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Atorvastatin improves the response to sildenafil in hypercholesterolemic men with erectile dysfunction not initially responsive to sildenafil


Despite the initial enthusiasm, the significant number of patients in whom sildenafil is contraindicated or ineffective is a major challenge to all urologists. Our aim was to determine the safety and efficacy of adjunctive atorvastatin in restoring normal erectile function in hypercholesterolemic (low-density lipoprotein (LDL) cholesterol >120 mg per 100 ml) sildenafil nonresponders. The study comprised 131 men with ED not responding to sildenafil citrate. They were randomized either to 40 mg atorvastatin daily (n=66, group 1) or matching placebo (n=65, group 2) for 12 weeks while they were taking on-demand 100 mg sildenafil. Erectile function was subjectively assessed using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire and response to the global efficacy question (GEQ). Serum biochemical and lipid profile (total cholesterol, triglycerides, LDL cholesterol and high-density lipoprotein cholesterol) analyses were performed at baseline and repeated at post-treatment weeks 6 and 12. Compared with the placebo group (59 patients, mean age±s.d. 61.9±6.1, mean years ED 3.9±1.8), the atorvastatin group (59 patients, mean age±s.d. 63.9±6.9, mean years ED 3.7±1.6) had significantly greater improvements in all IIEF-5 questions (P=0.01) and GEQ (P=0.001). Subgroup analyses did reveal trends in the atorvastatin group to indicate that a change in the IIEF-5 score is affected by age, severity of ED and baseline serum levels of LDL. Patients with moderate (r=0.28, P=0.01) and severe (r=0.20, P=0.01) ED had better positive response rates to adjunctive atorvastatin than patients with mild to moderate ED. None of the patients taking atorvastatin achieved a response of 5 to the IIEF-5 questions and none of the patients regained normal erectile function as defined by the IIEF-5 score >21. Subjects experienced a statistically significant but modest improvement in erectile function. Further investigation is needed to test the usefulness of long-term atorvastatin administration to restore erectile function in sildenafil nonresponders.


Community-based epidemiological studies indicate that ED is common.1, 2 ED affects roughly 150 million men worldwide and the number is likely to exceed 300 million men by the year 2025.3, 4

Sildenafil citrate is effective oral first-line medication for ED. It appears to be effective for symptomatic relief of ED in a wide variety of men.5 However, not all men suffering from ED have effectively responded to sildenafil.6 Early treatment discontinuation rates for the drug attributed to the patients' dissatisfaction range from 14% to as high as 47%.7 The most common cause for patient dissatisfaction is lack of consistent efficacy.7 A substantial number of sildenafil nonresponders can be rescued with appropriate instructions and education followed by rechallenge.8, 9 Sildenafil's efficacy is also lower in patients with some risk factors and diseases such as diabetes mellitus,10, 11 hypertension,12 multiple sclerosis13 and combat-related post-traumatic stress disorder.14

Centrally acting drugs, such as dopamine agonists15 and melanocortin analog,16 have been used as less invasive modalities (vs intracavernous injection, vacuum constrictive device and penile prosthesis) with various success rates to salvage sildenafil nonresponders. However, the growing numbers of men with ED, and the significant number of patients for whom this treatment is ineffective or contraindicated, make sildenafil nonresponders a great challenge for urologists.

Hyperlipidemia is a significant risk factor for ED, and 42% of patients with ED have hyperlipidemia only.17 Patients with ED but without clinical evidence for cardiovascular disease have a peripheral vascular defect in endothelium-dependent and -independent vasodilation.18 Oxidized low-density lipoprotein (LDL) inhibits vascular smooth muscle relaxation through endothelial cells.19 Also, high LDL-cholesterol level may influence the severity of ED.20 Indeed, atherosclerotic biomarkers for endothelial function, thrombosis and dyslipidemia are associated with the degree of ED.21 In a longitudinal population-based study, after adjustment for the classical risk factors, severely decreased erectile rigidity has a hazard ratio of 2.6 and decreased erectile rigidity a hazard ratio of 1.6 for cardiovascular disease.22 Three-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decrease the action of oxidized LDL on endothelial cells, resulting in increased NO activity.23 The main vasodilator involved in penile erection is NO. Atorvastatin increases the sildenafil-induced vasodilation through NO-mediated mechanisms.24 It has been proposed that in patients with hyperlipidemia, treatment with statin has a protective effect on erectile function.17 In an experimental study, atorvastatin improved diabetes-related ED and restored sildenafil responsiveness.25 Statin therapy was effective on early return of potency after nerve-sparing radical retropubic prostatectomy in men without hypercholesterolemia.26 In men with hypercholesterolemia as the only risk factor for ED, erectile function improves with atorvastatin treatment.27 In a placebo-controlled pilot study, treatment with atorvastatin improved the erectile function domain score and the response to oral sildenafil in sildenafil nonresponders.28

