No oral medication has proved to be clearly beneficial for Peyronie's disease (PD). We investigated the safety and efficacy of coenzyme Q10 (CoQ10) supplementation in patients with early chronic PD. We conducted a randomized clinical trial of 186 patients with chronic early PD. Patients were randomly assigned to either 300 mg CoQ10 daily (n=93) or similar regimen of placebo (n=93) for 24 weeks. Erectile function (EF), pain during erection, plaque volume, penile curvature and treatment satisfaction using patient versions of the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire were assessed at baseline and every 4 weeks during study period. EF was assessed using International Index of Erectile Function (IIEF-5), and pain was evaluated with a visual analog scale (VAS, 0–10). All patients also responded to a Global Assessment Question, ‘Has the treatment you have been taking during this study improved your erections?’ After 24 weeks, mean IIEF-5 score, mean VAS score and mean EDITS score improved significantly in patients receiving CoQ10 (all P<0.01). Mean plaque size and mean penile curvature degree were decreased in the CoQ10 group, whereas a slight increase was noted in the placebo group (both P=0.001). Mean index of IIEF-5 in 24-week treatment period was 17.8±2.7 in the CoQ10 group and 8.8±1.5 in the placebo group (P=0.001). Of the patients in CoQ10 group, 11 (13.6%) had disease progression vs 46 (56.1%) in placebo group (P=0.01). In patients with early chronic PD, CoQ10 therapy leads plaque size and penile curvature reduction and improves EF.
Peyronie's disease (PD) is an acquired idiopathic localized fibrosis of the penis involving the tunica albuginea of the corpus cavernosum resulting in penile curvature and sexual dysfunction.1 PD is a common penile disorder affecting 3–9% of men.2 Clinically, PD presents as any combination of penile pain, penile curvature and ED, and depresses the patient and partner both physically and psychologically.3 Many cases resolve with no treatment; but if left untreated PD can cause fibrotic, nonexpansible thickening of relatively distinct areas of the corpora tunica, known as plaque formation. Clinical manifestations of penile plaque are penile deformity, penile pain and varying degrees of ED.4, 5 PD has three distinct different phases, namely, acute, early chronic and chronic.6 Oral medical treatments are indicated in acute and early chronic phases. The exact pathogenic mechanism of this disease has yet to be identified. However, in recent years, increased expression of transforming growth factor (TGF)-β1 in fibrotic plaques of patients with PD has been described.7 Furthermore, an increase in oxidative stress has been postulated as potentially damaging for the tunica albuginea in acute phase of the disease.8
Coenzyme Q10 (2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone, CoQ10) is a fat-soluble, vitamin-like quinone commonly known as ubiquinone or ubidecarenone. Ubiquinone is reduced to ubiquinole (CoQ10H2) via semiubiquinone radical (CoQ10H).9 The fully reduced form of CoQ10 (CoQ10H2) exerts strong effects against the oxidative damage of polyunsaturated fatty acids.10, 11 It is to be noted that CoQ10 is known to be the only endogenously synthesized lipid-soluble antioxidant.9 Decreased CoQ10 levels in serum,12 as well as a decrease of the CoQ10H2/CoQ10 ratio,13 have been demonstrated in diseases associated with oxidative stress. PD is characterized by an initial inflammatory reaction (acute phase) followed by fibrous inelastic scar formation (chronic phase).14 Inflammation produces oxygen-free radicals and it could be speculated that as inflammation in an acute or early chronic phase persists, an inability to respond to this with antioxidants may result in disease progression. CoQ10 is one of the most potent antioxidants, which is used to regenerate other antioxidants (tocopheryl and ascorbate), and may serve important roles in protection against oxidative stress and free radical oxygen damage.15 TGF-β1 is a key fibrogenic mediator. It has been reported that solubilized CoQ10 suppresses the expression of TGF-β1 induced by dimethylnitrosamine in mouse liver and mouse embryonic fibroblast cells.16 In addition, CoQ10 activates NF-E2-related factor-2 (Nrf2).16 Nrf2 overexpression itself reduces the basal expression of α-smooth muscle actin and TGF-β1.16 Therefore, CoQ10-induced Nrf2 activation may suppress TGF-β1 expression. This study is the first prospective, double-blind, placebo-controlled randomized study on the effects of CoQ10 supplementation in men with early chronic PD.
