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Preliminary Observations of Sildenafil Treatment for Erectile Dysfunction in Dialysis Patients
Preliminary Observations of Sildenafil Treatment for Erectile Dysfunction in Dialysis Patients Sylvia E. Ftosas, MD, Alan Wasserstein, MD, Sidney Kobrin, MD, and Harold I. Feldman, MD • Erectile dysfunction is common in dialysis patients. We report our experience with sildenafil citrate in patients undergoing dialysis therapy. Male subjects attending the Outpatient Dialysis Unit at the University of Pennsylvania (Philadelphia, PA) who were prescribed sildenafil by their primary physician or nephrologist were asked to complete the International Index of Erectile Function before their first dose of sildenafil and after at least 4 weeks of therapy. Subjects' mean age was 50.3 -+ 14.63 (SD) years. Ninety-three percent of the subjects were black. Based on a global efficacy question, 66.7% of the subjects believed that treatment had improved their erections. Subjects reported no increase in the sexual desire domain despite experiencing a significant increase in erectile function, orgasmic function, and satisfaction with intercourse. Sildenafil was well tolerated in a selected group of patients who reported improved sexual function with no major adverse effects. © 2001 by the National Kidney Foundation, Inc. INDEX WORDS: Dialysis; sildenafil; erectile dysfunction (ED); International Index of Erectile Function (IIEF).
RECTILE DYSFUNCTION (ED) is common among patients on dialysis therapy.l-4 The prevalence of ED in the dialysis population is not known. In the past, a variety of definitions have been used to evaluate ED in the hemodialysis population in a number of small studies. Perhaps because of the varied definitions of ED and study design, the estimates of prevalence have ranged broadly from 41% to 93%. 1,3,44 Treatment of ED is frequently frustrating for dialysis patients and their physicians. Therapy for this disorder has included treatment of endocrine disorders, correction of anemia, avoidance of certain medications, vacuum tumescence therapy, intracavernous injections, transurethral suppository of prostaglandin El, and penile prostheses. A recent report showed poor effectiveness of testosterone replacement therapy in dialysis patients with proven hypogonadism compared with vacuum tumescence therapy (18.5% versus 73.1%)2 Some studies have shown improvement in sexual function in dialysis patients with the use of recombinant human erythropoietin m and after renal transplantation, t 1,~2
E
From the Department o[ Biostatistics and Epidemiology, Center jbr Clinical Epidemiology and Biostatistics, Renal, Electrolyte, and Hypertension Division qflthe Department of Medicine, University of Pennsyh'ania. Philadelphia, PA. Received October 22, 1999; accepted in revised .fi,'rn August 18, 2000. Address reprint requests to Sylvia E. Rosas, MD, 927 Blocklev Hall, 423 Guardian D~, Unive~wiO, of Pennsylvania, PhilacMphia, PA 19104. E-maih [email protected]~enn.edu © 2001 by the National Kidney Foundation, hw. 0272-6386/01/3701-002053.00/0 doi: 10.1053/ajkd.2001.20608 134
Sildenafil, a potent inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase enzyme in the corpus cavernosum, has been recently approved as the first oral therapy for ED. A recent report by Goldstein et al t3 concluded that oral sildenafil is an effective welltolerated treatment for men with ED. Unfortunately, subjects with renal disease were excluded; therefore, the efficacy and safety of sildenafil among patients with end-stage renal disease (ESRD) is not known. We report our experience with sildenafil citrate among patients undergoing dialysis therapy. SUBJECTS AND METHODS A prospective cohort study was performed among adult men attending the Outpatient Dialysis Unit of the University of Pennsylvania (Philadelphia, PA) who were prescribed sildenafil by their primary physician or nephrologist. Subjects were asked to complete the International Index of Erectile Function (fIEF) before their first dose of sildenafil and after at least 4 weeks of therapy. The IIEF is a brief self-administered measure of erectile function. It has been used in studies that showed treatment-related changes in the population at large with ED. 13,14The IIEF has five domains: erectile function (six questions), orgasmic function (two questions), sexual desire (two questions), intercourse satisfaction (three questions), and overall satisfaction (two questions). The score lbr each item ranges from 0 to 5 for questions 1 through 10 and from 1 to 5 lk)r questions 11 through 15. The maximum score for the erectile function domain is 3(1. Subjects who scored less than 25 in this domain are considered to have ED. t5 The maximum score for intercourse satisfaction is 15. For all other domains, the maximum score is 10. Efficacy of sildenafil was determined using two questions from the IIEF addressing frequency of obtaining an erection suitable for penetration and maintenance of erection after administration of the drug. Scores for
