Prevalence of ED

More than 150 million men are affected by ED worldwide. In Africa, an estimated 11.5 million men are affected, says Dr Prithy Ramlachan, Past- President of the African Society for Sexual Medicine.¹

Studies show that one in 20 men aged 40 have a complete inability to attain and/or maintain an erection compared to one in seven men aged >70.¹

In a real-world study of 48 million men, Goldstein et al found that the prevalence of ED is around 6%.³However, notes Dr Ramlachan, this may be an underestimation as only diagnosed men seeking medical treatment were included.¹

Within South Africa, an exploratory study at a primary healthcare clinic in KwaZulu-Natal demonstrated an overall prevalence of 64.9%  in a sample of men aged 18 and older.  Of these men 14.6% reported mild, 19.9%  moderate and 30.4% severe ED.⁴

In men attending primary care clinics in Western Cape, >70% experienced some degree of ED, with 45% experiencing moderate or complete ED.⁵

Men with ED at risk of CVD, diabetes, and depression

The study by Goldstein et al showed that ED is associated with an increased risk of cardiovascular disease (CVD), diabetes and depression - even in younger men (30- to 39-years).³

Men with ED in this study had:³

• 18% prevalence of CVD
• 24% prevalence of diabetes
• 11% prevalence of depression.

In men with diabetes incident ED was a better predictor of CV events than hypertension ,dyslipidaemia and microalbuminuria.⁷

ED not only affects older men

According to Capogrosso et al, the prevalence of ED among younger men are increasing. In their study, 25.9% of men <40-years were diagnosed with ED.⁷

A study by Rastrelli and Maggi found that organic, psychological, and relational conditions are at the root of ED in younger and apparently fit men. The organic causes of ED can be classified into three categories: metabolic and CV, endocrine, and neurologic conditions.⁸

Table 1: Pathophysiology of ED⁹

Psychological impact of ED

Although ED is a benign disease, it has a profoundly negative impact on an individual’s life and well-being, says Dr Ramlachan.¹

It can lead to:¹  

• Reduced quality of life
• Social stigma
• Feeling of emasculation
• Reduced self-esteem
• Depression
• Anxiety
• Significant impact on partner
• Predictor of CV events
• Risk of diabetes.

Can ED be reversed?

According to Dr Ramlachan, ED does not always require medical or device intervention. Furthermore, he says, ED can be reversed or improved if offending drugs or medications are withdrawn and comorbid conditions are well controlled (eg testosterone deficiency, obesity, and metabolic syndrome).¹

What are some of the factors that must be considered when developing a treatment approach?

Dr Ramlachan recommends an individualised risk stratification to determine individual risk factors.  In addition, a sexual history and a focused  diagnostic work-up is mandatory for a successful outcome.¹

Furthermore, he says, risk factors and comorbidities need to be addressed effectively, and both the patient and his partner (if possible) should receive psychological counselling. Numerous studies have shown improved erectile function when couples undergo psychosocial counselling to address for example performance anxiety.¹

Treatment should be initiated based on patient preference, sexual function, and the risk of CVD. Apart from pharmacotherapy, other treatment options include control of risk factors with lifestyle changes (engaging in physical activity, weight loss [about 10% of body weight], introducing healthy eating habits, cigarette smoking cessation, and decreasing alcohol intake).¹

In some instances, ED can be treated with intracavernosal injection therapy, vacuum devices, testosterone (if appropriate) and shockwave therapies.¹

First-line treatment: What do guidelines recommend?

The American Urology Association (AUA) and the European Urology Association (EAU) guidelines recommend oral phosphodiesterase type 5 inhibitor (PDE5i) as first-line treatment for the management of ED.^10,11

When prescribing a PDE5i, the clinician must balance the goals of the man and his partner for successful sexual activity, the need to prescribe an effective PDE5i dose, and the need to minimise adverse effects such as dyspepsia, headache, flushing, back pain, nasal congestion, myalgia, visual disturbance, and dizziness.¹⁰

The EUA guidelines caution that PDE5i is not initiators of an erection and that sexual stimulation to facilitate an erection is required.¹¹

Approved PDE5is include for example sildenafil and tadalafil. Sildenafil was launched in 1998 and was the first PDE5i available on the market. Sildenafil is effective 30-60 minutes after administration. Its efficacy is reduced after a heavy, fatty meal due to delayed absorption. Efficacy may be maintained for up to 12 hours.^10,11

Tadalafil was licensed for the treatment of ED in 2003 and is effective from 30 minutes after administration, with peak efficacy after about two hours. Efficacy is maintained for up to 36 hours and is not affected by food. Usually, tadalafil is administered in on-demand doses of 10mg and 20mg or a daily dose of 5mg.¹¹

Currently, tadalafil is the only oral ED medication approved for daily use, rather than on an as-needed basis.¹²   

A review of the literature and meta-analysis showed that sildenafil and tadalafil have similar efficacy and side-effect profiles. However, tadalafil had improved psychological outcomes including satisfaction with ED treatment, suggesting that this should be considered when deciding which oral medication to prescribe.¹²

