Vacuum Erectile Device for Penile Rehabilitation

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1 Review Article Vacuum Erectile Device for Penile Rehabilitation Haocheng Lin 1, Grace Wang 1, Run Wang 1,2 1 Division of Urology, University of Texas, Medical School at Houston, 2 Department of Urology, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA Abstract The vacuum erectile device (VED) uses negative pressure to increase blood inflow and oxygen into the corpora cavernosum, with a ring at the base of the penis to maintain the erection for intercourse or without a ring for penile rehabilitation. As the limitation of phosphodiesterase 5 inhibitors (PDE5I) showed in the treatment of refractory erectile dysfunction (ED), the use of VED resurged and is becoming the first-line therapy in treatment of ED after radical prostatectomy. Currently, the combination therapy of VED and PDE5I and of VED and intracavernous injection are advocated. Furthermore, there has been increasing interest in the use of VED to preserve penile length in inflatable penile prosthesis preoperation procedure and Peyronie s disease. Hereby, we reviewed the underlying mechanisms, the status of VED in penile rehabilitation, the combination therapy and the expanded use of VED. Key words: Erectile dysfunction, penile rehabilitation, vacuum erectile device INTRODUCTION The vacuum erectile device (VED) consists of a closed-end clear plastic cylinder, a vacuum pump and constriction rings. [1] The vacuum pump uses negative pressure to increase blood flow to the penis by distending the corporeal sinusoids. [2] Constriction rings can be used to maintain an erection for penetration. [1] It was previously named as a vacuum constriction device, vacuum tumescence device, and so on. In earlier years, research data showed the VED was mainly used to induce artificial erection for coitus with a constriction ring at the root of the penis. During that time, VED was applied successfully for nearly all etiologies of erectile dysfunction (ED). Patients and their partners showed a high sexual satisfaction of the VED with constriction rings. [3,4] In the recent years, the VED was mainly expanded as a penile rehabilitation approach Address for correspondence: Dr. Run Wang, Division of Urology, University of Texas Medical School at Houston, 6431 Fannin Street, Suite 6.018, Houston, Texas 77030, USA. run.wang@uth.tmc.edu Quick Response Code: Access this article online Website: DOI: / to increase blood inflow with oxygen into the penis without constriction rings. Now, it is becoming a first-line therapy for penile rehabilitation of erectile function following treatment for prostate cancer. [5] VACUUM ERECTILE DEVICE AND ERECTILE DYSFUNCTION AFTER RADICAL PROSTATECTOMY Pathology of erectile dysfunction after radical prostatectomy Prostate cancer is the most common solid cancer in men and second as a cause of death. [6] Radical prostatectomy (RP) is the primary option for treatment of clinically localized prostate cancer with excellent long-term results. [7] However, ED after RP is very common with an incidence of 14-89%. [8] Although technology and surgical skills have been improving, there is almost inevitably damage to the cavernous nerve due to the proximity of the nerves to the prostate. [9] These nerves tend to take 6-18 months, or even longer to reach a new baseline functional status. [10] A reduction in arterial inflow due to ligation of the accessory internal pudendal arteries during RP [11,12] has also been reported. The combination of the nerve damage with the decreased arterial inflow may cause penile tissue hypoxia leading to apoptosis and collagen deposits, which ultimately results in the damage of the veno-occlusive system. These above pathological changes eventually induce organic ED and penile atrophy. [13-18] 4

