Assessment of sexual behaviour and fertility indices in male rabbits following chronic codeine use.

BACKGROUND: Codeine is the latest trend of drug abuse, particularly in Nigeria and regarded as the gateway to the abuse of other substances. OBJECTIVES: The present study examined the effects of graded doses of codeine on sexual behaviour and fertility profile. MATERIALS AND METHODS: Rabbits were either administered normal saline (0.2 mL), 4mg/kg b.w of codeine (low dose), or 10mg/kg b.w of codeine (high dose) p.o for 6 weeks. RESULTS AND DISCUSSION: Findings of the study showed that codeine administration significantly increased libido as witnessed by significantly short mount latency (ML), intromission latency (IL), post-ejaculatory interval (PEI) and significantly increased mount frequency (MF), intromission frequency (IF) and ejaculation latency (EL). Furthermore, codeine caused a marked rise in penile reflexes evident by a significant increase in erections, quick flips, long flips and total penile reflexes. However, copulatory efficiency and fertility index were significantly lower in codeine-treated groups when compared with the control. Serum levels of testosterone were also significantly lower in the treated groups. CONCLUSIONS: The present study demonstrates that codeine-induced enhancement of sexual performance is via a testosterone-independent mechanism. It also reveals that although codeine enhances copulatory locomotor activity, it is a potential risk factor for infertility.

[Assessment of the erectile function and patients' perception of improvement in Spanish patients with erectile dysfunction]. / Evaluación de la función eréctil y la percepción de mejoría en pacientes españoles con disfunción eréctil.

OBJECTIVE: This study has been carried out to assess the hardness of erection and the perception of improvement in erectile function with the treatments received during the last month. MATERIAL AND METHOD: Descriptive, observational, multicenter, cross-sectional study carried out in 30 urology sites in Spain. Patients diagnosed of erectile dysfunction receiving treatment during at least the last month have been enrolled. Hardness of erection has been assessed with the erection hardness score and improvement perception has been estimated with the global assessment question. RESULTS: A 63% of patients had a hardness of erection that was insufficient for penetration, but 75% of patients referred that their erectile function had improved with treatment. After adjustment for other factors, erection hardness score values were not significantly different among patients being treated with alprostadil topical cream, compared to patients being treated with the combination of phosphodiesterase 5 (PDE5) inhibitors plus alprostadil topical cream or with PDE5i other than sildenafil alone. However, patients treated with alprostadil topical cream had a significantly higher chance of referring an improvement in their erectile function compared to patients treated with PDE5i, despite the fact that they had received treatment for a shorter period of time. CONCLUSION: Hardness of erection is just another factor of erectile function, but it is not the only one influencing improvement perception by patients.

Validity and Clinically Meaningful Changes in the Psychosexual Daily Questionnaire and Derogatis Interview for Sexual Function Assessment: Results From the Testosterone Trials.

BACKGROUND: Limited information is available on the performance characteristics of 2 questionnaires commonly used in clinical research, the Psychosexual Daily Questionnaire (PDQ) and the Derogatis Interview for Sexual Function (DISF)-II Assessment, especially in older men with low testosterone (T) and impaired sexual function. AIM: To determine reliability of PDQ and DISF-II by assessing the correlation within and between domains in the questionnaires and to define clinically meaningful changes in sexual activity (PDQ question 4 [Q4]) and desire (DISF-II sexual desire domain [SDD]) domains. METHODS: Data from 470 men participating in the T Trials were used to calculate Spearman correlation coefficients of individual items and total score among questionnaires to determine convergent and construct validity. Clinically meaningful changes for sexual desire and activity were determined by randomly dividing the sample into training and validation sets. Anchor- and distribution-based clinically meaningful change criteria were defined in the training set, and selected changes were evaluated in the validation set. OUTCOMES: Validity of the PDQ and DISF-II and clinically meaningful changes in sexual desire and activity were determined in older men in T Trials. RESULTS: Moderate to strong correlations were shown within and between domains from different questionnaires. Using Patient Global Impression of Change as an anchor, clinically meaningful change in PDQ sexual activity was ≥0.6, and in DISF-SDD was ≥5.0. Applying these change cut-points to the validation set, a greater proportion of T-treated men achieved clinically meaningful improvement in their sexual desire and activity compared to placebo-treated men. CLINICAL IMPLICATIONS: The PDQ-Q4 and DISF-II-SDD can be used to reliably assess clinically meaningful changes in sexual activity and sexual desire in hypogonadal men treated with T. STRENGTHS & LIMITATIONS: Strengths of this study include a large sample size, long trial duration, and inclusion of men with low libido and unequivocally low T levels. Limitations include using data from a single study that enrolled only older hypogonadal men, and only 1 anchor for both sexual desire and activity. CONCLUSION: Moderate to strong correlations were demonstrated within and between different sexual domains of the PDQ and DISF-II confirming construct and convergent validity. Clinically meaningful improvement in elderly hypogonadal men was change of ≥0.6 score in the PDQ-Q4 and ≥5.0 in the DISF-SDD. Improvements in sexual activity and desire in the T Trials were modest but clinically meaningful. Wang C, Stephens-Shields AJ, DeRogatis LR, et al. Validity and Clinically Meaningful Changes in the Psychosexual Daily Questionnaire and Derogatis Interview for Sexual Function Assessment: Results From the Testosterone Trials. J Sex Med 2018;15:997-1009.

