ORIGINAL ARTICLE
Dysregulation of male sex hormones in chronic hepatitis C patients A. T. El-Serafi1,2, S. Osama3, H. El-Zalat4 & I. M. EL-Deen3 1 2 3 4
Faculty of Medicine, Suez Canal University, Ismaillia, Egypt; College of Medicine, University of Sharjah, Sharjah, UAE; Faculty of Science, Port-Said University, Port-Said, Egypt; Port-Said Tropical Hospital, Port-Said, Egypt
Keywords Androstenedione—dehydroepiandrosterone sulphate—hepatitis C—prolactin—testosterone Correspondence Dr. Ahmed Taher El-Serafi, M27-138, College of Medicine, Sharjah University City, Sharjah, UAE. Tel.: +971553798583; Fax: +97165585879; E-mail: [email protected] Accepted: February 24, 2015 doi: 10.1111/and.12425
Summary Chronic hepatitis C (HCV) infection is a serious problem all over the world and has a special importance in Egypt, where the prevalence of infection is 14.7% of population. In males, HCV is associated with sexual dysfunction and changes in the semen parameters. This study aimed at estimation of a panel of the most important related hormones in the serum of patients and illustration of their correlation to the routine laboratory investigations. The four studied hormones showed alteration in the patients in comparison with the controls. While androstenedione, prolactin and testosterone were significantly increased in patients, dehydroepiandrosterone sulphate was decreased. These changes in the hormones were not related to the liver functions, pathological grade or even viral load. We hypothesised a model of how HCV can induce these hormonal changes and recommended to add these hormones to the follow-up panel of male patients with HCV.
Introduction Chronic hepatitis C viral infection (HCV) is a worldwide serious health problem that is associated with morbidity and mortality. The life quality of the patients could be markedly affected prior to diagnosis, during treatment or with relapse and chronicity. Egypt is well known to have the highest prevalence of HCV in the world (Lavanchy, 2011). The most common genotype in Egypt is HCV 4a, which is refractory to treatment and associated with longterm complications (Quinti et al., 1997). The prevalence of HCV-infected patients in Egypt is about 14.7% and reaches 32% in middle-aged males, which make such health hazard as a national challenge (reviewed in Mohamoud et al., 2013). Extrahepatic manifestations are reported in 40–74% of patients with HCV. HCV may affect skin, eyes, joints, immune system, nervous system, kidneys and even male germinal cells (Blackard et al., 2006). HCV-related sexual problems are more common in males in comparison with females and are associated in many cases with erectile dysfunction which has an impact in their overall quality of life. Replicating HCV has been isolated from the CNS and correlated with changes in the neurotransmitter levels in the brain. At the mean time, 82
the antiviral drugs and elevated gamma glutamyl transferase may contribute to such dysfunction (Danoff et al., 2006; Foster, 2009). El-Aterbi et al. reported sexual dysfunction in males with chronic HCV infection in Egyptian patients. Onefifth to one-third of the participants complained from such a problem prior to treatment. Sexual dysfunction reached more than 70% during the treatment, particularly in patients over 40 years old. In addition, the affection of sexual activity varied in relation to the liver status (ElAtrebi et al., 2011). According to Hofny et al., about one-third of patients in mid-thirties were diagnosed with primary infertility. In addition, many semen parameters in patients diagnosed with HCV for more than a year were deteriorated. Such parameters included sperm count, abnormal forms and motility (Hofny et al., 2011). This study investigated the changes of the level of steroid hormones that directly affect the process of spermatogenesis as well as the male sexual desire and mood. The hormonal panel included testosterone, the key hormone in male pattern behaviour and sexual function; dehydroepiandrosterone sulphate (DHEA-S), which acts as precursor to testosterone and has androgenic effect on its own and androstenedione, the common precursor of sex hormones. In addition to prolactin, which is a peptide © 2015 Blackwell Verlag GmbH Andrologia 2016, 48, 82–86
