Jae Seog Hyun

Correlation between Lower Urinary Tract Symptoms (LUTS) and Sexual Function in Benign Prostatic Hyperplasia: Impact of Treatment of LUTS on Sexual Function

INTRODUCTION Although many reports have shown a relationship between lower urinary tract symptoms (LUTS) and sexual function (SF), it is not known which symptom(s) among LUTS should be treated to improve SF. AIM Thus, the aim of this study was to investigate correlations between LUTS and SF and to determine which symptom(s) should be improved to increase SF. MAIN OUTCOME MEASURE The correlation between the severity of LUTS and erectile dysfunction (ED) was investigated, and changes in LUTS were compared and analyzed to determine which symptom(s) should be eliminated to improve SF. METHODS The correlation between LUTS and SF was investigated in 365 men (62.04 +/- 8.26) with benign prostatic hyperplasia. To measure the severity of the LUTS and ED, the International Prostate Symptom Score (IPSS), frequency of nocturia, uroflowmetry, residual urine, transrectal ultrasonography, and the International Index of Erectile Function (IIEF)-5 were performed at the first visit. After 3 months of treatment with alpha-blockers (n = 304), they were assessed again to evaluate the effectiveness of the treatment. RESULTS All parameters of LUTS (IPSS, age, residual urine, uroflow rate, and nocturia) except prostate volume correlated significantly with the total and each domain of IIEF-5 (P < 0.01). After 3 months, the changed scores in the IPSS-VD domain and IPSS-quality of life (QoL) correlated significantly with the improvement in total IIEF-5 and the domains of IIEF-5 (P < 0.05). The changed rates of the mean uroflow correlated significantly with the improvement in total IIEF-5 and the EF domain (P < 0.05). CONCLUSION Among the LUTS parameters, improvement in the IPSS-VD domain, IPSS-QoL, and mean uroflow significantly correlated with an increased score in the IIEF-5 EF domain. Thus, it is expected that the improvement of voiding symptoms and uroflow will be associated with the improvement in erectile function.

Efficacy and safety of avanafil for treating erectile dysfunction: results of a multicentre, randomized, double‐blind, placebo‐controlled trial

Study Type – Therapy (RCT)

Expression and Activity of Heme Oxygenase‐1 in Artificially Induced Low‐Flow Priapism in Rat Penile Tissues

INTRODUCTION The inducible isoform of heme oxygenase (HO)-1 regulates the vascular smooth muscle tone and responds to hypoxia. AIM To investigate the role of HO-1 in a low-flow priapism. MATERIALS AND METHODS Sixty male Sprague-Dawley rats were divided into five groups of six rats each. Each group of rats was sacrificed at 0 hour (group 1, control), 4 hours (group 2), 8 hours (group 3), 12 hours (group 4), and 24 hours (group 5) after inducing an artificial veno-occlusive priapism. The changes of the expression and activity of HO-1, and the expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS), and levels of cyclic guanosine monophosphate in the penis were examined in a low-flow priapism. In addition, the HO-1 expression level in the aortas from each group was simultaneously measured to determine whether the changes in HO-1 were systemic. MAIN OUTCOME MEASURES The expression and activity of HO-1 was examined in artificially induced veno-occlusive priapism in rat penile tissues. RESULTS The expression of the HO-1 protein and the HO-1 enzyme activities in the penile tissues were gradually increased as time increased from 0 to 24 hours (P < 0.01). HO-1 immunoreactivities were localized in the endothelial layer of the cavernosal sinusoids. The expression of iNOS were also increased at 12 and 24 hours. The cyclic guanosine monophosphate level was also significantly increased at 24 hours (P < 0.05). However, the expression of the eNOS protein showed no statistically significant change with time, and the expression of the HO-1 protein in the aorta also showed no significant change with time. CONCLUSIONS A higher induction of HO-1 with time was observed in artificially induced veno-occlusive priapism, which might play a protective role against hypoxic injury. However, this may also play an important role in the vicious circle observed in a low-flow priapism.

ORIGINAL RESEARCH—ED PHARMACOTHERAPY: The Efficacy and Safety of Udenafil [Zydena] for the Treatment of Erectile Dysfunction in Hypertensive Men Taking Concomitant Antihypertensive Agents

