- Email: [email protected]
Re: Can Atorvastatin Improve the Response to Sildenafil in Men with Erectile Dysfunction Not Initially Responsive to Sildenafil? Hypothesis and Pilot Trial Results
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european urology 50 (2006) 155–161
interpret because no clear-cut diagnostic criteria are available. The classical Meares-Stamey test is rarely used either by general practitioners or by urologists, even in its simplified form (urine culture after prostatic massage, integrated by a midstream culture if positive). The value of a sperm culture in the definition of bacterial prostatitis is still controversial and no definite cut-off point exists regarding the significance of colony counts. If sperm cultures are routinely performed and if U. urealyticum and C. trachomatis are also considered as causative agents, then the number of cases of CBP will become greater than the conventional 5% figure. It may even become higher if we consider as affected by latent infection all the patients who respond to antibiotic therapy. The
importance of this syndrome is underestimated, if we consider the high number of patients in whom a diagnosis of CP/CPPS is suspected or established. Despite recent advances, it still remains a clinical enigma and treatment remains empirical in most cases.
Re: Can Atorvastatin Improve the Response to Sildenafil in Men with Erectile Dysfunction Not Initially Responsive to Sildenafil? Hypothesis and Pilot Trial Results Herrmann HC, Levine LA, Macaluso J Jr, Walsh M, Bradbury D, Schwartz S, Mohler ER, Kimmel SE
(sildenafil [Viagra; Pfizer], tadalafil [Cialis; Lilly], and vardenafil [Levitra; Bayer]) as first-line symptomatic treatment of men with ED, 30–35% of patients fail to respond [1]. Besides inadequate patient education, incorrect drug usage, drug tolerance. and psychosocial factors, endothelial dysfunction, penile atherosclerosis, and hypogonadism are the most prevalent causes of treatment failure. The latter conditions are all components of the metabolic syndrome, which is a clustering of factors associated with an increased risk for atherosclerotic cardiovascular disease and diabetes. The core ‘‘metabolic risk factors’’ are atherogenic dyslipidaemia, elevated blood pressure, elevated plasma glucose level, a prothrombotic state, and a proinflammatory state. According to current views, there are two major underlying causes of the metabolic syndrome: obesity (especially abdominal obesity) and insulin resistance. Other factors that aggravate the syndrome include physical inactivity, advancing age, hypogonadism, and genetic aberrations [2,3]. To date, it is well recognized that PDE-5 inhibition as first-line treatment for ED should be combined with improvement of comorbid conditions, in this case the metabolic syndrome. There are two potential therapeutic approaches. One strategy is to identify and treat each risk factor separately, unrelated to its clustering with other risk factors (in this study HMGCoA reductase inhibition, in previous studies angiotensin-converting enzyme inhibition [4] or testosterone supplementation [5]). However, there are two drawbacks to the single risk factor approach. First, it can provide a disincentive for lifestyle therapies to treat all risk factors simultaneously, and second, as the metabolic syndrome advances in severity, targeting single risk factors exclusively eventually leads to the problem of polypharmacy. Of great clinical
J Sex Med 2006;3:303–8. Expert’s summary: Herrmann and coworkers tested the hypothesis that men with erectile dysfunction (ED) resistant to a phosphodiesterase 5 (PDE-5) inhibitor (sildenafil) can be rescued with the addition of a 3-hydroxy3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (atorvastatin). They based their hypothesis on the notion that sildenafil ‘‘nonresponders’’ have more severe atherosclerosis and might benefit from a therapy targeted at their underlying vascular disease process. In this regard, the anti-inflammatory effect of HMG-CoA reductase inhibitors is claimed to rapidly improve endothelial function even before lowering apoprotein B-containing lipoproteins. In a placebo-controlled trial, 12 men reporting an inadequate response to a maximal dose (100 mg) of sildenafil received 80 mg atorvastatin daily for a period of 12 weeks. Treatment with atorvastatin improved erectile response to sildenafil in men who did not initially respond to treatment with sildenafil. Furthermore, the study results support the hypothesis that vascular endothelial dysfunction contributes to ED in sildenafil non-responders. Expert’s comments: Although large multicentre clinical trials have shown the efficacy and tolerability of PDE-5 inhibitors
References [1] Egan KJ, et al. Pain 1997;69:213–8. [2] Ku JH, et al. Urology 2005;66:696–701. Michele Pavone Macaluso University of Palermo, Palermo, Italy DOI: 10.1016/j.eururo.2006.04.027
160
european urology 50 (2006) 155–161
importance is the fact that lifestyle change—weight reduction, increased physical activity, and an antiatherogenic diet composition—will improve all of the metabolic risk factors. It has been well demonstrated that if weight can be reduced to desirable levels and if regular exercise can be sustained, all of the risk factors of the syndrome will be improved, and progression to more advanced stages will be slowed. The issue about lifestyle intervention for patients with the metabolic syndrome is not about efficacy of intervention but the level of commitment of society and the medical community to the lifestyle approach. To enhance this commitment, a trial to assess the erectogenic effect of lifestyle intervention in men with ED and the metabolic syndrome should be a priority.