To our knowledge, this is the largest randomized clinical trial addressing the safety and efficacy of adjunctive atorvastatin treatment in hypercholesterolemic men with ED who have not responded to sildenafil.

Materials and methods

Study participants

Between February 2006 and November 2007, 182 sildenafil nonresponders 18–70 years old were recruited for screening. They presented at our Urology Clinic on being disappointed by the efficacy of sildenafil. All participants were married and engaged in regular sexual activity at least once a week. ED was defined as the consistent inability to achieve or maintain an erection sufficient for satisfactory sexual intercourse.29 All patients were given a sildenafil instruction sheet. The instruction sheet emphasized its use on an empty stomach, the proper timing of sildenafil administration (30 min–2 h before sexual attempt) and the absolute need for appropriate sexual stimulation. Erectile function was categorized as follows using the 5-item version of the International Index of Erectile Function (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).30, 31 Participants were further categorized into five age groups according to their age: 18–30, 31–40, 41–50, 51–60 and 61–70. After instruction on correct usage in the sildenafil failure confirmation phase, all participants were rechallenged with sildenafil 100 mg on at least four occasions. Only patients who scored 21 on the IIEF-5 were recruited into the study.

The medical ethics committee of the Urology and Nephrology Research Center approved this study, and all patients provided written informed consent. The study was conducted in accordance with the Declaration of Helsinki.

Inclusion/exclusion criteria

Key inclusion criteria were inadequate response to rechallenge with 100 mg sildenafil after proper usage instruction (score 21 on the IIEF-5); total cholesterol <200 mg per 100 ml and LDL-cholesterol <160 mg per 100 ml; clinical diagnosis of ED >6 months; a stable relationship with a female partner for >6 months; and absence of a contraindication to either statin therapy or sildenafil use.

Patients were excluded from enrollment if they had clinically significant renal (serum creatinine level >2 mg per 100 ml), or hepatic diseases (serum aspartate aminotransferase or alanine aminotransferase >1.5 times the upper limit of normal (45 U l−1 for alanine aminotransferase, 31 U l−1 for aspartate aminotransferase); creatine kinase level >25% above the upper limit of normal; neurological or psychiatric disorders; endocrinopathies such as poorly controlled diabetes mellitus; uncontrolled cardiovascular disease such as hypertension (blood pressure >150/100 mm Hg), hypotension (blood pressure <90/50 mm Hg), coronary artery disease and cardiac arrhythmia; stroke; previous genitourinary or pelvic disease or surgery; alcohol use; use of medications that cause ED; relationship problems; and a history or current use of any serum lipid-altering agents. Patients who discontinued sildenafil because of tolerance-associated problems such as side effects and unwillingness to treatment were also excluded.


Detailed history was obtained and a complete physical examination was performed. The following laboratory tests were carried out: detailed biochemical analysis, serum lipid profile (total cholesterol, triglycerides, LDL cholesterol, high-density lipoprotein cholesterol) and complete blood count. Biochemical and serum lipid profile analyses were repeated at post-treatment weeks 6 and 12. The IIEF-5, which is referred to as the Sexual Health Inventory of Men, was used to evaluate erectile function.30, 31 The IIEF-5 is a validated, multidimensional, self-administered questionnaire that is often used in clinical researches.31 The full version of the IIEF consists of 15 questions (IIEF-15) that are used to assess several domains of male sexual function. The IIEF-5 questionnaire uses five specific questions (questions 2, 4, 5, 7 and 15) from the IIEF-15:

  • Question 2: When you had erection with sexual stimulation, how often were your erections hard enough for penetration?

