Sildenafil — evidence-based review (for educational purposes only)

Disclaimer: This article is for informational and educational purposes only. It does not replace professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare professional regarding personal medical decisions.

Quick summary

• Sildenafil is a prescription medication most commonly used to treat erectile dysfunction (ED) and pulmonary arterial hypertension (PAH).
• It works by increasing blood flow through inhibition of the enzyme phosphodiesterase type 5 (PDE5).
• Strong clinical evidence supports its effectiveness for ED and PAH.
• Common side effects include headache, flushing, nasal congestion, and indigestion; serious side effects are rare but possible.
• It should not be used with nitrates (often prescribed for chest pain) due to the risk of dangerous drops in blood pressure.

What is known

1. Mechanism of action (how it works)

Sildenafil belongs to a class of drugs called PDE5 inhibitors. It blocks the enzyme phosphodiesterase type 5, which normally breaks down cyclic guanosine monophosphate (cGMP). Higher levels of cGMP relax smooth muscle and widen blood vessels (vasodilation).

In erectile tissue, this enhances blood flow in response to sexual stimulation. In the lungs, it reduces vascular resistance, which helps in pulmonary arterial hypertension.

2. Effectiveness for erectile dysfunction (ED)

Multiple randomized controlled trials and long-term studies show that sildenafil significantly improves erectile function compared to placebo. It has been studied in men with diabetes, cardiovascular disease, spinal cord injury, and after prostate surgery.

Major organizations such as the American Urological Association (AUA) and the European Association of Urology (EAU) recommend PDE5 inhibitors, including sildenafil, as first-line therapy for ED in appropriate patients.

3. Effectiveness for pulmonary arterial hypertension (PAH)

Sildenafil is also approved for pulmonary arterial hypertension under specific brand names. Clinical trials show improvement in exercise capacity (measured by 6-minute walk distance), hemodynamic parameters, and some quality-of-life measures.

Guidelines from the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) include PDE5 inhibitors among recommended therapies for certain PAH patients.

4. Safety profile

Common side effects:

• Headache
• Facial flushing
• Indigestion (dyspepsia)
• Nasal congestion
• Visual changes (bluish tint, light sensitivity)

Less common but serious risks:

• Severe low blood pressure (especially with nitrates)
• Sudden hearing loss (rare)
• Priapism (erection lasting more than 4 hours, medical emergency)
• Cardiovascular events in high-risk individuals

When prescribed appropriately and taken as directed, sildenafil is generally considered safe for most eligible patients.

5. Drug interactions

The most important interaction is with nitrates (e.g., nitroglycerin, isosorbide mononitrate), which can cause a life-threatening drop in blood pressure.

Caution is also required with:

• Alpha-blockers
• Strong CYP3A4 inhibitors (e.g., certain antifungals, macrolide antibiotics, protease inhibitors)
• Other PDE5 inhibitors

What is unclear / where evidence is limited

• Long-term cardiovascular outcomes: While sildenafil appears safe in stable cardiovascular disease when used appropriately, data on long-term cardiovascular outcomes in all populations are limited.
• Use in women: Evidence for sildenafil in female sexual dysfunction is inconsistent and not sufficient for routine recommendation.
• Performance enhancement: Studies on athletic performance at sea level show little to no benefit in most individuals.
• Over-the-counter supplements: Many “natural” sexual enhancement products secretly contain sildenafil or similar substances, but these are unregulated and potentially dangerous.

Overview of approaches

Management depends on the underlying condition (e.g., erectile dysfunction vs pulmonary hypertension) and overall health status.

For erectile dysfunction

• Assessment of cardiovascular risk
• Identification of contributing factors (diabetes, smoking, medications, psychological stress)
• First-line pharmacologic options: PDE5 inhibitors such as sildenafil

Typical dosing information for erectile dysfunction can be found in the official U.S. prescribing information from the FDA:
FDA-approved prescribing information database.

For pulmonary arterial hypertension

• Risk stratification and specialist evaluation
• Combination therapy depending on severity
• Monitoring of functional status and hemodynamics

Official dosing and administration details are available through regulatory agencies such as the
European Medicines Agency (EMA).

Importantly, medication choice and adjustments should always be guided by a qualified healthcare professional.

Related topics

You may also find helpful information in our articles on:

• Erectile dysfunction: causes and evaluation
• Cardiovascular risk and sexual activity
• Pulmonary hypertension overview

Evidence summary table

Statement	Confidence level	Why
Sildenafil improves erectile function compared to placebo.	High	Supported by multiple randomized controlled trials and guideline recommendations.
Sildenafil improves exercise capacity in PAH.	High	Backed by controlled trials and incorporated into international guidelines.
Sildenafil is safe in most appropriately selected patients.	High	Extensive post-marketing surveillance and long-term clinical use data.
Sildenafil improves athletic performance in healthy individuals.	Low	Studies show inconsistent or minimal benefit at sea level.
Sildenafil is effective for female sexual dysfunction.	Low–Medium	Evidence is mixed and not sufficient for routine clinical use.

Practical recommendations

General safety measures

• Do not combine sildenafil with nitrates or recreational “poppers.”
• Inform your doctor about all medications and supplements.
• Avoid purchasing sildenafil from unverified online sources.
• Seek urgent medical care for chest pain after use or an erection lasting more than 4 hours.

When to see a doctor

• If erectile dysfunction is new, worsening, or associated with other symptoms.
• If you have heart disease, uncontrolled blood pressure, or diabetes.
• If you experience visual or hearing changes after taking the medication.
• If you are being evaluated for pulmonary hypertension symptoms such as unexplained shortness of breath.

How to prepare for a consultation

• List all medications (including over-the-counter and herbal products).
• Be ready to discuss cardiovascular history.
• Describe symptom duration, severity, and associated factors.
• Ask about benefits, risks, alternatives, and monitoring.

Sources

• American Urological Association (AUA). Erectile Dysfunction Guideline.
• European Association of Urology (EAU). Guidelines on Sexual and Reproductive Health.
• European Society of Cardiology (ESC) / European Respiratory Society (ERS). Guidelines for Pulmonary Hypertension.
• U.S. Food and Drug Administration (FDA). Prescribing Information for sildenafil.
• European Medicines Agency (EMA). Public assessment reports for sildenafil-containing products.