The mechanism of action of the phosphodiesterase type 5 (PDE5) inhibitors (i.e., sildenafil, tadalafil, and vardenafil) involves inhibition of the PDE5 isoenzyme located in penile vascular smooth muscle cells. Sexual stimulation triggers the release of nitric oxide (NO), stimulating the release of guanylyl cyclase, leading to an increase in intracellular cyclic guanosine monophosphate (cGMP) concentrations, a decrease in intracellular calcium, and ultimately relaxation of the vascular smooth muscle in the corpus cavernosum and penile erection. The PDE5 inhibitors have no effect on the penis in the absence of sexual stimulation. Although the various PDE5 inhibitors differ with respect to selectivity and pharmacokinetic profiles, efficacy and safety of these agents are comparable in broad populations of men with erectile dysfunction (ED), including those with diabetes or those taking multiple antihypertensive agents. The most frequently reported adverse events of the PDE5 inhibitors are related to their mild vasodilatory effects and include headache, flushing, dyspepsia, and nasal congestion or rhinitis. Side effects are generally reversible and tend to diminish during continued treatment. Differences in pharmacokinetic properties among the PDE5 inhibitors include the fact that sildenafil and vardenafil have a shorter duration of action (approximately 4 h) compared with the longer period of responsiveness observed with tadalafil (up to 36 h). In addition, in the presence of high-fat food, absorption of sildenafil and vardenafil may be delayed; however, the rate and extent of tadalafil absorption are unaffected by high-fat food.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2004

Priapism.

Priapism is a relatively uncommon condition that may present as a medical emergency associated with significant pain and anxiety in the veno-occlusive or low-flow variant. Pharmacologic advances and, specifically, the availability of intracavemosal alpha-agonist therapy have dramatically improved the prospects of resolution for patients with low-flow priapism presenting within the first few hours of the acute episode. High-flow priapism is not considered an emergency and treatment measures are typically conservative aimed at preservation of potency. Urologists, radiologists, and other health care personnel caring for the patient with priapism must be familiar with various etiologic factors implicated in low-flow and high-flow priapism to formulate a logical step-care approach. Differentiation of the low-flow from the high-flow state is perhaps the most critical initial diagnostic challenge that determines the sequence of further interventions including surgical shunts in low-flow priapism refractory to medical therapy.

Adult↗

PubMed2004

Male Sexual Health Questionnaire (MSHQ): scale development and psychometric validation.

OBJECTIVES: To validate a new, self-administered questionnaire for assessing key domains of sexual function and satisfaction in aging men with urogenital health concerns. METHODS: The initial items were identified by patient interviews, review of current reports, and expert panel solicitation. The resulting 25-item questionnaire was subjected to psychometric evaluation and refinement using two discriminant validity studies in aging men with urogenital symptoms compared with age-matched controls. Psychometric tests of reliability, discriminant, and criterion validity were performed. RESULTS: Qualitative testing revealed adequate comprehension and content validity of the initial item set. Two domains of sexual function (ejaculation, erection) were identified in the first discriminant validity study, each of which showed a high degree of internal consistency (alpha = 0.81 and alpha = 0.90, respectively) and test-retest reliability (r = 0.86 and r = 0.87, respectively). Both sexual function domains discriminated well between men with and without urogenital manifestations of lower urinary tract symptoms (LUTS) and sexual dysfunction (P <0.001). An additional domain of sexual satisfaction was added in the second validation study, with similarly high internal consistency (alpha = 0.90) and test-retest reliability (r = 0.88). Tests of convergent and divergent validity, including correlations with standardized scales for depression (Center for Epidemiologic Studies-Depressed Mood Scale), sexual function (International Index of Erectile Function), and life satisfaction (Fugl-Meyer), confirmed the criterion validity of the new measure. CONCLUSIONS: The Male Sexual Health Questionnaire assesses sexual function and satisfaction in older men with urogenital symptoms of LUTS and sexual dysfunction. This new instrument has excellent psychometric properties and is well suited for use in clinical and research settings.

Age Factors↗

PubMed2004

Erectile dysfunction: etiology, evaluation, and treatment options.

The evaluation and treatment of male sexual dysfunction has evolved into a more extensive evaluation. This new evaluation should now include evaluation of hypogonadism, ejaculatory function, lower urinary tract symptoms, and depression. The evaluation may be readily accomplished with the use of questionnaires. The management of these entities is discussed, including the novel phosphodiesterase-5 for male erectile dysfunction. Inclusion of the partner in the evaluation and management scheme will provide added benefit and may produce a better outcome.

Depression↗

PubMed2004

Benign intrascrotal lesions.