  • Question 4: During sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner?

  • Question 5: During sexual intercourse, how difficult was it to maintain your erection to the completion of intercourse?

  • Question 7: When you attempted sexual intercourse, how often was it satisfactory for you?

  • Question 15: How do you rate your confidence that you could get and keep an erection?

These questions measure the erectile function domain. The maximum achievable score for the IIEF-5 is 25 with a cutoff value of 21 for ED.

The response options for all questions are as follows:

0=did not attempt intercourse,

1=almost never/never,

2=a few times (much less than half the time),

3=sometimes (about half the time),

4=most times (much more than half the time),

5=almost always/always

Finally, a total of 131 patients who met the inclusion and exclusion criteria and consented with the study protocol were enrolled in the study.

Treatment protocol

The study included a 4-week baseline screening period and a 12-week double-blind treatment period. After screening, patients were randomized to atorvastatin 40 mg day−1 (n=66, group 1) or matching placebo (n=65, group 2). Patients were instructed to take 100 mg sildenafil as needed 1 h before sexual stimulation. All study patients were asked to have sexual intercourse at least once a week. The investigator, prescriber and subjects were blinded to the treatment condition. Drug compliance was assessed by direct questioning.

Outcome measures

To assess any improvement in erectile function, the IIEF-5 questionnaire was administered at the baseline, at the initiation of treatment with adjunctive atorvastatin, and every 2 weeks during the treatment period. The primary end point was improvement in erectile function as measured by the IIEF-5 total score. Secondary end points were the responses to question 4 (maintenance of erections after penetration) and question 5 (maintenance of erections to completion of intercourse). The subjective measure of success was based on the patient's response to a global efficacy question (GEQ), ‘Did the treatment you were taking improve your erections?’


Treatment-emergent adverse events were evaluated by recording all patient-reported adverse events and any changes in clinical laboratory tests and vital signs. Treatment-emergent adverse events were defined as any adverse event that first occurred or worsened after baseline assessment.

Statistical analysis

Data are presented as mean±s.d. A 116 patient sample size (58 in each group) would be required to provide 85% power with an á of 0.05 to detect a 25% difference in response rates for the primary outcome measure (IIEF-5 total score) between the placebo (estimated to be 15%) and active treatment (estimated to be 55%) groups. Assuming a 10% dropout rate, we therefore enrolled 130 patients. All efficacy variables were analyzed using intent-to-treat principals. Safety analysis included all subjects who had a baseline evaluation and at least one follow-up visit after the randomization. The last observation carried forward was used to account for patient dropouts at each time point. Basal demographic and clinical characteristics were compared between the two groups using the unpaired t-tests. Responses (yes or no) to the GEQ were analyzed by logistic regression. The relationship between statin therapy and IIEF-5 scores was assessed by the Wilcoxon sign rank test. Paired t-tests were used to determine significant differences in mean LDL, and IIEF-5 scores before and after treatment with atorvastatin. Between-group comparisons of treatment-emergent adverse events were performed with Fisher's exact test. A P-value <0.05 was accepted as statistically significant. The data were analyzed using the Statistical Package for Social Sciences, version 11.5 (SPSS, Chicago, IL, USA).


Patient disposition and characteristics

The mean patient age was 62.7±6.4 years and the mean duration of ED was 3.8±1.7 years. Patient age ranged from 41 to 70 years. Of 131 patients who were randomized, 118 (90.1%) (59 in each group) completed the whole study protocol. The reasons for non-completion are shown in Figure 1. In general, treatment groups were well matched with regard to demographic and clinical characteristics (Table 1). The mean number of sildenafil taken per patient was 18.8 for the atorvastatin group and 12.4 for the placebo group (P=0.01).

Figure 1

Flow chart of recruited subjects.

