Effect of low-dose tadalafil once daily on glycemic control in patients with type 2 diabetes and erectile dysfunction: a randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: Phosphodiesterase type 5 inhibitors restore nitric oxide signaling, that plays a significant role in erectile function, and appears to counteract insulin resistance in animal and human models. This study was aimed to evaluate the glycemic and metabolic effects of low-dose tadalafil once daily in patients with type 2 diabetes and erectile dysfunction. METHODS: A 6-month, randomized, double-blind, placebo-controlled pilot trial was conducted. Eligible patients were randomly assigned in a ratio of 2:1 to the tadalafil 5 mg and placebo groups; all patients received either tadalafil or placebo once a day. The primary efficacy endpoint was the absolute change in glycated hemoglobin (HbA1c) levels during the 6-month study period. The secondary efficacy endpoints included metabolic parameters and erectile function. RESULTS: Of the 68 patients who completed this study, 45 and 23 patients were allocated to the tadalafil and placebo groups, respectively. The mean HbA1c level was significantly different between the groups over the 6-month study period (P = 0.021). After 6 months of treatment, the HbA1c decrement in the tadalafil group was greater than that in the placebo group (- 0.14 ± 0.53% vs. 0.20 ± 0.69%, P = 0.030). The International Index of Erectile Function-5 scores improvement was significantly greater in the tadalafil group than in the placebo group at 6 months (P = 0.003). CONCLUSION: This prospective pilot study showed that low-dose tadalafil administered once a day was effective in improving glycemic control and erectile function in patients with type 2 diabetes and erectile dysfunction. Trial registration KCT0005666.

Association between the symptoms of benign prostatic hyperplasia and social disparities: Does social capital promote prostate health?

This cross-sectional study investigated the relationships between socioeconomic factors and social capital and benign prostatic hyperplasia symptoms. The participants were 100,000 adult men who participated in the Korea Community Health Survey. The surveyors used the International Prostate Symptom Score. As regards occupation, the prevalence of benign prostatic hyperplasia was higher in men with blue-collar occupations or those who were unemployed than in those with white-collar jobs. In terms of marital status, the prevalence of benign prostatic hyperplasia was 1.319 times higher among divorced men than married men. As regards social capital, the prevalence of benign prostatic hyperplasia in men with positive attitudes towards one's community scores that reflected good, poor and very poor community scores was 1.228, 1.246 and 1.447 times higher than that of men who had very good scores respectively. The groups with good, poor, and very poor community participation scores had 1.115, 1.202 and 1.364 times higher prevalence of benign prostatic hyperplasia than the group with very good scores. Social disparities and social capital of a community were associated with the prevalence of benign prostatic hyperplasia. Thus, the use of social capital in the community setting will be effective in the management of the condition.

The Correlation between Body Mass Index and Routine Parameters in Men Over Fifty.

PURPOSE: This study aimed to investigate the relationships between body mass index (BMI) and prostate-specific antigen (PSA) levels, international prostate symptom score (IPSS), quality of life (QoL), and prostate volume (PV). MATERIALS AND METHODS: Height, weight, PSA levels, PV, and IPSS were analyzed in 15,435 patients who underwent a prostate examination between 2001 and 2014. Patients aged <50 years or with a PSA level ≥10 ng/mL were excluded. The relationships between BMI and PSA, IPSS, QoL, and PV were analyzed by a scatter plot, one-way analysis of variance, and the Pearson correlation coefficient. RESULTS: The mean age was 71.95±7.63 years, the mean BMI was 23.59±3.08 kg/m², the mean PSA level was 1.45±1.45 ng/mL, the mean IPSS was 15.53±8.31, the mean QoL score was 3.48±1.25, and the mean PV was 29.72±14.02 mL. PSA, IPSS, and QoL showed a tendency to decrease with increasing BMI, and there were statistically significant differences for each parameter (p≤0.001). PV showed a significant tendency to increase with BMI (p<0.001). In the correlation analysis, BMI showed a statistically significant correlation (p<0.001) with PSA, IPSS, and QoL, although the correlations were very weak. In contrast, BMI showed a significant correlation with PV (p<0.001), with a meaningful Pearson correlation coefficient of 0.124. CONCLUSIONS: Higher BMI was associated with lower PSA levels and higher IPSS and QoL scores. Meanwhile, PV increased with BMI. Although obese individuals had a greater PV, obesity did not aggravate lower urinary tract symptoms.

