Correlation between non-alcoholic fatty liver disease and erectile dysfunction: A systematic narrative review

Abstract

BACKGROUND

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, as well as a growing public health concern. Erectile dysfunction (ED) is one of the most common sexual dysfunctions in men. Currently, clinical research on the relationship between NAFLD and ED is limited.

AIM

To systematically review and narrative synthesize the existing evidence on the association between NAFLD and ED, and to elucidate potential underlying mechanisms.

METHODS

We conducted a comprehensive search of various electronic databases to identify original observational studies investigating the association between NAFLD and ED. However, due to significant heterogeneity among the included studies and the limited number of eligible investigations, we opted for a narrative synthesis instead of a meta-analysis.

RESULTS

A total of seven observational studies, involving 4442 participants (2043 of whom had NAFLD), were included in the analysis. The evidence consistently indicates a significant positive association between NAFLD and ED. Key influencing factors identified across the studies included age, components of metabolic syndrome, insulin resistance, serum testosterone levels, and psychological factors such as anxiety.

CONCLUSION

Existing evidence indicates a strong correlation between NAFLD and ED. The strength of this association is influenced by various factors, including age, insulin resistance, testosterone levels, and anxiety. NAFLD is an important risk factor for ED. Further high-quality studies are needed to confirm this relationship and explain its underlying mechanisms.

Key Words: Non-alcoholic fatty liver disease; Erectile dysfunction; Chronic liver diseases; Sexual dysfunction; Metabolic syndrome; Insulin resistance; Systematic review; Narrative synthesis

Core Tip: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver condition worldwide. It often occurs alongside metabolic disorders, such as obesity and type 2 diabetes. Erectile dysfunction (ED) is a common sexual health issue in men. However, there is limited high-quality evidence systematically examining the relationship between ED and NAFLD. This systematic narrative review summarizes the existing research and confirms that NAFLD is a significant risk factor for ED. The strength of this association depends on various factors, including age, insulin resistance, testosterone levels, and anxiety. This study provides evidence-based support for the early identification of ED risk in NAFLD patients, which is significant for advancing comprehensive metabolic interventions, both socially and clinically.

INTRODUCTION

Non-alcoholic fatty liver disease (NAFLD) is an umbrella term for various liver conditions that affect approximately 25% to 30% of adults worldwide[1]. This spectrum ranges from simple steatosis to non-alcoholic steatohepatitis, which can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD is not only a liver disease, but also the primary hepatic manifestation of metabolic syndrome[2]. NAFLD often occurs alongside metabolic disorders such as obesity, type 2 diabetes, and insulin resistance, presenting an increasingly significant public health challenge.

Erectile dysfunction (ED) is defined as the consistent inability to achieve or maintain an erection sufficient for satisfactory sexual intercourse. It is one of the most common sexual dysfunctions in men[3]. Its prevalence increases with age, affecting approximately 52% of men aged 40 to 70[4]. ED can severely impact patients’ quality of life and their relationships with partners. ED is also recognized as an early warning sign of cardiovascular disease. ED has a multifactorial etiology, often resulting from the combined effects of vascular, neurological, endocrine, and psychological factors[5].

Both NAFLD and ED share a pathophysiological basis involving insulin resistance and chronic, low-grade inflammation[6]. Research also suggests the existence of liver-specific pathways that promote ED development independently[7], including gender hormone metabolism disorders and impaired detoxification function[8,9]. However, clinical studies directly investigating the association between NAFLD and ED are limited. This study aims to synthesize existing evidence systematically using a narrative review methodology. The review will qualitatively examine the association between NAFLD and ED, their potential mechanisms, and clinical implications. The results will inform clinical practice and guide future research.

MATERIALS AND METHODS

Research question identification

What is the association between NAFLD and ED?

