Abstract

This review systematically examines the underlying mechanisms linking erectile dysfunction (ED) with arthritis and explores multidisciplinary management strategies. Epidemiological studies confirm that patients with various arthritis—including osteoarthritis (OA), rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and gouty arthritis—exhibit significantly higher ED prevalence and incidence risks compared to the general population. This association remains independent of confounding factors such as age and comorbidities. Core mechanisms linking the two include chronic inflammation disrupting the “NO–cGMP–PKG” erectile molecular axis, vascular endothelial dysfunction causing insufficient penile blood supply, endocrine-metabolic disorders (e.g., insulin resistance, reduced testosterone), neuropsychological factors (anxiety, depression, chronic pain), and the synergistic effects of therapeutic agents (methotrexate, nonsteroidal anti-inflammatory drugs, glucocorticoids). Clinical recommendations advocate an “active screening-tiered assessment” approach, utilizing the International Index of Erectile Function (IIEF) combined with disease activity tools (e.g., DAS28, BASDAI) for screening and evaluation. Management should follow a multidisciplinary team (MDT) model integrating “control of underlying disease + individualized ED treatment + psychological intervention + lifestyle optimization” to improve patients’ overall health outcomes ultimately.

1 Introduction

Erectile dysfunction (ED) refers to a pathological condition in which men persistently or recurrently fail to achieve and/or maintain sufficient penile rigidity for satisfactory sexual intercourse (McCabe et al., 2016). As a highly prevalent sexual health disorder among men, its prevalence exceeds 50% in males aged 40–70 years (Saffati et al., 2025), exhibiting a significant age-related increase with further heightened risk in men over 70 (Wang et al., 2023). The etiology of ED is highly complex, resulting from the interplay of bio-psycho-social multidimensional factors (Hatzichristou et al., 2016). Clinically, it is categorized into three types: Psychogenic ED, triggered by psychological stress, emotional disorders, or interpersonal conflicts; Organic ED, further subdivided into neurogenic, hormonal, arterial, cavernosal (veno-occlusive), and drug-induced subtypes (Goyal et al., 2024); and Mixed ED, the most common clinical presentation due to the combined influence of organic pathology and psychological factors (Salonia et al., 2021). The current treatment framework for ED is relatively well-established, with phosphodiesterase type 5 inhibitors (PDE5Is) serving as the first-line therapy. Secondary interventions include intracavernosal injections, vacuum erection devices, and penile prosthesis implantation (Stern et al., 2025) (Nemr et al., 2025) (Lowy and Ramanathan, 2022). However, due to the sensitive nature of the topic, patients often avoid seeking medical help out of shame. Some healthcare providers may also hesitate to initiate discussions due to awkwardness or insufficient attention to patients’ sexual health needs. This results in low rates of spontaneous debate about sexual topics between doctors and patients, ultimately leading to persistently high rates of clinical underdiagnosis of ED (Miller, 2000) (Vasan et al., 2025). Notably, ED not only directly impacts patients’ sexual quality of life (QoL) but is also regarded as an “early warning signal” for male cardiovascular health, exhibiting close pathological associations with metabolic diseases like diabetes and hypertension (Yafi et al., 2016). Thus, achieving early diagnosis and proactive intervention for ED is essential for improving patients’ overall health outcomes.

Arthritis constitutes a complex group of diseases characterized by joint inflammation, encompassing over 100 subtypes. Common clinical forms include osteoarthritis (OA), rheumatoid arthritis (RA), psoriatic arthritis (PsA), gouty arthritis (Gout), ankylosing spondylitis (AS), and axial spondyloarthritis (axSpA) (Fallon et al., 2023) (Britto et al., 2025). Despite this diversity, all forms share common pathological manifestations: mononuclear cell infiltration, synovial inflammation and swelling, localized abscess formation, joint stiffness, and progressive cartilage destruction (Tang, 2019). Severe cases may progress to joint deformity or functional loss, significantly impacting patients’ physical and mental health and QoL (Pei et al., 2025). Epidemiological data indicate that arthritis exhibits a high global prevalence, affecting individuals across all age groups (with higher incidence among middle-aged and elderly populations) (Fallon et al., 2023) (Lites et al., 2023). Its long-term disabling effects and substantial healthcare expenditures constitute a significant socioeconomic burden. Clinical management of arthritis centers on “alleviating inflammation, controlling symptoms, and delaying progression.” Conventional interventions include nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), and glucocorticoids, often combined with physical therapies like acupuncture and heat therapy for synergistic effects (Kolasinski et al., 2020). However, arthritis is not confined to localized joint lesions; it frequently involves multiple extra-articular complications spanning cardiovascular disease, metabolic disorders, and mental health abnormalities (Katz and Bartels, 2024) (Hin et al., 2024). Research confirms that approximately one-third of arthritis patients over 45 years old exhibit anxiety or depression symptoms, with anxiety occurring significantly more frequently than depression (Guglielmo et al., 2018). This state of psychosomatic comorbidity is a significant factor contributing to poor treatment response, chronic recurrence, and difficulty achieving complete remission. Crucially, the systemic chronic inflammatory response, vascular endothelial damage, mental health abnormalities, and metabolic disorders associated with arthritis represent key pathogenic mechanisms underlying ED. Recent clinical studies further confirm a significantly elevated comorbidity rate between ED and arthritis, suggesting a potential shared pathophysiological basis.

