Frequency and Associated Factors of Erectile Dysfunction among Patients with Liver Cirrhosis in Parakou, Republic of Benin in 2022 ()
1. Introduction
Erectile dysfunction (ED) is defined as the inability to achieve or maintain a penile erection sufficient for full sexual intercourse [1] . It is one of the most common chronic diseases in men and its prevalence increases with age [2] . ED shares common risk factors with cardiovascular disease (lack of physical exercise, obesity, smoking, high cholesterol level and metabolic syndrome). Some factors are modifiable [3] . ED can be organic, psychogenic and mixed [1] . In the past, most cases of ED were considered to be of psychological origin, but nowadays organic causes are found in at least 80% of cases [4] . The causes of ED are variable and can include arterial, neurogenic, hormonal, cavernosal, iatrogenic and psychogenic disorders [2] .
End-stage liver disease (cirrhosis) is known to cause hormonal dysregulation in both men and women [5] . The pathogenesis of ED in patients with chronic liver disease remains multifactorial and poorly understood. Hypogonadism is secondary to a reduction in the synthetic function of the liver. Impaired hormone production, malnutrition, depression, consumption of alcohol and some medications can all contribute to the development of ED in this population [6] . ED is often under-diagnosed in this category of patients. Few data are available on ED in patients with chronic liver disease at the stage of cirrhosis [7] . The available studies were conducted in patients suffering from decompensated cirrhosis or awaiting a liver transplantation or suffering from alcoholic cirrhosis [8] . The severity of liver cirrhosis has been shown to correlate with the severity of ED [1] . It is under-diagnosed given its taboo character, especially in our context.
The prevalence of ED in the general population varies between 5% and 50% [9] . Recent studies show that the prevalence of ED in patients with liver cirrhosis is approximately 50% [7] . In Africa, few studies are available on ED among patients with liver cirrhosis. In Benin Republic, few studies have evaluated the frequency and factors associated with ED in patients with chronic liver disease, which explains the present study. The objective of this work is to study erectile dysfunction among subjects with cirrhosis in Parakou in 2022.
2. Patients and Methods
2.1. Type and Period of Study
This was a descriptive and analytical cross-sectional study with prospective data collection, conducted from February 1 to June 30, 2022.
2.2. Study Sites
The study took place in the internal medicine department of the Regional Teaching Hospital of Borgou-Alibori (CHUD-B/A) and in the hepato-gastroenterology unit of the Military Teaching Hospital (HIA-CHU) in Parakou.
2.3. Study Population
It consisted of patients with liver cirrhosis followed up in the internal medicine department of CHUD/B-A and in the hepato-gastroenterology unit of HIA-CHU.
2.4. Inclusion Criteria
Any man with cirrhosis regardless of the cause and having given his informed verbal consent was included.
2.5. Exclusion Criteria
Any man with cirrhosis who had not performed a minimum biological tests allowing calculation of the Child Pugh score and/or any subject with ED before the diagnosis of cirrhosis was excluded. Comatose patients were also excluded.
2.6. Judgment Criteria
· Diagnosis of cirrhosis
The positive diagnosis of cirrhosis was non-invasive, based on a range of clinical, biological and morphological arguments, namely:
o Signs of portal hypertension (abdominal collateral circulation, splenomegaly, thrombocytopenia, portal vein dilatation, recanalized umbilical vein).
o Signs of liver failure (gynecomastia, palmar erythema, Terry’s nails, drop in prothrombin time, hypoalbuminemia).
o Changes in the hepatic appearance (hard and painless hepatomegaly with a firm lower edge, a granular anterior surface, atrophy, dysmorphia, heterogeneous appearance with irregular contours on ultrasound).
o Aspartate aminotransferase to Platelet Ratio Index (APRI) score ≥ 2.
In terms of etiological diagnosis, cirrhosis was caused by hepatitis B when the HBs antigen was positive. The hepatitis C virus was incriminated when the anti-HCV antibody was positive and the HCV RNA was detectable. When the auto-antibodies were detected, the diagnosis of autoimmune cirrhosis was made. Cirrhosis was assumed to be of alcoholic origin when: 1) the subject consumed more than 30 grams of alcohol per day; 2) there were clinical and biological signs of alcoholic consumption; 3) hepatitis B and C serologies were negative.
