Relationship between serum testosterone and nocturia in men without benign prostate enlargement.

Recent studies have focused on the relationship between nocturia and serum testosterone because testosterone is thought to be an important factor of prostate growth. However, it remains unclear whether altered serum concentrations of testosterone is associated with an increased risk of nocturia because patients who were taking diuretics or who had a large prostate, which may precipitate nocturia, were not excluded from most previous studies. We analyzed the clinical records of 596 non-benign prostatic enlargement (BPE) male patients to explore the relationship between serum total testosterone and nocturia. All patients were evaluated using a serum prostate-specific antigen (PSA) assay, measurement of serum total testosterone, transrectal ultrasonography, uroflowmetry, and a compilation of the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF) questionnaires. Nocturia was defined as ≥2 nocturnal voiding episodes. The number of nocturia episodes was assessed using IPSS question 7. To evaluate the effect of serum testosterone on nocturia, multivariate regression analysis was performed including the covariates of age, IPSS, IIEF score, body mass index, PSA, prostate volume, and maximal urine flow rate. Based on multivariate linear analysis, serum testosterone level was not significantly associated with the severity of nocturia. However, with regard to the relationship between prevalence of nocturia and serum testosterone, prevalence of nocturia was significantly positively associated with age (OR = 1.048, p = 0.005), total IPSS (OR = 1.217, p < 0.001), and testosterone level (OR = 1.150, p = 0.041). Therefore, in men without an enlarged prostate, testosterone may play an opposing role in the etiology of nocturia.

Increased expression of TRPC4 channels associated with erectile dysfunction in diabetes.

In recent reports, an association between altered TRPC channel function and the development of various diabetic complications has drawn the attention of many investigators. The aim of this study was to investigate the expression of TRPC4 channels of corpus smooth muscle (CSM) cells in diabetes, and to evaluate the association between erectile dysfunction (ED) and altered TRPC4 channel function. The expression of TRPC4 in the penile tissue of human, normal and diabetic rat was investigated using RT-PCR, western blotting and immunohistochemistry (IHC). In vivo gene transfer of dominant negative (DN) TRPC4 into the CSM of rat was conducted. In vivo pelvic nerve stimulation was performed to measure erectile function. Expression of TRPC1, TRPC3, TRPC4 and TRPC6 in human and rat CSM tissues was confirmed by RT-PCR, western blot and IHC. In the diabetic rat, the expression levels of mRNA and protein of the TRPC4, and TRPC6 were significantly increased compared to control rats (p < 0.05). The change in TRPC4 expression in the diabetic rats was higher than those of the other TRPC subunits (p < 0.05). The IHC showed that only TRPC4 expression had a higher intensity in the diabetes compared to normal rats (p < 0.05). Gene transfection with TRPC4(DN) into the diabetic rats restored erectile function to levels similar to that of normal controls. Gene expression of TRPC4(DN) in CSM tissue was confirmed by RT-PCR 2 weeks after transfection. This study demonstrated that TRPC4 channel expression increased in the penile CSM cells of diabetic rats. The down-regulation of TRPC4 with DN form restored erectile function in the diabetic rats. The alteration of TRPC4 channel is one of pathophysiology of ED and could be a target for drug development for ED.

Radiotelemetric assessment of intracavernosal pressure in apomorphine-induced erection: hypercholesterolemic rats vs normal control.

A recording of the intracavernosal pressure (ICP) in conscious rats using telemetry has the advantage of being able to evaluate erection under physiological conditions. The aim of this study was to determine whether the radiotelemetric assessment of ICP in apomorphine-induced erection is appropriate for assessing erectile function in an animal model of disease. Seven rats were assigned to the normal group, and another nine rats were assigned to the hypercholesterolemia group. A telemetric pressure sensor was implanted in the corpus cavernosum. Pressure was recorded in freely moving animals after apomorphine injection. Sexual events were visually identified and recorded. Only the pressure increase occurring during sexual behavior was analyzed. The main outcome measures were as follows: latency for first peak after injection (latency), duration, maximum ICP (Max ICP) and area under the curve (AUC). The mean latency, mean duration of each episode, mean Max ICP, mean AUC and mean summed AUC were 389.9 ± 59.4 s, 61.6 ± 7.8 s, 140.0 ± 22.5 mm Hg, 1834.4 ± 358.2 mm Hg s and 3259.1 ± 795.9 mm Hg s, respectively, for the normal group vs 652.8 ± 102.2 s, 32.4 ± 5.2 s, 92.7 ± 6.4 mm Hg, 572.9 ± 73.6 mm Hg s and 739.9 ± 87.2 mm Hg s, respectively, for the hypercholesterolemia group. There was a significant difference in mean latency, mean AUC and mean summed AUC. Additionally, we cannot find any obvious immediate adverse events after surgical implantation in both normal control and hypercholesterolemic rats. And, no catheter displacement and no adverse local reaction, including fibrosis to the implant, were observed. In conclusion, radiotelemetric assessment of ICP in apomorphine-induced erection provided consistent and accurate data during erectile events, and was appropriate for assessing erectile function in an animal model of disease.

The prevalence of premature ejaculation and its clinical characteristics in Korean men according to different definitions.