American Journal of Kidney Diseases, Vo137, No 1 (January), 2001 : pp 134-137
SILDENAFIL IN DIALYSIS PATIENTS
the five response domains of male sexual function derived from the 15-item IIEF were also evaluated. The questionnaire administered after at least 4 weeks of therapy also inquired about the method of payment for sildenafil+ dose used, and duration of relationship with their present sexual partner. The side effects explicitly evaluated included headache, flushing, dyspepsia, rhinitis, and visual disturbance. A global efficacy question was also asked. Medical history was obtained from subjects and their medical records. Instructions for the use of sildenafil, including the appropriate escalation of dose, were provided to each patient by the prescribing physician and not the research team. Categorical variables were summarized by frequencies. Mean, SD, and range were used to describe all continuous variables. Paired t-test was used to evaluate responses alter treatment. All tests of hypotheses were two-sided. All analyses were performed using Stata software (College Station, TX). RESULTS
Fifteen subjects completed the study protocol. Their mean age was 50.1 _+ 14.1 years, with a range of 29 to 75 years. Ninety-three percent of the subjects were black. Hemodialysis was the therapeutic dialysis modality for 87%, whereas only two subjects were on peritoneal dialysis therapy. All subjects' present relationship had lasted more than 6 months, and more than 92% of our subjects lived with their partner. Most of the subjects were married (41%); 25% were single, and 33% were cohabiting. Half the subjects had never smoked, and 29% were active smokers. Sixty-seven percent of the subjects had experienced ED for more than 1 year, and approximately 54% of the subjects, more than 3 years. The average time on dialysis therapy was 3.92 _+ 3.5 years (median, 21 months). Hypertension was the single most common cause of ESRD (53%), followed by diabetes (19%). Two patients had an unknown cause of ESRD. Ninety-three percent of the subjects had hypertension, and 33% had diabetes. The mean duration of hypertension was 6.9 years, and diabetes mellitus, 11 years. Although no patient had a diagnosis of myocardial infarction or coronary artery bypass surgery, 23% of the patients had hypercholesterolemia, and 31% recalled a history of coronary artery disease. Mean albumin level was 4 _+ 0.5 mg/dL, with a range of 3.2 to 4.8 mg/dL. Average hematocrit was 34.1% _+ 4.2%, with a range of 26.7% to 40%. Ninety-two percent of the patients were on erythropoietin therapy.
135
Sildenafil was covered by an insurance plan for only two patients. After 4 to 6 weeks of treatment, 18% of the subjects were taking 25 rag, 36% were taking 50 rag, and 27% were taking 100 mg of sildenafil. The subjects found that sildenafil had a mean time to onset of 133 _+ 228.4 minutes (median, 60 minutes). Mean duration of action was 58.3 _+ 61.14 minutes (median, 30 minutes). Based on the global efficacy question, 66.7% of the subjects believed the treatment had improved their erections. Item 3 of the IIEF ("When you attempted sexual intercourse, how often were you able to penetrate (enter) your partner") had the following possible responses: 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); and 5, Almost always/always. Median scores were 1 at baseline and 4 after treatment. Item 4 of the IIEF ("During sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner") had the same possible responses as item 3. Median scores were 2 at baseline and 4 after treatment. Table 1 lists the IIEF questionnaire scores according to five domains. Erectile function, orgasmic function, and intercourse satisfaction domains showed significant improvement after oral therapy with sildenafil. The mean score in the erectile function domain increased from 11.4 _+ 2.3 to 21.2 _+ 2.7 after sildenafil use. The 95% confidence intervals of the difference between the baseline and follow-up scores for the different domains are listed. There was no increase in the sexual desire domain, although there was a notable increase in orgasmic function and intercourse satisfaction domains.
