Irvin H. Hirsch, MD
BASICS
DESCRIPTION
• An idiopathic, localized connective tissue disorder with increased collagen deposition in the tunica albuginea, resulting in a fibrous plaque that leads to pain and penile angulation (1)[C]
• Plaque (2)[C]:
– Most commonly dorsal plaque on side of penis to which curvature directed
• Penile angulation may cause dyspareunia and even preclude sexual intercourse
• First described by French surgeon François Gigot de Peyronie
• Synonym(s): Acquired penile curvature, chronic inflammation of the tunica albuginea (CITA), penile induration, Induratio penis plastica
EPIDEMIOLOGY
Incidence
• Affects males 40–70 yr old, with 0.4–3.2% incidence (1)[C]
• 3–7% men 40–70 yr old have PD (3)[C]
• Mean age: 53
Prevalence
Estimated 388 in 100,000 men (1,2)[C]
RISK FACTORS
• Inherent tendency to produce abnormal fibrous tissue
• Erectile trauma or injury to the tunica albuginea of the penis may incite fibrotic reaction from repetitive microvascular injury and healing
• Intracorporal injection therapy and oral pharmacotherapy for ED not implicated as risk (2)[C]
Genetics
Association with Dupuytren contracture (in 9–39%) and HLA-B7 antigens (1)[C]
PATHOPHYSIOLOGY
• Idiopathic (1,2)[C]
• Origin of initial inflammatory process that leads to fibrosis, calcification, elastic fiber alterations, and plaque formation in tunica albuginea unknown, but likely predisposing genetic alteration with inciting trauma
• Acute phase:
– Occurs in 1st 6–18 mo
– Proliferation of fibroblasts, myofibroblasts, and collagen deposition
– Pain with erections, slight penile curvature, and nodule formation
– Medical therapy most effective in acute phase
• Chronic phase:
– Remodeling of connective tissue into a dense fibrotic plaque
– Stable plaque size, penile curvature possibly causing ED, erections less painful
• Natural history: Minority of patients (10%) will have spontaneous regression, yet most patients will not develop disease significant enough to require surgery
ASSOCIATED CONDITIONS
• ED: Occurs in 20% men with PD (1)[C]
– Comorbidities: Diabetes, hypertension, dyslipidemia, smoking, coronary disease
• PD is found in 10% men with ED
– Urethral stricture may coexist
GENERAL PREVENTION
Avoidance of penile trauma during intercourse
DIAGNOSIS
HISTORY
• Distress and depression resulting from Peyronie disease
• Duration and onset of symptoms, history of erectile trauma. Severe pain or snap or popping during intercourse
• Pain: With or without erection; during intercourse
• Penis: Induration; degree and direction of penile angulation; hourglass deformity; lateral indentation; shortening; sensory loss, partner’s perception
• Erections: Quantify rigidity; sufficient for intercourse
• History of Dupuytren contractures or hand surgery for deformity
PHYSICAL EXAM
• Penile exam noting plaque size, tenderness and location
• Autophotography may be helpful in assessing degree of angulation
– Examine the palmar fascia for associated Dupuytren contracture
DIAGNOSTIC TESTS & INTERPRETATION
Lab
N/A
Imaging
No imaging necessary for diagnosis/medical therapy
Diagnostic Procedures/Surgery
• Preoperative assessment of stretched penile length and sensory threshold (Biothesiometry)
• Preoperative Doppler US with intracavernous vasoactive challenge: Assess plaque size, calcification, vascular hemodynamics of penis and erectile curvature
• Preoperative intracavernous injection of vasoactive agent and genital sexual stimulation with measurement of erectile curvature
• Photographic confirmation by the patient of degree of curvature is often helpful
Pathologic Findings
Excess collagen deposition and inflammatory infiltrate is found in the tunica albuginea
DIFFERENTIAL DIAGNOSIS
• Cancer: Primary or metastatic to corpora
• Chordee: Usually associated with hypospadias
• Kelami syndrome: Fibrosis of the corpus spongiosum that limits expansion of the ventral corpora cavernosa
• Penile fracture (hematoma)
TREATMENT
GENERAL MEASURES
• A small percent of men will undergo spontaneous remission.