· Evaluation of the prognosis of cirrhosis
Child-Pugh score was used. It is based on 5 parameters: bilirubin, albumin, prothrombin time (PT), ascites and encephalopathy.
· Diagnosis and assessment of ED severity
The International Index of Erectile Function-5 (IIEF-5) was used. This is a validated score, aimed at determining the presence of ED severity in men [10] . This questionnaire assesses sexual function over the past 6 months.
2.7. Sampling
· Sample size
The size of our sample corresponded to the number of patients with liver cirrhosis seen in consultation or hospitalization in the two hospitals during the study period.
· Sampling technique
All patients with cirrhosis seen in consultation or in hospital who met the inclusion criteria were recruited.
2.8. Data Collection
· Data collection technique and tool
The tool used to collect the information was a questionnaire. The information was collected during a semi-structured individual interview. A part of the questionnaire was designed by the initiators of this study. Some standard and recognized scores have been added. It includes 21 questions grouped into 5 items. It has been pre-tested before the start of the study. The questionnaire is appended.
· Method of data collection
Patient recruitment was done daily. After obtaining their informed verbal consent, the patients selected for the survey were interviewed through a semi-structured interview. The information related to the paraclinical tests was completed on the survey form as soon as the results were available.
2.9. Study Variables
The dependent variable was the existence of an ED. The independent variables were: sociodemographic, socioeconomic, toxic history and habits, diagnosis of cirrhosis, stage of cirrhosis and diagnosis of ED.
2.10. Data Analysis
Data were analyzed with Odense Denmark (2009) and Epi Data analysis 2.3 software from Epi Data Association. Qualitative variables were described using sizes and percentages. The quantitative variables were expressed as mean ± standard deviation when the distribution is normal, otherwise as medians [1st interquartile-3rd interquartile]. Data comparison was made using Pearson’s chi-square test or Fisher’s exact test as appropriate. The significance threshold was set at 5%.
2.11. Ethical Consideration
Before carrying out this study, the protocol was submitted to the Local Ethics Committee for Biomedical Research of the University of Parakou (CLERB-UP) for approval. This study was conducted with the informed verbal consent of the patients. Medical secrecy and patient rights were respected throughout the study. Patients were reassured about the anonymity and confidentiality of the information collected. Patients with erectile dysfunction were referred for urological consultation and follow-up.
3. Results
3.1. Study Population
During the study period, 103 subjects with cirrhosis were consulted and/or hospitalized in the internal medicine department of CHUD-B/A (n = 88) and the hepato-gastroenterology unit of HIA-CHU of Parakou (n = 15). Among these 103 patients, 64 were men (CHUD-B/A n = 51 and HIA-CHU n = 15) and the subject of the present study.
3.2. Sociodemographic Data of the Study Population
The mean age of the subjects included in this study was 43.53 ± 13.13 years with the extremes of 22 and 75 years. Thirty-eight (38 or 59.38%) came from rural areas and half of them (32% or 50%) were farmers. Twenty subjects (31.25%) had an excessive alcohol consumption and 8 (12.50%) were smokers. Among the subjects included in the study, 5 (7.81%) suffered from high blood pressure and 4 (6.25%) from diabetes. Table 1 summarizes the sociodemographic data of
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Table 1. Distribution of men with cirrhosis according to socio-demographic data (CHUD-B/A, HIA-CHU, Parakou, 2022, n = 64).
patients included in this study.
3.3. Cirrhosis Data
Cirrhosis was secondary to chronic hepatitis B virus infection in 55 patients (85.94%). In this study, 42 patients (65.63%) with cirrhosis had both edema and ascites as decompensation. 42 of them (65.63%) had hepatocellular carcinoma. Regarding the prognosis, 31 patients (48.44%) were in Child-Pugh class B. Table 2 shows the data relating to cirrhosis.
3.4. Erectile Dysfunction Data
ED was found in 27 patients with cirrhosis out of the 64 patients included, representing a frequency of 42.19%. Among the 27 patients with cirrhosis and ED, 12 (44.44%) had moderate erectile dysfunction. The other sexual disorders found in patients were a decrease in libido and ejaculation disorders. Table 3 summarizes the ED data.
