Q&A 407.2
What oral treatments are effective at treating Peyronie’s disease?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at
Date prepared:21st October 2014
Background
Peyronie’s disease (PD) is a condition which causes the penis to become curved when erect, due to the formation of a plaque in the penis shaft. The condition can be distressing, causing pain and difficulty during sexual intercourse[1]. The pathophysiology of PD tends to follow three phases: acute, early chronic, and chronic[2]. The acute phase involves an inflammatory reaction and may be associated with the most pain. In the chronic phase, fibrosis starts to develop and eventually stabilises, leaving a calcified plaque2,[3].
The cause of PD is as yet unknown. It is most common in men over 40 years of age, although it can occur at any age1. The plaque is benign and the condition is not contagious[4]. This unknown aetiology means it is difficult to find effective curative therapies[5].
In mild cases without pain, treatment may not be required1. Conservative treatments are indicated in the acute or early chronic phases before fibrosis and calcification have stabilised2. In severe cases, a number of surgical options may be considered1,4,5. Whilst some oral therapies are in use, the evidence base for these is limited. Up to approximately 15-50% of cases may spontaneously resolve3,5, whilst others require no specific treatment. Local injections, such as steroids and collagenase have also been used1. Patients with larger plaques may be less likely to respond to conservative treatment strategies[6]
Answer
Vitamin E
Vitamin E is used in Peyronie’s for its antioxidant effect, which is thought to reduce the development of fibrosis following the initial inflammatory stage of the disease[7],[8]. Theoretically, vitamin E use in the early stages of the disease may change the course of the disease, reducing pain, size of plaque, and extent of deformity7.
Vitamin E appears to be treatment of choice for some physicians, even despite the lack of robust evidence of its efficacy. This is based on the fact that is it of low expense and is generally well tolerated8,[9].
No large clinical trials have assessed the efficacy of vitamin E alone in Peyronie’s disease. One randomised, double blind, placebo controlled study by Safarinejad et al assessed vitamin E 300mg alone vs propionyl-L-carnitine against placebo and a combination of both. There were 236 patients enrolled in the study, 58 of whom were given vitamin E alone. The vitamin E only arm saw a decrease in pain in 60.4%, reduction of curvature in 18.9% and a decrease in plaque size in 11.3% of patients, however no significant differences were found between the groups[10].
Potassium para-aminobenzoate (PotabaTM)
Potaba has immunomodulatory effects, so counteracts the inflammatory reaction in areolar tissue before it progresses to fibrosis8. It stabilises serotonin monoamine oxidase activity within the tissue, along with inhibiting secretion of glycosamineglycane from fibroblasts[11].
One prospective, placebo controlled study appears in the literature. Weidner et al performed a randomised, double-blind study involving 103 patients for a duration of 12 months. There was a high drop out rate; only 75 patients completed the study (35 in the treatment group and 40 in the placebo group), due to adverse effects or poor compliance. The resulting data were not subject to intention to treat analysis. A response rate (defined as either full resolution or reduction in plaque size or penile curvature of ≥30%) of 74.3% with Potaba and 50% with placebo was observed (p=0.016). The difference between groups for plaque size was said to be significant (p=0.042), but lack of a power calculation in the study limits its reliability.
Potaba has been linked to several cases of acute liver injury. An example of these case reports is a 70 year old man suffering with Peyronie’s disease unresponsive to vitamin E plus colchicine. The patient was reported to have clinical symptoms and test results consistent with hepatocellular injury, which resolved after discontinuation of his medications, which included Potaba. However, no definite causal link was established[12].
Colchicine
Colchicine inhibits microtubule formation, and is thought to stimulate collagenase production and activity, and decrease collagen synthesis. The net effect is a reductionin collagen synthesis, and may in turn reduce plaque formation. Colchicine also has anti-inflammatory activity due to interference with phagocyte activity8.
A randomised controlledtrial compared colchicine against placebo in 84 patients with Peyronie’s disease of 6-42 months duration. At baseline, there were no significant differences between the treatment and placebo groups in plaque size, curvature, age at disease onset, or duration. The study found no significant differences in any endpoint, including penile curvature, patient’s perception of plaque volume, pain, or ability to perform intercourse[13].
