Joseph P. Alukal

A Pilot Study to Determine Penile Oxygen Saturation Before and After Vacuum Therapy in Patients with Erectile Dysfunction After Radical Prostatectomy

INTRODUCTION Provoked and spontaneous nocturnal erections are thought to play a role in maintenance of male sexual health through oxygenation of the corpus cavernosa. Conversely, hypoxia is thought to be an etiological factor in the pathogenesis of cavernosal fibrosis and long-term erectile dysfunction. It has been hypothesized that the early penile hypoxia after radical prostatectomy (RP) may lead to fibrosis and consequently a decrease in stretched penile length and long-term erectile dysfunction. AIM The aim of this study was to assess the changes in penile tissue oxygenation with vacuum erection device (VED) use. METHODS Twenty men between 2 and 24 months following RP were enrolled prospectively. Each man cycled a VED to achieve full erection 10 consecutive times over a period of approximately 2 minutes without constriction ring. MAIN OUTCOME MEASURES Tissue oximetry was measured at baseline and immediately after VED using a tissue oximeter at five sites: right thigh, right corpora, glans, left corpora, and left thigh. Additional measurements were captured over the course of an hour. RESULTS Mean age and time from surgery was 58.2 years and 12.6 months, respectively, and the average Sexual Health Inventory for Men score was 7. Use of the VED significantly increased both glanular and corporal oximetry relative to the baseline values for the entire 60 minutes. An initial increase of 55% was seen in corporal oxygenation with VED use. CONCLUSIONS This is the first study demonstrating that a single, brief application of the VED without a constriction ring results in significant improvement in penile oxygen saturation. The use of a VED has significant benefits for patients both with regard to cost and invasiveness when compared with other penile rehabilitation protocols.

Long-Term Satisfaction and Predictors of Use of Intracorporeal Injections for Post-Prostatectomy Erectile Dysfunction

PURPOSE Intracorporeal injections have low use rates and high discontinuation rates. We examined factors associated with intracorporeal injection use, long-term satisfaction with intracorporeal injection and reasons for discontinuation in men treated with radical prostatectomy. MATERIALS AND METHODS Between October 2000 and September 2003, 731 men who underwent open radical retropubic prostatectomy were enrolled in a prospective outcomes study. The 8-year followup evaluation included the UCLA-PCI, and a survey capturing intracorporeal injection use, satisfaction and reasons for discontinuation. Logistic regression was used to determine associations between intracorporeal injection use and preoperative variables. RESULTS The 8-year self-assessment was completed by 368 (50.4%) men. Of these men 140 (38%) indicated prior or current intracorporeal injection use, with only 34 using intracorporeal injection at 8 years. Overall, 44% of the men were satisfied with intracorporeal injections. Reasons for discontinuation included dislike (47%), pain (33%), return of erection (19%), inefficacy (14%) and no partner (6%). Men trying intracorporeal injections had greater preoperative UCLA-PCI sexual function scores (75.2 vs 65.62, p = 0.00005) as well as greater decreases in this score at 3 months (p = 0.0002) and 2 years (p = 0.003). Higher preoperative sexual function scores were independently associated with the use of intracorporeal injections in a model adjusted for age, marital status, nerve sparing status and body mass index (OR 1.021, 95% CI 1.008-1.035). CONCLUSIONS Men pursuing intracorporeal injections have better baseline erectile function and experience greater deterioration in erectile function during the early postoperative period. Despite the high efficacy of injections, many men discontinue intracorporeal injections due to dislike or discomfort. Satisfaction rates for intracorporeal injections indicate their long-term role in restoring sexual function in men with post-prostatectomy erectile dysfunction.

Trends in Testosterone Prescription and Public Health Concerns.

Testosterone supplementation therapy (TST) has become increasingly popular since the turn of the century. Most prescriptions in the U.S. are written by primary care providers, endocrinologists, or urologists. The FDA has requests pharmaceutical companies provide more long term data on efficacy and safety of testosterone products. Results from these studies will help define the appropriate population for TST going forward. It is hoped that these data combined with physician and public education will minimize inappropriate prescribing and allow those likely to benefit from TST to receive it.

The Role of Testosterone Therapy in Cardiovascular Mortality: Culprit or Innocent Bystander?

