Peyronie’s Disease: Therapeutic Considerations
Thomas A. Kruzel, ND
Peyrone’s disease (PD) is an acquired, inelastic fibrous plaque deformity of the penis, resulting in a physically and psychologically debilitating condition. Also known as “indurations plastica penis,” the condition results in penile deformity, consisting of curvature, narrowing and shortening, resulting in painful erections and, in most cases, an inability to have intercourse. The plaques formed impede tunical expansion during erection, resulting in penile bending.1 The degree of pathology that develops is variable, with some men experiencing minor discomfort and minimal deformity, and others experiencing considerable pain and marked deformity, with plaque calcification.1
Because great variability is seen with this condition, men with PD may complain of a variety of symptoms. Penile curvature, lumps in the penis, painful erections, soft or incomplete erections, and difficulty with penile penetration due to curvature are common concerns that bring men with PD to their physicians. More often, however, men will complain of erectile dysfunction, particularly difficulty maintaining erections.
Prevalence of PD
While a certain degree of penile curvature is considered normal, about 4% to 10% of men are born with congenital penile curvature.2 This is associated with hypospadias or chordee, the latter of which is a condition characterized by downward bending of the penis. This condition is to be distinguished from Peyronie’s disease, which involves curvature and deformity of the penile shaft following injury.
Depending upon the source consulted, the prevalence of PD is estimated to be anywhere from 1% to 4%, or up to 23% in men between the ages of 40 and 70, with the average age of onset being 53.3 The number of cases may, in fact, be higher due to the underreporting of the condition. In a study of 100 men with no symptomology of PD, asymptomatic plaque lesions were found in the tunica albugenia,4 suggesting that plaque development is part of the normal course of aging and sexual activity.
PD was first reported by Fallopius in 1561, and then further described in 1743 by Francois de La Peyronie. Since then, the disease has born his name.5
Causes of PD
The underlying cause of PD is not well-understood, but is associated with trauma or injury to the penis, most often associated with sexual intercourse. Initially, men may not be aware that the initial injury has occurred, often not experiencing symptoms until sometime later.
The most likely reason for the development of PD is thought to be repeated tunical mechanical stress and microvascular trauma from excessive bending during erection or blunt trauma to the erect penis. This results in bleeding into the subtunical spaces, or tunical delamination, at the point where the septum integrates into the inner circular layer of the tunica albuginea.6
While genetic links to PD have not as yet been discovered, an autoimmune component has been suggested by studies that report abnormalities in immunological testing, alterations in cell-mediated immunity, increases in autoimmune diseases, and the finding of anti-elastin antibodies in the serum of PD patients.7,8 Additionally, the use of some beta-blockers has also been implicated as an etiologic agent in the development of PD.9
The most commonly associated comorbidities and risk factors are diabetes, hypertension, lipid abnormalities, ischemic cardiomyopathy, erectile dysfunction, smoking, and excessive alcohol consumption. Paget’s disease, Dupuytren’s contracture, and specific HLA subtypes are associated with PD, as are rheumatoid arthritis and hypertension.3,10-12 Dupuytren’s contracture is more commonly associated with penile curvature.
Peyronie’s disease patients are generally classified into 3 categories1,13:
- patients with asymptomatic plaques or some penile bending that does not affect intercourse (type I)
- patients whose plaques exacerbate penile bending to the point that intercourse is either painful and/or no longer physically possible (type II)
- patients whose Peyronie’s disease is also associated with erectile dysfunction (type III)
Unlike normal wound healing following trauma, in the chronic stages of the disease in patients with PD, plaques do not resolve subsequent to inflammation and cessation of pain.1,14 This is thought to be due to an overproduction of collagen and defects in other tissue remodeling mechanisms, resulting in an inability to resolve the injury; this process ultimately contributes to plaque formation. The implication here is that the more chronic the condition, the greater the chance that the plaques will continue to form and to eventually ossify.
During chronic disease states, in addition to fibrogenesis and an increase in connective tissue, there is an increase in oxidative stress.15 This stress, in the form of free radicals such as superoxide, peroxynitrite, and peroxide-generated species, can result in lipid peroxidation and tissue damage, as well as stimulate connective tissue synthesis in fibroblasts and increase activity in inflammatory phagocytic cells such as neutrophils and macrophages.16
The plaques of Peyronie’s disease most commonly develop on the upper (dorsal) side of the penis although they may also occur on the bottom (ventral) or side (lateral) of the penis, causing a downward- or sideways-bending. Some men present with more than 1 plaque, which can cause complex curvatures.
