Importantly, ED is associated with an increased risk of cardiovascular (CV) events and is considered an early warning sign of coronary artery and peripheral vascular disease.¹

Men with ED have an increased risk of all-cause mortality odds ratio (OR) 1.26 and CVD mortality OR 1.43. Furthermore, men with ED are 1.33- to 6.24-times more likely to have benign prostatic hyperplasia (BPH), and 1.68-times more likely to develop dementia.²

 Classification and risk factors

ED can be classified as:^1,3,4

• Organic: Vascular, neurogenic (eg multiple sclerosis, epilepsy), Peyronie's disease (a non-cancerous condition resulting from fibrous scar tissue that develops on the penis and causes curved, painful erections), medication side effects (eg antidepressants, finasteride, anxiolytics, neuroleptics, muscle relaxants), and endocrinologic sources (eg diabetes, metabolic syndrome, Klinefelter's syndrome, congenital hypogonadotropic hypogonadism, acquired hypogonadotropic hypogonadism and cryptorchidism).
• Psychogenic: Psychological factors such as self-reported depressive symptoms (OR=2.88), pessimistic attitudes (OR=3.89), a negative outlook on life, self-reported emotional stress (OR=3.56), a history of sexual coercion (OR=3.52) and socioeconomic factors, including a decrease in household income during the past five years.
• Mixed: Most cases have mixed aetiology.

Apart from the above-mentioned, other risk factors for ED include age, diabetes, dyslipidaemia, hypertension, obesity, smoking, atrial fibrillation, hyperthyroidism, vitamin D deficiency, and chronic kidney disease.¹

Emerging evidence suggests associations between ED and sleep disorders, psoriasis, gouty arthritis, and ankylosing spondylitis. Furthermore, cycling, and pelvic ring fractures may result in the onset of ED, especially in younger men.¹

Urological conditions like lower urinary tract symptoms (LUTS), chronic prostatitis, bladder pain syndrome, and premature ejaculation are often associated with ED. Surgical treatments for BPH-LUTS have varying effects on erectile function and urethral reconstructive surgery and prostate biopsy have also been linked to temporary ED risk.¹

 How is ED diagnosed?

The 2023 European Association of Urology guidelines recommend that every patient should undergo a thorough physical examination, focusing on the genitourinary, endocrine, vascular, and neurological systems. This examination can unveil unexpected conditions like Peyronie's disease, genital lesions, prostatic abnormalities, or signs of hypogonadism.¹

It's essential to assess prior or concurrent penile issues, and measure blood pressure, heart rate, body mass index (BMI), or waist circumference to evaluate comorbidities such as metabolic syndrome, if not measured in the past three to six months.¹

The EAU recommends that laboratory testing should be based on a patient's complaints and risk factors. If not done in the past year, patients should undergo fasting blood glucose or HbA1_c, lipid profile, and early morning fasting total testosterone measurements.¹

Bio-available or calculated-free testosterone values may be necessary in some cases. However, ED typically signifies more severe hypogonadism, with a low threshold for testosterone.

Diagnostic evaluation for ED involves various tests and assessments. Nocturnal penile tumescence and rigidity testing measures erectile episodes, rigidity, and duration during sleep. It helps differentiate between organic and psychogenic ED.¹

Intra-cavernous injection tests assess vascular status based on erectile response. Dynamic duplex ultrasound studies penile blood flow. Arteriography is considered for penile revascularisation, while psychopathological and psychosocial assessments explore mental health, relationship factors, and cognitive influences.¹

Tailored interviews and self-reported measures are used. Additionally, sexual minority groups may have unique psychological risks associated with ED, requiring specialised assessment and care.¹

Additional tests, like total prostate-specific antigen, prolactin, and luteinizing hormone, may be considered in specific cases. While physical examination and lab evaluations may not pinpoint the exact cause, they help identify comorbid conditions associated with ED.¹

 What are the treatment goals in ED?

Overall, treatment goals should be individualised to restore sexual satisfaction for patients and/or couples and improve QoL based on patients' expressed needs and desires.¹

Patient education is crucial for addressing ED, as understanding the condition's psychological and physiological aspects can improve sexual satisfaction. Treatment options for ED vary based on the underlying causes, which can be modifiable or linked to other conditions.¹

Lifestyle changes, such as managing diabetes or hypertension, are essential initial steps. The EAU guidelines recommend physical activity, weight loss, and pharmacotherapy targeting CVD risk factors. Statin-based lipid-lowering therapy demonstrates a positive impact on erectile function according to meta-analysis data.¹

Can ED be cured?