Long-Term Safety and Longevity of a Mixture of Polymethyl Methacrylate and Cross-Linked Dextran (Lipen-10®) after Penile Augmentation: Extension Study from Six to 18 Months of Follow-Up.

PURPOSE: The goal of this study was to investigate the long-term efficacy and safety of a mixture of polymethyl methacrylate (PMMA) and cross-linked dextran Lipen-10® used for penile augmentation under the physical impact generated during sexual intercourse. MATERIALS AND METHODS: From March 2010 to October 2011, a total of 20 patients with a mean age of 44 years (interquartile range, 20~70 years) who requested penile augmentation participated in this study. Lipen-10® filler is a mixture of 75% cross-linked dextran, 15% PMMA, and 10% hypromellose solution. With the patient in the supine position, Lipen-10® was injected into the subcutaneous tissue between the dartos fascia and Buck's fascia of the penis using a fanning technique. Penile length and circumference were measured before the procedure and six, 12, and 18 months after the procedure. Values were compared using the Student's t-test and the paired t-test. RESULTS: A total of 15 patients completed this study. The increases in circumference and length observed six months after the procedure were found to have been maintained without change at 12 and 18 months of follow-up. At 12 and 18 months of follow-up, no abnormal findings were observed. Pelvic magnetic resonance imaging conducted at 18 months of follow-up showed no trace of the injected filler having migrated to other sites, and the volume was well maintained. CONCLUSIONS: Lipen-10®, a mixture of PMMA and cross-linked dextran, showed good durability and tolerability over 18 months of follow-up during which the participants were sexually active.

Tadalafil once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia: a randomized placebo- and tamsulosin-controlled 12-week study in Asian men.

OBJECTIVES: To examine the efficacy and safety of tadalafil in Asian men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. METHODS: Asian men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia were randomized to once-daily placebo (n=154), tadalafil 2.5 mg (n=151), tadalafil 5.0 mg (n=155) or tamsulosin 0.2 mg (active control, n=152) for 12 weeks. RESULTS: Total International Prostate Symptom Score least-squares mean changes from baseline to end-point significantly improved with tadalafil 2.5 mg (-4.8, P=0.003) and 5 mg (-4.7, P=0.004) versus placebo (-3.0). Significant improvement in the International Prostate Symptom Score versus placebo was observed earlier (week 2) for tadalafil 5.0 mg than for tadalafil 2.5 mg (week 8). Significant improvements (P<0.05) in both tadalafil groups versus placebo were observed for the International Prostate Symptom Score voiding subscore, International Prostate Symptom Score Quality of Life, and for Patient and Clinician Global Impressions of Improvement. Significant improvements versus placebo were observed in the International Prostate Symptom Score storage subscore for tadalafil 5.0 mg (-1.7, P=0.021), but not tadalafil 2.5 mg (-1.5, P=0.072). No significant improvements in benign prostatic hyperplasia Impact Index or improvements in peak urinary flow rates were observed with tadalafil 2.5 mg or 5.0 mg versus placebo. Tamsulosin treatment resulted in significant improvements versus placebo across all efficacy parameters, except for peak urinary flow rates. Safety results were consistent with the known tadalafil and tamsulosin safety profiles. CONCLUSIONS: Tadalafil once daily represents an effective and well tolerated medical treatment for Asian men presenting with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

Changes in sexual function in benign prostatic hyperplasia patients taking dutasteride: 1-year follow-up results.