Materials and methods
A prospective, double-blind, placebo-controlled randomized clinical trial was performed from June 2006 to May 2009 on 214 consecutive male patients aged 35–60 years affected by early chronic PD. They were selected from a tertiary specialized sexual dysfunction clinic. Early chronic PD was defined as pain during erection, penile curvature not affecting vaginal penetration, palpable hyperechoic plaque(s) without pain and calcifications, with a total area of <2 cm2, which was limited to the albuginea.6 All the included patients had at least two previous failed medical treatments for their PD and reported ED with painful penile curvature of at least 12-month duration. ED was defined as the consistent inability to achieve or maintain an erection sufficient for satisfactory sexual intercourse.17 Previous treatments for PD included oral therapy with propionyl-L-carnitine (25, 13.6%), potassium aminobenzoate (161, 87.5%), colchicine (69, 37.5%), tamoxifen (72, 39.1%) and various vitamins, including vitamin E and B6 (155, 84.2%). All patients gave informed consents and the investigation was conducted in accordance with the International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) guidelines and the principles of the Declaration of Helsinki.
Inclusion criteria were disease duration >12 months, patient age between 18 and 60 years, presence of ED without any obvious organic causes other than PD, presence of penile plaque demonstrated by basal and dynamic ultrasonography and by palpation with a maximum size of 2 cm2, previous failed medical therapies for PD, stable sexual relationship, presence of painful erections and penis recurvatum. Exclusion criteria included presence of other sexual dysfunction, the absence of a penile curvature, previous penile surgery or pelvic trauma, endocrinopathy, significant renal impairment (serum creatinine >1.8 mg per 100 ml), alcohol or tobacco use, supplementation with vitamins or traditional herbs in the previous 3 months, and therapies interfering with CoQ10 such as antioxidants.
Baseline evaluation included a detailed medical and sexual history, physical examination, dynamic penile duplex ultrasonography (DPDU) before and after an intracavernous injection with 20 μg of prostaglandin E1, with measurement, in the state of full erection, of angle and direction of curvature (by means of two rigid rulers), and manual examination of plaque for detection of its volume, location and consistency. Data regarding disease duration, presence and severity of painful erections, erectile function (EF), penile plaque size and penile curvature degree were obtained at baseline evaluation. Laboratory analysis included measurement of serum luteinizing hormone, follicle stimulating hormone, total testosterone and prolactin. Additional safety evaluations, including measurement of serum aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase, creatine kinase, alkaline phosphatase and glucose, were also performed at baseline and at each follow-up point. EF was evaluated with the International Index of Erectile Function (IIEF-5),18 and Sexual Encounter Profile (SEP) diary questions 2 (‘Were you able to insert your penis into your partner's vagina?’) and 3 (‘Did your erection last long enough for you to have successful intercourse?’). EF was categorized as follows using the IIEF-5 total scores: no ED (22–25), mild ED (17–21), mild to moderate ED (12–16), moderate ED (8–11) and severe ED (5–7).19, 20 Presence and severity of painful erections was determined on a conventional 10-point visual analog pain scale (VAS) score ranging from 0 to 10, with 0 being no pain and 10 being severe pain. Plaque size and status (fibrous or calcified) assessment was conducted by ultrasound and plain X-rays. Plaque size was determined as the product of length and width in square centimeters. For a subjective judgment of penile curvature, patients were asked to sketch the erected penis. During DPDU, the hemodynamics of penile blood vessels, including peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistivity index (RI) of the left and right cavernous, were quantified by measuring. The values used for different vascular status definitions were as follows: pure arterial insufficiency (AI), a PSV of <25 cm s−1; borderline AI, PSV 25–30 cm s−1; pure veno-occlusive dysfunction, PSV >30 cm s−1, EDV >5 cm s−1and RI<0.8; mixed vascular disorder, PSV <25 cm s−1and EDV >5 cm s−1; nonvascular disorder, PSV>30 cm s−1, EDV ⩽5 cm s−1 and RI>0.8.21, 22, 23 The radiologist was unaware of the patient allocation. The radiologist performing DPDU did not know the treatment allocation of subjects. To evaluate varying degrees of curvature and plaque size, a modified form of the Kelami classification system was used.24 Patients were categorized into three groups: class I, plaque length ⩽1 cm and curvature of ⩽30°; class II, plaque between 1 and 2 cm and 30–60° curvature; and class III, plaque >2 cm and curvature >60°. Patients who cannot be categorized into any of the classes (for example, patients with penile curvature >60° and plaque length <2 cm) were classified to be in a higher category.21, 25 Before randomized procedure, all the eligible patients received single-blind placebo capsules for 1 week (week −1). Those who reported a decrease of ⩾20% in pain VAS score (placebo responders) were excluded. Of 214 recruited subjects, 186 met inclusion and exclusion criteria and consented to proceed with the study protocol.
