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The article presents abstracts related to pharmacology including an evaluation of the dose-related efficacy and safety of intranasal bremelanotide, a study on the efficacy and safety of orally inhaled apomorphine (VR004) in the treatment of erectile dysfunction, and a classification and regression tree analyses in 3,488 tadalafil-treated men with erectile dysfunction.

Benign prostatic hyperplasia (BPH) and sexual dysfunction are both features of ageing. In recent years there has been considerable research into the question of whether there is any direct pathophysiological relationship between the two conditions. This research seems to suggest a relationship between lower urinary tract symptoms (which are commonly due to BPH) and erectile dysfunction, although the mechanism is unclear. What is clear is that any therapy for BPH will have an effect upon differing aspects of sexual dysfunction. Traditional surgery (Transurethral prostatectomy) will cause retrograde ejaculation and may cause erectile dysfunction, while the different drugs used to treat BPH have varying effects. [ABSTRACT FROM AUTHOR]

Vardenafil is a new phosphodiesterase type-5 inhibitor for the treatment of men with erectile dysfunction (ED). It was licensed in Europe in spring 2003 and in the USA in late 2003. It is a potent and selective inhibitor of the enzyme phosphodiesterase type 5, and in the presence of an erectile stimulus potentiates the intracellular actions of cyclic guanylate monophosphate. Several large, placebo-controlled trials have demonstrated efficacy both in the broad population of men with ED and in men with more difficult to treat ED. It is well tolerated with a side effect profile typical of this class of drugs. It has a rapid onset of action and has demonstrable efficacy for men using the medication for up to 2 years. [ABSTRACT FROM AUTHOR]

Two papers in this section deal with well-known pharmacological agents used to treat male erectile dysfunction. In the first of these, authors from the UK compared the efficacy and safety of sildenafil and apomorphine in such patients. This open-label crossover trial suggested that sildenafil was better than apomorphine, where the primary endpoint was the erectile function domain of the International Index of Erectile Function. The second paper is an update on the efficacy and safety of tadalafil. It describes the results of its use in a large number of men with erectile dysfunction, compared to placebo. Once again, the erectile function domain was one of the primary endpoints. Tadalafil was an effective and well tolerated treatment for this condition. To compare the efficacy and safety of sildenafil and apomorphine in the treatment of men with erectile dysfunction (ED). In all, 139 men with ED who were naïve to treatment were entered into an open-label crossover trial with two treatment periods, each of 8 weeks, separated by a 2-week washout period. Men were randomized to receive either sildenafil then apomorphine or apomorphine then sildenafil, and were allowed to titrate the dose on both drugs. The primary endpoint was the erectile function (EF) domain of the International Index of Erectile Function (IIEF), and other endpoints included diary data, the other domains of the IIEF, overall assessment questions and the Erectile Dysfunction Index of Treatment Satisfaction (EDITS) questionnaire. The EF domain score after treatment was 25.2 for sildenafil and 15.9 for apomorphine. The treatment difference of the adjusted means was 9.3 points (95% confidence interval 7.6–11.1; P < 0.001). After sildenafil the successful intercourse rate was 75%, vs 35% for apomorphine ( P < 0.001), and the EDITS scores were 82.5 for sildenafil and 46.8 for apomorphine ( P < 0.001). Of the men, 96% expressed a preference for sildenafil as a treatment for their ED. The side-effect profiles for both drugs were in keeping with published data. By all measurable endpoints sildenafil was superior to apomorphine in this open-label crossover study of men with ED who were naïve to therapy [ABSTRACT FROM AUTHOR]

To provide an update on the efficacy and safety of tadalafil, a phosphodiesterase-5 inhibitor, in the treatment of erectile dysfunction (ED). In all, 2102 men (mean age 56 years) with mild-to-severe ED of various causes were randomized to placebo or tadalafil, taken as needed with no food restrictions, at fixed ‘on-demand’ doses of 10 or 20 mg in 11 randomized, double-blind, placebo-controlled trials lasting 12 weeks. The three co-primary outcomes were changes from baseline in the erectile function domain of the International Index of Erectile Function (IIEF) and the proportion of ‘yes’ responses to questions 2 and 3 of the Sexual Encounter Profile (SEP). Additional efficacy instruments included a Global Assessment Question (GAQ). Compared with placebo, tadalafil gave significantly better outcomes. Patients receiving either dose of tadalafil had a significant mean improvement of 6.5 and 8.6, respectively, in the IIEF erectile function domain score from baseline ( P < 0.001 vs placebo). At both doses the mean success rate for intercourse attempts (SEP-Q3) was 58% and 68%, respectively, compared with 31% in the placebo group ( P < 0.001), and 71% and 84% reported improved erections at the endpoint (GAQ), vs 33% on placebo ( P < 0.001). Tadalafil was effective up to 36 h after dosing and was effective regardless of disease severity and causes, and in patients of all ages. The most frequent adverse events were headache, dyspepsia, back pain and myalgia. Tadalafil was an effective and well-tolerated treatment for ED. [ABSTRACT FROM AUTHOR]

The first study in this section was conducted to give a better understanding of the sexual habits of men and women over 40 years old in the UK. This large population-based study has provided the first report on the frequency and timing of sexual activity in British men and women; it also suggested that there were subtle differences in attitudes between men and women. To obtain a greater understanding of sexual behaviour and habits among men with and without erectile dysfunction (ED), and their female partners, to improve the management of ED in heterosexual men. A population-based study was conducted amongst men and women aged > 40 years. None of the subjects were partners in the same sexual relationship. Interviews were conducted on the Internet via a panel-based questionnaire. In all, 225 (32%) men had self-reported ED and 88 (26%) women reported that their partner had ED. For all men (with or without ED) the mean time from first thinking of intercourse to beginning intercourse was just under 1 h. During their most recent period of sexual activity, 87% of men with and 78% of men without ED had intercourse with ejaculation at most once within 24 h; 81% of men and 89% of women felt that it was neither very nor extremely important to have intercourse with ejaculation more than once in a 24-h period. This study reports for the first time the frequency of sexual activity in British men and women in heterosexual relationships, and describes the usual timings of sexual events. Few significant differences were identified between men with or with no ED. [ABSTRACT FROM AUTHOR]

Background: Erectile dysfunction is a common, multi-factorial disorder.Aims: To evaluate the efficacy, tolerability and frequency of use of sildenafil citrate in men with mild to moderate erectile dysfunction of no established organic cause.Method: This double-blind, randomised, placebo-controlled, flexible-dose, two-way crossover study was conducted at four centres in the UK in 44 men with mild to moderate erectile dysfunction of no clinically obvious organic cause. The study included two 28-day treatment periods, during which time sildenafil or placebo (25-75 mg, based on efficacy) was taken as required.Results: Compared with placebo, sildenafil was associated with increases in frequency of use, erections adequate for sexual intercourse and level of sexual satisfaction (P:<0.0001). More patients receiving sildenafil stated they would use the treatment again compared with those receiving placebo (P:<0.0001). There were no discontinuations due to sildenafil treatment.Conclusions: Sildenafil is effective and well tolerated in men with mild to moderate erectile dysfunction of no clinically identifiable organic cause. [ABSTRACT FROM AUTHOR]

Objective To examine nitric-oxide (NO)-mediated relaxation in cavernosal smooth muscle in a rat model of diabetes, as previous experiments showed that HbA1c (an isoform of glycosylated haemoglobin and a marker of long-term diabetic control) impaired NO-mediated relaxation of normal corpus cavernosal tissue through the generation of superoxide anions. Materials and methods Eight weeks after the induction of diabetes, male Wistar rats were killed and cavernosal tissue obtained. Strips were contracted with 1 µmol/L noradrenaline before applying acetylcholine or electrical field stimulation (EFS) or sodium nitroprusside (SNP). Relaxation responses were repeated in the presence of l-arginine (100 µmol/L), indomethacin (10 µmol/L) or superoxide dismutase (SOD, 120 IU/mL). Young and age-matched control animals were examined in the same way. Results Eight weeks of uncontrolled diabetes caused a significant impairment in mean relaxation responses to acetylcholine (P < 0.05) and to EFS (P < 0.05), but not to SNP, compared with young and age-matched controls, respectively. l-arginine, indomethacin and SOD had no significant effect on this impairment. Ageing caused a lesser but significant impairment in EFS-mediated cavernosal smooth muscle relaxation (P < 0.05). Conclusion Diabetes impairs endothelial and neuronal NO-mediated cavernosal smooth muscle relaxation in rats in vitro. This effect is not mediated by an alteration in the intracellular action of NO, the availability of NO, superoxide anion inactivation of NO or the generation of constrictor prostanoids. It is possible that cholesterol or advanced glycation end products are responsible for the effect of diabetes on penile smooth function. [ABSTRACT FROM AUTHOR]

Thirty-three impotent men underwent pharmacocavernometry and cavernography. Ten patients had a good clinical response to 60 mg papaverine, nine had a moderate clinical response and in 14, the response was judged to be a poor one. Twelve patients had evidence of abnormal venous leakage from the corpora. Subsequent investigation with isotope phallography showed six patients to have arterial insufficiency and in three of these patients this was amenable to reconstructive vascular surgery. We conclude that pharmacocavernometry provides a useful, cheap and reliable method for the investigation of impotent men which may be performed on an outpatient basis. [ABSTRACT FROM AUTHOR]

Objectives: Erectile dysfunction (ED) represents a shared sexual concern for couples. Despite the availability of highly effective therapies for ED, many men do not seek or utilize treatment. The Female Experience of Men''s Attitudes to Life Events and Sexuality (FEMALES) study explored women''s perceptions, beliefs and attitudes regarding their partner''s ED, and investigated whether these factors are associated with the likelihood of men seeking medical advice and using phosphodiesterase type-5 (PDE-5) inhibitor treatment. Design and method: Questionnaires were sent to partners of men with ED who participated in the Men''s Attitudes to Life Events and Sexuality (MALES) 2004 study, and who consented to their partner''s involvement. FEMALES questionnaire responses were analysed in relation to responses to equivalent questions provided by male study participants. Results: There were significant associations between the woman''s belief that her partner''s ED was permanent and men''s treatment-seeking behaviour (Chi-square=86.43; p<0.0001) and PDE-5 inhibitor use (Chi-square=18.79; p=0.001); and the woman''s perception that her partner''s ED was more severe and men''s treatment seeking (Chi-square=92.84, p<0.0001) and PDE-5 inhibitor use (Chi-square=23.80, p=0.001). Significant associations were also observed between men''s treatment-seeking and PDE-5 inhibitor utilisation and women''s perceptions, beliefs and attitudes relating to various other aspects of ED. Conclusions: This study highlights the importance of the female partner''s attitudes to ED in the treatment-seeking behaviour and PDE-5 inhibitor utilisation of the male partner. [Copyright &y& Elsevier]

Objectives: Erectile dysfunction (ED) impacts greatly on men and their female partners. The Female Experience of Men''s Attitudes to Life Events and Sexuality (FEMALES) study assessed levels of concordance or divergence among couple members’perceptions of the specific functional impairments characterising the male partner''s ED, and their attitudes, beliefs and experiences relating to ED. Design and method: Questionnaires were sent to partners of men with ED who participated in the Men''s Attitudes to Life Events and Sexuality (MALES) 2004 study, and who consented to their partner''s involvement. FEMALES questionnaire responses were analysed in relation to responses to equivalent questions provided by male study participants. Results: Women''s perceptions of the specific functional impairments characterising their partner''s ED and the frequency of his erection difficulty were highly associated with assessments by the man. Significant associations were observed between couple members’responses regarding their attitudes, beliefs and experiences relating to ED. A number of sex-specific findings were highlighted, where couple members held divergent views on the effect of ED on the couples’everyday and sexual life. Conclusions: A high degree of concordance in couple member''s perceptions of the male partner''s ED, and their attitudes and beliefs about ED was observed. However, a number of differences between males’and females’perceptions and attitudes were evident. Instances of discordance may be significant for the couple, and may contribute to treatment avoidance or conflict. [Copyright &y& Elsevier]

Presents various studies related to impotence. Enhancement of force generation by corpus cavernosum smooth muscle in rabbits with partial bladder outlet obstruction; Immunohistochemical identification and localization of advanced glycation endproducts in the penis; Histopathological effects of sildenafil on corpus cavernosum in rat.