Diagnosis is made based upon history and physical examination, and ultrasound provides conclusive evidence of Peyronie’s disease, helping to rule out congenital curvature or other disorders.17
Treatment should be initiated at the first signs of the disease, due to the chronic inflammatory nature of PD. Without treatment, about 12-13% of patients will spontaneously improve over time, 40-50% will get worse, and the rest will be relatively stable.18
Vitamin E use in the treatment of PD has been around for a considerable period of time. A number of studies16,19,20 both support and do not support its role as an antioxidant treatment in PD, while other studies suggest that when used in combination with other agents, vitamin E is effective.21,22 While the evidence is largely inconclusive, most of the studies on vitamin E are done after the fact, ie, when the lesions have already formed. So it stands to reason that by itself, vitamin E would not appreciably affect PD. Its value is undoubtedly in the earlier stages of lesion development, to help reduce oxidative stress. This property makes it a valuable addition to other natural therapies as the damaged tissue begins to remodel.
Coenzyme Q10(CoQ10), at a dose of 300 mg, was shown to decrease mean plaque size and degree of curvature after 24 weeks in patients with PD. In contrast, the placebo group showed a slight increase.23 In another study, the same investigator examined the use of omega-3 fatty acids for PD; however, no benefit was observed.24
Potassium amino-benzoate may offer some benefit for PD, with respect to plaque size, but not curvature, according to a retrospective study.25 Its effectiveness may be explained by its inhibition of abnormal fibroblast proliferation, acid mucopolysaccharide, and glycosaminoglycan secretion.26
In their review of oral therapies for Peyronie’s disease, Mynderse and Monga cite several studies that reported improvement from potassium amino-benzoate, in terms of penile discomfort, plaque size, and penile angulation.26 A complete resolution of penile angulation was observed in 26% of patients, with the average interval to improvement being 4.2 months. As a cautionary note, this medication has been associated with a high rate of stomach upset, which leads many men to stop taking it.
Tamoxifen is a non-steroidal anti-estrogen medication that has been proven effective in the treatment of desmoid tumors, a condition with properties similar to Peyronie’s disease. Tamoxifen is believed to impact the inflammatory response through modulation of TGF-b1 secretion from fibroblasts. An early study treated men for 3 months with 20 mg of tamoxifen BID.27Improvements in pain (80%), plaque size (34%) and penile curvature (35%) were reported.
Colchicine is an anti-inflammatory agent that acts in both inflammatory and collagen production (fibrotic) phases of Peyronie’s disease. By binding to tubulin, colchicine decreases collagen development, which in turn inhibits the formation and function of the mitotic spindle during mitosis. However, colchicine’s effect on microtubules also has an impact on many other cell functions as well, resulting in side effects such as diarrhea and nausea, hence its discontinuation by many men before any benefits are achieved.26
Carnitine is an antioxidant compound that reduces inflammation and abnormal wound healing. Like many other therapies for Peyronie’s, uncontrolled trials have demonstrated some benefit using this treatment. One study compared the effectiveness of acetyl-L-carnitine (1 g BID) with tamoxifen (20 mg BID) for 3 months in men with PD.28 The men taking acetyl-L-carnitine experienced greater improvements in curvature and pain, and had far fewer side effects as compared to tamoxifen.
L-Arginine is an amino acid that combines with oxygen to ultimately form nitric oxide (NO), one of the steps involved in the development of an erection. Inducible NOS (iNOS) is expressed in the fibrotic plaques of PD, and iNOS suppression worsens tissue fibrosis. In a rat model, Valente et al29 reported that L-arginine produced an 80%-95% reduction in plaque size and in the collagen/fibroblast ratio when administered daily in the drinking water of a rat model with TGF-1-induced PD plaques. In addition, L-arginine was found to be antifibrotic in vitro. These findings suggest that L-arginine, as a biochemical precursor of NO, might be effective in reducing PD plaque size.28
Superoxide dismutase formulations have also been reported to be effective in Peyronie’s disease.30
Collagenase Clostridium histolyticum is an enzyme produced by the bacterium and made into a drug that was originally approved by the FDA to treat Dupuytren’s contracture. It is now also an FDA-approved injectable drug for treatment of Peyronie’s disease, is reported to work by breaking down the excess collagen in the penis that causes Peyronie’s disease.31
Penile Injections of drugs directly into the plaque of Peyronie’s disease represent an attractive alternative to oral medications. Injection permits direct introduction of drugs into the plaque, permitting higher doses and more local effects. To improve patient comfort, a local anesthetic is usually given prior to the injection.
Verapamil Injections are of interest in the treatment of Peyronie’s disease, due to its disruption of collagen production. Verapamil, a calcium channel blocker, is usually used in the treatment of high blood pressure.
A randomized, single-blind study suggests that intralesional injection of verapamil may be a reasonable intervention in select PD patients who have non-calcified plaque and penile angulation of less than 30 degrees.32 Patients whose plaque failed to respond to intralesional verapamil therapy within 3 months or whose angulation was greater than 30 degrees at presentation were more likely to benefit from surgery.