Eligible patients were randomly assigned to double-blind, fixed-dose treatment with either CoQ10 or placebo. The randomization codes were centrally assigned by the coordination center after checking the main eligibility criteria. At baseline (week 0), the patients were randomly assigned to take 300 mg of CoQ10 (Kaneka, Osaka, Japan) orally daily (group 1, n=93), or a similar regimen of placebo (group 2, n=93) during the 24-week treatment period. The placebo was a starch compound with the same color and size of CoQ10. The following procedures were adopted to ensure blindness. Independent pharmacists prepared, anonymized and certified starch tablets; and filled and sealed anonymous color-coded boxes containing drugs or placebos. The randomization codes were opened only after all subjects had completed the study. Compliance was assessed by comparing the number of pills ingested with the number of days between dispensing visits.
For the analysis of efficacy and safety, all patients were evaluated in each visit (every 4 weeks) by the investigator. There were two primary subjective outcome measures including plaque size and degree of curvature, and two primary objective outcome measures including a decrease in pain during erections and improvement of EF. The four designated secondary end points were: (i) the mean number of sexual attempts per week; (ii) responses to a Global Assessment Question (GAQ), ‘Has the treatment you have been taking during this study improved your erections?’; (iii) treatment satisfaction as assessed using patient versions of the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire;26 and (iv) improvement in penile artery indices. Follow-up points were weeks 4, 8, 12, 16, 20, 24, and 4 weeks after stopping treatment. The following variables were assessed at each follow-up visit: EF by IIEF-5 and SEP diary questions 2 and 3; plaque characteristics by ultrasound and X-ray; subjective changes in penile curvature by sketch and pain during erection by VAS; mean sexual intercourse per week, responses to GAQ and treatment satisfaction by EDITS. DPDU was repeated at the end of trial (1 month after stopping medication) to assess objective changes in penile curvature and penile artery spectral traces. For the purposes of this trial, a ⩾10% change in plaque size, a ⩾5° change in penile curvature, a ⩾20% change in pain during erection, and/or any changes in EDV, RI and PSV, and/or any change in IIEF-5 score and SEP diary questions 2 and 3 were considered an alteration (improvement or worsening).27
Safety and tolerability assessments
Safety and tolerability were evaluated on the basis of spontaneously reported adverse events (AEs), clinical laboratory tests and physical examinations. All AEs observed by the investigator and reported by the patients were recorded. They were categorized using the Medical Dictionary for Regulatory Activities coding dictionary.
Values are given as the mean ±s.d. A sample size of 160 evaluable patients (80 per group) would be required to detect a significant difference (defined as a 10° change in penile curvature) with 85% power for a type I error rate of α=0.05 between CoQ10 and placebo (two sided). Assuming a 15% dropout rate, it was planned to randomize at least 184 patients. All analyses used an intention-to-treat principle, with inclusion of all randomized participants who completed at least one follow-up visit. The last observation carried forward was performed in the case of missing values for efficacy measures. Baseline and follow-up continuous parameters were compared using the two-tailed Student's t–test, whereas categorical variables were compared statistically using the χ2-test. The paired t-test was used to compare the mean difference in pre- and post-treatment IIEF-5 scores. The Spearman's rank correlation coefficient, rs, was used to assess associations between study variables. A value of P<0.05 was considered statistically significant. Statistical Package for Social Sciences for Windows, version 17.0 (SPSS, Chicago, IL, USA), was used for statistical analysis.
