[Painful ejaculation: a review].

Pain at ejaculation/orgasm perceived in perineum, urethra and/or urethral meatus, has a profound impact on the quality of life of the affected man. Although underestimated, this condition is reported to have a 1-9.7% prevalence over the general population. METHODS. Structured review of the relevant available literature. RESULTS. Among the main causes of pain experienced at ejaculation/orgasm are: prostatevesicular causes (LUTS/BPH, prostatitis, ejaculatory duct obstruction, vesicular stone), postsurgical causes (radical prostatectomy, inguinal hernioplasty), pharmacologic causes (antidepressants), psychogenic causes (psychosexual conflicts, sexual abuse), rare causes. For these pathologies, diagnostic and therapeutic strategies have been proposed. CONCLUSIONS. Ejaculatory pain is associated with a high level of personal distress, and represents a possible request for help within the andrologic/urologic area. Each field specialist should be competent in correctly interpreting every single case, in order to manage it appropriately.

Diagnosing erectile dysfunction: instruments for the study of smooth muscle relaxation.

Complete cavernosal smooth muscle relaxation is the pre-requisite for the reliability of every evaluation of the integrity of the corporal veno-occlusive system. Such evaluation is needed whenever reaching a diagnostic conclusion on the haemodynamic status of a given patient is clinically relevant. Clinical challenges that a laboratory evaluation of veno-occlusive integrity face comprise both the induction of complete smooth muscle relaxation, and the possibility to monitor it. This article will review the relevant aspects of normal range values of veno-occlusive function, existing strategies aimed to promote complete smooth muscle relaxation, and available techniques to monitor the cavernosal smooth muscle status.

Testosterone replacement therapy in male late onset hypogonadism: available pharmacological strategies.

During the last few years, the general aging of the population and the growing knowledge about male hormonal changes in older age have lead the scientific community to focus on the clinical aspects of secondary hypogonadism in aging males. This syndrome is well defined by the term late-onset hypogonadism (LOH). Although the pathophysiology and the diagnostic aspects have been studied and defined and various preparations are available, the debate on androgen supplementation therapy is still ongoing. As the spectrum of effects of endogenous testosterone is essentially based on its metabolism to dihydrotestosterone and estradiol, testosterone is the treatment of choice for male hypogonadism. The aim of the therapy is to establish a physiological concentration of serum testosterone in order to correct the androgen deficiency, relieve its symptoms and prevent long-term sequelae. All of the available products, despite their varying pharmacodynamic and pharmacokinetic profiles, are able to reach this goal. Here we examine the indications for therapy, the characteristics of the different routes of administration and how to monitor therapy in order to make the treatment safe and effective.

Advanced diagnostics in erectile dysfunction: beyond the concept of hemodynamics.

Axial rigidity is the most important characteristic of a functional erection. Three factors determine axial rigidity: intracavernosal pressure (addressed by hemodynamics), cavernosal tissue mechanical properties ("tissue expandability"), and the ratio between the two dimensions of the penis: length and circumference ("penile geometry"). Intracavernosal pressure only is addressed by hemodynamic diagnostics, dynamic cavernosometry being the only investigation that allows its direct determination. The appreciation of these three rigidity determinants has the implication that there might exist cases of erectile dysfunction for pure geometric reasons, i.e. an excessive erect length/circumference ratio (L/C R). We report our series of 57 consecutive dynamic cavernosometries with concomitant axial rigidity and penile dimensions recording. Six cases of purely "geometric erectile dysfunction (ED)", i.e. patients unable to physiologically develop a rigid erection for a pathologic L/C R were identified. These patients are characteristically young men (mean age: 28 yrs, range 22-33) with life-long ED not responding to oral or intracavernosal treatment. Our L/C R cut-off value for pure geometric ED is 1.31. We also report two surgical strategies that could possibly address pure geometric ED. In conclusion, hemodynamics is not sufficient to assess the potency status, as other factors come to determine penile rigidity. In particular, there are cases of pure geometric ED which, potentially, is surgically curable. These cases should not be erroneously labelled as psychogenic cases.

Peyronie's disease: prevalence and association with cigarette smoking. A multicenter population-based study in men aged 50-69 years.