In clinical practice, ED is often overlooked due to its “private” nature, leading to long-term neglect of arthritis patients’ sexual health needs. Therefore, clarifying the characteristics and potential mechanisms associated with ED and arthritis and establishing targeted standardized screening and management protocols are of significant practical importance for comprehensively improving patients’ overall health outcomes. This review will systematically organize epidemiological evidence linking the two conditions, deeply explore potential pathophysiological mechanisms, analyze the intrinsic connections between their interactions, and outline future research directions. It aims to provide new insights for ED prevention and treatment while offering references for the clinical management of arthritis and related conditions.

2 Epidemiological evidence of erectile dysfunction and arthritis

Existing observational studies, cohort studies, and meta-analyzes consistently indicate that patients with various types of arthritis have a higher prevalence and incidence risk of ED compared to the general population. The strength of this association varies depending on disease type, disease activity, and comorbidities (Table 1).

Study (Authors, year)DiseaseStudy typeNumber of cases (mean age in years)Number of controls (mean age in years)Diagnostic/Screening tool usedMain findingsLiu, C. et al. (2024) ChinaOACross-sectional study228 (60.0 ± 13.4)2,851 (42.4 ± 14.8)(NHANES)(1) Among the different types of arthritis, OA was significantly associated with ED.
(2) 39.4% of patients with arthritis developed ED, which was much greater than the 14.0% among those without arthritisYan et al. (2024) ChinaOACross-sectional study247 (NA)3,123 (NA)(NHANES)(1) After fully adjusting for all potential confounders, OA showed a significant positive correlation with ED.
(2) A remarkable ED prevalence of 16.56% among OA-diagnosed individuals, significantly surpassing the rates of 4.38% among non-OA counterparts and 7.33% within the NHANES cohortLamey et al. (2025) EgyptOACohort Study100 (37.3 ± 9.72)NAIIEF-5Egyptian obese males undergoing LSG demonstrated significant improvements in erectile function, osteoarthritis, and serum testosterone levelsKarabulut et al. (2022) TurkeyRACohort Study48 (45.58 ± 2.14)NAIIEF-5, DAS28, HAQ-DI(1) After 6 months of tofacitinib treatment, the IIEF-5 score showed significant improvement (p < 0.001)
(2) Changes in IIEF-5 scores were significantly correlated with reductions in DAS28 scores and improvements in HAQ-DI scores (p < 0.001)El Miedany et al. (2012) EgyptRACross-sectional study91 (51.4 + 9.4)NAPROMs, SHIM(1) Among 91 male RA patients, the prevalence of ED reached 53.8%
(2) ED significantly correlated (p < 0.01) with pain score, cardiovascular disease, age, disease activity, fatigue score, and tender joint countYan et al. (2024) ChinaRACross-sectional study182 (NA)3,123 (NA)(NHANES)(1) After fully adjusting for all potential confounders, RA showed a significant positive correlation with ED.
(2) The prevalence of ED among patients with RA was notably higher at 11.11%, markedly surpassing the rates of 3.82% observed among non-RA participants and the broader general population prevalence of 5.51%Wilton et al. (2021a) AmericaRACohort Study260 (57.6 [SD 14.4])260 (57.7 [SD 14.4])REDCapED incidence was not increased in men with RA and ED diagnosis was not associated with an increased risk of cardiovascular disease in RA.Wilton et al. (2021b) AmericaPsACohort Study128 (42.3 [SD 13.1])128 (42.4 [SD 13.1])CASPAR Criteria(1) The cumulative incidence of ED in PsA was higher than the cumulative incidence in comparators, with an increasing divide between the men with PsA and the comparators with time
(2) The 45% increased risk of ED in men with PsA compared to men without PsA did not reach statistical significanceLobo et al. (2024) BrazilPsACross-sectional study12 (52.1 ± 9.7)NACASPAR Criteria, MSQ, IIEF(1) Among the male patients, sexual performance was good to excellent (50%) or fair (50%) according to the MSQ.
(2) Eleven of 12 patients (91.7%) had some degree of ED in at least one domain of the IIEF, with a predominance of mild ED.Dhakad et al. (2015) IndiaASCase-control study100 (age range: 20–56)100 (age range: 20–50)IIEF, HADS, BASFI, BASDAI, VAS, PGAED was associated with higher patient age, longer AS duration, anxiety, depression and higher BASFI in AS patientsRostom et al. (2013) MoroccoASCross-sectional study110 (38.9 ± 12.5)NABASDAI, BASFI, BASMI, HADS, Hamilton Anxiety Scale, MAF(1) Thirty (41%) male AS patients reported experiencing ED.
