[Erectile function disorders. Epidemiology, physiology, etiology, diagnosis and therapy]. / Erektile Funktionsstörungen. Epidemiologie, Physiologie, Atiologie, Diagnostik und Therapie.

Erectile dysfunction is a common, age-dependent functional disturbance of men associated to various comorbidities. Interdisciplinary cooperation with neurologists in ca-ses of a suspected neurological aetiology and with psychiatrists in cases with normalorganic diagnostic findings is necessary. Hormone replacement and psychotherapy can cure certain patients. Oral pharmacotherapy is the most effective therapy for erectile dysfunction with the highest patient preference. Oral PDE-5-inhibitors(sildenafil, tadalafil, vardenafil) are superior in effectiveness to centrally acting drugs (apomorphin, yohimbine). Local pharmacotherapy (MUSE, ICI) is a second line therapy in cases of failure or contraindications for oral pharmacotherapy. Vacuum therapy and operative procedures(penile implants) complete the therapeutic options of erectile dysfunction.

[Erectile dysfunction. Epidemiology, physiology, etiology, diagnosis and therapy]. / Erektile Funktionsstörungen. Epidemiologie, Physiologie, Atiologie, Diagnostik und Therapie.

Erectile dysfunction is a common, age-dependent functional disturbance of men associated to various comorbidities. Interdisciplinary cooperation with neurologists in cases of a suspected neurological aetiology and with psychiatrists in cases with normal organic diagnostic findings is necessary. Hormone replacement and psychotherapy can cure certain patients. Oral pharmacotherapy is the most effective therapy for erectile dysfunction with the highest patient preference. Oral PDE-5-inhibitors (sildenafil, tadalafil, vardenafil) are superior in effectiveness to centrally acting drugs (apomorphin, yohimbine). Local pharmacotherapy (MUSE, ICI) is a second line therapy in cases of failure or contraindications for oral pharmacotherapy. Vacuum therapy and operative procedures (penile implants) complete the therapeutic options of erectile dysfunction.

Involvement of cyclic nucleotides in renal artery smooth muscle relaxation.

The elevation of vascular smooth muscle tone in the renal arteries during kidney transplantation and nephron-sparing surgery plays a major role in postsurgical organ dysfunction. Therefore, a better understanding of the intracellular mechanisms of contraction and relaxation is of fundamental interest to improve urological treatment. The present study was designed to investigate the complex intracellular system of cyclic nucleotides involved in the regulation of smooth muscle relaxation by using swine renal artery rings in the Schuler organ bath. Phenylephrine (PE) induced dose-dependent and fully reversible isometric contractions with a threshold concentration of 10 nM and an EC(50) of 804 nM. The receptor was identified as alpha(1A)-subtype by the selective antagonist WB4101. Increasing the intracellular concentration of cyclic 3':5'-adenosine monophosphate (cAMP) by dibutyryl-cAMP (5 mM) and forskolin (5 micro M) resulted in a decreased contractiltity of 48.0% and 76.3%, respectively. Elevation of the cytosolic content of cyclic 3':5'-guanosine monophosphate (cGMP) using dibutyryl-cGMP (1 mM), sodium nitroprusside (100 micro M) and SIN-1 (100 micro M) decreased the average PE-induced contraction by 16.4%, 41.9% and 62.4%, respectively. The unselective phosphodiesterase inhibitors theophylline (1 mM), papaverine (100 micro M) and IBMX (5 mM) reduced the PE-induced contraction by 37.3%, 93.1% and 95.5%, respectively. Furthermore, selective inhibition of phosphodiesterases by milrinone (PDE(3)-selective) resulted in a decreased contractility by 1.3% (50 micro M), 29.5% (100 micro M) and 93.5% (5 mM), and using rolipram (PDE(4) selective), the PE-induced contraction was inhibited by 57.9% (50 micro M) and 81.9% (100 micro M). The results suggest the involvement of cAMP and cGMP in the relaxation of renal artery smooth muscle cells. Moreover, phosphodiesterases, especially PDE(3) and PDE(4), seem to play a critical role in the regulation of renal artery smooth muscle tone.

