Peyronie disease (PD) is characterized by a fibrous inelastic

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1 Journal of Andrology, Vol. 24, No. 1, January/February 2003 Copyright American Society of Andrology Peyronie Disease in Younger Men: Characteristics and Treatment Results LAURENCE A. LEVINE, CARLOS R. ESTRADA, DOUGLAS W. STORM, AND THOMAS G. MATKOV From the Department of Urology, Rush Medical College, Chicago, Illinois. ABSTRACT: We retrospectively reviewed our experience with 30 men with Peyronie disease (PD) younger than age 40 years to describe their clinical presentation, physical examination findings, and treatment outcomes. In addition, we performed a literature review to define the typical patient with PD and to compare our findings with those in the literature. The mean age of our study population was 31 years (range years). The prevalence of patients under the age of 40 presenting with PD was 1.5%. In this population, 97% reported normal erectile capacity, and 100% presented with a palpable plaque. Medical and surgical treatments were used in the young population with results comparable to published data. According to the published literature we reviewed, patients with PD were less likely to recall a specific traumatic event, less likely to complain of painful intercourse, they had different directions of penile curvature, and different locations of penile plaques. Younger men with PD commonly present with complaints and physical examination findings that differ from the typical patient with PD. Key words: Penis, male sexual dysfunction. J Androl 2003;24:27 32 Peyronie disease (PD) is characterized by a fibrous inelastic scar involving the tunica albuginea of the corpora cavernosa. This scar produces the recognized findings of a palpable plaque on the penile shaft; erectile deformity including curvature, narrowing, and shortening; pain; and difficulty with coitus. Its incidence, prevalence, symptomatology, etiology, clinical course, and response to medical and surgical therapy have been extensively investigated and presented in the modern urological literature. Although variations of these characteristics are reported, the literature has supported an image of the patient with PD as a man typically presenting in his mid- 50s to 60s with compromised sexual function due to penile deformity and not infrequently diminished rigidity. The incidence of PD is reported to be 26 per with a prevalence of 389 per (Lindsay et al, 1991). In that series, the mean age was 53 years with 42% of patients between ages 50 and 59, and 87% between ages 40 and 70 years at diagnosis. This age distribution is consistent with other reports in the literature, with the vast majority of patients between the ages of 45 and 86, with a mean age of approximately 55 years. The prevalence of PD in men aged has been reported to be 1.5% (Schwarzer et al, 2001). This was found in a large, general population study. The clinical course and natural history of patients with PD varies widely from spontaneous resolution of symptoms and deformity to progressive unstable curvature and erectile dysfunction. The excessive scarring and subsequent deformity appear to be due to abnormal wound healing following penile trauma. The precise pathophysiology is not clearly understood, but appears to be related to a prolonged inflammatory phase, exuberant scar formation, abnormal remodeling occurring independently or simultaneously, or a combination of these (Levine et al, 1994; Devine et al, 1997; Ehrlich, 1997; Jarow and Lowe, 1997). The treatment of PD varies relative to its presentation and clinical course, because patients may present at different phases of the disease process. Nonsurgical treatment approaches have been employed to reverse, interrupt, or attenuate the proposed disease mechanisms with varying success. Surgical intervention has been reserved for patients who fail conservative measures and who have stable disease. Although PD in a younger male population has been recently reported, we examined our larger group of younger men with PD to characterize disease presentation, symptomatology, natural history, and results of therapy at our institution (Tefekli et al, 2000). Identifying differences in these variables in comparison with older men with PD may afford a more complete understanding of the disease. In addition, this may allow the treating urologist to direct more age-specific care to these patients. Correspondence to: Dr Laurence A. Levine, Department of Urology, Rush Medical College, 1725 West Harrison Street, Suite 920, Chicago, IL Received for publication April 24, 2002; accepted for publication July 24, Materials and Methods Between July 1992 and January 2000, 626 consecutive patients with PD presented for evaluation at our institu-