OBJECTIVES: We present a multicenter, population-based epidemiological survey aimed at assessing the prevalence of Peyronie's disease (PD) and its potential risk factors in the general population. METHODS: In each of the ten centers throughout Italy, a uroandrologist contacted all the men in the age range 50-69 years registered with a general practitioner (GP). The subjects recruited were evaluated on the basis of their medical history, including alcohol consumption and cigarette smoking. The following questionnaires were administered: IIEF, IIPSS symptom score, premature ejaculation and PD. RESULTS: All the subjects registered with a GP were invited to participate in the study. Of the 1,180 subjects, 647 (53%) entered over survey. In this population, 46 cases of PD were identified, accounting for a prevalence of 7.1%. The prevalence rate increased with age even if the trend is not statistically significant. The multivariate analysis showed a significant correlation between cigarette smoking and PD, with an odds ratio (OR) of 4.6 (CL 95%) confidence limit 1.506- 14.287). Smoking as single variable had an OR of 7.2 (95% CL 2.34-24.93). No significant association was observed between PD and the other variables such as cardiovascular diseases, diabetes, hypertension and alcohol consumption. CONCLUSIONS: PD is a much more frequent condition in the general population than previously reported. According to our results, cigarette smoking may be considered a risk factor for developing PD. If further and more targeted studies confirm that giving up smoking may reduce the risk of developing PD, then there will be new prospects for primary and secondary prevention and for curbing the progression of the disease.

Audiovisual sexual stimulation by virtual glasses is effective in inducing complete cavernosal smooth muscle relaxation: a pharmacocavernosometric study.

Audiovisual sexual stimulation (AVSS) is frequently employed to promote cavernosal smooth muscle relaxation (SMR) in hemodynamic diagnostic settings for erectile dysfunction. Our aim has been to adapt conventional AVSS to the particular test conditions of pharmacocavernosometry and pharmacocavernosography (DICC), by the use of virtual glasses. Thirty-seven consecutive patients undergoing DICC were randomized in two groups: no-AVSS and AVSS through commercially available virtual glasses (VG-AVSS) with tri-dimensional capabilities and stereophonic headphones. Such device partially excludes the patient from the surrounding environment. In both groups a standard dose of vasoactive agents was intracavernosally administered, and possibly repeated (re-dosing), until complete SMR was obtained (3 doses/patient maximum). Psychometric tests (State Trait Anxiety Inventory and ad hoc visual analogue scales for embarrassment, stress and pain) were administered before and after DICC. The no-AVSS group consisted of 18 patients, the AVSS group of 19. Number of needed vasoactive agent doses: in the no-AVSS group 6 patients needed 1 dose, 3 patients 2, 9 patients 3 (mean dose number: 2.17); in the AVSS group 15 patients needed 1 dose, 1 patient 2, 3 patients 3 (mean dose number: 1.37). The difference in the number of doses used in the two groups was statistically significant (Student's t-test P = 0.007). Complete SMR, regardless of the number of used doses: in the no-AVSS group 9 patients (50%) achieved complete SMR, in the AVSS group 16 patients (84.2%). The difference in the two groups was statistically significant (chi-square P = 0.026). From evaluated psychometric measures no statistically significant difference between the two groups was detected. VG-AVSS significantly promotes complete SMR without increasing test related stress or anxiety. Its induced arousal suggests the possibility of performing dynamic evaluations of the erectile function with the oral agent sildenafil in place of intracavernosally administered vasoactive agents. VG-AVSS furthermore constitutes a promising tool for the investigation of normal physiology and pathophysiology of female sexual function.

Self-injection devices for intracavernosal pharmacotherapy: operational classification and safety considerations.