2 MECHANISMS OF VACUUM ERECTILE DEVICE FOR PENILE REHABILITATION The VED uses negative pressure to draw blood into the penis and was thought to increase oxygenation of the penis. [19] There has been growing evidence to support this. Diederichs et al. noted that the negative pressure induces dilation of penile tissue followed by increasing blood flow in primates; the authors believed that the increased blood flow was of arterial origin. [20] Broderick et al. showed that a transient vacuum application increases the peak flow velocity of cavernous arteries in humans. [21] Donatucci et al. further determined that long-term use of VED increases cavernous arterial flow in men with mild vasculogenic ED as measured using a duplex ultrasonography. [22] Bosshardt et al. performed blood gas analysis before VED application, immediately after the application of a constriction ring, and repeated blood gas analysis 15 and 30 min later with the constriction ring in place in ED patients. This test showed that the mean oxygen saturation of corporal blood immediately after VEDinduced erection was 79.2%, which translates as arterial and venous contributions of flow of 58% and 42%, respectively. In addition, after 30 min of continuous application of a constriction ring, blood gas analysis showed ischemia of the penile blood. [23] Müller et al. applied hyperbaric oxygen therapy on a bilateral cavernous nerve crush (BCNC) rat model and showed that hyperbaric oxygen therapy improved erectile function. [24] To explore the molecular mechanism of VED, a rat-specific VED, which simulates human VED, was successfully created and applied on a BCNC rat model by our group. [25] Our previous study showed that daily VED therapy significantly improved the intracavernosal pressure/ mean artery pressure ratios, decreased the level of hypoxiainducible factor-1α, transforming growth factor-β1, collagen and apoptosis, and increased the level of endothelial nitric oxide synthase and α-smooth muscle actin. [26] We further tested oxygen saturation (SO 2 ) level in rat penis. The results indicated that 62% of the blood is arterial in origin at the point of time right after VED application, compared to only 27% by traction and 12% in a flaccid state. [27] Recently, a pilot study by Welliver et al. tested oxygen pre- and post-ved application on RP patients by tissue oximetry. Tissue oximetry was measured at baseline and immediately after VED at five sites: Right thigh, right corpora, glans, left corpora, and left thigh. Additional measurements were captured over the course of an hour. Their data suggested use of the VED significantly increased both glanular and corporal oximetry relative to the baseline values for the entire 60 min. An initial increase of 55% was seen in corporal oxygenation with VED use. [28] These studies verified the hypothesis from different perspectives that the use of VED increases blood inflow with oxygen into the penis, which reverses the hypoxic status of corpus cavernosum, suppresses the cell apoptosis and tissue fibrosis, and finally preserves the veno-occlusion mechanism. This is the rationale for the use of VED as penile rehabilitation (PR) modality without a constriction ring. [23] All the VED scientific data are shown in Table 1. The concept behind penile rehabilitation is the recovery of erectile function following RP by prevention and reversal of some of the aforementioned pathological changes. [29] Although nerve recovery takes time, the fibrotic changes following RP can be prevented by increasing oxygenation of the corpora. [26] Regular oxygenated blood flow to the corpora is required for smooth muscle maintenance, which has been found to atrophy 4-8 months after RP. [30] Thus, early intervention with penile rehabilitation is the key for preventing ED and penile atrophy post-rp. However, phosphodiesterase 5 inhibitors (PDE5I) have limited efficacy in RPED due to the reduced release of NO by the injured cavernous nerves. [31] VED uses negative pressure, regardless of the nerve damage, to increase blood inflow directly into the penis and to improve oxygen Table 1: Science of VED Authors Year published Object of study Significant findings Welliver et al Humans VED increases both glanular and corporal oximetry relative to the baseline values for the entire 60 min Lin et al Rats VED increases oxygen saturation level compare with traction and flaccid state Yuan et al Rats VED increases ICP/MAP ratios and the level of enos and α-sma, decreases the level of HIF-1α, TGFβ-1, collagen and apoptosis Müller et al Rats Improved erectile function Bosshardt et al Humans Mean O 2 saturation of corporal blood immediately after VED-induced erection was 79.2%. Ischemia of the penile blood after 30 min Donatucci 1992 Humans VED usage increases cavernous arterial flow in men with mild vasculogenic ED Broderick et al Humans VED increases the peak flow velocity of the cavernous arteries Diederichs et al Primates Negative pressure induces expansion of penile tissue followed by increase in blood flow VED: Vacuum erectile device; ICP: Intracranial pressure; MAP: Mean arterial pressure; enos: Endothelial nitric oxide synthase; α-sma: α-smooth muscle actin; HIF: Hypoxia-inducible factor-1α; TGFβ-1: Transforming growth factor-β1; ED: Erectile dysfunction 5