Literature search strategy

This study conducted a systematic search of multiple Chinese and English databases, including PubMed, EMBASE, MEDLINE, Google Scholar, Scopus, Wiley, Web of Science, Cochrane, ScienceDirect, and other English-language resources, as well as Chinese databases such as CBM and CNKI. With the help of research librarian Wang J, who played a key role in designing and refining the search strategy, the team developed a core retrieval strategy. To comprehensively cover unpublished gray literature, the study searched the two major preprint platforms, medRxiv and bioRxiv, simultaneously. Additionally, manually tracing the reference lists of the included studies supplemented and refined the comprehensiveness of the retrieval results.

The search process used Boolean logic operators to combine keywords. The core search terms were “non-alcoholic fatty liver disease”, “sexual dysfunction”, “erectile dysfunction”, “erection”, and “impotence”, as well as their synonyms and related terms. This approach balanced recall and precision. There were no restrictions based on publication date or language, and the last update was conducted on October 10, 2025.

Study selection criteria

We included original studies published online that directly examined the association between NAFLD and ED. We excluded news reports, case reports, animal studies, and studies with missing or unobtainable key data. We only considered studies that provided sufficient key information in their abstracts for data extraction and analysis.

Data extraction and synthesis

Due to significant methodological heterogeneity among the included studies and the limited number of eligible investigations, we opted for a narrative synthesis approach instead of a quantitative meta-analysis. This approach better addresses the diversity of the current clinical and methodological evidence base. Two researchers conducted an independent screening study. The subjects were limited to adult males with confirmed NAFLD. The outcome was the incidence of ED or related assessment metrics. In cases of disagreement, consensus was reached through discussion. If resolution remained elusive, a third researcher was consulted for arbitration.

The initial search yielded 298 publications, and one additional record was identified manually. After removing duplicates and screening the titles and abstracts of the remaining publications, 68 full-text articles were assessed for eligibility. Ultimately, seven studies were included in this systematic review[3,10-15]. Figure 1 illustrates the process of visualizing literature retrieval. Two researchers independently extracted data using a standardized form. Key elements included the characteristics of the studies, demographics of the participants, methods used to diagnose NAFLD, tools used to assess ED, and main findings. The extracted data were systematically organized and summarized in Table 1.

Figure 1  Flow diagram of literature search.

Table 1 Characteristics of the studies included in the systematic review, n (%)/mean ± SD.

Ref.	Country of origin	Study design	Time period	Participants (n)	NAFLD patients (n)	Mean age, years	BMI (kg/m2)	ED risk	Population	Diagnostic methods for NAFLD	Assessment tools for ED	Main findings
Tarik Kani et al[3], 2021	Turkey	Retrospective study	From 2017 to 2018	1362	684	48.65 ± 11.83	30.98 ± 6.43	68 (50.0)	Patients were diagnosed with NAFLD at a single gastroenterology outpatient clinic	Ultrasonography	IIEF-5	ED is common among patients with NAFLD. Age, obesity, and hypertension are also associated with ED in these patients
				03	685	42.63 ± 10.52	29.02 ± 3.55
Youcheng et al[10], 2025	China	Cross-sectional study	From 2001 to 2004	14982	4834	51.5 ± 18.6	28.0 ± 5.6	483 (32.2)	Adult males who participated in the 2001-2004 National Health and Nutrition Examination Survey in the United States	US-FLI score	Answer the questions	Participants with NAFLD had a significantly increased risk of developing ED compared with those without fatty liver disease
				22653	10155
Duman et al[11], 2016	Turkey	Prospective study	20151	402	134	38.3 ± 11.2	27.88 ± 3.13	13 (32.5)	Male NAFLD patients aged 18 years to 75 years	Biopsy	IIEF-5	There is a significant association between NAFLD and ED
				03	275	41.0 ± 9.8	28.62 ± 3.66
Yilmaz et al[12], 2021	Turkey	Cross-sectional study	From February 2018 to January 2019	1062	744	51.47 ± 10.34	28.51 ± 3.57	74 (69.8)	Male patients presenting to the urology outpatient clinic with symptoms of erectile dysfunction	Ultrasonography	IIEF-5	NAFLD is a significant risk factor for ED. Patients with NAFLD are 292 times more likely to experience ED than those without NAFLD
				403	325
Eren and Horsanali[13], 2019	Turkey	Retrospective study	From January 2016 to March 2018	2562	NA4	61.02 ± 9.27	27.4 ± 3.5	NA	Male patients are diagnosed with lower urinary tract symptoms or benign prostatic hyperplasia	Ultrasonography	IIEF-5	NAFLD is an independent predictor of IIEF-5 scores. The severity of NAFLD is negatively correlated with IIEF-5 scores
				1003	NA5		29.67 ± 4.16
Hasanain et al[14], 2017	Egypt	Prospective study	From April 2013 to February 2015	1922	884	42.4 ± 7.7	NA	88 (45.8)	A series of male patients with NAFLD were admitted across multiple disciplines	Ultrasonography	IIEF-5	ED is a common condition among male NAFLD patients. Insulin resistance and low serum testosterone levels jointly contribute to its development
				03	1045
Ragab et al[15], 2024	Egypt	Observational study	From November 2021 to November 2022	712	414	38.9 ± 10.3	26.91 ± 3.12	41 (57.7)	NAFLD patients with normal liver function and NAFLD patients with abnormal liver function	Ultrasonography	IIEF-5	Abnormal levels of nitric oxide and adropin may play a potential role in the development and progression of erectile dysfunction in patients with nonalcoholic fatty liver disease
				943	305	39.1 ± 10.7	27.26 ± 3.63

