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H--ed special issue-出版文件-sp.mdiAsian J Androl 2008; 10 (1): 79–87 Non-surgical therapy of Peyronie’s disease Department of Urology, Rush University Medical Center, Chicago 60612, USA Abstract
The present paper provides a review of the available non-surgical treatments for Peyronie’s disease (PD). A review of published literature on oral, intralesional, external energy and iontophoresis therapies for PD was performed,and the published results of available treatment options reviewed. The authors’ recommendations for appropriatenon-surgical management of PD are provided. Although there are many published reports that show the efficacy ofnon-surgical therapies for PD, there is a lack of large scale, multicenter controlled clinical trials, which makes treat-ment recommendations difficult. Careful review of the literature does suggest that there are treatment options thatmake scientific sense and appear to stabilize the disease process, reduce deformity, and improve function. Offeringno treatment at all will encourage our patients to pursue alternative treatments, which might do harm, and misses theopportunity to do some good. Clearly further work is necessary to develop safe and effective non-surgical treatmentsfor PD. (Asian J Androl 2008 January; 10: 79–87) Keywords: Peyronie's disease; penile induration; humans; injections intralesional; vitamin E; pentoxifylline; amino acids
formation of hypertrophic scars. Recent investigationshave focused on the mechanisms of wound healing, Peyronie’s disease (PD) is a psychologically and physi- fibrosis, scar formation as well as scar remodeling, and cally devastating disorder that manifests as a fibrous in- have correlated their findings to the Peyronie’s population.
elastic scar of the tunica albuginea, causing penile Study of the molecular etiology of PD has unearthed defor mity, pen ile cur vatur e, h in gin g, n ar r owin g, several important growth factors, which can be divided shortening, and painful erections. Despite multiple treat- into profibrotic and antifibrotic groups. Profibrotic fac- ment options offered since Francois de la Peyronie de- tors include TGF-1, which is an activator of collagen I scribed PD in 1743 , this disorder remains a consi- synthesis , and which is released by neutrophils and derable therapeutic dilemma to practicing physicians.
macrophages during the acute and proliferative phasesof wound healing. El Sakka et al.  found that in PD 2 Mechanism
plaques, TGF-1 protein expression, as measured byWestern blot, was overexpressed as compared to controls.
Contemporary thinking would considers PD as a dis- In addition, TGF-2 and TGF-3 expression was not order of wound healing, and as such it is similar to the enhanced, suggesting that TGF-1 overexpression mightplay a role in PD development. Subsequently, TGF-1 wasused to induce PD in a rat model, further solidifying its Correspondence to: Dr Frederick L. Taylor, Department of Urology, role as a central modulator of collagen deposition in PD Rush University Medical Center, 1653 W. Congress Parkway, Suite 348 Professional Building, Chicago, IL 60612, USA.
A second group of profibrotic enzymes includes the fibrin/plasminogen activator inhibitor 1 (PAI-1) system.
Plasmin breaks down the extracellular matrix both directly *Laurence A. Levine is a consultant with Pfizer, Lilly, American and indirectly by activating matrix metalloproteinases Medical Systems, Auxilium and Coloplast, a speaker for Pfizer,Lilly, Coloplast and Auxilium, and an investigator with fsPhysioMed (MMP) to break down collagen. PAI-1 in turn inhibits MMP as well as plasminogen activator, which stimulates Tel:
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2008, Asian Journal of Andrology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences. All rights reserved.
Non-surgical therapy of Peyronie’s disease plasmin . Fibrin itself has been recognized as an in- groups, including MMP-2, MMP-9, and thymosins TM10 ducer of PD [6, 7], and has been used in causing PD in an animal model . It has been documented that levelsof TGF-1 and PAI-1 are increased in fibrin-induced PD 3 Non-surgical therapy for PD
The major identified anti-fibrotic enzymes are the Since the first description of PD in the published MMP. Although many different MMP have been identified, literature, clinicians have been searching for medical there are a few that appear more relevant in PD research.
therapy options with few showing reliable results. Con- Collagen I breakdown is mediated by MMP 1 and 13, while sistent success with medical therapies continues to evade for collagen III MMP 1, 3, 10 and 13 are most active.