(2) Fatigue and sleep disturbance were independently associated with erectile dysfunctionSantana et al. (2017) BrazilASCross-sectional study40 (45.8 ± 11.41)40 (46.0 ± 11.1)IIEF-5, BASDAI, HAQ, ASDAS(1) AS patients had a median score on IIEF of 22.0, while controls had 29, with p < 0.0001
(2) Only 17.5% of the AS patients had no erectile dysfunction, in contrast to 87.5% of controls (p < 0.0001)
(3) Multiple regression showed that BASDAI was the only variable independently associated with IIEF.Nisihara et al. (2021) BrazilASCross-sectional study35 (52.8 ± 7.1)104 (51.9 ± 8.0)IIEF-5, BASDAI, ASDAS-CRP(1) AS patients had lower IIEF scores than controls (P = 0.02)
(2) Among AS patients, IIEF scores showed significant negative correlations with BASDAI (P = 0.001) and ASDAS-CRP (P = 0.02)Zhang Y. et al., (2023) ChinaASMeta analysis393(NA)NAIIEF/IIEF-5, BASDAI(1) The ED prevalence estimate was 44% with statistical heterogeneity
(2) Men with AS were at a significantly higher risk for ED when compared with the general population without AS.
(3) Patients with AS had significantly lower values in the IIEF erectile function domain as compared with the healthy control subjectsFan et al. (2015) ChinaASMeta analysis535(NA)430(NA)IIEFEach domain of the IIEF score was lower in men with AS than in controlsSariyildiz et al. (2013) TurkeyASCross-sectional study70 (36.4 ± 7.4)60 (35.2 ± 7.7)IIEF, BASDAI, BASFI, BASMI, BASRI, ASQoL, HADS(1) The patients with AS had significantly lower scores in each of the 5 domains of the IIEF compared to the healthy control group (p < 0.05)
(2) The BASDAI, BASFI, BASMI, BASRI, ASQoL, HADS scores and CRP levels were negatively correlated with IIEF (p < 0.05)Erdem et al. (2020) TurkeyASCase-control study50 (37.7 ± 7.6)50 (37.0 ± 6.8)IIEF-5, BDI, BAI, BASDAI, BASFI, BASMI, ASQoL(1) The mean IIEF-EF domain score of the AS group was significantly lower than that of the control group (p = 0.004)
(2) The mean IIEF score was lower in patients with AS, and this had a negative correlation with BASDAI, BASFI, ASQoL, BDI and BAI scoresHu et al. (2025) Chinar-axSpACross-sectional study113 (30.9 ± 7.3)73 (29.1 ± 4.3)SEQ, BASDAI, ASDAS, VAS, HADS(1) Patients with r-axSpA scored significantly lower on erectile function score, individual satisfaction score and couple satisfaction score, and total score based on SEQ (p < 0.05)
(2) The two-sample MR analysis demonstrated no causal effect of r-axSpA on the risk of ED based on the inverse variance weighted methodLeila et al. (2021) TunisiaSpA, RACase-control study50 (44.3 ± 12.1)50 (48.8 ± 13.9)IPSS, IIEF-5, BASDAI, ASDAS, BASFI(1) The prevalence of ED in RD patients was not significantly higher than in controls
(2) The severity of LUTS for patients with RD (RA and SpA) was significantly associated with ED (p = 0.008)Abdul Sultan et al. (2017) EnglandGoutCohort Study9,653(NA)38,218(NA)(CPRD)(1) The absolute rate of ED post-gout diagnosis was 193 per 10,000 person-years. This corresponded to a 31% increased relative risk and 0.6% excess absolute risk compared to those without gout
(2) Compared to those unexposed, the risk of ED was also high in the year before gout diagnosisHsu et al. (2015) ChinaGoutCohort Study35,265 (49.6 [SD = 16.20])70,529 (49.1 [SD = 16.50])(NHIRD)(1) Men with gout were more likely to have an increased risk of ED than those without gout
(2) Patients with gout were 1.52 times more likely to develop OED and 1.18 times more likely to develop PED than patients in the control group
(3) The risk of developing ED was greater for patients with comorbidities of CKD, diabetes, hyperlipidemia, depression, and anxietyChen et al. (2015) ChinaGoutCohort Study19,368 (42.7 ± 12.0)77,472 (42.7 ± 12.0)(NHIRD)(1) The gout cohort exhibited a 1.21-fold adjusted HR of subsequent ED development compared with the non-gout cohort
(2) Compared to patients without gout and comorbidities, the patients with both gout and any type of comorbidity exhibited a 2.04-fold risk of developing ED.Kim et al. (2019) KoreaGoutCross-sectional study80 (52 [44–59])70 (50 [42–55])IIEF-5, HOMA-IR(1) Gout patients were more likely to have ED than controls
(2) HOMAIR was an independent predictor of ED.Yigit et al. (2024) TurkeyGoutCross-sectional study134 (56 [48–62])104 (47 [40.5–54.5])IIEF-EF, HOMA-IR(1) The mean IIEF-EF score of gout patients was significantly lower than that of healthy subjects
(2) Multivariable logistic regression revealed that increased CIMT was the only factor independently associated with ED.