Baseline demographic and clinical characteristics relative to the both groups are reported in Table 1. Differences in pretreatment characteristics between CoQ10 and placebo groups were not statistically significant. In all, 81 (87.1%) patients in CoQ10 group and 82 (88.2%) patients in placebo group completed the whole study period (Figure 1). The disease duration was 19.4±6.4 and 19.6±6.5 months in CoQ10 and placebo groups, respectively.
Objective treatment results
Intergroup analysis revealed significant differences in terms of mean plaque size and mean penile curvature degree. In the CoQ10 group, the overall improvement in penile curvature was 54.3% (n=44, Table 2). In 32 patients (39.5%), the deviation angle was decreased by more than 10°. The mean curvature reduction was 12° (range: 4–20°). The duration of the disease significantly affected the reduction of penile angulation (P=0.032). In 11 patients (13.6%), the penis was almost straight at 1-month follow-up period. In the placebo group, no significant difference regarding penile curvature was observed during the study period (P=0.001, Table 3). The objective improvements in penile curvature are shown in Figure 2, which was documented by DPDU after intracavernosal injection of prostaglandin E1. Concerning plaque size, there were significant differences after treatment in CoQ10 group compared with placebo group (P=0.001). In CoQ10 and placebo patients, 8.6 and 45.1% developed new plaque, and 6.6 and 23.6% developed plaque calcification, respectively, at the end of trial (both P=0.001). In the CoQ10, the plaque size decreased objectively by 40% and increased by 35.7% in the placebo group (P=0.001). In general, in 23 patients (28.4%), the plaque was not palpable after CoQ10 treatment. There was significant negative correlation between the decrease in plaque size and pretreatment plaque size (r=−0.67, P=0.025). According to intergroup analysis, penile artery spectral traces were significantly improved in the CoQ10 group (Figure 3, Table 3). Mean RI in both right and left penile artery increased by about 13% in CoQ10 group, whereas a slight decrease was noted in the placebo group. Between-group differences were statistically significant (P=0.001). Mean PSV and EDV increased in both groups, but significant differences were found vs baseline values only in CoQ10 group (P=0.01 and 0.001, respectively) (Figure 3, Table 3). Penile vascular status further deteriorated in the placebo group, and significant differences were found vs baseline values (Figure 4, Table 3). In the CoQ10 group, pure AI, borderline AI and pure veno-occlusive dysfunction decreased by 22.2, 47.4 and 47.8%, respectively, but the related changes in placebo group were −5.3%, +38.9% and −16.7%, respectively (P=0.01, 0.0001 and P=0.01, respectively). At the end of trial of patients in CoQ10 and placebo groups, 54.1 and 26.1% had nonvascular status, respectively (P=0.001).
Subjective treatment results
At the end of study of patients in CoQ10 and placebo groups, 14 (17. 3%) and 16 (19.5%), respectively, reported pain during erection (Table 4). Mean VAS score decreased by 75.9 and 72.7% of patients in CoQ10 and placebo group, respectively. Thus, no significant difference in pain disappearance was seen between the two groups (P=0.78). At 1-month follow-up, out of 81 patients assigned to the CoQ10 group, 49 (60.5%) reported improved penile curvature and 14 (17.3%) reported increased curvature; penile curvature remained stable in 18 patients (22.2%). In the placebo group, 14 (17.1%) patients reported improved penile curvature, 15 (18.3%) reported curvature stability and 53 (64.6%) reported curvature worsening (Table 2). The IIEF-5 total score went from 8.2±1.7 to 17.8±2.7 in CoQ10 group, and from 8.1±1.5 to 8.8±1.5 in placebo group (P=0.001) (Table 4). Among the patients in CoQ10 and placebo groups, the IIEF-5 total score increased by 117.1 and 8.6%, respectively (P=0.001) (Figure 5). A significant difference in terms of SEP-2 and -3 questions was also reported in the CoQ10 group when compared with baseline values, whereas no significant differences were found in the placebo group (Figure 5, Table 4). The EDITS data of patients are shown in Table 5. At the end of trial, the corresponding mean EDITS index scores (maximum index score 100) were 68.6±11.7 and 36.4±10.6 for patients who took CoQ10 and placebo, respectively (P=0.01). Overall, the proportion of patients satisfied with treatment, defined by Lewis et al.28 as a final EDITS score of >50, was 71.6% for the CoQ10 and 12.2% for the placebo group (P=0.01). Similarly, mean intercourse per week was significantly higher when compared with baseline only in the CoQ10 group (Table 4). Intergroup analysis revealed significant differences in terms of patient perception of plaque volume and penile curvature. Mean plaque size and mean penile curvature degree decreased in the CoQ10 group and increased in the placebo group (Table 4). The number of patients answering yes to the GAQ question was 62.7% in CoQ10 group and 12.4% in placebo group (P=0.001). At the end of trial, 24 (29.6%) of the 81 patients in CoQ10 group reported that the results did not meet their expectations and requested another type of treatment.