Several self-injection devices have been recently proposed as an aid to home intracavernosal self-injection treatment for erectile dysfunction, with the purpose of allowing an easier drug administration, decreasing the artificiality of intracavernosal pharmacotheraphy, with the overall goal of increasing the acceptability of this treatment. We propose a classification of these devices according to the type of mechanical impact on the cavernosal tissue: self-injection pens, allowing for manual needle insertion and manual drug delivery; autoinsertors, with automatic needle insertion and manual drug delivery, and autoinjectors, that provide both automatic needle insertion and automatic drug delivery. The use of autoinjectors bears two theoretical risks: extra-corporal drug delivery in cases of wrong injection site, and trabecular damage due to high delivery pressure. In one device pressures 15 times higher the values reached by manual injection, and statistically higher than pressures obtained by maximal strength manual injection, were observed in an in-vitro investigation. Specific studies are needed to define a threshold pressure value for trabecular damage in the flaccid state; accordingly, information on autoinjector developed pressures should be provided by manufacturers. Clinical studies with adequate follow-up are needed as well, to verify the risk of autoinjector-induced extracorporal drug delivery, and the occurrence of intracavernosal nodules or penile curvature, compared to manual self-injection.

Damage to the erectile function following radical pelvic surgery: prevalence of veno-occlusive dysfunction.

A retrospective study was carried out to investigate the prevalence of venoocclusive dysfunction (VOD) in 44 patients who developed impotence following radical cystectomy (24 patients, 55%) and radical prostatectomy (20 patients, 45%) for invasive cancer, performed using a non nerve-sparing technique. Patient evaluation included sexual history, hormone profile, intracavernosal injection test and, in the nonresponders to the test, dynamic infusion cavernosometry and cavernosography (DICC). The follow-up period investigated ranged from 6 months to 9 years and 5 months (average 2.5 years). Our data indicate a 11% prevalence (5 patients) of postsurgical VOD with impotence following radical cystectomy and a 5% prevalence (2 patients) of impotence following radical prostatectomy. In the 7 patients (5 after cystectomy and 2 after prostatectomy) who underwent DICC, cavernosal artery insufficiency was detected. No correlation was found between VOD and the time from surgery (from 6 months to 9 years, average 4.4 years), in both the post-cystectomy and post-prostatectomy groups. Our data indicate that there are not only neurogenic causes of impotence following radical pelvic surgery, VOD and cavernosal artery insufficiency can also be partly responsible. Furthermore, it was shown that erectile inactivity, even in the long-term, does not affect the possible return of drug-induced sexual potency.

Physiological aging and penile erectile function: a study in the rat.

Erectile function of adult (8-month-old) and aged (27-month-old) rats was investigated by in vivo and in vitro assays. Reflexogenic tonic erections were evoked in vivo by electrostimulation of the dorsal nerve of the penis. Aged rats developed tendentially low intracavernosal pressures, and the kinetics of erection and detumescence were significantly lower than in adult animals. The erectile tissue isolated from aged rats exhibited poor response to papaverine. When precontracted with norepinephrine, aged tissues required a 3-fold increase of papaverine concentration to full relaxation. Functional measurements were coupled with morphological analysis of elastic fibres of the tunica albuginea. Light microscopy showed degenerative signs of elastic fibres of aged rat specimens. Taken together, the present findings show that physiological aging is associated with penile tissue stiffness and abnormal corporal compliance.

In vivo assessment of trabecular smooth muscle tone, its application in pharmaco-cavernosometry and analysis of intracavernous pressure determinants.

A pharmaco-cavernosometry based clinical study was designed to define hemodynamic parameters consistent with complete trabecular smooth muscle relaxation, establish a methodology for overcoming incomplete trabecular smooth muscle relaxation, and determine under controlled conditions the contribution of venous outflow and arterial inflow to the steady-state equilibrium intracavernous pressure. Flow-pressure relationships were analyzed in 21 patients each of whom was assumed to have complete smooth muscle relaxation by virtue of the full, rigid and maintained erectile response following intracavernous vasodilator administration, which required intracavernous adrenergic agonists to achieve detumescence. Flow-to-maintain values increased linearly with intracavernous pressure while venous outflow resistance values were high and constant. Based on these relationships, trabecular smooth muscle tone was assessed in 123 impotent patients. In 14%, 63% and 14% of the patients (112 of 123 overall), respectively, 1, 2 and 3 doses of vasoactive agents were required to achieve hemodynamic relationships consistent with complete trabecular smooth muscle relaxation. In 9% of the patients such hemodynamic relationships were unable to be reached. In the 112 patients the influence of different engineering based measures of corporeal veno-occlusive function, including flow-to-maintain, pressure decay, venous outflow resistance and corporeal capacitance, was analyzed against the spectrum of equilibrium steady-state intracavernous pressures. Two distinct equilibrium pressure groups were identified reflecting different capacitance states: pressures greater than 60 mm. Hg (associated with low capacitance values) and pressures less than 50 mm. Hg (associated with high capacitance values), with pressures 50 to 59 mm. Hg representing a hemodynamic transition zone. When analyzed during complete trabecular smooth muscle relaxation, corporeal veno-occlusive hemodynamic variables in conjunction with cavernous arterial perfusion pressure determine the steady-state equilibrium intracavernous pressure. Failure to assess corporeal veno-occlusive function under such conditions will overestimate the degree of suspected corporeal structural disease.

