Even nerve-sparing radical prostatectomy damages the cavernous nerves and leads to temporary erectile dysfunction (ED) in men recovering from prostate cancer surgery. Historically, patients recovering from prostate cancer surgery have been advised that the return of erectile function (EF) can take from 6 to 18 months, or even longer. Unfortunately, the return of sexual function in these patients remains variable, but is generally thought to be dependent on the individual patient's pre-surgery EF, as well as the degree of cavernous nerve disruption during prostate removal. Recently, there has been a growing movement to proactively treat patients postoperatively for presumed nerve damage to stimulate nerve recovery and possibly reduce the degree of irreversible damage. This would reduce the on-demand therapy these patients would require, and hopefully remove the requirement for an implantable prosthesis. The underlying hypothesis is that the artificial induction of erections shortly after surgery facilitates tissue oxygenation, reducing cavernosal fibrosis in the absence of nocturnal erections, potentially increasing the likelihood of preserving EF. Vacuum erection devices (VED), because of their ability to draw blood into the penis regardless of nerve disturbance, have become the centerpiece of penile rehabilitation protocols. This review will discuss the pathophysiology of radical prostatectomy induced ED and the rationale for rehabilitation. It will then discuss current protocols, including those involving the VED.
Prostate cancer is the leading cause of non-cutaneous cancer in men in the United States, with 232 000 men diagnosed and 30 350 men dying of the disease in 2005.1 One of the current gold standards for treatment of localized disease is the radical prostatectomy (RP). The number of these surgeries performed has increased significantly since the early 1980's for two primary reasons. First, the number of prostate cancer cases detected has increased secondary to the advent of the prostate specific antigen.2 Also, the anatomical discoveries made by Walsh and Donker3 have revolutionized this approach by devising cavernous nerve-sparing procedures, making the procedure more patient friendly.
Whereas potency rates as high as 70–86% have been reported in academic centers, community surgeons report a much lower rate, from 20 to 50%.4, 5, 6, 7 Furthermore, the exact definition of potency varies across studies. It is not surprising that sexual dysfunction is considered the most pressing quality of life issue 2 years after prostate surgery.8
After surgery, a period of neurapraxia is almost universally experienced by men, leading to at least transient erectile dysfunction (ED). Indeed, Mulhall and colleagues9 have shown that solely exposing the nerves without a formal injury leads to decreased erectile response. This cavernosal nerve disruption, even if brief, can lead to permanent smooth muscle damage and decreased long-term erectile function (EF).10, 11 Provoking an artificial erection during this time is thought to minimize cavernous tissue fibrosis, leading to potentially improved erection quality or decreased need for supplemental agents. These early observations have led to the development of post-RP penile rehabilitation protocols that employ various combinations of oral12, 13, 14 and intercavernosal agents,15 as well as the vacuum erection device (VED).16, 17
Given recent advances in surgical technique, it is logical that careful examination should be dedicated to the establishment and validation of a post-RP protocol that improves EF outcomes. This review will discuss the pathophysiology of post-prostatectomy ED, the various rehabilitation protocols being studied and the use of the VED for this condition.
The neurapraxia caused by RP, be it nerve sparing or non-nerve sparing, is a multifactorial process, which is still not completely understood. During the procedure, mechanical damage to the nerves can occur by stretching, cutting or by thermal injury during electrocautery. Ischemia to the nerves can occur during hemostasis, and local inflammatory effects can prove deleterious both intra- and postoperatively.18 In fact, even under the best of nerve-sparing conditions, some nerve damage is inevitable due to the proximity of the nerves to the prostate gland and the traction damage incurred during surgery.4 Even though it may be temporary, this damage may lead to denervation atrophy of the corpora cavernosa, which in turn leads to at least temporary ED.
