Erectile Dysfunction in Liver Transplant Patients

Transcription

1 American Journal of Transplantation 2008; 8: Wiley Periodicals Inc. C 2008 The Authors Journal compilation C 2008 The American Society of Transplantation and the American Society of Transplant Surgeons doi: /j x Erectile Dysfunction in Liver Transplant Patients E. Huyghe a,d,, N. Kamar b,e,f.wagner d, S. J. Yeung d,a.h.capietto d,l.el-kahwaji b, F. Muscari c,p.plante a,d and L. Rostaing b,f a Department of Urology and Andrology, b Nephrology, Dialysis, and Multiorgan Transplant Unit, c Digestive Surgery Department, University Hospital, CHU Rangueil, Toulouse, France d EA 3694, Paul Sabatier University, CHU Paule de Viguier, Toulouse, France e INSERM U858, IFR 31, Toulouse, France f INSERM U563, IFR 30, Toulouse, France Corresponding author: Eric Huyghe, huyghe.e@chu-toulouse.fr The objectives of the study were to determine the frequency of erectile dysfunction (ED) after liver transplantation (LT) and discuss potential risk factors. Of 123 eligible LT men, 98 (79.7%) responded to a questionnaire about sexual function at a mean time posttransplant of 5.4 ± 4.0 years (1.0 21). Erection was evaluated using the five-question international index for erectile function score, and sexual satisfaction by the patient-baseline treatment-satisfaction status (TSS) score. Questions also focused on patient perception of changes overtime. We found that after LT, the proportion of sexually inactive men decreased from 29% to 15% (p = 0.01), but the proportion of men with ED remained unchanged. The absence of sexual activity was associated with pretransplant sexual inactivity (p = 0.001), age (p = 0.008), cardiovascular disease (p = 0.03), use of diuretics (p = 0.04), anticoagulants (p = 0.001), statins (p = 0.01) and treatment for diabetes (p = 0.03). Cardiovascular disease (p = 0.05), posttransplantation diabetes (p = 0.04), alcohol abuse (p = 0.03), antidepressants (p = 0.05) and angiotensin II receptor blockers (p = 0.05) were associated with having ED after LT. Having a low TSS score was associated with a history of endocrine disease (p = 0.03), antidepressants (p = 0.04) and diuretics (p = 0.03). In conclusion, LT improves sexual activity, but ED is multifactorial and remains a long-term condition in the majority of patients. Key words: End-stage liver disease, erectile dysfunction, liver transplantation, questionnaire, sexual activity Received 28 April 2008, revised 06 August 2008 and accepted for publication 18 August 2008 Introduction The increase in liver transplantation (LT) procedures over the last years and the increased survival following LT (1) have rendered quality-of-life issues, in particular sexuality, a new challenge of care (2). Erectile dysfunction (ED), defined as the inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance is a major domain of male sexuality (3). However, data concerning ED in male LT patients are, so far, limited. Most existing studies have used small samples, nonvalidated questionnaires, have concerned both genders (4 6), or have been published in the non-english literature (4). Moreover, few studies have assessed whether ED is a long-term problem after LT or if ED resolves overtime (5). All in all, risk factors for ED in LT patients are largely unknown. A major problem in determining risk factors in this population is that patients who are candidates for LT often have diabetes (7 11), hypertension (9,11,12), cardiovascular disease (8,9,11) and are affected by alcohol intake and cigarette smoking (13,14), all conditions also identified as risk factors for ED in community-based studies. A better understanding of coexisting chronic medical conditions and drug exposures that increase the risk of ED in LT patients is essential in developing adaptive strategies. Sexual satisfaction from erection is an important issue that is difficult to evaluate because it involves perceptual life domains; however, satisfaction scales have recently been developed to accurately assess this issue (15). This study is the first to evaluate ED and satisfaction with erection using validated scales in men with LT. It also assesses risk factors in erectile function after LT. Answering these