Treatment results across different Kelami classifications
The response to the treatment significantly differed across different Kelami classifications (Table 2). Of the patients with class I, II and III deformity in CoQ10 group, 4.6, 22.7 and 31.2% had deterioration of the curvature and 64.7, 45.5 and 31.2% had improvement, and the results obtained in this group were significantly better than those obtained in placebo group (all P<0.01). Of patients treated with CoQ10, the treatment resulted in improved sexual function in 65.1, 40.9 and 31.2% of patients with class I, II and III deformity, respectively; the respective values in the placebo group were 9.3, 9.1 and 6.2% (all P=0.001).
Penile artery spectral traces
Table 3 demonstrates mean PSV, EDV and RI values in each group after treatment. When comparing penile vascular status in both groups, 30.1% of the men in the CoQ10-treated group and 29.0% in the placebo group demonstrated nonvascular status at baseline. The right and left cavernosal artery PSV, EDV and RI changed significantly at the end of study. Mean PSV changes after therapy compared with baseline were statistically significant between CoQ10 (R (right), +13.3%, L (left), +13.8) and placebo-treated (R, +1.3, L, −6.5) patients (both P=0.001; Figure 3). There were also statistically significant differences in EDV and RI among the group (Table 3). At the end of trial of patients in the CoQ10 and placebo groups, 49 (53.8%) and 24 (26.1%) had nonvascular status, respectively (P=0.001, Figure 4). When comparing differences in penile artery indices, patients with dorsolateral penile curvature had the highest rate of AI, at 39.1%. Patients with ventrolateral penile curvature had the best penile artery spectral traces, with a nonvascular status recorded in 73% of patients.
Safety and tolerability
Significant drug-related adverse effects did not occur in the two studied groups. No patient discontinued therapy because of side effects.
Of patients in the CoQ10 group, 11 (13.7%) had disease progression, whereas 46 (56.1%) did so in the placebo group (P=0.01). Two patients (2.5%) in CoQ10 group needed surgery, whereas 79 (97.5%) did not; in placebo group, 22 (26.8%) required surgery, whereas 60 (73.2%) did not (χ2=4.619, P=0.001).
The distribution of baseline severity was similar, with similar numbers of mild (14, 15.1 vs 15, 16.1%), moderate (32, 34.4 vs 31, 33.3%) and severe (47, 50.5 vs 47, 50.5%) ED in the CoQ10 and placebo groups, respectively. Subgroup analyses did reveal trends in the CoQ10 group to indicate that change in the IIEF-5 total score is affected by severity of ED. Improvement in the mean total score of IIEF-5 was higher in patients with moderate and severe ED. Subjects with moderate ED who received CoQ10 showed the highest increase (138%) in the IIEF-5 total score at the end of the study compared with those who had mild (68%, P=0.001) and severe (94%, P=0.01) ED. Improvements were also significantly superior in the 40–50 years age group (72%) compared with the <40 and >50 years age groups (49 and 58%, respectively) over the total IIEF-5 score at the end of study (both P<0.01). There was a significant negative correlation between disease duration and a positive response to CoQ10 (r=−0.72, P=0.001), and between the Kelami class (r=0.74, P=0.001) and objective improvements and PSV (r=0.52, P=0.01). A positive response to CoQ10 was significantly associated with treatment duration (r=0.76, P=0.001). There was a significant correlation between the degree of baseline ED and improvement in EF in response to CoQ10 administration. Patients with moderate (r=0.68, P=0.001) and severe (r=0.52, P=0.01) ED had better positive response rates to CoQ10 therapy than patients with mild ED.