Much like other muscle groups, when its innervation is removed, cavernosal smooth muscle fibers degenerate sometime in the first 3–6 months.19 Apoptosis is also likely to play a role, as this has been shown in rat penile tissue after cavernous nerve denervation.20 Decreased smooth muscle tissue is accompanied by increased collagen type I and III deposition in rats after bilateral neurectomy and in men after RP.21, 22 It is possible that corporal smooth muscle apoptosis and increased collagen deposition seen in the rat nerve-crush model may also be present in human patients recovering from RP. This may be associated with the time-dependent increase in the incidence of venous leak found in patients as they recover from RP.23
The partial pressure of oxygen (pO2) within the corpus cavernosum is significantly higher in the erect vs the flaccid state.24 Furthermore, patients after RP lose the normal 3–5 nocturnal erections per night, a source of high arterial oxygen tension for 1 to 3.5 h per night.25 Lack of erections therefore leads to poorly oxygenated cavernosal tissue. Sustained hypoxia causes overexpression of transforming growth factor-β 1.26 This leads to increased synthesis of endothelin-1, which is a constrictor of penile smooth muscle and a profibrotic agent.27 This fibrosis leads to decreased EF.28, 29, 30 Low oxygen tension also decreases the level of prostaglandin-E1, which normally inhibits collagen formation by inhibiting transforming growth factor-β 1. Hence, hypoxia also causes fibrosis by loss of this ‘back-up mechanism’.31 Oxygen tension therefore is likely the critical regulator of the delicate balance of smooth muscle and connective tissue by these molecular mechanisms. Under hypoxic conditions, cavernosal smooth muscle is replaced by collagen and the veno-occlusive mechanism required for EF may be significantly injured.
Fraiman et al. were among the first to show changes in penile length and girth after nerve-sparing radical prostatectomy (NSRP). Using a cohort of 100 men undergoing NSRP and matched controls, it was shown that flaccid and erect measurements of length and circumference decreased 8 and 9%, respectively. In addition, a 19 and 22% change by volume in the flaccid and erect states, respectively, were documented between 4 and 8 months postoperatively.10
However, the measurement, which most accurately represents erect length, is stretched flaccid penile length as it is not influenced by state of mind, subjectivity or room temperature.32 This factor was studied 3 months after RP, and it showed that 48% had shortening greater than 1.0 cm.33 It is likely that the injuries, which lead to ED postoperatively, are also responsible for this decrease in size.
Recognizing a vascular component to post-RP ED, Mulhall and colleagues have studied the hemodynamics of corporal tissue after RP in patients receiving no vasoactive medication to correlate changes with the recovery of EF. Ninety-six men after bilateral NSRP underwent cavernosometry or penile ultrasonography at varying postoperative time points. Among them, 35% of men had normal vascular status, 59% had arterial insufficiency and 26% had venous leakage overall. All patients with venous leakage had concomitant arterial insufficiency. Patients tested later in the study had higher degrees of venous leakage than those tested earlier, although this did not hold true for arterial insufficiency.23 Patients with venous leakage had significantly higher levels of ED than those solely with arterial insufficiency or normal hemodynamics, as it is likely the end result of fibrosis. As a result, these patients are not likely to have a satisfactory response to phosphodiesterase-5 inhibitors (PDE5I's).
This arterial inflow decrease seen has been theorized as being secondary to the transection of the accessory pudendal arteries.23, 34 These structures, existing in upwards of 70% of men, 35 course alongside the prostate gland and may be difficult to spare. This decreased arterial flow potentiates the hypoxic state and hastens the post-prostatectomy changes seen.