Factors associated with erectile dysfunction
In this study, in bivariate analysis, the factors statistically associated with ED were:
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Table 2. Distribution of men with cirrhosis according to cirrhosis data (CHUD-B/A, HIA-CHU, Parakou, 2022, n = 64).
*A patient can have several causes at the same time; **A patient can have several decompensations at the same time.
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Table 3. Distribution of men with cirrhosis according to erectile dysfunction data (CHUD-B/A, HIA-CHU, Parakou, 2022, n = 64).
· Age (p < 0.001), the risk of developing ED was 6 times greater in patients aged at least 40 years (PR = 6.03). Of the 27 patients over 40 years old, 22 (81.48%) had an ED, compared with 5 out of 37 (13.51%) under 40 years old.
· Excessive alcohol consumption (p = 0.001), patients with excessive alcohol consumption had about 3 times the risk of developing ED (PR = 2.70). Of the 13 patients who consumed more than 30 g of alcohol per day, 11 (84.62%) had ED, compared with 16 out of 51 patients (31.37%) who consumed little or no alcohol.
· Hepatocellular carcinoma (p = 0.021), patients with hepatocellular carcinoma had about twice the risk of developing ED (PR = 2.31). In this study, 22 of the 42 patients (52.38%) with hepatocellular carcinoma had ED. Whereas ED was noted in 5 out of 22 patients (22.73%) without hepatocellular carcinoma.
· Class C of the Child-Pugh score (p = 0.010), patients in Child-Pugh class C had about twice the risk of developing ED (PR = 2.13). Of the 26 patients in Child Pugh class C score, 16 (61.54%) had an ED; compared to 11 of the 38 patients (28.95%) with a Child Pugh class B or A score.
Table 4 shows the relationship between ED and patient data.
4. Discussion
This study made it possible to calculate the frequency of erectile dysfunction, to determine the other associated sexual disorders and to identify the associated factors of ED among patients with cirrhosis in Parakou. This is one of the rare studies addressing this topic in Benin. Standard and validated criteria (Child-Pugh score, IIEF-5 score) were used during this study. Its prospective nature made it possible to collect the information and research the factors associated with ED in this population group.
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Table 4. Relationship between erectile dysfunction and data of men with cirrhosis in bivariate analysis (CHUD-B/A, HIA-CHU, Parakou, 2022, n = 64).
ED = Erectile dysfunction.
In the present study, the frequency of ED was 42.19%. This result is similar to the frequency of 41.2% reported by Thakur et al. [11] in India in 2019. It is lower than that noted by Guèye et al. [12] in 2022 in Senegal (52.2%) and by Toda et al. [7] in Japan in 2014 (92.3%). This result is superior to 29.4% found by El Atrebi et al. [13] in Egypt in 2011. This disparity in results could be related to the subjective nature of the statements made by patients about erectile dysfunction. It is a frequent pathology that affects the quality of life. Its actual frequency is under-estimated because of its taboo character.
The mean age of the subjects included in this study was 43.53 ± 13.13 years. This result is similar to 41 years reported by Guèye et al. [14] in Senegal in 2018. Dia et al. [15] also reported a mean age of 44 years in Senegal in 2019. The age of patients was associated with ED (p < 0.001). Patients aged at least 40 years were six times more likely to have ED (PR = 6.03). In the study conducted by Maimone et al. [16] in Italy in 2018, age was statistically associated with ED (OR = 1.058 95% CI = 1.015 - 1.103 p = 0.008). The frequency increased significantly with age. In 2014, Janini et al. [17] in Europe noticed that men with ED were older than those without ED. The same observation was made by Toda et al. [7] in 2019 in Japan, which found that advanced age was significantly associated with ED. Given the young age of the patients in the present study, ED would be related to cirrhosis and not to aging.