Main characteristics of epidemiological studies on arthritis and ED.

Abbreviations: ED, erectile dysfunction; OA, osteoarthritis; RA, rheumatoid arthritis; PsA, psoriatic arthritis; AS, ankylosing spondylitis; SpA, spondyloarthritis; r-axSpA, rheumatoid factor-negative axial Spondyloarthritis; CASPAR, criteria, Classification of Psoriatic Arthritis Criteria; IIEF, international index of erectile function; IIEF-5, International Index of Erectile Function-5; IIEF-EF, International Index of Erectile Function-Erectile Function domain; SHIM, sexual health inventory for men; MSQ, male sexual quotient; SEQ, sexual experience questionnaire; NHANES, national health and nutrition examination survey; REDCap, Research Electronic Data Capture; CPRD, clinical practice research datalink; NHIRD, national health insurance research database; DAS28, Disease Activity Score in 28 Joints; HAQ-DI, Health Assessment Questionnaire-Disability Index; PROMs, Patient-Reported Outcome Measures; HADS, hospital anxiety and depression scale; BASFI, bath ankylosing spondylitis functional index; BASDAI, bath ankylosing spondylitis disease activity index; VAS, visual analog scale for pain; PGA, patient global assessment scale; MAF, multidimensional assessment of fatigue; BASMI, bath ankylosing spondylitis metrology index; ASDAS, ankylosing spondylitis disease activity score; ASDAS-CRP, Ankylosing Spondylitis Disease Activity Score-C-reactive Protein; BASRI, bath ankylosing spondylitis radiology index; ASQoL, ankylosing spondylitis quality of life questionnaire; IPSS, international prostate symptom score; HOMA-IR, homeostasis model assessment of insulin resistance; LSG, laparoscopic sleeve gastrectomy; NA, not available.

2.1 OA

OA is the most common degenerative joint disease, arising from the gradual wear and tear of articular cartilage over time. It can affect one or multiple synovial joints, including small joints of the hands and large joints such as the knees and hips. Primary symptoms of OA include joint pain, transient morning stiffness, and crepitus during joint movement. Ultimately, it may lead to joint instability and physical dysfunction, thereby impairing QoL (Martel-Pelletier et al., 2016). Traditionally viewed as a “wear-and-tear degenerative disease” caused by chronic joint overload and biomechanical abnormalities, OA has been primarily associated with cartilage destruction and subsequent inflammatory responses. However, it is now well-established that OA represents a complex pathophysiological process driven by both inflammatory mediators and metabolic abnormalities. This involves multi-tissue, multi-molecular coordinated regulation, rather than being solely the consequence of “mechanical injury” (Abramoff and Caldera, 2020).

