Kwangsung Park

International Society for Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation.

INTRODUCTION Over the past 20 years our knowledge of premature ejaculation (PE) has significantly advanced. Specifically, we have witnessed substantial progress in understanding the physiology of ejaculation, clarifying the real prevalence of PE in population-based studies, reconceptualizing the definition and diagnostic criterion of the disorder, assessing the psychosocial impact on patients and partners, designing validated diagnostic and outcome measures, proposing new pharmacologic strategies and examining the efficacy, safety and satisfaction of these new and established therapies. Given the abundance of high level research it seemed like an opportune time for the International Society for Sexual Medicine (ISSM) to promulgate an evidenced-based, comprehensive and practical set of clinical guidelines for the diagnosis and treatment of PE. AIM Develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of PE for family practice clinicians as well as sexual medicine experts. Method.  Review of the literature. RESULTS This article contains the report of the ISSM PE Guidelines Committee. It affirms the ISSM definition of PE and suggests that the prevalence is considerably lower than previously thought. Evidence-based data regarding biological and psychological etiology of PE are presented, as is population-based statistics on normal ejaculatory latency. Brief assessment procedures are delineated and validated diagnostic and treatment questionnaires are reviewed. Finally, the best practices treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with PE, in facilitating treatment of their patients. CONCLUSION Development of guidelines is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to a more complete understanding of the pathophysiology as well as new efficacious and safe treatments for this sexual dysfunction. Therefore, it is strongly recommended that these guidelines be re-evaluated and updated by the ISSM every 4 years.

Blood-oxygenation-level-dependent functional magnetic resonance imaging for evaluating cerebral regions of female sexual arousal response.

OBJECTIVES To evaluate, for the first time, the cerebral regions associated with female sexual arousal evoked by visual stimulation using noninvasive blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI). METHODS A total of 6 healthy right-handed female volunteers (mean age 33 years, range 25 to 41) underwent fMRI on a 1.5-T MR scanner, in which the BOLD technique was used to create fMR images reflecting local brain activities. Real-time visual stimulation was performed with alternatively combined erotic and nonerotic films to identify the activated brain regions associated with sexual response. The perceived sexual arousal response was assessed using a scale ranging from 1 (no change) to 5 (maximal increase). RESULTS The mean score for perceived sexual arousal by erotic visual stimulation was 2.7 on the 5-point scale and was unchanged by nonerotic stimulation. During the visual task, the occipital cortex was activated by both the erotic and the nonerotic films; however, the following cerebral areas were significantly (P <0.05) activated, varying from 4 of 6 to 6 of 6 women: inferior frontal lobe, cingulate gyrus, insula gyrus, corpus callosum, thalamus, caudate nucleus, globus pallidus, and inferior temporal lobe. CONCLUSIONS This study is the first to evaluate noninvasive BOLD-fMRI in identifying cerebral regions associated with sexual arousal response evoked by visual stimulation in women.

ORIGINAL RESEARCH—PHYSIOLOGY: Assessment of Cerebrocortical Areas Associated with Sexual Arousal in Depressive Women Using Functional MR Imaging

INTRODUCTION Mental illness is closely related with sexual dysfunction. A number of investigators have reported that depressive women have difficulties in sexual arousal. AIM The purpose of this study was to compare the cerebrocortical regions associated with sexual arousal between the healthy and depressive women using functional magnetic resonance imaging (fMRI) based on the blood-oxygenation-level-dependent (BOLD) technique. METHODS Together with nine healthy women (mean age: 40.3), seven depressive women (mean age: 41.7 years, mean Beck Depression Inventory: 35.6, mean Hamilton Rating Scale Depression-17: 34.9) underwent fMRI examinations using a 1.5T MR scanner (Signa Horizon; GE Medical Systems, Milwaukee, WI, USA). The fMRI data were obtained from seven oblique planes using gradient-echo EPI. Sexual stimulation paradigm began with a 1-minute rest and then 4-minute stimulation using an erotic video film. The brain activation maps and their resulting quantification were analyzed by the statistical parametric mapping (SPM99) program. The number of pixels activated by each task was used as brain activity, where the significance of the differences was evaluated by using independent t-test. MAIN OUTCOME MEASURES We measured brain activation areas using BOLD-based fMRI with visual sexual stimulation in healthy volunteers and depressive patients. RESULTS Healthy women were significantly (P < 0.05) activated in the regions of middle occipital gyrus, middle temporal gyrus, inferior frontal gyrus, insula, hypothalamus, septal area, anterior cingulate gyrus, parahippocampal gyrus, thalamus, and amygdala by erotic visual stimulation. In comparison with the healthy women, the depressive women gave lower activity, especially in the brain regions of hypothalamus (55.5:3.0), septal area (49.6:8.6), anterior cingulate gyrus (23.5:11.0), and parahippocampal gyrus (18.2:5.8). CONCLUSIONS This preliminary study performed by fMRI gives valuable information on differentiation of the activated cerebral regions associated with visually evoked sexual arousal between healthy and depressive women. In addition, these findings might be useful to understand neural mechanisms for female sexual dysfunction in depressive women.