Cessation and Adverse Effects Half the subjects had used sildenafil up to three times; one quarter of the subjects, three to five times; and one quarter of the subjects, more than five times. Three subjects discontinued sildenafil use during the first month. One patient did so because of adverse side effects (headache, nausea), one patient because of an insufficient response, and the third patient for an unspecifed reason. Headache was reported in two subjects,
136
ROSAS ET AL
Table 1.
Mean Score by Domain of IIEF at Baseline and After 4 to 6 Weeks of Sildenafil Therapy
Domain
Baseline
Erectile function Orgasmic function Intercourse satisfaction Sexual desire Overall satisfaction
11.4 5 6.8 7.1 5.8
_+ 2.3 _+ 1.0 _+ 1.15 _+ 0.45 _+ 0.63
Follow-Up 21.2 7.6 10.2 7.8 7.1
- 2.7 ÷ 0.9 + 1.17 _+ 0.46 _+ 0.88
P
Difference 95% CI
0.002 0.03 0.02 0.23 0.12
-15.1- -4.5 -4.9--0.31 -6.2- -0.57 -1.83-0.49 -2.9-0.40
NOTE. Values expressed as mean _+ SE unless noted otherwise. The erectile function, orgasmic function, and intercourse satisfaction domains show significant improvement after oral therapy with sildenafil. As expected, there was no difference in the sexual desire domain. The 95% confidence interval (CI) between the difference of the baseline and follow-up scores for the different domains is provided.
and flushing, in one subject. Another subject reported diarrhea. No subjects reported priapism. DISCUSSION
We found that sildenafil improved ED in hemodialysis patients and was well tolerated. In the dialysis population, the causes of ED are multifactorial; therefore, treatment of underlying causes, if possible, is recommended. ED in hemodialysis patients is common, with estimates of the prevalence ranging broadly from 41% to 93%. L3,4.s ED is associated with poorer quality of life among men without kidney disease. ~6 As we make important advances to improve survival on hemodialysis therapy, improvement in quality of life should also be of utmost importance and should include an evaluation for ED. ED may improve in patients with renal failure after the initiation of hemodialysis therapy. Procci and Martin 17 reported that 23 patients started on chronic hemodialysis therapy and followed up prospectively for 2.5 years experienced an increase in frequency of intercourse despite stability of nocturnal penile tumescence measures. This may be caused by adequacy of dialysis or erythropoietin administration.IS.J9 ED may also improve after renal transplantation./2 Our ESRD population was three times more likely to have hypertension and more than twice as likely to have diabetes than the non-ESRD population described in other studies, ~3but similar results were obtained with the use of sildenafil. Median onset and duration of action of sildenafil appear similar to those reported for patients without renal impairment, but because sildenafil is partially excreted by the kidney, it is advisable to recommend a lower initial dosage.
Our study has several limitations. This was not a randomized clinical trial, and we cannot be certain the unblinded nature of our observations did not lead to perceived improvement in erectile function greater than actually occurred. There may be differences in the treatment and evaluation of patients with regard to ED. Instruction for sildenafil use was not performed in a standardized manner, making it more difficult to detect a benefit from sildenafil if one occurred. It is also not known whether the subjects had undergone previous treatment for ED. Medication safety is difficult to interpret in small studies and is not the purpose of the present study. Results should be interpreted cautiously because of the lack of a comparison group. Nevertheless, sildenafil in this group of patients was as effective and had a similar adverse-effect profile as reported in other studies or in subjects without renal disease. This study supports the performance of larger, randomized, control trials examining the efficacy and safety profile in patients with renal failure. Sildenafil was well tolerated in a selected group of hemodialysis patients who reported improved sexual function with no major adverse effects. Larger studies of patients with ESRD are warranted, including those that assess the prevalence of ED in this population and how improvement of ED affects associated quality of life. REFERENCES 1. Rodger RS, Fletcher K, Dewar JH, Genner D, McHugh M, Wilkinson R, Ward MK, Kerr DN: Prevalence and pathogenesis of impotence in one hundred uremic men. Uremia Invesl 8:89-96, 1984 2. Levy NB: Sexual adjustment to maintenance hemodialysis and renal transplantation: National survey by question-
