A prospective, randomized, placebo-controlled trial of on-Demand vs. nightly sildenafil citrate as assessed by Rigiscan and the international index of erectile function.

Multiple studies have evaluated the use of PDE5 inhibitors in penile rehabilitation following nerve-sparing prostatectomy. These studies have evaluated the use of various pharmacologic agents as well as various approaches to treatment (on-demand vs. rehabilitative). Most of these studies relied on self-reported outcomes to determine efficacy of the therapy which could allow response bias to affect their results. The aim of this study was to evaluate the effects of nightly sildenafil citrate therapy during penile rehabilitation, using nocturnal penile rigidity (RigiScan(™), Gotop Medical, Inc., St. Paul, MN, USA) in addition to the IIEF-EF. Patients with localized prostate cancer and normal erectile function prior to nsRP were randomized to take either nightly 50 mg sildenafil citrate or placebo starting the night following surgery. Both groups were allowed on-demand sildenafil citrate. Erectile function was evaluated at 2 weeks, 3, 6, 9 and 12 months post-operatively, with a final assessment made at 13 months, following a 1 month drug washout. At all time points, self-reported (IIEF-EF) and objective (RigiScan(™)) measures were obtained and evaluated. About 74 of 97 randomized patients completed the study. On completion, 40% of patients in each group had normal erectile function based on RigiScan(™) (p = 1.0). Additionally, no statistical differences were seen using the IIEF-EF domain (32.4% of placebo, 29% of treatment; p = 0.79). Multivariable analysis showed no significant differences in erectile function based on treatment intervention. Results did show that African-American men in this cohort were at higher risk for lower RigiScan(™) scores over time (OR: 0.48, p = 0.0399). This study demonstrates that nightly sildenafil citrate does not provide a therapeutic benefit for recovery of erectile function post-prostatectomy when compared to on-demand dosing using both self-reported as well as objective measures. Differences in objective recovery parameters based on patients' race/ethnicity warrant further investigation.

Direct androgen regulation of PDE5 gene or the lack thereof.

Inhibition of phosphodiesterase-5 (PDE5) is a well-known mechanism for the effective treatment of erectile dysfunction (ED). Androgen supplementation has also been prescribed for treating ED. However, it has been widely accepted that androgen can upregulate PDE5 expression, and thus creating a paradox in which a positive regulator of erectile function (androgen) could possibly increase the level of a negative regulator (PDE5). To solve this paradox, we conducted a systematic search of the PubMed and a non-systematic search of the Internet using PDE5, erectile, penis, testosterone and androgen as keywords. The retrieved papers were analyzed for data concerning the expression and regulation of PDE5 by androgens. Human and rat PDE5A gene sequences were retrieved from GenBank and computer-analyzed. The results showed that a putative androgen-response element (ARE) was reported in a study of human PDE5A gene promoter, and this prompted a separate study on whether androgen regulates PDE5 expression. The positive outcome in the latter study has since been cited in 17 review and editorial articles as the underlying mechanism for androgen's therapeutic effects on ED. In addition, five other research studies also reached the same conclusion. On the other hand, two independent studies on the genome-wide searches for androgen-regulated genes did not find PDE5A as a candidate. Sequence analysis conducted in this study also failed to find ARE in rat PDE5A gene. Two independent studies on Leydig cells also failed to find positive regulation of PDE5 expression by androgen. Two other studies found concomitant reduction of cavernous smooth muscle and PDE5 expression in castrated rats. One of these studies also found no effect of androgen on PDE5 expression in cultured cavernous smooth muscle cells. Thus, it appears that reduced PDE5 expression in castrated animals is due to reduced smooth muscle content and that PDE5A gene is not directly regulated by androgens.

How curved is too curved? The severity of penile deformity may predict sexual disability among men with Peyronie's disease.

Peyronie's disease (PD) is caused by progressive fibrotic scarring of the tunica albuginea resulting in curvature or other deformities of the erect penis. The severity of penile curvature or other deformity may contribute to a man's inability to have intercourse (sexual disability), due to difficulty with penetration, partner pain or emotional stress. To determine whether the degree of curvature or type of penile deformity predicts sexual disability among men with PD. This cross-sectional analysis of consecutive men evaluated for PD at a single tertiary referral center used a PD-specific questionnaire to evaluate risk factors for sexual disability in men with PD, who did not have erectile dysfunction (ED). Multivariate logistic regression was used to determine the clinical predictors of sexual disability. Sexual disability as defined by the inability to have penetrative intercourse. A total of 202 men were evaluated and 88 men with ED were excluded. Sexual disability was associated with relationship problems, penile curvature and penile length loss in bivariate, but not multivariate analysis. We found that although many of the demographic, medical and sexual function domains were significant predictors of inability to have sex, the only significant predictor of sexual disability in multivariate analysis was curvature>60° (odds ratio 3.23 95%CI 1.08-9.67). PD can be sexually disabling in many men without ED. Severe penile curvature is a robust independent predictor of the ability to have intercourse. Other penile deformities fail to predict sexual disability. This is important for counseling patients with newly diagnosed PD and those who are considering medical or surgical intervention.

A coculture system of cavernous endothelial and smooth muscle cells.

In erectile dysfunction (ED) research, monocultures of cavernous endothelial cells (CECs) and smooth muscle cells (CSMCs) have been reported, but a CEC-CSMC coculture system is still lacking. In the present study, we wished to investigate the feasibility of setting up such a system and test whether it can be used for diabetic ED research. Cavernous tissues were obtained from patients undergoing surgery for penile prosthesis. CSMCs were isolated by explant culture and verified by calponin staining. CECs were isolated by binding to CD31 antibody, followed by magnetic capture. These CECs were nearly 100% pure endothelial cells as determined by flow cytometric analysis for endothelial markers CD31, vWF and eNOS. Functional analyses, that is, low-density lipoprotein (LDL) uptake and capillary tube formation, also confirmed their endothelial phenotype. When cocultured with CSMCs, CECs formed capillary-like structures, and based on the extent of this capillary-like network, it was determined that a ratio of 1:4 in cell number between CECs and CSMCs was better than ratios of 1:1 and 1:9. It was also found that direct contact between CECs and CSMCs was necessary and a coculture period of 3 weeks was optimal. Autologous CSMCs were better than allogeneic CSMCs, and fibroblasts were completely incompetent. When treated with high glucose (25 mM), the CEC-CSMC coculture expressed significantly lower level of CD31 but significantly higher level of collagen-IV (Col-IV), and the diameter of the capillaries increased significantly, when compared with normal glucose (5 mM)-treated cocultures. These data are consistent with previously observed changes in the cavernous tissues of diabetic patients and thus suggest that the coculture system could be utilized for diabetic ED research.

Tracking intracavernously injected adipose-derived stem cells to bone marrow.

The intracavernous (i.c.) injection of stem cells (SCs) has been shown to improve erectile function in various erectile dysfunction (ED) animal models. However, the tissue distribution of the injected cells remains unknown. In this study we tracked i.c.-injected adipose-derived stem cells (ADSCs) in various tissues. Rat paratesticular fat was processed for ADSC isolation and culture. The animals were then subject to cavernous nerve (CN) crush injury or sham operation, followed by i.c. injection of 1 million autologous or allogeneic ADSCs that were labeled with 5-ethynyl-2-deoxyuridine (EdU). Another group of rats received i.c. injection of EdU-labeled allogeneic penile smooth muscle cells (PSMCs). At 2 and 7 days post injection, penises and femoral bone marrow were processed for histological analyses. Whole femoral bone marrows were also analyzed for EdU-positive cells by flow cytometry. The results show that ADSCs exited the penis within days of i.c. injection and migrated preferentially to bone marrow. Allogenicity did not affect the bone marrow appearance of ADSCs at either 2 or 7 days, whereas CN injury reduced the number of ADSCs in bone marrow significantly at 7 but not 2 days. The significance of these results in relation to SC therapy for ED is discussed.

Association of lower urinary tract symptoms and erectile dysfunction: pathophysiological aspects and implications for clinical management.

There is strong evidence from multiple epidemological studies that lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are correlated, independent of age or comorbidities as diabetes or hypertension. Although a direct causal relationship is not established yet, four pathophysiological mechanisms can explain the relationship. These include alteration in nitric oxide bioavailability, α1-adrenergic receptor hyperactivity, pelvic atherosclerosis and sex hormones. This association has different clinical implications on the management of both disorders. Men seeking care for one condition should always be screened for complaints of the other condition. Sexual function should be assessed and discussed with the patient when choosing the appropriate management strategy for LUTS, as well as when evaluating the patient's response to treatment. Multiple large clinical trials have shown an improvement in LUTS after phosphodiesterase-5 (PDE5)-inhibitor treatment. PDE5 inhibitors show promise as a future treatment for LUTS, either in conjunction with existing therapies or as a primary treatment. There may be a potential therapeutic role for testosterone in LUTS treatment in cases of testosterone deficiency that needs to be investigated. Much further investigation is required, but it is evident that the association between LUTS and ED is fundamental for future therapies and possible preventative strategies.

Peyronie's disease: a critical appraisal of current diagnosis and treatment.

Peyronie's disease is a fibrotic disorder of the tunica albuginea of the penis resulting in varying degrees of penile curvature and sexual dysfunction. Diagnosis of the disorder is made by detailed sexual history and focused physical examination. A wide range of medical treatments has been employed to treat the disorder. Verapamil treatment administered by intraplaque injection is supported by generally consistent randomized controlled trials (RCT). Some RCT evidence exists to support the use of colchicine, potaba, L-carnitine and liposomal superoxide dismutase. Future studies of medical efficacy should focus on improving RCT design, implementation and results reporting to improve the quality of evidence generated by each study. The surgical treatment of Peyronie's disease is a viable and recommended alternative for men with compromised sexual function due to severe curvature or lesions causing penile instability. The choice of corrective procedure should be tailored to each patient after a detailed evaluation of disease severity and sexual function.

Drugs designed to improve endothelial function: effects on erectile dysfunction.

Endothelial dysfunction (EtD) has emerged as a critical master pathway in the pathogenesis of both vascular disease and erectile dysfunction (ED). Drugs that have been developed for vascular diseases and/or found to have beneficial endothelial effects may be helpful in the management of ED. In this manuscript we summarize the current state of the art with respect to endothelial active drugs and discuss the evidence supporting their use in the management of ED. Pubmed query for the terms Endothelial dysfunction, erectile dysfunction, pharmaceuticals, "endothelium", "function", "pharmaceutical", "eNOS", "erectile dysfunction" and "erectile function" was conducted. Relevant articles were reviewed and summarized. A variety of cardiovascular medications have mechanisms of action that involve the endothelium. Examples include HMG-CoA Reductase inhibitors ("statins"), Angiotensin Converting Enzyme Inhibitors (ACEI), Angiotensin Receptor blockers (ARB), Endothelin Receptor Antagonists (ERA), certain beta blockers, and some oral hypoglycemics. Some of these drugs have been found to improve penile erection, although an endothelium dependent mechanism has not been conclusively demonstrated in all studies. Drugs that improve endothelial function in the cavernous arteries and the erectile tissues of the corpora cavernosa hold great promise in treating or at least minimizing the vascular damage that contributes to ED. ACEI and ARB appear to hold great promise in this regard, while statins and oral hypoglycemics may play a potentially useful role as adjunctive therapy for ED. Improvements in endothelial function may help reverse ED in some cases, which would be a marked improvement over management with currently available "on demand" ED therapies.

Health issues of men: prevalence and correlates of erectile dysfunction.

PURPOSE: The Cross-National Survey on Men's Health Issues was a population based, international survey of men using the health care systems of participating countries. The prevalence of erectile dysfunction (ED) and its correlation with patient age, overall health and comorbidities were assessed. MATERIALS AND METHODS: Men who were 20 to 75 years old in the United States, Germany, United Kingdom, France, Italy and Spain were recruited to participate in the study. During visits to physician offices participants completed a screening questionnaire about their overall health, and problems with prostate, urination and penile erection. Men who reported ED completed a followup questionnaire. RESULTS: A cohort of 28,691 men completed the screening questionnaire and provided their age. Respondents in the oldest age group (70 to 75 years) were at 14-fold higher relative risk for ED than respondents in the youngest age group (20 to 29 years). ED correlated positively with poor overall health, and prostate and urinary problems. The prevalence of comorbid conditions increased with ED severity. Only a small percent of men with ED (2% to 8%) were using nitrates for comorbid cardiac disorders. Approximately 10% to 20% of men were on beta-blockers. CONCLUSIONS: The results of this survey are consistent with those of other population based reports showing a high correlation between ED prevalence and patient age, and ED and lower urinary tract symptoms. The prevalence of comorbidities, such as vascular conditions, increased with ED severity, which may indicate that ED is a prognostic marker of overall health and an important medical condition.

Growth factor therapy and neuronal nitric oxide synthase.

Trauma to the cavernous nerve is a known cause of erectile dysfunction, with lengthy and often incomplete recovery. Using rat models, we have previously shown that injury to the cavernous nerves or ligation of pudendal arteries causes a significant decrease of neuronal nitric oxide synthase (nNOS) in the dorsal nerve of the penis and intracavernosal tissue as well as loss of erectile response to neurostimulation. Intracavernous injection of vascular endothelial growth factor or brain-derived neurotrophic factor facilitates the recovery of nNOS and erectile function. Studies are underway to elucidate the molecular mechanism of cavernous nerve regeneration and the potential of using growth factors to enhance the recovery of erectile function in patients after radical pelvic surgery. International Journal of Impotence Research (2004) 16, S38-S39. doi:10.1038/sj.ijir.3901214

Effect of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 complex in cavernous nerve cryoablation.

The purpose of this work was to study the effect of insulin-like growth factor 1 (IGF-1) and its binding protein (IGFBP-3) on the recovery of erectile function in a rat model for neurogenic impotence. In all, 28 male Sprague-Dawley rats were divided into four groups: seven underwent a sham operation; seven underwent bilateral cavernous nerve freezing (control group); seven underwent bilateral cavernous nerve freezing followed by intraperitoneal injection of IGF-1; and seven underwent bilateral cavernous nerve freezing followed by intraperitoneal injection of IGFBP-3. Erectile response was assessed by cavernous nerve electrostimulation at 3 months, and samples of penile tissue were evaluated histochemically for nitric oxide synthase (NOS)-containing fibers. In the sham and IGF-1 group, there were significantly higher maximal intracavernous pressures compared to the IGFBP-3 complex and the control group. Correspondingly in the cavernosum, there were significantly more NOS-containing nerve fibers in the sham and IGF-1 groups. In conclusion, administration of IGF-1 can facilitate the regeneration of NOS-containing nerve fibers in penile tissue and enhance the recovery of erectile function after bilateral cavernous nerve cryoablation. The reverse effect was noted with the IGFBP-3 complex injection.

Downregulation of androgen, estrogen and progesterone receptor genes and protein is involved in aging-related erectile dysfunction.

We hypothesize that downregulation of sex hormone receptors (androgen, estrogen and progesterone receptors) is involved in aging-related erectile dysfunction. To test this hypothesis, we investigated the expression of sex hormone receptors in penile crura of aging rats. A total of 40 rats were divided into four groups based on age (6, 12, 18 and 24 months), and the erectile function was analyzed by the measurement of intracavernous pressure. Gene and protein expressions of sex hormone receptors were analyzed by RT-PCR and immunostaining, respectively. The mean intracavernous pressures of 6-, 12-, 18- and 24-month-old rats were 110.1, 89.6, 73.5 and 42.7 cm H(2)O, respectively. Gene and protein expressions for androgen receptor, estrogen receptor-beta and progesterone receptor were present in similar levels in 6-, 12- and 18-month-old rat crura, but significantly lower or absent in 24-month-old crura. This is the first study to demonstrate that downregulation of sex hormone receptors in aging rat crura is associated with erectile dysfunction.

Wogonin suppresses cellular proliferation and expression of monocyte chemoattractant protein 1 in Peyronie's plaque-derived cells.

OBJECTIVE: To test the effect of wogonin on cellular proliferation and expression of monocyte chemoattractant protein 1 (MCP-1) in cells derived from normal and diseased tunica albuginea (TA), as related to Peyronie's disease (PD). MATERIALS AND METHODS: Cells with characteristics of fibroblasts were isolated from three tissue sources. Those from the plaque of patients with PD were designated as P cells, those from the adjacent, normal-appearing tissue as C cells, and those from the TA of patients without PD as N cells. These cells were treated with wogonin at doses of 0, 10, 20 and 40 micromol/L for 24 h or treated at a fixed dose of 40 micromol/L for 1, 8 and 24 h. Cell proliferation was assayed with a commercial kit, MCP-1 mRNA expression by reverse transcription-polymerase chain reaction, and secreted MCP-1 by enzyme-linked immunosorbent assay. RESULTS: Wogonin suppressed cell proliferation in a dose-dependent manner; the effect was more pronounced against P cells at 8 and 24 h. Wogonin down-regulated MCP-1 mRNA expression, especially in P cells. Wogonin suppressed the level of secreted MCP-1 by 59-88%. P cells, which secreted far more MCP-1 than N and C cells at 1 h, were suppressed by 88%. C cells were the least suppressed at all three times. CONCLUSIONS: Wogonin suppressed the proliferation, the expression of MCP-1 mRNA, and the expression of secreted MCP-1 in TA-derived cells. In most cases, the effect of wogonin was greatest against cells derived from the plaque. Wogonin appears to be a worthy candidate for preclinical trials in men with PD.

The treatment of priapism--when and how?

Priapism is a condition first described by Tripe in 1845. It has been defined as a pathological condition of penile erection that persists beyond or is unrelated to sexual stimulation. Two variants of priapism have been well described. The ischemic priapism (also known as low-flow priapism) and nonischemic priapism (or high flow priapism) have unique and distinct causes. It is important to distinguish these two conditions as the treatment for each is different. This review will focus on the two types of priapism and the appropriate diagnostic work-up for each. As well, the medical and surgical treatment options for these two conditions will be described in detail. A third entity known as stuttering priapism will also be discussed as will its unique treatment alternatives.

Neurotrophic effects of vascular endothelial growth factor and neurotrophins on cultured major pelvic ganglia.

OBJECTIVE: To investigate the feasibility of using a ganglial culture system to screen various growth factors as potential therapeutic agents for pelvic nerve injuries. MATERIALS AND METHODS: The major pelvic ganglia (MPG) were isolated from male rats and attached to culture dishes with the aid of Matrigel (Becton Dickinson, Mountain View, CA, USA). Alternatively, the dorso-caudal region (DCR) of MPG, from which the cavernous nerves originate, was dissected and then attached to a Matrigel-coated coverslip. The MPG or DCR was cultured in serum-free medium supplemented with phosphate-buffered saline (PBS, control), 50 ng/mL of vascular endothelial growth factor (VEGF), 20 ng/mL of a neurotrophin (BDNF, NT3, or NT4), or combinations of these growth factors. After 2 days of incubation, the ganglial tissues with their outgrowing nerve fibres were stained for the expression of NADPH-diaphorase, tyrosine hydroxylase (TH) and acetylcholinesterase (AChE). The length and staining intensity of nerve fibres were analysed. RESULTS: The outgrowing fibres were significantly longer in MPG treated with any of the four tested growth factors than in PBS-treated MPG. The combination of VEGF and NT3 induced the best fibre growth. Improvements to the culturing conditions allowed a histological examination of the outgrowing fibres for the expression of nitric oxide synthase (NOS), TH and AChE. VEGF and BDNF were equally capable of inducing NOS- and TH-expressing fibres. BDNF was much weaker than VEGF for inducing AChE-expressing fibres. CONCLUSIONS: This improved culturing system is potentially useful for screening nerve-regenerating factors; VEGF had neurotrophic effects comparable with BDNF, NT3, or NT4.

The effect of vascular endothelial growth factor and brain-derived neurotrophic factor on cavernosal nerve regeneration in a nerve-crush rat model.

OBJECTIVE: To test the hypothesis that an intracavernosal injection with brain-derived neurotrophin factor (BDNF) and vascular endothelial growth factor (VEGF) can facilitate nerve regeneration and recovery of erectile function after cavernosal nerve injury. MATERIALS AND METHODS: The study included 25 Sprague-Dawley rats; four had a sham operation, seven bilateral nerve crushing with no further intervention, and 14 bilateral nerve crushing with either an immediate (seven) or delayed for 1 month (seven) intracavernosal injection with BDNF+VEGF. Erectile function was assessed by cavernosal nerve electrostimulation at 3 months, and neural regeneration by NADPH-diaphorase staining and tyrosine hydroxylase (TH) staining of penile tissue and major pelvic ganglia (MPG). RESULTS: After nerve crushing, the functional evaluation at 3 months showed a lower mean (SD) intracavernosal pressure (ICP) with cavernosal nerve stimulation, at 33.9 (15.3) cmH2O, than in the sham group, at 107.8 (18.1) cmH2O. With an immediate injection with BDNF+VEGF the ICP was significantly higher than in the controls, at 67.8 (38.5) cmH2O. Even delayed injection with BDNF+VEGF improved the ICP, to 78.0 (21.8) cmH2O. Histological analysis of specimens stained for NADPH and TH showed a significant change in the morphology of terminal branches of the cavernosal and dorsal nerves, and the staining quality of the neurones in the MPG. The number of positively stained nerve fibres tended to revert to normal after treatment with BDNF+VEGF. CONCLUSION: An intracavernosal injection with BDNF+VEGF appears to both prevent degeneration and facilitate regeneration of neurones containing neuronal nitric oxide synthase in the MPG, dorsal nerve and intracavernosal tissue. Therefore it might have therapeutic potential for enhancing the recovery of erectile function after radical pelvic surgery.

Isolation of two isoforms of phosphodiesterase 5 from rat penis.

Inhibition of cGMP-specific phosphodiesterase type 5 (PDE5) has been shown to improve penile erection in patients with erectile dysfunction. We have reported previously the cloning of three PDE5 isoforms from human penile tissues. Here we report the cloning of two PDE5 isoforms from rat penile tissues. The similarity between rat and human PDE5A1-specific sequences were 68 and 88% at the nucleotide and amino-acid levels, respectively. Like the bovine and canine PDE5A1 sequences, the rat PDE5A1 sequence lacks the polyglutamine tract that appears to be unique to the human PDE5A1 sequence. The similarity between rat and human PDE5A2-specific sequences were 64 and 100% at the nucleotide and amino-acid levels, respectively. The equivalent of human PDE5A3-specific sequence was identified in the rat PDE5A gene; however, repeated efforts to clone the putative rat PDE5A3 isoform were not successful. Expression of PDE5A1 and A2 mRNA in various tissues was examined by Northern blotting and reverse transcription-polymerase chain reaction. Results from the two experimental procedures were largely in good agreement and indicated that PDE5A1 and A2 mRNA were expressed in a tissue-specific manner with PDE5A2 being the dominant isoform. International Journal of Impotence Research (2003) 15, 129-136. doi:10.1038/sj.ijir.3900983

Intracavernosal vascular endothelial growth factor (VEGF) injection and adeno-associated virus-mediated VEGF gene therapy prevent and reverse venogenic erectile dysfunction in rats.

Penile veno-occlusive dysfunction (venogenic erectile dysfunction) is a common cause of erectile dysfunction (ED). We investigated whether vascular endothelial growth factor (VEGF) can be used to prevent and reverse venogenic ED in a rat model. Pharmacological cavernosometry was developed and validated using adult male rats with either arteriogenic or venogenic ED. Castrated animals were treated with intracavernous VEGF as either a recombinant protein (C+VEGF) or adeno-associated virus (AAV)-mediated VEGF gene therapy (C+VEGF gene) in an attempt to prevent the development of venogenic ED. Other animal groups received testosterone replacement (C+testosterone) or intracavernous AAV-LacZ gene (C+LacZ). Animals with documented venogenic ED were treated with intracavernous VEGF in an attempt to reverse their ED. Functional analysis (pharmacological infusion cavernosometry) was performed following treatment. Penile specimens were harvested for immunohistochemistry and electron microscopic evaluation. Castrated rats showed a decrease in papaverine-induced intracavernous pressure and an increase in maintenance and drop rates during pharmacological cavernosometry. These changes were prevented by systemic testosterone and intracavernous VEGF or AAV-VEGF therapy. Moreover, intracavernous VEGF was able to reverse the venogenic ED produced by castration. The quantity of penile smooth muscle detected by alpha actin staining decreased after castration but not in the C+T, C+VEGF, or C+VEGF gene groups. Transmission electron microscopy revealed atrophy of penile smooth muscle cells and nerves in the castrated rats. In VEGF-treated rats, regeneration of smooth muscle and nerves as well as endothelial cell hypertrophy and hyperplasia were the prominent features. In our animal model, systemic testosterone replacement or intracavernous VEGF (protein and VEGF gene) prevented the veno-occlusive dysfunction in castrated animals. In rats with established venous leakage, VEGF treatment reversed the cavernosometric findings of leakage. Intracavernous injection of either VEGF protein or VEGF gene may be a preferred therapy to preserve erectile function in patients in whom testosterone therapy is contraindicated.

Surgical management: saphenous vein grafts.

Peyronie's disease is a medically and surgically challenging condition to manage. Most surgical techniques to correct the penile deformity often shorten the penis and do not address the issue of hourglass deformity when present. We describe our indications, rationale and technique for the use of a saphenous vein graft after a curvature correcting plaque incision. In reviewing multiple series, this approach yields similar results-incidence of residual curvature: 4-20%, decreased potency: 5-20%, penile shortening: 17-40%. While harvesting the vein would require a second incision, the use of autologous vein appears to be associated with the least amount of intracavernosal fibrosis. We propose that saphenous vein is currently the best material available for tunical patching. The technique and results of circular venous grafting for patients with severe penile shortening secondary to Peyronie's disease is also discussed.