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Testosterone therapy in patients with erectile dysfunction: When to start? When to give alone? When to combine? And for how long?
WCMH Abstracts Conclusions: In elderly men with diabetes mellitus 2 the prevalence of SLOH is about 75%, while ED is about 65% and were more common than in population of elderly men without diabetes. The T/LH index was more sensitive in these men as the criteria of diagnosis of SLOH
and ED than total testosterone concentrations. In all the patients with diabetes mellitus the possibility of SLOH and ED should be investigated. In the other hand, elderly men with SLOH also must be screening to exclude the symptoms of diabetes and erectile dysfucntions.
24 The influence of testosteone replacement therapy on erectile dysfunctions in aging men with testosterone deficiency and diabetes mellitus type 2 Micha» Rabijewski, Wojciech Zgliczyn´ski
Micha» Rabijewski Department of Endocrinology, Medical Centre for Postgraduate Education, Warsaw, Poland Wojciech Zgliczyn´ski Department of Endocrinology, Medical Centre for Postgraduate Education, Warsaw, Poland
Objective: The role of testosterone in the anatomy and physiology of erection is becoming clear. Erectile dysfunctions (ED) are very common observed in men with diabetes mellitus type 2 (DM2). The aim of the study was to determine the efficacy of testosterone adminisartions in elderly men with ED and DM2. Material and methods: We investigated 41 men mean aged 65,4 years with late onset hypogonadism according Polish Endocrine Society recommendations and DM2 according ADA recommendations, who had not been treated with PDE5 inhibitors. All men received testosterone enanthate in dose of 200 mg. i.m. every second week. Durations of treatment was mean 12 weeks. Efficacy of treatment was measured by the IIEF domain before and after 4 and 12 weeks of treatment. All of men were treated with oral antidiabetic drugs or insulin. Hypogonadism was expected on the
basis of low testosterone concentration (3.5 mg/L) and the index T/LH 1. Results: After 4 weeks of treatment 21/41 patients showed improvement in erections. At the and of 4 month 32/41 patients showed improvement in the score on IIEF (from 7.9 3.2 to 12.3 3.4; p < 0.05). There were inverted correlations between testosterone levels and efficacy of testosterone treatment and also between duration of DM2 and IIEF score. Conclusions: In elderly men with hypogonadism related to aging (late-onset hypogonadism) and diabetes mellitus 2 after 1 month of testosterone replacement therapy there was a small number of patients in whom treatment results in erectile improvement, but many more patients benefit after 3 months of therapy. Testosterone therapy is time-dependent and combination with PDE5 inhibitors should start only after at least 3-months of monotherapy with testosterone.
25 Testosterone therapy in patients with erectile dysfunction: When to start? When to give alone? When to combine? And for how long? Aksam A. Yassin, Farid Saad, Svetlana Kalenchenko
Aksam A. Yassin Clinic of Urology/ Andrology, Segeberger Kliniken, NorderstedtHamburg, Germany and Department of Urology, Gulf Medical College School of Medicine, Ajman, UAE Farid Saad Bayer Schering AG, Berlin and Research Department Gulf Medical College School of Medicine, Ajman, UAE Svetlana Kalenchenko Institute of Endocrinology, Moscow, Russian Federation
370
Background: The introduction of the phosphodiesterase type 5 inhibitors (PDE 5-inhibitors) has been a step forward in the treatment of erectile dysfunction. The success of the PDE 5inhibitors rendered androgens as treatment for erectile problems in the average patient as something of the past. . . Over the last 15 years the age-related decline of circulating testosterone in men has received serious attention. Moreover, new research has presented convincing evidence that testosterone has profound effects on tissues of the penis involved in the mechanism of erection and that testosterone deficiency impairs the anatomical and physiological substrate of erectile capacity, at least in part reversible upon androgen replacement. There are androgen receptors in the human corpus cavernosum. The expression of nitric oxide (NO) synthesis is regulated by
Vol. 4, No. 3, pp. 357–378, September 2007
androgens. Several studies show that androgen plays a critical role in restoring and maintaining the penile trabecular smooth muscle structure and function as well as regulating the cell apoptosis. Testosterone deficiency induces both biological and structural/functional changes in the trabecular cavernosal tissues. Adipocyte accumulation in penile subtunical area of the corpus cavernosum emphasized the potential mechanism for veno-occlusive dysfunction in androgen deficiency. So, in androgen-deficient men, testosterone may restore the anatomical/ biochemical substrate on which the PDE-5 inhibitors act. The above argues for measurement of testosterone in men with complaints of erectile dysfunction. Several studies, including our own, show that testosterone treatment alone, or in addition to PDE-5 inhibitors, may restore erections in these men.