the practicing urologist, although current research into The only MMP produced by mammals that have been the molecular pathophysiology of PD might one day lead shown to substantially degrade Collagen 1 and III are types to medical cure. Several nonsurgical options, however, 1, 8 and 13 . In addition, current studies are currently are currently available which may stabilize or reduce de- underway examining the possibility of fibrosis regression, formity and improve sexual function. The evaluation of through the induction of the nitric-oxide synthase (NOS) their efficacy has been compromised by small size of published clinical trials and most without any placebo Recent work has further elucidated the molecular control. Data outcomes are difficult to interpret without biology of PD, and has unearthed potential targets for a validated questionnaire, and is complicated by the fact molecular-based therapies. Ryu et al.  evaluated the that there is a spontaneous improvement rate of 5%– efficacy of a TGF-1 inhibitor in the treatment of induced 12% [13–16]. The nonsurgical options for treatment of PD in a rat model. The rats were injected with TGF-1 the pain and curvature of PD, including oral, topical, into the tunica albuginea, inducing a PD-like state. The intralesional, external energy and combination therapies, rats were randomized into four groups: the control, PD are presented in the following subsections (Table 1).
group without treatment, PD with saline injections, andPD with IN-1130 injections. IN-1130 is a small mo- 3.1 Oral therapies
lecule that inhibits activin receptor-like kinase 5 (ALK5),which is a receptor for TGF-1. The rats with PD that were treated with IN-1130 showed significant reduction Vitamin E was the first oral therapy described for the in curvature and fibrosis when compared to those re- treatment of PD . Vitamin E is a fat soluble vitamin ceiving either no injections or saline injections. The treat- that is metabolized in the liver, excreted in bile, and is ment group recorded post-treatment curvatures of 9.1° postulated to have antioxidant properties in humans. Oxi- vs. 23.0° and 32.6° for the no injection and saline injec- dative stress and the production of reactive oxygen spe- cies (ROS) is known to be increased during the acute Del Carlo et al.  investigated the role of MMP and proliferative phases of wound healing, as it is neu- and tissue inhibitors of matrix metalloproteinases (TIMP) trophils and macrophages that produce these ROS spe- in the pathogenesis of PD using harvested plaque from cies , and the inflammatory phase of wound healing human PD patients. PD tissue samples were found to has been shown to be prolonged in Peyronie’s patients have reduced or absent levels of MMP 1, 8 and 13 when . Therefore, a biochemical mechanism does exist compared to patient-matched perilesional tunica. PD fi- for Vitamin E use. Gelbard et al.  compared vitamin broblasts were then cultured with soluble MMP and TIMP E therapy to the natural history of PD in 86 patients; no after treatment with either TGF-1 or IL-1. They found significant differences were found between the two that IL-1 stimulation increased the production of MMP groups in terms of curvature, pain, or the ability to have 1, 2, 8, 9, 10 and 13 in PD fibroblasts, while TGF-1 intercourse. In 1983, Pryor et al.  conducted a increased the production of only MMP 10, and decreased double-blind, placebo-controlled crossover study evalu- the production of MMP-13, but markedly increased the ating vitamin E for the treatment of PD in 40 patients.
production of all TIMP. These findings suggest that PD No significant improvements were noted in plaque size fibroblasts may be manipulated to encourage scar re- or penile curvature. The authors do not recommend vi- modeling in the final phase of wound healing.
tamin E for the treatment of PD as there is no meaning- It is reasonable to consider that a genetic predisposi- ful evidence of benefit in placebo-controlled trials.
tion towards impaired wound healing and PD exists. Qianet al.  compared gene expression profiles in samples taken from PD tunica albuginea plaques, Dupuytren’s Colchicine is an antigout agent that inhibits fibrosis contractures and normal palmar fascia, and found several and collagen deposition primarily by inhibiting neutrophil gene family similarities between the PD and Dupuytren’s microtubules . Colchicine has been used both as a http://www.asiaandro.com; [email protected]
Asian J Androl 2008; 10 (1): 79–87 primary oral therapy for PD as well as in combination competing with estrogen binding sites in target tissues.
with other modalities. Akkus et al.  administered an In addition, tamoxifen affects the release of TGF from escalating dose of colchicine in a non-randomized, non- fibroblasts, and blocks TGF-receptors, thus potentially placebo controlled fashion to 19 patients with PD over a reducing fibrogenesis [29, 30]. In 1992, Ralph et al. 3–5-month period . Of these patients, 36% noted a  investigated tamoxifen in 36 patients with recent reduction in curvature, and 63% reported an improve- onset PD (duration less than 4 months) . 80% of ment in the palpable plaque. Of the patients that were patients reported a reduction in pain, 35% noted a sub- experiencing painful erections at the time of treatment jective reduction in curvature, and 34% reported a de- initiation, 78% had resolution of this symptom. Kadioglu crease in plaque size. A follow-up study in 1999 by et al.  treated 60 patients with PD using 1 mg of colchi- Teloken et al.  failed to show any statistically sig- cine twice daily, with a mean follow-up of 11 months .
nificant difference between tamoxifen and a placebo, and They found significant improvement of pain in 95% of there was an indidental report of alopecia in the active men; however, while 30% of patients reported improved treatment group. We do not recommend the use of curvature, 22% of patients reported worsened curvature.