Interferon Injections have been shown to have antifibrotic effects in the treatment of keloid scars and scleroderma, a rare autoimmune disease affecting the body’s connective tissue. Men who received intralesional injection of interferon-alpha-2b (IFN-a-2b) experienced a significant reduction in penile curvature, diminished pain with erection, and decreased size of the plaque.33
Surgery is reserved for men with severe, disabling penile deformities that prevent satisfactory sexual intercourse. Most physicians recommend avoiding surgery until the plaque and deformity have stabilized and the patient has been pain-free for at least 6 months.34 A number of different surgical procedures are available:
- Autologous tissue grafts: These grafts are made of tissue taken from another part of the patient’s body during surgery
- Non-autologous allografts: These grafts are sheets of tissue that are commercially-produced using human or animal sources
- Synthetic inert substances: Materials such as Dacron mesh or GORE-TEX are seldom used for Peyronie’s surgeries in the modern era
Naturopathic Approach to Treatment
Because of the common delay in seeking treatment, patients with PD frequently present with a continuum of pathology which must be assessed in order to develop a treatment plan. Most of the cases I have seen are of the type I, and II variety. Other treatments for type III PD will need to address the underlying cause of the erectile dysfunction, even with successful resolution of the pathology caused by the Peyronie’s disease.
The goal of treatment is to stop the underlying inflammatory process while also providing therapy that allows the damaged tissue to remodel. To accomplish this, I use the following protocol:
- Vitamin E: 1000 IU/day
- Vitamin C: 3000-5000 mg/day
- CoQ10: 300 mg/day
- L-Arginine: 1000 mg/day
- A homeopathic combination remedy of Arnica 30C, Bellis perennis 30C, and Calendula 30C: 10 drops BID
- Topical potassium iodide applied at bedtime to the lesion
- Wet shorts treatment at bedtime to increase blood flow
- Pulsed ultrasound 2 to 3 times per week, initially with potassium iodide and DMSO, for 10 minutes in order to break up the underlying plaques and fibrous tissue. Pulsed ultrasound must be used, as continuous ultrasound will cause a burn.
Therapy is administered at least twice a week in-office, with the patient also following the home protocol. Clearly the longer the patient has had the condition, the more therapy will be needed to resolve the underlying pathology. This therapeutic protocol has provided some degree of benefit in almost every case.
Thomas A. Kruzel, ND, received his Doctorate of Naturopathic Medicine from NCNM and is in private practice at the Rockwood Natural Medicine Clinic in Scottsdale, AZ. Dr Kruzel is also a board-certified medical technologist. He completed 2 years of family practice medicine residency at the Portland Naturopathic Clinic, where he was Chief Resident prior to entering private practice. He also completed a fellowship in geriatric medicine through the Oregon Geriatric Education Center and the Portland VA hospital. Dr Kruzel has been an associate professor of Medicine at NCNM, where he has taught Clinical Laboratory Medicine, Geriatric Medicine, and Clinical Urology. He is the author of the Homeopathic Emergency Guide: A Quick Reference Handbook to Effective Homeopathic Care, and has also published numerous articles. Dr Kruzel was past-president of the AANP, and was selected as Physician of the Year by the AANP in 2000, and Physician of the Year by the AZ Naturopathic Medical Association in 2003.
- Moreland R, Nehra A. Pathophysiology of Peyronie’s disease. Int J Impot Res. 2002;14(5):406-410.
- Hatzimouratidis K, Eardley I, Giuliano F, et al. EAU guidelines on penile curvature. Eur Urol. 2012;62(3):5435-5452.
- Lindsay MB, Schain DM, Grambsch P, et al. The incidence of Peyronie’s disease in Rochester, Minnesota, 1950 through 1984. J Urol. 1991;146(4):1007-1009.
- Smith BH. Subclinical Peyronie’s disease. Am J Clin Pathol. 1969;52(4):385-390.
- Mathes SJ. Plastic Surgery. 2nd Philadelphia, PA: Saunders, Elsevier; 2006.
- Jarow JP, Lowe FC. Penile trauma: an etiologic factor in Peyronie’s disease and erectile dysfunction. J Urol. 1997;158(4):1388-1390.
- Schiavino D, Sasso F, Nucera E, et al. Immunologic findings in Peyronie’s disease: a controlled study. Urology. 1997;50(5):764-768.
- Stewart S, Malto M, Sandberg L, Colburn KK. Increased serum levels of anti-elastin antibodies in patients with Peyronie’s disease. J Urol. 1994;152(1):105-106.
- Peyronie’s disease: Causes. Mayo Clinic Web site. http://www.mayoclinic.org/diseases-conditions/peyronies-disease/basics/causes/con-20028765. Accessed August 15, 2014.