SILDENAFIL IN DIALYSIS PATIENTS
naire: Preliminary report. Trans Am Soc Artif Intern Organs 19:138-143, 1973 3. Thurm J: Sexual potency of patients on chronic hemodialysis. Urology 5:60-62, 1975 4. Levy NB: Sexual dysfunctions of hemodialysis patients. Clin Exp Dial Apheresis 7:275-288, 1983 5. Alleyne S, Dillard P, McGregor C, Hosten A: Sexual function and mental distress status of patients with end-stage renal disease on hemodialysis. Transplant Proc 21:38953898, 1989 6. Glass CA, Fielding DM, Evans C, Ashcroft JB: Factors related to sexual functioning in male patients undergoing hemodialysis and with kidney transplants. Arch Sex Behav 16:189-207, 1987 7. Procci WR: The study of sexual dysfunction in uremic males: Problems for patients and investigators. Clin Exp Dial Apheresis 7:289-302, 1983 8. Milne JR Golden JS, Fibus L: Sexual dysfunction in renal failure: A survey of chronic hemodialysis patients. Int J Psychiatry Med 8:335-345, 1977 9. Lawrence IG, Price DE, Howlett TA, Harris KR Feehally J, Walls J: Correcting impotence in the male dialysis patient: Experience with testosterone replacement and vacuum tumescence therapy. Am J Kidney Dis 31:313-319, 1998 10. Evans R, Rader B, Mannimen D: The quality of life of hemodialysis recipients treated with recombinant human erythropoietin. JAMA 263:825-830, 1990 11. Salvatierra O Jr, Fortmann JL, Belzer FO: Sexual function of males before and after renal transplantation. Urology 5:64-66, 1975
137
12. Holdsworth SR, de Kretser DM, Atkins RC: A comparison of hemodialysis and transplantation in reversing the uremic disturbance of male reproductive function. Clin Nephrol10:146-150, 1978 13. Goldstein I, Lue TE Padma-Nathan H, Rosen RC, Steers WD, Wicker P: Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med 338:1397-1404, 1998 14. 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 dysfunction. Urology 49:822-830, 1997 15. Cappelleri J, Rosen R, Smith M, Mishra A, Osterloh I: Diagnostic evaluation of the erectile function domain of the International Index of Erectile Function. Urology 54:346351, 1999 16. Jonler M, Moon T, Brannan W, Stone NN, Heisey D, Bruskewitz RC: The effect of age, ethnicity and geographical location on impotence and quality of life. Br J Urol 75:651-655, 1995 17. Procci WR, Martin DJ: Effect of maintenance hemodialysis on male sexual performance. J Nerv Ment Dis 173:366-372, 1985 18. Lawrence IG, Price DE, Howlett TA, Harris KR Feehally J, Walls J: Erythropoietin and sexual dysfunction. Nephrol Dial Transplant 12:741-747, 1997 19. Sobh MA, Abd el Hamid IA, Atta MG, Refaie AF: Effect of erythropoietin on sexual potency in chronic haemodialysis patients. A preliminary study. Scand J Urol Nephrol 26:181-185, 1992
RECTILE DYSFUNCTION (ED) is common among patients on dialysis therapy.l-4 The prevalence of ED in the dialysis population is not known. In the past, a variety of definitions have been used to evaluate ED in the hemodialysis population in a number of small studies. Perhaps because of the varied definitions of ED and study design, the estimates of prevalence have ranged broadly from 41% to 93%. 1,3,44 Treatment of ED is frequently frustrating for dialysis patients and their physicians. Therapy for this disorder has included treatment of endocrine disorders, correction of anemia, avoidance of certain medications, vacuum tumescence therapy, intracavernous injections, transurethral suppository of prostaglandin El, and penile prostheses. A recent report showed poor effectiveness of testosterone replacement therapy in dialysis patients with proven hypogonadism compared with vacuum tumescence therapy (18.5% versus 73.1%)2 Some studies have shown improvement in sexual function in dialysis patients with the use of recombinant human erythropoietin m and after renal transplantation, t 1,~2
E
From the Department o[ Biostatistics and Epidemiology, Center jbr Clinical Epidemiology and Biostatistics, Renal, Electrolyte, and Hypertension Division qflthe Department of Medicine, University of Pennsyh'ania. Philadelphia, PA. Received October 22, 1999; accepted in revised .fi,'rn August 18, 2000. Address reprint requests to Sylvia E. Rosas, MD, 927 Blocklev Hall, 423 Guardian D~, Unive~wiO, of Pennsylvania, PhilacMphia, PA 19104. E-maih [email protected]~enn.edu © 2001 by the National Kidney Foundation, hw. 0272-6386/01/3701-002053.00/0 doi: 10.1053/ajkd.2001.20608 134