WCMH Abstracts Objective: Evaluating the impact of testosterone therapy on erectile dysfunction, also in combination with PDE-5 inhibitors, besides impact on penile fibro-elastic properties and veno-occlusive insufficiency as well as cavernosographic changes in hypogonadal patients with obesity and metabolic syndrome and ED. Methods: (1) Review of our studies in terms of Testosterone therapy alone, and in combination with PDE-5 inhibitors in patients with erectile dysfunction. (2) Study review of changes in penile cavernography and venous leakage under testosterone therapy in hypogonadal patients with ED. Results: (1) 54% of the our hypogonadal patients reported restored erectile function sufficient for sexual intercourse after 10 resp. 12 weeks of testosterone therapy alone. (2) Studies of Shabsigh, Yassin and Kalinchenko, provided the evidence to convert about 63% hypogonadal non-responders to PDE-5 inhibitors alone into responders within 10 to 12 weeks in combination with testosterone.
Patients with veno-occlusive dysfunction with Diabetes or metabolic syndrome, and severe ED could improve their sexual function under Nebido. Cavernosography showed dramatic improvement in many subjects within 3–6 months under Testosterone undecanoate injections. Conclusion: ED and hypogonadism are prevalent; the population at risk includes those diagnosed with diabetes mellitus, metabolic syndrome, chronic renal failure, and aging. Screening these populations will yield men who can benefit from testosterone therapy. Testosterone plays a key role in the central and peripheral modulation of erectile function. New research in the laboratory and in humans is shaping a refinement of the role of testosterone therapy in ED. Testosterone deficiency induces both biological and structural/ functional changes in the trabecular cavernosal tissues. Adipocyte accumulation in penile subtunical area of the corpus cavernosum in orchietomized rabbit emphasized the potential mechanism for veno-occlusive dysfunction in androgen deficiency (Traish et al. 2005). We can suggest or hypothesize that penile venous leak could be a metabolic disorder –which can be reversible in some cases under testosterone substitution- rather than a pure mechanical lesion. This hypothesis should be tested in further studies.
26 The associated link between Erectile Dysfunction, Metabolic Syndrome, and Hypogonadism Aksam A. Yassin, Farid Saad
Aksam A. Yassin Clinic of Urology/ Andrology, Segeberger Kliniken, NorderstedtHamburg, Germany, and Department of Urology, Gulf Medical College School of Medicine, Ajman, UAE Farid Saad Bayer Schering AG, Berlin and Research Department Gulf Medical College School of Medicine, Ajman, UAE
Background, Introduction and Objectives: The metabolic syndrome, characterized by central obesity, insulin resistance, dyslipemia and hypertension, is highly prevalent. When left untreated, it significantly increases the risk of diabetes mellitus and cardiovascular disease, pathologies associated with erectile dysfunction. Hypogonadism is a frequent occurrence in the metabolic syndrome, which may be again an etiological factor in erectile dysfunction often found in men with the metabolic syndrome which is explained by endothelial dysfunction and oxidative stress, key elements in the metabolic syndrome, affecting various components of the vascular biology of the penis. It has been suggested that hypogonadism may be an additional component of metabolic syndrome. The metabolic syndrome, appears to have a major association with erectile dysfunction (ED). On a mechanistic level, their common grounds may involve
endothelial dysfunction; the conditions of oxidative stress understood to be a pathologic element of the syndrome also may affect various components of the vascular biology of the penis. Erectile dysfunction is predictive of the metabolic syndrome. This finding suggests that erectile dysfunction may provide a warning sign and an opportunity for early intervention in men otherwise considered at lower risk for the metabolic syndrome and subsequent cardiovascular disease. Our own studies have shown that normalizing testosterone levels in men with the metabolic syndrome improves ED. Methods: 771 patients consulting for erectile dysfunction over a two-year period received comprehensive screening for symptoms of the metabolic syndrome and for hypogonadism. Results: The average abdominal girth of these men was 104 cms (far above the 2005
Vol. 4, No. 3, pp. 357–378, September 2007
371
and ED than total testosterone concentrations. In all the patients with diabetes mellitus the possibility of SLOH and ED should be investigated. In the other hand, elderly men with SLOH also must be screening to exclude the symptoms of diabetes and erectile dysfucntions.