Penile and perianal pudendal nerve somatosensory evoked potentials in the diagnosis of erectile dysfunction.

Neurophysiologic examinations in differential diagnosis of erectile dysfunction comprise electromyogramme of the pelvic floor, pudendal nerve terminal motor latency (PNTML) and evaluation of pudendal somatosensory evoked potentials (SSEP). We focused our interest on comparing diagnostic importance of penile and perianal pudendal nerve SSEP. We examined 20 patients suffering from erectile dysfunction and 20 patients without any manifestation of impotence. The stimulus was administered using penile ring electrodes at the base of the penis (cathode) and distally on the penis shaft (anode), as well as a perianal surface electrode applied at 3 o'clock in lithotomy position and 5 cm laterally on the gluteal skin. The potentials were recorded with intradermal needle electrodes at C(z)-2 cm (different) and F(z) (indifferent). 500 stimuli were averaged for a single tracing. The stimulus strength was set at an average of 3-4 times the stimulus threshold. Cortical latency of P 40 ranged from 39.0 to 45.6 ms (penile) and from 33.6 to 43.2 ms (perianal) in the control group, in the patient group latencies ranged from 38.8 to 51.6 (penile) and 34.0 to 44.8 ms (perianal). In two patients no potential was recordable after perianal stimulation, one patient showed a marked prolongation of the penile response with a normal perianal latency. Penile and perianal latencies of P 40 were significantly prolonged in the patient group compared to the control group (P<0.05). The combination of penile and perianal pudendal SSEP may provide valuable additional information in differential diagnosis of erectile dysfunction, especially allowing to identify different sites of neurogenic lesions. In contrast to perianal pudendal SSEP, penile stimulation may help to discover pathologic changes in the distal course of the pudendal nerve, especially the dorsal nerve of the penis.

[Pathogenetic and clinical aspects of low estradiol level in the man]. / Pathogenetische und klinische Gesichtspunkte niedriger Ostradiolspiegel beim Mann.

To elucidate a possible role of low estradiol (E2) levels in blood serum of men, normal values were determined in 91 healthy men (age 20-75 years), classified as high or low complaint-index due to a psychological questionnaire. Statistical analysis gave no correlation of estradiol levels to age or complaint index in normal men whereas testosterone (T) could be significantly correlated to complaint-index (p < 0.01) and free testosterone (fT) could be significantly correlated to age (p < 0.001) and complaint-index (p < 0.01). T and E2 were determined in 1370 clinical patients with various urological diseases, T, fT and E2 in 1261 ambulant patients. In 72/1370 (5.2%) and 76/1261 (6%) patients, low E2-levels (< 10 pg/ml) were found in blood serum. In 56/76 (74%) patients with low E2-levels, T or fT was simultaneously low. Isolated low E2-levels were found in 20/1261 (1.6%) patients. In clinical patients, no special urological disease correlated to low E2-levels. Due to these results, low E2 levels in men are in most cases the result of low testosteron levels. The adequate hormonal treatment in men is therefore the replacement of testosteron. Substitution of E2 in men is at that time an experimental therapy, that is limited on selected cases.

Detection of adeno-associated virus in human semen: does viral infection play a role in the pathogenesis of male infertility?