In this study, 55 patients out of the 64 included (85.94%), has a cirrhosis secondary to chronic hepatitis B virus infection. This high prevalence cirrhosis secondary to hepatitis B is explained by the fact that the study was carried out in an environment with high endemicity for hepatitis B virus infection. Excessive alcohol consumption was statistically associated with ED (p = 0.001). Patients with excessive alcohol consumption had about 3 times more risk of developing ED (PR = 2.70). This finding is corroborated by the study of Gueye et al. [12] in Senegal in 2022. The authors reported that alcoholic cirrhosis was statistically associated with ED (p = 0.015). This could be explained by the fact that high doses of alcohol reduce testosterone production. In addition, alcohol consumption over several years could lead to alcoholic neuropathy.
In the present study, hepatocellular carcinoma was associated with the presence of ED (p = 0.021). Patients with hepatocellular carcinoma had about twice the risk of developing ED (PR = 2.31). Hepatocellular carcinoma is a serious complication of cirrhosis. It is characterized by a significant deterioration of the general health condition and the latter could explain the occurrence of ED.
The majority of the 64 patients included in this study were in Child-Pugh class B, however it was Child-Pugh class C that was associated with ED (p = 0.010). Patients in Child-Pugh class C had twice the risk of developing ED (PR = 2.13). This result could be explained by the worsening of liver failure in Child-Pugh class C leading to a hyperestrogenemia. This result is similar to those of Paternostro et al. [18] in Austria in 2018 who had reported a high frequency of ED among patients in Child-Pugh class B (n = 35; 43.8%) compared to 18.7% in Child-Pugh class C (n = 15). According to their study, the severity of ED increased significantly throughout the classes of Child-Pugh score. Child-Pugh class C was statistically associated with the presence of ED (p = 0.037). This result is also similar to those found by Guèye et al. [12] in 2022 in Senegal. Half of the patients were in Child-Pugh class B (50%) but Child-Pugh class C was statistically associated with ED (6%; p = 0.002). In Nigeria in 2014, Adékanle et al. [19] demonstrated more signs of ED in Child-Pugh class B (n = 26; 43.33%; p < 0.05) and class C (n = 17; 28.33%; p < 0.05).
The main limitations of this study are the small sample size, the absence of testosterone test in these patients and the subjectivity of information given by the patients. Further prospective studies including a large number of patients with cirrhosis is needed to better study ED in this population group.
5. Conclusion
In Parakou, erectile dysfunction, although taboo and underestimated, is common in patients with liver cirrhosis. It is noted in approximately two out of five patients with cirrhosis. It is more frequent when the cirrhosis is severe and the patients are elderly. Apart from erectile dysfunction, patients with cirrhosis also have low libido and ejaculation disorder. Aggravating and associated factors of the severity of erectile dysfunction among patients with cirrhosis in Parakou in 2022 are: advanced age, hepatocellular carcinoma, alcoholism and the Child-Pugh class C. The modifiable factors (excessive alcohol consumption, non-follow-up of cirrhosis progressing to a Child-Pugh class C) must be avoided in order to prevent erectile dysfunction. The latter must be systematically sought in all patients with cirrhosis to ensure comprehensive care, thus improving their quality of life.
Appendix: Survey Sheet
Frequency and associated factors of erectile dysfunction among patients with liver cirrhosis in Parakou, Republic of Benin in 2022
Date of investigation: ……/……/……. Medical record number: ………….
Identification number: / / Center : ………………………….
I. Sociodemographic Data
Q-1. Age (years): …………………………………………………… / /
Q-2. Ethnicity: ………………………………………………………/ /
1-Otamari and related 2-Bariba and related 3-Fulani 4-Dendi and related
5-Lokpa 6-Fon and related 7-Yom 8-Nagot 9-Yoruba 10-Other ………………………………………………
Q-3. Religion: ………………………………………………………. / /
1-Christianity 2-Islam 3-Animism 4-Other ……………......
Q-4. Residence: Urban Rural
Q-5. Socio-professional status: …………………………………… / /
I-Unemployment 2-Pupil/Student 3-Employee (public or private) 4-Artisan/Laborer 5-Farmer 6-Breeder 7-Trader 8-Housekeeper
9-Other:……………
II. Clinical and Paraclinical Data
1. Interview
Q-6. Reason for consultation : ………………………………… / /
1-Poor general condition 2-Ascites 3-Edema and ascites 4-Abdominal pain
5-Altered state of consciousness 6-Abdominal mass 7-Other ………………
Q-7. Admission method: ……………………………………. / /
1-Emergency 2-Outpatient consultation 3-Referral
Q-8. Date of onset of illness: …………………………………...