3 saturation in the corpus cavernosum. [27,28] In return, erectile function as well as penile size was improved by VED through antihypoxic, antifibrotic, and antiapoptotic mechanisms. [26,27] Thus, the VED seems an ideal modality to form the basis of penile rehabilitation. [29] Early application of vacuum erectile device preserves and improves erectile function for patients postradical prostatectomy It was reported that the early use of VED in penile rehabilitation without constriction rings following RP results in 60% improvement in spontaneous erections, as well as a significant improvement in International Index of Erectile Function (IIEF) scores. [31] A study by Raina et al. in 2006 showed that early use of a VED after RP resulted in the mean IIEF-5 score improved from 4.8 before treatment to 16 after treatment at 9 months postoperatively. Furthermore, 17% of patients have regained sufficient erection for penetration, compared with only 11% without treatment. [30] In addition, this team conducted a long-term study with 141 patients who accepted penile rehabilitation after RP procedure. At 5 years, 62% of patients remained sexually active, of whom 71% had natural erections sufficient for intercourse without assistance. Almost 60% of them had used a VED as early prophylaxis. [8] Early application of vacuum erectile device preserves penile size for patients postradical prostatectomy Penile shortening after RP is common. The mechanisms of penile shortening are unclear. Currently, the most common explanation given by urologists to patients is that the extirpation of the prostate results in shortening of the urethra by several centimeters, which results in penile shortening. However, this explanation was criticized as having no scientific foundation. [32] There are some commonly accepted theories, including cavernous nerve injury induced denervation, structural alterations, hypoxia related ultra-structural changes in penis, and sympathetic hyper-innervation. [32,33] Vasconcelos et al. showed that nearly 1 cm of penile shortening after RP maybe expected for up to 12 months. [34] User et al. have reported penile wet weight and DNA content were significantly decreased at each time point after bilateral cavernous nerve transection in an animal study. They suggested that the penile wet weight loss and DNA content decrease related to the apoptotic mechanisms. [13] Until date, there are clinical data showing that the VED user has fewer complaints of penile shortening. Köhler et al. conducted a study to compare early intervention (1 month postnervesparing RP) to traditional intervention (6 months after surgery) of VED. Preliminary results showed that the early use of VED for rehabilitation significantly improves the IIEF-EF scores and preserves penile length compared to the control group. [31] Raina et al. found 23% VED users versus 85% non-ved users reported penile shrinkage compared with controls in a 9-month study with total of 109 patients who underwent nerve-sparing or nonnerve-sparing RP. [30] In ba sic science, an animal study conducted by us showed that VED therapy started at day 10 after BCNC injury could significant preserve the penile length, and girth compare with control groups. [27] Our data indicates the underlying mechanisms may relate to penile aerobic exercise inhibiting cell apoptosis in penile tissue. Combined therapy of vacuum erectile device and phosphodiesterase 5 inhibitors showed synergetic effects Of late, more evidence showed the synergistic effects when the VED is used in conjunction with PDE5I in early penile rehabilitation after RP. Chen et al. conducted a randomized controlled study where 161 patients with ED were randomized to either take sildenafil or use a VED for a period of 2 months. About 41 men were unhappy with monotherapy, and formed a selected combination cohort using both VED and sildenafil before sexual intercourse. Comparing pre- and post-treatment IIEF scores, both PDE5I and VED monotherapy only have a significant increase in the erectile function domain. However, the combination therapy group had significantly increased scores in all five domains of the IIEF. [35,36] Raina et al. assessed 74 patients who were instructed to use the VED 3 times weekly for a total of 9 months beginning 4 