questions will help us determine what specific management strategies are needed for patients after LT, and when the strategies should be implemented. Patients and Methods Patients Male patients with a LT, from the University Hospital of Toulouse (France), were recruited to participate in a cross-sectional cohort questionnaire to evaluate erectile function after LT. Eligible patients were adult men who had received a LT at least 1 year before, and had completed a pretransplant questionnaire on erectile function. From 1986 to 2006, 470 LTs in 433 patients were performed at our institution (283 men, 150 women). Among the 283 men, 99 patients had died at the time of the survey (35%). Other 2580

2 Erectile Dysfunction in Liver Transplant Patients screening and diagnosis of ED and severity of ED in clinical practice and research. A review of SHIM-related literature in 2005, found that the SHIM was an integral measure in at least 21 studies on the prevalence of ED and 23 studies on the efficacy of ED interventions (18). Figure 1: Time elapsed between LT and the survey. exclusions were 25 men who had more than one transplant (9%), 6 who had cirrhosis in their LT (2%), 24 for whom follow-up after LT was shorter than 12 months (8%) and 6 who were younger than 18 or older than 70 years (2%). This left a total of 123 eligible men who were asked to participate in the survey. Survey The survey was developed at a mean time posttransplant of 5.4 ± 4.0 years (min max: ; median: 4). The duration of the time between LT and posttransplant survey is summarized in Figure 1. An introductory letter was mailed to the patients that included the questionnaire, the names of research contact persons, and phone numbers for further information. Evaluations were completed by mail and a reminder letter was sent if the questionnaire was not returned within 4 weeks. Those who completed the questionnaire were considered to be participants in the study. Only 25 patients refused to take part (participation rate: 79.7%). We then obtained information concerning liver disease and transplantation, as well as erectile function after LT from 98 patients. We checked that there were no differences in demographic, medical or surgical parameters between responders and nonresponders (data not shown). Measures The questionnaire used for the posttransplant evaluation of erectile function was the same as that used at pretransplant to ensure meaningful comparisons could be made. The questionnaires given were the five-item International Index of Erectile Function (IIEF-5, also known as the sexual health inventory for men (SHIM)), the patient-baseline treatment satisfaction scale (TSS), plus a few additional questions concerning changes overtime (these were selected after a process of item pretesting). The IIEF-5, also called SHIM is an abbreviated version of the IIEF, using five questions with the highest discriminating power to diagnose ED (16). It consists of four items on erectile function, and one item on intercourse satisfaction (Appendix 1). Item responses are scored on a five-point scale. IIEF scores are obtained by calculating the sum of the item responses: with totals of 5 being the worst possible score and 25 being the best. In order to analyze the severity of ED, we used the accepted classes: a score of 5 to 7 defined severe ED, 8 to 11 moderate ED, 12 to 16 mild to-moderate ED,17to21mildEDandascoreabove22noED(16).LiketheIIEF,the IIEF-5 has been translated into 32 languages (in this study, we used the French version). Validity and sensitivity were analyzed in four large placebocontrolled trials. For a cutoff score of 21 or less for ED, sensitivity was 0.98 and specificity 0.88 (17). The IIEF-5 has become a widely used scale for The TSS was developed to provide a comprehensive insight into the sexual satisfaction of men with ED and of their partners (19). This multidimensional scale, which has good internal consistency, reliability and concurrent validity with the IIEF, is highly responsive to changes overtime, and is brief and practical to use (19). In this study, we used the patient-baseline module of TSS (Appendix 2). The domains assessed are ease of erection (item 1), erectile function satisfaction (items 2, 3 and 4), pleasure from sexual activity (item 5), Satisfaction with orgasm (item 6) and confidence to complete sexual activity (items 7, 8). Like IIEF-5, item responses for TSS are also scored on a five-point scale. TSS scores are computed by taking the mean of each item s responses and converting the result to a scale, with 0 being the worst possible score and 100 being the best (19). Men who were lacking the opportunity for sexual activity and those not expressing their sexuality with penetration were considered as sexually inactive. Statistical methods Statistical analyses were done using STATA SE 8.2 R (State Corporation College Station, TX) and R version using a 95% confidence interval. Descriptive statistics were performed for all studied variables with a normality test for all quantitative variables. Inter-group comparisons were performed using the chi-squared (or Fisher s exact) test for qualitative variables, and the Mann Whitney test for quantitative variables. As the IIEF and TSS scores did not follow a normal distribution, except for the TSS score after transplantation (normality test: IIEF before LT, p = 0.02; IIEF after LT, p = 0.01; TTS before LT, p = 0.002; TSS after LT, p = 0.60), nonparametric tests were used. Comparisons of scores (IIEF, TSS) before and after LT were performed using the Wilcoxon test. Associations between IIEF score (or TSS score) and the studied variables were sought with the Mann Whitney test and correlations by the Spearman test. Time to onset of ED was assessed using the Kaplan Meier method after we had tested that our data conformed to the proportional hazards hypothesis. The log-rank test was used for inter-group comparisons. Results Table 1 summarizes the characteristics of the population. As a result of an extension of the indication of LT for hepatocarcinoma in our center (five tumors at most, with the largest being 5 cm) (20), primary diagnosis in patients presenting for LT was hepatocarcinoma in 46 cases (46.9%). Less frequent diagnoses were hepatitis B and/or C in 9 cases (9.2%), alcohol abuse in 28 cases (28.6%), alcohol abuse + hepatitis C in 8 cases (8.2%) and other etiologies (Caroli disease, sclerosing cholangitis, autoimmune hepatitis, cryptogenic cirrhosis) in 7 cases (7.1%). Table 2 shows treatments received by the patients after LT. Sexual activity At the time of the survey, 65 patients (66%) who were sexually active before LT, continued to be sexually active, 5 patients (5%) who were sexually active before LT become sexually inactive, 10 patients (10%) who were sexually American Journal of Transplantation 2008; 8:

3 Huyghe et al. Table 1: Characteristics of the population before and after transplantation Before After transplantation transplantation N = 98 N (%) N (%) Age Mean ± SD 52.9 ± ± 9.40 Median Min max Diabetes 21 (21) 60 (61.2) Cardiovascular disease 1 32 (32.6) 46 (46.9) Dyslipidemia 8 (8) 67 (68.4) Hypertension 25 (25.5) 94 (95.9) Tobacco 55 (56) Alcohol abuse 55 (57) 15 (15.3) Endocrinological disease 9 (9) 11 (11.2) Neurological disease 6 (6) 17 (17.5) Hepatic encephalopathy 24 (24.5) Surgery possibly resulting in ED 9 (9) 7 (7.1) ED = erectile dysfunction. 1 Cardiovascular diseases = thrombophlebitis or pulmonary embolism, obesity, valvulopathy, trouble with rhythm or conduction, angina pectoris, cardiac insufficiency, atherosclerosis, myocardial infarction, cerebral vascular infarction. inactive before LT continued to be sexually inactive and 18 patients (19%) who were sexually inactive before LT became sexually active. Overall, the proportion of sexually inactive patients decreased from 29% (before LT) to 15% after LT (p = 0.01). Sexually inactive patients before LT were significantly more likely to remain sexually inactive after LT (p = 0.001). Other Table 2: Treatments after LT Number pts Percentage Cardiovascular treatments Angiotensin II receptor blockers Calcium-channel blockers Diuretics Alpha blockers Beta blockers Antiarrhythmics Angiotensin-converting enzyme inhibitors Vasodilators Anticoagulants/NSAIDs Psychotropic treatments Antidepressants Anxiolytics Antipsychotics Hypnotics Immunosuppressive treatments Tacrolimus Mycophenolic acid Prednisone Ciclosporine