Testosterone therapy is recommended for men with symptomatic androgen deficiency and unequivocally low testosterone levels. Although the prevalence of hypogonadism seems relatively constant, studies of prescribing patterns in both the United States and the United Kingdom show a dramatic increase in testosterone prescription in recent years, possibly due to increased marketing and inappropriate therapy. Concurrent with this, there has been growing concern regarding the potential adverse effects of testosterone therapy, particularly its cardiovascular risks. In this review, we present our current understanding of the implications of testosterone deficiency, as well as the conflicting evidence surrounding the cardiovascular effects of testosterone replacement therapy. Although there is a lack of adequate data, based on the current evidence, we conclude that testosterone therapy can be safely considered in men with appropriately diagnosed clinical androgen deficiency and increased cardiovascular risk after a thorough discussion of potential risks and with guideline recommended safety monitoring.

Widespread transcriptional scanning in testes modulates gene evolution rates

A long-standing question in molecular biology relates to why the testes express the largest number of genes relative to all other organs. Here, we report a detailed gene expression map of human spermatogenesis using single-cell RNA-Seq. Surprisingly, we found that spermatogenesis-expressed genes contain significantly fewer germline mutations than unexpressed genes, with the lowest mutation rates on the transcribed DNA strands. These results suggest a model of ‘transcriptional scanning’ to reduce germline mutations by correcting DNA damage. This model also explains the rapid evolution in sensory- and immune-defense related genes, as well as in male reproduction genes. Collectively, our results indicate that widespread expression in the testes achieves a dual mechanism for maintaining the DNA integrity of most genes, while selectively promoting variation of other genes.

Testosterone Deficiency and the Prostate

Male hormonal physiology plays an important role in the function and development of the prostate. Moreover, benign prostatic hyperplasia and prostate cancer, two common and bothersome conditions of the prostate, are also influenced by hormonal activity. This article reviews the existing data regarding these complex relationships.

Quantitative Proton Spectroscopy of the Testes at 3 T: Toward a Noninvasive Biomarker of Spermatogenesis

Objectives The aim of this study was to compare testicular metabolite concentrations between fertile control subjects and infertile men. Materials and Methods Single voxel proton magnetic resonance spectroscopy (1H-MRS) was performed in the testes with and without water suppression at 3 T in 9 fertile control subjects and 9 infertile patients (8 with azoospermia and 1 with oligospermia). In controls only, the T1 and T2 values of water and metabolites were also measured. Absolute metabolite concentrations were calculated using the unsuppressed water signal as a reference and correcting for the relative T1 and T2 weighting of the water and metabolite signals. Results Testicular T1 values of water, total choline, and total creatine were 2028 ± 125 milliseconds, 1164 ± 105 milliseconds, and 1421 ± 314 milliseconds, respectively (mean ± standard deviation). T2 values were 154 ± 11 milliseconds, 342 ± 53 milliseconds, and 285 ± 167 milliseconds, respectively. Total choline concentration was lower in patients (mean, 1.5 mmol/L; range, 0.9–2.1 mmol/L) than controls (mean, 4.4 mmol/L; range, 3.2–5.7 mmol/L; P = 4 × 10−5). Total creatine concentration was likewise reduced in patients (mean, 1.1 mmol/L; range, undetectable −2.7 mmol/L) compared with controls (mean, 3.6 mmol/L; range, 2.5–4.7 mmol/L; P = 1.6 × 10−4). The myo-inositol signal normalized to the water reference was also lower in patients than controls (P = 4 × 10−5). Conclusions Testicular metabolite concentrations, measured by proton spectroscopy at 3 T, may be valuable as noninvasive biomarkers of spermatogenesis.

Demographics of Cancer in the Reproductive Age Male

This chapter discusses the demographics of cancer, impact of treatment, and fertility preservation techniques in the reproductive aged male. As men delay fatherhood, the likelihood of developing cancer increases. Leukemia, central nervous system tumors, lymphoma, and testis cancer are the most common pediatric and adolescent cancers. Different chemotherapeutic agents have a low, medium, or high potential of having a negative impact on spermatogenesis. Radiation to the cranium has not been shown to have any detrimental effect on the hypothalamus pituitary axis, whereas whole-body irradiation and radiation to the testes has been shown to damage testicular components. Impact of treatment on fertility should be discussed with each reproductive aged male with cancer, and fertility preservation should be offered prior to treatment.