Q-9. Lifestyle: ……………………………………………………...
-Excessive consumption of alcohol: Yes No
If yes, quantification in grams per day: <30 grams ≥30 grams
-Smoking: Yes No
If yes, Number of package/year ……………. Not applicable
Q-10. Medical history and comorbidities: …………………………… / /
1- Diabetes 2-HBP 3-prostatic adenocarcinoma 4-Cardiopathy
5-Prostatic neoplasia 6- Stroke 7-Epilepsy 8-Others……..
Q-11. Previous treatment: …………………………………. / /
1-Beta blockers 2-Hormone therapy 3-Anxiolytics
4-Antidepressant 5-Others…………………
2. DIAGNOSIS OF LIVER CIRRHOSIS
Q-13. Signs of portal hypertension:…………………………… / /
1-Abdominal collateral circulation 2-Splenomegaly 3-Thrombocytopenia 4-portal vein dilatation
Q-14. Signs of liver failure: ……………… / /
1-Gynecomastia Yes No
2-Palmar erythema Yes No
3-Terry’s nails Yes No
4-Prothrombin Time < 70% Yes No
5-Hypoalbuminemia Yes No
Q-15. Hepatomegaly Yes No
-Painful ……… 1-Yes 2-No
-Surface………… 1-smooth 2-irregular 3-nodular
-Consistency……… 1-firm 2-hard 3-stony
-Bottom edge……. 1-soft 2-firm 3-indeterminate
Q-16. Causes: ………………………………….. / /
1-HBV infection Yes No
2-HCV infection Yes No
3-Alcohol Yes No
4-Autoimmune hepatitis Yes No
Q-17. Child-Pugh score: …………../ /
Child-Pugh A: 5 to 6 Child-Pugh B: 7 to 9 Child-Pugh C: 10 to15
3-DIAGNOSIS OF ED
Q-18. Existence of ED: ………………………… / /
1-Yes 2-No
Q-19. Severity assessment: (IIEF-5 Score):
I-How do you rate your confidence that you could get and keep an erection?
1. Very low 2. Low 3. Moderate 4. High 5. Very high
II-When you had erections with sexual stimulation, how often your erection hard enough for penetration?
0. I was not sexually stimulated 1. Almost never or never 2. Rarely (much less than half the time)
3. Sometimes (about half the time) 4. Most of the time (much more than half the time)
5. Almost always or always
III-During sexual intercourse, how often were you able to maintain your erection after you had penetrated your partner ?
0. I haven’t tried to have sex 1. Almost never or never 2. Rarely (much less than half the time)
3. Sometimes (about half the time) 4. Most of the time (much more than half the time)
5. Almost always or always
IV-During sexual intercourse, how difficult was it to maintain your erection to completion of intercourse?
0. I haven’t tried to have sex 1. Extremely difficult 2. Very difficult
3. Difficult 4. Slightly difficult 5. Not difficult
V-When you attempted sexual intercourse, how often was it satisfactory for you?
0. I haven’t tried to have sex 1. Almost never or never 2. Rarely (much less than half the time)
3. Sometimes (about half the time) 4. Most of the time (much more than half the time)
5. Almost always or always
Interpretation:……………………………………... / /
1-Severe erectile dysfunction: 5 to 10, 2-Moderate erectile dysfunction: 11 to 15
3-16 à 20 Mild erectile dysfunction: 16 to 20 4-Normal erectile function: 21 to 25
5- Not interpretable: 1 to 4
4-EXISTENCE OF OTHER SEXUAL DISORDERS
1-Decreased libido Yes No
2-Ejaculation disorder Yes No
Q-20. Other biological tests (Blood Count)
Hb = ……g/dl MCV =……fl MCHC =…..g/dl MCH=……pg
Q-21. Complications and type of decompensation
1-Ascites Yes No
2-Gastrointestinal bleeding Yes No
3-Hepatic encephalopathy Yes No
4-Hepatocellular carcinoma Yes No
5-Hydrothorax Yes No
6-Hepatorenal syndrome Yes No