microemulsion Sirolimus NSAIDs = nonsteroidal antiinflammatory drugs. variables associated with the absence of sexual activity after LT were age(p = 0.008), a history of cardiovascular disease (p = 0.03), the use of diuretics (p = 0.04), anticoagulant/nonsteroidal antiinflammatory drugs (p = 0.001), statins (p = 0.01) or treatment for diabetes (p = 0.03). The type, number and associations of immunosuppressive drugs were not correlated with sexual activity after LT. Quality of erections Except for the aforementioned decrease in the proportion of sexually inactive patients, the only significant change was an increase in the proportion of patients with moderate ED (from 5% before LT to 22% after LT). Other categories remained relatively stable (i.e. patients with severe ED: 7% before LT vs. 8% after LT; and patients with mild to moderate ED and above: 59% before LT vs. 55% after LT). All the patients who became sexually inactive after LT had an IIEF score of <16 before LT. A great majority of patients (15,18) who were sexually inactive before LT, and who became sexually active after LT, had moderate or severe ED. Table 3 summarizes the associations between medical conditions and treatments, and posttransplantation IIEF scores. Significant factors associated with having a low IIEF score after LT include history of cardiovascular disease (p = 0.05), occurrence of posttransplantation diabetes (p = 0.04), alcohol abuse (p = 0.03), antidepressant usage (p = 0.05) and angiotensin II receptor blocker treatment (p = 0.05). There were no correlations between immunosuppressive treatments (type of immunosuppressant, number of immunosuppressants or immunosuppressive regimen). There was a positive association between posttransplant IIEF score and the duration of the delay between transplantation and posttransplant evaluation (Spearman s rho = 0.24, p = 0.03). Evolution of ED overtime After LT, 58 of the 98 patients perceived an improvement in erectile function. The median delay between the date of LT and the occurrence of an improvement (estimated by the Kaplan Meier method) was 18 months (95% CI = 12 60; Figure 2A). The log-rank test shows a significant association between delayed improvement of erectile function and posttransplantation diabetes (24 months in diabetic patients vs. 12 months in nondiabetic patients, p = 0.03; Figure 2B), and treatment by angiotensin II receptor blockers (p = 0.03; Figure 2C). In contrast, patients who had liver failure of viral origin (HBV or HCV) had better (80% of cases) and faster improvement (6 months vs. 18 months; Figure 2D). Sexual satisfaction (TSS score) The global TSS scores (%) is 52.0 ± 27.8 after LT, versus 50.6 ± 30.8 before LT (Wilcoxon test, p = 0.81). Mean TSS scores by domain were: 2.1 ± 1.2 (/4) for ease of 2582 American Journal of Transplantation 2008; 8:

4 Table 3: Factors associated with ED (IIEF score) after LT Erectile Dysfunction in Liver Transplant Patients Mean ± SD Median Min max z-value p-value (Mann Whitney) Etiology Cancer No 15.2 ± Yes 15.9 ± Virus (HCV or HBV) No 15.3 ± Yes 17.7 ± Alcohol abuse No 15.9 ± Yes 14.5 ± Alcohol abuse + HVC No 15.6 ± Yes 14.2 ± Others No 15.5 ± Yes 15.5 ± Cardiovascular disease before LT No 14.9 ± Yes 12.0 ± Diabetes before LT No 16.2 ± Yes 12.9 ± Cardiovascular disease after LT No 15.4 ± Yes 15.9 ± Diabetes after LT No 17.2 ± Yes 14.4 ± Dyslipidemia No 15.5 ± Yes 15.6 ± Hypertension No 16 ± Yes 15.6 ± Tobacco No 16.8 ± Yes 14.6 ± Alcohol abuse after LT No 16.6 ± Yes 12.6 ± Endocrine disease No 15.5 ± Yes 16.3 ± Neurological disease No 15.3 ± Yes 16.2 ± Surgery at risk of ED No 15.5 ± Yes 15.1 ± Antidepressants No 16.2 ± Yes 12.5 ± Anxiolytics No 15.8 ± Yes 15.2 ± Antipsychotics No 15.9 ± Yes 13.2 ± Angiotensin II receptor blockers No 16.3 ± Yes 13.2 ± Continued. American Journal of Transplantation 2008; 8:

5 Huyghe et al. Table 3: Continued. Mean ± SD Median Min max z-value p-value (Mann Whitney) Calcium-channel blockers No 15.0 ± Yes 17.2 ± Diuretics No 15.8 ± Yes 14.6 ± Alpha blockers No 15.8 ± Yes 14.6 ± Beta blockers No 15.0 ± Yes 17.0 ± Angiotensin-converting enzyme inhibitors No 14.9 ± Yes 17.8 ± Anticoagulants/NSAIDs No 15.6 ± Yes 15.3 ± Statins No 15.7 ± Yes 15.2 ± Immunosuppressants Tacrolimus No 14.0 ± Yes 16.1 ± Mycophenolic acid No 15.0 ± Yes 16.0 ± Prednisone No 16.2 ± Yes 14.9 ± Ciclosporine microemulsion No 15.6 ± Yes 14.0 ± Sirolimus No 15.9 ± Yes 13.0 ± ED = erectile dysfunction; LT = liver transplant, HBV = hepatitis B virus;hcv = hepatitis C virus; NSAIDs = nonsteroidal antiinflammatory drugs. erection, 1.9 ± 1.2 (/4) for satisfaction with erectile function, 2.3 ± 1.2 (/4) for pleasure, 2.1 ± 1.2 (/4) for satisfaction with orgasm and 1.9 ± 1.3 (/4) for sexual confidence. Significant factors associated with having a low TSS score after LT (Table 4) were a history of endocrine disease (p = 0.03), antidepressant treatment (p = 0.04) and diuretic treatment (p = 0.03). There were no correlations between TSS score after LT and the type of immunosuppressive drug, the number of immunosuppressive drugs, and the immunosuppressive regimen. Discussion In this study, we observed that if an improvement in sexual function occurs following LT, it is usually modest: the only clear positive impact of LT for male sexuality was an increase in the proportion of sexually active men (by 14%). In contrast, the quality of erection did not seem to be favorably impacted by LT, as the proportion of patients with a IIEF score >12 remained unchanged. Ho et al. found that there was an increase in number of sexual problems after LT (47% vs. 24% before LT). However, their study was not limited to male patients and the results were not detailed by gender. Moreover, their method used to evaluate erectile function only gave information on how often the patients had ED, and mistakenly concluded that patients who stated having erectile problems a few times or sometimes had ED (5). Sorrell et al. also reported a trend of more frequent ED problems happening after LT than before; however, the small number of men who answered their questionnaire about ED (n = 25) does not enable further analysis (6). Also, these two studies did not take into account changes in sexual activity after LT. Based 2584 American Journal of Transplantation 2008; 8:

6 Erectile Dysfunction in Liver Transplant Patients Figure 2: Kaplan Meier representation of improvement in erectile function after LT; (A) the overall population; (B) posttransplantation diabetes; (C) angiotensin II receptor blockers; (D) viral origin. on our observations that men who become sexually active after LT often have ED, the assessment of erectile function without considering this group of newly active patients may lead to biased results. However, all the data confirm that men who have received a LT are at high risk for ED (85.5% after LT in our study). Therefore, this population should benefit from interventions on sexuality. Those patients who perceived an improvement in erectile function after LT declared that it occurred relatively late: on average 18 months after LT. We identified that diabetic patients and patients treated with angiotensin II receptor blockers had a delayed onset of improvement of erectile function. Recovery of health status may explain this phenomenon because a meta-analysis of six studies regarding Karnofsky performance status (KPS) after LT showed that improvement of KPS was only significant after 1-year post- LT (p < ). The KPS status at 1 year was qualified as able to perform normal activities with some effort, has minor symptoms, whereas, at 2 years it was able to perform normal activities, but has minor complaints (2). These data give important clues to understanding that a delay longer than 1 year is often necessary to observe an improvement in erectile function. By asking their patients what, in their opinion, was the main contributing factor to their sexual dysfunction, Ho et al. noted that 36% of patients thought that their trouble was related to medications versus 33% to liver diseases, and 10% to depression (5). We cautiously investigated the impact of treatments on erectile function because LT patients often have multiple treatments (notably immunosuppressants, cardiovascular medications, psychotropic drugs). We did not observe any significant differences according to the type of immunosuppressants, the association of immunosuppressants used or the number of immunosuppressants