weeks after RP surgery. About 42% patients were unsatisfied with this monotherapy and were offered 100 mg of sildenafil and VED for intercourse. About 77% of them subsequently improved in the following domains: Perceived rigidity, patient/spousal sexual satisfaction, successful penetration rate, overall IIEF score, and return of nocturnal erection. [37] Canguvenet et al. studied 69 patients who failed in standard PDE5I therapy. The patients were then treated with VED and PDE5I for 4 weeks and the clinical efficacy of combination therapy was evaluated using IIEF, sexual encounter profile (SEP)-2, SEP-3, and the global patient assessment scale (GPAS). With the combination therapy, 79% and 70% of patients responded yes to SEP-2 and SEP-3, respectively, 74% of patients reported improvement on GPAS, and the IIEF was also significantly improved. [38] A study by Engel randomized 23 bilateral nerve-sparing robotic prostatectomy ED patients to receive tadalafil, 20 mg 3 times weekly (n = 10), or tadalafil plus a VED, 10 min unbanded/day for at least 5 days weekly (n = 13). The combination regimen group 6

4 had a significantly high score of IIEF-5 at months 6, 9, and 12, and greater penile hardness scores at 6 and 9 months compared with the monotherapy group. After 12 months 92% of combination patients responded yes to the vaginal penetration question versus 57% of the tadalafil group; corresponding figures were 92% and 29%, respectively, for intercourse to orgasm. Compliance to the VED combination group was superior to that of tadalafil group. [39] According to the Oxford Center of Evidencebased Medicine s Levels of Evidence, there appears to be levels 2 and 4 evidence supporting higher patient satisfaction with combination PDE5I and VED. [36] Vacuum erectile device combined intracavernous injections for poor response to intracavernous injections patients In combination, the VED used with intracavernous injections (ICI) has shown some synergistic effect on refractory ED. Chen et al. studied the effect of combining VED and ICI in 10 men with ED who previously failed attempts at treatment with either method as single therapy. The mean buckle pressure in the combined group was significantly greater than the single therapy groups (565.0 ± 56.8 g vs ± 38.3 g vs ± 53.6 g, P < ). After 10 mo nths of follow-up three subjects were still using the combination and were satisfied with the erectile response, 1 found that he no longer needed the external vacuum after using combination therapy for 3 months, 1 used the combination for 9 months and then stopped because of an intervening acute illness, 1 lost the partner due to death, 2 found the combination therapy to be too cumbersome and 2 were lost to follow-up. [40] Patients using VEDs have also been found to have a reduction in the pain experienced with intracorporeal injections owing to improved tissue health, which was thought to be the result of penile tissue becoming used to filling and emptying. [38] Preoperative use of vacuum erectile device to preserve penile size for inflatable penile prosthesis Inflatable penile prosthesis (IPP) is typically the last resort for refractory ED. Penile atrophy as a result of IPP is the most common postoperative complaint, which reduced overall satisfaction with the procedure. The early and daily use of a VED soon after RP may lower penile length loss. In a study of postrp patients, Dalkin and Christopher found that only 1/36 (3%) of patients had a decrease in stretched penile length of 1.0 cm when the VED is used regularly after surgery. This decrease in penile length loss is significant when compared to earlier studies where 48% of men after surgery had a significant reduction in penile length (P < ). [41] Recently, it has been proposed to use the VED pump 2-3 months prior to IPP surgery because preliminary studies suggest that preoperative stretching with a VED may allow longer cylinder placements at the time of the penile prosthetic surgery. [5] However, the use of VED is generally not used after IPP surgery as there is an inherent risk of prosthetic cylinder damage. [42] Overall, ther e is convincing evidence that VEDs are playing a crucial role in the early treatment of ED following RP. The maverick mechanisms made it omnipotent in combination therapy. The distinct penile size preservation function has been gaining more and more interest in penile rehabilitation. The summary of VED for penile rehabilitation trails is shown in Table 