What is PDE5, and how do PDE5 inhibitors work?

Erectile dysfunction (ED) is incredibly common, and if you’ve been researching treatments, you’ve probably come across medicines like Sildenafil or Tadalafil. These belong to a group of drugs called PDE5 inhibitors, but what does that actually mean? And how do they support better erections?

Let’s take a closer look at the science behind these ED medicines.

What is PDE5?

PDE5 stands for phosphodiesterase type 5. It’s an enzyme found in the walls of blood vessels throughout your body, including those in the penis. Its job is to help regulate blood flow by breaking down a molecule called cyclic guanosine monophosphate (cGMP).

cGMP is the chemical messenger that relaxes blood vessels, allowing them to widen so more blood can flow through. When PDE5 breaks cGMP down, those blood vessels tighten again, and blood flow returns to normal. In other words:

• cGMP = relaxes blood vessels (improves flow)
• PDE5 = breaks down cGMP (reduces flow)

Both are essential for controlling blood flow to specific areas in the body, including increasing blood flow to the penis to give an erection. But if PDE5 acts too quickly or strongly, it can interrupt the process that allows an erection to form or last long enough to enjoy sex.

How erections work

An erection might seem simple from the outside, but it’s actually the result of a finely tuned series of reactions involving the brain, nerves, hormones, and blood vessels. Here’s a closer look:

1. Erections start in the brain. When you become sexually aroused, your brain sends signals down the spinal cord to the nerves in the penis.
2. These signals cause the nerve endings in the penis to release nitric oxide (NO). This is the key chemical trigger that initiates the erection process.
3. Nitric oxide stimulates the production of cGMP, the molecule that relaxes the smooth muscles lining the blood vessel walls in the penis.
4. As the muscles relax, the arteries widen, and blood flow into the penis increases. This causes the penis to fill, harden, and become erect.
5. Blood is temporarily trapped inside the penis, helping to maintain your erection for as long as you feel sexually aroused.

When sexual stimulation ends, the erection naturally subsides — which is where PDE5 comes in.

What PDE5 does in the erection process

PDE5 is responsible for helping the body return to its normal, non-aroused state. It does this by breaking down cGMP, the chemical that keeps blood vessels relaxed during an erection.

This is a completely normal process that ensures erections don’t last indefinitely. But in some men, PDE5 can break down cGMP too quickly, which means the blood vessels constrict before the erection is fully firm or sustained. These men may struggle with getting or maintaining an erection.

That’s where PDE5 inhibitors like Sildenafil or Tadalafil may help. They gently slow down this process and help blood flow last longer during arousal (1).

What PDE5 inhibitors do

PDE5 inhibitors work by blocking the PDE5 enzyme from breaking down cGMP too quickly. This means cGMP stays active for longer, keeping the blood vessels relaxed and allowing more blood to stay in the penis during sexual arousal.

The result is that erections may become easier to achieve and maintain, but only when you’re sexually stimulated (2–3). Think of it like this: PDE5 inhibitors don’t create an erection. They support the body’s natural response by making it easier for the signals that start one to do their job properly.

What PDE5 inhibitors don’t do

• They don’t increase your sex drive. They work on blood vessels, not desire.
• They don’t cause automatic erections. They only work when you’re already aroused.
• They don’t permanently improve erections. You need to take the medicine each time you plan to have sex.

Are PDE5 inhibitors safe and effective?

Yes, PDE5 inhibitors are well-researched, clinically approved medicines that have been used safely for decades. They are prescribed to millions of men worldwide and are considered first-line treatments for erectile dysfunction (4).

Side effects can occur, but they’re usually mild and temporary (2–3). Your doctor will help determine which option and dose are right for you to minimise side effects while maximising your results.

Understanding your options

Erectile dysfunction can feel discouraging, but it’s also one of the most treatable sexual health conditions. PDE5 inhibitors offer an evidence-based, practical way to support firmer erections when sexually aroused and improve your confidence in the bedroom.

At Oxford Online Pharmacy, our UK-registered doctors can help you explore PDE5 inhibitors or other safe, effective ED treatments through a simple, discreet online ED consultation.

References

1. NHS. Erectile dysfunction (impotence) [Internet]. nhs.uk. 2019.
2. NHS. Common questions about sildenafil [Internet]. nhs.uk. 2022.
3. NHS. Common questions about tadalafil [Internet]. nhs.uk. 2022.
4. BSSM. A practical guide on managing erectile dysfunction [Internet]. bssm.org.uk. 2024.