A positive intracavernous injection test implies normal veno-occlusive but not necessarily normal arterial function: a hemodynamic study.

During impotence evaluations a positive intracavernous injection test has been presumed to signify normal erectile hemodynamics. This premise was tested by obtaining hemodynamic data in 80 patients 17 to 65 years old with positive injection tests: patients achieved maximal circumference responses and equilibrium intracavernous pressures of 80 mmHg or more (range 80 to 136) sustained for 30 minutes or longer. Corporeal veno-occlusive testing revealed that flow-to-maintain (0.5 to 3 ml. per minute) and pressure decay (0 to 47 mmHg) values as well as pharmaco-cavernosography findings (absent or minimal contrast medium in venous structures in 92% of the cases) were all consistent with low outflow erection states. Arterial testing revealed right and/or left cavernous systolic arterial blood pressures always at 80 mmHg or more, consistent with a prerequisite cavernous artery pressure value for a positive injection test. Systemic-cavernous systolic arterial blood pressure gradients were 0 to 24 mmHg, 25 to 34 mmHg and 35 mmHg or more in 47 (59%), 18 (22%) and 15 (19%) patients, respectively. Large systemic-cavernous pressure gradients suggested the presence of arterial occlusive disease. In 8 patients with positive injection tests and gradients of 35 mmHg or more pharmaco-arteriography revealed hemodynamically significant arterial occlusions. In conclusion, hemodynamic data in selected patients with positive injection tests revealed low outflow erection states, threshold cavernous artery pressures and disparities in systemic-cavernous systolic pressure gradients that suggested arterial disease in 19% of the cases. The erectile response in a positive test is equal to or greater than a threshold response, not always the maximum response as determined by the systemic blood pressure. A positive intracavernous injection test did not necessarily signify normal erectile hemodynamics.

Ultrastructural analysis of the cavernous and dorsal penile nerves in experimental diabetes.

The present study was designed to investigate whether experimental diabetes determines structural changes in peripheral nerves involved in reflexogenic erection, namely the cavernous and the dorsal nerve of the penis. Myelinated axons were examined in the dorsal nerve of the penis from rats with streptozotocin-induced diabetes (3- and 6-month duration). Morphometric analysis disclosed a significant decrease of myelinated fibre size most likely due to a progressive axonal atrophy. In addition, morphological analysis revealed diffuse accumulation of glycogen within axons, lipid droplets in Schwann cells and pronounced sequestration of axoplasm by adaxonal Schwann cell processes. These signs were particularly prominent in 6-month-diabetic rats. Myelinated and unmyelinated axons of the cavernous nerve were analysed in 6-month-diabetic animals. No substantial ultrastructural abnormalities were found in the cavernous nerves. These results suggest that in experimental diabetes regionally specific structural changes occur in neuronal pathways subserving erectile function.

Priapism of the clitoris: a case report following trazodone use.

We report a case of painful priapism of the clitoris lasting 24 hours, which was believed to be pathophysiologically associated with the administration of trazodone hydrochloride. Drug-induced unusual erectile activity in the clitoris has been described previously. However, to our knowledge this is the first reported case of drug-induced priapism of the clitoris. Management involved discontinuation of the offending agents and administration of adrenergic agonists to induce clitoral smooth muscle contraction. Clitoral function, proposed to be the ability to engorge and enable extrusion of the glans clitoris, was not obviously adversely affected by the priapistic episode.

Effect of streptozotocin-induced diabetes on electrically evoked erection in the rat.