2 28 Journal of Andrology January/February 2003 Table 1. Clinical Presentation and History of Young Men with Peyronie Disease Mean Age Presenting Complaint Pain Lump Curve Gradual Onset Sudden Specific Event Coitus Intercourse Family History 31 13/30 (43%) 14/30 (47%) 10/30 (33%) 22/30 (73%) 8/30 (27%) 17/30 (57%) 29/30 (97%) 16/29 (59%) 24/27* (89%) 16/24 (67%) 1/30 (3%) * Denominator 27: 29 patients with erections; 2 virgins not evaluable for coitus. tion. At the first visit, all patients completed a specific PD questionnaire to provide detailed medical and sexual history, symptoms, and duration of disease. All patients were subsequently examined, evaluated, and treated by one urologist (L.A.L.), and findings at subsequent visits were recorded in patients charts. The diagnosis of PD was dependent on the existence of a palpable penile plaque. Penile curvature was assessed by protractor measurements taken after pharmacological erection, which was induced using intracavernosal injection of papaverine (30 90 mg). Repeated dosing was used as necessary to accomplish optimal erectile response. The deformity was graded using a modified Kelami classification: grade I, less than 30 ; grade II, ; and grade III, greater than 60. PD plaque dimensions and location were assessed with duplex Doppler ultrasound. We used a retrospective clinical record review to identify a subset of 30 men younger than 40 years of age. We reviewed the results of their initial questionnaires, subsequent interviews, initial and subsequent physical examinations, disease progression, and treatment outcomes. Post-treatment erectile function was evaluated by in-office interview. We reviewed the available modern literature on PD to describe the typical patient. Our criteria for inclusion in this review were those papers that included information on presenting characteristics of the disease, including age, presenting complaints, erectile capacity, and any other descriptive data describing the clinical presentation of the disease. The selected articles were all in peer-reviewed journals and in the English language. The Medline database was queried using Peyronie s Disease, penile curvature, penile deformity, penile plaque, and penis as text and key words. A selected literature review was chosen over an internal control because we wanted to compare our patients with the published international experience with PD as described by multiple authors, thereby limiting our own observer bias. The selected literature review yielded a vast and varied international experience in more than 1500 patients with PD. These reports vary greatly in their patient populations and characteristics, and in the intended goal of the published report, which by and large described nonrandomized treatment outcomes. Accordingly, our description of the typical patient with PD is an amalgam of many different patient populations and authors perspectives. Whereas this review is not exhaustive, it does reflect a major and popular portion of the literature. Results Younger Men In our patient population of 626 men, 30 men younger than age 40 presented with complaints, physical examination findings consistent with PD, or both. The prevalence of PD in younger men in our study was 4.8% (30 of 626). The mean age at presentation in this group was 31 years (range years), and the mean follow-up period was 43 months (range months). The specific presenting complaint was penile pain in 13 patients (43%), penile curvature in 10 (33%), and a palpable nodule in 14 (47%). The onset of disease appeared to be gradual in 22 men (73%) and sudden (1 3 days) in 8 (27%). Seventeen patients (57%) attributed the onset of disease to a specific flaccid or erect penile trauma: 15 during sexual intercourse, 1 during masturbation, and 1 following a sports-related injury. The trauma was described as an episode of pain during the reported activity. No patient had a history consistent with a full thickness tunica albuginea tear or penile fracture. Twenty-nine (97%) patients were able to achieve erection (one with the aid of sildenafil). Sixteen men reported pain with erections (59%). Twenty-seven of 29 men with erectile capacity could be evaluated for their experience with intercourse (2 virgins). Of these 27, 24 (89%) reported that intercourse was possible, albeit compromised by penile deformity. Of these 24, 16 (67%) reported painful intercourse. In the 3 men (11%) unable to achieve coitus, 2 reported that it was secondary to curvature, and 1 reported inability secondary to pain and flaccidity. One patient (3%) reported a family history of PD (Table 1). Known risk factors for erectile dysfunction (ED) were identified in only 10 (30%) patients. Of these, 9 were smokers, and 1 had hypertension. On physical examination, all patients presented with a palpable plaque. The plaque location was distal in 14 (47%) patients, midshaft in 6 (20%), and proximal in 13 (43)%, with multiple plaques noted in 6 (20%) patients. The cumulative location of the plaques exceeds 100% because of the multiple plaque locations found in these men.