Exploratory Decision-Tree Modeling of Data from the Randomized REACTT Trial of Tadalafil Versus Placebo to Predict Recovery of Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy.

BACKGROUND: Understanding predictors for the recovery of erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) might help clinicians and patients in preoperative counseling and expectation management of EF rehabilitation strategies. OBJECTIVE: To describe the effect of potential predictors on EF recovery after nsRP by post hoc decision-tree modeling of data from A Study of Tadalafil After Radical Prostatectomy (REACTT). DESIGN, SETTING, AND PARTICIPANTS: Randomized double-blind double-dummy placebo-controlled trial in 423 men aged <68 yr with adenocarcinoma of the prostate (Gleason ≤7, normal preoperative EF) who underwent nsRP at 50 centers from nine European countries and Canada. INTERVENTION: Postsurgery 1:1:1 randomization to 9-mo double-blind treatment with tadalafil 5mg once a day (OaD), tadalafil 20mg on demand, or placebo, followed by a 6-wk drug-free-washout, and a 3-mo open-label tadalafil OaD treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Three decision-tree models, using the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score at the end of double-blind treatment, washout, and open-label treatment as response variable. Each model evaluated the association between potential predictors: presurgery IIEF domain and IIEF single-item scores, surgical approach, nerve-sparing score (NSS), and postsurgery randomized treatment group. RESULTS AND LIMITATIONS: The first decision-tree model (n=422, intention-to-treat population) identified high presurgery sexual desire (IIEF item 12: ≥3.5 and <3.5) as the key predictor for IIEF-EF at the end of double-blind treatment (mean IIEF-EF: 14.9 and 11.1), followed by high confidence to get and maintain an erection (IIEF item 15: ≥3.5 and <3.5; IIEF-EF: 15.4 and 7.1). For patients meeting these criteria, additional non-IIEF-related predictors included robot-assisted laparoscopic surgery (yes or no; IIEF-EF: 19.3 and 12.6), quality of nerve sparing (NSS: <2.5 and ≥2.5; IIEF-EF: 14.3 and 10.5), and treatment with tadalafil OaD (yes and no; IIEF-EF: 17.6 and 14.3). Additional analyses after washout and open-label treatment identified high presurgery intercourse satisfaction as the key predictor. CONCLUSIONS: Exploratory decision-tree analyses identified high presurgery sexual desire, confidence, and intercourse satisfaction as key predictors for EF recovery. Patients meeting these criteria might benefit the most from conserving surgery and early postsurgery EF rehabilitation. Strategies for improving EF after surgery should be discussed preoperatively with all patients; this information may support expectation management for functional recovery on an individual patient level. PATIENT SUMMARY: Understanding how patient characteristics and different treatment options affect the recovery of erectile function (EF) after radical surgery for prostate cancer might help physicians select the optimal treatment for their patients. This analysis of data from a clinical trial suggested that high presurgery sexual desire, sexual confidence, and intercourse satisfaction are key factors predicting EF recovery. Patients meeting these criteria might benefit the most from conserving surgery (robot-assisted surgery, perfect nerve sparing) and postsurgery medical rehabilitation of EF. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01026818.