Sildenafil, a potent inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase enzyme in the corpus cavernosum, has been recently approved as the first oral therapy for ED. A recent report by Goldstein et al t3 concluded that oral sildenafil is an effective welltolerated treatment for men with ED. Unfortunately, subjects with renal disease were excluded; therefore, the efficacy and safety of sildenafil among patients with end-stage renal disease (ESRD) is not known. We report our experience with sildenafil citrate among patients undergoing dialysis therapy. SUBJECTS AND METHODS A prospective cohort study was performed among adult men attending the Outpatient Dialysis Unit of the University of Pennsylvania (Philadelphia, PA) who were prescribed sildenafil by their primary physician or nephrologist. Subjects were asked to complete the International Index of Erectile Function (fIEF) before their first dose of sildenafil and after at least 4 weeks of therapy. The IIEF is a brief self-administered measure of erectile function. It has been used in studies that showed treatment-related changes in the population at large with ED. 13,14The IIEF has five domains: erectile function (six questions), orgasmic function (two questions), sexual desire (two questions), intercourse satisfaction (three questions), and overall satisfaction (two questions). The score lbr each item ranges from 0 to 5 for questions 1 through 10 and from 1 to 5 lk)r questions 11 through 15. The maximum score for the erectile function domain is 3(1. Subjects who scored less than 25 in this domain are considered to have ED. t5 The maximum score for intercourse satisfaction is 15. For all other domains, the maximum score is 10. Efficacy of sildenafil was determined using two questions from the IIEF addressing frequency of obtaining an erection suitable for penetration and maintenance of erection after administration of the drug. Scores for
American Journal of Kidney Diseases, Vo137, No 1 (January), 2001 : pp 134-137
SILDENAFIL IN DIALYSIS PATIENTS
the five response domains of male sexual function derived from the 15-item IIEF were also evaluated. The questionnaire administered after at least 4 weeks of therapy also inquired about the method of payment for sildenafil+ dose used, and duration of relationship with their present sexual partner. The side effects explicitly evaluated included headache, flushing, dyspepsia, rhinitis, and visual disturbance. A global efficacy question was also asked. Medical history was obtained from subjects and their medical records. Instructions for the use of sildenafil, including the appropriate escalation of dose, were provided to each patient by the prescribing physician and not the research team. Categorical variables were summarized by frequencies. Mean, SD, and range were used to describe all continuous variables. Paired t-test was used to evaluate responses alter treatment. All tests of hypotheses were two-sided. All analyses were performed using Stata software (College Station, TX). RESULTS
Fifteen subjects completed the study protocol. Their mean age was 50.1 _+ 14.1 years, with a range of 29 to 75 years. Ninety-three percent of the subjects were black. Hemodialysis was the therapeutic dialysis modality for 87%, whereas only two subjects were on peritoneal dialysis therapy. All subjects' present relationship had lasted more than 6 months, and more than 92% of our subjects lived with their partner. Most of the subjects were married (41%); 25% were single, and 33% were cohabiting. Half the subjects had never smoked, and 29% were active smokers. Sixty-seven percent of the subjects had experienced ED for more than 1 year, and approximately 54% of the subjects, more than 3 years. The average time on dialysis therapy was 3.92 _+ 3.5 years (median, 21 months). Hypertension was the single most common cause of ESRD (53%), followed by diabetes (19%). Two patients had an unknown cause of ESRD. Ninety-three percent of the subjects had hypertension, and 33% had diabetes. The mean duration of hypertension was 6.9 years, and diabetes mellitus, 11 years. Although no patient had a diagnosis of myocardial infarction or coronary artery bypass surgery, 23% of the patients had hypercholesterolemia, and 31% recalled a history of coronary artery disease. Mean albumin level was 4 _+ 0.5 mg/dL, with a range of 3.2 to 4.8 mg/dL. Average hematocrit was 34.1% _+ 4.2%, with a range of 26.7% to 40%. Ninety-two percent of the patients were on erythropoietin therapy.