Efficacy and Safety of Once-Daily Dosing of Udenafil in the Treatment of Erectile Dysfunction: Results of a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

BACKGROUND A once-daily dosing regimen with a phosphodiesterase type 5 inhibitor is needed for the treatment of erectile dysfunction (ED), in part because of the behavioral complexities associated with sexual intimacy. Many patients prefer spontaneous rather than scheduled sexual activities or they anticipate frequent sexual encounters. The pharmacokinetic profiles of udenafil with a time of maximal concentration of 1.0-1.5h and a terminal half-life of 11-13 h make udenafil a good candidate for once-daily dosing. OBJECTIVE To evaluate the efficacy and safety of once-daily dosing of udenafil in the treatment of ED. DESIGN, SETTING, AND PARTICIPANTS This multicenter randomized double-blind, placebo-controlled, fix-dosed clinical trial involved 237 patients with ED. The subjects, who were treated with placebo or udenafil (25mg, 50mg, or 75 mg) once daily for 12 wk, were asked to complete the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and the Global Assessment Questionnaire (GAQ) during the study. MEASUREMENTS The primary outcome parameter was the change from baseline for the IIEF erectile function domain (EFD) score. The secondary outcome parameters were SEP questions 2 and 3, the shift to normal rate (EFD ≥ 26), and the response to the GAQ. RESULTS AND LIMITATIONS Compared with placebo, patients who took 50mg or 75 mg of udenafil had a significantly improved IIEF-EFD score. Similar results were observed in comparing questions 2 and 3 in the SEP diary and the GAQ. Flushing was the most common treatment-related adverse event, which was transient and mild to moderate in severity. CONCLUSIONS Udenafil significantly improved erectile function among ED patients when administered in doses of 50mg or 75 mg once daily for 12 wk. Daily administration of udenafil (50mg) may be another treatment option for ED.

Effects of Korean red ginseng on sexual arousal in menopausal women: placebo-controlled, double-blind crossover clinical study.

INTRODUCTION Many menopausal women experience climacteric symptoms including impairment of sexual function. Recent reports have suggested that Korean red ginseng (KRG) has a relaxing effect on the clitoral cavernosal muscle and vaginal smooth muscle in rats. AIM We assessed whether KRG extracts would improve sexual function in menopausal women. METHODS Thirty-two menopausal women participated in a placebo-controlled, double-blind, crossover clinical study with administration of either three capsules of ginseng (1 g per capsule) or placebo daily. After completing the KRG or placebo arm, the participants were crossed over to the other arm after a 2-week washout period. The efficacy and safety of the KRG extracts were measured by using questionnaires. MAIN OUTCOME MEASURES Female Sexual Function Index (FSFI) and Global Assessment Questionnaire (GAQ). RESULTS Twenty-eight women completed the study. They were, on average, 51.2 + or - 4.1 years old, and their mean menopausal state was for a duration of 37.4 + or - 2.9 months. Few carryover effects were noted in either study arm. The ginseng extract significantly improved scores on the FSFI from 3.10 + or - 0.87 to 3.50 + or - 0.72 in the sexual arousal domain (P = 0.006). The GAQ was more significantly affected by ginseng extracts than by placebo (P = 0.046). There were no severe adverse events in the KRG group, although two cases of vaginal bleeding occurred during KRG treatment. CONCLUSIONS Oral administration of KRG extracts improved sexual arousal in menopausal women. Red ginseng extracts might be used as an alternative medicine in menopausal women to improve their sexual life.

ORIGINAL RESEARCHORIGINAL RESEARCH—PHYSIOLOGY: Assessment of Cerebrocortical Areas Associated with Sexual Arousal in Depressive Women Using Functional MR Imaging

INTRODUCTION Mental illness is closely related with sexual dysfunction. A number of investigators have reported that depressive women have difficulties in sexual arousal. AIM The purpose of this study was to compare the cerebrocortical regions associated with sexual arousal between the healthy and depressive women using functional magnetic resonance imaging (fMRI) based on the blood-oxygenation-level-dependent (BOLD) technique. METHODS Together with nine healthy women (mean age: 40.3), seven depressive women (mean age: 41.7 years, mean Beck Depression Inventory: 35.6, mean Hamilton Rating Scale Depression-17: 34.9) underwent fMRI examinations using a 1.5T MR scanner (Signa Horizon; GE Medical Systems, Milwaukee, WI, USA). The fMRI data were obtained from seven oblique planes using gradient-echo EPI. Sexual stimulation paradigm began with a 1-minute rest and then 4-minute stimulation using an erotic video film. The brain activation maps and their resulting quantification were analyzed by the statistical parametric mapping (SPM99) program. The number of pixels activated by each task was used as brain activity, where the significance of the differences was evaluated by using independent t-test. MAIN OUTCOME MEASURES We measured brain activation areas using BOLD-based fMRI with visual sexual stimulation in healthy volunteers and depressive patients. RESULTS Healthy women were significantly (P < 0.05) activated in the regions of middle occipital gyrus, middle temporal gyrus, inferior frontal gyrus, insula, hypothalamus, septal area, anterior cingulate gyrus, parahippocampal gyrus, thalamus, and amygdala by erotic visual stimulation. In comparison with the healthy women, the depressive women gave lower activity, especially in the brain regions of hypothalamus (55.5:3.0), septal area (49.6:8.6), anterior cingulate gyrus (23.5:11.0), and parahippocampal gyrus (18.2:5.8). CONCLUSIONS This preliminary study performed by fMRI gives valuable information on differentiation of the activated cerebral regions associated with visually evoked sexual arousal between healthy and depressive women. In addition, these findings might be useful to understand neural mechanisms for female sexual dysfunction in depressive women.