Venous leakage treatment revisited: pelvic venoablation using aethoxysclerol under air block technique and Valsalva maneuver.

OBJECTIVE: We evaluated the effectiveness of pelvic vein embolization with aethoxysclerol in aero-block technique for the treatment of impotence due to venous leakage in men using sildenafil for intercourse. The aim of the procedure was to reduce the use of sildenafil. METHODS: A total of 96 patients with veno-occlusive dysfunction, severe enough for the need of PDE5 inhibitors for vaginal penetration, underwent pelvic venoablation with aethoxysclerol. The mean patient age was 53.5 years. Venous leaks were identified by Color Doppler Ultrasound after intracavernous alprostadil injection. Under local anesthesia a 20-gauge needle was inserted into the deep dorsal penile vein. The pelvic venogram was obtained through deep dorsal venography. Aethoxysclerol 3% as sclerosing agent was injected after air-block under Valsalva manoeuver. Success was defined as the ability to achieve vaginal insertion without the aid of any drugs, vasoactive injections, penile prosthesis, or vacuum device. Additionally, a pre- and post- therapy IIEF score and a digital overnight spontaneous erections protocol (OSEP) with the NEVA™-system was performed. RESULTS: At 3 month follow-up 77 out of 96 patients (80.21%) reported to have erections sufficient for vaginal insertion without the use of any drug or additional device. Four (4.17%) patients did not report any improvement. Follow up with color Doppler ultrasound revealed a new or persistent venous leakage in 8 (8.33%) of the patients. No serious complications occurred. CONCLUSIONS: Our new pelvic venoablation technique using aethoxysclerol in air-block technique was effective, minimally invasive, and cost-effective. All patients were able to perform sexual intercourse without the previously used dosage of PDE5 inhibitor. This new method may help in patients with contra-indications against PDE5 inhibitors, in patients who cannot afford the frequent usage of expensive oral medication or those who do not fully respond to PDE5-inhibitors.

Comparisons of apomorphine-induced erection and spontaneous erection in rats by telemetric assessment of intracavernosal pressure.

Although there are several methods for assessing erectile function in rats, the standard methods for telemetric monitoring have not been established. Theoretically assessment of spontaneous erection (SE) seems to be a physiologic method but it needs long measuring time and additional efforts. Apomorphine-induced erection (AIE) is one available and simple method; however, the correlation with SE has not been assessed. We compared erection profiles of AIE and SE in normal and two disease rat models using telemetric assessment of intracavernosal pressure (ICP). Seven-week-old male Sprague-Dawley rats were assigned to normal control, diabetes mellitus (DM) and hypercholesterolemia (HC) group. After 19 weeks a telemetric pressure sensor (C40; Data Sciences) was surgically implanted in the corpus cavernosum. One week later, ICP was recorded in freely moving rats after intraperitoneal apomorphine (100 µg/kg) injection (AIE) or during SE. Sexual events were visually identified and recorded. Only the pressure increases that occurred during sexual behavior were analyzed. We compared the erectile profiles such as duration, maximal ICP and the area under the curve (AUC, area under time × ICP curves). Two-way anova revealed no significant effect of the measuring methods on the mean AUC (F1,43 = 2.756, p-value = 0.104), but a significant effect of different disease models on mean AUC (two-way anova: F2,43 = 12.929, p-value < 0.001) was observed. The mean AUC of normal control rats was significantly higher than that of DM and HC rats (Bonferroni post hoc test: p < 0.001 and p = 0.001, respectively). ICP measurements using a telemetric device showed no significant difference in AUC between AIE and SE. AIE is easy and requires less time than SE measurements. Therefore, AIE could be a useful method to evaluate ICP in rats.

Risk-benefit assessment of oral phosphodiesterase type 5 inhibitors for treatment of erectile dysfunction: a multiple criteria decision analysis.