prescribed. m-tor inhibitors (sirolimus, everolimus) have proved to have effects on the sex-hormone level in kidney transplant patients (21,22), as well as heart transplant patients (23). However, since only nine patients had received sirolimus, our study cannot rule out an effect of this treatment on male erectile function. We observed that treatment with angiotensin II receptor blockers is associated with an increased risk of developing an ED, and that diuretic treatment after LT is also a factor associated with lower sexual satisfaction. Other cardiovascular treatments with a lower risk of ED could be proposed to LT patients who want to conserve sexual function. It is interesting to note the high frequency of psychotropic treatments: 38% of patients had anxiolytic, 16% antidepressant and 12% antipsychotic treatments. Only antidepressant treatments were linked with a lower TSS score. However, because it is well known that depression typically involves a lack of satisfaction, it is impossible to differentiate what is related to the disease and what to the treatment. Limitations As part of a program to improve the sexual health of men with a LT, we designed this study to target those within this population who were concerned about sexual functionality. However, although this study gives a comprehensive overview of erectile function in this population, it does not capture the entire picture. Those groups with a presumed high prevalence of sexual inactivity, that is, men older than 70 years, and those whose general health status was too altered, were excluded. Teens were also not included, as their sexual activity and problems may significantly differ from those of adults. American Journal of Transplantation 2008; 8:

7 Huyghe et al. Table 4: Factors associated with lowered sexual satisfaction (TSS score) after LT Mean ± SD Median Min Max z-value p-value (Mann Whitney) Etiology Cancer No 52.9 ± Yes 50.2 ± Virus (HCV or HBV) No 50.4 ± Yes 64.6 ± Alcohol abuse No 51.9 ± Yes 50.9 ± Alcohol abuse + HVC No 51.6 ± Yes 51.1 ± Others No 51.8 ± Yes 48.5 ± Cardiovascular disease before LT No 54.9 ± Yes 45.4 ± Diabetes before LT No 53.6 ± Yes 43.9 ± Cardiovascular disease after LT No 53.1 ± Yes 50.7 ± Diabetes after LT No 58.4 ± Yes 47.7 ± Dyslipidemia No 58.4 ± Yes 49.2 ± Hypertension No 37.9 ± Yes 52.6 ± Tabacco No 57.0 ± Yes 48.2 ± Alcohol abuse after LT No 54.8 ± Yes 48.8 ± Endocrine disease No 51.3 ± Yes 56.7 ± Neurological disease No 51.6 ± Yes 51.0 ± Surgery at risk of ED No 51.8 ± Yes 48.1 ± Antidepressants No 54.5 ± Yes 39.5 ± Anxiolytics No 54.1 ± Yes 48.4 ± Antipsychotics No 52.6 ± Yes 48.0 ± Continued American Journal of Transplantation 2008; 8:

8 Table 4: Continued. Erectile Dysfunction in Liver Transplant Patients Mean ± SD Median Min max z-value p-value (Mann Whitney) Angiotensin II receptor blockers No 55.2 ± Yes 42.0 ± Calcium-channel blockers No 49.3 ± Yes 60.1 ± Diuretics No 55.6 ± Yes 40.3 ± Alpha blockers No 52.6 ± Yes 49.3 ± Beta blockers No 50.1 ± Yes 56.2 ± Angiotensin-converting enzyme Inhibitors No 50.0 ± Yes 57.8 ± Anticoagulants/NSAIDs No 55.6 ± Yes 42.6 ± Statins No 54.0 ± Yes 48.4 ± Immunosuppressants Tacrolimus No 47.4 ± Yes 53.6 ± Mycophenolic acid No 49.5 ± Yes 53.7 ± Prednisone No 53.6 ± Yes 50.0 ± Ciclosporine microemulsion No 52.1 ± Yes 47.1 ± Sirolimus No 52.1 ± Yes 50.6 ± ED = erectile dysfunction; LT = liver transplant; NSAIDs = nonsteroidal antiinflammatory drugs; HBV = hepatitis B virus; HCV = hepatitis Cvirus. The evaluation mainly focused on erectile function as this was the main domain within the short version of the IIEF questionnaire (IIEF-5). Therefore, a more comprehensive assessment of sexual function that includes other sexual domains should be conducted to further understand sexual problems and to determine effective interventions. The cross-sectional cohort design of the study resulted in three limitations. First, we could not ascertain if the factors identified with lower erectile scores were true risk factors. Second, the delay between LT and the survey varied from one patient to another. Therefore, we were unable to thoroughly evaluate the exact time-scales within which any erectile-function changes occurred. For