PURPOSE: Sexual adverse events (AEs), a major cause for discontinuing 5α-reductase inhibitor (5ARI) therapy for benign prostatic hyperplasia (BPH), are known to occur most frequently early in therapy and appear to decline over time. The aim of this study was to investigate the changes in sexual function occurring with dutasteride treatment during a 1-year follow-up period in Korean men. MATERIALS AND METHODS: Using the International Index of Erectile Function, we prospectively evaluated, after 1, 3, 6, 9, and 12 months of treatment, the changes in sexual function of 55 outpatients (mean age 62.3±7.2 years) with BPH (mean volume 48.9±16.0 g) who had relatively good erectile function (EF) and were treated with dutasteride for at least 1 year. RESULTS: EF scores showed the most significant decrease at 1 month (p<0.01). Function gradually recovered thereafter but was still significantly decreased after 12 months of treatment (p<0.05). The scores for orgasmic function and sexual desire also showed the most significant reduction at 1 month but were restored to the baseline level at 6 months. No significant correlation was observed between changes in sexual function and prostate-specific antigen level, prostate volume, or International Prostate Symptom Scores. CONCLUSIONS: After 1 month of treatment, dutasteride therapy resulted in a significant reduction in all investigated sexual functions. Overall, recovery in sexual function was noted at 3 months, and orgasmic function and sexual desire were restored to baseline levels at 6 months. However, EF was still significantly reduced at 12 months.

Men's health in South Korea.

Over the last four decades, rapid industrialisation and a Westernized lifestyle have changed disease patterns in South Korea. This study was conducted to review the current state of men's health in South Korea. By reviewing reports of government authorities and domestic and foreign studies related to men's health, we found that in men ≥ 65 years of age, 28.4% considered their health status good, whereas 38.3% considered their health status poor. The prevalence of moderate-to-severe lower urinary tract symptoms was similar to that in Caucasians. The prevalence of erectile dysfunction was higher than the global average. The incidence of cryptorchidism and hypospadias showed a tendency towards increase. The prevalence of diabetes mellitus continuously increased by 10.8% in 2008 and was the fifth leading cause of death in 2008. The prevalence of obesity increased from 26.0% in 1998 to 31.7% in 2007. The prevalence of ischaemic heart disease has continuously increased, with heart diseases causing one of every 12 deaths. The prevalence of chronic obstructive pulmonary disease in 2005 was 17.2% among adults ≥ 45 years of age. The top five prevalent cancers in men, in descending order, were cancers of the stomach, lung, liver, large bowel and prostate, among which the incidence of stomach, lung and liver cancers decreased by 0.7%, 0.6% and 2.2%, respectively, from 1999 to 2007, whereas the incidence of large bowel and prostate cancers increased by 7.0% and 13.2%, respectively. The prevalence of depression, dementia and sleep disorders was estimated as 17.3%, 4.21% and 20.2%, respectively. Together, these findings suggest that disease patterns in South Korean men are becoming Westernized.

Leptin enhances nitric oxide-dependent relaxation of the clitoral corpus cavernosum.

PURPOSE: The effects of leptin on female sexual behaviors are controversial, and studies on this topic are limited. The objectives of this study were to evaluate the direct effects of leptin on clitoral vasoreactivity in vitro and to determine the mechanism of action. MATERIALS AND METHODS: Isometric tension studies were conducted to determine the effects of pretreatment with leptin (10(-8) M) on the contractile responses of rabbit clitoral corpus cavernosal smooth muscle strips. The effects of leptin were assessed on precontraction induced by phenylephrine (PE; 10(-9)-10(-4) M) and KCl (35-140 mM). We also examined the effect of leptin on relaxation induced by acetylcholine (ACh; 10(-9)-10(-4) M), verapamil (10(-10)-10(-6) M), and sodium nitroprusside (10(-9)-10(-4) M) in PE-precontracted (10(-5) M) strips. RESULTS: Leptin enhanced ACh-induced relaxation in PE-precontracted strips. L-NAME pretreatment significantly reduced the effect of leptin on ACh-induced relaxation, whereas L-arginine potentiated the effect of leptin. Leptin decreased the KCl-induced contractile responses. Leptin increased verapamil-induced relaxation responses. The relaxation effects of leptin on KCl-induced contraction were inhibited by 10(-5) M methylene blue and L-NAME pretreatment. CONCLUSIONS: A high concentration of leptin enhances ACh-dependent relaxation in clitoral cavernosal smooth muscles. These relaxation effects of leptin may occur through an NO-dependent mechanism and voltage-dependent calcium channel blockade.