BACKGROUND: Erectile dysfunction (ED) is a common male sexual disorder worldwide. Three oral phosphodiesterase type 5 inhibitors (PDE5Is) - sildenafil, tadalafil and vardenafil - are available for treatment of ED. This study quantitatively evaluated the therapeutic efficacy and safety of these medications to assist treatment decision making. METHODS: We used multiple criteria decision analysis (MCDA) to assess the totality of risk-benefit of PDE5Is. We created two models: (i) the overall model included 'overall improvement in erections' and 'any adverse events' and (ii) the detailed model included 'erectile function domain', 'ability for sexual intercourse', 'duration of erection last', 'serious adverse events', 'headache', 'flushing' and 'dyspepsia'. We calculated a synthetic utility for each drug accounting for all of its benefits and risks. RESULTS: Considering the overall risk-benefit, vardenafil had the highest synthetic utility among three medications; in the order of synthetic utilities: vardenafil (0.568), tadalafil (0.478) and sildenafil (0.437). However, when specific risk and benefit criteria were assessed, tadalafil had the highest synthetic utility (0.602) according to the conjoint evaluation (synthetic utility for vardenafil is 0.491 and sildenafil is 0.442, respectively). The sensitivity analysis based on the uncertainties of weight on risks of any adverse events (including serious adverse events and headache) suggested our results were robust. CONCLUSIONS: This study provides a useful approach that comprehensively and systematically assesses and compares the risk-benefit of several treatment alternatives. Our study not only rank treatment alternatives by synthetic utilities based on the risk-benefit balance but also compare specific risk and benefit criteria between these medicines. Our results provide valuable evidence that can guide clinicians and patients in making treatment decisions.

Erection hardness score for the evaluation of erectile dysfunction: further psychometric assessment in patients treated by intracavernous prostaglandins injections after radical prostatectomy.

INTRODUCTION: Erectile dysfunction (ED) affects quality of life in patients treated by radical prostatectomy (RP). The Erection Hardness Score (EHS) is a single-item scale that has demonstrated good psychometric properties for assessing erectile function (EF) in patients treated by sildenafil, but its applicability to other treatment contexts has not yet been tested. AIM: This study aims to test the validity and time and treatment responsiveness of the EHS to assess ED in men with post-RP ED treated with alprostadil injections. METHODS: This is a 1-year follow-up cohort study of 75 patients treated by RP for localized prostate cancer in a urology department setting between January 2007 and December 2008. Data were prospectively collected at 6 and 12 months post-RP. MAIN OUTCOME MEASURES: The EHS, the International Index of Erectile Function (IIEF) reference questionnaire, the Global Assessment Questionnaire (GAQ), and Numeric Pain Scale (NPS) were collected. Convergent validity (Spearman correlation coefficients with IIEF domains), known-groups validity (comparing EHS scores across ED severity groups), time and treatment responsiveness (effect size with/without treatment and over the follow-up period), and predictive ability (area under the receiver operating characteristics curve [AUC-ROC]) were analyzed for this study. RESULTS: The EHS showed good convergent validity (all Spearman coefficients significant at the P<0.05 level), adequate known-groups validity (global differentiation between IIEF-EF severity groups; P<0.001), and treatment responsiveness (effect size: +1.8 [6 months], +2.1 [12 months]), but limited time responsiveness and predictive ability of the EHS for a normal EF at 12 months follow-up when compared with the IIEF-EF domain (AUC-ROC: 0.72 vs. 0.85; P<0.01). CONCLUSION: Our findings support the overall good psychometric properties of the EHS in patients with post-RP ED treated with alprostadil injections. However, evidence for limited predictive validity and responsiveness to change over time should be considered for its use in clinical follow-up in this population.