Table 1 Demographic and clinical characteristics of patients in two subject groups

Treatment efficacy

Mean IIEF-5 total scores were comparable between groups at baseline. Throughout the study, patients who received atorvastatin with sildenafil had greater improvement in the IIEF-5 question scores than those who received sildenafil with placebo (Figure 2). This difference reached statistical significance at week 6. Thereafter, there was no significant change in the measured variables until the end of the study (week 12), whereas a smaller and progressive improvement was observed in the placebo group. Of the patients in the atorvastatin and placebo groups, 22 (37.3%) and 7 (11.9%), respectively, had statistically significant IIEF-5 score improvement (P=0.01). Patients who received atorvastatin had a greater mean IIEF-5 (Sexual Health Inventory of Men) score at the end of the trial (13.9±3.7 vs 10.5±3.3) (P=0.001) (Table 2). However, none of the patients regained normal erectile function as defined by the IIEF-5 score >21.

Figure 2

Percentage change in IIEF-5 scores through the study period. IIEF, International Index of Erectile Function.

Table 2 Comparative efficacy of atorvastatin and placebo as measured by IIEF-5 scores (mean±s.d.) at baseline and after trial

Overall, 27 (45.8%) of the patients were satisfied (score >3 for question 7) with the level of sexual function with atorvastatin citrate (P=0.01).

The mean change from the baseline IIEF-5 score in patients who received atorvastatin (33.7%) was significantly higher than in patients who received placebo (4%) (P=0.001). The mean change in questions 2 (erection hardness) and 5 (maintenance ability) for patients taking atorvastatin was 35% and 38.1%, respectively (Figure 2). None of the patients taking atorvastatin achieved a response of 5 to the IIEF-5 questions.

Subgroup analyses did reveal trends in the atorvastatin group to indicate that change in the IIEF-5 score is affected by age, severity of ED and baseline serum levels of LDL (Table 3). Improvements in the mean scores of all IIEF-5 questions, as well as the total score, were higher in patients with moderate and severe ED (Figure 3), the older age group (Figure 4), and in patients with lower baseline serum levels of LDL (130 mg−1 per 100 ml). Subjects with moderate ED who received atorvastatin with sildenafil showed the highest increase (43%) in the IIEF-5 total score at the end of the study compared with those who had mild to moderate (18.2%, P=0.001) and severe (41.9%, P=0.08) ED (Figure 3). Improvements were also significantly superior in the 61–70 age group (42.7%) compared with the 41–50 and 51–60 age groups (39.9% and 34.9%, respectively) over the total IIEF-5 score at week 12 (P=0.001) (Figure 4). Moreover, atorvastatin was effective in improving ED, even in cases with concomitant risk factors such as diabetes mellitus (Table 3).

Table 3 Comparative efficacy of atorvastatin and placebo across different clinical characteristics and concomitant risk factors as measured by IIEF-5 scores (mean±s.d.) at baseline and after trial
Figure 3

Percentage change in IIEF-5 total score across subjects with different severity of erectile dysfunction through the study period. IIEF, International Index of Erectile Function.

Figure 4

Percentage change in IIEF-5 total score across different age groups through the study period. IIEF, International Index of Erectile Function.

After 12 weeks of treatment, the mean scores for GEQ had improved significantly for men receiving atorvastatin compared with placebo (P=0.001) (Table 4). The percentage of subjects who responded with ‘yes’ on the GEQ indicated a threefold higher level of satisfaction during sexual intercourse for patients who received atorvastatin (61%) compared with the percentage of subjects who received placebo (17%).

Table 4 Comparative efficacy of atorvastatin and placebo across different clinical characteristics and concomitant risk factors as measured by number GEQ responses (%) after trial

Secondary analysis

There was a weak but significant correlation between the degree of baseline ED and response to atorvastatin. Patients with moderate (r=0.28, P=0.01) and severe (r=0.20, P=0.01) ED had better positive response rates to adjunctive atorvastatin than patients with mild to moderate ED. Atorvastatin significantly decreased total cholesterol (P=0.01), triglycerides (P=0.01) and LDL-cholesterol (P=0.001) (Table 2). Multivariate analysis showed that atorvastatin therapy produced a significant reduction in the serum LDL-cholesterol level (odds ratio=2.54; 95% confidence interval, 1.36–3.92; P=0.01). The odds ratio for serum LDL-cholesterol reduction in patients receiving atorvastatin compared with those treated by placebo was 2.68 (95% confidence interval, 1.46–3.99; P=0.001). There was a modest correlation between the baseline serum level of LDL and satisfaction with atorvastatin (r=0.32, P=0.01). However, there was no correlation between the degree of LDL decrease and improvement in the IIEF-5 score (r=0.11, P=0.3). A correlation with a higher probability of responsiveness to adjunctive atorvastatin was shown for patients with lower baseline IIEF score (r=0.54, P=0.01).

