Metabolic and hormonal biomarkers of erectile dysfunction: the role of atherogenic index and testosterone-to-estradiol ratio

Biomarcadores metabólicos y hormonales de la disfunción eréctil: el papel del índice aterogénico y de la relación testosterona/estradiol

Background: We aimed to investigate the relationship between erectile dysfunction (ED), the atherogenic index of plasma (AIP) and the testosterone-to-estradiol (T/E2) ratio. Given the role of metabolic and hormonal imbalances in ED, we sought to determine whether these parameters could serve as potential biomarkers for ED risk assessment. Methods: A retrospective included 117 ED patients and 115 controls. Participants’ demographic, clinical and biochemical data were collected, including body mass index (BMI), lipid profile and hormone levels. The AIP was calculated as log10 (triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C)) and the T/E2 ratio was determined. Univariate and multivariate logistic regression analyses were conducted to assess the associations between these factors and ED. Results: ED patients had significantly higher AIP levels (0.639 ± 3.02) compared to controls (0.131 ± 0.15, p < 0.001). Additionally, the T/E2 ratio was significantly lower in ED patients (10.96 ± 5.97) than in controls (17.31 ± 8.12, p < 0.001). Obesity, as indicated by a higher BMI, was also strongly associated with ED (p < 0.001). Multivariate analysis identified BMI Odds Ratio (OR: 1.354, p < 0.001), E2 levels (OR: 1.080, p < 0.001) and AIP (OR: 2.31, p < 0.001) as independent predictors of ED. Conclusions: We suggest that both metabolic and hormonal imbalances contribute to ED pathophysiology. The increased AIP levels observed in ED patients highlight the potential role of lipid metabolism dysfunction and atherosclerosis in erectile function impairment. The reduced T/E2 ratio indicates the influence of hormonal imbalance, particularly the detrimental effects of increased aromatization of testosterone into estradiol. Given that AIP and T/E2 are associated with cardiovascular and endocrine health, they may serve as valuable biomarkers for early ED risk assessment. These results emphasize the importance of lifestyle interventions, weight management and metabolic optimization in preventing and managing ED.

Resumen

Antecedentes: Nuestro objetivo fue investigar la relación entre la disfunción eréctil (DE), el índice aterogénico del plasma (IAP) y la relación testosterona/estradiol (T/E2). Dado el papel de los desequilibrios metabólicos y hormonales en la fisiopatología de la DE, se evaluó si estos parámetros pueden servir como biomarcadores potenciales para la evaluación del riesgo de DE. Métodos: Se realizó un estudio retrospectivo con 117 pacientes con DE y 115 controles. Se recopilaron datos demográficos, clínicos y bioquímicos, incluidos el índice de masa corporal (IMC), el perfil lipídico y los niveles hormonales. El IAP se calculó como log10 (triglicéridos/colesterol HDL), y se determinó la relación T/E2. Se aplicaron análisis de regresión logística univariada y multivariada para evaluar las asociaciones entre estos factores y la DE. Resultados: Los pacientes con DE presentaron niveles significativamente más altos de IAP (0.639 ± 3.02) en comparación con los controles (0.131 ± 0.15, p < 0.001). Además, la relación T/E2 fue significativamente menor en los pacientes con DE (10.96 ± 5.97) que en los controles (17.31 ± 8.12, p < 0.001). La obesidad, reflejada en un mayor IMC, también se asoció fuertemente con la DE (p < 0.001). El análisis multivariado identificó al IMC (razón de probabilidades (OR): 1.354, p < 0.001), los niveles de E2 (OR: 1.080, p < 0.001) y el IAP (OR: 2.31, p < 0.001) como predictores independientes de la DE. Conclusiones: Nuestros hallazgos sugieren que los desequilibrios metabólicos y hormonales contribuyen de manera significativa a la disfunción eréctil. El aumento del IAP observado en pacientes con DE resalta el posible papel de la disfunción del metabolismo lipídico y la aterosclerosis en la alteración de la función eréctil. La reducción de la relación T/E2 indica un impacto hormonal desfavorable, particularmente por el aumento de la aromatización de testosterona a estradiol. Dado que el IAP y la relación T/E2 están relacionados con la salud cardiovascular y endocrina, pueden constituir biomarcadores útiles para la evaluación temprana del riesgo de DE. Estos resultados subrayan la importancia de las intervenciones sobre el estilo de vida, el control del peso y la optimización metabólica en la prevención y manejo de la DE.