3 Levine et al Peyronie Disease in Younger Men 29 Table 2. Physical Examination Findings Objective Curvature Curvature Mean Direction of Curvature Dorsal Ventral Lateral Septal Plaque Plaque Location Distal Middle Proximal Palpable Nodule Hinge Dupuytren Contracture 27/30 (90%) 20.8% (5 70 ) 11/27 (41%) 4/27 (15%) 22/27 (81%) 8/30 (27%) 14/30 (47%) 6/30 (20%) 13/30 (43%) 30/30 (100%) 10/30 (33%) 1/30 (3%) Septal plaques were noted in 8 (27%) patients. Ten patients (33%) were found to have shaft narrowing and hinge-effect that caused buckling during coitus. Twentyseven of the 30 patients (90%) presented with penile curvature. Of these, 22 (81%) patients presented with lateral curvature, 11 (41%) with dorsal curvature, and 4 (15%) with ventral curvature. Eleven patients (37%) had 2 different simultaneous curvature directions, thus making the cumulative curvature direction in excess of 100%. Mean curvature was 20.8 (range 5 70 ). According to the modified Kelami classification, 16 of 27 patients (59%) had grade I, 9 of 27 (33%) had grade II, and 2 of 27 (7%) had grade III penile deformity. All patients were carefully examined for Dupuytren contracture, which was found in 1 patient (3%) (Table 2). Typical Patients With Peyronie Disease In the literature review of more than 1500 patients with PD, the mean reported age at disease presentation was 53.5 years. Presenting complaints included penile pain in 27%, penile curvature in 49%, and a palpable plaque in 39%. Twenty percent of men were able to recall a specific event that they attributed to the onset of PD. Erectile function was reported in 29%, and painful erections in 54%. Ability to achieve coitus was found in 25%, and painful intercourse was reported in 14%. A family history of PD was found in 2% (Table 3). Physical examination findings revealed a palpable plaque in 67% of patients. In the papers describing plaque location, distal location was reported in 30%, midshaft in 42%, and proximal in 28%. Penile curvature was reported in 87% of patients. The direction of curvature was lateral in 20%, dorsal in 77%, and ventral in 9%. A septal plaque was reported in 15%. Dupuytren contracture on physical examination was reported in 10% (Table 4) (Scardino et al, 1949; Williams and Thomas, 1970; Bystrom and Rubio, 1976; Pryor and Fitzpatrick, 1979; Wild et al, 1979; Palomar et al, 1980; Goldstein et al, 1984; Gelbard et al, 1990; Lindsay et al, 1991; Jordan and Angermeier, 1993; Ganabathi et al, 1995; Poulsen and Kirkeby, 1995; Ralph et al, 1995; Levine, 1997; Rehman et al, 1997; Weidner et al, 1997; Riedl et al, 2000). Treatment for Younger Men Treatment for young men included verapamil injection (17; 57%), observation (5; 17%), collagenase injection (during a double-blind trial protocol) (1; 3%), tunica albuginea plication (TAP) (3; 10%), dermal grafting (2; 7%), and combination TAP/dermal grafting (2; 7%) (Table 5). Verapamil injections were administered according to a previously published protocol of up to 12 percutaneous intraplaque injections of 10 mg verapamil every 2 weeks (Levine, 1997). Of the 17 patients treated with verapamil, 10 (59%) had subjective improvement in erection quality, 5 (29%) noted no change, and 2 (12%) had subjective worsening of erection quality. Seven of the 13 patients that presented with pain were treated with verapamil. Of these, 1 (14%) had substantial improvement and 6 (86%) had complete resolution of pain following treatment. The mean follow-up period for patients treated with verapamil was 36 months (range months). Of the 13 patients with curvature that were treated with verapamil injections, 7 (54%) experienced subjective improvement, 4 (31%) noted no change, and 2 (15%) reported worsening of curvature. Objective postverapamil injection curvature measurements were available for 10 of these 13 patients using pharmacologically induced erections. Duplex ultrasound in these patients was performed by a technician who was blinded to the treatment as well as the original ultrasound results. Five patients (50%) exhibited a mean improvement of 18 (range ), 2 (20%) showed no change, and 3 (30%) had a mean worsening of 22 (range 5 35 ). Overall, 2 patients treated with verapamil went on to have surgery. The one patient treated with collagenase injection had an objective reduction of curvature to 10 (30 dorsal pretreatment). He was followed for 14 months, but was then Table 3. Literature Review of Typical Patients with Peyronie Disease, Clinical Presentation and History Mean Age Presenting Complaint Pain Lump Curve Gradual Onset Sudden Specific Event Coitus Intercourse % 39% 49% N/A N/A 20% 29% 54% 25% 14% 2% Family History

4 30 Journal of Andrology January/February 2003 Table 4. Literature Review of Typical Patients with Peyronie Disease, Physical Examination Findings Curvature Direction of Curvature Dorsal Ventral Lateral Septal Plaque Plaque Location Distal Middle Proximal Palpable Plaque Dupuytren Contracture 87% 77% 9% 20% 15% 30% 42% 28% 67% 10% lost to follow-up. All patients who underwent surgery (7 of 30, 23%) had resolution of curvature and preservation of potency with a mean follow-up of 60 months (range months). All five patients who received no therapy and observed presented with a palpable nodule, minimal curvature, no pain, and no difficulty with coitus. In a mean follow-up period of 46 months (range months), no change in their complaints or physical examination was noted. Discussion The variety of presenting symptoms and physical examination findings in men with PD creates a therapeutic challenge for clinicians. Age-specific differences in presenting complaints and physical examination findings introduce other potentially confusing variables. The most current available data