The results of this study have shown that CoQ10 therapy produced improvements in plaque size, penile curvature, impaired sexual function and pain on erection. In addition to the complete improvement or significant reduction in penile plaque volume and the reduction in degree of penile curvature, subjective variable such as IIEF-5 total score and mean per-patient percent yes responses to GAQ improved after CoQ10 supplementation (117 and 62.7%, respectively) in our participants. Furthermore, CoQ10 administration prevented the progress of PD in 86% of patients and helped to stabilize the disease process. We could not find similar studies in literature for comparison. The chance of spontaneous resolution of PD (except of pain) is low. Current natural history studies on PD suggest spontaneous resolution rate of 5–13%.5, 29 Our results underline the progressive nature of PD in placebo patients, characterized by a slow increase of both plaque size (35.7%) and penile curvature (28%). In this study, we also assessed the outcome of treatment objectively. A significant limitation of most previous studies is inaccuracy due to subjective assessments of outcome measures.30 In a study by Mulhall et al.,29 the percentage of untreated patients complaining of some degree of ED was 32% with a mean IIEF-5 score of 19.2. Mean IIEF-5 scores we reported at baseline evaluation in both groups were much lower than to those reported by Mulhall et al.29 However, similar to Mulhall et al., mean IIEF-5 total score did not change significantly in patients receiving no active treatment. This study reveals that, of the patients with PD, 19.9% were found to have pure AI by DPDU, whereas 25.3 and 29.6% revealed veno-occlusive dysfunction and mixed vascular disease, respectively. According to our results, it appears that the lowest improvement rate in sexual function were in men with pure AI. This would suggest that men with more advanced arterial-inflow disorders would be less likely to show an improvement in their ED. The role of oral medication to modify the course of PD may be limited to the 12–18 months of plaque maturation during which time penile pain and induration is gradually resolving. Once nonpainful penile curvature has been ensued, the probability of significant success with oral therapy appears limited.
PD negatively affects quality of life of both patients and partners, causing psychological distress.31 The anxiety associated with the disease and the worrisome about intercourse because of pain and penile curvature are responsible for performance anxiety, thus contributing to impairment of EF. In our study of patients taking CoQ10 and placebo, 51.9 and 8.5% reported subjective improvement in sexual function, respectively (P=0.001).
The postulated possible therapeutic mechanism of CoQ10 on PD is that the reduced form of CoQ10 (ubiquinone-10) is a potent lipophilic antioxidant.32 In acute phase of PD, inflammation produces oxygen-free radicals. An inability to respond to this with antioxidants may cause the progress of the disease into chronic phase.
CoQ10 is one of the most potent antioxidants, and may serve important roles in protection against ischemia and free radical oxygen injury.15 Ohhara et al.33 found that CoQ10 protected against ischemia and reperfusion in the heart. CoQ10 can interfere with the spontaneous progression of the disease through a stabilizing effect and shares the possible advantage of avoiding the need for surgery. Such an effect could be clinically relevant. Recent studies suggest that expression and activity of Smad transcription factors of the TGF-β pathway is increased in fibroblasts of patients with PD. Alterations in the TGF-β pathway appear to be a pathogenetic factor in the development of PD.7 It has been demonstrated that TGF-β1 downregulates the expression levels and activity of antioxidant enzymes, including glutathione S-transferase, glutamate-cysteine ligase, superoxide dismutase and glutathione peroxidase.34, 35 TGF-β1 inhibits antioxidant enzyme expression through Smad3/ATF-dependent Nrf2 inactivation.36 CoQ10 decreases α-smooth muscle actin and TGF-β1 expressions in Nrf2 wild-type mouse embryonic fibroblast cells.16 Also, it has been reported that Nrf2 could initiate signal transduction pathways that regulate cell proliferation during development and in response to injury.37
Several medical treatment options have been used in PD, with no confirmed benefit in clinical trials.21, 25, 30, 38 However, various beneficial effects with some oral medications such as tamoxifen39 and pentoxifylline40 have also been reported. Despite many advances in identifying potential pathophysiological mechanisms, PD remains a therapeutic challenge, as no causal therapy is available until now. Our results confirm that CoQ10 is safe and well tolerated. Most patients are satisfied and would like to continue the treatment.
