How Do Erectile Dysfunction Tablets Work, and Why Might They Fail?

Medication is one of the first steps in erectile dysfunction, following accurate diagnosis and assessment of lifestyle factors. The best known members of this group are the oral drugs known in medical terms as PDE5 inhibitors. Despite their widespread use, these tablets are frequently misunderstood: some men expect them to create sexual desire, while others conclude after a single unsuccessful attempt that the medication does not suit them.

In a significant proportion of cases where the tablets are thought not to work, however, the problem is not that the drug is ineffective but how it is taken, the dose chosen, or an underlying cause that has not been addressed. This article covers how PDE5 inhibitors act, when they do not deliver the expected benefit, the most common mistakes in use, and which patients should not take them.

How does an erection happen?

To understand how these drugs act, it helps to look briefly at how an erection occurs. With sexual stimulation, a molecule called nitric oxide is released from nerve endings and from the inner lining of blood vessels. This molecule triggers a series of reactions in the vessel walls of the penis, leading to a rise in a second molecule called cGMP.

As cGMP rises, the vascular muscle relaxes, blood flow into the penis increases and the erectile tissue fills with blood. The filled tissue compresses the veins that carry blood away from within, so inflow increases while outflow decreases and rigidity is maintained. When sexual stimulation ends, an enzyme called PDE5 breaks down cGMP, the vessels return to their previous state and the penis becomes flaccid.

An erection is therefore a process in which the nervous system, the blood vessels and hormonal balance work together. A problem at any link in this chain can lead to erectile dysfunction.

What do PDE5 inhibitors do?

These drugs temporarily block PDE5, the enzyme that breaks down cGMP. As a result cGMP remains active for longer, vascular relaxation is strengthened, and an erection is achieved and maintained more easily.

There is a crucial detail here: these drugs support the continuation of the chain, not its beginning. Without sexual stimulation, nitric oxide release does not start and there is no process for the drug to support. PDE5 inhibitors therefore do not produce an erection on their own; they strengthen the response to sexual stimulation.

This distinction is the point patients most often get wrong. Expecting an erection after taking a tablet without any stimulation creates the impression that the drug is ineffective.

Do these tablets increase sexual desire?

No. PDE5 inhibitors act at the level of the blood vessels and have no direct effect on sexual desire (libido). Reduced desire relates more to hormonal causes, depression, relationship difficulties, chronic fatigue and the side effects of certain medications.

An indirect contribution can be mentioned, however: a man who gains confidence about his erections may experience less performance anxiety, which can indirectly affect his interest in sexual activity. But where the real cause of low desire is hormonal or psychological, these drugs alone are not the answer; testosterone levels and psychological factors need separate assessment.

Why might the medication not work?

In men who do not see the expected benefit, the first step is to review whether the drug is actually being used correctly. The most common reasons are:

• Insufficient sexual stimulation: The drug supports the response to stimulation; no effect should be expected without it.
• Unsuitable dose or timing: Each drug has a different onset and window of action; not following the timing specified by the physician directly affects the result.
• Fatty meals and alcohol: Absorption of some drugs can be delayed after a heavy, fatty meal, while alcohol further weakens the erectile response.
• Judging after a single attempt: Assessing these drugs generally requires several attempts at an appropriate dose; a first unsuccessful attempt does not mean the drug is unsuitable.
• Performance anxiety: Anxiety increasing after a first unsuccessful attempt can adversely affect subsequent ones.
• An underlying cause left unaddressed: Medication alone may not be enough in the presence of uncontrolled diabetes, untreated testosterone deficiency, sleep apnoea or advanced vascular disease.
• Other medications: Some blood pressure drugs, antidepressants and prostate medications can adversely affect erections.
• Nerve damage: The response may be lower than expected where nerves have been affected by radical prostate surgery or advanced diabetes.

Reviewing these reasons allows medication to be reassessed in a large proportion of patients and often improves the response. The conclusion that “the tablet does not work for me” should therefore not be reached without reviewing it with a physician.

Who should not take these drugs?

PDE5 inhibitors cannot be used safely by every patient. The most important restriction concerns people taking nitrate medication for heart disease (sublingual tablets, sprays or certain cardiac drugs). Taking the two groups together can cause a severe drop in blood pressure and carries a risk to life.

Other situations requiring assessment include a recent heart attack or stroke, markedly low blood pressure, uncontrolled arrhythmia, severe liver failure and certain eye conditions. Dose and timing are also adjusted separately when they are used alongside alpha-blocker medication prescribed for prostate enlargement.

Obtaining these drugs online or without a prescription carries serious risks, both because the contents may be unreliable and because these restrictions have not been assessed. Treatment started without assessment in a man with heart disease can have dangerous consequences.

Are erectile dysfunction tablets a risk to the heart?

In appropriately assessed patients these drugs are generally well tolerated. There is, however, an important point that is often overlooked: erectile dysfunction itself can frequently be a warning sign relating to vascular health.

The arteries of the penis are narrower than the larger vessels elsewhere in the body, so the effects of deterioration in the vessel wall may appear here earlier. In a man presenting with erectile dysfunction it is therefore important to assess cardiovascular risk factors rather than simply prescribing a tablet.

In other words, the real question about these drugs should not be “will they harm the heart” but “is there a vascular problem underlying this complaint that needs assessment”.

What comes next if medication does not work?

Where an adequate response is not achieved despite correct use and correction of underlying causes, treatment moves to the next step. These steps are generally as follows:

• Addressing the cause: Blood sugar control, treatment of testosterone deficiency, review of current medications, stopping smoking and weight management.
• Injection therapy into the penis: An option considered in men who do not respond to oral drugs.
• Regenerative approaches: Applications that may be considered in selected cases and where expectations need to be discussed realistically.
• Penile implant surgery: The surgical option assessed in patients who do not benefit from the other steps.

This sequence does not progress at the same pace in every patient; some steps may be skipped where there is advanced vascular disease or nerve damage. The decision follows detailed assessment.

What should be considered for correct use?

Several points stand out in obtaining the expected benefit from medication:

• Taking the drug at the dose and timing specified by the physician
• Understanding that sexual stimulation is necessary for the process
• Avoiding heavy, fatty meals and alcohol before an attempt
• Reviewing the outcome with a physician after several attempts
• Reporting all medications used, including herbal products
• Avoiding products obtained without a prescription or over the internet

Oral medication for erectile dysfunction is an effective step in the right patient when used correctly; but it does not create sexual desire and does not remove the underlying cause. Where no response is obtained, rather than immediately regarding the drug as ineffective, the way it is used, the dose and the underlying causes should be reviewed. Assoc. Prof. Dr. Zülfü Sertkaya practises in urology and andrology in Istanbul; treatment planning in erectile dysfunction is carried out with individual assessment and confidentiality.

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