- Nyberg LM Jr, Bias WB, Hochberg MC, Walsh PC. Identification of an inherited form of Peyronie’s disease with an autosomal dominant inheritance and association with Dupuytren’s contracture and histocompatability B7 cross-reactive antigens. J Urol. 1982;128(1):48-52.
- Ralph DJ, Schwartz G, Moore W, et al. The genetic and bacteriological aspects of Peyronie’s disease. J Urol. 1997;157(1):291-294
- Leffell MS. Is there an immunogenetic basis for Peyronie’s disease? J Urol. 1997;157(1):295-297.
- Krane RJ. The treatment of loss of penile rigidity associated with Peyronie’s disease. Scand J Urol Nephrol Suppl. 1997;179:147-150.
- Van der Water L. Mechanisms by which fibrin and fibronectin appear in healing wounds: implications for Peyronie’s disease. J Urol. 1997;157(1):306-310.
- Poli G, Parola M. Oxidative damage and fibrogenesis. Free Radic Biol Med. 1997;22(1-2):287-305.
- Sikka SC, Hellstrom WJ. Role of oxidative stress and antioxidants in Peyronie’s disease. Int J Impot Res. 2002;14(5):353-360.
- Amin Z, Patel U, Friedman EP, et al. Colour Doppler and duplex ultrasound assessment of Peyronie’s disease in impotent men. British J Radiol. 1993;66(785):398-402.
- Gelbard MK, Dorey F, James K. The natural history of Peyronie’s disease. J Urol. 1990;144(6):1376-1379.
- Scandino PL, Scott WW. The use of tocopherols in the treatment of Peyronie’s disease. Ann NY Acad Sci. 1949;52:390-396.
- Steinberg CL. Tocopherols in treatment of primary fibrositis, including Dupuytren’s contracture, periarthritis of the shoulders and Peyronie’s disease. AMA Arch Surg. 1951;63(6):924-833.
- Prieto Castro RM, Leva Vallejo ME, Regueiro Lopez JC, et al. Combined treatment with vitamin E and colchicine in the early stages of Peyronie’s disease. BJU Int.2003;91(6):522-524.
- Paulis G, D’Ascenzo R, Nupieri P, et al. Effectiveness of antioxidants (propolis, blueberry, vitamin E) associated with verapamil in the medical management of Peyronie’s disease: a study of 151 cases. Int J Androl. 2012;35(4):521-527.
- Safarinejad MR. Safety and efficacy of coenzyme Q10 supplementation in early chronic Peyronie’s disease: a double-blind, placebo-controlled randomized study. Int J Impot Res. 2010;22(5):298-309.
- Safarinejad MR. Efficacy and safety of omega-3 for treatment of early-stage Peyronie’s disease: A prospective, randomized, double-blind placebo-controlled study. J Sex Med. 2009;6(6):1743-1754.
- Carson CC. Potassium para-aminobenzoate for the treatment of Peyronie’s disease: is it effective? Tech Urol. 1997;3(3):135-139.
- Mynderse LA, Monga M. Oral therapy for Peyronie’s disease. Int J Impot Res. 2002;14(5):340-344.
- Ralph DJ, Brooks MD, Botazzi GF. The treatment of Peyronie’s disease with tamoxifen. Br J Urol. 1992;70(6):648-651.
- Taylor FL, Levine LA. Non-surgical therapy of Peyronie’s disease. Asian J Androl. 2008;10(1):79-87.
- Valente EG, Vernet D, Ferrini MG, et al. L-Arginine and phosphodiesterase (PDE) inhibitors counteract fibrosis in the Peyronie’s fibrotic plaque and related fibroblast cultures. Nitric Oxide. 2003;9(4):229-244.
- Riedl CR, Sternig P, Gallé G, et al. Liposomal recombinant human superoxide dismutase for the treatment of Peyronie’s disease: a randomized placebo-controlled double-blind prospective clinical study. Eur Urol. 2005;48(4):656-661.
- FDA NEWS RELEASE. FDA approves first drug treatment for Peyronie’s disease. December 6, 2013. FDA Web site. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm377849.htm. Accessed August 15, 2014.
- Rehman J, Benet A, Melman A. Use of intralesional verapimil to dissolve Peyronie’s disease plaque: a long-term single-blind study. Urology. 1998;51(4):620-626.
- Lacy GL 2nd, Adams DM, Hellstrom WJ. Intralesional interferon-alpha-2b for the treatment of Peyronie’s disease. Int J Impot Res. 2002;14(5):336-339.
- Qassim YN. Dermis as an Interposing Graft for Reconstructing Peyronies Disease. The Iraqi Postgraduate Medical Journal. 2012;11(2):220-225.