Assessment of androgen replacement therapy for erectile function in rats with type 2 diabetes mellitus by examining nitric oxide-related and inflammatory factors.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) has become a major public health issue and is considered a risk factor for erectile dysfunction (ED). T2DM is also associated with androgen deficiency. However, there have been few basic studies on androgen replacement therapy (ART) for ED treatment in T2DM animal models, and the mechanism underlying the effect of ART on T2DM-induced ED is unclear. AIM: To investigate the effect of ART on ED in T2DM rats by examining inflammatory and nitric oxide (NO)-related factors. METHODS: Otsuka Long-Evans Tokushima Fatty (OLETF) rats and their controls, Long-Evans Tokushima Otsuka (LETO) rats, were distributed into three groups: LETO, OLETF, and ART. In the ART group, OLETF rats were treated daily with testosterone (3 mg/kg/day, subcutaneously) from 20 to 25 weeks of age; LETO and OLETF rats received vehicle only. MAIN OUTCOME MEASURES: We measured erectile function by using measurements of the ratio between intracavernosal pressure (ICP) and mean arterial pressure (MAP) following electrical stimulation of the cavernous nerve and by evaluating the endothelial function of the corpus cavernosum in an isometric tension study. Expression of endothelial NO synthase (eNOS), inducible NO synthase (iNOS), sirtuin-1 (Sirt1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) mRNA was detected using polymerase chain reaction. RESULTS: The ICP/MAP ratio in the OLETF group was significantly decreased and that in the ART group was significantly improved (P < 0.01). The response to acetylcholine was significantly decreased in the OLETF group and improved in the ART group (P < 0.01). Although expression of eNOS and Sirt1 mRNA was decreased and that of iNOS, IL-6, and TNF-α mRNA was increased in the OLETF group, ART improved mRNA expression. CONCLUSIONS: ART suppressed inflammation in rats with T2DM and metabolic disorders and improved their endothelial and erectile functions. ART could be effective for T2DM-induced ED and may be considered a potential ED treatment method.

A comparative study of the efficacy of intralesional verapamil versus normal saline injection in a novel Peyronie disease animal model: assessment of immunohistopathological changes and erectile function outcome.

PURPOSE: While intralesional injections improve penile curvature and decrease plaque volume, the exact mechanism of action on Peyronie disease is unknown. We evaluated penile curvature, immunohistology and erectile function outcomes after intralesional injections of verapamil and normal saline in a previously described Peyronie disease animal model. MATERIALS AND METHODS: Peyronie plaque was induced in 12 adult male rats using an established Peyronie disease animal model. At 4 weeks the rats were divided into group 1-5 with 0.1 mg/0.1 ml intralesional verapamil injected every second day for 2 weeks, group 2-5 with 0.1 ml intralesional normal saline injection and group 3-2 that served as controls. At weeks 6 and 8 penile pressure was measured and serial immunohistochemical staining of penile tissue sections was done. RESULTS: Intralesional injection of verapamil and normal saline resulted in macroscopic and microscopic changes to penile curvature and Peyronie plaque size. Decreased collagen and elastin fibers were measured with a significant reduction in smooth muscle α-actin (p <0.05). Changes were greater in group 1 than group 2 (p <0.05). Intralesional verapamil injection was associated with greater recovery of electrostimulated penile pressure, a surrogate of erectile function, than in the saline and control groups. CONCLUSIONS: To our knowledge this novel study offers for the first time histological evidence of cellular changes and improvement in penile pressure studies in rats with Peyronie plaque after intralesional verapamil injection therapy in a Peyronie disease animal model.

Can simvastatin improve erectile function and health-related quality of life in men aged ≥40 years with erectile dysfunction? Results of the Erectile Dysfunction and Statins Trial [ISRCTN66772971].