¹Manuscript receipt date.

²Non-alcoholic fatty liver disease.

³Without non-alcoholic fatty liver disease.

⁴Erectile dysfunction.

⁵Without erectile dysfunction.

NAFLD: Non-alcoholic fatty liver disease; ED: Erectile dysfunction; BMI: Body mass index; US-FLI: Ultrasonographic fatty liver index; IIEF-5: Five-item version of the International Index of Erectile Function; NA: Not available.

Quality assessment

We conducted a systematic assessment of the methodological quality of the seven included studies[3,10-15]. We evaluated the cohort and case-control studies using the Newcastle-Ottawa Scale, and we applied the Agency for Healthcare Research and Quality’s criteria to the cross-sectional studies. The results of the assessment indicated that the studies’ overall quality was moderate (Table 2).

Table 2 Quality assessment of the studies included in the systematic review.

Ref.	Study design	Assessment tools	Assessment results	Interpretation of results
Tarik Kani et al[3], 2021	Retrospective study	NOS	7 stars	The maximum total score is nine stars. A score of seven or more stars generally indicates high-quality research, while a score of five or six stars indicates medium quality, and a score of less than five stars indicates low quality
Youcheng et al[10], 2025	Prospective study	NOS	6 stars
Duman et al[11], 2016	Retrospective study	NOS	6 stars
Yilmaz et al[12], 2021	Prospective study	NOS	7 stars
Eren and Horsanali[13], 2019	Cross-sectional study	AHRQ	8 points	This standard comprises 11 items, each of which is answered with “Yes”, “No”, or “Uncertain”. A “Yes” response earns 1 point. A total score of 0-3 indicates low quality, 4-7 indicates medium quality, and 8-11 indicates high quality
Hasanain et al[14], 2017	Cross-sectional study	AHRQ	7 points
Ragab et al[15], 2024	Observational study	AHRQ	6 points

NOS: Newcastle-Ottawa Scale; AHRQ: Agency for Healthcare Research and Quality.

Risk of bias assessment

Throughout the analysis, we thoroughly considered potential biases. Since this study employed a narrative synthesis rather than a meta-analysis and did not quantitatively pool results, statistical methods such as Begg’s test were not used to assess publication bias quantitatively. We acknowledge the possibility of publication bias and discuss it qualitatively in the limitations section, clarifying its potential impact on our conclusions.