OBJECTIVE: To evaluate the occurrence of adeno-associated virus (AAV) DNA and/or human papillomavirus (HPV) DNA in the semen of infertile men as a possible factor in the pathogenesis of male infertility. DESIGN: Descriptive pilot study. SETTING: University-based diagnostic and research laboratory. PATIENT(S): Semen specimens were collected from 30 men with diagnosed infertility and from 8 control subjects. INTERVENTION(S): Diagnostic spermiograms were made and the semen specimens were separated into seminal fluid, nonspermatozoal cells, and spermatozoa using a Ficoll gradient technique. MAIN OUTCOME MEASURE(S): The presence of AAV and HPV DNA in the different fractions of the ejaculates from the infertile men and the control subjects was detected by polymerase chain reaction. Semen quality was analyzed according to World Health Organization guidelines. RESULT(S): Adeno-associated virus DNA was detected in 30% (9/30) of the ejaculates from the infertile men. No AAV DNA was found in the ejaculates from the 8 control subjects. In 8 of 9 samples, AAV DNA could be found only in the spermatozoal fraction of the specimen. Seven of 9 semen specimens that contained viral DNA also demonstrated oligoasthenozoospermia. Both AAV and HPV DNA was found in the spermatozoal fraction of 3 of 30 specimens. CONCLUSION(S): The data demonstrate for the first time the occurrence of AAV infection in human semen. Sperm motility seems to be affected by the presence of AAV.

Interdisciplinary assessment and follow-up of patients with erectile dysfunction--psychiatric aspects.

The objectives of this investigation were to assess the psychiatric comorbidity and patients' satisfaction with treatment in a sample of 73 men with erectile dysfunction (ED) who were consecutively admitted to an andrologic outpatient centre. After comprehensive interdisciplinary assessment, 49% of these patients were assigned an organic etiology, 33% had psychogenic impotence, and in 18% somatic and psychogenic factors seemed to be relevant. 63% of all patients received a psychiatric diagnosis (according to ICD-9). Depressive disorders were found in 25%. Organic psychosyndromes (nonpsychotic) were prominent in the somatic group. In a follow-up after 29.4 +/- 5.0 months, 41 out of 73 patients could be reevaluated, of which 85% of organic patients had received some kind of therapy, but 65% were not satisfied with the chosen treatment. These results underline the importance of close interdisciplinary co-operation in the assessment and therapy of patients with erectile importance. Potential reasons for drop-out and limited acceptance of the offered treatments are discussed.

Treatment of erectile dysfunction with external vacuum devices.

In a retrospective study, the medical and psychological outcome of the use of external vacuum devices in the treatment of erectile dysfunction in 190 patients was evaluated, using a questionnaire and a clinical examination. 110/190 patients (57.8%) answered the questionnaire. 22/110 patients (20%) rejected the device primarily and 34/110 (30.9%) after a period of up to 16 weeks (primary rejection rate 50.9%). A secondary drop-out rate of 8/110 (7.3%) was observed after an intermediate time of 10.5 months. 46/110 (41.8%) patients were long-term users (median 27.6 months, range 7-70 months). Long-term users were mainly patients who did not respond to intracavernosal pharmacotherapy. In the group of long-term users, 98% of patients and 85% of their partners were satisfied with the vacuum therapy. Complications were minor (hematoma 9.8%; skin injury 2.2%), 69.8% of long-term users never had problems with the device. 74% of users reported regular orgasm. Vacuum therapy is a safe and effective non-invasive treatment of erectile dysfunction with a limited primary acceptance and low drop-out rates in long-term follow-ups.

Treatment of erectile dysfunction by an external ischiocavernous muscle stimulator.

OBJECTIVE: The aim of the present study was to evaluate the therapeutic potency of an electrotherapy of striated ischiocavernous muscles in patients with erectile dysfunction. PATIENTS AND METHODS: Transcutaneous electrostimulation of striated ischiocavernous muscles by self-adhesive penile or perineal skin electrodes was performed in 48 patients with erectile dysfunction. 6/48 patients (R) responded to intracavernous pharmacotherapy while 42/48 (NR) did not show significant penile rigidity even to intracavernous papaverine/phentolamine/PGE1 triple drug medication. RESULTS: Within the observation time of 3 months, 10/48 patients dropped out. 22/38 patients reported a penile rigidity for sufficient sexual intercourse whereby 3/22 NR required additional intracavernous pharmacotherapy. Penile rigidity could be objectivated by triple drug medicaton in 12/14 NR after ischiocavernous muscle stimulation (EIS) therapy. 5/6 R were treated successfully for premature erection loss. During EIS treatment neither discomfort nor complications could be observed. CONCLUSION: Transcutaneous electrostimulation of ischiocavernous muscles is a new, noninvasive therapy for the improvement of penile rigidity. The clinical results underline the importance of the striated ischiocavernous muscles for penile rigidity.