Safarinejad performed a randomized, placebo controlledtrial of colchicine in 2004 with 84 men . It was demonstrated that colchicine was no better than a pla- Carnitine is a naturally occurring metabolic interme- cebo in improving pain, curvature angle, or plaque size diate. Carnitine facilitates the entry of long chain fatty as measured by ultrasound. Colchicine was not recom- acids into muscle mitochondria, which are then used as mended by the authors due to its lack of demonstrated an energy substrate. Carnitine  is a hypothesized to efficacy in placebo-controlled trials. The agent is also inhibit acetyl coenzyme-A, which may help in the repair associated with gastrointestinal distress, including sig- of damaged cells. Biagiotti and Cavallini examined the nificant diarrhea, and rarely aplastic anemia.
use of carnitine for PD in 2001. In their study, 48 menwere divided into two groups to receive either tamoxifen at 20 mg twice daily for 3 months or acetyl-L-carnitine Potassium aminobenzoate (Potaba, Glenwood) is a 1 g twice daily for 3 months. Overall, the men taking member of the vitamin B complex that is believed to in- carnitine saw greater improvement in curvature, and had crease the activity of monoamine oxidase in tissues, statistically significant improvement in pain. In addition, thereby decreasing local levels of serotonin and, therefore, the patients taking carnitine reported far fewer side ef- possibly decreasing fibrogenesis. Potassium amino- fects as compared to tamoxifen. At this time, more study benzoate is used for other medical conditions, including is needed to elucidate the role of carnitine in the treat- scl er od e r m a , d er m a t om yosi t i s a n d p em p h i g u s.
Zarafonatis and Horrax  first described the use ofpotassium aminobenzoate for the treatment of PD, and a subsequent European study published in 1978 reported a L-Arginine is an amino acid that, when catalyzed by 57% improvement rate, with 9% complete resolution in NOS, combines with oxygen to ultimately form nitric a pooled cohort of 2 653 patients . This study, oxide (NO). It is known that inducible NOS (iNOS) is however, had no control or placebo group. In 1999, expressed in the fibrotic plaques of PD and suppression Weidner et al.  published a randomized, placebo con- of iNOS exacerbates tissue fibrosis . In 2003, Valente trolled trial of potassium aminobenzoate given 3 g orally et al.  reported that L-arginine, given daily in the four times per day for 1 year in 103 men. The only drinking water of a rat model with TGF-1 induced PD significant difference found between the two groups was plaques caused an 80%–95% reduction in plaque size and plaque size, which in itself was not correlated with a in the collagen/fibroblast ratio . In addition, L-arginine decrease in penile curvature. A 2005 follow-up study was found to be antifibrotic in vitro. This suggests that L- also by Weidner et al.  suggested that the use of arginine, as a biochemical precursor of NO, might be ef- potassium amionobenzoate may protect against progres- fective in reducing PD plaque size. Further confirmatory sion in PD plaques. Potassium amin oben zoate is h uman trials ar e needed befor e th is agent can be expensive, and has low tolerability because of severe gastrointestinal side effects. It is also not recommendedby the authors due to a lack of evidence regarding its Pentoxifylline is a nonspecific PDE inhibitor. Valente et al.  found that normal human and rat tunica albuginea, as well as PD plaque tissue, express PDE5A- Tamoxifen is a nonsteroidal antiestrogen that acts by 3 and PDE4A, B and D. In their in vitro study, PD Tel: +86-21-5492-2824; Fax: +86-21-5492-2825; Shanghai, China
Non-surgical therapy of Peyronie’s disease Table 1. Nonsurgical therapies for Peyronie’s disease (PD). ESWT, electroshock wave therapy.
Antioxidant that theoretically reverses or stabilizes Limited side effects, low cost. Efficacy not proven.
pathologic changes in the tunica albuginea.
Inhibits fibrosis and collagen deposition.
Mixed reports of efficacy in non-controlled trials.