Tadalafil Administered Once Daily for Treatment of Lower Urinary Tract Symptoms in Korean men with Benign Prostatic Hyperplasia: Results from a Placebo-Controlled Pilot Study Using Tamsulosin as an Active Control.

OBJECTIVES: Assess the efficacy and safety of once-daily tadalafil or tamsulosin versus placebo during 12 weeks on lower urinary tract symptoms (LUTS) in Korean men with benign prostatic hyperplasia (BPH). METHODS: Following a 4-week placebo run-in period, 151 Korean men were randomly assigned to receive once-daily tadalafil 5 mg, tamsulosin 0.2 mg, or placebo for 12 weeks. RESULTS: The International Prostate Symptom Score (IPSS) least squares mean changes from baseline to endpoint were numerically but not significantly improved in the tadalafil (-5.8) and tamsulosin (-5.4) groups compared with placebo (-4.2, P > 0.05). Decreases in IPSS obstructive and irritative subscores, IPSS Quality of Life score, and BPH Impact Index from baseline to endpoint were largest in the tadalafil group followed by tamsulosin, though none separated significantly from placebo. Increases in maximum urinary flow rate were small and not significantly different than placebo; the increase was largest in the tadalafil group (2.5 mL/sec), followed by the placebo (2.3 mL/sec) and tamsulosin (2.1 mL/sec) groups. The percentage of subjects reporting at least one treatment-emergent adverse event was 26.5, 13.7 and 3.9% in the tamsulosin, tadalafil and placebo groups, respectively. CONCLUSIONS: In this pilot study in Korean men, those with BPH and treated with tadalafil 5 mg or tamsulosin 0.2 mg once daily experienced a reduction in LUTS, which was numerically (but not statistically) significant compared with the placebo. Tadalafil was well tolerated and few subjects discontinued the study due to treatment-emergent adverse events. Larger studies in Asian men with BPH and LUTS treated with phosphodiesterase type 5 inhibitors are needed.

Efficacy and safety of mirodenafil in men taking antihypertensive medications.

INTRODUCTION: Mirodenafil is a recently developed oral phosphodiesterase type 5 inhibitor, which was observed to significantly improve erectile function and was well tolerated in men with broad-spectrum erectile dysfunction (ED). AIM: To investigate the efficacy and safety of mirodenafil treatment compared with placebo in men taking at least one antihypertensive medication. METHODS: A multicenter, double-blind, placebo-controlled, parallel group, fixed-dose study was conducted with 109 subjects who were randomized to placebo or mirodenafil 100 mg for 12 weeks on an "as needed" basis. MAIN OUTCOME MEASURES: The primary efficacy measures were the changes from baseline in sum of scores on International Index of Erectile Function-erectile function domain (IIEF-EF) questions 1 to 5 and 15 with treatment. The secondary efficacy measures included scores on IIEF question 3 and 4 (Q3 and Q4), all domain scores of IIEF, and Sexual Encounter Profile Question 2 and 3 (SEP2 and SEP3) along with responses to Global Assessment Question (GAQ) and Life Satisfaction Checklist (LSC). The safety assessments included laboratory tests, vital signs, 12-lead electrocardiogram recordings, and patients' reporting of adverse events. RESULTS: The mirodenafil group showed significantly greater increase in IIEF-EF scores at 12 weeks compared with the placebo group (9.35 ± 6.86 vs. 2.66 ± 6.44, P<0.001). The mirodenafil group also demonstrated significantly greater improvement in scores of IIEF Q3 and Q4, other four domains of IIEF, SEP2, SEP3, and LSC along with percentages of patients responding positively to GAQ compared with the placebo group. During the study, no clinically significant changes were observed regarding blood pressure, heart rate, electrocardiographic findings, or laboratory values. Facial flushing and headache were the most common treatment-associated adverse events, which were mild or moderate in severity, resolving spontaneously. CONCLUSIONS: Mirodenafil was effective and safe in men with ED concomitantly taking antihypertensive medications.

