of these patients would define symptoms congruent with PE. The complaints of acquired PE patients may be more severe, whereas complaints of patients experiencing premature-like ejaculatory dysfunction seem to be least severe among men with various forms of PE. Although numerous treatment modalities have been proposed for management of PE, only antidepressants and topical anaesthetic creams have currently been proven to be effective. However, as none of the treatment modalities have been approved by the regulatory agencies, further studies must be carried to develop a beneficial treatment strategy for PE.

The pre-treatment prevalence and types of sexual dysfunction among patients diagnosed with prostate cancer

Erectile dysfunction (ED) following prostate cancer therapy is a common condition that is well documented in literature. Despite the significant focus placed on ED and prostate cancer, very little is known regarding the baseline prevalence of other aspects of sexual dysfunction (SD) in this specific cohort of patients. The objective of the current manuscript was to assess the prevalence of subtypes of SD, including ED, ejaculatory dysfunction (EjD) and decreased libido among men with newly diagnosed prostate cancer. To achieve this objective, patients presenting to our clinic with a new diagnosis of prostate cancer from July 2011 and May 2012 completed the Male Sexual Health Questionnaire (MSHQ) to assess baseline sexual function. A total of 60 patients completed an MSHQ, with a mean age of 60.28 ± 6.25 (range 44–73 years). Of patients surveyed, 14% reported no sexual activity within the previous month, while 53% had sex at least once weekly. The percentage of patients reporting ED, EjD and decreased sexual desire ≥50% of the time was 37, 26 and 48% respectively. Eleven to 18% of patients reported that these symptoms were ‘very’ or ‘extremely’ bothersome. Patients noted dissatisfaction with the quality of their sexual relationship, frequency of sexual activity and quality of sex in 18, 31 and 20%, respectively. Overall findings suggest that patients with newly diagnosed prostate cancer experience a high rate of SD at baseline. Knowledge of these prevalence rates may assist physicians managing patients expectations with planned therapies.

Advances in understanding and treating premature ejaculation.

Over the past several years, many advances have been made in our understanding of the epidemiology, pathophysiology, and management of premature ejaculation. Newly developed definitions of premature ejaculation are now available, and our perception of the classification, prevalence, aetiological factors, and treatment options for premature ejaculation have evolved. Despite ongoing research, there remains much to be learned about all aspects of this common sexual disorder, in particular effective clinical diagnosis and treatment options.

Side Effects of 5‐Alpha Reductase Inhibitors: A Comprehensive Review

INTRODUCTION 5α-reductase inhibitors (5ARI) include finasteride and dutasteride, and are commonly prescribed in the treatment of benign prostatic hyperplasia and androgenic alopecia. 5ARIs are associated with several known adverse effects (AEs), with varying reported prevalence rates. AIM The aim was to review and summarize findings from published literature detailing AEs associated with 5ARI use. A secondary aim was to review potential mechanisms of action, which may account for these observed and reported AEs. METHODS A PubMed search was conducted on articles published from 1992 to 2012, which reported AEs with 5ARIs. Priority was given to randomized, placebo-controlled trials. Studies investigating potential mechanisms of action for 5ARIs were included for review. MAIN OUTCOME MEASURES AE data reported from available trials were summarized and reviewed. RESULTS Reported AEs with 5ARIs include sexual dysfunction, infertility, mood disorders, gynecomastia, high-grade prostate cancer, breast cancer, and cardiovascular morbidity/risk factors, although their true association, prevalence, causality, and clinical significance remain unclear. A pooled summary of all randomized, placebo-controlled trials evaluating 5ARIs (N = 62,827) revealed slightly increased rates over placebo for decreased libido (1.5%), erectile dysfunction (ED) (1.6%), ejaculatory dysfunction (EjD) (3.4%), and gynecomastia (1.3%). The limited data available on the impact of 5ARIs on mood disorders demonstrate statistically significant (although clinically minimal) differences in rates of depression and/or anxiety. Similarly, there are limited reports of reversible, diminished fertility among susceptible individuals. Post-marketing surveillance reports have questioned the actual prevalence of AEs associated with 5ARI use and suggest the possibility of persistent symptoms after drug discontinuation. Well-designed studies evaluating these reports are needed. CONCLUSIONS 5ARIs are associated with slightly increased rates of decreased libido, ED, EjD, gynecomastia, depression, and/or anxiety. Further studies directed at identifying prevalence rates and persistence of symptoms beyond drug discontinuation are required to assess causality. Trost L, Saitz TR, and Hellstrom WJG. Side effects of 5-alpha reductase inhibitors: A comprehensive review. Sex Med Rev 2013;1:24-41.