Erectile dysfunction (ED); Atherogenic index of plasma (AIP); Testosterone-to-estradiol ratio (T/E2)

Palabras Clave

Disfunción eréctil; Índice aterogénico del plasma (IAP); Relación testosterona/estradiol (T/E2)

[1] Bruening A, Perez M, Josephs J. Overall mental health and misuse of erectile dysfunction medication among sexual minority men. Substance Use & Misuse. 2019; 54: 1825–1833.

[2] Leslie SW, Sooriyamoorthy T. Erectile dysfunction. Treasure Island (FL): StatPearls Publishing: United States. 2024.

[3] Miner M, Parish SJ, Billups KL, Paulos M, Sigman M, Blaha MJ. Erectile dysfunction and subclinical cardiovascular disease. Sexual Medicine Reviews. 2019; 7: 455–463.

[4] Diaconu CC, Manea M, Marcu DR, Socea B, Spinu AD, Bratu OG. The erectile dysfunction as a marker of cardiovascular disease: a review. Acta Cardiologica. 2020; 75: 286–292.

[5] Piegza M, Smolarczyk J, Piegza J. Sexual and cardiovascular health. Factors influencing on the quality of sexual life of coronary heart disease patients—a narrative review. Vascular Health and Risk Management. 2025; 21: 51–60.

[6] Kaltsas A, Zikopoulos A, Dimitriadis F, Sheshi D, Politis M, Moustakli E, et al. Oxidative stress and erectile dysfunction: pathophysiology, impacts, and potential treatments. Current Issues in Molecular Biology. 2024; 46: 8807–8834.

[7] Lorigo J, Gomes D, Ramalho AR, Silva E, Mendes P, Figueiredo A. Reassessing cardiovascular risk stratification in men with erectile dysfunction. Archivio Italiano di Urologia e Andrologia. 2024; 96: 12427.

[8] Ermis E, Ozbay Ozyilmaz S, Salabas E, Senol C, Cengiz M, Allahverdiyev S, et al. The relationship between erectile dysfunction and the atherogenic index of plasma. International journal of impotence research. 2020; 32: 462–468.

[9] Fernández-Macías JC, Ochoa-Martínez AC, Varela-Silva JA, Pérez-Maldonado IN. Atherogenic index of plasma: novel predictive biomarker for cardiovascular illnesses. Archives of Medical Research. 2019; 50: 285–294.

[10] Lumu W, Bahendeka S, Wesonga R, Kibirige D, Kasoma RM, Ssendikwanawa E. Atherogenic index of plasma and its cardiovascular risk factor correlates among patients with type 2 diabetes in Uganda. African Health Sciences. 2023; 23: 515–527.

[11] Bai S, Chen T, Li Y, Li X, Du R. Comparison of prognostic value of triglyceride-glucose index and atherogenic index of plasma in patients with acute coronary syndrome: a retrospective study. JRSM Cardiovascular Disease. 2025; 14: 20480040251341155.

[12] Chen Y, Lu C, Ju H, Zhou Q, Zhao X. Elevated AIP is associated with the prevalence of MAFLD in the US adults: evidence from NHANES 2017–2018. Frontiers in Endocrinology. 2024; 15: 1405828.

[13] Bolat MS, Ozbek ML, Şahin B, Yılmaz M, Kocamanoglu F, Buyukalpelli R, et al. Impact of high visceral adiposity index associated with metabolic syndrome on erectile function in sexually active men: results of a cross-sectional study. International Journal of Clinical Practice. 2021; 75: e14111.

[14] Corona G, Rastrelli G, Vignozzi L, Maggi M. Androgens and male sexual function. Best Practice & Research Clinical Endocrinology & Metabolism. 2022; 36: 101615.

[15] Chen Z, Jiang J, Jiang R. A low testosterone level impairs erectile function by increasing endocan expression in rat penile corpus cavernosum. The Journal of Sexual Medicine. 2024; 21: 663–670.