Dysregulation of male sex hormones in HCV patients
A. El-Serafi et al.
hormone that is affected negatively by the testosterone level and which affects the maturation of sperms and sexual function (Gill-Sharma, 2009), normal level of prolactin is required by Sertoli cells for the expression of the follicular-stimulating hormone receptors, by germ cells for the spermatocyte–spermatid conversion and by the prostate to increase the androgen receptors, to concentrate the insulin-like growth factor I and its receptor as well as to increase the prostatic secretions (reviewed in Bole-Feysot et al., 1998). Subjects and methods This study has a cross-sectional, case–control, single-centre design. The subjects were 55 male patients with chronic hepatitis C and 21 matched controls. The patients were recruited from the hepatology clinic in The Health Insurance Hospital, Port-Said, Egypt. The control group included healthy volunteers who were matched with the patients’ group regarding the age and marital status. The diagnosis with HCV infection was confirmed using polymerase chain reaction, according to the policy of the Ministry of Health. Patients were chosen randomly, and their medical records were reviewed after obtaining their ethical consent. Venous blood samples were collected, and serum was kept in 20 °C. Serum was defrosted and used for the estimation of androstenedione, testosterone, DHEA-S and prolactin. These hormones were assayed using commercially available, solid phase, chemiluminescent enzyme immunometric assay kits on the automated system ‘Siemens Immulite’ according to the manufacturer’s guidelines and recommendations. The data were statistically analysed, and the statistical significance threshold was considered as 0.05. Results The patients and the control groups showed no statistical difference regarding the age distribution or the number of married versus single participants in both groups. There was no statistical difference between the subjects in the two groups regarding the haemoglobin level, fasting blood glucose, cholesterol, triglyceride or TSH levels as well as the INR, albumin and the levels of ALT, AST and alkaline phosphatase. The bilirubin levels, both total and direct, were significantly higher in the patients. The mean SD for total bilirubin was 1.1 0.7 mg dl 1 in patients and 0.6 0.2 mg dl 1 in controls, while direct bilirubin was 0.4 0.4 mg dl 1 in patients and 0.1 0.1 mg dl 1 in controls, which was expected in patients with chronic hepatitis (Table 1). The results of the investigated hormonal panel were summarised in Table 2. Briefly, androstenedione, © 2015 Blackwell Verlag GmbH Andrologia 2016, 48, 82–86
Table 1 Main laboratory findings for routine investigations in the two groups Patients (mean SD) ALT (IU dl 1) AST (IU dl 1) ALP (IU l 1) Hb (gm dl 1) INR TB (mg dl 1) DB (mg dl 1) FBS (mg dl 1) Albumin (gm dl 1) Cholesterol (mg dl 1) TSH (U ml 1) Triglycerides (mg dl 1)
34.6 32.6 166 14.5 1.2 1.1 0.4 105 5.3 176.3 1.66 145
21.4 20.6 63 2.3 0.09 0.7 0.4 18 0.5 48 0.9 100
Controls (mean SD) 40.9 29.3 98 14.0 1.1 0.6 0.1 94 4.4 157 0.9 129
34.4 18.5 74 1.0 0.06 0.2a 0.1b 13 0.4 28 0.2 49
P-value is
Dysregulation of male sex hormones in chronic hepatitis C patients A. T. El-Serafi1,2, S. Osama3, H. El-Zalat4 & I. M. EL-Deen3 1 2 3 4
Faculty of Medicine, Suez Canal University, Ismaillia, Egypt; College of Medicine, University of Sharjah, Sharjah, UAE; Faculty of Science, Port-Said University, Port-Said, Egypt; Port-Said Tropical Hospital, Port-Said, Egypt
Keywords Androstenedione—dehydroepiandrosterone sulphate—hepatitis C—prolactin—testosterone Correspondence Dr. Ahmed Taher El-Serafi, M27-138, College of Medicine, Sharjah University City, Sharjah, UAE. Tel.: +971553798583; Fax: +97165585879; E-mail: [email protected] Accepted: February 24, 2015 doi: 10.1111/and.12425
Summary Chronic hepatitis C (HCV) infection is a serious problem all over the world and has a special importance in Egypt, where the prevalence of infection is 14.7% of population. In males, HCV is associated with sexual dysfunction and changes in the semen parameters. This study aimed at estimation of a panel of the most important related hormones in the serum of patients and illustration of their correlation to the routine laboratory investigations. The four studied hormones showed alteration in the patients in comparison with the controls. While androstenedione, prolactin and testosterone were significantly increased in patients, dehydroepiandrosterone sulphate was decreased. These changes in the hormones were not related to the liver functions, pathological grade or even viral load. We hypothesised a model of how HCV can induce these hormonal changes and recommended to add these hormones to the follow-up panel of male patients with HCV.