In this study, significant differences were noted between baseline mean VAS score, mean IIEF-5 score and mean SEP-2 and -3 questions and post-treatment values in patients with early chronic PD receiving CoQ10. Also, significant differences in terms of mean plaque volume and preexisting mean penile curvature degree were evident in patients receiving CoQ10. The increasing of plaque size and worsening of penile curvature in the placebo group may suggest a potential protective effect of CoQ10 on disease progression.
Pryor J, Akkus E, Alter G, Jordan G, Lebret T, Levine L et al. Peyronie's disease. J Sex Med 2004; 1: 110–115.
Lindsay MB, Schain DM, Grambsch P, Benson RC, Beard CM, Kurland LT . The incidence of Peyronie's disease in Rochester, Minnesota, 1950 through 1984. J Urol 1991; 146: 1007–1009.
Savoca G, Trombetta C, Ciampalini S, De Stefani S, Buttazzi L, Belgrano E . Long-term results with Nesbit's procedure as treatment of Peyronie's disease. Int J Impot Res 2000; 12: 289–293.
Erdogru T, Savas M, Yilmaz N, Faruk Usta M, Koksal T, Ates M et al. Evaluation of penile hemodynamic status and adjustment of treatment alternatives in Peyronie's disease. Asian J Androl 2002; 4: 187–190.
Kadioglu A, Tefekli A, Erol B, Oktar T, Tunc M, Tellaloglu S . A retrospective review of 307 men with Peyronie's disease. J Urol 2002; 168: 1075–1079.
Biagiotti G, Cavallini G . Acetyl-Lcarnitine vs tamoxifen in the oral therapy of Peyronie's disease: a preliminary report. BJU Int 2001; 88: 63–67.
Haag SM, Hauck EW, Szardening-Kirchner C, Diemer T, Cha ES, Weidner W et al. Alterations in the transforming growth factor (TGF)-β pathway as a potential factor in the pathogenesis of Peyronie's disease. Eur Urol 2007; 51: 255–261.
Bivilacqua TJ, Champion HC, Hellstrom WJG . Implications of nitric oxide synthase isoforms in the pathophysiology of Peyronie's disease. Int J Impotence Res 2002; 14: 345–352.
Ernster L, Dallner G . Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1995; 1271: 195–202.
Mukai K, Tokunaga A, Itoh S, Kanesaki Y, Ohara K, Nagaoka S et al. Structure activity relationship of the free-radical-scavenging reaction by vitamin E (α-, β-, γ-, δ-tocopherols) and ubiquinol-10: pH dependence of the reaction rates. J Phys Chem B 2007; 111: 652–662.
Nohl H, Gille L, Kozlov AV . Antioxidant-derived prooxidant formation from ubiquinol. Free Radic Biol Med 1998; 25: 666–675.
Folkers K, Osterborg A, Nylander M, Morita M, Mellstedt H . Activities of vitamin Q10 in animal models and a serious deficiency in patients with cancer. Biochem Biophys Res Commun 1997; 234: 296–299.
Yamamoto Y, Yamashita S, Fujisawa A, Kokura S, Yoshikawa T . Oxidative stress in patients with hepatitis, cirrhosis, and hepatoma evaluated by plasma antioxidants. Biochem Biophys Res Commun 1998; 247: 166–170.
Usta MF, Bivalacqua TJ, Jabren GW, Myers L, Sanabria J et al. Relationship between the severity of penile curvature and the presence of comorbidities in men with Peyronie's disease. J Urol 2004; 171: 775–779.
Hoppe U, Bergemann J, Diembeck W, Ennen J, Gohla S, Harris I et al. Coenzyme Q10, a cutaneous antioxidant and energizer. Biofactors 1999; 9: 371–378.
Choi HK, Pokharel YR, Lim SC, Han HK, Ryu CS, Kim SK et al. Inhibition of liver fibrosis by solubilized coenzyme Q10: role of Nrf2 activation in inhibiting transforming growth factor-beta1 expression. Toxicol Appl Pharmacol 2009; 240: 377–384.
NIH Consensus Development Panel on Impotence. NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993; 270: 83–90.
Rosen RC, Capelleri JC, Smith MD . Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile function. Int J Impot Res 1999; 11: 319–326.
Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A . The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile function. Urology 1997; 49: 822–830.
Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Pena BM . Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res 1999; 11: 319–326.