• Surgery is not a common 1st-line option but ultimately offers definitive resolution of curvature and deformity.
• The lack of randomized, placebo-controlled trials makes evaluation of efficacy and comparison between any medical therapies for PD difficult.
• Patients most likely to respond to medical therapy: Young patients in acute phase. (1,2)[C]
• All medical therapies provide varying decrease in pain, curvature, or plaque size; complete resolution of curvature is uncommon.
MEDICATION
First Line
• Oral therapy (2):
– No therapy has proven more or less effective than another
– Vitamin E (tocopherol):
800–1,000 U/d PO in divided doses
Antioxidant effects; may cause bleeding
– Potassium aminobenzoate (Potaba):
3 g PO q6h
May increase monoamine oxidase, decrease serotonin, or increase utilization of oxygen by tissues; Expensive, GI side effects
– Colchicine:
0.6 mg PO q8h
May decrease collagen synthesis and increase collagenase activity
– Pentoxifylline:
Growth factor blocker and anti-inflammatory
400 mg PO BID
– Other reported oral therapy: Tamoxifen, acetyl-L-carnitine,
• Intralesional therapy (2):
– Collagenase clostridium histolyticum (CCH (4)[C]:
Breaks down collagen, promotes remodeling
FDA approved for curvature deformity of the penis due to the presence of a plaque in PD. Restricted distribution through Risk Evaluation and Mitigation Strategy (REMS) due to the risks of serious adverse reactions, including penile fracture and other serious penile injury
A cycle consists of 2 CCH injection procedures and a penile modeling procedure
Induce a penile erection (eg, intracavernosal injection of 10–20 mcg of alprostadil)
With the erection, identify and mark the target area in the Peyronie plaque
The penis should be in a flaccid state before injecting CCH. Inject 0.58 mg CCH into the target plaque of a flaccid penis once on each of 2 days, 1–3 days apart
Perform a manual penile modeling procedure 1–3 days after the 2nd injection of each treatment cycle. For each plaque causing the curvature deformity, up to 4 treatment cycles may be administered. Each treatment cycle may be repeated at approximately 6-wk intervals. If the curvature deformity is <15 degrees after the 1st, 2nd, or 3rd treatment cycle, or if further treatment is not indicated, then subsequent treatment cycles should not be administered
10,000 U in 0.25 cm3 per injection
– No other intralesional therapy has proven more or less effective than another
– Verapamil (5)[C]:
12 injections (10 mg/10 mL) given once every 2–4 wk
Calcium blockage inhibits extracellular transport of collagen; increases collagenase activity in vitro; must commit to full course
Applicable for young patients in acute phase
– Interferon α2a or 2b (6)[C]:
5 × 106 U biweekly for 3–6 mo
Inhibits fibroblast proliferation, diminishes collagen production, increases collagenase
Applicable for young patients in acute phase
Flu-like side effects
– Intralesional corticosteroids no longer recommended due to local side effects
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Indications: Curvature or erectile dysfunction that precludes intercourse (2)[C]
• Patient must be in chronic phase with stable painless plaques
• Preoperative US with intracavernous vasoactive challenge is useful to evaluate vasculature and anatomy of penis, as described above
• Plication procedures:
– Candidates: Longer penis, mild, distal curvature, good erectile function
– Relative to corporal plaque, plication of opposite aspect of corpora cavernosa with a 12–24-point plication. A relaxing incision of plaque is rarely required
– Complications/side effects: Hematoma, stitch erosion/granuloma, penile shortening
• Plaque excision with grafting:
– Candidates: Shorter penis, proximal plaque, severe curvature, hourglass deformity, lateral indentation and good erectile function
– Plaque incised/excised and corporotomy defects grafted with small intestine submucosal graft (Surgisis, Cook Biotech)
– Complications: Loss of sensitivity, infection, hematoma, shortening, de novo venoocclusive erectile dysfunction
• Inflatable penile prosthesis placement:
– Candidates: Significant erectile dysfunction, severe curvature
– Modeling:
When prosthesis placement alone fails to straighten penis, manual modeling is recommended, with good outcomes
Forcible manual manipulation of penis (“modeling” over inflated prosthesis)
– Complications: Infection (1–3%), erosion (<5%), mechanical malfunction (5–10%), urethral injury
ADDITIONAL TREATMENT
Radiation Therapy
Mixed results reported; not recommended
Additional Therapies
Extracorporeal shockwave therapy: No good placebo-controlled studies to document efficacy; studies report decreased pain after ESWL therapy (2)
Complementary & Alternative Therapies
• Penile traction therapy may have utility when combined with other therapies
• Carnitine supplementation: Mixed results
ONGOING CARE
PROGNOSIS
See “Pathophysiology–Natural History”
COMPLICATIONS
• PD can impact quality of life and cause relationship difficulties
• Depression can be associated
FOLLOW-UP
Patient Monitoring
• Patients should be re-examined frequently to assess disease status and response to therapy.
• Recent studies suggest up to 48% of men with PD have clinically relevant signs of depression and should be considered for mental health screening. (7)
Patient Resources
• AUA Urology Care Foundation. http://www.urologyhealth.org/urology/index.cfm?article=115
• The Peyronie Disease Society. www.peyroniessociety.org
REFERENCES
1. Hellstrom WJ, Bivalacqua TJ. Peyronie’s disease: Etiology, medical, and surgical therapy. J Androl. 2000;21(3):347–354.
2. Wespes E, Eardley I, Giuliano F, et al. Guidelines on penile curvature. Eur Urol. 2012;62:543–552.
3. Sommer F, Schwarzer U, Wassmer G, et al. Epidemiology of Peyronie’s disease. Int J Impot Res. 2002;14:379–383.
4. Gelbard M, Goldstein I, Hellstrom WJ, et al. Clinical efficacy, safety and tolerability of collagenase clostridium histolyticum for the treatment of Peyronie disease in 2 large double-blind, randomized, placebo controlled phase 3 studies. J Urol. 2013;190(1):199–207.
5. Levine LA and Constabile RA. Is intralesional verapamil effective therapy for peyronie’s disease? J Urol. 2012;188:704–706.
6. Hellstrom WJ, Kendirci M, Matern R, et al. Single-blind, multicenter, placebo controlled, parallel study to assess the safety and efficacy of intralesional interferon α-2b for minimally invasive treatment for Peyronie’s disease. J Urol. 2006;176:394–398.
7. Nelson JN, Diblasio C, Kendirci M, et al. The chronology of depression in men with Peyronie’s disease. J Sex Med. 2008;5:1985–1990.
ADDITIONAL READING
Abern MR, Larsen S, Levine LA. Combination of penile traction, intralesional verapamil, and oral therapies for Peyronie’s disease. J Sex Med. 2012;9:288–295.
See Also (Topic, Algorithm, Media)
• Chordee
• Erectile Dysfunction/Impotence (ED)
• Penis, Curvature and/or Pain
• Penis and Corporal Body Mass
• Peyronie Disease Image 
CODES
ICD9
• 607.84 Impotence of organic origin
• 607.85 Peyronie’s disease
• 608.89 Other specified disorders of male genital organs
ICD10
• N48.6 Induration penis plastica
• N52.9 Male erectile dysfunction, unspecified
• N53.12 Painful ejaculation
CLINICAL/SURGICAL PEARLS
• Diagnosis of Peyronie disease is exclusively based on history and physical exam.
• Patients with mild curvature and no evidence of erectile dysfunction should be observed.
• New data suggests that CCH can significantly reduce the symptoms of Peyronie disease.
• The ideal candidate for CCH is having Peyronie disease for at least 12 mo, has stable disease, and a curvature of 30 degrees or greater.