Single randomized controlled trial failed to show benefit. Might cause gastrointestinal disturbances, Member of the vitamin B complex, thought to Significant reduction in plaque size, but not increase the activity of monoamine oxidase, curvature. Expensive, and difficult to tolerate thereby decreasing local serotonin levels, due to gastrointestinal side effects.
which might contribute to fibrogenesis.
Might reduce TGF-release from fibroblasts and Efficacy not proven. Side effects might include might block TGF-β receptors, resulting in Believed to inhibit acetyl coenzyme-A.
Efficacy not proven, and more investigation is Amino acid substrate in the formation of nitric Improvement in plaque size and collagen/fibroblast oxide, which is thought to be lacking in PD tissue.
ratio in a rat model. Well tolerated.
Nonspecific phosphodiesterase inhibitor that may Improvement in plaque size and collagen/fibroblast reduce collagen levels in PD plaques.
Increases extracellular matrix collagenase secretion When administered topically the drug does not through fibroblast inhibition and decreases collagen appear to penetrate into the tunica albuginea.
and fibronectin synthesis and secretion. Decreases Intralesional
Anti-inflammatory and cause reduction in collagen Treatment with steroids is discouraged by the authors. Effects are unpredictable, and may cause atrophy and distortion of tissue planes.
Statistically significant improvement in curvature has been noted in men with mild to moderate disease.
Controlled and noncontrolled trials show promise as improvements in plaque volume, pain, and curvature Decreased the rate of proliferation of fibroblasts Recent encouraging results with reports of improve- in Peyronie’s plaques in vitro, reduced production ment in curvature and pain. Dosing regimens and side of extracellular collagen and increased production effect profiles yet to be determined.
No statistically significant improvement noted in resultant plaque lysis, improved vascularity, and the creation of contralateral scarring.
Effect of verapamil and steroids discussed previously.
Objective improvements of plaque size and curvature Electric current itself might have some beneficial have been noted. Adverse effects include erythema at http://www.asiaandro.com; [email protected]
Asian J Androl 2008; 10 (1): 79–87 Table 1 (continued). Nonsurgical therapies for Peyronie’s disease (PD). ESWT, electroshock wave therapy.
Discussed previously. Synergistic effect possible.
Improvements in curvature and plaque size have been Discussed previously. Synergistic effect possible.
Significant improvement in plaque size compared Discussed previously. Synergistic effect possible.
Statistically significant subjective improvement in curvature, plaque size and erectile function in patients treated with carnitine and intralesional Penile traction devices
Expansion of contracted tissue might result in the Early results demonstrate improvement in curvature, increase in length, and improvement in hinge effect.
Side effects were limited to mild discomfort with fibroblasts were cultured with pentoxifylline and found The powerful anti-inflammatory effect of steroids to have increased cAMP levels and reduced collagen I made them obvious agents for intralesional therapy of levels as compared to controls. In addition, pentoxyfilline PD. In 1954, Bodner et al.  reported improvement given orally to a TGF-1 induced PD rat model caused a in 17 patients treated with intralesional hydrocortisone decrease in PD plaque size and the collagen/fibroblast and cortisone. In 1975, Winter and Khanna  showed ratio. Brant et al.  reported a single case report of no difference between patients treated with dexametha- successful PD treatment using pentoxifylline alone .
sone injections and the natural history of the disease. In Further studies are required to definitively examine 1980, Williams and Green  published a prospective pentoxifylline for the treatment of PD; however, its study using intralesional triamcinolone. All patients were known biochemical effect and early animal-model suc- observed for 1 year after study enrollment; during that cess make it an attractive option for consideration.
time only 3% of patients reported improvement. Triam-cinolone was administered every 6 weeks for 36 weeks; 33% of patients reported subjective improvement, par- ticularly in pain and plaque size. Currently, the use of Interest in topical verapamil for the treatment of PD intralesional steroids is discouraged because of the side followed its success as an intra-lesional agent (see below).
effects of local t issue a tr oph y, fibr osis, im mun e However, investigation has demonstrated that effective suppression, and lack of objective measures of benefit.
tunica albuginea tissue concentrations of verapamil arenot achievable via topical application . A recent three- arm trial without placebo demonstrated some benefit with Collagenase was first studied in vitro by Gelbard et al. topical verapamil , but this study was significantly in 1982 . A subsequent clinical trial by that group compromised . Therefore, the use of verapamil as a demonstrated subjective improvement in 64% of patients topical agent for PD is not recommended.
