Oral Therapies in .NET

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A number of oral therapies have been investigated for the treatment of Peyronie s disease
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Vitamin E
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Mechanism of action: Antioxidant properties First investigated by Scott and Scardino [21] in 1948, vitamin E was theorized to be of clinical ef cacy secondary to its anti-oxidant activities The use of vitamin E today continues and remains a choice for many practicing urologists, predominantly due to the minimal adverse event pro le and the low cost However, most studies do not address the natural history of the disease, nor have they included a control arm Gelbard et al [22] investigated vitamin E therapy in comparison to the natural history of Peyronie s disease in 86 patients, and revealed no signi cant difference between the treatment and control groups for curvature, pain, and the ability to have intercourse
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Mechanism of action: Inhibition of collagen synthesis and anti- brotic effects Colchicine was rst proposed by Akkus and colleagues [23] in 1994 where, in 19 patients, a progressively increasing dose was given over a three to ve month period Alterations in curvature were noted in 36% of the patients (n = 7) and palpable plaque improvement in 63% (n = 12) Erectile quality was improved in 78% (n = 7); however, no placebo or control arm was used in the
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Therapeutics and the Molecular Pathology of Peyronie s Disease
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How do these mechanisms correlate with current therapeutic treatment of this disease There are two
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14 the treatment groups compared with the placebo arm
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studies In a subsequent control study by Kadioglu [24], 60 patients were evaluated with Colchicine 1 mg twice a day, with mean follow up of 11 months Pain improvement in 95% (n = 57), with reduction in curvature in 30% (n = 19) and progressive worsening of curvature in 22% (n = 13), were noted Adverse events: Severe diarrhea
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Carnitine (Carnitor, Sigma-Tau)
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Mechanism of action: Inhibition of acidyl coenzyme-A Published initially by Biagiotti et al [30] in 2001, 48 patients were randomized to receive either carnitine or tamoxifen The rst group received tamoxifen 20 mg twice daily for three months, while the second group received acetyl-L-carnitine at a dose of 1 mg twice daily for three months While the authors reported a greater bene t with respect to curvature in the carnitine arm, no objective parameters were measured
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Potassium amino benzoid (Potaba, Glenwood)
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Potaba is historically used in dermatologic patients particularly scleroderma, dermatomyositis, and pemphigus Mechanism of action: Increasing activity of monoamine oxidase in tissues, a subsequent decrease in serotonin levels, and thus a reduction in brogenesis, with subsequent decreased scar tissue formation The use of potassium amino benzoid was described initially by Zarafonatis in 1959 [25] A large, pooled European study in 1978 involving 2653 patients, reported a 57% success rate with complete resolution in 9% [26] However, this study had no study arm or placebo group, nor were any objective parameters assessed Weidner et al [27] reported a randomized prospective double-blind trial of potassium amino benzoid at a dose of 3 mg four times per day for one year, versus oral placebo Statistically, an improvement between the two groups was noted in plaque size that did not correlate with a reduction in the curvature Adverse events: Severe gastrointestinal side effects
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Topical Therapies
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Mechanism of action: Increased extracellular matrix collagenic secretion, and decreased collagen and bronectin synthesis and secretion Martin and coworkers in 2002 [31] investigated tissue concentrations in men who applied verapamil topically While this drug was found to be present in urine samples, no verapamil was detected in the tunica albuginea specimens obtained at the time of penile prostheses implantations The authors subsequently concluded that topical application of verapamil had no scienti c basis, and given the fact that no control trial has been performed, the current use of topical verapamil is not recommended
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Intra-lesional Therapies
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Mechanisms of action: Anti-in ammatory and reduction in collagen synthesis Proposed in 1954 by Teasley [32] in 29 patients, with results that were at best equivocal Subsequently in 1954, Boedner et al [33] reported successful outcomes in 17 patients who were treated with intra-lesional hydrocortisone and cortisone injections A study by Winter and Khanna [34] in 1975 demonstrated no statistical difference between patients treated with intra-lesional dexamethasone injections, when compared with the natural history of the disease in their general patient population A prospective study by Williams and Green [35] in 1980 using intra-lesional triamci-
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Tamoxifen citrate (Nolvadex, Astrozenica)
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Mechanism of action: The potential bene t is based on its effect on the release of transforming growth factor beta (TGF- ) from broblasts, and blocking the TGF receptor sites, resulting in decreased brogenic activity This was rst introduced by Ralph et al in 1992 [28], at a dose of 20 mg given twice a day for three months in 36 patients The results demonstrated a reduction in pain in 80% of patients (n = 29), reduction in curvature in 35% of patients (n = 13), and a decrease in plaque size in 34% (n = 12) However, a control trial by Teloken et al [29] in 1999 at a similar dose revealed no signi cant improvement between
Peyronie s Disease nolone revealed only 3% had spontaneous resolution of symptoms at one year with observation, and, following the administration of triamcinolone every six weeks for 36 weeks, 33% of patients reported improvement in particular pain and plaque size At present, the use of intra-lesional steroid injections is not encouraged