Synonyms: penile fibrosis, induratio penis plastica

This a disorder of penile connective tissue, first brought to widespread medical attention by François Gigot de Peyronie in 1743.¹ Fibrous plaque formation occurs in the corpus cavernosum's tunica albuginea. There is inflammatory thickening with fibrin deposition, increased collagen production, decreased quantity of elastic fibres and subsequent fibrosis ± calcification. This leads to penile angulation or an hourglass-like deformity with distal flaccidity. It usually affects only the erect penis. Sexual intercourse can become painfully difficult or impossible. It is thought to occur (but nobody really knows) as a result of one-off or repeated penile vascular trauma causing leakage and immunological reaction in the relatively avascular tunica albuginea. Genetic susceptibility is thought to play a role² and one study suggested a link with low testosterone levels.³

Epidemiology

Exact figures for prevalence and incidence are hard to come by, as many men may not seek help due to embarrassment. Based on the current literature, the prevalence seems to be 3-9% with an average age of onset in the fifth life decade.⁴

Associated conditions

Purportedly Dupuytren's contracture, phenytoin therapy, diabetes mellitus and hypertension.^2,5,6

Presentation²

When Peyronie's disease (PD) first presents it tends to be with penile pain during erections, penile angulation (this can be seen in some cases in a flaccid penis), palpable fibrous plaque at the site of angulation, and erectile dysfunction. After 18-24 months the pain settles and plaque, angulation and calcification tend to predominate.

Investigations²

• Penile X-ray and ultrasound can demonstrate calcified and non-calcified plaques respectively. In specialist hands, corpus cavernosography can help to demonstrate cavernosus deformity and vascular blockage.^7,8
• MRI is used but adds little to clinical diagnosis in most cases.
• Penile scintigraphy with technetium Tc 99m human immunoglobulin G has been used to help distinguish unstable PD, which is best treated medically, from stable PD, which may require surgical intervention.⁹

Management

Studies of the natural history of the disease suggest that it is a self-limiting condition which goes through an active, scarring phase followed by a mature quiescent phase. This makes the interpretation of pharmaceutical trials difficult to interpret. Most pharmacotherapy reduces scarring and is therefore most effective during the active phase.¹⁰ Before embarking on intra-lesional or surgical approaches, several months should therefore be allowed to pass to allow resolution to occur. The role of conservative therapy is controversial and evidence-based guidelines are needed.¹¹ Psychosexual difficulties are an unsurprising byproduct of the condition and referral to a psychologist/counsellor/psychiatrist skilled in this area may significantly reduce the burden of the disease on the patient.¹²

Non-drug

External penile traction is a new technique that is currently being evaluated.¹³

Drugs

• Oral: drugs which have been tried for this condition include para-aminobenzoate, tocopherol (vitamin E), colchicine, tamoxifen, propoleum, acetyl-L-carnitine and pentoxyfilline. Few have shown any consistent effect in placebo-controlled trials. Para-aminobenzoate may decrease plaque size and curvature and acetyl-L-carnitine may reduce erectile pain and inhibit disease progression.¹⁴ Pentoxyfilline, which is licensed in the UK for the treatment of peripheral vascular disease, has also been used on an unlicensed basis for this condition and may be moderately effective in reducing penile curvature and plaque volume in early disease, but more research is needed.^2,15,16
• Intralesional: the current standard of care involves injection with interferon-alpha-2a or -2b, verapamil or collagenase over 2-week intervals for a period of 5-6 months. Of these, interferon has the largest evidence base but is also the most likely to produce adverse effects (fever and other flu-like symptoms).¹⁴
• Iontophoresis - electromotive drug administration (EMDA): a variety of researchers have used electrical current (up to 5 mA) to deliver charged drug molecules to the affected area - usually a combination of dexamethasone, verapamil and/or orgotein and lidocaine. Some well-designed trials have shown significant benefits in subjective and objective criteria, particularly in men suffering the early phase of the disease. There appear to be no significant adverse effects apart from mild, local erythema. Further randomised controlled trials in this area may prove EMDA to be a useful first-line therapy for the early phase of Peyronie's disease.^17,18

Surgical

Careful selection, patient education and discussion of patient expectation help to improve satisfaction post-surgery.¹⁹ Various techniques are available:

• Extracorporeal shock wave therapy: NICE has produced guidance for professionals and public on the use of this technique in this context. Essentially, whilst there are no significant safety concerns, NICE is not convinced of any proof of efficacy for the procedure; it advises it be used in carefully-controlled, well-audited programmes or as part of a research trial, with detailed explanation given to patients during the consenting process.²⁰
• 'Cold steel' surgery²: this surgery should be reserved for patients with significant morbidity who fail to respond to medical therapy. It should be deferred until 12-18 months, after which time changes to plaques and angulation are unlikely. Options include:
  • The Nesbit tuck procedure: normal tunica albuginea is removed from the side of the penile shaft opposite the plaque to straighten and shorten the penis. Potency should be normal and the penile curvature should be less than 60°.
  • Tunica plication procedure: this involved plication rather than excision of the unaffected tunica albuginea to straighten the penis. This technique also causes penile shortening.
  • Plaque excision and grafting: this is performed to preserve penile length when the curvature is greater than 60°.
  • Plaque excision and penile prosthesis insertion: this is useful when severe erectile dysfunction is also a problem.
  • One study found that the insertion of a soft penile prosthesis gave a good result and preserved erectile function.²¹
  • Carbon dioxide laser: this has been used to good effect in some cases to thin the plaque.