24 The influence of testosteone replacement therapy on erectile dysfunctions in aging men with testosterone deficiency and diabetes mellitus type 2 Micha» Rabijewski, Wojciech Zgliczyn´ski
Micha» Rabijewski Department of Endocrinology, Medical Centre for Postgraduate Education, Warsaw, Poland Wojciech Zgliczyn´ski Department of Endocrinology, Medical Centre for Postgraduate Education, Warsaw, Poland
Objective: The role of testosterone in the anatomy and physiology of erection is becoming clear. Erectile dysfunctions (ED) are very common observed in men with diabetes mellitus type 2 (DM2). The aim of the study was to determine the efficacy of testosterone adminisartions in elderly men with ED and DM2. Material and methods: We investigated 41 men mean aged 65,4 years with late onset hypogonadism according Polish Endocrine Society recommendations and DM2 according ADA recommendations, who had not been treated with PDE5 inhibitors. All men received testosterone enanthate in dose of 200 mg. i.m. every second week. Durations of treatment was mean 12 weeks. Efficacy of treatment was measured by the IIEF domain before and after 4 and 12 weeks of treatment. All of men were treated with oral antidiabetic drugs or insulin. Hypogonadism was expected on the
basis of low testosterone concentration (3.5 mg/L) and the index T/LH 1. Results: After 4 weeks of treatment 21/41 patients showed improvement in erections. At the and of 4 month 32/41 patients showed improvement in the score on IIEF (from 7.9 3.2 to 12.3 3.4; p < 0.05). There were inverted correlations between testosterone levels and efficacy of testosterone treatment and also between duration of DM2 and IIEF score. Conclusions: In elderly men with hypogonadism related to aging (late-onset hypogonadism) and diabetes mellitus 2 after 1 month of testosterone replacement therapy there was a small number of patients in whom treatment results in erectile improvement, but many more patients benefit after 3 months of therapy. Testosterone therapy is time-dependent and combination with PDE5 inhibitors should start only after at least 3-months of monotherapy with testosterone.
25 Testosterone therapy in patients with erectile dysfunction: When to start? When to give alone? When to combine? And for how long? Aksam A. Yassin, Farid Saad, Svetlana Kalenchenko
Aksam A. Yassin Clinic of Urology/ Andrology, Segeberger Kliniken, NorderstedtHamburg, Germany and Department of Urology, Gulf Medical College School of Medicine, Ajman, UAE Farid Saad Bayer Schering AG, Berlin and Research Department Gulf Medical College School of Medicine, Ajman, UAE Svetlana Kalenchenko Institute of Endocrinology, Moscow, Russian Federation
370
Background: The introduction of the phosphodiesterase type 5 inhibitors (PDE 5-inhibitors) has been a step forward in the treatment of erectile dysfunction. The success of the PDE 5inhibitors rendered androgens as treatment for erectile problems in the average patient as something of the past. . . Over the last 15 years the age-related decline of circulating testosterone in men has received serious attention. Moreover, new research has presented convincing evidence that testosterone has profound effects on tissues of the penis involved in the mechanism of erection and that testosterone deficiency impairs the anatomical and physiological substrate of erectile capacity, at least in part reversible upon androgen replacement. There are androgen receptors in the human corpus cavernosum. The expression of nitric oxide (NO) synthesis is regulated by
Vol. 4, No. 3, pp. 357–378, September 2007
androgens. Several studies show that androgen plays a critical role in restoring and maintaining the penile trabecular smooth muscle structure and function as well as regulating the cell apoptosis. Testosterone deficiency induces both biological and structural/functional changes in the trabecular cavernosal tissues. Adipocyte accumulation in penile subtunical area of the corpus cavernosum emphasized the potential mechanism for veno-occlusive dysfunction in androgen deficiency. So, in androgen-deficient men, testosterone may restore the anatomical/ biochemical substrate on which the PDE-5 inhibitors act. The above argues for measurement of testosterone in men with complaints of erectile dysfunction. Several studies, including our own, show that testosterone treatment alone, or in addition to PDE-5 inhibitors, may restore erections in these men.