Given the deleterious effects documented during the period of neuropraxia after RP, there is a compelling need to establish a standard protocol for use during NSRP recovery. No single protocol is currently considered the ‘standard of care’. Indeed, the first line use of therapies after surgery varies drastically. Oral PDE5I's, intracavernous injection (ICI), intraurethral prostaglandins and VED have been used, with too few trials having adequate comparisons with placebo or with other therapies to produce standard guidelines. The initiation of therapies also varies, with some physicians beginning therapy immediately after surgery, some waiting until the urethral catheter is removed and others waiting even longer.36
In the first known trial, Montorsi used prophylactic ICI with prostaglandin-E1 starting 1 to 2 months after RP. A total of 30 previously potent patients underwent NSRP. Among them, 15 started injections three times a week for 12 weeks and 15 were observed. Twelve patients completed the entire treatment regimen, of which eight reported return of spontaneous erection sufficient for intercourse. Only 20% of the observation group reported the same findings. Again, it was postulated that the induced artificial erections decreased hypoxia, and thus cellular damage. For obvious reasons, this trial lacked a placebo group, making comparisons difficult.37
Mulhall et al., studied long-term follow-up (18 months) with ICI as part of his rehabilitation protocol. The overall goal of therapy was to induce erection in men 4 weeks after RP three times weekly with either oral sildenafil or ICI. Men who had adequate EF preoperatively were given sildenafil postoperatively. Non-responders were switched to ICI administered at the same frequency. Men who did not want as aggressive of a protocol were treated on demand. After 18 months, the treatment group had 52% medication-unassisted erections as compared with 19% in the on-demand group. Treated men also had a much higher response to sildenafil after 18 months, as well as higher IIEF–EF domain scores.38 It is noted that the use of needles dissuades men from strict ICI rehabilitation protocols, as the attrition rate is quite high several months into treatment.39
Intraurethral prostaglandins as a rehabilitation agent has been tested in the form of the Medicated Urethral System for Erection (MUSE; Vivus Inc., Mountain View, CA, USA). This medication is prostaglandin E1 that is placed as a suppository intraurethrally. One study involved patients treated immediately after catheter removal with 125 μg MUSE per night for a month, which was then increased to 250 μg per night, which they remained on for 8 months. Both of those doses are sub-erectogenic. Corporal oximetry was then measured. It was found that even at these low doses, blood was arterialized in the penis both immediately after treatment, as well as the day after. As discussed earlier, this increased oxygen tension is the key to avoiding penile fibrosis,40 and MUSE is thus an under-utilized post-RP modality.
An oral-based protocol would likely have higher compliance rates in men (and hence make a placebo controlled study more feasible), given its relatively non-invasive nature. In a 76-patient trial, Padma-Nathan et al. randomized patients to receive sildenafil 50 mg, sildenafil 100 mg or placebo nightly for 36 weeks beginning 4 weeks after NSRP. At the conclusion of the drug administration, a washout period of 8 weeks was provided. The International Index of Erectile Function questionnaire was then administered, revealing that 27% of the treatment group reported return of spontaneous erection sufficient for intercourse versus 4% in the placebo group 1 year after surgery.41
A further study was performed to test nocturnal penile tumescence using a 54-patient subset of this group. A total of 10 out of 35 treatments (4/17 of 50 mg sildenafil recipients and 6/18 of 100 mg sildenafil recipients) and 1 out of 19 placebo recipients were responders, defined by at least 55% penile-based rigidity for at least 10 min.42
The mechanism by which sildenafil is beneficial to early rehabilitation is also a bit puzzling; PDE5I's require intact nerves producing nitric oxide for proper function; the neurapraxia discussed earlier precludes this. There have been theories that PDE5I's may work through a separate, neuron-independent endothelial cell mechanism, but this remains unproven.43
Although multiple trials have suggested some promise with using sildenafil for penile rehabilitation, little has been published on the use of other PDE5I's, and there has been a relative dearth of multi-institutional studies. Montorsi et al. recently completed a multicenter double blinded, parallel group study with preoperatively potent men who underwent NSRP using vardenafil as treatment. Patients were divided into groups based on whether they received vardenafil nightly, on demand or placebo for a total of 9 months. This was followed by a 2-month placebo washout phase and consequently by a 2-month open label on-demand treatment phase with the primary outcome measure being IIEF scores ⩾22. Patients in the on-demand treatment group had greater success than those in the nightly and placebo groups (48.2 vs 32.0 and 24.8%, respectively.). This advantage continues into IIEF scores ⩾26 as well (36.2, 20.1 and 16.8%.) Conversely, no statistical significance was seen in the groups during the washout or open-label phases, suggesting that regular nightly dosage may not hasten return of spontaneous erections, but on-demand use does seem definitely advantageous.44