Light and transmission electron microscopic comparisons of sperms between petrochemical factory workers and public servants in a nonindustrialized area.

In this study, we compared the semen characteristics on light microscopy and ultrastructural sperm morphology on transmission electron microscopy between workers in an industrialized area with petrochemical complexes and public servants in a nonindustrialized area. Occupational exposure to petrochemical compounds seems to decrease sperm motility and deteriorate the sperm ultrastructural arrangement, which may lead to this decrease in sperm motility.

The effects of dehydroepiandrosterone (DHEA)/DHEA-sulfate (DHEAS) on the contraction responses of the clitoral cavernous smooth muscle from female rabbits.

INTRODUCTION: Dehydroepiandrosterone (DHEA) is a multifunctional steroid that is increasingly available as a supplement aimed at improving libido and well-being in postmenopausal women in the recent times. Together with its sulfate version, DHEA-sulfate (DHEAS), it is the most abundant steroid in humans. The clitoris is an important component of the female sexual response, with its increased vascular response during sexual arousal that results in erection. AIMS: To elucidate the direct effects of DHEA/DHEAS on the vasomotor reactivity of the rabbit clitoral cavernosum. METHODS: Twenty New Zealand white female rabbits weighing approximately 2.5-3 kg were used in the study. MAIN OUTCOME MEASURES: The contractile response of clitoral cavernous smooth muscle strips in response to phenylephrine (PE; 10(-9)-10(-4) M) were observed in rabbits. Additionally, DHEA/DHEAS effects on phenylephrine-induced contraction and/or acetylcholine-induced relaxation of phenylephrine-induced contraction were measured. RESULTS: DHEA/DHEAS did not elicit any remarkable response in the resting state. However, both DHEA and DHEAS evoked dose-dependent relaxations of PE-induced contraction. The contractile responses to high potassium were significantly decreased in the DHEA/DHEAS-pretreated strips, compared with the DHEA/DHEAS-nontreated strips. Additionally, contractions by Bay K 8644 (10(-7)-10(-6) M) treatment were also significantly inhibited by DHEA/DHEAS. DHEA-induced relaxation responses were stronger than DHEAS-induced relaxation responses. Various K channel blockers, tetraethylammonium (TEA; 1 mM, 10 mM), 4-aminopyridine (10 microM) and glibenclamide (10 microM) did not affect the DHEA/DHEAS-induced relaxation on muscle strips contracted by PE. Relaxation responses by acetylcholine or sodium nitroprusside (SNP) were not changed after DHEA/DHEAS pretreatment. CONCLUSIONS: DHEA/DHEAS was found to induce a relaxation response in rabbit clitoral cavernosal smooth muscle, and this is thought to be mediated by direct inhibition of a voltage-dependent calcium channel.

A possible relationship between testosterone and lower urinary tract symptoms in men.