Population studies demonstrate a significant association between OA and ED. An analysis based on the US National Health and Nutrition Examination Survey (NHANES 2001–2004) revealed markedly elevated ED risk among OA patients. The study showed an ED prevalence of 48.9% in the OA group versus 14.0% in the non-arthritis group (p < 0.001), indicating substantially higher ED incidence among OA patients. After fully adjusting for all potential confounders, OA remained significantly positively correlated with ED, with an OR of 1.11 (95% CI: 1.03–1.20, P = 0.017) (Liu C. et al., 2024). Another analysis based on NHANES 2001–2004 similarly demonstrated a significant positive correlation between OA and ED. The study showed that after fully adjusting for all potential confounders, OA patients still had a 113% increased risk of ED compared to non-OA patients (OR = 2.13, p < 0.0001). Suggesting the association between OA and ED is independent of other risk factors (Yan et al., 2024). Furthermore, an Egyptian follow-up study of 80 patients undergoing laparoscopic sleeve gastrectomy (LSG) found that among obese men with OA, the prevalence of OA decreased from 50.0% preoperatively to 18.8% 1 year postoperatively. Concurrently, ED-related indicators improved, with significant reductions in both subjective ED scores and objective hormonal markers (Lamey et al., 2025). Although this study did not directly analyze the independent association between OA and ED, it suggests that the relationship between OA and ED may be influenced by body weight status.

2.2 Autoimmune/inflammatory arthritis

Autoimmune/inflammatory arthritis (IA) constitute a group of chronic immune-mediated inflammatory conditions collectively termed IA. They are characterized by recurrent episodes of joint inflammation and progressive destruction of joint structures resulting from abnormal immune system activation (Chang and Nigrovic, 2019) (Noversa de Sousa et al., 2024). Clinically common forms of IA include RA, AS, PsA, and other forms of spinal arthritis (SpA) (Wu, 2020).

2.2.1 RA

RA is a chronic, systemic, autoimmune inflammatory disease primarily affecting joints and surrounding soft tissues (Smolen et al., 2018). It leads to joint dysfunction, bone and cartilage damage, and may cause permanent functional impairment or disability (Behl et al., 2022) (Smolen et al., 2016). Most RA patients experience an insidious onset with slow progression, initially presenting as joint pain and swelling affecting one or a few joints, which gradually evolves into symmetrical polyarthritis (Di Matteo et al., 2023). RA can cause complications affecting multiple systems, many of which severely impact patients’ QoL and significantly increase mortality risk (Zeng et al., 2025).

Multiple studies have documented the association between RA and ED: A prospective Turkish survey of tofacitinib (a JAK inhibitor) in RA patients showed that among 48 patients with concomitant ED, the International Index of Erectile Function (IIEF-5) score increased from a baseline of 9.35–9.90 (P < 0.001) after 6 months of treatment. And the change in IIEF-5 score was significantly correlated with reduced disease activity score on 28 joints (DAS28) and improved QoL as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI) (p < 0.001), suggesting that controlling RA inflammation may improve ED (Karabulut et al., 2022). A cross-sectional study in Egypt involving 231 RA patients found that among the 91 male participants, the prevalence of ED reached 53.8%. ED was significantly associated with disease activity, pain scores, cardiovascular disease, and age (p < 0.01) (El Miedany et al., 2012). This suggests that male RA patients with higher disease activity, more severe joint pain, and concomitant cardiovascular disease have a higher risk and more severe degree of ED. A meta-analysis of 11 RA studies showed that in eight studies examining sexual function, the prevalence of ED/sexual dysfunction (SD) among male RA patients (33%–62%) was significantly higher than in healthy controls (11%–40%). This was similarly associated with disease activity and pain, and ED was frequently accompanied by decreased libido and reduced sexual intercourse satisfaction (Perez-Garcia et al., 2020). A cross-sectional study analyzing 3,305 participants further confirmed a strong positive correlation between ED and RA. This association remained significant even after fully adjusting for all potential confounders (OR = 1.67, 95% CI: 1.08–2.57, P = 0.0216), suggesting the relationship is independent of other risk factors (Yan et al., 2024).

However, existing research findings vary. An American cohort study (260 RA patients and 260 healthy controls) showed that the incidence of ED in RA patients did not differ significantly from age-matched controls and was unaffected by age stratification. However, RA patients with ED exhibited an increased risk of peripheral artery disease (PAD), with a significant interaction between RA and ED on PAD risk. Concurrently, these patients demonstrated reduced risks of myocardial infarction, heart failure, and mortality (Wilton et al., 2021a).

Current studies on the association between RA and ED exhibit varying results due to differences in geographic location, study design, and sample characteristics. Future research should involve larger sample sizes, multicenter settings, and long-term follow-up in prospective studies to clarify the differences in the association between the two conditions across different populations and identify key influencing factors.