[Electromyography of the sphincter vesicae externus muscle. Technique, indications and outcome]. / EMG des M. sphincter vesicae externus. Technik, Indikation und Ergebnisse.

Electrophysiological examinations provide important findings for the clarification of urogenital dysfunctions. A routine electromyogram (EMG) of the external anal sphincter is used together with stimulation of the pudendal nerve to determine lesions of the somatomotor tract. An alternative is the electromyographical examination of the external vesical sphincter. This special method requires more time and sufficient experience. We see an indication for EMG of the voluntary vesical sphincter in urogenital dysfunctions that cannot be sufficiently differentiated with EMG of the external anal sphincter and also in disturbances that selectively affect the external vesical sphincter.

[Electrophysiologic diagnosis in erectile dysfunction]. / Elektrophysiologische Diagnostik bei der erektilen Dysfunktion.

So far, electrophysiological examinations have rarely been used in the diagnosis of erectile dysfunction (ED) mainly because the methods available only allow somatic neuron pathways to be examined whose relevance for the mainly autonomically controlled crection is evaluated differently. At present, impaired penile nerve supply as the possible cause of ED can only be evaluated through neurophysiological screening of the somatic and autonomic pathways of the pelvic floor, and not just by one simple method. Diagnosing ED should include testing of motoric efferences through electroneurography of the pudendal nerve and electromyography of the external anal sphincter and the urethral sphincter. Sensitive afference is tested with somatosensory evoked potentials of the pudendal nerve. New methods that are available for the examination of autonomic pathways are the penile sympathetic skin response and the EMG of the corpus cavernosum. Together with the other electrophysiological examinations, they allow neurogenic causes to be determined and differentiate not only between central and peripheric lesions, but also between acute and chronic changes. Prognosis can also be estimated. A crucial diagnostic deficit is the fact that it is still not possible to test the parasympathetic system directly.

[Prostaglandin E1 (PGE1) in diagnosis and long-term therapy of erectile dysfunction]. / Prostaglandin E1 (PGE1) in der Diagnostik und Langzeittherapie der erektilen Dysfunktion.

The aim of this retrospective study was to determine the worth of prostaglandin E1 (PGE1) for the diagnosis and therapy of erectile dysfunction using the study of documents, a questionnaire and a clinical control. In testing, 58.3% of 300 patients responded completely to PGE1. Complications were pain (13%) and prolonged erections of more than 3 h (5%). Sixty-four of 300 patients began continuous therapy. Forty-three of 64 patients were evaluated retrospectively (time 5/88-9/94). Nine of 43 primary patients and 16/34 secondary patients dropped out after a medium therapy of 1 year. The main reasons for the dropouts were pain and fear of complications related to the therapy. Complications in long-term therapy were pain (35.3%), prolonged erection (0.4%), and local fibrosis (5.9%). PGE1 is not a magic drug in erectile dysfunction. The advantage of fewer prolonged erections compared to papaverine/phentolamin is restricted by the high incidence of pain. The relative lack of acceptance of autoinjection therapy in long-term follow-up demonstrates its limited value in the therapy of erectile dysfunction.

Regulation of prostatic smooth muscle contractility by intracellular second messengers: implications for the conservative treatment of benign prostatic hyperplasia.