PURPOSE: In this study we searched for possible associations between serum testosterone levels and the severity of lower urinary tract symptoms in men. MATERIALS AND METHODS: In 278 patients with a mean age of 62 years blood levels of total testosterone, albumin, sex hormone-binding globulin, fasting glucose, fasting insulin and high sensitivity C-reactive protein were measured. Free testosterone, bioavailable testosterone and homeostasis model assessment of insulin resistance were calculated. Prostate volume was measured by transrectal ultrasonography and the severity of lower urinary tract symptoms was assessed using the International Prostate Symptom Score. RESULTS: Calculated free testosterone and bioavailable testosterone were negatively related to International Prostate Symptom Score total scores and subscores (voiding symptoms) after adjusting for age, prostate volume, high sensitivity C-reactive protein and homeostasis model assessment of insulin resistance (p <0.05). In addition, calculated free testosterone and bioavailable testosterone were significantly related to the presence of severe lower urinary tract symptoms (International Prostate Symptom Score 20 or greater) using unadjusted and adjusted models (p <0.05), although the odds ratio of bioavailable testosterone was lower than that of calculated free testosterone on multivariate analysis. High sensitivity C-reactive protein was negatively correlated with serum total testosterone (r = -0.128, p = 0.038) and bioavailable testosterone (r = -0.126, p = 0.041), and homeostasis model assessment of insulin resistance was negatively correlated with serum total testosterone (r = -0.236, p <0.001), calculated free testosterone (r = -0.179, p = 0.003) and bioavailable testosterone (r = -0.162, r = 0.007). However, no significant correlation was found between high sensitivity C-reactive protein or homeostasis model assessment of insulin resistance, and International Prostate Symptom Score total scores, voiding symptoms scores and storage symptoms scores. CONCLUSIONS: Our findings support the favorable role of endogenous testosterone in lower urinary tract function and suggest that testosterone deficiency may be a pathophysiological mechanism connecting lower urinary tract symptoms and the metabolic syndrome in men.

Men's lower urinary tract symptoms are also mental and physical sufferings for their spouses.

Lower urinary tract symptoms (LUTS) in men may have an adverse effect on spouse health-related quality of life (HRQL), and these effects are probably influenced by cultural and perceptional differences. This study was conducted to explore the impact of LUTS in Korean men on their spousal HRQL in relation to symptom severities and other demographic parameters. A total of 130 spouses, whose husbands had a nocturia, frequency of greater than once per night, who shared a bed with their husbands, and accompanied husbands at consultation, were subsequently enrolled and asked to complete a structured questionnaire. Almost all spouses (98%) suffered one or more inconveniences that affected HRQL to some degree. Sleep disturbance was rated to be most inconvenient. The sleep disturbances were significantly correlated with nocturia frequency and husband co-morbidity. Husband's LUTS caused partners to feel fatigued (62%), embarrassed (79%), concerned about the possibilities of cancer (69%) and surgery (81%), sexual life deteriorated (58%), and dissatisfied, unhappy, or terrible (36%). Spouse's perception on HRQL was found to be well correlated with husband's quality of life. Men with LUTS need to understand that their LUTS is also mental and physical sufferings for their spouses.

Efficacy and safety of oral SK3530 for the treatment of erectile dysfunction in Korean men: a multicenter, randomized, double-blind, placebo-controlled, fixed dose, parallel group clinical trial.

AIM: To evaluate the efficacy and safety of SK3530, a newly developed type 5 phosphodiesterase inhibitor (PDE5I), in Korean men with erectile dysfunction (ED). METHODS: A total of 119 patients were randomized at 10 centers in Korea to receive either SK3530 (50, 100, or 150 mg; n = 89) or placebo (n = 30) taken l h before anticipated sexual activity for an 8-week period. The patients were evaluated at baseline and 4 and 8 weeks after beginning therapy. Efficacy was assessed using the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and the Global Assessment Question (GAQ). Safety was analyzed by adverse events, laboratory values and vital signs. RESULTS: At the end of the study, all the primary and secondary efficacy end-points were statistically significantly improved by SK3530 compared with placebo (P<0.05). Of the 89 patients in the treatment arm, 36 (42.3%) achieved normal erectile function after treatment, including six patients with severe ED. Treatment-related adverse events occurred in 32 patients. The most common adverse events were flushing, headache, dizziness and eye redness (10.9%, 7.6%, 2.5% and 2.5%, respectively), and most were mild. Only two patients discontinued treatment during the study period because of adverse events. CONCLUSION: The results of our phase II study have confirmed the efficacy and safety of SK3530 in a broad population of men with ED of various etiologies and severity. The optimal doses in terms of efficacy and safety were determined to be 50 mg and 100 mg, respectively.