INTRODUCTION Erectile dysfunction (ED) and hypertension are frequent comorbid conditions. The vasodilating properties of type 5 phosphodiesterase inhibitor (PDE5I) are the major concerns for the treatment of ED patients on antihypertensive medications. AIM To evaluate the efficacy and safety of Udenafil [Zydena] (Dong-A, Seoul, Korea), a newly developed PDE5I, for the treatment of ED patients on antihypertensive medication. METHODS It was a multicentered, randomized, double-blind, placebo-controlled, fix-dosed clinical trial among 165 ED patients receiving antihypertensive medications. The subjects treated with placebo, 100 mg or 200 mg of Udenafil for 12 weeks were asked to complete the Sexual Encounter Profile (SEP) diary, the International Index of Erectile Function (IIEF), and the Global Assessment Question (GAQ) during the study period. MAIN OUTCOME MEASURES Primary parameter: the change from baseline for IIEF erectile function domain (EFD) score; Secondary parameters: the IIEF Question 3 and 4, SEP Question 2 and 3, the rate of achieving normal erectile function (EFD > or = 26) and the response to GAQ. RESULTS Compared to placebo, patients receiving both doses of Udenafil showed significantly improved the IIEF-EFD score. The least squares means for the change from baseline in IIEF-EFD scores were 8.4 and 9.8 for 100 mg and 200 mg Udenafil groups, respectively; those values were significantly higher than that of placebo (2.4, P < 0.0001). Similar results were observed in the comparison of Q3 and Q4 of IIEF, SEP diary and GAQ. Headache and flushing were the most common treatment-emergent adverse events, which were transient and mild-to-moderate in nature. No parameters of efficacy and safety were affected among the subsets stratified according to either the number of antihypertensive medication received or the previous experience of PDE5Is treatment. CONCLUSION Udenafil significantly improved erectile function among ED patients with hypertensive symptom treated with concomitant antihypertensive medication. The treatment did not increase the frequency or severity of adverse events.

Effects and Mechanism of Action of a Tribulus terrestris Extract on Penile Erection

Purpose Tribulus terrestris has been used as an aphrodisiac. However, little is known about the effects and mechanism of action of T. terrestris on penile erection. Therefore, the effect of a T. terrestris extract and the mechanism of action of the extract on relaxation of the corpus cavernosum (CC) were investigated. The erectogenic effects of an oral preparation of the extract were also assessed. Materials and Methods The relaxation effects and mechanism of action of the T. terrestris extract on rabbit CC were investigated in an organ bath. The intracavernous pressure (ICP) was calculated after oral administration of the extract for 1 month to evaluate whether the relaxation response of the CC shown in the organ bath occurred in vivo. Additionally, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were measured in the CC by immunoassay. Smooth muscle relaxation was expressed as the percentage decrease in precontraction induced by phenylephrine. The ICP was also assessed in rats after oral administration of the extract for 1 month, and changes in concentrations of cGMP and cAMP were monitored. Results Concentration-dependent relaxation effects of the extract on the CC were detected in the organ bath study. Relaxation of the CC by the T. terrestris extract was inhibited in both an endothelium-removed group and an L-arginen methyl ester pretreatment group. The ICP measured after oral administration of the T. terrestris extract for 1 month was higher than that measured in the control group, and a significant increase in cAMP was observed in the T. terrestris extract group. Conclusions The T. terrestris extract induced concentration-dependent relaxation of the CC in an organ bath. The mechanism included a reaction involving the nitric oxide/nitric oxide synthase pathway and endothelium of the CC. Moreover, in an in vivo study, the T. terrestris extract showed a significant concentration-dependent increase in ICP. Accordingly, the T. terrestris extract may improve erectile function.

Localization of peripheral dopamine D1 and D2 receptors in rat corpus cavernosum

Objective  To detect and locate anatomically peripheral dopamine D1 and D2 receptors in rat cavernosa, as dopamine is important in sexual drive and penile erection through receptors located in the central nervous system.

Impact of Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia Treatment with Tamsulosin and Solifenacin Combination Therapy on Erectile Function

Purpose To examine the effects on erectile function of concomitant treatment with an alpha-blocker (tamsulosin) and an antimuscarinic agent (solifenacin) in patients with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). Materials and Methods Fifty-seven male patients with LUTS/BPH were assessed for the degree of LUTS and erectile function. In group 1 (tamsulosin) and group 2 (tamsulosin and solifenacin), changes in the International Prostate Symptom Score [IPSS: total scores, storage symptoms (ST), voiding symptoms (VD), and quality of life (QoL)], prostate-specific antigen, trans-rectal ultrasonography, urine flowmetry, residual urine, and a 5-item version of the International Index of Erectile Function (IIEF-5) were assessed after a 3-month treatment period. In both groups, it was determined whether treatment was associated with changes in LUTS and erectile function and whether improvement in the IPSS was correlated with the IIEF-5. Comparative analysis was also done to examine the linear relationship between improved IPSS scores and IIEF-5 scores. Results A comparison of the degree of improvement in all the parameters indicated that both groups showed significant improvement in total IPSS, IPSS-ST, IPSS-VD, and IPSS-QoL (p<0.05). A comparison of the degree of improved sexual function associated with improved LUTS in each patient showed significant improvement in the IIEF-5 score associated with the degree of improvement in the IPSS-ST domain in group 1, but no significant associations were found in group 2. In cases in which tamsulosin was administered, the IIEF-5 score significantly improved as the IPSS-ST domain score improved. In the group in which tamsulosin and solifenacin were concomitantly administered, improvement of the IPSS-ST domain score had no significant effect on the IIEF-5 score. Conclusions In patients with LUTS/BPH, tamsulosin and solifenacin combination therapy was effective for LUTS, but erectile function was not significantly improved. Therefore, although effective for improving LUTS, combination therapy with an alpha-blocker and an antimuscarinic agent was not effective for improving erectile function.