MP60-04 VASAL PROTEIN PROFILE AND MICROSCOPIC SPERM PRESENCE AT TIME OF VASECTOMY REVERSAL

RESULTS: Four weeks after subcutaneous autograft of LSCs in combination with Sertoli and myoid cells in castrate mice, the cells in graft expressed 3B-HSD, SOX-9 and A-SMA. Serum testosterone in castrated mice that received autograft was significantly higher compared to mice that did not receive autograft (22.4þ/-1.9 VS 11.9þ/0.8 Ng/DL, p<0.05). Importantly, mice that received LSC autograft maintained production of LH and FSH with levels higher than mice that received testosterone pellet implant (LH 3.09þ/-1.47 VS 0.01þ/-0.01 ng/ml) (FSH 102.6þ/-28.1 VS 51.7þ/-7.4ng/ml) respectively. Furthermore, T levels consistently increased at 15, 30 and 60 days following subcutaneous autograft (12.01þ/-0.87ng/DL (neg CTL) vs 15.1þ/1.50ng/DL (15 days Autograft) vs 22.26þ/-1.33ng/DL (30 days Autograft) vs 37.3þ/-9.6ng/DL (60 days Autograft)), demonstrating differentiating LSC within the autograft. In addition, we found that levels of 3BHSD were induced upon SAG (DHH inducer) treatment in-vitro conditions. Immunostaining autografts (4 weeks), containing LSCs treated with SAG before subcutaneous implantation, showed higher levels of SOX9, and ASMA. Importantly, T levels were significantly higher (p<0.05) in mice received SAG treated autografts vs negative controls (23.95þ/4.11 Ng/DL vs 11.91þ/-0.80 Ng/DL). Collectively these results establish that Hedgehog signalling induces survival of adjacent testicular cells and regulates graft function. CONCLUSIONS: Our results demonstrate that subcutaneous autograft of LSC in combination with Sertoli cells and myoid cells can increase serum testosterone without inhibiting circulating LH and FSH in castrate mice. Extratesticular LSC appear to be regulated by Hedgehog signalling. Leydig stem cell autograft can a novel therapeutic approach to increase serum testosterone while simultaneously preserving hypothalamic-pituitary-gonadal axis. Factors involved in hedgehog signalling can be utilized to enhance graft efficacy.

Neutrophil-to-lymphocyte ratio is elevated in recurringnonmuscle invasive bladder cancer

BACKGROUND/AIM Although it has been shown that the neutrophil-to-lymphocyte ratio (NLR) may predict the progression of nonmuscle invasive bladder cancer (NMIBC), its association with the recurrence of NMIBC has been poorly studied. The aim of this study is to evaluate the association between NLR and disease recurrence in patients with NMIBC. MATERIALS AND METHODS The medical records of 428 consecutive initially diagnosed NMIBC patients who underwent transurethral resection between January 2010 and July 2014 were retrospectively reviewed. Patients without a preoperative NLR (n = 6), without a minimum of 6 months of follow-up (n = 56), who were lost to follow-up (n = 38), or who had progressive disease during follow-up (n = 42) were excluded. The demographics, tumor characteristics, and NLRs of patients with and without tumor recurrence were compared. RESULTS Of 286 patients who met the inclusion criteria, 68 (17.43%) had recurrent disease. Tumor size (P = 0.198), tumor type (P = 0.929), and the presence of carcinoma in situ (P = 0.373) were also similar between groups. Patients with recurrent disease had a higher mean NLR (2.62 ± 0.99 vs. 2.2 ± 0.96, P = 0.002). CONCLUSION Our results show that NLR may be used as a predictor of recurrence in patients with NMIBC; however, prospective studies are required to validate these findings.

Premature ejaculation: do we have effective therapy?

Introduction Premature ejaculation (PE) is the most common sexual dysfunction, with the majority of PE patients remaining undiagnosed and undertreated. Despite its prevalence, there is a current paucity of data regarding available treatment options and mechanisms. The objective of the current investigation is to review and summarize pertinent literature on therapeutic options for the treatment of PE, including behavioral/psychologic, oral pharmacotherapy, and surgery. Methods A pubmed search was conducted on articles reporting data on available treatment options for PE. Articles describing potential mechanisms of action were additionally included for review. Preference was given towards randomized, controlled trials, when available. Results PE remains an underdiagnosed and undertreated disease process, with limited data available regarding potential underlying mechanisms and long-term outcomes of treatment options. Psychological/behavioral therapies, including the stop-start, squeeze, and pelvic floor rehabilitation techniques have demonstrated improvements in short-term series, with decreased efficacy with additional follow-up. Topical therapies, which are commonly utilized result in prolonged intravaginal ejaculatory latency time (IELT) at the expense of potential penile/vaginal Hypothesia. Oral therapies similarly demonstrate improved IELTs with variable side effect profiles and include selective serotonin reuptake inhibitors (daily or on demand), phosphodiesterase-5 inhibitors, alpha-1 adrenergic antagonists, and tramadol. Alternative therapies such as acupuncture have shown benefits in limited studies. Surgery is not commonly performed and is not recommended by available guidelines. Conclusions PE is a common condition, with limited data available regarding its underlying pathophysiology and treatment. Available therapies include topical, oral, behavioral/psychologic modification, or a combination thereof. Additional research is required to assess the optimal treatment strategies and algorithms as well as to better define the mechanisms for PE and its management.