|Year : 2015 | Volume
| Issue : 1 | Page : 40-44
Prevalence and risk factors of erectile dysfunction among chronic hepatitis C male patients treated with pegylated interferon-α and ribavirin
Nagy Fawzy1, Hesham A Atia2, Sherif M Galal3, Jihan A Shawky3
1 Department of Psychiatry, Zagazig University, Zagazig, Egypt
2 Department of Internal Medicine, Zagazig University, Zagazig, Egypt
3 Department of Tropical Medicine, Zagazig University, Zagazig, Egypt
|Date of Web Publication||23-Mar-2015|
Department of Psychiatry, Zagazig University, Zagazig, Sharkya
Source of Support: None, Conflict of Interest: None
The aim of the study was to determine the prevalence and risk factors of erectile dysfunction (ED) among chronic hepatitis C male patients treated with pegylated interferon-α and ribavirin.
Patients and methods
The sample consisted of 85 male patients treated with pegylated interferon-α2a and ribavirin for 12 months, recruited from Tropical and Internal Medicine outpatients of Zagazig University Hospitals. ED was prospectively studied by International Index of Erectile Function questionnaire, depression was assessed by Hospital Anxiety and Depression Scale, and routine laboratory investigations in addition to serum total and free testosterone were evaluated before, during, and 6 months after treatment.
Prevalence of ED among chronic hepatitis C male patients was 40% (34 patients). There was significant deterioration of International Index of Erectile Function scores and Hospital Anxiety and Depression Scale with respect to basal values and a significant decrease in total and free testosterone with gradual improvement toward the end of treatment period. Emotional state and physical profiles were the most significant risk factors for sexual dysfunction.
ED is common among hepatitis C virus patients treated with pegylated interferon-α and ribavirin and it is multifactorial.
Keywords: hepatitis C, male patients, pegylated interferon-α, ribavirin, sexual dysfunction
|How to cite this article:|
Fawzy N, Atia HA, Galal SM, Shawky JA. Prevalence and risk factors of erectile dysfunction among chronic hepatitis C male patients treated with pegylated interferon-α and ribavirin. Egypt J Psychiatr 2015;36:40-4
|How to cite this URL:|
Fawzy N, Atia HA, Galal SM, Shawky JA. Prevalence and risk factors of erectile dysfunction among chronic hepatitis C male patients treated with pegylated interferon-α and ribavirin. Egypt J Psychiatr [serial online] 2015 [cited 2021 Jan 21];36:40-4. Available from: http://new.ejpsy.eg.net/text.asp?2015/36/1/40/153776
| Introduction|| |
Egypt reports the highest prevalence of hepatitis C virus (HCV) worldwide, ranging from 40% to more than 60% among regions and demographic groups (Lehman and Wilson, 2009). In addition, correlations between sexual dysfunction (SD) and sociodemographic, medical, biological, and psychological variables are also studied. Hepatitis C is commonly accompanied by fatigue and depression, followed by a decreased interest in sex. In addition, antiviral medications typically used to battle hepatitis C may cause SD and decreased libido. SD is the most frequently encountered side effect of many antidepressant medications used to treat the depression and anxiety associated with HCV combination treatment (Nicole, 2007). SD was reported to be more common in patients with chronic hepatitis C than in persons without known liver disease (Danoff et al., 2006). The recommended therapy for chronic hepatitis C, pegylated interferon and ribavirin for 24 or 48 weeks, has many known adverse side effects (Hoofnagle and Seeff, 2006). Common side effects of pegylated interferon and ribavirin therapy include nonspecific symptoms such as fatigue, muscle aches, headaches, low-grade fever, gastrointestinal symptoms such as nausea, abdominal pain, weight loss, poor appetite, bone marrow effects such as anemia, neutropenia, and thrombocytopenia, and psychological difficulties such as emotional lability, anxiety, depression, difficulty sleeping, and trouble concentrating (Fattovich et al., 1996; Fried, 2002). Sexual side effects are infrequently mentioned as a complication of pegylated interferon and ribavirin (Strader et al., 2004; Dienstag and McHutchison, 2006). Although sexual transmission has been an area of research in HCV-positive patients, sexual functioning of these patients receives very limited attention. In contrast, as psychosocial influences and pathological consequences of the disease might hamper sexual functioning in HCV-infected patients, it is possible to predict SDs in this population (Marumo et al., 2001). Supporting these premises in male patients, a high rate of erectile dysfunction (ED) was diagnosed in 39% of HCV-positive patients in comparison with 14% of control individuals (Ferri et al., 2002). Screening for SD and identifying its correlates is a step toward developing better insight into overall sexuality issues in HCV patients. The major aim of this preliminary study was to identify the point prevalence of SD in a sample of HCV-infected patients.
