Erectile dysfunction pattern in patients with end stage renal disease on regular dialysis

Abstract

Introductions:

Evaluating the epidemiology, pattern, and contributing factors of sexual dysfunction in end-stage renal disease (ESRD) patients is the cornerstone in understanding and enhancing these patients’ quality of life. In this study, we aimed to identify the different patterns of erectile dysfunction (ED) among 100 patients undergoing hemodialysis.

Materials and methods:

A single-center, cross-sectional, study was conducted on 100 patients with ESRD on hemodialysis. Patients were assessed using the International index of erectile dysfunction (IIEF) and Doppler assessment of the penis.

Results:

A total of 100 patients were included in this study with a mean age of 48.77 ± 9.66 years old. The mean erectile index was 7.10 ± 4.62; while the mean free and total testosterone were 10.07 ± 7.69 and 2.93 ± 1.4 ng/dL, respectively. Overall, 67% of the patients had abnormal hormonal levels. Concerning the penile vasculature, 71% of the patients had arterogenic importance and 19% had venous impotence. The comparative analysis demonstrated that hypertensive patients had lower erectile index (p = 0.002). In addition, smokers had lower erectile index (p < 0.001). There was statistical significance between normal hormonal and abnormal hormone level according to erectile index, with lower index in patients with abnormal hormonal level (p = 0.03).

Conclusion:

In conclusion, our findings indicate that the most common causes of ED with renal failure were hormonal disturbance, including testosterone, and prolactin. Hypertension and smoking are major contributing factors that should be managed carefully to reduce the risk of ED and improve the quality of life.

Keywords

Chronic kidney disease sexual dysfunction quality of life testosterone hemodialysis

Introduction

Patients with chronic kidney disease (CKD) are usually associated with many hormonal changes, especially in end-stage renal disease (ESRD).¹ Hypothalamic–pituitary-gonadal axis disruption due to ESRD results in substantial impairment in males’ sexual function.^2,3 Therefore, male sexual dysfunction is highly frequent in ESRD patients. Many reports showed a significant decline in testosterone levels in 40%–60% of ESRD patients receiving dialysis, resulting in hypogonadism.^3,4 Moreover, a significant association was observed between testosterone and the clinical condition of ESRD patients; some reports used the testosterone level as a predictor of mortality in hemodialysis patients.⁵ The testicular size was also observed to be reduced with histological abnormalities, including interstitial fibrosis and seminiferous tubular derangement. These abnormalities are linked with a noticeable shortage in the kidney’s ability to extract some hormones like prolactin, leading to hyperprolactinemia, which in turn leads to hypogonadotropic hypogonadism.⁶ Infertility, reduced libido, and erectile dysfunction (ED) are the most common hypogonadotropic hypogonadism features.⁷ Many studies reported that ED prevalence is 90% in elderly patients receiving hemodialysis.⁸ Similarly, decreased libido was reported in 86%.⁹ Simultaneously, delayed or inadequate ejaculation during sexual intercourse was observed in 52%.¹⁰ The attention given to sexual problems in patients receiving renal replacement therapy (RRT) is low in clinical practice. This may be caused by a lack of knowledge among these patients of the high incidence of sexual disorders.¹¹ In addition, another contributing factor could be restraints when addressing sexual problems with patients. Therefore, determining the epidemiology, pattern, and contributing factors of sexual dysfunction in ESRD patients is the cornerstone in understanding and improving these patients’ quality of life. In this study, we aimed to identify the different patterns of ED among 100 patients undergoing hemodialysis.

Materials and methods

The study’s protocol gained the ethical approval from ethics committee of the authors’ institute. We followed that standards of STROBE guideline during the preparation of this manuscript.¹²

Study design and population

A single-center, cross-sectional, study was conducted on 100 patients, who were recruited from Urology and Nephrology Departments of Al-Zahraa University hospital through the period from January 2019 to May 2020. Patients with ESRD requiring hemodialysis were included. The ESRD was defined as an estimated glomerular filtration rate (eGFR) of less than 15 mL/min/m².¹³ We excluded all patients with uncontrolled hypertension, uncontrolled diabetes, and/or neurological disease.

Data collection

At screening, the following data were collected from eligible patients: age, disease duration, and risk factors for ESRD. Then, patients were assessed using the International index of erectile dysfunction (IIEF) and global assessment questionnaire of erectile dysfunction (GAQ). The erectile function (EF) domain of IIEF is a questionnaire composed of six, 5-likert scale, questions; the total score ranges from 0 to 30 with score less than 25 indicating ED.¹⁴ On the other hand, patients were asked binary questions about their ability to penetrate the partners’ vagina and the adequacy of the duration of erection. In addition, patients underwent laboratory investigations in the form of complete blood count (CBC), hepatic functions, renal functions, glycemic parameters, lipid profile, and hormonal assays. All patients underwent Doppler assessment of the penis using high frequency transducer (7.5–9.0 MHz). Peak systolic and diastolic velocities of <30 cm/s and >5 cm/s were used for diagnosis of arteriogenic and venous impotence, respectively.