Effect of tamsulosin on ejaculatory function in BPH/LUTS

This study was undertaken to determine the impact on ejaculatory function of tamsulosin (0.2 mg) given once daily (OD) for 12 weeks and to identify risk factors for ejaculatory dysfunction in patients undergoing this treatment. Males with an International Prostatic Symptom Score (IPSS) ≥8 were enrolled in this study. All participants completed questionnaires, including the IPSS and the Male Sexual Health Questionnaire (MSHQ), and serum prostate-specific antigen, transrectal ultrasound and uroflowmetry with post-void residual were measured. After initiating 0.2 mg OD tamsulosin, patients were re-evaluated on the fourth and twelfth weeks of medication. The chi-squared test, the independent t-test and one-way ANOVA were used to compare means. Binary logistic regression analysis was used to calculate the odds ratio for all risk factors. A total of 177 men constituted the study cohort. No significant difference was observed between baseline and follow-up for the erectile function, ejaculatory function, satisfaction, sexual activity and desire domains (EFD, EjFD, SDA and ADD) or for erectile or ejaculatory bother mean scores. After 12 weeks, the overall incidence of ejaculatory dysfunction (EjD) was 13.4%. Incidences of the seven different types of EjD (decreased frequency, delay, dryness, decreased strength/force, decreased volume, decreased pleasure and pain at ejaculation) were 2.4%, 3.1%, 3.9%, 3.9%, 6.3%, 7.1% and 3.1%, respectively. Baseline EjFD scores were higher for IPSS responders than for non-responders (26.09 vs. 24.06, P=0.03). An EjFD score reduction was more frequent in IPSS responders. The incidence of EjD was small, but not negligible and was more frequent in patients with less lower urinary tract symptoms, a smaller prostate, higher baseline MSHQ totals and higher EjFD scores.

The pericyte as a cellular regulator of penile erection and a novel therapeutic target for erectile dysfunction

Pericytes are known to play critical roles in vascular development and homeostasis. However, the distribution of cavernous pericytes and their roles in penile erection is unclear. Herein we report that the pericytes are abundantly distributed in microvessels of the subtunical area and dorsal nerve bundle of mice, followed by dorsal vein and cavernous sinusoids. We further confirmed the presence of pericytes in human corpus cavernosum tissue and successfully isolated pericytes from mouse penis. Cavernous pericyte contents from diabetic mice and tube formation of cultured pericytes in high glucose condition were greatly reduced compared with those in normal conditions. Suppression of pericyte function with anti-PDGFR-β blocking antibody deteriorated erectile function and tube formation in vivo and in vitro diabetic condition. In contrast, enhanced pericyte function with HGF protein restored cavernous pericyte content in diabetic mice, and significantly decreased cavernous permeability in diabetic mice and in pericytes-endothelial cell co-culture system, which induced significant recovery of erectile function. Overall, these findings showed the presence and distribution of pericytes in the penis of normal or pathologic condition and documented their role in the regulation of cavernous permeability and penile erection, which ultimately explore novel therapeutics of erectile dysfunction targeting pericyte function.

Impact of erectile function and age in men with lower urinary tract symptoms on ejaculatory dysfunction and premature ejaculation

Lower urinary tract symptoms (LUTSs) and ED are clearly correlated, but to date no correlation with ejaculatory dysfunction (EjD) has been identified. Therefore, this study evaluated the impact of erectile function in men with LUTS on EjD and premature ejaculation (PE). Erectile function, PE and EjD of 239 men (mean age, 53.0±10.65 years), International Prostate Symptom Score (IPSS), International Index of Erection Function (IIEF), intravaginal ejaculatory latency time (IELT) and the seven-item Male Sexual Health questionnaire (MSHQ)-EjD were used to compare with the degree of LUTS. Ages were divided into five groups (<40, 40–49, 50–59, 60–69 and >70 years). The IPSS categorized patients into three symptom groups: mild, 1–7; moderate, 8–19; and severe, >19. ED was classified into five categories based on IIEF-EF scores: severe (0–6), moderate (7–12), mild-to-moderate (13–18), mild (19–24) and normal (25–30). The correlations among age, IIEF-EF, IELT and the MSHQ-EjD domain were studied through regression and cross-tabulation analyses. The results revealed that aging significantly affected each item of the MSHQ-EjD (P<0.05). The IIEF-EF domain was also correlated with each question on the MSHQ-EjD (P<0.05). PE (IELT <1 min) increased in incidence as patients got older but was not linked to IIEF-EF (P>0.05). These results indicate that EjD is closely related to age and erectile function, and that PE is closely related to age, although PE is not related to erectile function.