The effects of interleukin-6 on the contraction and relaxation responses of the cavernous smooth muscle from rats.

The purpose of this study is to elucidate the effect of IL-6 on the vasomotor reactivity of the corpus cavernosum of the rats. The strips were either left untreated or treated with 1 ng/ml of IL-6 for 60 min. By increasing concentrations of phenylephrine, acetylcholine, or sodium nitroprusside, we assessed concentration-contraction or relaxation responses. The IL-6-treated strips were incubated for 30 min with or without L-NAME (N(W)-nitro-L-arginine methyl ester), L-arginine, indomethacin, BQ-123 (an endothelin receptor A inhibitor), or SQ 29,548 (a thromboxane A(2) [TXA(2)] receptor blocker), and the effects on phenylephrine-induced contraction or acetylcholine-induced relaxation of phenylephrine-induced contraction were measured. The contractile responses to phenylephrine were significantly enhanced in the IL-6-treated strips, compared with the IL-6-nontreated strips, and the relaxation responses to acetylcholine were significantly inhibited in the IL-6-treated group compared with the IL-6-nontreated group. But after endothelial denudation, there was no difference between the IL-6-treated strips and the IL-6-nontreated strips on the contraction-relaxation responses to phenylephrine or acetylcholine. The relaxation responses to sodium nitroprusside were not inhibited in both groups. L-NAME completely inhibited the relaxation response to acetylcholine in the IL-6-treated strips, as well as the IL-6-nontreated strips. Indomethacin and SQ 29,548 significantly inhibited the increased contractile responses to phenylephrine in the IL-6-treated strips. But BQ 123 rarely affected the same responses. L-arginine reversed the inhibited relaxation responses to acetylcholine in the IL-6-treated strips. Therefore, IL-6 inhibits endothelium-dependent, NO-mediated relaxation and also enhances alpha(1)-adrenergic receptor-mediated contraction via an endothelium-dependent TXA(2)-mediated mechanism in the corpus cavernosum of the rat.

Sexual attitude and perception on sexual relationship among long-term users of sildenafil.

INTRODUCTION: High discontinuation rates of sildenafil were reported in its responders. AIM: To investigate perception on and attitude toward sex among long-term users of sildenafil. METHODS: A survey was conducted using random face-to-face interviews and a structured questionnaire on a population of 105 long-term sildenafil users (mean age; 57.8 years), who first took sildenafil 5 years or more previously and continued its use in the previous 6 months. MAIN OUTCOME MEASURES: Six point-scale of perception on and attitude toward sex and valuation of sildenafil. RESULTS: Among the long-term users, 98% perceived that it is desirable to have sex even though they get old if they are healthy, 93% had a positive attitude toward sex, and 97% had an intercourse-focused perception of sexual relationship; these rates were higher for those with a lower income and less education. And 59% had intercourses and 40% took sildenafil one to two times a week. They ranked prominence in rigidity of erection as the major reason for the long-term sildenafil use. The rigidity was maintained after more than 5-year use. CONCLUSION: An overall majority of the long-term users of sildenafil had a positive attitude toward sex, an active sexual behavior, and an intercourse-focused perception on sexual relationship. Sildenafil provided an optimal fit for the patients' needs. Prominence in rigidity of erection was ranked as the major reason for the long-term use.