2.2.2 PsA

PsA is a chronic immune-mediated inflammatory disease and a seronegative inflammatory arthritis closely associated with psoriasis (Perez-Chada et al., 2025). Approximately 25%–30% of psoriasis patients develop PsA (Ganatra and Chandran, 2025) (Mehta et al., 2025). PsA can systematically affect joints, skin, and the musculoskeletal system, manifesting as inflammation-mediated multi-tissue damage (Feldkamp and Raychaudhuri, 2025) (Scrivo et al., 2023).

Two existing studies indicate a trend toward increased ED risk in male PsA patients: A U.S. cohort study of 128 age-matched pairs of PsA patients and controls showed a higher prevalence of pre-diagnosis ED in males (7%) compared to controls (3%) at baseline. And after long-term follow-up, the 20-year cumulative incidence of ED in the PsA group (19%) was also higher than that in the control group (13%), with PsA males having a 45% increased risk of ED compared to non-PsA males (Wilton et al., 2021b). Although the above comparison was not statistically significant, the gap in cumulative ED incidence between the two groups gradually widened with longer follow-up, suggesting a higher ED risk in PsA males. A Brazilian cross-sectional study involving 23 PsA patients found that 11 out of 12 male patients (91.7%) exhibited some degree of SD in at least one domain of the IIEF, predominantly mild SD. Additionally, the severity of psoriatic skin lesions (PASI) showed a significant positive correlation with patients’ overall sexual satisfaction, further supporting the association between PsA and increased ED risk in men (Lobo et al., 2024). However, existing studies are limited by small sample sizes and geographically concentrated populations. Future research should conduct multicenter, large-sample, cross-regional cohort studies to enhance statistical power through larger sample sizes and determine whether this association is statistically significant.

2.2.3 AS

AS is a rheumatic and autoimmune disease associated with chronic, progressive inflammatory responses (Ni et al., 2024) (Zhang W. et al., 2023), primarily affecting the axial skeleton, such as the spine and sacroiliac joints, while also presenting with peripheral joint involvement and extra-articular manifestations (Martini et al., 2024). AS involves concurrent inflammation, bone erosion, and pathological ossification, disrupting the balance of bone remodeling (Feng et al., 2023). Clinically, it commonly manifests as pain, stiffness, or limited mobility in the spine and sacroiliac joints. Severe cases may lead to joint deformity, destruction, and even lifelong disability (Zhang W. et al., 2023).

A prospective case-control study involving 100 male AS patients and 100 healthy male controls demonstrated a significantly higher prevalence of ED in the AS group compared to healthy controls (OR = 3.04, 95% CI 1.52–6.13, P = 0.0006) (Dhakad et al., 2015), indicating a significantly higher risk of ED in AS patients compared to the healthy population. Another cross-sectional study involving 110 male AS patients found that 41% of sexually active male AS patients experienced ED, which was independently positively correlated with fatigue and sleep disorders (Rostom et al., 2013). A Brazilian cross-sectional study of 40 AS patients demonstrated that only 17.5% of the AS group had no ED, compared to 87.5% in the control group, representing a significant difference (p < 0.0001). Multivariate regression analysis further revealed that only the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score was an independent predictor of ED (Santana et al., 2017), indicating that AS patients have a significantly higher ED prevalence than healthy individuals, with more severe ED associated with higher disease activity. A separate Brazilian cross-sectional observational study corroborated these findings. This study included 35 AS patients and 104 healthy controls, revealing that only 28.5% of AS patients reported “no ED” significantly lower than the 53.8% in the control group. Conversely, the “severe ED” rate reached 17.1% among AS patients, substantially higher than the 4.8% in controls. It also confirmed that AS patients overall had significantly weaker erectile function than healthy individuals, and ED showed a significant negative correlation with BASDAI and the Ankylosing Spondylitis Disease Activity Score - C-reactive protein (ASDAS-CRP) (Nisihara et al., 2021).