The relationship of concomitant risk factors to the change in ED score over the study period was investigated by multiple regression analysis including only concomitant risk factors as dependent variables. When stratified for risk factors, patients with diabetes mellitus, hypertension and ischemic heart disease had similar percentage increases in the IIEF-5 score (#40%). However, the increase in smokers was 52.6% (P=0.02). Of the patients in group 1, 31 (62.5%) stated that they would continue to use atorvastatin, but only 25 (42.4%) confirmed that the medication met their expectations.

Adverse events

In this study, atorvastatin was well tolerated. No serious adverse events were noted. Several adverse events were considered by the investigator to be related to atorvastatin treatment, including constipation in 7.6%, dyspepsia in 6.1%, and abdominal pain, headache and myalgia (each 3%). They were mostly mild to moderate in nature. However, 4 (6.1%) atorvastatin-treated patients discontinued because of adverse events. There was no significant increase in the levels of aspartate aminotransferase, alanine aminotransferase and creatine kinase values compared with the placebo group.


In this study, 37% of patients overall who had failed to respond to sildenafil reported improved erectile function with adjunctive atorvastatin. Statins included atorvastatin, fluvastatine, simvastatin, pravastatin and rosuvastatin. Their pharmacological properties related to endothelium-mediated vasoactive, antithrombotic, antiproliferative, anti-inflammatory and antidyslipidemic activities.23, 32 Our results are consistent with those of Herrmann et al.28 and Bank et al.33 Using the IIEF-15 erectile function domain questionnaire, Herrmann et al.28 found an improvement in the domain score of 7.8 (P=0.036) in 12 men with moderate-to-severe ED and serum LDL-cholesterol 100 mg per 100 ml. Bank et al.33 found that, compared with placebo, atorvastatin significantly improved symptoms of ED as measured by the IIEF-5 questionnaire.

In this study, despite significant improvements in erectile function, none of the patients achieved normal erectile function (IIEF-5 >21). It has been shown that short-term treatment will not likely cause alterations in the penile vasculature anatomy. In men with severe coronary artery disease, aggressive treatment with cholesterol-lowering agents causes atheroma regression but this occurrence needs more than a year.27 Most men would have several risk factors for ED, and thus they would need a longer treatment course. However, we did not observe progressive beneficial effects after 6-week atorvastatin administration. The probability of ED in men with some risk factors, such as hypertension, smoking, dyslipidemia, cardiovascular disease and diabetes mellitus is high.29, 34 We noted significantly lower pretreatment IIEF scores in patients with associated comorbidities. Likewise, adjunctive atorvastatin was effective in the subpopulations of patients with different comorbidities. The most important observation in this study was the correlation between baseline sexual function and response to adjunctive atorvastatin. Unlike their expectations, patients with better baseline sexual function did not have higher improvement rates with medication. There was a 17.5% increase in the IIEF-5 score among patients with mild to moderate ED compared with 42% in patients with severe ED (P=0.001). Perhaps patients with more severe ED have more severe vascular endothelial abnormalities. It has been shown that statins, especially atorvastatin, exert their beneficial effects on vascular endothelial cells independent of the lipid-lowering effects. Their favorable effects on the vascular bed related to endothelium-mediated vasoactive, antithrombotic, antiproliferative and anti-inflammatory activities.23, 35 Therefore, patients with more vascular endothelial abnormalities will benefit more. However, some studies have shown the occurrence of reversible ED with statins.36 Case reports of this occurrence have been previously reported. Five men with coronary artery disease developed ED following therapy with simvastatin.37 A total of 42 cases of ED associated with simvastatin usage have also been reported by the Australian Adverse Drug Reactions Committee.38 In addition, Solomon et al.39 reported that statin therapy in high-risk patients may lead to further deterioration of ED. One possible mechanism is the relative lipophilicity of the statin prescribed. Simvastatin is highly lipophilic and therefore might act both centrally and peripherally. Simvastatin may induce a drug-related peripheral neuropathy in the penile nerves.39 Another reason for the aforementioned findings could be inherent in the methodology that different studies used for the assessment of erectile function. Other explanations could be linked to the patient population (age, associated risk factors, concomitant medications, and so on) or study setting (medically-based clinic vs urology-based clinic) and interact with other agents that are also concerned in the development of ED.36

