Daily tadalafil administration improves cardiac autonomic regulation in men with non-organic erectile dysfunction: a prospective heart rate variability study

Abstract Background Non-organic ED patients have cardiac autonomic dysfunction measurable by heart rate variability (HRV). Tadalafil reduces cardiovascular mortality, but exact mechanisms remain unclear. Aim To evaluate daily tadalafil effects on cardiac autonomic regulation in non-organic ED and identify clinical predictors of HRV response. Methods In this prospective study, 82 men with non-organic ED (mean age 46.8 ± 5.0 years) received tadalafil 5-10 mg daily. Assessment included International Index of Erectile Function-Erectile Function (IIEF-EF), echocardiography, laboratory tests, and 24-hour Holter ECG. HRV was analyzed via time-domain (standard deviation of NN intervals [SDNN], root mean square of successive differences [RMSSD]) and frequency-domain (low-frequency power [LF], high-frequency power [HF], LF/HF ratio) parameters. Post-treatment recordings were blindly evaluated. Early response to tadalafil was defined as achievement in the severity-adjusted Minimal Clinically Important Difference (MCID) in IIEF-EF or final IIEF-EF score ≥26. Outcomes Primary: ΔSDNN. Secondary: ΔHF power, ΔLF/HF ratio. Results IIEF-EF improved significantly (15 to 23, P < .001) and 74.4% were early responders (n = 61). In the overall cohort, SDNN increased (42.39 to 52.39 ms, P < .01), HF power increased (267.86 to 294.44 ms2,P < .001), and LF/HF ratio decreased (2.78 to 2.31, P < .01). Both groups showed HRV improvements without between-group differences (P > .05), suggesting autonomic modulation independent of erectile response. Multivariable regression: diabetes negatively predicted SDNN improvement; higher testosterone, higher baseline IIEF-EF score, and lower BMI predicted greater HF enhancement. Only 1.1% of patients discontinued the treatment (due to dyspepsia). Clinical Implications Daily tadalafil treatment may enhance parasympathetic modulation in men with non-organic ED regardless of clinical erectile improvement, suggesting a potential mechanism for its observed cardiovascular benefits. Strengths and Limitations Strengths include rigorous, blinded Holter assessment. Limitations include the lack of a placebo control, short follow-up (28 days), and a small non-responder subgroup. Conclusion Daily tadalafil enhanced parasympathetic modulation and reduced sympathovagal imbalance independently of erectile improvement.