within 4 weeks of treatment . A decade after theirinitial study, they published their findings of a double blind trial in 49 men . Statistically significant im- provement in curvature was noted in the collagenase Tel: +86-21-5492-2824; Fax: +86-21-5492-2825; Shanghai, China
Non-surgical therapy of Peyronie’s disease treated group; however, maximal improvement ranged dicated in patients with ventral plaques or extensive plaque from 15° to 20° and was only seen in the patients with curvatures of less than 30° and plaques of less than 2 cmin length. Larger scale controlled trials of collagenase Duncan et al.  reported in 1991 that IFNs de- crease the rate of proliferation of fibroblasts in Peyronie’s plaques in vitro, reduce the production of extracellular Verapamil is a calcium channel blocker that has been collagen, and increase the activity of collagenase. Initial shown in in vitro studies to inhibit local extracellular matrix studies performed by Wegner et al. [51, 52] demon- p r od u ct i on by fi br obl a st s, t o r ed u ce fi br obl a st strated low rates of improvement, but a high incidence proliferation, to increase local collagenase activity and to of side effects, including myalgias and fever. In 1999, affect the cytokine milieu of fibroblasts [44, 45]. In Ahuja et al.  reported on 20 men who received 1994, Levine et al.  reported on 14 men who under- 1 × 106 units of IFN-α-2b biweekly for 6 months. Of went a dose-escalation trial of biweekly intralesional in- these patients, 100% reported softening of plaque, 90% jections of verapamil for 6 months. Significant improve- of men presenting with pain had improvement, and 55% ment in plaque associated narrowing was noted in all had a subjective reduction in plaque size. Dang et al. patients, and curvature was improved in 42%. The first  administered 2 × 106 units to 21 men biweekly for randomized single-blind trial of intralesional verapamil was 6 weeks, and found objective curvature improvements published in 1998 . Significant improvement were in 67%, and improvement in pain in 80%. Seventy-one noted in terms of erection quality and plaque volume. A per cen t of patien ts r ep or ted impr ovemen t in ED non-statistical trend towards improvement in curvature symptoms. In 2006, Hellstrom et al.  reported on a was also noted. As a follow-up, Levine and Estrada  placebo controlled, multicenter trial of 117 patients who reported on 156 men enrolled in a prospective non-ran- underwent biweekly injections of 5 × 106 units for a to- domized trial of PD men with a mean follow-up of tal of 12 weeks. Average curvature in the treatment group 30.4 months. A local penile block was performed with improved 13°, versus 4° in the placebo arm, and 27% of 10–20 mL 0.5% bupivicaine, followed by injection of patients in the treatment group had measured improve- 10 mg verapamil diluted in 6 mL sterile normal saline (total ment versus 9% of the saline group. Pain resolution was volume 10 mL) into the Peyronie’s plaque using 1–5 skin noted in 67% of the treatment patients versus 28% for the punctures, but with multiple passes through the plaque.
placebo. IFN therapy requires investigation to further define The goal is to leave the drug in the needle tracks, not to efficacy, dosing regimens, and side effect profiles.
tear or disrupt the plaque. Injections were administeredevery 2 weeks for a total of 12 injections. Of patients with pain, 84% achieved complete resolution, 62% were 3.4.1 Penile electroshock wave therapy (ESWT) found on objective measurement to have improved cur- Local penile ESWT has been suggested to be of be- vature ranging from 5–75° (mean 30°), and only 8% of nefit for the treatment of PD. Various hypotheses about patients had measured worsening of curvature. More its mechanism of action exist, including direct damage recently, Bennett et al.  administered six intralesional to the plaque resulting in an inflammatory reaction with injections (10 mg in 5 mL) every 2 weeks to 94 con- increased macrophage reaction leading to plaque lysis, secutive patients with PD . Follow-up was at improved vascularity resulting in plaque resorption, and 5.2 months after completion of the 6th injection. Of the creation of contralateral scarring of the penis result- patients, 18% (n = 17) were found to have improved ing in “false” straightening . Hauck et al.  ran- curvatures (average improvement 12°), 60% (n = 56) domized 43 men to ESWT or oral placebo for 6 months had stable curvature, and 22% (n = 21) had increased . No significant effect was noted in ter ms of curvature (average increase 22°). All patients with pre- curvature, plaque size, or subjective improvement in se- treatment penile pain had improvement at follow-up. The xual function or rigidity. More recent work from a Ger- authors suggest that these data support intralesional man group randomized 102 men to ESWT or to receive verapamil for the stabilization of PD. It might be that six placebo shocks [58, 59]. There was no statistically sig- injections provides stabilization but is insufficient to ac- nificant difference found between the groups for plaque complish reduction of curvature. Currently, we recom- size, improvement of deformity, or sexual function post- mend a trial of six injections with each injection occur- treatment. ESWT is currently not recommended as ring every 2 weeks. If no improvement is noted by the patient, the therapy may be terminated, the verapamil dosecan be increased to 20 mg, or interferon (IFN) injec- tions may be offered. We consider verapamil contrain- Iontophoresis involves the transport of ions through http://www.asiaandro.com; [email protected]