RESULTS

Characteristics of studies

A total of seven studies[3,10-15] were included in the final analysis. These studies had a combined sample size of 4442 participants, 2043 of whom had NAFLD. The study designs included two prospective studies[11,14] and five observational studies[3,10,12,13,15]. No randomized controlled trials were included. Of the included studies, four were from Turkey[3,11-13], two were from Egypt[14,15], and one was from China[10]. All of the studies spanned the period from 2001 to 2022. Regarding diagnostic methods for NAFLD, five studies used ultrasound examinations[3,12-15], one study used a liver biopsy[11], and one study used the ultrasonographic fatty liver index score[10]. ED was primarily assessed using the International Index of Erectile Function (IIEF-5) questionnaire.

Evidence synthesis

A narrative synthesis of seven studies[3,10-15] revealed consistent evidence supporting an association between NAFLD and ED. Table 3 summarizes the factors associated with ED in NAFLD patients identified across the included studies. Four studies identified NAFLD severity scores as significant factors associated with ED[10-13]. Age was independently associated with ED in four studies[3,12-14]. Other significant factors included hypertension, insulin resistance, anxiety scores [generalized anxiety disorder-7 (GAD-7)], serum testosterone levels, adropin levels, and creatinine levels.

Table 3 Factors influencing the development of erectile dysfunction in non-alcoholic fatty liver disease patients.

Ref.	Influencing factors	Conclusions
Tarik Kani et al[3], 2021	Age, obesity, hypertension	Older age, obesity, and hypertension are associated with ED in the NAFLD cohort
Youcheng et al[10], 2025	US-FLI	NAFLD is positively correlated with ED
Duman et al[11], 2016	NAFLD score	There is a significant association between NAFLD and ED
Yilmaz et al[12], 2021	Age, MetS, NAFLD score	As NAFLD-related liver damage progresses, symptoms of ED show a significant worsening trend
Eren and Horsanali[13], 2019	Age, MetS, NAFLD score	The higher the NAFLD grade, the lower the IIEF-5 score
Hasanain et al[14], 2017	Age ≥ 40 years, IR, low serum testosterone	Age, insulin resistance, and low serum testosterone levels are independently associated with ED
Ragab et al[15], 2024	Serum adropin, creatinine, GAD-7 score	GAD-7 scale scores, creatinine levels, and adropin were the only strong independent predictors of IIEF-5 scores

US-FLI: Ultrasonographic fatty liver indicator; NAFLD: Non-alcoholic fatty liver disease; ED: Erectile dysfunction; MetS: Metabolic syndrome; IR: Insulin resistance; GAD-7: Generalized anxiety disorder-7; IIEF-5: Five-item version of the International Index of Erectile Function.

Heterogeneity assessment

Significant clinical and methodological heterogeneity was observed across studies, particularly about the following four factors: (1) Participant characteristics (e.g., age distribution and metabolic comorbidities); (2) Diagnostic criteria for NAFLD, including the use of imaging vs biochemical markers; (3) ED assessment methods; and (4) Control of potential confounding factors (e.g., diabetes status and cardiovascular risk factors). These variations limited the feasibility of meaningful quantitative synthesis.

DISCUSSION

What is the association between NAFLD and ED?

This systematic review summarizes the results of seven studies[3,10-15] examining the relationship between NAFLD and ED. Despite their methodological limitations and heterogeneity, the studies consistently indicate a significant association between the two conditions. Specifically, multiple studies provide quantitative evidence of this association. For example, Yilmaz et al[12] found that patients with NAFLD were approximately 2.92 times more likely to experience ED than those without NAFLD. A cross-sectional study based on the National Health and Nutrition Examination Survey showed a positive correlation between a high fatty liver index score and ED[10]. However, caution should be exercised when interpreting the relationship between the two conditions. A mendelian randomization study failed to confirm a direct causal effect of NAFLD on ED at the genetic level[16]. This suggests that the overall causal effect of NAFLD on ED may be limited in the general population, and that the significant associations observed in observational studies may be influenced by confounding factors.

What are the potential mechanisms underlying ED in patients with NAFLD?