PURPOSE: We summarize important clinical, pathological and diagnostic features of benign intrascrotal lesions, including paratesticular lesions (adenomatoid tumors, fibrous pseudotumors, cystadenomas, spermatoceles, hydroceles, varicoceles and hernias) and intratesticular lesions (tunica albuginea cysts, testicular simple cysts, epidermoid cysts, cystic ectasia of the rete testis, intratesticular varicocele, adrenal rest tumors and splenogonadal fusion). This review provides the reader with a better understanding of benign lesions that occur in the scrotum. MATERIALS AND METHODS: A directed MEDLINE literature review of benign scrotal lesions and of each individual lesion was performed. This information was enhanced with relevant information from select journals and texts. Particular emphasis was placed on clinical, pathological and diagnostic features. RESULTS: Intrascrotal lesions continue to provide a diagnostic challenge for physicians. A diagnosis can be made with a thorough history, physical examination and understanding of the pathophysiological processes of the structures contained within the scrotum. Lesions that are suspicious for malignancy should prompt urological consultation and radiological imaging. Ultrasound aids in the diagnosis in instances of uncertainty. Ultimately surgery may be necessary to make a histological diagnosis. CONCLUSIONS: Clinical assessment, physical examination and an understanding of benign intrascrotal processes are key to making a diagnosis. Ultrasound has an important role and adds essential information. If surgery is necessary and a benign process is recognized, a testis sparing procedure should be performed.

Adenomatoid Tumor↗

PubMed2004

The prevalence of hypertension, hyperlipidemia, diabetes mellitus and depression in men with erectile dysfunction.

PURPOSE: We quantified the prevalence of diagnosed hypertension, hyperlipidemia, diabetes mellitus and depression in male health plan members with erectile dysfunction (ED). MATERIALS AND METHODS: We used a nationally representative managed care claims database that covered 51 health plans with 28 million lives for 1995 through 2002. Based on 272325 identified patients with ED population and age specific prevalence rates were calculated for the same period. RESULTS: The crude population prevalence rates were 41.6% for hypertension, 42.4% for hyperlipidemia, 20.2% for diabetes mellitus, 11.1% for depression, 23.9% for hypertension and hyperlipidemia, 12.8% for hypertension and diabetes mellitus, and 11.5% for hyperlipidemia and depression. The crude age specific prevalence rates varied across age groups significantly for hypertension (4.5% to 68.4%), hyperlipidemia (3.9% to 52.3%), and diabetes mellitus (2.8% to 28.7%), and significantly less for depression (5.8% to 15.0%). Region adjusted population prevalence rates were 41.2% for hypertension, 41.8% for hyperlipidemia, 19.7% for diabetes mellitus and 11.9% for depression. Only 87163 patients with ED (32%) had no comorbid diagnosis of hypertension, hyperlipidemia, diabetes mellitus or depression. CONCLUSION: Hypertension, hyperlipidemia, diabetes mellitus and depression were prevalent in patients with ED. This evidence supported the proposition that ED shares common risk factors with these 4 concurrent conditions. Therefore, as a pathophysiological event, ED could be viewed as a potential observable marker for these concurrent diseases. This finding suggests that clinicians could include ED in the assessment profile of these concurrent conditions for earlier detection and treatment.

Adolescent↗

PubMed2004

The efficacy and safety of tadalafil in United States and Puerto Rican men with erectile dysfunction.

PURPOSE: We evaluate the efficacy and safety of tadalafil, taken as needed, in men with mild to severe erectile dysfunction (ED) and assess sexual intercourse attempt patterns. MATERIALS AND METHODS: In this multicenter, double-blind, placebo controlled, parallel study conducted in the United States and Puerto Rico 207 men with ED were randomized to placebo or 20 mg tadalafil for 12 weeks. The primary efficacy variables were changes from baseline in the mean International Index of Erectile Function erectile function domain score and mean per patient percentage of "yes" responses to Sexual Encounter Profile (SEP) diary questions 2 (successful penetration) and 3 (successful intercourse). The Global Assessment Question was a secondary end point and post hoc analyses on sexual intercourse attempt patterns were conducted. RESULTS: Men treated with tadalafil compared with placebo reported greater mean changes from baseline on the erectile function domain score (9.3 vs 0.3 with placebo, p <0.001) and on the mean per patient percentage of successful penetration (SEP question 2, 31.6% vs 2.3% with placebo, p <0.001) and successful intercourse attempts (SEP question 3, 43.6% vs 3.5% with placebo, p <0.001). The per treatment group percentage of successful intercourse attempts during treatment was higher for tadalafil than placebo (67.6% vs 24.1%, respectively, p <0.001) and most successful intercourse attempts occurred between 4 and 36 hours after taking tadalafil. Of the men treated with tadalafil 82.8% reported improved erections versus 19.6% taking placebo (Global Assessment Question, p <0.001). The most common treatment emergent adverse events were headache (15.7% vs 6.3% with placebo), back pain (8.8% vs 0%), and dyspepsia (7.5% vs 0%). CONCLUSIONS: Tadalafil (20 mg) significantly improved erectile function and patients did not closely temporally link sexual intercourse attempts with taking tadalafil. Tadalafil was also well tolerated in both groups of men with mild to severe ED.

3',5'-Cyclic-GMP Phosphodiesterases↗