| Patients and methods|| |
The present study was conducted from January 2012 to January 2014 in the Departments of Tropical and Internal Medicine of Zagazig University Hospitals. Approval was obtained from the Institutional Review Board (IRB) and the Department of Psychiatry, Zagazig University. All patients with chronic HCV infection were diagnosed clinically, biochemically, and ultrasonographically. To be included in the study, male patients were required to complete full duration of treatment (12 months of pegylated interferon/ribavirin treatment and the negative PCR patients at 12 and 24 weeks), age should range from 25 to 45 years, and they should have compensated liver disease. Patients were excluded if they had history of psychiatric disorders, drug dependence, any medication rather than standard treatment for HCV, organic SD, or general physical disorders. Informed written consent was obtained from all participants; in addition, patients were subjected to a semistructured psychiatric interview and collection of sociodemographic data, physical, and sexual activity. The following investigations were evaluated before, during, and 6 months after treatment.
Detection of ED was performed using International Index of Erectile Function (IIEF) questionnaire (Cappelleri et al., 2000). The IIEF is a widely used, multidimensional self-report instrument for the evaluation of male sexual function. It has 15 items divided into five domains of sexual function: erectile function (six items), orgasmic function (two items), sexual desire (two items), intercourse satisfaction (three items), and overall satisfaction (two items). Subsequently, among men in a stable relationship who attempted sexual activity and intercourse, severity of ED was classified into five diagnostic categories: no ED (EF score = 26-30), mild ED (EF score = 22-25), mild to moderate (EF score = 17-21), moderate (erectile function (EF) score = 11-16), and severe (EF score = 6-10) (Cappelleri et al., 1999).
Detection of anxiety and depression among the studied patients was performed by Hospital Anxiety and Depression Scale (HADS). It was originally developed by Zigmond and Snaith (1983). The HADS is a 14-item scale that generates ordinal data. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression.
Testosterone analysis: A testosterone test checks the level of this male hormone (androgen) in the blood. Testosterone affects sexual features and development. In men, it is made in large amounts by the testicles; most of the testosterone in the blood is bound to a protein called sex hormone-binding globulin. Testosterone that is not bound ('free' testosterone) may be checked if a man or a woman is having sexual problems (Allan and Brett, 2012). Total testosterone was assayed by a solid-phase, competitive chemiluminescent enzyme immunoassay on an Immunolite 1000 analyzer (Immulite 1000, Immunoassay System). Free testosterone was estimated using radioimmune assay.
Routine laboratory investigations included complete blood picture, blood glucose, and liver and renal function tests.
Data were expressed as number and percentage for qualitative variables; other correlation was performed and analyzed by the personal computer using the statistical software program SPSS (version16) (SPSS Inc., 2007). P-value was considered significant if less than 0.05 and highly significant if less than 0.001.
| Results|| |
The present study reported sociodemographic characteristics of study groups as shown in [Table 1]. There was significant decrease in total and free testosterone reaching the lowest level at 12th week with gradual improvement toward the end of treatment period, and there is a significant reduction of IIEF scores with respect to basal values, with variable improvement for all administered items ([Table 2]). We detected a significant increase in HADS scores at 12th week then showing gradual improvement ([Table 3]). Total testosterone levels showed a significant increase in patients with sustained virological response (SVR) when compared with the relapsers, whereas free testosterone levels did not show any significant difference between the two groups 6 months after end of treatment; in addition, all items of IIEF scores and HADS showed a significant improvement in patients with SVR when compared with the relapsers ([Table 4] and [Table 5]). When we compared patients with SD with those without SD, we could not detect any significant difference between the two groups with respect to their hormonal profile, whereas emotional state and physical profiles showed significant deterioration in patients complaining of SD ([Table 6]).
|Table 2 IIEF and serum testosterone among the studied patients throughout the treatment|
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|Table 4 IIEF and serum testosterone among the studied patients 6 months after treatment|
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|Table 6 Comparison between patients with and without ED with respect to their hormonal, physical profi le, and emotional state throughout the treatment period|
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| Discussion|| |
Sexual health is separated into three elements: desire, function, and satisfaction. Persons may have high levels of sexual desire and normal sexual function but may be dissatisfied with their sexual life. In contrast, people may have declines in sexual function and desire but may not express diminished satisfaction occurring with age (Lindau et al., 2007).