OBJECTIVE: To evaluate the effectiveness and cost-effectiveness of simvastatin on erectile function and health-related quality of life in men aged ≥40 years with erectile dysfunction (ED). PATIENTS AND METHODS: ED is common in men aged ≥40 years and impacts upon their overall health-related quality of life and that of their partners. Men aged ≥40 years who were not receiving lipid lowering or anti-hypertensive medication and not at high cardiovascular risk were recruited from 10 general practices in the East of England. In total, 173 eligible men with untreated ED were randomized to double-blind treatment with 40 mg of simvastatin or placebo once daily for 6 months. Data were collected at three points over 30 weeks. The main outcome was erectile function (International Index of Erectile Function-5 score). Secondary outcomes included male ED-specific quality of life (MED-QoL), quality-adjusted life years (QALYs) using the generic Euroqol measure (EQ-5D), endothelial function, cardiovascular risk, cholesterol and health service costs. RESULTS: There was no significant difference in erectile function between the simvastatin and placebo groups (mean change, 1.28 vs 0.07, z = 1.1, p = 0.27), although a significant improvement in MED-QoL was observed (5% vs 2%, z = 2.09, p = 0.04). Both 10-year cardiovascular risk and low-density lipoprotein were reduced (cardiovascular risk, z = -3.67, p < 0.001; low-density lipoprotein, z = -5.46, p < 0.001), with no consistent change in endothelial function. The frequency of sexual encounters is correlated with improved erectile function. The joint distribution of costs and QALY benefits indicates that the probability of simvastatin being cost-effective for willingness-to-pay thresholds of £20,000 and £30,000 is 86% and 83%, respectively. CONCLUSIONS: Identifying men with ED provides an opportunity to modify future cardiovascular risk and to improve MED-QoL by treating them with 40 mg of simvastatin. The joint analysis of costs and QALY benefits suggests that there is high probability that simvastatin is a cost-effective strategy in men with ED. The findings could influence urological and primary care practice by including questions on ED during routine consultations and relevant clinical protocols. This provides an opportunity to impart lifestyle advice.

The role of PDE5 inhibitors in penile septal scar remodeling: assessment of clinical and radiological outcomes.

INTRODUCTION: Effective oral medication for use in men with Peyronie's disease (PD) has been an area of interest of the medical community and lay public for decades. Isolated septal scars (ISS) without evidence of penile deformity is a relatively new clinical entity, and at present, there is paucity in the published literature regarding its treatment. Current research into the use of phosphodiesterase type 5 (PDE5) inhibitors in regulating penile erectile response has revealed an alternative role for PDE5 inhibitors in decreasing oxidative stress-associated inflammatory change as seen in PD. AIM: To examine the presence of ISS and assess the efficacy of PDE5 inhibitor use in septal scar remodeling. METHODS: Retrospective review of prospective database on all men who underwent penile Doppler ultrasound between December 2007 and December 2009. MAIN OUTCOME MEASURES: Of the 65 men with ultrasonographic-confirmed ISS, 35 men received tadalafil 2.5 mg daily over a 6-month period. The clinical outcomes between the two groups were compared using International Index of Erectile Function (IIEF)-5 score and 6 months penile Doppler ultrasound follow up. RESULTS: The mean age for the tadalafil group was 43.2 (20-65) years, similar to the control group at 44.2 (34-72) years. The length of time from onset to presentation was 22 (6 to 40) months. The majority of ultrasonographic-proven ISS was not clinically palpable and complaint of decreased penile rigidity (66%) was the predominant feature. Treatment with low-dose daily tadalafil did not result in any significant side effects (such as headache and flushing) or discontinuation. The tadalafil group reported higher IIEF-5 score (pretreatment 11/25 to post-treatment 18/25) (P < 0.01) and resolution of septal scar were recorded in 24 patients (69%) compared to three patients (10%) in the control group. CONCLUSION: Low-dose daily tadalafil is a safe and effective treatment option in septal scar remodeling.

Commentary: sildenafil in phallometric testing--an evidence-based assessment of sexual offenders.

The field of medicine has moved toward best practices based on evidence. There is pressure on all medical disciplines, including forensic psychiatry, to adopt this approach. Some areas of forensic psychiatry have a stronger scientific basis that clearly fits the definition of evidence-based medicine than do other areas. One of these areas is the assessment and treatment of sexual offenders, which has a strong scientific basis and meets the definition of evidence-based medicine, as defined by Sackett et al. in 2007. Phallometric testing is an objective, physiological indicator of deviant sexual preferences that support the diagnosis of paraphilias and the assessment of sexual offenders. The current article by Kolla et al. is an effort to improve the reliability of phallometric testing related to diagnosis by pharmacologic stimulation.

Efficacy and safety of two different testosterone undecanoate formulations in hypogonadal men with metabolic syndrome.

AIM: To investigate efficacy and safety of two different preparations of testosterone undecanoate (TU) in 52 hypogonadal men [mean age 57 yr and mean testosterone (T) < 320 ng/dl] with metabolic syndrome (MS). SUBJECTS AND METHODS: Randomized, double-blind, double-dummy study with three parallel treatment arms [oral TU; transdermal placebo gel (P); im TU] administration for 12 months (mo). Each subject was randomized (1:1:3) to receive either oral TU (2 capsules of 40 mg/twice per day at breakfast and dinner, equalling a total dose of 160 mg/day; no.=10) for 6 mo and continued with im TU for further 6 mo, or P (3-4 g/day; no.=10) and im TU (1000 mg/12 weeks from week 6; no.=32) for 12 mo. RESULTS: After 6 mo, im TU increased T and free- T levels (p<0.0001), and improved metabolic parameters [reduction in Homeostasis Model Assessment (HOMA) index, p<0.0001; waist circumference and fat mass, p<0.001, respectively], in International Index of Erectile Function-5 and Aging Males' Symptoms scores (p<0.01, respectively). After 12 months, im TU produced further increases in T and free- T levels (p<0.0001) and metabolic parameters (reduction in HOMA-index, p<0.0001; waist circumference p<0.0001; fat mass, p<0.001). No major adverse event due to T treatment occurred. CONCLUSIONS: Clinical efficacy of T replacement therapy in hypogonadal men with MS is reached when its plasmatic levels approach into the medium-high range of normality (>5 ng/ml), although subjective threshold values may be different. Administration of im TU was more effective than oral TU to reach the target for T levels and to improve MS parameters. TU was safe over 12 months and discontinuation rates were similar to placebo.

[Ultrasonographic assessment of erectile function after oral administration of sildenafil citrate in normal men].

OBJECTIVE: To investigate the ultrasonographic indexes in the evaluation of complete penile erection after oral administration of sildenafil citrate in men with normal erectile function. METHODS: The subjects lay supine, with the penis raised upwards, its back clinging to the abdomen. The probe was placed at the base of the ventral side of the penis for longitudinal and transverse section scanning. Observations were made on the corpus cavernosum, deep artery and deep dorsal vein of the penis at the time of flaccidity and complete erection after oral administration of sildenafil citrate, respectively. RESULTS: The examinations were acceptable to all the subjects both physically and psychologically, and all were completed successfully with no complications. Compared with the flaccid state of the penis, obvious changes were observed in the state of complete erection, including marked increases in the diameter of the corpus cavernosum ([18.57 +/- 2.50] mm, increased by [106.8 +/- 62.1]%), the inside diameter of the deep artery ([1.18 +/- 0.26] mm, increased by [54.9 +/- 29.0]%), the peak systolic velocity ([32.5 +/- 10.7] cm/s, increased by [209.3 +/- 112.9]%), and the systolic acceleration ([5.71 +/- 2.71] cm/s2, increased by [179.3 +/- 138.2]%). CONCLUSION: Oral administration of sildenafil citrate followed by ultrasonography is a new approach to the objective evaluation of penile erection, characterized by convenience, safety, non-invasiveness, non-complication, easy acceptability and easy clinical application.

The erection hardness score and its relationship to successful sexual intercourse.

INTRODUCTION: The Erection Hardness Score (EHS), recently validated, was developed in 1998 as a simple (one-item) method to quantify erection outcome data. Although it is intuitive that erection hardness and successful sexual intercourse (SSI) are related, the link has not been directly established. OBJECTIVE: To evaluate the relationship between erection hardness (assessed by EHS) and SSI, establishing the EHS as a clinically useful tool. METHODS: The data set (N = 307) was from a multinational, double-blind, placebo-controlled trial (with open-label extension) of sildenafil citrate in men with erectile dysfunction. MAIN OUTCOME MEASURES: Event-based modeling used every intercourse attempt and the EHS to estimate the odds ratio of SSI between adjacent EHS categories. Mean-based modeling used mean EHS per patient to determine its relationship to percentage of SSI. Mediation-based modeling used mean EHS and mean percentage of SSI over the double-blind phase to estimate the direct effect of sildenafil treatment on SSI and the indirect effect of sildenafil treatment on SSI via erection hardness. RESULTS: The odds of SSI for EHS 3 (hard enough for penetration but not completely hard) were 41.9 times (95% confidence interval [CI], 33.0-53.2; P < 0.0001) that for EHS 2 (hard but not hard enough for penetration), and the odds of SSI for EHS 4 (completely hard and fully rigid) were 23.7 times (95% CI, 19.5-28.9; P < 0.0001) that for EHS 3. The percentage of SSI increased approximately curvilinearly with the increase in mean EHS, from almost 60% at EHS 3 to 78.5% at EHS 3.5 and to 93.1% at EHS 4. The indirect effect of sildenafil treatment on SSI via erection hardness accounted for almost 90% of the total effect on SSI (P < 0.0001). CONCLUSION: The close and direct relationship between erection hardness and SSI supports the broader use of the EHS-a simple, valid, reliable, and responsive measure-in clinical practice.