The link between NAFLD and ED stems from various mechanisms and multifactorial interactions. A thorough understanding of these mechanisms is essential for the early clinical identification and treatment of ED.

Insulin resistance and vascular endothelial dysfunction: Insulin resistance suppresses endothelial nitric oxide synthase (eNOS) activity, thereby reducing nitric oxide production[17,18]. Nitric oxide is a key mediator of smooth muscle relaxation in the corpus cavernosum[19]. Additionally, proinflammatory factors, such as tumor necrosis factor-α and interleukin-6, released from visceral fat tissue further inhibit eNOS, thereby exacerbating vascular endothelial dysfunction[20]. Together, these factors contribute to ED.

Synergistic effects of shared metabolic risk factors: Both NAFLD and ED originate from metabolic syndrome. Obesity, diabetes, dyslipidemia, and hypertension promote atherosclerosis and cavernosal fibrosis synergistically[21,22]. NAFLD is a manifestation of metabolic dysfunction in the liver, whereas ED is an early manifestation of metabolic dysfunction in the penile vasculature.

The role of hepatocyte-specific pathways and hepatocyte-derived factors: One study suggests that patients with NAFLD are at a significantly higher risk of ED, even if they do not have diabetes[11]. However, a mendelian randomization analysis by Chen et al[16] failed to detect a significant genetic causal association between NAFLD and ED. This implies that the contribution of specific subgroups or intrahepatic pathways cannot be ruled out entirely in certain contexts. These findings suggest that NAFLD may cause ED via liver-specific pathways, independently of diabetes-related factors[23]. These mechanisms include hepatic dysregulation of sex hormone metabolism[8], impaired detoxification function[24], and the secretion of hepatocyte factors, such as fetuin-B[25]. Once in the bloodstream, these liver-derived factors directly impair systemic vascular endothelial function (including that of the penile cavernosal arteries) by inhibiting nitric oxide production, inducing oxidative stress, and promoting endothelial inflammation. Together, these processes establish the “liver-vascular-erectile dysfunction axis” as a potential pathological pathway.

Which factors influence ED in patients with NAFLD?

Our synthesis revealed several significant factors associated with ED in populations with NAFLD.

Age: Of the seven studies included in this systematic review, four explicitly identified age as an independent predictor of ED in patients with NAFLD[3,12-14]. Epidemiological investigations indicate that ED prevalence increases significantly with advancing age[26]. Mechanistically, aging is associated with a progressive decline in vascular endothelial function, worsening of atherosclerosis, decreased testosterone levels, and heightened chronic inflammation. These factors collectively contribute to the development of ED[27].

Metabolic syndrome and insulin resistance: Of the seven studies included in this systematic review, two indicated that metabolic syndrome is a risk factor for ED[12,13]. Metabolic syndrome is characterized by obesity, abnormal blood glucose levels, dyslipidemia, and hypertension. It shares a core pathophysiological basis with NAFLD and ED. Insulin resistance inhibits eNOS activity, reducing nitric oxide production and directly impairing penile cavernosal vasodilation. Additionally, insulin resistance promotes chronic inflammation and oxidative stress, which further exacerbates vascular endothelial dysfunction[27].

Serum testosterone level: NAFLD is often associated with hypogonadism, which creates a cycle of low testosterone levels[28]. Visceral obesity increases aromatase activity, promoting the conversion of testosterone to estrogen. This suppresses the hypothalamic-pituitary-gonadal axis further[29]. Low testosterone levels affect libido and directly impair eNOS activity and cavernous vasodilation capacity[30].

Psychological factors and anxiety states: The GAD-7 scale is commonly used to assess anxiety. Anxiety can exacerbate endothelial dysfunction and inhibit nitric oxide signaling pathways by activating the hypothalamic-pituitary-adrenal axis and increasing cortisol release[31]. Studies indicate a negative correlation between GAD-7 scores and IIEF-5 scores[15,32]. This suggests that anxiety may exacerbate the inflammatory responses and insulin resistance associated with NAFLD[32].