Nevertheless, the effects of statins on human cavernous vessels have yet to be identified. In this study, we enrolled hypercholesterolemic men. It has been reported that impaired endothelium-dependent and -independent vasodilation in patients with ED is similar to that of patients with hypercholesterolemia.40 In addition, some studies have shown that hypercholesterolemia results in an increase in sympathetic activity.41

Current medical treatments for ED, such as PDE5 inhibitors, are palliative. The treatment of ED should be directed not only toward improvement of erectile function (symptom), but also toward eradicating any medical conditions contributing to ED. In other words, PDE5 inhibitors are not curative. In addition to sildenafil nonresponders, we are faced with a significant number of patients who discontinue sildenafil despite its efficacy in ameliorating the symptoms of ED. Of patients who respond to sildenafil, 20–50% discontinue its use.7 In this era of a growing number of patients for whom sildenafil is either contraindicated, unsuitable or ineffective, developing new effective oral pharmacotherapy for ED is mandatory.

Our study is not without limitations. We did not use any objective measures such as RigiScan measurements and penile duplex ultrasonography. We wanted to test minimally invasive treatments for ED in sildenafil nonresponders before proceeding to a more invasive form of therapy (intracavernosal injections). Additional study is required to determine whether atorvastatin or other statins with different treatment regimens can provide better efficacy.


In hypercholesterolemic sildenafil nonresponders, adjunctive atorvastatin successfully improved erectile function in about one-third of patients. However, this medication does not restore normal erectile function. By this trial, long-term effects could not be evaluated. Controlled studies will be needed to know for sure.

Conflict of interest

The authors declare no conflict of interest.


  1. 1

    Laumann EO, Paik A, Rosen RC . Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999; 281: 537–544.

    CAS  Article  Google Scholar 

  2. 2

    Safarinejad MR . Prevalence and risk factors for erectile dysfunction in a population-based study in Iran. Int J Impot Res 2003; 15: 246–252.

    CAS  Article  Google Scholar 

  3. 3

    Aytaç IA, McKinlay JB, Krane RJ . The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int 1999; 84: 50–56.

    Article  Google Scholar 

  4. 4

    McKinlay JB . The worldwide prevalence and epidemiology of erectile dysfunction. Int J Impot Res 2000; 12 (Suppl 4): S6–11.

    Article  Google Scholar 

  5. 5

    McMahon CG, Samali R, Johnson H . Efficacy, safety and patient acceptance of sildenafil citrate as treatment for erectile dysfunction. J Urol 2000; 164: 1192–1196.

    CAS  Article  Google Scholar 

  6. 6

    Brisson TE, Broderick GA, Thiel DD, Heckman MG, Pinkstaff DM . Vardenafil rescue rates of sildenafil nonresponders: objective assessment of 327 patients with erectile dysfunction. Urology 2006; 68: 397–401.

    Article  Google Scholar 

  7. 7

    Seftel AD . Challenges in oral therapy for erectile dysfunction. J Androl 2002; 23: 729–736.

    PubMed  Google Scholar 

  8. 8

    Barada J . Successful salvage of sildenafil (Viagra) failures: benefits of patient education and rechallenge with sildenafil. Int J Impot Res 2001; 13 (Suppl 4): S49.

    Google Scholar 

  9. 9

    Jiann BP, Yu CC, Su CC, Huang JK . Rechallenge prior sildenafil nonresponders. Int J Impot Res 2004; 16: 64–68.

    CAS  Article  Google Scholar 

  10. 10

    Rendell MS, Rajfer J, Wicker PA, Smith MD . Sildenafil for treatment of erectile dysfunction in men with diabetes. JAMA 1999; 281: 421–426.