Vacuum erection devices
The first medically relevant VED was invented for personal use in the 1960's by Geddings D Osbon, Sr given FDA approval in 1982, the technology was eventually adopted into the medical community with the aid of two urologists, Drs Perry Nadig and Roy Witherington, who conducted the first studies regarding its efficacy,45, 46, 47, 48 and the first device received Federal Food and Drug Administration (FDA) approval in 1982.48
The components of the device are generally threefold. The cylinder consists of an open-ended tube constructed of plastic. The vacuum pump attaches to the cylinder and is generally hand activated (but may alternatively be battery powered). Finally, an occlusion ring is placed at the base of the penis after erection is achieved to limit venous leakage and maintain the erection for the duration of intercourse. The patient generally holds the cylinder over his penis with one hand and pumps the device with the other. Negative pressure generated by the pump leads to engorgement of all tissue within the penis. When optimum rigidity is achieved, the occlusion ring is delivered from the base of the device to the penile base. Manufacturers generally recommend that the ring not stay in place for more than 30 min to avoid hypoxic injury to the penis. The usual time required to achieve an adequate penile erection ranges from 30 s to 7 min.46, 49
The complications of VED are generally considered minor; pain with use of the pump and the constriction ring is generally self-limiting. The ring also may cause ejaculatory discomfort or anejaculation secondary to urethral constriction. The penis also may become cool, have a numb feeling, or become bruised, which can initially be disturbing to both partners. As the penis is flaccid proximal to the ring, it may be ‘hinged’ and may require added manipulation during intercourse. Despite the on-demand nature of the device, patients and partners also comment about the lack of spontaneity, much like other interventions.
The overall success rate for VED use varies in the literature. Sidi et al.49 reported a 68% overall satisfaction rate in 1990, and Nadig45, 47 showed over an 80% satisfaction rate for both patient and partner short-term (3-month follow-up) and long-term (29-month follow-up). Witherington46 stated 92% of 1517 patients mailed a retrospective survey were satisfied, with 77% reportedly using it at least every 2 weeks.
However, results from the Netherlands showed only 31% satisfaction in patients who had failed alternative therapies earlier.50 Furthermore, Dutta and Eid51 reported a 35% satisfaction rate based on attrition, despite significant instruction on device use. They also showed that the patients with the highest success with VED were classified as having ‘moderate’ ED or were able to achieve spontaneous firmness for insertion, but unable to maintain it until completion of intercourse. Patients with mild ED almost invariably discontinued use in lieu of alternative treatments.
Regardless, little need for testing is required before VED use, and there are no medical contraindications to its use other than intermittent priapism and significant bleeding disorder. Patients who have failed other forms of treatment can generally be offered this as therapy with little hesitation. VED success has been seen in patients who had previously failed therapy with ICI, and use of the VED was also shown to have a significantly lower attrition rate than injections.52, 53 In patients who had failed oral medication or ICI as monotherapy, combination therapy with one of those and VED was shown to have a greater patient satisfaction rate.54, 55 VED has also been the only modality to be proven successful in patients who had earlier had an explanted penile implant.56
In 2006 the Osbon ErecAid (Timm Medical Technologies Inc., Eden Prairie, MN, USA) received extended labeling from the FDA to specify that patients may use the device to provide arterial (oxygen-rich) blood to the penis, whereas recovering from RP. Preliminary data has shown the VED's ability to stretch smooth muscle fibers leads to improvement of overall EF and potentially the maintenance of penile length.57, 16, 17
VED in rehabilitation protocols
Given its low complication rate, relatively high compliance rate and independence from the nitric oxide pathway, the VED is an ideal modality to use in penile rehabilitation protocols after RP.
Bosshardt et al.,58 measured blood gasses of patients using VED both before and 15 and 30 min after constriction ring application; corporal blood oxygen saturation was 79.2% immediately after VED was applied. It was not surprising that this dropped significantly after 30 min of ring constriction. The constriction ring is not used during rehabilitation protocols for this reason, but it can be used occasionally if patients wish to attempt intercourse early after surgery.