Introduction Chronic hepatitis C viral infection (HCV) is a worldwide serious health problem that is associated with morbidity and mortality. The life quality of the patients could be markedly affected prior to diagnosis, during treatment or with relapse and chronicity. Egypt is well known to have the highest prevalence of HCV in the world (Lavanchy, 2011). The most common genotype in Egypt is HCV 4a, which is refractory to treatment and associated with longterm complications (Quinti et al., 1997). The prevalence of HCV-infected patients in Egypt is about 14.7% and reaches 32% in middle-aged males, which make such health hazard as a national challenge (reviewed in Mohamoud et al., 2013). Extrahepatic manifestations are reported in 40–74% of patients with HCV. HCV may affect skin, eyes, joints, immune system, nervous system, kidneys and even male germinal cells (Blackard et al., 2006). HCV-related sexual problems are more common in males in comparison with females and are associated in many cases with erectile dysfunction which has an impact in their overall quality of life. Replicating HCV has been isolated from the CNS and correlated with changes in the neurotransmitter levels in the brain. At the mean time, 82
the antiviral drugs and elevated gamma glutamyl transferase may contribute to such dysfunction (Danoff et al., 2006; Foster, 2009). El-Aterbi et al. reported sexual dysfunction in males with chronic HCV infection in Egyptian patients. Onefifth to one-third of the participants complained from such a problem prior to treatment. Sexual dysfunction reached more than 70% during the treatment, particularly in patients over 40 years old. In addition, the affection of sexual activity varied in relation to the liver status (ElAtrebi et al., 2011). According to Hofny et al., about one-third of patients in mid-thirties were diagnosed with primary infertility. In addition, many semen parameters in patients diagnosed with HCV for more than a year were deteriorated. Such parameters included sperm count, abnormal forms and motility (Hofny et al., 2011). This study investigated the changes of the level of steroid hormones that directly affect the process of spermatogenesis as well as the male sexual desire and mood. The hormonal panel included testosterone, the key hormone in male pattern behaviour and sexual function; dehydroepiandrosterone sulphate (DHEA-S), which acts as precursor to testosterone and has androgenic effect on its own and androstenedione, the common precursor of sex hormones. In addition to prolactin, which is a peptide © 2015 Blackwell Verlag GmbH Andrologia 2016, 48, 82–86
Dysregulation of male sex hormones in HCV patients
A. El-Serafi et al.
hormone that is affected negatively by the testosterone level and which affects the maturation of sperms and sexual function (Gill-Sharma, 2009), normal level of prolactin is required by Sertoli cells for the expression of the follicular-stimulating hormone receptors, by germ cells for the spermatocyte–spermatid conversion and by the prostate to increase the androgen receptors, to concentrate the insulin-like growth factor I and its receptor as well as to increase the prostatic secretions (reviewed in Bole-Feysot et al., 1998). Subjects and methods This study has a cross-sectional, case–control, single-centre design. The subjects were 55 male patients with chronic hepatitis C and 21 matched controls. The patients were recruited from the hepatology clinic in The Health Insurance Hospital, Port-Said, Egypt. The control group included healthy volunteers who were matched with the patients’ group regarding the age and marital status. The diagnosis with HCV infection was confirmed using polymerase chain reaction, according to the policy of the Ministry of Health. Patients were chosen randomly, and their medical records were reviewed after obtaining their ethical consent. Venous blood samples were collected, and serum was kept in 20 °C. Serum was defrosted and used for the estimation of androstenedione, testosterone, DHEA-S and prolactin. These hormones were assayed using commercially available, solid phase, chemiluminescent enzyme immunometric assay kits on the automated system ‘Siemens Immulite’ according to the manufacturer’s guidelines and recommendations. The data were statistically analysed, and the statistical significance threshold was considered as 0.05. Results The patients and the control groups showed no statistical difference regarding the age distribution or the number of married versus single participants in both groups. There was no statistical difference between the subjects in the two groups regarding the haemoglobin level, fasting blood glucose, cholesterol, triglyceride or TSH levels as well as the INR, albumin and the levels of ALT, AST and alkaline phosphatase. The bilirubin levels, both total and direct, were significantly higher in the patients. The mean SD for total bilirubin was 1.1 0.7 mg dl 1 in patients and 0.6 0.2 mg dl 1 in controls, while direct bilirubin was 0.4 0.4 mg dl 1 in patients and 0.1 0.1 mg dl 1 in controls, which was expected in patients with chronic hepatitis (Table 1). The results of the investigated hormonal panel were summarised in Table 2. Briefly, androstenedione, © 2015 Blackwell Verlag GmbH Andrologia 2016, 48, 82–86
Table 1 Main laboratory findings for routine investigations in the two groups Patients (mean SD) ALT (IU dl 1) AST (IU dl 1) ALP (IU l 1) Hb (gm dl 1) INR TB (mg dl 1) DB (mg dl 1) FBS (mg dl 1) Albumin (gm dl 1) Cholesterol (mg dl 1) TSH (U ml 1) Triglycerides (mg dl 1)
34.6 32.6 166 14.5 1.2 1.1 0.4 105 5.3 176.3 1.66 145
21.4 20.6 63 2.3 0.09 0.7 0.4 18 0.5 48 0.9 100
Controls (mean SD) 40.9 29.3 98 14.0 1.1 0.6 0.1 94 4.4 157 0.9 129
34.4 18.5 74 1.0 0.06 0.2a 0.1b 13 0.4 28 0.2 49
P-value is