This study was designed to investigate whether experimental diabetes in rats could functionally affect reflexogenic erection. Erection was elicited by means of electrical stimulation of the dorsal nerves of the penis and recorded as intracorporeal pressure. Rats were examined 1, 3 and 6 months after diabetes induction by streptozotocin. Three and 6 month diabetes caused a significant decrease of latency for erection and a slower phase of detumescence when compared to age-matched controls. In addition, a trend for a lower developed intracorporeal pressure was present in the 6 month diabetes group. Our results indicate that experimental diabetes is associated with alterations of reflexogenic erection.

Prostaglandin E1 diluted solution: preparation technique and stability evaluation.

The authors describe their prostaglandin E1 dilution method for the treatment of male erectile dysfunction. Preparation stability was investigated. Results suggest that PGE1 diluted solution can last as long as 90 days, while decreased concentrations of PGE1 are detected after three months.

Electrical stimulation of the dorsal nerve of the penis evokes reflex tonic erections of the penile body and reflex ejaculatory responses in the spinal rat.

An animal model using the spinal rat was characterized. Electrical stimulation of the dorsal nerve of the penis elicited reflex tonic erections of the penile body and reflex bulbospongiosus muscle activity, flips and ejaculations. The tonic erections of the penile body are independent from contractions of the bulbospongiosus muscle and appear to be the result of a neurovascular process. Our observations suggest that reflex bulbospongiosus muscle activity, flips and ejaculations are a single complex reflex response, which we define as reflex ejaculatory response. Two parameters predicted the occurrence and type of reflex response. The visualization of bulbospongiosus muscle activity during surgical isolation of the dorsal nerve of the penis was sufficient to anticipate the elicitability of reflex ejaculatory responses. The latter, together with a systemic systolic pressure > or = 73 mmHg., warranted the elicitability of reflex tonic erections. The similarities found in the physiology of rat tonic penile body erections and of human erections make this model promising for further elucidation of sexual function. Moreover, the present model may prove useful for the investigation of neurogenic erectile dysfunction, and of neurogenic ejaculatory disorders.

Intraluminal device pressures in 3-piece inflatable penile prostheses: the "pathophysiology" of mechanical malfunction.

The role of intraluminal device pressure in the development of mechanical failures in 3-piece inflatable penile prostheses was investigated in a 2-part study. An in vitro study was performed in which mean intraluminal device pressures were recorded in Mentor IPP, Mentor Alpha-1, AMS 700 CX and AMS Ultrex devices. At maximum inflated volumes mean intraluminal device pressures exceeded 600 and 1,000 mm. Hg at rest, and 850 and 1,300 mm. Hg following external loading in Mentor and AMS products, respectively. The AMS 700 CX was associated with the highest mean intraluminal device pressure, with values approaching 1,400 mm. Hg following external loading. A 4-year clinical review at our institution was performed comparing the mechanical malfunctions in 51, 3-piece implants with connectors between the pump and cylinders (AMS 700 CX) to the mechanical malfunctions of 50, 3-piece implants with pre-connected tubing between the pump and cylinders (Mentor Alpha-1). Fluid leaks were identified in 16% of the former and 4% of the latter devices. It is proposed that the high intraluminal device pressures are an important factor in the pathophysiology of the mechanical malfunctions in 3-piece inflatable penile prostheses and that connectors are considered components at risk for pressure-associated fluid leaks. The ideal penile prosthesis should maintain the superior rigidity and cosmetic features of the 3-piece inflatable penile prosthesis. However, the device should be pre-connected and designed to mimic more closely the anatomy of the human penis to achieve functional erections at lower intraluminal device pressure values.

Bilateral renal cell carcinoma with caval invasion in a woman with duplicated inferior vena cava.

Workup of a woman presenting with a palpable right flank mass, detected bilateral renal solid lesions, later proved to be renal cell carcinomas, and caval invasion in the presence of duplicated inferior vena cava. This association does not appear to have been previously described. The patient underwent right radical nephrectomy, cavotomy and auriculotomy with caval thrombus removal and delayed enucleation of left renal masses and left adrenalectomy. Eighteen months after surgery the patient is alive and without local and distant recurrence.