Re: Transobturator Vaginal Tape Inside Out for the Surgical Treatment of Female Stress Urinary Incontinence: Anatomical Considerations Bonnet P, Waltregny D, Reul O, de Leval J J Urol 2005;173:1223–8. Experts’ summary: The cadaver study outlining anatomic considerations of the relatively novel transabdominal vaginal tape inside-out (TVT-O) technique in patients with stress urinary incontinence (SUI) has been published by a group of recognized experts led by de Laval [1,2]. The study was performed on 12 female cadavers, wherein the standard TVT-O procedure was followed by a careful anatomic dissection of pelvic structures to analyse the passage of the tape. The path is well-described using photographs and anatomic sketches. The authors discuss their finding in comparison with those of Delmas et al. [3], a similar study that had been performed to describe the anatomic considerations of the outside-in technique. Experts’ comments: A few questions may arise while reviewing this paper. First, are the anatomic studies on cadavers are actually needed in the development of the new techniques of surgical treatment of SUI? One may argue that such data do not have much clinical relevance, because the new technique has to be validated in randomised clinical trials anyway. Second, do the data obtained from such studies performed on ‘‘healthy’’ cadavers actually represent the deviated anatomy of patients with SUI of various stages? A significant number of patients come to
References [1] [2] [3] [4] [5]
Fagelman E, et al. Urology 2001;57:1141–4. Grundy S, et al. Circulation 2005;112:2735–52. Eckel R, et al. Lancet 2005;365:1415–28. Speel T, et al. J Sex Med 2005;2:207–12. Arver S, et al. J Urol 1996;155:1604–8. Eric J.H. Meuleman Free University Medical Centre, PO Box 7057, 1007 MB Amsterdam E-mail address: [email protected] Tel. +31204440255/+31204440272 Fax: +31206425085.
DOI: 10.1016/j.eururo.2006.04.028
urologic wards following various surgeries on the pelvis or after unsuccessful attempts to correct SUI [4]. Such patients have intrinsically jeopardised tissues with diminished elasticity, local scarring, and intrapelvic adhesions and require additional attention and surgical skills [5]. We do not agree with authors’ positivism regarding the little variability among their subjects as well as relative independence of the outcome from the surgeon’s experience. For research purposes a cohort of patients with high degrees of vaginal prolapse and cystocele could be taken into a single-arm imaging study, where the results of the operation are assessed using computed tomography scanning high-resolution imaging. Overall, up to 30% of all patients with SUI present with cystocele or vaginal prolapse, where normal anatomy of the pelvis is grossly deviated. Such patients require outmost attention. In these situations the TVT-O becomes a surgery of first choice because it allows a skilled surgeon to pass the tape without excessive mobilisation of periurethral tissues. Despite our selective skepticism, we have found this study to be useful, especially in its details of coursing away from vascular and nerve structures. Recent results from a small randomised trial comparing retropubic and transobturator routes were published, suggesting in very little difference in the outcome. Nevertheless, there is a tendency that for larger trials, fewer short- and long-term complications are expected with TVT-O. Although the authors strongly suggest that this operation does not require cystoscopy, we advocate an elective approach. Patients with severe stages of cystocele and prolapse may need direct visualisation of the
european urology 50 (2006) 155–161
interpret because no clear-cut diagnostic criteria are available. The classical Meares-Stamey test is rarely used either by general practitioners or by urologists, even in its simplified form (urine culture after prostatic massage, integrated by a midstream culture if positive). The value of a sperm culture in the definition of bacterial prostatitis is still controversial and no definite cut-off point exists regarding the significance of colony counts. If sperm cultures are routinely performed and if U. urealyticum and C. trachomatis are also considered as causative agents, then the number of cases of CBP will become greater than the conventional 5% figure. It may even become higher if we consider as affected by latent infection all the patients who respond to antibiotic therapy. The
importance of this syndrome is underestimated, if we consider the high number of patients in whom a diagnosis of CP/CPPS is suspected or established. Despite recent advances, it still remains a clinical enigma and treatment remains empirical in most cases.
