Erectile dysfunction is a frequently observed disorder characterized by the persistent inability to achieve or maintain a satisfactory penile erection necessary for a fulfilling sexual experience (1). It primarily affects males over the age of 40 (2), data from the Massachusetts Male Aging Study revealed that degrees of ED, from mild to severe, affected 52% of males aged between 40 and 70 (3). The etiology of ED is multifaceted, involving both psychogenic and organic factors (4). ED has a strong correlation with a range of risk factors and comorbidities, including but not limited to obesity, lack of physical activity, tobacco use, alcohol addiction, diabetes, hypertension, dyslipidemia, and hypogonadism. Additionally, it is worth noting that ED can serve as a prognostic marker for cardiovascular disorders such as CVD, coronary heart disease, and stroke (5, 6). Identifying modifiable risk factors that contribute to this condition is pivotal, considering the substantial influence of ED on the health-related quality of life among aging men. This identification will facilitate the development of effective strategies for prevention and management. A comprehensive understanding of the intricate connections between ED and its associated risk factors is essential for mitigating the consequences of this condition on affected individuals and society at large.

Telomeres, which are evolutionarily conserved nucleoprotein structures found at the ends of chromosomes, play a crucial role as aging markers by regulating cellular senescence (7). As cells divide, the protective telomeric repeats undergo a natural shortening process. When telomeres shorten beyond a crucial length, cells halt their division and either enter a state of senescence or experience programmed cell death. Factors (8–12) such as chronic inflammation, oxidative stress, unhealthy lifestyles, and nutrition can accelerate this shortening, leading to adverse health conditions (13–16) such as infection, cardiovascular disease, cancer, mental illness, and other age-related disorders. Hence, comprehending the primary factors attributing to telomere diminution is imperative in unraveling the underlying pathophysiological mechanisms accountable for these enduring ailments.

Thus far, there exists a scarcity of research investigating the potential link between LTL and ED. To expand our comprehension of the influence of LTL on ED and offer valuable perspectives for its prevention, this cross-sectional investigation endeavors to explore the correlation between LTL and ED in a cohort of American adults. The data utilized for this study is extracted from the NHANES.

Our study aimed to investigate the potential correlation between the LTL and ED using a nationally representative cross-sectional design. This topic has received limited research attention, highlighting the gap in knowledge that our study addresses. We found a negative correlation between LTL and ED, suggesting that longer LTL are associated with an decreased risk of ED. To account for confounding factors, we conducted multiple logistic regression analysis and various sensitivity analyses, ensuring the stability and robustness of our results. Additionally, this is the first population-based cross-sectional analysis to examine the influence of LTL on ED, adding valuable insights to the existing literature in this field.

Extensive research (21–25) has demonstrated a significant correlation between telomere shortening and the development and progression of aging, cancer, and various diseases. Thorough exploration into the functionality and regulation of telomere holds great promise in enhancing our understanding of its impact on human health and disease. This knowledge creates opportunities for potential future therapeutic interventions.

Previous studies (25–29) have linked shorter LTL to traditional risk factors for ED, such as smoking, diabetes mellitus, cardiovascular disease, hypertension, and obesity. In our study, we collected an extensive range of indicators, including demographic data, lifestyle habits, and medical history, while also considering potential confounding factors related to ED. Consistent results were obtained through the use of diverse adjustment models. Initially, we observed a non-linear relationship between LTL and ED in the unadjusted model. However, this relationship disappeared after accounting for confounding factors. Further investigation is necessary to clarify the nature of this non-linear relationship.

Patients with ED often have multiple chronic conditions (30–32). The impact of LTL on ED may be influenced by different disease states. Subgroup analyses indicated that longer LTL had a more pronounced protective effect against ED in control groups compared to disease groups among individuals with cardiovascular disease, hypertension, and chronic kidney disease. Conversely, individuals with diabetes mellitus showed an opposite trend. No interactions were observed between the subgroups, thus reinforcing the stability of the findings.

To validate the reliability of our findings concerning LTL and ED, we additionally narrowed down the definition of ED as individuals who reported being “never able” to maintain an erection. Remarkably, even after adjusting for different models, the results remained robust and consistent.