2. Table 2: Summary table of VED for penile rehabilitation trials Authors Year published Treatment regimen Study design n Raina et al PDE5I and/or VED or ICI or MUSE Canguven et al Combination therapy of PDE5I and VED Köhler et al VED, 1 month after RP versus 6 month after RP Significant findings Prospective 141 Early combination treatment with VED had better compliance, efficacy, and fewer economic constraints Prospective 69 Improvements over baseline were seen in IIEF-5, SEP-2, SEP-3, and GPAS measures following 4 weeks of combination therapy Prospective, randomized Raina et al VED Prospective, randomized control Raina et al VED combined with PDE5I Chen et al VED combined with PDE5I 28 Initiating the use of a VED protocol at 1 month after RP improves early sexual function and helps to preserve penile length 109 Early use of VED following RP facilitates early sexual intercourse, early patient/spousal sexual satisfaction, potentially an earlier return of natural erections sufficient for vaginal penetration and reduces penile shortening Prospective 31 Improved sexual satisfaction and penile rigidity in patients unsatisfied with VED alone after RP Increase IIEF score and penile rigidity score Prospective 161 Improved satisfaction. Older (age >60 years) participants reported better overall satisfaction Chen et al VED combined with ICI Prospective 10 VED can augment a partial response to ICI VED: Vacuum erectile device; PDE5I: Phosphodiesterase 5 inhibitors; ICI: Intracavernous injections; MUSE: Medicated urethral system for erection; IIEF: International Index of Erectile Function; SEP: Sexual encounters profile; GPAS: Global patient assessment scale; GPAS: Global patient assessment scale; RP: Radical prostatectomy 7

5 EXPANDED APPLICATION OF VACUUM ERECTILE DEVICE Vacuum erectile device with constriction rings to access artificial erection for intercourse In earlier years, research data showed the VED was mainly used to achieve artificial erection for intercourse and had significantly high sexual satisfaction. A study showed 13/41 individuals with spinal cord injury (SCI), who accepted 2 months use of VED, responded an increase in frequency of intercourse and increased sexual satisfaction. [43] A retrospective study in a total of 1517 users who acquired the device between 1974 and 1987 completed a questionnaire concerning the system. About 92% either achieved an erection or an erection-like state that was satisfactory for intercourse and 77% of them had intercourse at least every 2 weeks. [4] A prospective study showed that the VED was effective in producing erections in 89% of the men (n = 29) who regularly used VED for 6 months. [3] Now-a-days, although VED without constriction rings is a main approach for penile rehabilitation, VED with constriction rings may still show high sexual satisfaction in sexual intercourse early after RP. The study by Raina et al. in 2006 showed that the early use of a VED after RP resulted in 80% of patients successfully having intercourse with a constriction ring, with a spousal satisfaction rate of 55%. [30] VACUUM ERECTILE DEVICE AND PEYRONIE S DISEASE Recently, there has also been interest in the use of VED to help to reduce penile curvature and maintain penile length for Peyronie s disease (PD). Raheem et al. investigated 31 patients with PD who used the VED 10 min twice daily for 12 weeks. The result showed a clinically and statistically significant improvement in penile length, angle of curvature and pain after 12 weeks of using the VED. About 21/31 PD patients had a reduction in the angle of curvature by The curvature was corrected surgically in 15 patients while the remaining 16 (51%) were satisfied with the outcome. The author suggested VED therapy can improve or stabilize the curvature of PD, is safe to use in all stages of the disease, and might reduce the number of patients going on to surgery. [44] VED therapy appears to be a reasonable option for men with PD. [45] The possible mechanisms may relate to the mechanical traction exercise by negative pressure. VACUUM ERECTILE DEVICE AND OTHER REFRACTORY ERECTILE DYSFUNCTION In the past, VED was used for almost all etiologic ED with a high satisfaction rate. A study was conducted in 272 patients with ED of various etiologies. About 93.3% of VED users showed favorable results, 94% of them presented no complications. [46] Seckin et al. investigated 32 VED users with SCI. The data suggest that VED is a feasible, safe, noninvasive