on the natural history of PD suggests that 13% will gradually resolve, 47% will remain stable, and 40% will worsen (Gelbard et al, 1990). Because there is no known way to determine who will spontaneously improve, treatment is directed at the great majority of patients in whom there is subjective disease progression, objective disease progression (or both), or stability. In addition, treatment requires tailoring to individual presenting symptoms, including pain, deformity, and erectile capacity. Consistent among all patient populations, the treatment end points should include erection that is pain-free, coitus that is comfortable for patient and partner, and deformity that does not interfere with coitus. Fundamentally, preservation of erectile function underlies each of the end points of treatment. A comparison of the clinical history and presentation between the young men (ie, younger than age 40 years) with PD and the typical patient with PD yielded interesting findings. First, younger patients were more often able to recall a specific event that presumably incited their Table 5. Treatment of Young Patients with Peyronie Disease Treatment N (%) Observation Verapamil injection Collagenase injection Tunical albuginea plication (TAP) Dermal graft Combination TAP & dermal graft 5 (17%) 17 (57%) 1 (3%) 3 (10%) 2 (7%) 2 (7%) disease process. Two possible explanations include a more rapid disease development after insult, increased strength of erection, or both in younger men. A strong erection may contribute to a more acute trauma at the time of injury, rather than the brittle tissue-fatigue fracture in older men with diminished rigidity (Devine et al, 1997). The markedly better erectile capacity (97% vs 29%) in the younger population is very likely reflective of the different age groups and concurrent medical conditions affecting erectile capacity rather than the disease process itself. Second, a larger proportion of younger men complained of painful intercourse than was reported in the literature for the typical patient with PD. Possible explanations include more frequent intercourse with concomitant irritation, more rigid erections that produce greater stress on the inflamed tissue, and a more intense inflammatory response in younger men. The young men who presented with PD at our institution also had some differences in their physical examination findings compared with the typical PD patient. First, there was a difference in the direction of curvature; 41% and 81% of the younger men reported dorsal and lateral curvature, respectively, whereas the literature review yielded 77% dorsal and 20% lateral curvature. The clinical significance of this is unknown. A possible explanation is a difference in the mechanism of injury to the penis. Second, all the younger men presented with a palpable nodule, whereas in only 67% of typical patients was a plaque identified. This may be reflective of a more accelerated or robust scar-formation response in younger men. Finally, a midshaft plaque was found in 20% of younger men, whereas the finding was reported in 42% of the reviewed patients. This may also be a reflection of a difference in the mechanism of injury to the penis. Hinge-effect, shaft narrowing, and distal softening were infrequently reported in the literature and thus comparisons of these characteristics cannot reliably be made to our group. The treatment of the pain associated with PD has included such agents as vitamin E (Scardino et al, 1949), potassium aminobenzoate (Zarafonetis and Horrax, 1953), oral tamoxifen (Ralph et al, 1992), and colchicine (Kadioglu et al, 2000). Intralesional injections of steroids (Winter and Khanna, 1975), collagenase (Gelbard et al, 1993), and verapamil (Levine et al, 1994; Levine, 1997; Lasser et al, 1998) have also been described. Verapamil has been reported to have a 97% resolution of pain fol-

5 Levine et al Peyronie Disease in Younger Men 31 lowing a mean of 2.5 treatments, and was used as the first-line therapy in our young patients who presented with pain (Levine, 1997). In the seven patients presenting with pain who were treated with verapamil, all experienced improvement or complete resolution of pain following treatment. Other therapies designed to arrest the inflammatory phase of the disease may also prove effective. Treatment of the resultant deformity associated with PD is best approached on an individual case basis. Patients who have active disease with or without pain are best treated with a nonsurgical approach, because the disease may continue to evolve after surgery. In the 13 patients with active disease treated with verapamil injections, 54% reported improvement of curvature, 31% noted no change, and 15% reported worsening. Ten of these 13 patients had postverapamil treatment objective measurements with pharmacodynamic duplex ultrasound by a technician who was blinded to the treatment as well as original ultrasound results. Of these 10, 5 showed improvement, 2 showed no change, and 3 had worsening of deformity. The effect of verapamil on erection quality was subjectively assessed by post-treatment interview. Of the 17 patients treated with verapamil, 59% reported improved erection quality, 29% noted no change, and 12% reported worsened erection quality. Whereas verapamil may have some positive effect on promotion of penile vascularity (Levine et al, 1994), it is not an agent used for the enhancement of erectile function. The subjective assessment of erection quality is, therefore, reflective of the patient s satisfaction with his sexual function, which may be improved by a successful treatment of PD-associated signs and symptoms following verapamil therapy. For patients with stable disease, severe curvature, plaques