Re: Can Atorvastatin Improve the Response to Sildenafil in Men with Erectile Dysfunction Not Initially Responsive to Sildenafil? Hypothesis and Pilot Trial Results Herrmann HC, Levine LA, Macaluso J Jr, Walsh M, Bradbury D, Schwartz S, Mohler ER, Kimmel SE
(sildenafil [Viagra; Pfizer], tadalafil [Cialis; Lilly], and vardenafil [Levitra; Bayer]) as first-line symptomatic treatment of men with ED, 30–35% of patients fail to respond [1]. Besides inadequate patient education, incorrect drug usage, drug tolerance. and psychosocial factors, endothelial dysfunction, penile atherosclerosis, and hypogonadism are the most prevalent causes of treatment failure. The latter conditions are all components of the metabolic syndrome, which is a clustering of factors associated with an increased risk for atherosclerotic cardiovascular disease and diabetes. The core ‘‘metabolic risk factors’’ are atherogenic dyslipidaemia, elevated blood pressure, elevated plasma glucose level, a prothrombotic state, and a proinflammatory state. According to current views, there are two major underlying causes of the metabolic syndrome: obesity (especially abdominal obesity) and insulin resistance. Other factors that aggravate the syndrome include physical inactivity, advancing age, hypogonadism, and genetic aberrations [2,3]. To date, it is well recognized that PDE-5 inhibition as first-line treatment for ED should be combined with improvement of comorbid conditions, in this case the metabolic syndrome. There are two potential therapeutic approaches. One strategy is to identify and treat each risk factor separately, unrelated to its clustering with other risk factors (in this study HMGCoA reductase inhibition, in previous studies angiotensin-converting enzyme inhibition [4] or testosterone supplementation [5]). However, there are two drawbacks to the single risk factor approach. First, it can provide a disincentive for lifestyle therapies to treat all risk factors simultaneously, and second, as the metabolic syndrome advances in severity, targeting single risk factors exclusively eventually leads to the problem of polypharmacy. Of great clinical
J Sex Med 2006;3:303–8. Expert’s summary: Herrmann and coworkers tested the hypothesis that men with erectile dysfunction (ED) resistant to a phosphodiesterase 5 (PDE-5) inhibitor (sildenafil) can be rescued with the addition of a 3-hydroxy3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (atorvastatin). They based their hypothesis on the notion that sildenafil ‘‘nonresponders’’ have more severe atherosclerosis and might benefit from a therapy targeted at their underlying vascular disease process. In this regard, the anti-inflammatory effect of HMG-CoA reductase inhibitors is claimed to rapidly improve endothelial function even before lowering apoprotein B-containing lipoproteins. In a placebo-controlled trial, 12 men reporting an inadequate response to a maximal dose (100 mg) of sildenafil received 80 mg atorvastatin daily for a period of 12 weeks. Treatment with atorvastatin improved erectile response to sildenafil in men who did not initially respond to treatment with sildenafil. Furthermore, the study results support the hypothesis that vascular endothelial dysfunction contributes to ED in sildenafil non-responders. Expert’s comments: Although large multicentre clinical trials have shown the efficacy and tolerability of PDE-5 inhibitors
References [1] Egan KJ, et al. Pain 1997;69:213–8. [2] Ku JH, et al. Urology 2005;66:696–701. Michele Pavone Macaluso University of Palermo, Palermo, Italy DOI: 10.1016/j.eururo.2006.04.027
160
european urology 50 (2006) 155–161
importance is the fact that lifestyle change—weight reduction, increased physical activity, and an antiatherogenic diet composition—will improve all of the metabolic risk factors. It has been well demonstrated that if weight can be reduced to desirable levels and if regular exercise can be sustained, all of the risk factors of the syndrome will be improved, and progression to more advanced stages will be slowed. The issue about lifestyle intervention for patients with the metabolic syndrome is not about efficacy of intervention but the level of commitment of society and the medical community to the lifestyle approach. To enhance this commitment, a trial to assess the erectogenic effect of lifestyle intervention in men with ED and the metabolic syndrome should be a priority.