Prognosis

In one large study, all patients who reported penile pain had improvement and 89% reported complete resolution at one-year follow-up. The majority of patients were reported to have a decrease in flaccid length (average 12.2 cm decreasing to 11.4 cm). Of men with curvature, 12% had improved, 40% remained stable and 48% had worsened at follow-up.⁶

Document references

1. Francois de la Peyronie; whonamedit.com 2007
2. Zimmerman J, Laumann A, Bales G; Peyronie Disease eMedicine, Feb 2010.
3. Moreno SA, Morgentaler A; Testosterone deficiency and Peyronie's disease: pilot data suggesting a significant relationship. J Sex Med. 2009 Jun;6(6):1729-35. Epub 2009 Mar 30. [abstract]
4. Muller A, Mulhall JP; Peyronie's disease intervention trials: methodological challenges and issues. J Sex Med. 2009 Mar;6(3):848-61. Epub 2008 Dec 8. [abstract]
5. Summary of Product Characteristics, Epanutin® Capsules, Pfizer, revised November 2008, last accessed August 2009.
6. Mulhall JP, Creech SD, Boorjian SA, et al; Subjective and objective analysis of the prevalence of Peyronie's disease in a population of men presenting for prostate cancer screening. J Urol. 2004 Jun;171(6 Pt 1):2350-3. [abstract]
7. Lopez JA, Jarow JP; Penile vascular evaluation of men with Peyronie's disease. J Urol. 1993 Jan;149(1):53-5. [abstract]
8. Prando D; New sonographic aspects of peyronie disease. J Ultrasound Med. 2009 Feb;28(2):217-32. [abstract]
9. Erdogru T, Boz A, Koksal T, et al; Penile scintigraphy with 99mTc-human immunoglobulin G: a novel method for distinguishing the unstable and stable phases of Peyronie's disease. BJU Int. 2002 Nov;90(7):703-6. [abstract]
10. Jordan GH; Peyronie's disease: update on medical management and surgical tips. Can J Urol. 2007 Dec;14 Suppl 1:69-74. [abstract]
11. Vardi Y, Levine LA, Chen J, et al; Is there a place for conservative treatment in Peyronie's disease? J Sex Med. 2009 Apr;6(4):903-9. [abstract]
12. Smith JF, Walsh TJ, Conti SL, et al; Risk factors for emotional and relationship problems in Peyronie's disease. J Sex Med. 2008 Sep;5(9):2179-84. Epub 2008 Jul 14. [abstract]
13. Levine LA, Newell M, Taylor FL; Penile traction therapy for treatment of Peyronie's disease: a single-center pilot study. J Sex Med. 2008 Jun;5(6):1468-73. Epub 2008 Mar 26. [abstract]
14. Trost LW, Gur S, Hellstrom WJ; Pharmacological Management of Peyronie's Disease. Drugs. 2007;67(4):527-45. [abstract]
15. Brant WO, Dean RC, Lue TF; Treatment of Peyronie's disease with oral pentoxifylline. Nat Clin Pract Urol. 2006 Feb;3(2):111-5; quiz 116. [abstract]
16. Safarinejad MR, Asgari MA, Hosseini SY, et al; A double-blind placebo-controlled study of the efficacy and safety of pentoxifylline in early chronic Peyronie's disease. BJU Int. 2010 Jul;106(2):240-8. Epub 2009 Oct 26. [abstract]
17. Di Stasi SM, Giannantoni A, Capelli G, et al; Transdermal electromotive administration of verapamil and dexamethasone for Peyronie's disease. BJU Int. 2003 Jun;91(9):825-9. [abstract]
18. Montorsi F, Salonia A, Guazzoni G, et al; Transdermal electromotive multi-drug administration for Peyronie's disease: preliminary results. J Androl. 2000 Jan-Feb;21(1):85-90. [abstract]
19. Egydio PH; Surgical treatment of Peyronie's disease: choosing the best approach to improve patient satisfaction. Asian J Androl. 2008 Jan;10(1):158-66. [abstract]
20. Extra-corporeal shock wave therapy for Peyronie's disease; NICE IPG029 2003
21. Grasso M, Lania C, Fortuna F, et al; Preservation of cavernosal erectile function after soft penile prosthesis implant in Peyronie's disease: long-term followup. Adv Urol. 2008:646052. Epub 2008 Dec 2. [abstract]

Internet and further reading

• Cavallini G; Towards an evidence-based understanding of Peyronie's disease. Int J STD AIDS. 2005 Mar;16(3):187-94; quiz 94-5. [abstract]
• Hellstrom WJ; Medical management of Peyronie's disease. J Androl. 2009 Jul-Aug;30(4):397-405. Epub 2008 Oct 30. [abstract]
• Peyronie's Disease Society; American site, has a support forum

Acknowledgements