Assessment of comparative treatment satisfaction with sildenafil citrate and penile injection therapy in patients responding to both.

OBJECTIVE: To survey patient satisfaction, using validated questionnaires, in a group of men with erectile dysfunction who had used and responded to both sildenafil citrate and intracavernosal injection (ICI) therapy. PATIENTS AND METHODS: In all, 300 patients on ICI therapy were mailed questionnaire packets containing a survey enquiring about the patients' medical history, and two sets of the International Index of Erectile Function (IIEF) and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) sexual function surveys. If patients were using sildenafil alternating with ICI they were asked to complete the IIEF and EDITS questionnaires for each therapy. To identify only patients who had an adequate response to each agent, a score of >/=22 on the EF domain of the IIEF for sildenafil and ICI was required for inclusion in the final analysis. RESULTS: In all, 178 packets were evaluable; 123 men (69%) responded to ICI but not sildenafil, and 11 (6%) responded only to sildenafil and not ICI, leaving 37 patients who responded to both; these patients comprised the study population. There was no difference in EF domain score of the IIEF between the treatments; EDITS scores were significantly higher for ICI therapy than for sildenafil (P < 0.001). CONCLUSIONS: In patients who alternate the use of sildenafil and ICI therapy, satisfaction appears to be higher with ICI, although the erectogenic performance is similar. This suggests that patient satisfaction does not depend solely on erection performance, and that patients might benefit from various treatment options.

Clinical and duplex US assessment of effects of sildenafil on cavernosal arteries of the penis: comparison with intracavernosal injection of vasoactive agents--initial experience.

PURPOSE: To prospectively evaluate the clinical response and hemodynamic changes in cavernosal arteries after oral administration of sildenafil without and with audiovisual sexual stimulation and to compare those responses with responses from intracavernosal injections of vasoactive agents. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. Thirteen consecutive patients (age range, 22-77 years; mean, 60.4 years) with erectile dysfunction were evaluated with clinical assessment and cavernosal duplex ultrasonography (US). The patients were examined at two sessions 3 weeks apart. First, each patient received 100 mg of sildenafil citrate orally and was examined 60 minutes later without any sexual stimulation. Each patient then underwent repeat clinical and duplex US assessment after audiovisual sexual stimulation. Three weeks later, the patients underwent identical clinical evaluation and duplex US after intracavernosal injection of a commercially available combination of papaverine, prostaglandin E1, and phentolamine. Clinical and duplex US data (ie, peak systolic velocity [PSV]) were examined by using the Wilcoxon signed rank test for matched pairs. RESULTS: At rest, the overall mean cavernosal artery PSV was 1.08 cm/sec and remained unchanged after intake of sildenafil without any audiovisual stimulation, with no clinical evidence of erection. With the addition of audiovisual sexual stimulation, eight (62%) of 13 patients had penile congestion or erection, and six (46%) had a PSV greater than 25 cm/sec. With intracavernosal injection of the combination of three drugs, all 13 patients achieved congestion or erection, and 10 (77%) had a PSV greater than 25 cm/sec. Both clinical and duplex US responses to intracavernosal injection were significantly greater than they were to sildenafil with audiovisual sexual stimulation (P = .04 and .003, respectively). CONCLUSION: Oral sildenafil with audiovisual sexual stimulation led to a significant clinical response and increment in blood flow in the cavernosal arteries. However, more patients responded to intracavernosal injection of the combination of three drugs than to sildenafil, and the clinical response was significantly better.