Contractile changes of the clitoral cavernous smooth muscle in female rabbits with experimentally induced overactive bladder.

INTRODUCTION: Recently, growing clinical evidence has suggested that sexual dysfunction is more prevalent in women with overactive bladder (OAB). Aims. However, there has been no basic research to clarify the relationship between OAB and female sexual dysfunction. Therefore, we investigated this issue using a rabbit model of OAB. METHODS: Twenty-seven New Zealand white female rabbits were randomly divided into the OAB and control groups. MAIN OUTCOME MEASURES: The contractile responses of clitoral cavernous strips to K(+), phenylephrine (PE), Bay K 8644, and endothelin (ET)-1, and the relaxation responses of acetylcholine (ACh), sodium nitroprusside (SNP), and Y-27632 to PE-induced contraction by measuring isometric tension. Results. The contractile responses to K(+), PE, Bay K 8644, and ET-1 were significantly more increased in the OAB group in a dose-dependant manner than in the control group (P < 0.05), and the responses to ET-1 were more prominent than those to the remaining substances (P < 0.01). The increased contractile responses to ET-1 were blocked by BQ123 (ET(A) receptor antagonist) but not by BQ788 (ET(B) receptor antagonist). Clitoral cavernosal strips from the OAB group were more difficult to relax than those from the control group in terms of ACh- and SNP-induced relaxation (P < 0.05). The Y-27632-induced relaxant responses to PE- and ET-1-induced contraction were less prominent in the OAB group than in the control group. CONCLUSIONS; The results of this study provide evidence that female OAB may deteriorate clitoral engorgement, which is associated with a greater force generation by increased calcium sensitization and subsequently decreased of relaxation. The activation of ET and Rho-kinase system may be crucial to negatively effect the clitoral smooth muscle relaxation in experimentally induced OAB animal model. But whether these vasomotor effects are revived in human clitoris is still debatable.

The efficacy and safety of udenafil, a new selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction.

INTRODUCTION: Udenafil is a potent selective phosphodiesterase type 5 (PDE5) inhibitor newly developed for the treatment of erectile dysfunction (ED). AIM: This study was performed to evaluate the efficacy and safety of udenafil therapy in patients with ED. METHODS: In this multicenter, double-blind, placebo-controlled, fixed-dose, parallel-group phase III trial, 167 patients with ED of diverse origin and severity were randomized to take placebo or udenafil at fixed doses of 100 or 200 mg as needed for 12 weeks. MAIN OUTCOME MEASURES: Primary efficacy variable was change from baseline in erectile function (EF) domain scores of the International Index of Erectile Dysfunction (IIEF) questionnaire. Secondary efficacy variables include change from baseline in scores on the IIEF Questions 3 and 4 (IIEF Q3 and Q4), change from baseline in all domain scores of the IIEF, patients' responses to questions 2 and 3 of the Sexual Encounter Profile (SEP2 and SEP3), and patients' responses to the Global Assessment Question (GAQ). Any adverse events were also recorded during the trial. RESULTS: After 12 weeks of treatment, the patients treated with udenafil showed significantly greater change from baseline in the IIEF-EF domain score compared with placebo (placebo, 0.20; 100-mg udenafil, 7.52; and 200-mg udenafil, 9.93, respectively) (P < 0.0001). Compared with placebo, udenafil significantly enhanced the rates of successful penetration (SEP Q2) and maintenance of erection (SEP Q3) (P < 0.0001). Furthermore, significantly greater proportions of udenafil treatment groups responded positively to the GAQ compared with the placebo group (GAQ: placebo, 25.9%; 100-mg udenafil, 81.5%; and 200-mg udenafil, 88.5%, respectively) (P < 0.0001). Treatment-related adverse events were generally mild to moderate with facial flushing and headache being the most common. CONCLUSIONS: Udenafil is an effective and well-tolerated therapy for ED of broad-spectrum etiology and severity.