Other studies provide conflicting results, but methodological problems preclude any conclusions being drawn. For example, a retrospective review of 59 patients given colchicine monotherapy found a good response in 39% of patients. 36% found a reduction in plaque size, 46% had pain relief, and 32% found an improvement in curvature. However, this study had no control group, so it is difficult to extrapolate the results to effectiveness of colchicine therapy[14].
Interestingly, two cases have been reported of patients developing Peyronie’s disease whilst on colchicine therapy for Familial Mediterranean Fever. The authors concluded that two possibilites could have caused these cases: either colchicine has no effect on preventing inflammation and fibrosis in the tunica albugina, or a type of colchicine-resistant Peyronie’s Disease exists[15].
Tamoxifen
Tamoxifen, an anti-oestrogenic drug, is thought to work in Peyronie’s Disease due to modulatory actions on TGF-β1 secretion8.
A small, randomized, placebo controlled trial of 25 patients was reported by Teloken et al. However, randomization and blinding are poorly described in the study, and it is limited by its very small size. No significant differences in improvement were found between the tamoxifen group and the placebo group[16].
Pentoxifylline (PTX)
PTX is a phosphodiesterase inhibitor and has anti-inflammatory properties. It may also have anti-calcification properties which may be of benefit[17].
A retrospective cohort study of men with tunical calcification (representing the more chronic and severe phase of PD) saw stabilisation or improvement in calcification (as measured by sonography) in 91.9% of men treated with PTX (n=62), as opposed to 44.4% of patients who were given vitamin E or no treatment (n=9, p=<0.001). Patients who took PTX were also less likely to report a subjective worsening of their condition (21.7% vs. 75%, p=0.002)17. However, while these results are impressive there are a number of limitations in these data. There was no baseline randomisation, and objective measurements were not available for inclusion into the study, which was also too small to allow for any meaningful statistics to be obtained.
Sarafinejad et al performed a double-blind, placebo-controlled study which included 228 patients with early chronic phase PD. There was significantly less disease progression in the PTX group than the placebo group (11% vs 42%, p=0.01), and significant improvements in penile curvature (p=0.003) and plaque area (p=0.001). There were also significant improvements in erectile function in the treatment group (p=0.02). It was concluded by the authors that PTX may have moderate effects in some aspects of the treatment of PD, but that more study is needed to determine its effectiveness[18].
Acetyl-L-Carnitine:
Acetyl-L-Carnitine has several actions which may be relevant to its use in PD. It is a precursor to acetylcholine, enhances the Kreb’s cycle and mitochondrial respiration, and increases free radical and fatty acid metabolism2.
A study of 48 patients with acute or early chronic phase PD who were included in a randomised trial found a significant proportion of patients assigned acetyl-L-carnitine (92%) experienced erectile pain relief. This was significantly better than with tamoxifen (p<0.01). A significant reduction in penile curvature was also found with acetyl-L-carnitine (p<0.01). The authors conclude that acetyl-L-carnitine is “significantly more effective and safe than tamoxifen in the therapy of acute and early chronic Peyronie’s disease”. However, the small size of this trial and the lack of blinding mean the results may be difficult to extrapolate to clinical use2.
Summary
The causes and pathophysiology of PD are not clear at this time. It is therefore difficult to find a reliably effective oral treatment.
Vitamin E, potassium para-aminobenzoate, colcichine, tamoxifen, pentoxifylline, and acetyl-L-carnitine have all been investigated as treatment options.
No oral treatment has a robust evidence base supporting its use at this time. Some evidence is conflicting as to the effectiveness of treatments, but there are methodological limitations in much of the available literature.
More large, robust clinical trials are required to determine effectiveness of oral treatments.
Individual patients may benefit from oral treatments, but the current evidence base is too limited to determine which patients may benefit most.
Limitations
This Q&A does not consider non-oral therapies for Peyronie’s diease. Studies which assessed combination oral therapies or a combination of an oral therapy and a non-oral therapy were also not included.