The present study reported a decrease in sexual function in 40% of the patients. SD in chronic HCV patients treated with interferon-α and ribavirin has either psychological or organic origin (Dove et al., 2009). We observed a significant decline of total and free testosterone serum concentration within the normal range; this decrease reached the lowest level at 12th week with gradual improvement toward the end of treatment period. In addition, there was a significant deterioration of IIEF scores and HADS with respect to basal values, with variable improvement for all administered items.
Treatment with pegylated interferon and ribavirin in patients with chronic hepatitis C is associated with SD (Dove et al., 2009). This may be due to decrease in serum testosterone as a result of direct effects of pegylated interferon on the gonads or due to psychological influence of pegylated form on the patients, which can induce the partial impairment of sensation of sexual desire and satisfaction (Malaguarnera et al., 2001).
Corssmit et al. (2000) and Kraus and colleagues confirmed the previous data and assumed that the observed testosterone decrease in those patients is not mediated by alteration of the pituitary-testicular axis. However, they cannot exclude this possibility as they did not analyze gonadotropin secretion pulsatility.
Psychological influence of pegylated interferon on the patients could justify the partial impairment of sensation linked to sexual behavior such as desire and satisfaction as it crosses blood-brain barrier without structural changes and may modulate endorphin receptors (Dove et al., 2009). The majority of Egyptian patients considered that HCV is lethal virus and the patient behaves as dying persons, and this consideration increases the risk for depression. Another possibility is that the relationship between depressive symptoms and pegylated interferon/ribavirin treatment response may be related to bidirectional neuroimmune pathways that are involved in immune system and nervous system regulation (Herbert and Cohen, 1993). Moreover, usage of selective serotonergic reuptake inhibitors for depressive disorders in those patients can act on 5-HTz receptors that control the peripheral erectogenesis, sexual desire, and satisfaction; this could be treated by phosphodiesterase type-5 inhibitor (Nurnberg and Hensley, 2003).
Total testosterone levels in our study showed a significant increase among patients with SVR. Total testosterone levels can be affected by albumin and sex hormone-binding globulins levels (Christ-Crain et al., 2004), which may be responsible for this deceiving increase, as free testosterone levels did not show any significant increase in patients with SVR when compared with the relapser. In addition, we could not detect any significant difference between patients with SD when compared with those without SD with respect to their hormonal profile.
In this study, all items of IIEF scores and HADS showed a significant improvement in patients with SVR when compared with the relapser. Moreover, psychological and physical profiles showed significant deterioration in patients complaining of SD. Hence, it is obvious that emotional influence can affect sexual function and plays an important role in the development of this side effect including the attitude of patient's sexual partner toward the patient illness (Kraus et al., 2005; Malguarnera et al., 2008). In addition, we would like to mention a new player in the game, physical profile, which can affect the quality of life and sexual health in patients with pegylated interferon therapy (Dienstag and Ghany 2010) and can be improved with care of the general condition of the patient. Finally, we concluded that SD is common among HCV patients treated with pegylated interferon-α and ribavirin and it is multifactorial. However, the effect of drug on total and free testosterone seemed to be transient and did not reach pathological levels, whereas psychological and physical influence seemed to be more pronounced. In the future, it is recommended to study whether there is any difference between pegylated interferon-α2a and pegylated interferon-α2b or between monotherapy with interferon and dual therapy of interferon plus ribavirin with respect to this issue. In addition, a detailed study analyzing different items of IIEF score and correlating them with hormonal, psychological, and physical profiles is in trial to reach which profile is more affected from a simple questionnaire.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
| References|| |
Allan S (2012). Total testosterone or free testosterone? J Urol 187:1369.
Cappelleri JC, et al.
(1999). Diagnostic evaluation of the erectile function domain on the International Index of Erectile Function. Urology 54:346-351.
Cappelleri JC, Siegel RL, Osterloh IH, Rosen RC (2000). Relationship between patient self-assessment of erectile function and the erectile function domain of the International Index of Erectile Function. Urology 56:477-481.