Expert opinion suggests that combining daily tadalafil with on-demand sildenafil may result in improved erectile function, particularly in men with severe ED.¹²

Additionally, for men who have difficulty timing an on-demand PDE5i with sexual intercourse or for men experiencing bothersome side effects on higher-dose on-demand medications, the once-daily formulation of tadalafil may allow for better medication compliance, fewer side effects, and therefore better outcomes on the medication.¹²

There has been some recent controversy as to whether these medications can cause melanoma skin cancer or prostate cancer, but there is currently no evidence to support this, and PDE5i remain common and recommended first-line treatments for ED.¹²

Safety and efficacy of tadalafil

Efficacy and safety of tadalafil has been confirmed in post-marketing studies and in almost every subgroup of patients with ED, including difficult-to-treat subgroups.^11,13,14

Hatzichristou et al conducted the first study to determine the efficacy of once-daily tadalafil 2.5mg and 5mg in men living with diabetes and ED. A previous study confirmed the efficacy of the 10mg and 20mg taken on demand by this patient population.¹³

The primary endpoints were International Index of Erectile Function Erectile Function (IIEF EF) Domain score, and patient success rates for vaginal penetration and completion of intercourse. Patient satisfaction, endothelial function biomarkers, and safety were also assessed.¹³

Patients receiving either dose of tadalafil had clinically and statistically significant improvements in IIEF EF and statistically significant improvements in mean success rates for vaginal penetration, completion of intercourse, and overall treatment satisfaction. Endothelial dysfunction biomarkers were unchanged.¹³

Yuan et al showed that in recommended doses, oral PDE5i are more effective than placebo for ED, and tadalafil seems to be the most effective agent, followed by vardenafil. PDE5-Is are generally safe and well tolerated, and there is no major difference on the safety profile.¹⁴

Conclusion

ED is the persistent inability to attain and maintain penile erection sufficient for satisfactory sexual performance and can be caused by a variety of psychological and/or physiological factors, including depression, testosterone deficiency, ageing, and CVD. The prevalence of ED is greater in patients living with diabetes. the most commonly used treatments for ED are PDE-5is. These oral therapies are taken on demand prior to anticipated sexual activity and are efficacious and well tolerated. A unique feature of tadalafil is its mean elimination half-life of 17.5 hours, compared with about four to five hours for sildenafil.¹³

REFERENCES:

1. Personal correspondence. Dr Prithy Ramlachan. 25 July 2022.
2. Shiferaw WS, Akalu TY, Aynalem YA. Prevalence of Erectile Dysfunction in Patients with Diabetes Mellitus and Its Association with Body Mass Index and Glycated Hemoglobin in Africa: A Systematic Review and Meta-Analysis. Int J Endocrinol, 2020.
3. Goldstein I, et al. Real-world observational results from a database of 48 million men in the United States: Relationship of cardiovascular disease, diabetes mellitus and depression with age and erectile dysfunction. Int J Clin Pract, 2018.
4. Lockhat Y, et al. The prevalence of erectile dysfunction at a primary healthcare clinic in Durban, KwaZulu-Natal.South African Family Practice,
5. De Klerk H, De Villiers PJT. Prevalence and characteristics of erectile dysfunction in black and mixed race primary care populations of the Cape Flats and Helderberg Basin area of the Western Cape, South Africa. SA Fam Prac, 2003.
6. Pye SR, Huhtaniemi IT, Finn JD, et al. Late-onset hypogonadism and mortality in aging men. J Clin Endocrinol Metab, 2014.
7. Capogrosso P, Colicchia M, Ventimiglia E. One Patient Out of Four with Newly Diagnosed Erectile Dysfunction Is a Young Man—Worrisome Picture from the Everyday Clinical Practice. J Sex Med, 2013.
8. Rastrelli G and Maggi M. Erectile dysfunction in fit and healthy young men: psychological or pathological? Transl Androl Urol, 2017.
9. Adapted from Lue TF. Erectile dysfunction. N Engl J Med, 2000.
10. Burnett AL, et al. Erectile Dysfunction: AUA Guideline. The Journal of Urology, 2018.
11. Salonia A, et al. EAU Guidelines on Sexual and Reproductive Health. https://d56bochluxqnz.cloudfront.net/documents/full-guideline/EAU-Guidelines-on-Sexual-and-Reproductive-Health-2022_2022-03-29-084141_megw.pdf
12. Krzastek SC, et al. Recent advances in the understanding and management of erectile dysfunction. F1000Research, 2019.
13. Hatzichristou D, et al. Efficacy of tadalafil once daily in men with diabetes mellitus and erectile dysfunction. Diabet Med, 2008.
14. Yuan J, et al. Comparative effectiveness and safety of oral phosphodiesterase type 5 inhibitors for erectile dysfunction: a systematic review and network meta-analysis. Eur Urol, 2013.