Raina et al., conducted a prospective study with 109 patients undergoing RP, randomized to either undergo daily VED use for 9 months starting 1 month after surgery or to receive no treatment. Patients using the VED did so without a constriction ring except when attempting intercourse to avoid the hypoxic effect mentioned. At the end of the study, they showed a slightly higher rate of natural erections sufficient for vaginal penetration in the treatment vs placebo group (17 vs 11%). Of greater significance was that the treatment group was less likely to feel that their penis was shorter (85 vs 23%). Interestingly, these findings were independent of whether the surgery was nerve sparing or not.59
Dalkin and Christopher administered a prospective study with 42 men to assess the effect of VED on stretched penile length. The day after their catheter was removed, VED use was initiated daily for 90 consecutive days. Patients compliant with the protocol had a significantly decreased risk of having a loss of length greater than 1.0 cm (3%) compared with data from earlier studies in which 48% of men had a significant length reduction.60 This is likely due to the tumescence effect of VED, which oral medications do not usually replicate immediately postoperatively.
Kohler et al. tested stretched flaccid penile length in a prospective randomized trial. They assigned 28 men after RRP to either undergo daily VED usage without a constriction band starting 1 month after surgery for 5 months or to begin 6 months after surgery. The early intervention group had significantly higher IIEF scores in addition to preserved penile length. In contrast, patients not using the VED had approximately 2.0 cm decreased penile length at both 3 and 6 months (in five out of eleven patients).
Studies have been limited by the fact that the optimum length of therapy has not been determined yet; studies have arbitrarily chosen between 3 and 9 months, but the healing process after NSRP can be a year or more.8 Furthermore, some of the studies use subjective measurements, such as perceived length reduction, as end points. Although objective criteria such as stretched flaccid penile length and IIEF measurements have been tested, the numbers enrolled in these trials have been limited, and they have all been single institutional studies. More rigid protocols need to be developed and tested in broader studies with specific objective criteria to be determined.
The goals of early penile rehabilitation are promotion of earlier return of EF, decreased loss of penile length and girth, and overall increased sexual satisfaction. Enthusiasm for these approaches continues to grow. Although the first penile rehabilitation trials involved ICI, patient compliance has generally been low due to the need for a minimum of three injections per week. Intraurethral medications have been tried, but they are generally not as effective as injectables. Oral sildenafil has been actively studied for this purpose, but its mechanism is unclear in these neurapraxic patients, and full erections necessary for optimized healing are generally not obtained with its early use.
The VED, one of the first forms of ED treatment, has only recently been studied for rehabilitation applications. It has been shown to both increase corporal oxygenation and allow for early tumescence while avoiding the use of a needle. It also entails a one time purchasing cost, making it a more affordable long-term solution over oral medications, which can be extremely expensive. Furthermore, daily use of VED has been shown to prevent the loss of penile length usually experienced secondary to atrophy after pelvic surgery; this has not been shown in other rehabilitation modalities.
Extrapolating available studies to current practice, one could start patients on a daily VED regimen immediately after catheter removal. Patients could use a constricting ring with the VED only when intercourse is desired. A month or so after commencing rehabilitation, patients might replace the VED with sildenafil use only if it produces erection. If a patient is uncomfortable with or has a contraindication to VED use, ICI can be used in its place. This nightly therapy could be halted after spontaneous erections return, and patients could then use VED solely on demand if necessary.
Nonetheless, there is no consensus and the data is markedly limited. The VED, as well as other potential therapies need testing in larger prospective trials alone and in tandem as combination therapy. Until such landmark studies exist, the VED can be considered a frontline therapy for men after RP interested in preserving penile length and potentially aiding EF recovery; it is relatively inexpensive, easy to use, and can produce an erection immediately after surgery, which can increase sexual satisfaction for both the patient and his partner.
Jamal A, Murray T, Ward E, Samuels A . Cancer statistics, 2005. Cancer J Clin 2005; 55: 10–30.
Jones GW, Mettlin C, Murphy GP, Guinan P, Herr HW, Hussey DH et al. Patterns of care for carcinoma of the prostate gland: results of a national survey of 1984 and 1990. J Am Coll Surg 1995; 180: 545–554.
Walsh PC, Donker PJ . Impotence following radical prostatectomy: insight into etiology and prevention. J Urol 1982; 128: 492.
Walsh PC, Marschke P, Ricker D, Burnett AL . Patient reported urinary continence and sexual function after anatomic radical prostatectomy. Urology 2000; 55:58–61: following radical prostatectomy. J Urol 1993; 150: 905–907.