135
Sildenafil was covered by an insurance plan for only two patients. After 4 to 6 weeks of treatment, 18% of the subjects were taking 25 rag, 36% were taking 50 rag, and 27% were taking 100 mg of sildenafil. The subjects found that sildenafil had a mean time to onset of 133 _+ 228.4 minutes (median, 60 minutes). Mean duration of action was 58.3 _+ 61.14 minutes (median, 30 minutes). Based on the global efficacy question, 66.7% of the subjects believed the treatment had improved their erections. Item 3 of the IIEF ("When you attempted sexual intercourse, how often were you able to penetrate (enter) your partner") had the following possible responses: 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); and 5, Almost always/always. Median scores were 1 at baseline and 4 after treatment. Item 4 of the IIEF ("During sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner") had the same possible responses as item 3. Median scores were 2 at baseline and 4 after treatment. Table 1 lists the IIEF questionnaire scores according to five domains. Erectile function, orgasmic function, and intercourse satisfaction domains showed significant improvement after oral therapy with sildenafil. The mean score in the erectile function domain increased from 11.4 _+ 2.3 to 21.2 _+ 2.7 after sildenafil use. The 95% confidence intervals of the difference between the baseline and follow-up scores for the different domains are listed. There was no increase in the sexual desire domain, although there was a notable increase in orgasmic function and intercourse satisfaction domains.
Cessation and Adverse Effects Half the subjects had used sildenafil up to three times; one quarter of the subjects, three to five times; and one quarter of the subjects, more than five times. Three subjects discontinued sildenafil use during the first month. One patient did so because of adverse side effects (headache, nausea), one patient because of an insufficient response, and the third patient for an unspecifed reason. Headache was reported in two subjects,
136
ROSAS ET AL
Table 1.
Mean Score by Domain of IIEF at Baseline and After 4 to 6 Weeks of Sildenafil Therapy
Domain
Baseline
Erectile function Orgasmic function Intercourse satisfaction Sexual desire Overall satisfaction
11.4 5 6.8 7.1 5.8
_+ 2.3 _+ 1.0 _+ 1.15 _+ 0.45 _+ 0.63
Follow-Up 21.2 7.6 10.2 7.8 7.1
- 2.7 ÷ 0.9 + 1.17 _+ 0.46 _+ 0.88
P
Difference 95% CI
0.002 0.03 0.02 0.23 0.12
-15.1- -4.5 -4.9--0.31 -6.2- -0.57 -1.83-0.49 -2.9-0.40
NOTE. Values expressed as mean _+ SE unless noted otherwise. The erectile function, orgasmic function, and intercourse satisfaction domains show significant improvement after oral therapy with sildenafil. As expected, there was no difference in the sexual desire domain. The 95% confidence interval (CI) between the difference of the baseline and follow-up scores for the different domains is provided.
and flushing, in one subject. Another subject reported diarrhea. No subjects reported priapism. DISCUSSION
We found that sildenafil improved ED in hemodialysis patients and was well tolerated. In the dialysis population, the causes of ED are multifactorial; therefore, treatment of underlying causes, if possible, is recommended. ED in hemodialysis patients is common, with estimates of the prevalence ranging broadly from 41% to 93%. L3,4.s ED is associated with poorer quality of life among men without kidney disease. ~6 As we make important advances to improve survival on hemodialysis therapy, improvement in quality of life should also be of utmost importance and should include an evaluation for ED. ED may improve in patients with renal failure after the initiation of hemodialysis therapy. Procci and Martin 17 reported that 23 patients started on chronic hemodialysis therapy and followed up prospectively for 2.5 years experienced an increase in frequency of intercourse despite stability of nocturnal penile tumescence measures. This may be caused by adequacy of dialysis or erythropoietin administration.IS.J9 ED may also improve after renal transplantation./2 Our ESRD population was three times more likely to have hypertension and more than twice as likely to have diabetes than the non-ESRD population described in other studies, ~3but similar results were obtained with the use of sildenafil. Median onset and duration of action of sildenafil appear similar to those reported for patients without renal impairment, but because sildenafil is partially excreted by the kidney, it is advisable to recommend a lower initial dosage.