    CAS  Article  Google Scholar 

  11. 11

    Safarinejad MR . Oral sildenafil in the treatment of erectile dysfunction in diabetic men: a randomized double-blind and placebo-controlled study. J Diabetes Complications 2004; 18: 205–210.

    Article  Google Scholar 

  12. 12

    Guay AT, Perez JB, Jacobson J, Newton RA . Efficacy and safety of sildenafil citrate for treatment of erectile dysfunction in a population with associated organic risk factors. J Androl 2001; 22: 793–797.

    CAS  PubMed  Google Scholar 

  13. 13

    Safarinejad MR . Evaluation of the safety and efficacy of sildenafil citrate for erectile dysfunction in men with multiple sclerosis: a double-blind, placebo controlled, randomized study. J Urol 2009; 181: 252–258.

    CAS  Article  Google Scholar 

  14. 14

    Safarinejad MR, Kolahi AA, Ghaedi G . Safety and efficacy of sildenafil citrate in treating erectile dysfunction in patients with combat-related post-traumatic stress disorder: a double-blind, randomized and placebo-controlled study. BJU Int 2009; 104: 376–383.

    CAS  Article  Google Scholar 

  15. 15

    Safarinejad MR . Salvage of sildenafil failures with cabergoline: a randomized, double-blind, placebo-controlled study. Int J Impot Res 2006; 18: 550–558.

    CAS  Article  Google Scholar 

  16. 16

    Safarinejad MR, Hosseini SY . Salvage of sildenafil failures with bremelanotide: a randomized, double-blind, placebo controlled study. J Urol 2008; 179: 1066–1071.

    CAS  Article  Google Scholar 

  17. 17

    Doğru MT, Başar MM, Simşek A, Yuvanç E, Güneri M, Ebinç H et al. Effects of statin treatment on serum sex steroids levels and autonomic and erectile function. Urology 2008; 71: 703–707.

    Article  Google Scholar 

  18. 18

    Kaiser DR, Billups K, Mason C, Wetterling R, Lundberg JL, Bank AJ . Impaired brachial artery endothelium-dependent and -independent vasodilation in men with erectile dysfunction and no other clinical cardiovascular disease. J Am Coll Cardiol 2004; 43: 179–184.

    Article  Google Scholar 

  19. 19

    Kugiyama K, Ohgushi M, Sugiyama S, Murohara T, Fukunaga K, Miyamoto E et al. Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins. Circ Res 1992; 71: 1422–1428.

    CAS  Article  Google Scholar 

  20. 20

    Chang ST, Chu CM, Hsu JT, Lin PC, Shee JJ . Surveillance of cardiovascular risk factors for outpatients in different erectile dysfunction severity. Int J Impot Res 2009; 21: 116–121.

    Article  Google Scholar 

  21. 21

    Eaton CB, Liu YL, Mittleman MA, Miner M, Glasser DB, Rimm EB . A retrospective study of the relationship between biomarkers of atherosclerosis and erectile dysfunction in 988 men. Int J Impot Res 2007; 19: 218–225.

    CAS  Article  Google Scholar 

  22. 22

    Schouten BW, Bohnen AM, Bosch JL, Bernsen RM, Deckers JW, Dohle GR et al. Erectile dysfunction prospectively associated with cardiovascular disease in the Dutch general population: results from the Krimpen Study. Int J Impot Res 2008; 20: 92–99.

    CAS  Article  Google Scholar 

  23. 23

    McFarlane SI, Muniyappa R, Francisco R, Sowers JR . Clinical review 145: Pleiotropic effects of statins: lipid reduction and beyond. J Clin Endocrinol Metab 2002; 87: 1451–1458.

    CAS  Article  Google Scholar 

  24. 24

    Castro MM, Rizzi E, Rascado RR, Nagassaki S, Bendhack LM, Tanus-Santos JE . Atorvastatin enhances sildenafil-induced vasodilation through nitric oxide-mediated mechanisms. Eur J Pharmacol 2004; 498: 189–194.