Catalona WP, Basler JW . Return of erections and urinary continence following nerve-sparing radical retropubic prostatectomy. J Urol 1993; 150: 905–907.
Quinlan DM, Epstein JI, Cater BS, Walsh PC . Sexual function following radical prostatectomy: influence of preservation of neurovascular bundles. J Urol 1991; 145: 998–1002.
Rabbani F, Stapleton AM, Kattan MW, Wheeler TM, Scardino PT . Factors predicting recovery of erections after radical retropubic prostatectomy. Urology 1995; 45: 1000–1006.
Penson DF, Litwin MS . Quality of life after treatment for prostate cancer. Curr Urol Rep 2003; 4: 185.
Mullerad M, Donohue JF, Li PS, Scardino PT, Mulhall JP . Functional sequelae of cavernous nerve injury in the rat: is there model dependency. J Sex Med 2006; 3: 77–83.
Fraiman MC, Lepor H, McCullough AR . Changes in penile morphometrics in men with erectile dysfunction after nerve-sparing radical prostatectomy. Mol Urol 1999; 3: 109–115.
Gontero G, Galzerano M, Bartoletti R, Magnani C, Tizzani A, Frea B et al. New Insights into the pathogenesis of penile shortening after radical prostatectomy and the role of postoperative sexual function. J Urol 2007; 178: 602–607.
Padma-Nathan H, McCullough A, Forest C . Erectile dysfunction secondary to nerve-sparing radical retropubic prostatectomy: comparative phosphodiesterase-5 inhibitor efficacy for therapy and novel prevention strategies. Curr Urol Rep 2004; 5: 467–471.
Zippe CD, Raina R, Thukral M, Lakin MM, Klein EA, Agarwal A . Management of erectile dysfunction following radical prostatectomy. Curr Urol Rep 2001; 2: 495–503.
Zippe CD, Jhaveri FM, Klein EA, Kedia S, Pasqualotto FF, Kedia A et al. Role of Viagra after radical prostatectomy. Urology 2000; 55: 241–245.
Raina R, Pahlajani G, Agarwal A, Zippe CD . Early penile rehabilitation following radical prostatectomy: Cleveland clinic experience. Int J Impot Res 2008; 20: 121–126.
Raina R, Agarwal A, Ausmundson S, Lakin M, Nandipati KC, Montague DK et al. Early use of vacuum constriction device following radical prostatectomy facilitates early sexual activity and potentially earlier return of erectile dysfunction. Int J Impot Res 2006; 18: 77–81.
Kohler TS, Pedro R, Hendlin K, Utz W, Ugarte R, Reddy P et al. A pilot study on the early use of the vacuum erection device after radical retropubic prostatectomy. Brit J Urol 2007; 100: 858–862.
Burnett AL . Rationale for cavernous nerve restorative therapy to preserve erectile function after radical prostatectomy: results from CaPSURE. J Urol 2004; 171: 703–708.
Zealer DL, Hamdan AL, Rainey CL . Effects of denervation on posterior cricoarytenoid muscle physiology and histochemistry. Ann Otol Rhinol Laryngol 1994; 103: 780–788.
Klein LT, Miller MI, Buttyan R, Raffi AJ, Burchard M, Devris G et al. Apoptosis in the rat penis after penile denervation. J Urol 1997; 158: 626–630.
Polasek CA, Gonzalez CM, Zelner DJ, Jiang HB, Mckenna KE, McVary KT . Analysis of NOS isoform changes in a post radical prostatectomy model of erectile dysfunction. Int J Impot Res 2001; 13: S1–S15.
Iacono F, Giannella R, Somma P, Manno G, Fusco F, Mirone V . Histological alterations in cavernous tissue after radical prostatectomy. J Urol 2005; 173: 1673–1676.
Mulhall JP, Slovick R, Hotaling J, Aviv N, Valenzuela R, Waters WB et al. Erectile dysfunction after radical prostatectomy: hemodynamic profiles and their correlation with recovery of erectile function. J Urol 2002; 167: 1371–1375.