Re: Transobturator Vaginal Tape Inside Out for the Surgical Treatment of Female Stress Urinary Incontinence: Anatomical Considerations Bonnet P, Waltregny D, Reul O, de Leval J J Urol 2005;173:1223–8. Experts’ summary: The cadaver study outlining anatomic considerations of the relatively novel transabdominal vaginal tape inside-out (TVT-O) technique in patients with stress urinary incontinence (SUI) has been published by a group of recognized experts led by de Laval [1,2]. The study was performed on 12 female cadavers, wherein the standard TVT-O procedure was followed by a careful anatomic dissection of pelvic structures to analyse the passage of the tape. The path is well-described using photographs and anatomic sketches. The authors discuss their finding in comparison with those of Delmas et al. [3], a similar study that had been performed to describe the anatomic considerations of the outside-in technique. Experts’ comments: A few questions may arise while reviewing this paper. First, are the anatomic studies on cadavers are actually needed in the development of the new techniques of surgical treatment of SUI? One may argue that such data do not have much clinical relevance, because the new technique has to be validated in randomised clinical trials anyway. Second, do the data obtained from such studies performed on ‘‘healthy’’ cadavers actually represent the deviated anatomy of patients with SUI of various stages? A significant number of patients come to
References [1] [2] [3] [4] [5]
Fagelman E, et al. Urology 2001;57:1141–4. Grundy S, et al. Circulation 2005;112:2735–52. Eckel R, et al. Lancet 2005;365:1415–28. Speel T, et al. J Sex Med 2005;2:207–12. Arver S, et al. J Urol 1996;155:1604–8. Eric J.H. Meuleman Free University Medical Centre, PO Box 7057, 1007 MB Amsterdam E-mail address: [email protected] Tel. +31204440255/+31204440272 Fax: +31206425085.
DOI: 10.1016/j.eururo.2006.04.028
urologic wards following various surgeries on the pelvis or after unsuccessful attempts to correct SUI [4]. Such patients have intrinsically jeopardised tissues with diminished elasticity, local scarring, and intrapelvic adhesions and require additional attention and surgical skills [5]. We do not agree with authors’ positivism regarding the little variability among their subjects as well as relative independence of the outcome from the surgeon’s experience. For research purposes a cohort of patients with high degrees of vaginal prolapse and cystocele could be taken into a single-arm imaging study, where the results of the operation are assessed using computed tomography scanning high-resolution imaging. Overall, up to 30% of all patients with SUI present with cystocele or vaginal prolapse, where normal anatomy of the pelvis is grossly deviated. Such patients require outmost attention. In these situations the TVT-O becomes a surgery of first choice because it allows a skilled surgeon to pass the tape without excessive mobilisation of periurethral tissues. Despite our selective skepticism, we have found this study to be useful, especially in its details of coursing away from vascular and nerve structures. Recent results from a small randomised trial comparing retropubic and transobturator routes were published, suggesting in very little difference in the outcome. Nevertheless, there is a tendency that for larger trials, fewer short- and long-term complications are expected with TVT-O. Although the authors strongly suggest that this operation does not require cystoscopy, we advocate an elective approach. Patients with severe stages of cystocele and prolapse may need direct visualisation of the