A meta-analysis incorporating eight studies and 393 adult male AS patients revealed an ED prevalence of 44%, indicating nearly half of AS patients experience ED. The study also confirmed that AS patients have a significantly higher risk of developing ED compared to healthy individuals, with a pooled relative risk (RR) = 2.04 (95% CI: 1.28–3.25, P = 0.003) (Zhang Y. et al., 2023). Another Chinese meta-analysis incorporating 11 studies reached similar conclusions. This study included 535 male AS patients and 430 controls. The results showed that AS patients scored significantly lower than controls across all IIEF dimensions, with the most significant difference observed in intercourse satisfaction (IS), followed by orgasmic function (OF) and erectile function (EF). Additionally, the incidence of ED and comprehensive sexual dysfunction was significantly higher among male AS patients than in healthy individuals, with a median prevalence of sexual dysfunction reaching 33.6%. This association was prevalent in both Caucasian and Asian populations (Fan et al., 2015). Another bicenter cross-sectional study involving 70 male AS patients and 60 healthy controls from rehabilitation departments at two Turkish university hospitals revealed significantly lower scores across all five domains of the IIEF compared to healthy controls (P < 0.0001). Further analysis indicated that BASDAI, the Ankylosing Spondylitis Functional Index (BASFI), the Ankylosing Spondylitis Measurement Index (BASMI), the Ankylosing Spondylitis Radiographic Index (BASRI), the Ankylosing Spondylitis Quality of Life Scale (ASQoL), the Hospital Anxiety and Depression Scale (HADS), and the inflammatory marker C-reactive protein (CRP) levels were all negatively correlated with IIEF scores (P < 0.05) (Sariyildiz et al., 2013). Additionally, a prospective case-control study in Turkey enrolled 50 male patients with confirmed AS and 50 healthy male controls. Results showed that the incidence of ED among AS patients (38%) was higher than that in healthy controls (30%), though the difference was not statistically significant. However, AS patients exhibited significantly lower IIEF-EF scores, with those experiencing ED demonstrating even lower scores (Erdem et al., 2020).

Collectively, these prospective case-control studies, cross-sectional studies, and meta-analyzes demonstrate that male AS patients exhibit a significantly higher overall risk and severity of ED compared to healthy males. Only one Turkish prospective study failed to observe a statistically significant difference in ED prevalence. Yet, it still confirmed significantly lower IIEF-EF scores in AS patients, further substantiating the negative impact of AS on male erectile function.

2.2.4 SpA/axSpA

SpA is a group of chronic inflammatory rheumatic diseases often presenting with inflammation of the sacroiliac joints, peripheral joints, and spine, sharing overlapping genetic, clinical, and radiographic features (Lopalco et al., 2025; Rosine and Miceli-Richard, 2020; Toussirot and Wendling, 2005). AxSpA represents a subset of SpA primarily affecting the sacroiliac joints and spine, frequently progressing to ankylosis, severe disability, and functional impairment (Lopalco et al., 2025). Although chronic back pain and spinal stiffness are typical initial symptoms, peripheral (e.g., enthesitis, arthritis, and dactylitis) and extra-musculoskeletal (e.g., uveitis, inflammatory bowel disease, and psoriasis) manifestations are also common (Navarro-Compán et al., 2025) (Bittar and Deodhar, 2025). Based on the presence or absence of radiographic evidence of sacroiliac joint erosions and spinal ankylosis, axSpA can be classified as radiographic axSpA (r-axSpA) or non-radiographic axSpA (nr-axSpA) (Li et al., 2022) (McGonagle et al., 2024).

A Chinese cross-sectional study involving 113 male r-axSpA patients and 73 healthy male controls demonstrated that r-axSpA patients scored significantly lower than healthy controls on total sexual experience, erectile function, personal satisfaction, and partner satisfaction, with all differences being statistically significant (all p < 0.001). Multivariate linear regression analysis revealed that disease activity, physical disability, functional limitations, health status, sleep quality, and psychological state (anxiety/depression) were significant determinants of erectile dysfunction in r-axSpA patients (all p < 0.05). However, a two-sample Mendelian randomization (MR) analysis conducted as an extension of this study revealed no significant causal association between r-axSpA and ED risk (all p > 0.05) (Hu et al., 2025). These findings suggest that r-axSpA does not directly cause ED at the genetic level but somewhat indirectly mediates ED through disease-related symptoms and comorbid factors. Another cross-sectional case-control study involving 50 rheumatic disease (RD) patients (37 with SpA, 13 with RA) and 50 healthy controls showed an ED prevalence of 80% in the RD group versus 70% in healthy controls, with no statistically significant difference between groups (p = 0.2). Additionally, the study found that after stratifying patients based on the severity of lower urinary tract symptoms (LUTS) assessed by the International Prostate Symptom Score (IPSS) (mild/moderate/severe), the proportion of ED in RD patients showed a significant upward trend with increasing LUTS severity, with statistically significant differences between different LUTS severity groups (p = 0.03) (Leila et al., 2021). Although this study did not conclusively demonstrate that SpA directly increases ED prevalence, it suggests that RD may indirectly influence ED through other pathways. Further validation of these associations requires larger-scale longitudinal studies.