The increased sympathetic neurotransmission in benign prostatic hyperplasia (BPH) results in a alpha 1C-adrenoceptor-mediated increase in prostatic smooth muscle tone which seems to be responsible for the dynamic infravesical obstruction occurring in BPH. The prostatic smooth muscle contractions evoked by norepinephrine can be efficiently blocked by alpha 1-adrenoceptor blockers. Moreover, an impressive number of clinical trials illustrated the beneficial results of alpha 1-adrenoceptor blockers in the treatment of BPH. However, despite knowledge of alpha 1-adrenergic neurotransmission and the clinical application of its blockade by selective alpha 1-adrenoceptor antagonists, very little is known about the intracellular pathways involved in the regulation of prostatic smooth muscle contractility. To study the intracellular mechanism of the alpha 1C-adrenoceptor-induced prostatic smooth muscle contraction, the patch-clamp technique in the whole-cell configuration mode combined with the Fura-II fluorescence technique was used in human, enzymatically isolated smooth muscle cells obtained from patients undergoing transurethral resection of the prostate because of symptomatic BPH. Furthermore changes in prostatic smooth muscle contractility were registered in organ bath experiments. Application of the selective alpha 1-adrenoceptor agonist phenylephrine (PE) increased the L-type Ca(2+)-channel current (ICa) dose dependently from 8 up to 18.5 microA/cm2, simultaneously elevating the free cytoplasmic Ca2+ concentration ([Ca2+]i) up to 1.9 microM. Pretreating the myocytes with pertussis toxin, an exotoxin of Bordetella pertussis which inactivates GTP-binding proteins (G proteins) of the Gi and G(o) family by ADP ribosylation, reduced the PE-induced ICa stimulation by 71.5 +/- 5.6% (n = 21). Dialysis of the cytosol with the second messenger inositol-1,4,5-trisphosphate (IP3), which releases Ca2+ from intracellular non-mitochondrial, IP3-sensitive Ca2+ pools, imitated the PE-evoked responses. Pretreating the myocytes with the Ca(2+)-release blockers ryanodine (10-100 microM, n = 8), thapsigargin (0.1 microM, n = 11) or low-molecular weight heparin (n = 14) largely attenuated the PE-evoked responses. The experimental results suggest a coupling of alpha 1-adrenoceptors to phospholipase C-converting phosphoinositol-4,5-bisphosphate into diacylglycerol, an endogenous activator of the protein kinase C and IP3 which releases Ca2+ from intracellular stores stimulating ICa via Ca(2+)-calmodulin-dependent protein kinase induced phosphorylation of voltage-dependent Ca2+ channels. This knowledge could be of interest for conservative treatment in symptomatic BPH.

Penile sympathic skin response in erectile dysfunction.

Penile sympathic skin response (PSSR) was measured in 20 normal patients and in 46 patients with erectile dysfunction (ED). PSSR could be registered in 80% of normal patients. The latencies were 1,100-1,600 ms. In patients with ED, latencies were 1,240-3,640 ms. A reproducible normal latency of PSSR (< 1,600 ms) indicates a normal sympathic innervation of the penis. Long latencies (> 1,800 ms) indicate neuropathy of unmyelinated nerval fibers. The loss of a reproducible answer however allows no exact diagnostic information. PSSR is a useful diagnostic test for detecting neuropathy of unmyelinated nerval fibers as a possible cause of ED.

Muscular cavernous single cell analysis in patients with venoocclusive dysfunction.

Enzymatically isolated smooth muscle cells of the corpora cavernosa obtained from open biopsies of 15 patients, clinically nonresponding to papaverine/phentolamine and prostaglandin E1 (PGE1) and classified by cavernosometry, were examined using the patch-clamp technique in the whole-cell configuration mode simultaneously monitoring the intracellular calcium concentration by means of the Ca(2+)-sensitive fluorescence dye FURA-II. It could be demonstrated that extracellularly applied PGE1 induces smooth muscle relaxation by inhibition of voltage-dependent L-type Ca2+ currents (58 +/- 8%). Compared to intact cavenous tissue (n = 5), the smooth muscle cells of 14/15 PGE1 nonresponders had no evidence of functional disturbance. Due to intact smooth muscle cells in most cases, etiology of venoocclusive dysfunction remains unclear.