example, our methodology did not explore early changes in erectile function, such as improvement in erectile within the first few days of transplantation. Third, a cohort effect cannot be totally ruled out. However, as the criteria for selection and treatment did not change over the period of study, we consider that such a bias is unlikely to explain the changes that occurred in this series. Even though this is the largest series to focus on the sexual problems of LT patients, the size of this population did not highlight any significant factors in the multivariate analyses. It is well known that ED is multifactorial and, because of the disease and its treatment, men with a LT cumulate numerous potential risk factors for ED. Therefore, American Journal of Transplantation 2008; 8:

9 Huyghe et al. factors that were significant in univariate analyses need to be validated within a larger series as established risk factors. In conclusion, because the literature is limited regarding the sexual health of men with a LT, these preliminary data are valuable in helping us understand ED and to enable us to promote adequate interventions within this population. However, due to the cross-sectional cohort design of this study, our conclusions need further validation, which could be done in a prospective trial, or within a larger cohort study. Conclusion Patients who are candidates for LT are a population characterized by a high frequency of lack of sexual activity, and by a high prevalence of ED. LT improves sexual activity, but ED remains a long-term condition in the majority of patients. Satisfaction with sexuality also remains static after LT. If improvement occurs, it usually happens after more than 18 months. Therefore, LT patients should be followed up adequately before LT, and for at least the first year following LT (ideally for 2 years). Specific management of sexual problems should be promoted, including urological as well as psychosexual approaches, notably in the patients with cardiovascular disease or diabetes, and in case of treatment by antidepressants, diuretics or angiotensin II receptor blockers. Acknowledgment We thank Anas Zairi and Manuela Klapouszczak for their help. References 1. Said A, Einstein M, Lucey MR. Liver transplantation: An update Curr Opin Gastroenterol 2007; 23: Bravata DM, Olkin I, Barnato AE, Keeffe EB, Owens DK. Healthrelated quality of life after liver transplantation: A meta-analysis. Liver Transpl Surg 1999; 5: NIH Consensus development panel on impotence. JAMA 1993; 270: Coelho JC, Matias JE, Zeni Neto C, de Godoy JL, Canan Júnior LW, Jorge FM. Sexual function in males undergoing liver transplantation. Rev Assoc Med Bras 2003; 49: Ho JK, Ko HH, Schaeffer DF et al. Sexual health after orthotopic liver transplantation. Liver Transpl 2006; 12: Sorrell JH, Brown JR. Sexual functioning in patients with end-stage liver disease before and after transplantation. Liver Transpl 2006; 12: Grover SA, Lowensteyn I, Kaouache M et al. The prevalence of erectile dysfunction in the primary care setting: Importance of risk factors for diabetes and vascular disease. Arch Intern Med 2006; 166: Saigal CS, Wessells H, Pace J, Schonlau M, Wilt TJ. Urologic diseases in America project predictors and prevalence of erectile dysfunction in a racially diverse population. Arch Intern Med 2006; 166: Kleinman KP, Feldman HA, Johannes CB, Derby CA, McKinlay JB. A new surrogate variable for erectile dysfunction status in the Massachusetts male aging study. J Clin Epidemiol 2000; 53: Bacon CG, Mittleman MA, Kawachi I, Giovannucci E, Glasser DB, Rimm EB. Sexual function in men older than 50 years of age: Results from the Health Professionals Follow-up Study. Ann Intern Med 2003; 139: Ponholzer A, Temml C, Mock K, Marszalek M, Obermayr R, Madersbacher S. Prevalence and risk factors for erectile dysfunction in 2869 men using a validated questionnaire. Eur Urol 2005; 47: Selvin E, Burnett AL, Platz EA. Prevalence and risk factors for erectile dysfunction in the US. Am J Med 2007; 120: Keene LC, Davies PH. Drug-related erectile dysfunction. Adverse Drug React Toxicol Rev 1999; 18: Lue TF. Erectile dysfunction. N Engl J Med 2000; 342: Kubin M, Trudeau E, Gondek