Statistical analysis

We employed descriptive analysis (mean ± standard deviation (SD) and frequency for quantitative and qualitative data, respectively) to describe different parameters of the study. The independent t-test or Mann–Whitney test were used to assess the association between erectile index and different parameters. Data were analyzed using Statistical Program for Social Science (SPSS) version 20.0.

Results

A total of 100 patients were included in this study with a mean age of 48.77 ± 9.66 years old. The mean disease duration was 3.38 ± 1.87 years and 49% of the patients were hypertensive. In terms of sexual encounter profile, only 28% and 20% of the patients reported that they were able to penetrate partners’ vagina and had adequate duration of erection, respectively. Besides, 16% of the patients reported improved erection after treatment. The mean erectile index was 7.10 ± 4.62; while the mean free and total testosterone were 10.07 ± 7.69 and 2.93 ± 1.4 ng/dL, respectively (Table 1). Overall, 67% of the patients had abnormal hormonal levels. Concerning penile Duplex, 71% of the patients had arterogenic importance and 19% had venous impotence. The comparative analysis demonstrated that hypertensive patients had lower erectile index (p = 0.002). In addition, smokers had lower erectile index (p < 0.001). There was statistical significance between normal hormonal and abnormal hormone level according to erectile index, with lower index in patients with abnormal hormonal level (p = 0.03). The associations between erectile index and other laboratory parameters were not statistically significant (p > 0.05; Table 2). The correlation analysis showed that erectile index negatively correlated with age and duration of dialysis. Besides, it negatively correlated with FSH, prolactin, and lipid profile parameters (Table 3).

Table 1.

Demographic, sexual, and laboratory characteristics of the included patients.

Variables		Patients
Variables		(n = 100)
Age (years)		48.77 ± 9.66
Time of dialysis (years)		3.38 ± 1.87
Risk factors, %	HTN	49
	DM	16
	Smoker	29
SEP, %	Were you able to insert your penis into your partner’s vagina	28
SEP, %	Did your erection last long enough to have successful intercourse	20
Has the treatment you have been taking improved your erections		16
Erectile index		7.10 ± 4.62
FSH		10.45 ± 4.50
LH		3.44 ± 2.27
Prolactin		23.5 ± 10.14
Free testosterone		10.07 ± 7.69
T. Testosterone		2.93 ± 1.40
Cholesterol		188.94 ± 71.03
TG		135.93 ± 82.90
LDL		121.61 ± 59.09
HDL		38.87 ± 10.60
Serum creatinine		9.33 ± 2.18
Urea		142.78 ± 39.00

Table 2.

The comparative analysis.

Variable		Erectile index
Variable		Min.	Max	Mean	±SD	p-value
HTN	Normotensive	0	20	8.53	5.32	0.002
HTN	Hypertensive	0	10	5.61	3.17
DM	Non-diabetic	0	20	7.26	4.81
DM	Diabetic	0	10	6.25	3.42	0.424
Smoking	Non-smoker	0	20	8.38	4.53
Smoking	Smoker	0	10	3.97	3.1	<0.001
Able to insert your penis into your		0	15	5.36	3.83	0.058
Positive GAQ		0	5	2.81	2.56	<0.001
Duplex	Arterial	0	15	7.19	4.43
	Venous	0	20	8.42	6.47
	Normal	0	10	5.83	2.82	0.185
Abnormal hormone level		0	15	6.42	3.77	0.035

Table 3.

The correlation analysis.

Parameters	Erectile index
Parameters	R	p-value
Age (years)	−0.107	0.29
Time of dialysis (years)	−0.255	0.011
Risk factors	−0.463	<0.001
FSH	−0.325	0.016
LH	0.012	0.902
Prolactin	−0.256	0.027
Free testosterone	0.046	0.651
T. Testosterone	0.326	0.013
Cholesterol	−0.28	0.047
TG	−0.232	0.039
LDL	−0.227	0.025
HDL	−0.052	0.606
Serum creatinine	−0.06	0.552
Urea	−0.219	0.039