[16] Naamneh Elzenaty R, du Toit T, Flück CE. Basics of androgen synthesis and action. Best Practice & Research Clinical Endocrinology & Metabolism. 2022; 36: 101665.

[17] Rojas-Zambrano JG, Rojas-Zambrano A, Rojas-Zambrano AF. Impact of testosterone on male health: a systematic review. Cureus. 2025; 17: e82917.

[18] Traish A, Kim N. The physiological role of androgens in penile erection: regulation of corpus cavernosum structure and function. The Journal of Sexual Medicine. 2005; 2: 759–770.

[19] Salonia A, Bettocchi C, Boeri L, Capogrosso P, Carvalho J, Cilesiz NC, et al. European association of urology guidelines on sexual and reproductive health—2021 update: male sexual dysfunction. European Urology. 2021; 80: 333–357.

[20] Ma Y, Fan X, Han J, Cheng Y, Zhao J, Fang W, et al. Critical illness and sex hormones: response and impact of the hypothalamic-pituitary-gonadal axis. Therapeutic Advances in Endocrinology and Metabolism. 2025; 16: 20420188251328192.

[21] Auer MK, Joue G, Biedermann SV, Sommer T, Fuss J. The effect of short-term increase of estradiol levels on sexual desire and orgasm frequency in women and men: a double-blind, randomized, placebo-controlled trial. Psychoneuroendocrinology. 2024; 160: 106682.

[22] Traish AM. Negative impact of testosterone deficiency and 5α-reductase inhibitors therapy on metabolic and sexual function in men. Advances in Experimental Medicine and Biology. 2017; 1043: 473–526.

[23] El-Sakka AI. Impact of the association between elevated oestradiol and low testosterone levels on erectile dysfunction severity. Asian Journal of Andrology. 2013; 15: 492–496.

[24] Pan D, Xu ZH, Gao Q, Li M, Guan Y, Zhao ST. Relationship between penile erection and the ratio of estradiol to testosterone: a retrospective study. Andrologia. 2020; 52: e13701.

[25] Guo L, Nan Y, Yao L. Association between atherogenic indexes and erectile dysfunction: a cross-sectional analysis of the national health and nutrition examination survey 2001–2004. International Urology and Nephrology. 2024; 56: 2877–2885.

[26] Corona G, Mannucci E, Schulman C, Petrone L, Mansani R, Cilotti A, et al. Psychobiologic correlates of the metabolic syndrome and associated sexual dysfunction. European Urology. 2006; 50: 595–604.

[27] Lv J, Yao J, Zheng L, Shao J, Jin J, Zheng Q, et al. Association between atherogenic index of plasma and all-cause mortality and cardiovascular disease among individuals with non-alcoholic fatty liver disease or metabolic dysfunction-associated steatotic liver disease. Diabetology & Metabolic Syndrome. 2025; 17: 153.

[28] Mohammadrezaei A, Mokhtari Ardekani A, Abbasalizad-Farhangi M, Mesgari-Abbasi M, Mousavi R. Association between sex hormone-binding globulin, atherogenic indices of plasma among young sedentary males. Nutrition and Metabolic Insights. 2023; 16: 11786388231155006.

[29] Zhu D, Pham QM, Wang C, Colonnello E, Yannas D, Nguyen BH, et al. Erectile dysfunction and oxidative stress: a narrative review. International Journal of Molecular Sciences. 2025; 26: 3073.

[30] Engin A. Endothelial dysfunction in obesity and therapeutic targets. Advances in Experimental Medicine and Biology. 2024; 1460: 489–538.

[31] Okobi OE, Khoury P, De la Vega RJ, Figueroa RS, Desai D, Mangiliman BDA, et al. Impact of weight loss on testosterone levels: a review of BMI and testosterone. Cureus. 2024; 16: e76139.

[32] Defeudis G, Mazzilli R, Tenuta M, Rossini G, Zamponi V, Olana S, et al. Erectile dysfunction and diabetes: a melting pot of circumstances and treatments. Diabetes/Metabolism Research and Reviews. 2022; 38: e3494.