Christ-Crain M, Meier C, Huber P, Zimmerli L, Trummler M, Muller B (2004). Comparison of different methods for the measurement of serum testosterone in the aging male. Swiss Medical Weekly 134:193-197.
Corssmit EP, Endert E, Sauerwein HP, Romijn JA (2000). Acute effects of interferon-alpha administration on testosterone concentrations in healthy men. Eur J Endocrinol 143:371-374.
Danoff A, Khan O, Wan DW, et al.
(2006). Sexual dysfunction is highly prevalent among men with chronic hepatitis C virus infection and negatively impacts health-related quality of life. Am J Gastroenterol 101:1235-1243.
Dienstag JL, McHutchison JG (2006). American Gastroenterological Association technical review on the management of hepatitis C. Gastroenterology 130:231-264.
Dienstag JL, Ghany MG (2010). Changes in quality of life and sexual health are associated with low-dose peginterferon therapy and disease progression in patients with chronic hepatitis C. Aliment Pharmacol Ther 31:719-734.
Dove LM, Rosen RC, Ramcharran D, Wahed AS, Belle SH, Brown RS, Hoofnagle JH (2009). Decline in male sexual desire, function, and satisfaction during and after antiviral therapy for chronic hepatitis C. Gastroenterology 137:873-884.
Fattovich G, Giustina G, Favarato S, et al.
(1996). A survey of adverse events in 11,241 patients with chronic viral hepatitis treated with alfa interferon. J Hepatol 24:38-47.
Ferri C, Bertozzi MA, Zignego AL (2002). Erectile dysfunction and hepatitis C virus infection. JAMA 8:698-699.
Fried MW (2002). Side effects of therapy of hepatitis C and their management. Hepatology 36(Suppl 1):S237-S244.
Herbert TB, Cohen S (1993). Depression and immunity: a meta-analytic review. Psychol Bull 113:472-486.
Hoofnagle JH, Seeff LB (2006). Peginterferon and ribavirin therapy for chronic hepatitis C. N Engl J Med 355:2444-2451.
Kraus MR, Schafer A, Bentink T, Scheurlen M, Weissbrich B, Al-Taie O, Seufert J (2005). Sexual dysfunction in males with chronic hepatitis C and antiviral therapy: interferon-induced functional andogram deficiency or depression? J Endocrinol 185:345-352.
Lehman EM, Wilson ML (2009). Epidemic hepatitis C virus infection in Egypt: estimates of past incidence and future morbidity and mortality. J Viral Hepat 16:650-658.
Lindau ST, Schumm LP, Laumann EO (2007). A study of sexuality and healthy among older adults in United Sates. N ENgl J Med 357:762-774.
Malaguarnera M, laurino A, Di Fazio I, Pistone G, Castorina M, Guccione N, Rampello L (2001). Neuropsychiatric effects and type of IFN alpha in chronic hepatitis C. J Interferon Cytokine Res 21:273-278.
Malguarnera M, Vicari E, Calogero A, Cammalleri L, Di Fazio I, Gargante MP, et al.
(2008). Sexual dysfunction in chronic hepatitis C virus patients treated with interferon alpha and ribavirin. J Interferon Cytokine Res 28:603-610.
Marumo K, Nakashima J, Murai M (2001). Age-related prevalence of erectile dysfunction in Japan: assessment by the International Index of Erectile Function. Int J Urol 8:53-59.
Nicole C (2007): How hepatitis C can affect a patient's sex life. www.hepatitiscentral.com/news/March
Nurnberg HG, Hensley PL (2003). Selective phosphodiesterase type-5 inhibitor treatment of serotonergic uptake inhibitor antidepressant-associated sexual dysfunction: a review of diagnosis, treatment and prevelance. CNS Spectr 8:194-202
Snow KK, Bonkovsky HL, Fontana RJ, Kim HY, Sterling RK, Bisceglie AM Di, et al.
(2010). Changes in quality of life and sexual health are associated with low-dose peginterferon therapy and disease progression in patients with chronic hepatitis C. Aliment Pharmacol Ther 31:719-734.
SPSS Inc. (2007). SPSS for Windows (Statistical Package for the Social Sciences), version 16.0. Chicago: SPSS Inc.
Strader DB, Wright T, Thomas DL, et al.
(2004). American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C. Hepatology 39:1147-1171.
Zigmond AS, Snaith RP (1983). The Hospital Anxiety and Depression Scale. Acta Psychiatrica Scandinavica 67:361-370.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]