Kim N, Vardi Y, Padma-Nathan H, Daley J, Goldstein I, Saenz de Tejada I . Oxygen tension regulates the nitric oxide pathway: physiological role in penile erections. J Clin Invest 1993; 91: 437–442.
Fischer DC, Gross J, Zuch J . Cycle of penile erections synchronous with dreaming (REM) sleep: preliminary report. Arch Gen Psychiatry 1965; 12: 29.
Leungwattanakij S, Bivalacqua TJ, Usta MF, Yang DY, Hyun JS, Champion HC et al. Cavernous neurotomy causes hypoxia and fibrosis in rat corpus cavernosum. J Androl 2003; 24: 239–245.
Granchi S, Vannelli GB, Vignozzi L, Crescioli C, Ferruzzi P, Mancina R et al. Expression and regulation of endothelin-1 and its receptors in human penile smooth muscle cells. Mol Hum Reprod 2002; 8: 1053–1064.
Sakuda H, Nakashima Y, Kuriyama S, Sueishi K . Media conditioned by smooth muscle cells cultured in a variety of hypoxic environments stimulates in vitro angiogenesis: a relationship to transforming growth factor-beta 1. Am J Pathol 1992; 14: 1507–1516.
Saenz de Tejada I, Moreland RB . Physiology of erection, pathophysiology of impotence, and implications of PGE1 in the control of collagen synthesis in the corpus cavernosum. In: Goldstein I, Lue TF (eds). The Role of Alprostadil in the Diagnosis and Treatment of Erectile Dysfunction. Excerpta Medica: Princeton, 1993 pp 3–16.
Christ GJ, Lerner SE, Kim DC, Melman A . Endothelin-1 as a putative modulator of erectile dysfunction I: characteristics of contraction of isolated corporal tissue strips. J Urol 1995; 153: 1998–2003.
Moreland RB, Traish A, McMillin MA, Smith B, Goldstein I, Saenz de Tejada I . PGE1 suppresses the induction of collagen synthesis by transforming growth factor B1 in human corpus cavernosum smooth muscle. J Urol 1995; 153: 826–835.
Wessells H, Lue T, McAninch J . Penile length in the flaccid and erect states: guildelines for penile augmentation. J Urol 1996; 156: 995–999.
Munding MD, Wessells HB, Dalkin BL . Pilot study of changes in stretched penile length 3 months after radical retropubic prostatectomy. Urology 2001; 58: 567–569.
Mulhall JP, Graydon RJ . The hemodynamics of erectile dysfunction following nerve-sparing radical retropubic prostatectomy. Int J Impot Res 1996; 169: 1462–1464.
Breza J, Aboseif SR, Orvis BR, Lue TF, Tanagho EA . Detailed anatomy of penile neurovascular structures: surgical significance. J Urol 1989; 141: 437.
Teloken PE, Mesquita GG, Montorsi F, Mulhall JP . Post-radical prostatectomy pharmacological penile rehabilitation: current practice status. J Sex Med 2006; 3 (Suppl 5): 394.
Montorsi F, Guazzoni G, Strambi LF, Da Pozzo LF, Nava L, Barbieri L et al. Recovery of spontaneous erectile function after nerve-sparing radical retropubic prostatectomy with and without early intracavernous injections of alprostadil: results of a prospective, randomized trial. J Urol 1997; 158: 1408–1410.
Mulhall J, Land S, Parker M, Waters WB, Flanigan RC . The use of an erectogenic pharmacotherapy regimen following radical prostatectomy improves recovery of spontaneous erectile function. J Sex Med 2005; 2: 532–540.
Wang R, Huber N, Madsen L, Wood C, Babaian R . Compliance to penile rehabilitation program following radical prostatectomy: one year data. J Sex Med 2006; 3 (2 Supp): 151.
McCullough A . The effect of low dose intraurethral alprostadil (MUSE) on corporal oxygenation after nerve sparing radical prostatectomy. J Sex Med 2007; 4 (1 Suppl): 89.
Padma-Nathan H, McCullough AR, Levine LA, Lipschultz LI, Siegel R, Montorsi F et al. Randomized, double-blind, placebo-controlled study of postoperative nightly sildenafil citrate for the prevention of erectile dysfunction after bilateral nerve-sparing radical prostatectomy. Int J Impot Res 2008; 20: 479–486.