Quality Assurance
Prepared by
Hayley Johnson, Regional Drug & Therapeutics Centre
Date Prepared
21st October 2014
Checked by
Nancy Kane, Regional Drug & Therapeutics Centre
Date of check
21st October 2014
Search strategy
Embase (incorporating Medline search, via NHS Evidence)
PEYRONIE DISEASE/dt and *ALPHA TOCOPHEROL
PEYRONIE DISEASE/dt and *4 AMINOBENZOATE POTASSIUM
PEYRONIE DISEASE/dt and *TAMOXIFEN
PEYRONIE DISEASE/dt and *PENTOXIFYLLINE
PEYRONIE DISEASE/dt and *LEVACECARNINE
NHS Choices/Medline Plus
In-house resources
References
1
Available throughNICE Evidence Search at
[1] Is it normal to have a curved penis? NHS Choices, Accessed via on 21st October 2014 (page last reviewed 25th May 2013)
[2] Biagiotti G and Cavallini G. Acetyl-L-Carnitine vs tamoxifen in the oral therapy of Peyronie’s disease: a preliminary report. BJU International 2001; 88: 63-67
[3] Hauck E, Weldner W. Francois de la Peyronie and the disease named after him. The Lancet 2001; 357; 2049-2051
[4] Peyronie’s Disease: National Kidney and Urologic Diseases Clearinghouse. Accessed via on 21st October 2014 (page last updated 23rd July 2013)
[5] Levine L. Peyronie’s disease: a difficult sexual problem. Western Journal of Medicine 1998; 169(3): 168-169
[6] Hashimoto K, Hisasue S, Kato R et al. Outcome analysis for conservative management of Peyronie’s disease. International Journal of Urology 2006; 13: 244-247
[7] Prieto Castro R, Levo Vallejo M, Anglada Curado F et al. Combined treatment with vitamin E and colcichine in the early stages of Peyronie’s disease. British Journal of Urology International 2003; 91: 522-524
[8] Myderse L and Monga M. Oral Therapy for Peyronie’s disease. International Journal of Impotence Research 2002; 14: 340-344
[9] Wagner L and Costa P. Medical treatment of la Peyronie’s disease [French-Abstract only]. Andrologie 1998; 8(2): 160-164
[10] Safarinejad M, Hosseini S, and Kolahi A. Comparison of vitamin E and Propionyl-L-Carnitine, separately or in combination, in patients with early chronic Peyronie’s disease: a double-blind, placebo controlled, randomized study. Journal of Urology 2007; 178(4): 1398-1403.
[11] Weidner W, Hauck E, and Schnitker J. Potassium paraaminobenzoate (POTABATM) in the Treatment of Peyronie’s Disease: A prospective, Placebo-controlled, Randomised Study. European Urology 2005; 47: 530-536
[12] Roy J and Carrier S. Acute hepatitis associated with treatment of Peyronie’s Disease with potassium para-aminobenzoate (Potaba). Journal of Sexual Medicine 2008; 5(12): 2967-2969
[13] Safarinejad M. Therapeutic effects of colchicine in the management of Peyronie’s Disease: a randomized double-blind, placebo-controlled study.International Journal of Impotence Research. 2004; 16: 238-243
[14] Cortes-Gonzalez J and Glina S. Conservative treatment wof Peyronie’s Disease: colchicine vs colchicine plus vitamin E. Actas Urologicas Espanolas 2009; 34(5): 444-449
[15] Erdogru E, Usta M, and Ates M et al. Development of Peyronie’s Disease during long-term colchicine treatment.Internation Urology and nephrology 2003; 35: 207-208
[16] Teloken C, Rhoden E, Grazziotin T et al. Tamoxifen versus placebo in the treatment of Peyronie’s disease. The Journal of Urology 1999; 162: 2003-2005
[17] Smith J, Shindel A, Huang Y et al. Pentoxifylline treatment and penile calcifications in men with Peyronie’s Disease. Asian Journal of Andrology 2011; 13: 322-325
[18] Safarinejad M, Asgari M, Hosseini S et al. a double blind placebo controlled study of the efficacy and safety of pentoxyfylline in early chronic Peyronie’s disease. BJU International 2009; 106:240-248.