Our study has several limitations. This was not a randomized clinical trial, and we cannot be certain the unblinded nature of our observations did not lead to perceived improvement in erectile function greater than actually occurred. There may be differences in the treatment and evaluation of patients with regard to ED. Instruction for sildenafil use was not performed in a standardized manner, making it more difficult to detect a benefit from sildenafil if one occurred. It is also not known whether the subjects had undergone previous treatment for ED. Medication safety is difficult to interpret in small studies and is not the purpose of the present study. Results should be interpreted cautiously because of the lack of a comparison group. Nevertheless, sildenafil in this group of patients was as effective and had a similar adverse-effect profile as reported in other studies or in subjects without renal disease. This study supports the performance of larger, randomized, control trials examining the efficacy and safety profile in patients with renal failure. Sildenafil was well tolerated in a selected group of hemodialysis patients who reported improved sexual function with no major adverse effects. Larger studies of patients with ESRD are warranted, including those that assess the prevalence of ED in this population and how improvement of ED affects associated quality of life. REFERENCES 1. Rodger RS, Fletcher K, Dewar JH, Genner D, McHugh M, Wilkinson R, Ward MK, Kerr DN: Prevalence and pathogenesis of impotence in one hundred uremic men. Uremia Invesl 8:89-96, 1984 2. Levy NB: Sexual adjustment to maintenance hemodialysis and renal transplantation: National survey by question-
SILDENAFIL IN DIALYSIS PATIENTS
naire: Preliminary report. Trans Am Soc Artif Intern Organs 19:138-143, 1973 3. Thurm J: Sexual potency of patients on chronic hemodialysis. Urology 5:60-62, 1975 4. Levy NB: Sexual dysfunctions of hemodialysis patients. Clin Exp Dial Apheresis 7:275-288, 1983 5. Alleyne S, Dillard P, McGregor C, Hosten A: Sexual function and mental distress status of patients with end-stage renal disease on hemodialysis. Transplant Proc 21:38953898, 1989 6. Glass CA, Fielding DM, Evans C, Ashcroft JB: Factors related to sexual functioning in male patients undergoing hemodialysis and with kidney transplants. Arch Sex Behav 16:189-207, 1987 7. Procci WR: The study of sexual dysfunction in uremic males: Problems for patients and investigators. Clin Exp Dial Apheresis 7:289-302, 1983 8. Milne JR Golden JS, Fibus L: Sexual dysfunction in renal failure: A survey of chronic hemodialysis patients. Int J Psychiatry Med 8:335-345, 1977 9. Lawrence IG, Price DE, Howlett TA, Harris KR Feehally J, Walls J: Correcting impotence in the male dialysis patient: Experience with testosterone replacement and vacuum tumescence therapy. Am J Kidney Dis 31:313-319, 1998 10. Evans R, Rader B, Mannimen D: The quality of life of hemodialysis recipients treated with recombinant human erythropoietin. JAMA 263:825-830, 1990 11. Salvatierra O Jr, Fortmann JL, Belzer FO: Sexual function of males before and after renal transplantation. Urology 5:64-66, 1975
137
12. Holdsworth SR, de Kretser DM, Atkins RC: A comparison of hemodialysis and transplantation in reversing the uremic disturbance of male reproductive function. Clin Nephrol10:146-150, 1978 13. Goldstein I, Lue TE Padma-Nathan H, Rosen RC, Steers WD, Wicker P: Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med 338:1397-1404, 1998 14. 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 dysfunction. Urology 49:822-830, 1997 15. Cappelleri J, Rosen R, Smith M, Mishra A, Osterloh I: Diagnostic evaluation of the erectile function domain of the International Index of Erectile Function. Urology 54:346351, 1999 16. Jonler M, Moon T, Brannan W, Stone NN, Heisey D, Bruskewitz RC: The effect of age, ethnicity and geographical location on impotence and quality of life. Br J Urol 75:651-655, 1995 17. Procci WR, Martin DJ: Effect of maintenance hemodialysis on male sexual performance. J Nerv Ment Dis 173:366-372, 1985 18. Lawrence IG, Price DE, Howlett TA, Harris KR Feehally J, Walls J: Erythropoietin and sexual dysfunction. Nephrol Dial Transplant 12:741-747, 1997 19. Sobh MA, Abd el Hamid IA, Atta MG, Refaie AF: Effect of erythropoietin on sexual potency in chronic haemodialysis patients. A preliminary study. Scand J Urol Nephrol 26:181-185, 1992