with extensive calcification, plaques that cannot be treated conservatively (septal or ventral plaques), or a combination of these, surgery may be the best treatment option. Of the 7 men who underwent surgery, all experienced resolution of curvature and preservation of potency at a mean follow-up of 60 months, perhaps owing to the inherently better cavernous blood supply and quality of tissues. Comparisons between these two groups are flawed in several respects. The inclusion of surgical series in the literature review introduces selection bias of a more severe degree of disease to the characterization of the typical patient with PD. Fundamentally, a consistent and reliable characterization of a typical patient with PD is problematic and likely impossible given the varied author approaches, definitions, and reporting methods. It seems almost an oxymoron to define a typical patient with PD at all. However, the exercise is useful in hopes of elucidating differences in younger patients presenting with the disease, which may ultimately suggest a difference in disease mechanism, natural history, treatment response, or a combination of these. In addition, it is important to heighten awareness among practicing urologists of the presence of PD in younger men. The inclusion of all types of literature (ie, descriptive, medical, and surgical) yields a balanced approach that more completely contributes to the amalgam that we describe as the typical patient. The exclusion of the remaining 596 patients seen at our institution in the comparison was done in order to eliminate our internal observer bias. Finally, our younger patient population is relatively small compared with the population represented by the vast literature available, making comparison difficult. In a recent report by Tefekli et al (2000), PD in 19 men younger than age 40 was also described. In that study, the prevalence of PD in younger men was 8.2% compared with 4.7% in our series. All their patients presented with penile deformity, and 53% presented with painful erections. This is consistent with our findings of penile curvature in 90% and painful erections in 59%. The direction of curvature, however, differs from our experience. In their series, 42% had dorsal curvature, 42% had lateral curvature, and 16% had ventral curvature, whereas 41% of our patients had dorsal curvature, 81% had lateral curvature, and 15% had ventral curvature. This may be reflective of different mechanisms of penile injury. Three treatment strategies were offered to their patients based on phase and severity of disease: observation, oral colchicine, and surgery with plaque incision and venous grafting. Of the 5 patients who were observed, 60% had stable or slight improvement of curvature, and 40% worsened. In our five patients who were observed, all had stable disease with a mean follow-up of 46 months. This difference may be attributable to patient selection, because all of our patients had minimal curvature, no pain, and no difficulty with coitus. Overall, treatment results reported by Tefekly et al (2000) are similar to ours, with 36% noting improvement in curvature with oral colchicines versus 50% in our series with verapamil injections. All patients who underwent surgery in both study groups had complete correction of curvature and preservation of rigidity. In another recent report, Schwarzer et al (2001) reported the results of a large general population survey in which the overall prevalence of Peyronie disease was found to be 3.2%. In men aged the prevalence was found to be 1.5%. The relatively high prevalence reported in these reports and in ours is surprising, and indicates that younger men who present with complaints of ED, penile pain, penile curvature, penile plaque, or a combination of these should be evaluated for PD. Conclusions By and large, urologists expect the man who presents with PD to be in his 50s or 60s. A younger man pre-

6 32 Journal of Andrology January/February 2003 senting with penile pain, palpable nodule, erection deformity, or a combination of these is unusual, and may not be readily recognized as PD. Therefore, a younger man presenting with the usual signs and symptoms of PD may represent a challenging diagnostic and treatment dilemma for urologists. The clinical presentation and physical findings frequently differ from those traditionally reported, and which have become accepted norms. Treatment of these young men, like all patients with PD, should be directed at relief of pain and curvature, and preservation of potency. Nonsurgical therapies may be indicated for those patients whose disease is minimal or who still have active disease presenting with painful erections and unstable deformity. In our experience, younger patients with minimal deformity, no pain, and no difficulty with coitus may be observed, and intralesional verapamil injection seems to be equally efficacious in the two patient populations. Surgical treatment should be reserved for patients with severe disease or those not amenable to or who fail nonsurgical therapy. This younger patient population will conceivably have many more years of sexual activity than their older counterparts, and given the psychological distress that this disease may cause in these patients, great care should be taken before performing any irreversible therapy. The overall positive therapeutic outcome of the patient group described in this review may be reassuring to the young man presenting with Peyronie disease. References Bystrom J, Rubio C. Induratio penis plastica (Peyronie s disease): clinical features and etiology. Scand J Urol Nephrol. 1976;10: Devine CJ, Somers KD, Jordan GH, Schlossberg SM. 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