Asian J Androl 2008; 10 (1): 79–87 tissue by means of an electric current. Several studies receive intralesional verapamil plus oral carnitine or have investigated th e efficacy of topically applied intralesional verapamil plus oral tamoxifen. Statistically verapamil with or without dexamethasone with enhanced significant subjective improvements in curvature, plaque penetration using iontophoresis [60–63]. In 2002, Levine size and erectile function were found in the carnitine et al.  confirmed that verapamil was found within group. No difference in improvement of pain was noted the exposed tunica albuginea by examining surgically re- trieved tunica albuginea from patients after a single intra-operative exposure during plaque incision and grafting surgery. Di Stasi et al.  recently reported on a The use of tissue expanders has long been a main- prospective, randomized study of 96 patients treated with stay of treatment in the orthopedic, oral-maxillofacial and 5 mg verapamil plus 8 mg dexamethasone using ionto- plastic surgical fields. It is well-documented that gradual phoresis versus 2% lidocaine delivered electromotively.
expansion of tissue results in the formation of new bone Of patients in the verapamil/dexamethasone group, 43% and connective tissue. Initial work has been done to noted objective improvement in plaque size and curvature; evaluate th e efficacy of a pen ile exten der device no changes were noted in the lidocaine group. In 2005, (fsPhysioMed; FastSize LLC, Aliso Viejo, CA, USA)) for Greenfield et al.  reported on the use of 10 mg the treatment of PD. A pilot study at our institution of 10 verapamil versus saline iontophoresis. Patients were as- patients found that daily application of the fsPhysioMed sessed using papavarine-induced erections prior to and device for 2–8 h per day for 6 months resulted in a 33% 1 month after treatment. Of patients in the verapamil measured improvement in curvature (ranging from a 10° group, 65% demonstrated improvement in curvature, to 45° improvement and resulting in an improvement in versus 58% in the saline group. Mean curvature im- average curvature from 51° to 34°), an increase in flac- provement was 9.1° in the treatment group versus 7.6° cid stretched penile length ranging from 0.5–2.0 cm, and in the saline group, which is not as robust as intralesional an improvement in hinge effect in all those with advanced verapamil injections. The authors suggested that the elec- narrowing or indentation. No patients noted recurrence tric current itself might have some beneficial effect on or worsening of curvature during 6 months of follow- wound healing, which is known and supported in the up, and there was no incidence of local skin changes, dermatologic literature . Further investigation into ulceration, loss of sensation, or worsening of curvature.
Long term and larger studies are indicated.
A placebo controlled study by Preito Castro et al. Our current practice favors a multi-modal approach  randomized 45 patients to receive vitamin E and for non-surgical therapy for PD. All patients are pre- colchicine or ibuprofen. Statistically significant improve- scribed 400 mg pentoxifylline orally three times a day, ments in curvature and plaque size were noted in the with L-Arginine 1 000 mg twice a day. Patients are en- group treated with vitamin E and colchicine as compared couraged to use the fsPhysioMed device 2–8 h per day to the group receiving ibuprofen. Patients in the vitamin for 6 months, and are offered intralesional verapamil in- E and colchicine arm reported a greater decrease in pain, jections as a means to improve curvature and, if present, although this did not reach statistical significance.
pain. As a result of increased interest in this disorder aswell as more sophisticated basic science and clinical 3.5.2 ESWT with per perilesional verapamil injection research, effective and reliable non-surgical treatments In 1999, Mirone et al.  prospectively examined will hopefully emerge. In the meantime, there are a num- two groups of PD patients; one group was treated with ber of non-surgical treatment options that offer some ESWT, while the other received ESWT and perilesional benefit with respect to disease stabilization as well as verapamil injections. A 52% improvement in plaque size reduction of deformity and improved sexual function.
by ultrasound was noted in the ESWT-only group com-pared to 19% for the combination therapy. A follow-up References
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