alternative and possibly a better initial treatment for the management of impotence secondary to SCI. [47] Segenreich et al. conducted a study in 125 patients regardless of type of ED with VED treatment. The greatest degree of success is achieved when the patient comes for treatment together with his partner. [48] Another study was conducted by el-bahrawy et al. to test the effectiveness of VED on 21 patients. Among these patients, 5 with vasculogenic impotence due to venous leakage, 6 with diabetes mellitus with or without atherosclerotic cardiovascular disease, 2 paraplegic patients after SCI, 3 severely obese patients, and 5 patients with psychogenic impotence. As a result, a total of 81% patients achieved an erection or an erection-like state that was satisfactory for intercourse. [49] Segenreich et al. tested the VED combination with psychotherapy in 145 patients with different types of ED. The best results were noted in the psychogenic and organic ED patients. Of the 38 patients with psychogenic ED, 31.5% had coitus after treatment without any intervention, 60.5% had coitus with help of the VED. Of 53 patients with organic ED, 20.7% had coitus without any intervention, and 73.5% had coitus with help of the VED. Of the total study population, 21.3% had coitus without any intervention, 67.5% had coitus with help of the VED. [50] OTHER INTERESTING THOUGHTS OF VACUUM ERECTILE DEVICE IN HISTORY In history, some interesting thoughts of VED have sprung up and are worth mention. Segenreich et al. conducted a study to see if VED could be used for ED diagnosis. In that study, 224 patients with ED were enrolled. The VED was performed 3 times at intervals of 2-8 days. Negative pressure was created for 3-5 min, followed by the removal of the cylinder; the tension ring was left in place for an additional 1-2 min. During each procedure, they observed color and temperature changes in the glans penis and changes in the tumescence and maximal rigidity of the penis. Nocturnal penile tumescence, penile brachial index, and Doppler penile ultrasound were carried out for comparison and verification. They found that 10.3% had mild ED, 38.5% moderate ED, and 41.5% severe ED. The parallel tests confirmed the diagnosis reached by VED. They suggested the changes after vacuum procedures together with local symptoms can serve as criteria for determining the degree of severity of ED. [51] Rosselló Barbará designed a comp uterized and programmable electronic VED for etiological treatment of ED arising from fibrosis of the penile 8

6 vascular system. About 20 patients with grades I and II ED were treated with this new method and achieved high satisfaction. [52] Gus kov invented a vibrovacuum fallostimulator Sanos for treatment of vascular ED, which differs from conventional local decompression in a dynamic regimen of vacuum effect on the penis in the presence of vibration. The advantages of this Sanos were to reduce complications such as edema, hemorrhages, and necrosis of penile skin. About 330 patients with vascular ED were enrolled in this study and 92.1% of them showed recovery of arteriocavernous blood flow without complication had occurred. [53] Levin investigated the effect of VED with ErecAiD Classic Osbon unit on ED with premature ejaculation. Five patients accepted VED with ErecAid Classic Osbon unit. The results indicated ejaculatory latency increased insignificantly, but erection could sustain coitus for 30 min. [54] CONCLUSION The goals of penile rehabilitation are earlier return of erectile function, penile size preservation, and overall increased sexual satisfaction. Until date, no set regimen has been determined for penile rehabilitation. VED has shown to be an advantage in early intervention through the mechanism of increasing arterial inflow and oxygen in corpus cavernosum regardless of the nerve damage. The increased arterial inflow with oxygen reverses the hypoxic status, further inhibits apoptosis and fibrosis in the corpus cavernosum; thus, preserving erectile function as well as penile size during the cavernous nerve recovery period. These mechanisms constitute the basis of VED alone or combination therapy for penile rehabilitation. As clinical and basic research data grow, VED has been considered as first-line therapy as well as PDE5I therapy for penile rehabilitation. The unique penile size preservation effect has been expanding the use of VED. 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