Levine LA, McCullough AR, Padma-Nathan H . Longitudinal randomized placebo-controlled study of the return of nocturnal erections after nerve-sparing radical prostatectomy in men treated with nightly sildenafil citrate (abstract). J Urol 2004; 231: 171.
Sharabi FM, Daabees TT, El-Metwally MA, Senbel AM . Effect of sildenafil on the isolated rat aortic rings. Fundam Clin Phamacol 2005; 19: 449–456.
Montorsi F, Brock G, Lee J, Shapiro JA, Van Poppel H, Graefen M et al. Effect of nightly versus on-demand vardenafil on recovery of erectile function in men following bilateral nerve-sparing radical prostatectomy. Eur Urol 2008; 54: 924–931.
Nadig PW, Ware JC, Blumoff R . Non-invasive device to produce and maintain an erection-like state. Urology 1986; 27: 126–131.
Witherington R . Vacuum constriction device for management of erectile dysfunction. J Urol 1989; 141: 320–322.
Nadig PW . Six years experience with the vacuum constriction device. Int J Impot Res 1989; 1: 55–58.
Lewis RW, Witherington R . External vacuum therapy for erectile dysfunction: use and results. World J Urol 1997; 15: 78–82.
Sidi AA, Becher EF, Zhang G, Lewis JH . Patient acceptance of and satisfaction with an external negative pressure device for impotence. J Urol 1990; 144: 1154–1156.
Meinhardt W, Lycklama a Nijeholt AAB, Kropman RF, Zwartendijk J . The negative pressure device for erectile disorders: when does it fail? J Urol 1993; 149: 1285–1287.
Dutta TC, Eid JF . Vacuum constriction devices for erectile dysfunction: a long-term, prospective study of patients with mild, moderate, and severe dysfunction. Urology 1999; 54: 891–893.
Turner LA, Althof SE, Levine SB, Bodner DR, Kursh ED, Resnick MI . Twelve-month comparison of two treatments for erectile dysfunction: self-infection versus external vacuum devices. Urology 1992; 39: 139–144.
Marmar JL, DeBenedictis TJ, Praiss DE . The use of a vacuum constrictor device to augment a partial erection following an intracavernous injection. J Urol 1988; 14: 975–979.
Chen J, Sofer M, Kaver I, Matzkin H, Greenstein A . Concomitant use of sildenafil and a vacuum entrapment device for the treatment of erectile dysfunction. J Urol 2004; 171: 292–295.
Chen J, Godschalk MF, Katz PG, Mulligan T . Combining intracavernous injection and external vacuum as treatment for erectile dysfunction. J Urol 1995; 153: 1476.
Moul MW, McLeod DG . Negative pressure devices in the explanted penile prosthesis population. J Urol 1989; 142: 729–731.
Colombo F, Cogni M, Deiana G, Mastromarino G, Vecchio D, Patelli E et al. Vacuum therapy. Arch Ital Urol Nefrol Androl 1992; 64: 267–269.
Bosshardt RJ, Farwerk R, Sikora R, Sohn M, Jakse G . Objective measurement of the effectiveness, therapeutic success and dynamic mechanisms of the vacuum device. Brit J Urol 1995; 75: 786–791.
Raina R, Agarwal A, Ausmundson S, Lakin M, Nandipati KC, Montague DK et al. Early use of vacuum constriction device following radical prostatectomy facilitates early sexual activity and potentially earlier return of erectile function. Int J Impot Res 2006; 18: 77–81.
Dalkin BL, Christopher BA . Preservation of penile length after radical prostatectomy: early intervention with a vacuum erection device. Int J Impot Res 2007; 19: 501–504.
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Lehrfeld, T., Lee, D. The role of vacuum erection devices in penile rehabilitation after radical prostatectomy. Int J Impot Res 21, 158–164 (2009). https://doi.org/10.1038/ijir.2009.3
- prostate cancer
- radical prostatectomy
- erectile dysfunction
- penile rehabilitation
- vacuum erection device
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