    CAS  Article  Google Scholar 

  25. 25

    Morelli A, Chavalmane AK, Filippi S, Fibbi B, Silvestrini E, Sarchielli E et al. Atorvastatin ameliorates sildenafil-induced penile erections in experimental diabetes by inhibiting diabetes-induced RhoA/Rho-kinase signaling hyperactivation. J Sex Med 2009; 6: 91–106.

    CAS  Article  Google Scholar 

  26. 26

    Hong SK, Han BK, Jeong SJ, Byun SS, Lee SE . Effect of statin therapy on early return of potency after nerve sparing radical retropubic prostatectomy. J Urol 2007; 178: 613–616.

    Article  Google Scholar 

  27. 27

    Saltzman EA, Guay AT, Jacobson J . Improvement in erectile function in men with organic erectile dysfunction by correction of elevated cholesterol levels: a clinical observation. J Urol 2004; 172: 255–258.

    Article  Google Scholar 

  28. 28

    Herrmann HC, Levine LA, Macaluso Jr J, Walsh M, Bradbury D, Schwartz S et al. Can atorvastatin improve the response to sildenafil in men with erectile dysfunction not initially responsive to sildenafil? Hypothesis and pilot trial results. J Sex Med 2006; 3: 303–308.

    CAS  Article  Google Scholar 

  29. 29

    NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993; 270: 83–90.

    Article  Google Scholar 

  30. 30

    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.

    CAS  Article  Google Scholar 

  31. 31

    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.

    CAS  Article  Google Scholar 

  32. 32

    Haendeler J, Hoffmann J, Zeiher AM, Dimmeler S . Antioxidant effects of statins via S-nitrosylation and activation of thioredoxin in endothelial cells: a novel vasculoprotective function of statins. Circulation 2004; 110: 856–861.

    CAS  Article  Google Scholar 

  33. 33

    Bank AJ, Kelly AS, Kaiser DR, Crawford WW, Waxman B, Schow DA et al. The effects of quinapril and atorvastatin on the responsiveness to sildenafil in men with erectile dysfunction. Vasc Med 2006; 11: 251–257.

    Article  Google Scholar 

  34. 34

    Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB . Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994; 151: 54–61.

    CAS  Article  Google Scholar 

  35. 35

    Puddu P, Puddu GM, Muscari A . HMG-CoA reductase inhibitors: is the endothelium the main target? Cardiology 2001; 95: 9–13.

    CAS  Article  Google Scholar 

  36. 36

    Carvajal A, Macias D, Sáinz M, Ortega S, Martín Arias LH, Velasco A et al. HMG CoA reductase inhibitors and impotence: two case series from the Spanish and French drug monitoring systems. Drug Saf 2006; 29: 143–149.

    CAS  Article  Google Scholar 

  37. 37

    Jackson G . Simvastatin and impotence. Br Med J 1997; 351: 31.

    Article  Google Scholar 

  38. 38

    Boyd IW . Comment: HMG-CoA reductase inhibitor-induced impotence. Ann Pharmacother 1996; 30: 1199.

    CAS  Article  Google Scholar 

  39. 39

    Solomon H, Samarasinghe YP, Feher MD, Man J, Rivas-Toro H, Lumb PJ et al. Erectile dysfunction and statin treatment in high cardiovascular risk patients. Int J Clin Pract 2006; 60: 141–145.

    CAS  Article  Google Scholar 

  40. 40

    Creager MA, Cooke JP, Mendelsohn ME, Gallagher SJ, Coleman SM, Loscalzo J et al. Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans. J Clin Invest 1990; 86: 228–234.

    CAS  Article  Google Scholar 

  41. 41

    Acharya UR, Kannathal N, Sing OW, Ping LY, Chua T . Heart rate analysis in normal subjects of various age group. Biomed Eng Online 2004; 3: 24.

    Article  Google Scholar 

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Correspondence to M R Safarinejad.

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Dadkhah, F., Safarinejad, M., Asgari, M. et al. Atorvastatin improves the response to sildenafil in hypercholesterolemic men with erectile dysfunction not initially responsive to sildenafil. Int J Impot Res 22, 51–60 (2010).

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  • erectile dysfunction
  • statins
  • sildenafil
  • atorvastatin
  • treatment

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