Serum creatinine level: An elevated serum creatinine level reliably indicates impaired renal function. It is also associated with NAFLD and ED. Patients with NAFLD have significantly higher creatinine levels than individuals without NAFLD, and these levels are independently associated with the degree of insulin resistance[33]. Lower IIEF-5 scores are associated with decreased creatinine clearance. Together, these findings suggest that renal impairment may contribute to ED through mechanisms such as uremic toxin accumulation, increased oxidative stress, and vascular calcification[34].

Adropin: This study presents evidence that patients with NAFLD have significantly lower serum adropin levels[15]. Adropin exerts protective effects by improving insulin resistance and enhancing endothelial nitric oxide bioavailability, and suppressing inflammation. Decreased adropin levels may exacerbate insulin resistance and ED, thereby increasing the risk of ED[35]. However, direct mechanistic evidence is needed.

Strengths and limitations

To our knowledge, this is one of the few systematic reviews to comprehensively collate and integrate evidence of the link between NAFLD and ED. The review confirms the significant association between the two conditions, providing an in-depth explanation of the underlying pathophysiological mechanisms. It also sheds new light on this relationship within the cross-metabolic-vascular-endocrine axis.

However, this study also has several limitations. Firstly, we acknowledge that the original studies included in the analysis were predominantly based on cross-sectional or retrospective observational designs. The methodological characteristics of these designs make it difficult to control for confounding factors, thus precluding the establishment of a causal relationship between NAFLD and ED. Furthermore, a mendelian randomization study found no genetic-level causal association between the two conditions[16], suggesting that the observational findings may be influenced by residual confounding factors. Secondly, significant clinical and methodological heterogeneity was observed among the included studies regarding NAFLD diagnostic methods, ED assessment tools, and control of key confounders (e.g., diabetes status). Therefore, a quantitative synthesis (i.e., a meta-analysis) could not be performed, so a narrative synthesis was used instead. Consequently, precise pooled effect estimates could not be provided. Thirdly, the review carries a potential risk of bias. In addition to the selection and information biases inherent in observational studies, publication bias may also be present, whereby positive results are more likely to be published. Notably, most of the included studies failed to exclude diabetic patients or conduct subgroup analyses on non-diabetic NAFLD populations. This is a significant potential source of confounding bias. Finally, the included studies were geographically concentrated in the Middle East and North Africa, particularly in Turkey and Egypt. Relatively little evidence came from East Asia (e.g., China). Given the known variations in NAFLD prevalence, metabolic characteristics, and cultural lifestyles across different populations, this geographic limitation may affect how generalizable the study’s conclusions are to other populations worldwide, including Europeans, Americans, and East Asians.

Clinical and societal implications

Despite the limitations, these findings are clinically significant. In clinical practice, the strong correlation between NAFLD and ED suggests that ED may indicate vascular problems at an early stage in individuals with NAFLD. Therefore, ED screening should be incorporated into routine assessments for patients with NAFLD, particularly focusing on early identification in individuals aged 40 years and over. The clinical management strategy should aim to improve insulin resistance by encouraging lifestyle changes and, if necessary, prescribing metabolic regulators such as glucagon-like peptide-1 receptor agonists. Patients with central obesity or low testosterone should undergo an assessment of their hormone levels and psychological status. A multidisciplinary collaboration model integrating hepatology, metabolism, andrology, and psychology should be established to achieve comprehensive intervention and enhance both liver and sexual health.

CONCLUSION

This systematic narrative review identified consistent evidence of a link between NAFLD and ED, mediated via complex metabolic, hormonal, and inflammatory pathways. The strength of this association appears to be influenced by various factors, including age, insulin resistance, testosterone levels, and psychological state. Future research should focus on designing rigorously designed prospective cohort studies and exploring the clinical utility of integrated management strategies for these interrelated conditions.

ACKNOWLEDGEMENTS

The authors would like to thank Wang J for his expertise in developing and refining the literature search strategy.