Recently, Dilixiati et al. (33) presented a study that closely aligns with our investigation of the relationship between LTL and ED. Their research suggests an inverted J-curve relationship between LTL and ED, which is an intriguing concept. Although our study populations are similar, there are minor differences in the participant selection criteria that may have contributed to the observed variations in outcomes. Our research, in comparison to that of Dilixiati et al., incorporates a broader perspective on the relationship between LTL and ED, including BMI, anemia, albumin, CRP, SII, and AST, which are also known risk factors for ED and thus essential to consider. In addition to the variables included in their study, such as hyperlipidemia and ED medications, our study provides a broader perspective on potential confounding factors. While Dilixiati et al.’s logistic regression analysis initially revealed a negative correlation between LTL and ED in the unadjusted model, this relationship became positive after model adjustment, leading them to propose an inverted J-curve relationship. However, they noted that this curve did not fully explain the results of their multivariate logistic regression analysis. Our findings, on the other hand, consistently demonstrate a negative correlation across all analytical approaches, suggesting a potential L-shaped relationship between LTL and ED, which is also consistent with the results of our logistic regression analysis. This underscores the robustness of our observed association. The methodological differences in covariate adjustment, particularly regarding the treatment of age, may account for the divergent findings between the two studies. We selected age as a categorical variable based on preliminary evidence and clinical observations indicating a nonlinear association with ED. In contrast, Dilixiati et al. treated age as a continuous variable, offering an alternative perspective on the data. The nuanced differences between our results and those of Dilixiati et al. highlight the complexity of the LTL-ED relationship. Our study contributes an additional layer of understanding by suggesting that the method of covariate adjustment can significantly influence the interpretation of outcomes. We appreciate the valuable insights provided by Dilixiati et al. and believe that our findings, while distinct, complement the existing body of knowledge and contribute to a more comprehensive appreciation of the LTL-ED dynamic.

The potential mechanisms underlying the association between LTL and ED may be elucidated from the following perspectives: Firstly, studies (34, 35) indicate that telomerase is closely linked to endothelial cell aging. DNA damage and subsequent telomere attrition are implicated as key factors driving the development of endothelial cell aging in vascular diseases. Consequently, endothelial cell dysfunction resulting from cellular senescence can give rise to various vascular-related disorders, with ED emerging as an early clinical manifestation of subclinical endothelial dysfunction. Secondly, telomere shortening is widely recognized as a hallmark of aging and is intricately intertwined with other aging-related processes (21). The malfunctioning of telomeres can exacerbate these mechanisms and contribute to the occurrence and progression of aging-related diseases, including ED. Thirdly, telomere shortening can potentially increase the risk of oxidative stress and inflammatory responses (36–40), which in turn could have adverse effects on erectile function. This is due to the impact on endothelial cell function, vasodilation, and blood flow regulation, ultimately leading to difficulties in achieving and sustaining an erection. Lastly, telomere shortening may be linked to neuronal activity and signal transmission (41–43), which are essential components in the nervous system’s role in erectile function. Disruption of these neural processes by telomere shortening could further impact erectile function. Considering that LTL is associated with numerous diseases that can impact ED, in clinical settings, strategies aimed at slowing down the rate of telomere shortening hold promise for potentially mitigating the occurrence of ED.

The main strength of this study lies in the reliable data obtained from the NHANES database. The survey employed a rigorous design, reasonable sampling, and a large sample size, enabling the inclusion of abundant variables. Additionally, multiple regression analysis models were constructed to account for various confounding factors during data analysis. Furthermore, different forms of independent variables, including both continuous and categorical variables, were included in the models.

We would like to acknowledge a few limitations in our study that need to be considered. Firstly, the diagnosis of ED relied on self-reported information from the participants, without any clinical confirmation or assessment of the severity of ED. This could potentially introduce misclassification or recall bias. Secondly, due to the cross-sectional design of our study, we are unable to establish causal relationships between LTL and ED. To further investigate the role of LTL in ED and determine the persistence of the associations observed in our study, it is essential to conduct longitudinal studies with larger sample sizes and extended follow-up periods. Thirdly, it is important to highlight that the findings of our study may not directly apply to other racial/ethnic groups or geographical regions, as our study primarily focused on the population of the United States. Despite these limitations, our population-based study significantly adds to our understanding of the relationship between LTL and ED in adults.

Our study revealed a notable inverse relationship between LTL and the likelihood of ED. Individuals with longer LTL demonstrated a lower risk of developing ED. Therefore, interventions aimed at delaying or counteracting LTL shortening could potentially reduce the risk of ED.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.

The studies involving humans were approved by the National Health Statistics Center. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

XC: Writing – original draft. BL: Formal Analysis, Writing – original draft. JZ: Methodology, Writing – original draft. JL: Methodology, Software, Writing – original draft. WJ: Writing – review & editing. RX: Conceptualization, Validation, Writing – review & editing.