This study compared the prevalence of premature ejaculation (PE) diagnosed by the PE diagnostic tool (PEDT) score, self-reporting and stopwatch-recorded intravaginal ejaculation latency time (IELT). It examined the characteristics of males diagnosed with PE by each criterion. A questionnaire survey enrolled 2081 subjects from March to October, 2010. Stopwatch-recorded IELT was measured in 1035 of the 2081 subjects. We aimed to determine whether PE has an influence on the frequency and satisfaction of sexual intercourse, the degree of libido/erectile function and the satisfaction. These factors were evaluated according to different definitions of PE to assess whether the definition used yielded differences in the data. The prevalence of PE, based on a PEDT score of ≥11, self-reporting and stopwatch-recorded IELT of ≤1 min was 11.3%, 19.5% and 3%, respectively. The prevalence of PE diagnoses based on PEDT score and self-reporting increased with age, but stopwatch-recorded IELT-based diagnoses did not. Males experiencing PE showed lower levels of libido, erectile function and frequency and satisfaction of sexual intercourse compared with non-PE males. PE males felt that they did not satisfy their partners in terms of the partners' sexual satisfaction and frequency of orgasm, in comparison with non-PE males. PE is a highly prevalent sexual dysfunction in males. Regardless of whether the PE diagnosis was made on the basis of self-reporting, PEDT score or stopwatch-recorded IELT, subjective symptoms were similar among PE males.

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.

The relaxation effect and mechanism of action of higenamine in the rat corpus cavernosum.

Higenamine mediates cardiotonic, vascular relaxation and bronchodilator effects. The relaxation effects and the mechanism of action of higenamine on the rat corpus cavernosum (CC) were assessed to investigate the effect of higenamine on penile erection. Strips of CC and aorta were used in organ baths for isometric tension studies. Tension was measured with isometric force transducers, and muscle relaxation was expressed as the percent decrease in precontraction induced by phenylephrine (PE). The relaxation reactions were investigated in an endothelial-denuded group and groups pretreated with N(G)-nitro-L-arginine methyl ester (NO synthesis inhibitor), propranolol (ß-receptor blocker), indomethacin (COX inhibitor), glibenclamide (K(+)(ATP) channel inhibitor), 4-aminopyridine (membrane potential-dependent potassium channel inhibitor) and methylene blue (guanylyl cyclase inhibitor) for 30 min. Intracavernous pressure (ICP) was assessed in rats after the intravenous administration of higenamine, and changes in guanosine 3',5'-cyclic monophosphate and adenosine 3',5'-cyclic monophosphate (cAMP) concentrations were measured on the basis of the higenamine concentration. Also, the combined reaction of higenamine and the phosphodiesterase type-5 (PDE-5) inhibitors was assessed. Higenamine induced relaxation of the CC and the aortic strips precontracted with PE in a dose-dependent manner. The CC was significantly more relaxed than the aortic rings in response to the same higenamine concentration (P<0.05). The CC relaxation reaction was suppressed by the ß-receptor blocker propranolol. The cAMP concentration increased gradually with increased higenamine concentration (P<0.05). The ICP also increased with increased higenamine concentration in vivo (P<0.05). In the group pretreated with 10(-7) M higenamine, the relaxation reaction of CC induced by the PDE-5 inhibitor increased significantly, compared with CC exposed to the PDE-5 inhibitor but not pretreated with higenamine (P<0.05). In conclusion, higenamine induced relaxation of the rat CC in a dose-dependent manner. The effect may be mediated through ß-adrenoceptors. The results suggest that higenamine may be valuable as a new lead compound for treating erectile dysfunction.

Effects of sertraline on brain current source of the high beta frequency band: analysis of electroencephalography during audiovisual erotic stimulation in males with premature ejaculation.

To identify the effects of sertraline, a selective serotonin reuptake inhibitor, for the treatment of premature ejaculation (PE), changes in brain current-source density (CSD) of the high beta frequency band (22-30 Hz) induced by sertraline administration were investigated during audiovisual erotic stimulation. Eleven patients with PE (36.9±7.8 yrs) and 11 male volunteers (24.2±1.9 years) were enrolled. Scalp electroencephalography (EEG) was conducted twice: once before sertraline administration and then again 4 h after the administration of 50 mg sertraline. Statistical non-parametric maps were obtained using the EEG segments to detect the current-density differences in the high beta frequency bands (beta-3, 22-30 Hz) between the EEGs before and after sertraline administration in the patient group and between the patient group and controls after the administration of sertraline during the erotic video sessions. Comparing between before and after sertraline administration in the patients with PE, the CSD of the high beta frequency band at 4 h after sertraline administration increased significantly in both superior frontal gyri and the right medial frontal gyrus (P<0.01). The CSD of the beta-3 band of the patients with PE were less activated significantly in the middle and superior temporal gyrus, lingual and fusiform gyrus, inferior occipital gyrus and cuneus of the right cerebral hemisphere compared with the normal volunteers 4 h after sertraline administration (P<0.01). In conclusion, sertraline administration increased the CSD in both the superior frontal and right middle temporal gyrus in patients with PE. The results suggest that the increased neural activity in these particular cerebral regions after sertraline administration may be associated with inhibitory effects on ejaculation in patients with PE.