WCMH Abstracts Objective: Evaluating the impact of testosterone therapy on erectile dysfunction, also in combination with PDE-5 inhibitors, besides impact on penile fibro-elastic properties and veno-occlusive insufficiency as well as cavernosographic changes in hypogonadal patients with obesity and metabolic syndrome and ED. Methods: (1) Review of our studies in terms of Testosterone therapy alone, and in combination with PDE-5 inhibitors in patients with erectile dysfunction. (2) Study review of changes in penile cavernography and venous leakage under testosterone therapy in hypogonadal patients with ED. Results: (1) 54% of the our hypogonadal patients reported restored erectile function sufficient for sexual intercourse after 10 resp. 12 weeks of testosterone therapy alone. (2) Studies of Shabsigh, Yassin and Kalinchenko, provided the evidence to convert about 63% hypogonadal non-responders to PDE-5 inhibitors alone into responders within 10 to 12 weeks in combination with testosterone.
Patients with veno-occlusive dysfunction with Diabetes or metabolic syndrome, and severe ED could improve their sexual function under Nebido. Cavernosography showed dramatic improvement in many subjects within 3–6 months under Testosterone undecanoate injections. Conclusion: ED and hypogonadism are prevalent; the population at risk includes those diagnosed with diabetes mellitus, metabolic syndrome, chronic renal failure, and aging. Screening these populations will yield men who can benefit from testosterone therapy. Testosterone plays a key role in the central and peripheral modulation of erectile function. New research in the laboratory and in humans is shaping a refinement of the role of testosterone therapy in ED. Testosterone deficiency induces both biological and structural/ functional changes in the trabecular cavernosal tissues. Adipocyte accumulation in penile subtunical area of the corpus cavernosum in orchietomized rabbit emphasized the potential mechanism for veno-occlusive dysfunction in androgen deficiency (Traish et al. 2005). We can suggest or hypothesize that penile venous leak could be a metabolic disorder –which can be reversible in some cases under testosterone substitution- rather than a pure mechanical lesion. This hypothesis should be tested in further studies.
26 The associated link between Erectile Dysfunction, Metabolic Syndrome, and Hypogonadism Aksam A. Yassin, Farid Saad
Aksam A. Yassin Clinic of Urology/ Andrology, Segeberger Kliniken, NorderstedtHamburg, Germany, and Department of Urology, Gulf Medical College School of Medicine, Ajman, UAE Farid Saad Bayer Schering AG, Berlin and Research Department Gulf Medical College School of Medicine, Ajman, UAE
Background, Introduction and Objectives: The metabolic syndrome, characterized by central obesity, insulin resistance, dyslipemia and hypertension, is highly prevalent. When left untreated, it significantly increases the risk of diabetes mellitus and cardiovascular disease, pathologies associated with erectile dysfunction. Hypogonadism is a frequent occurrence in the metabolic syndrome, which may be again an etiological factor in erectile dysfunction often found in men with the metabolic syndrome which is explained by endothelial dysfunction and oxidative stress, key elements in the metabolic syndrome, affecting various components of the vascular biology of the penis. It has been suggested that hypogonadism may be an additional component of metabolic syndrome. The metabolic syndrome, appears to have a major association with erectile dysfunction (ED). On a mechanistic level, their common grounds may involve
endothelial dysfunction; the conditions of oxidative stress understood to be a pathologic element of the syndrome also may affect various components of the vascular biology of the penis. Erectile dysfunction is predictive of the metabolic syndrome. This finding suggests that erectile dysfunction may provide a warning sign and an opportunity for early intervention in men otherwise considered at lower risk for the metabolic syndrome and subsequent cardiovascular disease. Our own studies have shown that normalizing testosterone levels in men with the metabolic syndrome improves ED. Methods: 771 patients consulting for erectile dysfunction over a two-year period received comprehensive screening for symptoms of the metabolic syndrome and for hypogonadism. Results: The average abdominal girth of these men was 104 cms (far above the 2005
Vol. 4, No. 3, pp. 357–378, September 2007
371