2.3 Gout

Gout is an inflammatory arthropathy caused by hyperuricemia, characterized by the deposition of urate crystals (monosodium urate, MSU) in joints and surrounding tissues, leading to acute inflammatory responses, pain, and swelling (Dehlin et al., 2020). Gout is marked by episodic acute inflammation, alternating between acute flare-ups and asymptomatic hyperuricemic periods (Helget and Mikuls, 2024), representing the terminal stage of uric acid (UA) metabolism disorders (Xu et al., 2025). The risk of gout increases with age, making it more prevalent in the elderly population (Dehlin et al., 2020).

Gout frequently coexists with metabolic syndrome. Existing research reveals a significant association between gout and ED, with gout patients exhibiting higher ED prevalence, incidence risk, and severity compared to non-gout individuals (Liu Y. F. et al., 2024). Studies indicate that elevated serum UA levels increase the risk of erectile dysfunction by more than 2.5-fold (Shen et al., 2025), and each 1 mg/dL increase in UA doubles the risk of ED (Salem et al., 2014). A prospective cohort study from the UK Clinical Practice Research Datalink (CPRD) revealed that among 9,653 gout patients and 38,218 controls, the incidence rate of ED in gout patients was 193 per 10,000 person-years, with a hazard ratio (HR) = 1.31 (95% CI: 1.24–1.40, P < 0.001), with an excess absolute risk of 0.6%. The study also found that ED risk was elevated 1 year before gout diagnosis (RR = 1.63, 95% CI 1.27–2.08) (Abdul Sultan et al., 2017).

A Taiwanese study based on the National Health Insurance Research Database (NHIRD), involving 35,265 gout patients and 70,529 controls, showed that gout patients had a 1.21-fold higher overall risk of ED compared to non-gout individuals. Specifically, the risk of organic ED (OED) increased by 1.52-fold, and the risk of psychogenic ED (PED) increased by 1.18-fold. The study also found that the risk of ED further increased when gout patients had comorbidities such as chronic kidney disease, diabetes, hyperlipidemia, depression, or anxiety (Hsu et al., 2015). Another nationwide cohort study based on the NHIRD reached similar conclusions. This study included 19,368 gout patients and 77,472 controls. Results showed that the incidence rate of ED in the gout cohort was significantly higher than that in the control cohort (p < 0.001). Additionally, the study found that gout patients with any one chronic disease (such as diabetes, hypertension, ischemic heart disease, etc.) had a significantly increased risk of ED (adjusted HR = 2.04, 95% CI: 1.63–2.57, P < 0.001). Furthermore, the incidence of ED in both cohorts increased with advancing age (Chen et al., 2015). A case-control study involving 80 gout patients and 70 healthy controls demonstrated a significantly higher prevalence of ED (55.3%) among gout patients compared to healthy controls (41.4%, p = 0.047). The study also indicated that gout patients had approximately 1.3 times higher ED prevalence than controls (Kim et al., 2019). Furthermore, gout may indirectly increase ED risk by affecting bilateral carotid intima-media thickness (CIMT). A cross-sectional study in Turkey involving 134 male gout patients and 104 healthy controls demonstrated that the gout group exhibited significantly higher prevalence of ED and incidence of CIMT thickening compared to the control group (both p < 0.001). Moreover, among patients with gout and CIMT thickening, the ED prevalence reached 97.9%, significantly higher than the other three subgroups (p < 0.001) (Yigit et al., 2024).

The above research evidence consistently indicates a clear association between gout and ED. The incidence and risk of ED in gout patients are significantly higher than in non-gout individuals. Elevated serum uric acid levels, coexisting T2DM, chronic kidney disease, hyperlipidemia, depression/anxiety, and CIMT thickening further exacerbate this risk. Notably, the risk of ED begins to rise as early as 1 year before a definitive gout diagnosis, providing a potential basis for early warning of ED in gout patients.

To summarize, epidemiological evidence across osteoarthritis, autoimmune/IA (including RA, PsA, AS, SpA/axSpA), and gout consistently shows that diverse arthritides are independently associated with increased prevalence and incidence of ED. This holds even after adjusting for confounding factors, including age, comorbid metabolic diseases, and cardiovascular conditions. This cross-subtype association prompts a central mechanistic inquiry: do inflammatory and metabolic arthritides converge on common final pathways to induce ED, such as shared vascular endothelial injury or disruption of the NO–cGMP–PKG axis? Or do their distinct primary pathologies impart unique mechanistic signatures that ultimately lead to erectile dysfunction? Examples of such distinct pathologies include proinflammatory cytokine dysregulation in rheumatoid arthritis, HLA-B27-mediated autoinflammation in ankylosing spondylitis, and hyperuricemia-induced cellular toxicity in gout. The following section will systematically dissect these