Safarinejad MR, Hosseini SY, Kolahi AA . 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. J Urol 2007; 178: 1398–1403.
Montorsi F, Guazzoni G, Bergamaschi F, Consonni P, Rigatti P, Pizzini G et al. Vascular abnormalities in Peyronie's disease. The role of color Doppler sonography. J Urol 1994; 151: 373–375.
Wilkins CJ, Sriprasad S, Sidhu PS . Colour Doppler ultrasound of the penis. Clin Radiol 2003; 58: 514–523.
Kelami A . Classification of congenital and acquired penile deviation. Urol Int 1983; 38: 229–233.
Safarinejad MR . Therapeutic effects of colchicine in the management of Peyronie's disease: a randomized double-blind, placebo-controlled study. Int J Impot Res 2004; 16: 238–243.
Althof SE, Corty EW, Levine SB, Levine F, Burnett AL, McVary K et al. EDITS: development of questionnaires for evaluating satisfaction with treatments for erectile dysfunction. Urology 1999; 53: 793–799.
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: 1743–1754.
Lewis R, Bennett CJ, Borkon WD, Boykin WH, Althof SE, Stecher VJ et al. Patient and partner satisfaction with Viagra (sildenafil citrate) treatment as determined by the erectile dysfunction inventory of treatment satisfaction questionnaire. Urology 2001; 57: 960–965.
Mulhall JP, Schiff J, Guhring P . An analysis of the natural history of Peyronie's disease. J Urol 2006; 175: 2115–2118.
Hauck EW, Diemer T, Schmelz HU, Weidner W . A critical analysis of nonsurgical treatment of Peyronie's disease. Eur Urol 2006; 49: 987–997.
Rosen R, Catania J, Lue T, Althof S, Henne J, Hellstrom W et al. Impact of Peyronie's disease on sexual and psychosocial functioning: qualitative findings in patients and controls. J Sex Med 2008; 5: 1977–1984.
Kontush A, Reich A, Baum K, Spranger T, Finckh B, Kohlschütter A et al. Plasma ubiquinol-10 is decreased in patients with hyperlipidaemia. Atherosclerosis 1997; 129: 119–126.
Ohhara H, Kanaide H, Yoshimura R . A protective effect of coenzyme Q10 on ischemia and reperfusion of the isolated perfused rat heart. J Mol Cell Cardiol 1981; 13: 65–74.
Arsalane K, Dubois CM, Muanza T, Bégin R, Boudreau F, Asselin C et al. Transforming growth factor-beta1 is a potent inhibitor of glutathione synthesis in the lung epithelial cell line A549: transcriptional effect on the GSH rate-limiting enzyme gamma-glutamylcysteine synthetase. Am J Respir Cell Mol Biol 1997; 17: 599–607.
Kayanoki Y, Fujii J, Suzuki K, Kawata S, Matsuzawa Y, Taniguchi N . Suppression of antioxidative enzyme expression by transforming growth factor beta 1 in rat hepatocytes. J Biol Chem 1994; 269: 15488–15492.
Bakin AV, Stourman NV, Sekhar KR, Rinehart C, Yan X, Meredith MJ et al. Smad3-ATF3 signaling mediates TGF-beta suppression of genes encoding phase II detoxifying proteins. Free Radic Biol Med 2005; 38: 375–387.
Reddy NM, Kleeberger SR, Yamamoto M, Kensler TW, Scollick C, Biswal S et al. Genetic dissection of the Nrf2-dependent redox signaling regulated transcriptional programs of cell proliferation and cytoprotection. Physiol Genomics 2007; 32: 74–81.
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: 1743–1754.
Ralph D, Brooks M, Botazzi G . The treatment of Peyronie's disease with tamoxifen. Br J Urol 1992; 70: 648–651.
Safarinejad MR, Asgari MA, Hosseini SY, Dadkhah F . A double-blind placebo-controlled study of the efficacy and safety of pentoxifylline in early chronic Peyronie's disease. BJU Int 2009; 106: 240–248.
I thank all the participants for their enthusiastic cooperation, which made this study clinically and scientifically relevant. I thank Shiva Safarinejad and Nayyer Shafiei for their excellent technical assistance, and Saba Safarinejad for her advice regarding collection and statistical evaluation of data.
The author declares no conflict of interest.
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