Impact of diabetes mellitus on recurrence and progression in patients with non-muscle invasive bladder carcinoma: A retrospective cohort study

Objective:  The aim of the present study was to investigate the relationship between diabetes mellitus (DM) and tumor features in patients with non‐muscle invasive bladder cancer (NMIBC).

Diabetes Mellitus Induces Vaginal Tissue Fibrosis by TGF-beta; 1 Expression in the Rat Model

The commonly reported sexual problem in women with diabetes mellitus is lack of vaginal lubrication. It is our hypothesis that reduced vaginal lubrication in diabetic women may result from the structural changes of the vagina. The aim of this study was to investigate in the diabetic rat model the vaginal structures using histochemistry and the expression of TGF- g 1 using immunohistochemistry. Twenty female Sprague-Dawley rats (200-210 g) were divided into two groups: control and experimental. The experimental group ( n = 10) received intravenous injection of streptozotocin (50 mg/kg). After 4 weeks, blood glucose levels were measured, and the vagina of the rat was excised. Serial sections of the vagina were used to perform hematoxylin and eosin (H & E) and Massons trichrome stains, and for immunohistochemistry to identify TGF- g 1 expression. The mean blood glucose concentrations were 67 - 11 mg/dL (range; 50-85) in the control group and 522 - 61 mg/dl (range; 429-590) in the experimental group. In the diabetic animals, vaginal tissue revealed reduced epithelial layers and decreased vaginal submucosal vasculatures compared to the control animals. The collagen connective tissue in the submucosal area of the diabetic animal tissue showed a dense and irregular, distorted arrangement. The immunoreactivity of TGF- g 1 in the diabetic animals was prominent in the collagen connective tissue, fibroblasts, and smooth muscle fibers, whereas no immunoactivity was detected in the vaginal structures of the control animals. Diabetes mellitus may induce vaginal tissue fibrosis by TGF- g 1 expression in the rat model. This implies that reduced vaginal lubrication in the diabetic women may result from the structural changes of the vagina.

Distribution of interstitial cells of cajal and expression of nitric oxide synthase after experimental bladder outlet obstruction in a rat model of bladder overactivity

Recent studies have showed that interstitial cells (ICs) are widely distributed in the genitourinary tract and have suggested their involvement in spontaneous electrical activity and muscle contraction. Nitric oxide (NO) is thought to play a role in bladder overactivity related with bladder outlet obstruction (BOO). The purposes of this study were to investigate the effect of bladder overactivity induced by BOO on ICs and nitric oxide synthase (NOS) isoforms in rat urinary bladder.

Diabetes Induced Alteration of Clitoral Hemodynamics and Structure in The Rabbit

PURPOSE We investigated the effect of diabetes on clitoral hemodynamics and structures in the rabbit. MATERIALS AND METHODS A total of 25 New Zealand White female rabbits weighing 3 to 3.5 kg. were divided into 2 groups, including 5 in the control and 20 in the experimental group. Experimental animals received intravenous injection of alloxan hydrochloride (Sigma Chemical Co., St. Louis, Missouri) (100 mg./kg.). The development of diabetes was verified by measuring body weight and blood glucose levels. After 12 weeks clitoral cavernous blood flow in ml. per minute per 100 gm. tissue was measured with a laser Doppler flowmeter. Cross sections of the clitoris were used for histochemistry and histomorphometric image analysis. RESULTS After 12 weeks 5 animals were included in the diabetes group. Mean baseline flaccid and peak clitoral cavernous blood flow plus or minus standard deviation significantly decreased in the diabetic group compared with the control group (3.9 +/- 1.6 and 5.8 +/- 2.2 versus 7.2 +/- 2.5 and 12.9 +/- 5.8 ml. per minute per 100 gm. tissue, respectively, p <0.05). Histology revealed diffuse clitoral fibrosis in the diabetic group. On histomorphometry the mean proportion of clitoral cavernous smooth muscle in the diabetic group was significantly decreased compared with the control group (51.9% +/- 4.9% versus 62.3% +/- 3.1%, p < 0.05). CONCLUSIONS These results show that diabetes mellitus produces significant adverse effects on the hemodynamic mechanism of clitoral engorgement and leads to diffuse clitoral cavernous fibrosis. It implies that decreased sexual arousal in diabetic women may result from structural changes in the clitoris.