According to the EAU, most ED cases cannot be cured, but various therapies are available to improve the condition. The EAU recommends oral pharmacotherapy using phosphodiesterase type 5 inhibitors (PDE5Is). PDE5Is facilitate erection by promoting the formation of cyclic guanosine monophosphate and relaxing penile smooth muscles.¹

Tadalafil and sildenafil are the two most common PDE5Is used to treat ED. Tadalafil, approved for ED treatment in 2003, is effective within 30 minutes, with peak efficacy after about two hours and lasting up to 36 hours. It can be taken on-demand or as a daily dose. Adverse effects are generally mild and self-limited.^1,5

Tadalafil has demonstrated efficacy in various ED patient subgroups, including those with comorbid conditions like diabetes. Yildirim et al aimed to compare the efficacy of three tadalafil regimens for patients with type 2 diabetes mellitus, at least one microvascular complication and ED.^1,6

Patients were randomised into three groups: Group 1 used 5mg tadalafil daily, Group 2 used 20mg tadalafil two hours before sexual relations twice a week and Group 3 used 5mg tadalafil daily and an extra 15mg tadalafil two hours before sexual relations twice a week.⁶

After treatment, the median International Index of erectile function (IIEF-5) scores were significantly higher in Group 3 compared to Groups 1 and 2. The groups were comparable in terms of the percentage of positive responses to the sexual encounter profile (SEP) 2 and the Global Assessment Questionnaires (GAQ)-1. However, the percentage of patients with positive responses to SEP-3 (20%, 40% and 75%, respectively) and GAQ-2 (20%, 45% and 75%, respectively) was significantly higher in Group 3.⁶

Therefore, using a combination treatment (daily 5mg  plus 15mg when needed) to treat erectile function in patients with DM-related ED in the first stage may be more efficient with the same reliability and greater patient satisfaction.⁶

Furthermore, studies have shown that tadalafil significantly increases ejaculatory and orgasmic function (vs placebo) across all baseline ED, ejaculation disorders (EjD), and orgasmic dysfunction (OD) severity.⁶

In the tadalafil group, 66% of subjects with severe EjD reported improved ejaculatory function compared with 36% in the placebo group. Similarly, 66% of the tadalafil-treated subjects with severe OD reported improvement.⁶

Sildenafil vs tadalafil: What do patients prefer?

Although sildenafil and tadalafil showed similar results with regard to efficacy, tolerability, and patient satisfaction, randomised controlled trials showed that tadalafil seems to improve sexual confidence.⁵

To put this to the test, von Büren et al evaluated data of a large online prescription platform, specifically analysing patient (n=26 821) preference for tadalafil over sildenafil. ⁵

They found that tadalafil prescriptions increased significantly from 30% (first order) to 80% (last order) in patients who had already tested both drugs. Patients with age ≤40 years, BMI ≤25kg/m², and sustained morning erections preferred tadalafil to sildenafil.⁵

Conclusion

Tadalafil has emerged as a valuable and versatile treatment option for ED, a condition that can significantly impact the psychosocial health and quality of life of affected individuals. ED, with its complex interplay of organic, psychogenic, and mixed etiologies, often serves as an early warning sign for CV and other comorbidities, emphasising the importance of comprehensive evaluation.

The 2023 EAU guidelines underscore the significance of lifestyle modifications, including physical activity and weight management, alongside the management of CV risk factors.

Accurate diagnosis is pivotal, and the EAU guidelines recommend a thorough physical examination and tailored laboratory testing to identify underlying causes and comorbid conditions. Treatment goals should be individualised to enhance sexual satisfaction and QoL.

Tadalafil, with its long-lasting effects and minimal adverse effects, stands out as a leading oral option. It offers hope to a wide range of patient subgroups, including those with diabetes-related ED, ejaculation disorders, and orgasmic dysfunction. Patient preference studies have shown a growing inclination toward tadalafil, underscoring its role in improving sexual confidence.

References

1. Salonia A, Bettocchi C, Capogrosso P, et al. EAU Guidelines on Sexual and Reproductive Health. 2023 [Internet]. Available at: https://d56bochluxqnz.cloudfront.net/documents/full-guideline/EAU-Guidelines-on-Sexual-and-Reproductive-Health-2023.pdf
2. Kessler A, et al. The global prevalence of erectile dysfunction: A review. BJUI International, 2019.
3. Ludwig L, Phillips M. Organic Causes of Erectile Dysfunction in Men Under 40 . Urol Int,
4. Rosen RC. Psychogenic erectile dysfunction: Classification and Management. Urologic Clinics of North America, 2001.
5. von Büren M, Rodler S, Wiesenhütter I, et al. Digital Real-world Data Suggest Patient Preference for Tadalafil over Sildenafil in Patients with Erectile Dysfunction. European Urology Focus, 2022.
6. Yildirim C, Salman MY, Yavuz A, Bayar G. Comparison of three different tadalafil regimens for erectile dysfunction treatment in patients with diabetes mellitus microvascular complications. Andrologia, 2023.
7. Paduch DA, Bolyakov A, Polzer PK, Watts SD. Effects of 12 weeks of tadalafil treatment on ejaculatory and orgasmic dysfunction and sexual satisfaction in patients with mild to severe erectile dysfunction: integrated analysis of 17 placebo-controlled studies. BJU Int, 2013.