Discussion

In modern life, ED is a major health concern and is frequently underdiagnosed and underestimated due to the lack of physician’s knowledge or the patient’s embarrassment, leading to a high prevalence with a substantial effect on the quality of life. Many hypotheses aimed to explain the association between ESRD and ED. Inci et al.¹⁵ proposed that ESRD-induced vascular diseases, including penile atherosclerotic disease, are significantly associated with severe ED. Moreover, the carotid intima-media thickness is significantly correlated with a higher ED prevalence in hemodialysis patients.¹⁶ Another hypothesis relied on the hypothalamic-pituitary-gonadal axis, which is significantly disturbed in ESRD and leads to testosterone deficiency. Testosterone deficiency contributes to the downregulation of nitric oxide, which is necessary for erectile function.^17,18 The third hypothesis stated that patients with ESRD due to diabetes are frequently associated with neuropathy, which results in autonomic nervous system dysfunction and reduced nocturnal penile tumescence.¹⁹ Moreover, ESRD patients received several antihypertensive medications, including beta-blockers, diuretics, methyldopa, and calcium channel blockers, strongly linked with ED.²⁰ Besides, Lawrence et al.²¹ showed that in ESRD patients, anemia’s risk is increased twice compared to the general population. The lack of oxygen supply to the tissues during anemia is resulted in impaired synthesis of nitric oxide within the erectile tissues and decreased erectile function. Finally, the secondary hyperparathyroidism resulting from ESRD is associated with prolactin release and penile calcification, indicating hypogonadism and ED.²² In our study, the most common causes of ED in renal failure were hormonal disturbance, followed by vascular, mixed (hormonal and vascular), and neurogenic causes. Dean and Lue²³ showed that hormone levels are responsible for most ED cases. As we mentioned before, In the early stages of ESRD, a combination of testicular dysfunction and secondary pituitary-gonadal axis abnormalities may be detected and eventually worsen as the renal disease progresses.²⁴ Our findings demonstrated that prolactin level was higher in patients with renal failure and low score in ED index, which indicates a higher incidence of ED. The Prevalence of hyperprolactinemia in ESRD patients was reported to be 30%–65%, as a consequence of both reduced renal clearance and increased production.⁷ After kidney transplantation, such abnormalities appear to be resolved. Bromocriptine treatment can be also used to reduce the prolactin levels and prevent the complications of hyperprolactinemia.²⁵ The increased secretion of prolactin found in ESRD could be partly associated with the development of secondary hyperparathyroidism.²⁴ Therefore, partial inhibition of the release of parathyroid hormone by calcitriol administration led to an increase in plasma testosterone levels, a decrease in plasma gonadotropin concentrations, and improved sexual function.²⁶ In our study, the neurological causes were 6% of the patients. Abnormal response to Valsalva maneuver and impaired nocturnal penile tumescence resulted from autonomic and peripheral neuropathy are correlated to sexual dysfunction. This may be due to the long period of dialysis. In the study of Ali et al.²⁷ it has been shown that the prevalence of ED in patients with hemodialysis is extremely high (82.5%). This estimated prevalence, together with our findings, indicates that despite the improvement introduced in CRF patients’ treatment, the prevalence of ED remains high within the hemodialysis population. Cardiovascular diseases, hypertension, diabetes, smoking, alcohol abuse, and depression are major risk factors associated with a high ED prevalence.²⁰ Our findings showed a significant difference between hypertensive and non-hypertensive patients regarding erectile index (p = 0.002). Similarly, we found that smokers are more borne to the risk of ED (p < 0.001). Navaneethan et al.²⁸ conducted a meta-analysis to assess the prevalence of ED and its predictors in ESRD patients. Meta-regression showed that hypertensive ESRD patients were associated with a higher prevalence of ED Further, Costa and his colleagues²⁹ demonstrated that active smokers associated with a 2-folded risk of ED compared to ex-smokers (Odd ratio = 2.22, 95% CI, [1.25, 3.94], p = 0.007). Also, they found a strong relationship between the years of smoking and the risk of ED (p = 0.001). This study has some limitations, including the relatively small number of included patients, the self-reporting nature of the data collection, which may aggravate some sources of bias, and being a single-center study, which hindered our ability to generalize these findings.

Conclusion

our findings indicate that the most common causes of ED with renal failure were hormonal disruptions, including testosterone and prolactin. Hypertension and smoking are major contributing factors that should be managed carefully to reduce the risk of ED and improve the quality of life.

Footnotes

Authors contribution

All listed authors (MA., TA, AH., AE & KM.) have performed all four points specified below: A. Made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; B. Involved in drafting the manuscript or revising it critically for important intellectual content; C. Provided final approval of the version to be published. Each author should have participated sufficiently in the work to take public responsibility for appropriate portions of the content; D. Agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved; All authors read and approved the final manuscript.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the Institution and/or National Research Committee and the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The protocol and written informed consent were approved by the local ethical committee of Alzahraa university Hospital (affiliated to Al-Azhar University, Egypt. REC NO: 2531).

Informed consent

Informed written consent was obtained from all patients.

ORCID iD

Tamer Ali Abouelgreed

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