K, Seignobas E, Fugl-Meyer AR. Early conceptual and linguistic development of a patient and partner treatment satisfaction scale (TSS) for erectile dysfunction. Eur Urol 2004; 46: Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Peña 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: Cappelleri JC, Siegel RL, Glasser DB, Osterloh IH, Rosen RC. Relationship between patient self-assessment of erectile dysfunction and the sexual health inventory for men. Clin Ther 2001; 23: Cappelleri JC, Rosen RC. The sexual health inventory for men (SHIM): A 5-year review of research and clinical experience. Int J Impot Res 2005; 17: DiBenedetti DB, Gondek K, Sagnier PP, Marquis P, Keininger D, Fugl-Meyer AR. The treatment satisfaction scale (TSS): A multidimensional instrument for the assessment of treatment satisfaction for erectile dysfunction patients and their partners. Eur Urol 2005; 48: Michel J, Suc B, Montpeyroux F et al. Liver resection or transplantation for hepatocellular carcinoma? Retrospective analysis of 215 patients with cirrhosis. J Hepatol 1997; 26: Lee S, Coco M, Greenstein SM, Schechner RS, Tellis VA, Glicklich DG. The effect of sirolimus on sex hormone levels of male renal transplant recipients. Clin Transplant 2005; 19: Huyghe E, Zairi A, Nohra J, Kamar N, Plante P, Rostaing L. Gonadal impact of target of rapamycin inhibitors (sirolimus and everolimus) in male patients: An overview. Transpl Int 2007; 20: Kaczmarek I, Groetzner J, Adamidis I et al. Sirolimus impairs gonadal function in heart transplant recipients. Am J Transplant 2004; 4: APPENDIX 1: IIEF-5 or SHIM Instructions Each question has five possible responses. Circle the number that best describes your own situation. Select only one answer for each question American Journal of Transplantation 2008; 8:

10 Over the past 4 weeks: Erectile Dysfunction in Liver Transplant Patients 1. How do you rate your confidence that you could keep an erection? Very low Low Moderate High Very high 2. When you had erections with sexual stimulation, how often were your erections hard enough for penetration (entering your partner)? Almost never or never A few times (much less Sometimes (about half the time) Most times (much more Almost always or always 3. During sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner? Almost never or never A few times (much less Sometimes (about half the time) Most times (much more Almost always or always 4. During sexual intercourse, how difficult was it to maintain your erection to completion of intercourse? Extremely difficult Very difficult Difficult Slightly difficult Not difficult 5. When you attempted sexual intercourse, how often was it satisfactory for you? Almost never or never A few times (much less Sometimes (about half the time) Most times (much more Almost always or always Information for Clinicians Scoring instructions Add the numbers corresponding to the answers for questions one through five. A score at 21 or less defines ED and is an indication of specialized consult. The SHIM score characterizes the severity of the patient s ED in the following manner: No ED Mild ED Mild-to-moderate ED 8 11 Moderate ED 5 7 Severe ED Score: APPENDIX 2: TSS QUESTIONNAIRE Patient-Baseline Module Instructions To answer the following questions, please think about the past 4 weeks only. Please check or mark an x in one box only per question. IMPORTANT: When answering the questions keep in mind that sexual activity includes intercourse, caressing, foreplay, masturbation, etc., sexual stimulation includes situations such as foreplay with a partner, looking at erotic pictures, etc. Over the past 4 weeks: 1. How easy was it for you to get an erection when stimulated? 2. How satisfied were you with the amount of time it took before you could get an erection? 3. How satisfied were you with how long your erections lasted? 4. How satisfied were you with the hardness of your erections? 5. How much pleasure did you get from your sexual activity? None A little Some A lot Extreme 6. How satisfied were you with your orgasms? 7. How confident did you feel about initiating sex? 8. How confident were you that you could complete your sexual activity? American Journal of Transplantation 2008; 8: