- Email: [email protected]
The Long-Term Safety of Alprostadil (Prostaglandin-E1) in Patients With Erectile Dysfunction
628
SEXUAL FUNCTION AND DYSFUNCTION
3 and 6 months, the penises were excised and the corpus cavernosum processed for the study of PGI,, NO, CAMP and cGMP formation, using a range of stimulators and radioimmunoassays. Results PGI, formation in response to acetylcholine and phorbol ester, but not arachidonate, and cGMP formation in response to A23187 (NO-release dependent), was significantly diminished in diabetic rabbit corpus cavernosum compared with controls at both 3 and 6 months after the induction of DM. CAMP formation in response to forskolin and prostaglandin El was reduced after 6 but not 3 months, although nitroprusside-stimulated cGMP (activates guanylyl cyclase directly) was unaffected in cavernosal tissue from diabetic rabbits. Conclusions These results show that the formation of NO and PGI,, and adenylyl cyclase activity but not guanylyl cyclase, are impaired in the corpus cavernosum of diabetic rabbits. As NO and PGI, are produced by the endothelium, these studies consolidate the view that endothelial dysfunction is a major contributor to erectile dysfunction in diabetes mellitus.
Editorial Comment: Endothelial cell dysfunction leading to functional impairment occurs in a variety of disorders, such as hypertension, hypercholesterolemia and diabetes, and with cigarette smoking and aging. The mechanisms underlying the dysfunction are thought to be multifactorial. The arginindnitric oxide synthase system has been studied the most. Alterations in substrate (L-arginine) transportation and availability, level of nitric oxide synthase expression, nitric oxide signaling, tetrahydrobiopterin availability and reactive oxygen species are some of the proposed mechanisms involving the arginindnitric oxide synthase system. In this s t u d y of penile erectile tissue from rabbits with alloxan induced diabetes the production of prostacyclin and nitric oxide, and the activity of adenylate cyclase, but not the activity of guanylate cyclase, were significantly decreased, which reconfirms the importance of endothelial cells in erectile dysfunction. Others have also reported alterations of neuronal nitric oxide synthase and smooth muscle cells in experimental diabetic animals. Further studies are needed to unravel the multiple mechanisms involved to plot better strategies f o r the prevention and cure of erectile dysfunction associated with diabetes mellitus. Tom F. Lue, M.D. The Long-Term Safety of Alprostadil (Prostaglandin-El)in Patients With Erectile Dysfunction
THE EUROPEAN ALPROSTADILSTUDY GROUP Brit. J. Urol., 8 2 538-543, 1998 Objective To evaluate the long-term safety and efficacy of intracavernosal alprostadil (prostaglandin El, PGE,) in patients with erectile dysfunction (ED) and assess the feasibility of self-injection treatment. Patients and methods The study included 848 men (aged 18-75 years) with ED of 2 4 months’ duration. The initial home-use dose of alprostadil, defined as a dose producing an erection satisfactory for intercourse and lasting for ’-20 min, was determined for each patient in the investigator’s clinic and in the patient’s home. This dose-finding phase was followed by a 6-month, self-injection, home-maintenance phase. The efficacy and adverse effects were documented. Results An initial home-use dose was determined for 93% of the patients and in most (86%) it was ~ 2 0 pg. During the 6-month study period, 88% of injections assessed by the patients resulted in satisfactory sexual activity (intercourse or masturbation) and 90% of injections assessed by partners resulted in satisfactory intercourse. Penile pain occurred in 44% of patients, but this incidence decreased with time. In 52% of patients with pain it was mild and only 3% of patients discontinued the study because of pain. Prolonged erection and priapism occurred in 8% and 0.9% of patients, respectively. Penile fibrosis occurred in 4% of patients. Drug-related systemic medical events occurred in 5% of patients and none of these were serious. Haemodynamic events occurred in (1% of patients and were not considered to be clinically relevant. Conclusion Intracavernosal alprostadil is an effective and safe therapy for ED, provided that the individual dose is established by titration, patients are trained in the self-injection technique and supervised periodically. Intracavernous Self-Injection of Prostaglandin E l in the Treatment of Erectile Dysfunction
P. KUNELIUS AND 0. LUKXARINEN, Urological Unit, Surgical Clinic, University of Oulo, Oulu, Finland Int. J. Impotence Res., 11: 21-24, 1999 In a three-year follow-up study of 69 patients found that erectile dysfunction (ED) impairs many elderly men’s life: up to 25% of the men aged 65 y and 80% of those aged 75 y suffer from erectile dysfunction. The most effective non-surgical treatment of ED is intracavernosal pharmacotherapy, and the most common vasoactive agent currently used is prostaglandin E l (PGE1). The purpose of this study was to assess the long-term outcome of PGEl treatment and the patients’ overall satisfaction with their sexual life. Sixty-nine patients who had started ICI therapy three years earlier were invited to a control examination. The mean age of the patients was 60.5 y. The patients filled in a questionnaire, which included questions about the use of PGEl treatment at home. All the patients evaluated their own satisfaction with their erection, ejacula-
SEXUAL FUNCTION AND DYSFUNCTION
3 and 6 months, the penises were excised and the corpus cavernosum processed for the study of PGI,, NO, CAMP and cGMP formation, using a range of stimulators and radioimmunoassays. Results PGI, formation in response to acetylcholine and phorbol ester, but not arachidonate, and cGMP formation in response to A23187 (NO-release dependent), was significantly diminished in diabetic rabbit corpus cavernosum compared with controls at both 3 and 6 months after the induction of DM. CAMP formation in response to forskolin and prostaglandin El was reduced after 6 but not 3 months, although nitroprusside-stimulated cGMP (activates guanylyl cyclase directly) was unaffected in cavernosal tissue from diabetic rabbits. Conclusions These results show that the formation of NO and PGI,, and adenylyl cyclase activity but not guanylyl cyclase, are impaired in the corpus cavernosum of diabetic rabbits. As NO and PGI, are produced by the endothelium, these studies consolidate the view that endothelial dysfunction is a major contributor to erectile dysfunction in diabetes mellitus.
Editorial Comment: Endothelial cell dysfunction leading to functional impairment occurs in a variety of disorders, such as hypertension, hypercholesterolemia and diabetes, and with cigarette smoking and aging. The mechanisms underlying the dysfunction are thought to be multifactorial. The arginindnitric oxide synthase system has been studied the most. Alterations in substrate (L-arginine) transportation and availability, level of nitric oxide synthase expression, nitric oxide signaling, tetrahydrobiopterin availability and reactive oxygen species are some of the proposed mechanisms involving the arginindnitric oxide synthase system. In this s t u d y of penile erectile tissue from rabbits with alloxan induced diabetes the production of prostacyclin and nitric oxide, and the activity of adenylate cyclase, but not the activity of guanylate cyclase, were significantly decreased, which reconfirms the importance of endothelial cells in erectile dysfunction. Others have also reported alterations of neuronal nitric oxide synthase and smooth muscle cells in experimental diabetic animals. Further studies are needed to unravel the multiple mechanisms involved to plot better strategies f o r the prevention and cure of erectile dysfunction associated with diabetes mellitus. Tom F. Lue, M.D. The Long-Term Safety of Alprostadil (Prostaglandin-El)in Patients With Erectile Dysfunction
THE EUROPEAN ALPROSTADILSTUDY GROUP Brit. J. Urol., 8 2 538-543, 1998 Objective To evaluate the long-term safety and efficacy of intracavernosal alprostadil (prostaglandin El, PGE,) in patients with erectile dysfunction (ED) and assess the feasibility of self-injection treatment. Patients and methods The study included 848 men (aged 18-75 years) with ED of 2 4 months’ duration. The initial home-use dose of alprostadil, defined as a dose producing an erection satisfactory for intercourse and lasting for ’-20 min, was determined for each patient in the investigator’s clinic and in the patient’s home. This dose-finding phase was followed by a 6-month, self-injection, home-maintenance phase. The efficacy and adverse effects were documented. Results An initial home-use dose was determined for 93% of the patients and in most (86%) it was ~ 2 0 pg. During the 6-month study period, 88% of injections assessed by the patients resulted in satisfactory sexual activity (intercourse or masturbation) and 90% of injections assessed by partners resulted in satisfactory intercourse. Penile pain occurred in 44% of patients, but this incidence decreased with time. In 52% of patients with pain it was mild and only 3% of patients discontinued the study because of pain. Prolonged erection and priapism occurred in 8% and 0.9% of patients, respectively. Penile fibrosis occurred in 4% of patients. Drug-related systemic medical events occurred in 5% of patients and none of these were serious. Haemodynamic events occurred in (1% of patients and were not considered to be clinically relevant. Conclusion Intracavernosal alprostadil is an effective and safe therapy for ED, provided that the individual dose is established by titration, patients are trained in the self-injection technique and supervised periodically. Intracavernous Self-Injection of Prostaglandin E l in the Treatment of Erectile Dysfunction
P. KUNELIUS AND 0. LUKXARINEN, Urological Unit, Surgical Clinic, University of Oulo, Oulu, Finland Int. J. Impotence Res., 11: 21-24, 1999 In a three-year follow-up study of 69 patients found that erectile dysfunction (ED) impairs many elderly men’s life: up to 25% of the men aged 65 y and 80% of those aged 75 y suffer from erectile dysfunction. The most effective non-surgical treatment of ED is intracavernosal pharmacotherapy, and the most common vasoactive agent currently used is prostaglandin E l (PGE1). The purpose of this study was to assess the long-term outcome of PGEl treatment and the patients’ overall satisfaction with their sexual life. Sixty-nine patients who had started ICI therapy three years earlier were invited to a control examination. The mean age of the patients was 60.5 y. The patients filled in a questionnaire, which included questions about the use of PGEl treatment at home. All the patients evaluated their own satisfaction with their erection, ejacula-