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Medicines Q&As
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 www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
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 intercourse1. The pathophysiology of PD tends to follow three phases: acute,
early chronic, and chronic2. 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 therapies5.
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 stabilised 2. 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 strategies6
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
Available through NICE Evidence Search at www.evidence.nhs.uk
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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 established12.
Colchicine
Colchicine inhibits microtubule formation, and is thought to stimulate collagenase production and
activity, and decrease collagen synthesis. The net effect is a reduction in collagen synthesis, and
may in turn reduce plaque formation. Colchicine also has anti-inflammatory activity due to interference
with phagocyte activity8.
A randomised controlled trial 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 therapy14.
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
group16.
Pentoxifylline (PTX)
PTX is a phosphodiesterase inhibitor and has anti-inflammatory properties. It may also have anticalcification 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.
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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
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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-Lcarnitine 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
Available through NICE Evidence Search at www.evidence.nhs.uk
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PEYRONIE DISEASE/dt and *TAMOXIFEN
PEYRONIE DISEASE/dt and *PENTOXIFYLLINE
PEYRONIE DISEASE/dt and *LEVACECARNINE
NHS Choices/Medline Plus
In-house resources
References
1
Is it normal to have a curved penis? NHS Choices, Accessed via
http://www.nhs.uk/chq/pages/875.aspx?categoryid=61&subcategoryid=616 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
http://kidney.niddk.nih.gov/KUDiseases/pubs/peyronie/index.aspx 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 (POTABA TM) 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.
Available through NICE Evidence Search at www.evidence.nhs.uk
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