Tadalafil, sildenafil and longevity: what do the studies show?

Tadalafil and sildenafil have not been shown to extend life in healthy adults. Medical record studies associate them with fewer deaths, while trials measure their effects on blood flow to the brain. These findings explain the interest in these medicines within longevity research. Their relevance depends on what was measured, in whom, and against which comparison group.

This analysis covers publications identified up to 9 September 2026, including a brain study published on 13 August 2026. It examines the drug family introduced in our overview of longevity pharmacology.

One target, different medicines

Tadalafil, sildenafil, vardenafil and avanafil belong to a group of medicines called phosphodiesterase type 5 inhibitors, or PDE5 inhibitors. Their duration of action and adverse effects vary (PubMed).

PDE5 is an enzyme that breaks down cyclic guanosine monophosphate (cGMP). This messenger helps muscles in blood vessel walls relax. It acts downstream of nitric oxide, a signal produced by the body. By slowing cGMP breakdown, sildenafil helps blood vessels widen, allowing the blood flow needed for an erection (EMA). Researchers are asking whether this action could also preserve aspects of vascular function with age.

Tadalafil has an average half-life of 17.5 hours in healthy people. Half-life means the time needed for its concentration in the blood to fall by half. For sildenafil, it is around 3 to 5 hours. This difference explains the interest in prolonged exposure, without proving greater protection against ageing (EMA) (EMA).

The studies discussed here mainly concern tadalafil and sildenafil. Sharing their target does not establish the same mortality or cognition outcomes for vardenafil or avanafil. Improved erectile function is also a separate outcome from a longevity benefit.

Mortality: associations that warrant a trial

A 2024 meta-analysis, which brings together several studies, includes 16 papers and 1,257,759 participants, 99.4% of them men. Use of these medicines was associated with a 22% lower relative risk of combined cardiovascular events. For death, the relative risk was 30% lower. Median follow-up reached 4.3 years. The literature search ended in May 2023, and the data were almost entirely observational (PubMed).

A study published in the American Journal of Medicine in March 2025 adds data from TriNetX, a network of medical records. It studied men with erectile dysfunction. Observed three-year mortality was 1.95% with tadalafil versus 2.94% in controls made statistically comparable. For sildenafil, the proportions were 2.42% and 3.17%. These correspond to relative differences of 34% and 24%, in two separate comparisons (PubMed).

The findings vary. A 2025 study involved 4,582 veterans who had undergone an examination of their coronary arteries. After matching, which selects groups with comparable characteristics, the analysis included 1,124 people. At one year, the combined measure of several events affected 30.4% of users versus 31.1% of matched controls, with no statistically demonstrated difference (PubMed).

Users may differ in their health, physical or sexual activity, and access to care. A contraindication can also keep the most vulnerable patients out of the exposed group. Statistical adjustments account for measured characteristics; they cannot make unknown characteristics identical. A large database reduces statistical uncertainty without removing these biases.

The brain: what the 2026 studies add

Dementia findings remain inconsistent

In 2024, a UK study following 269,725 men with erectile dysfunction found an association with fewer Alzheimer's diagnoses. The adjusted relative difference was 18%, over a median follow-up of 5.1 years. It became inconclusive when the first three years of follow-up were excluded (PubMed). This sensitivity to timing matters: early changes linked to dementia can precede diagnosis and influence prescribing.

An Israeli study published in a 2025 journal issue found no association. It compared 5,204 new daily tadalafil users with 18,565 users of another medicine for urinary symptoms. Dementia risk was similar. A second analysis of 133,336 men with erectile dysfunction also found no reduction after an average follow-up of 7.9 years. It measured dementia of all causes, whereas the UK analysis focused on Alzheimer's disease (PubMed).

Trials mainly measure how blood vessels function

OxHARP, published in 2024, included 75 patients with disease affecting the brain's small blood vessels after a vascular event. Each participant received sildenafil, another medicine and a placebo in succession, in a randomly assigned order. The placebo contained no active medicine. Each period lasted three weeks. Sildenafil improved some measures of perfusion, meaning the blood supply to tissues. The planned primary measure, blood flow pulsatility, did not improve. Pulsatility describes how blood flow varies with each heartbeat (PubMed).

The latest finding comes from ETLAS-2. Published on 13 August 2026, its MRI analysis compares three months of tadalafil at 20 mg daily with placebo. Participants had disease affecting the brain's small blood vessels and a previous stroke or transient ischaemic attack. The latter is a brief interruption of blood flow to the brain. Among the 60 participants included in this substudy, 42 had usable perfusion data. Overall brain blood flow increased more with tadalafil. The difference was around 3.3 mL of blood per 100 g of tissue per minute. The other MRI measures studied did not differ (PubMed).

The cognitive substudy of the same trial, published in November 2025, found no overall benefit on testing after three months in 60 participants. Imaging and cognition therefore describe two aspects of a single experiment (PubMed). The main study also reports tolerability difficulties at this dose. Adverse events occurred in 76% of tadalafil participants versus 36% with placebo. These events were not necessarily all caused by the medicine (PubMed).

A further study, published online on 13 March 2026, reanalysed samples from 15 people with type 2 diabetes. Each had received six weeks of tadalafil at 20 mg daily and six weeks of placebo in succession. Some blood proteins used to investigate brain diseases decreased with tadalafil. The ratio between two forms of amyloid, a protein studied in Alzheimer's disease, remained unchanged, alongside several other markers. This analysis, planned after the trial, raises a biological hypothesis; it demonstrates neither improved memory nor Alzheimer's prevention (PubMed).

A negative heart trial adds context

PASSION shows how the population studied can change the balance of benefits and risks. This 2024 trial concerned a particular form of heart failure, with high pressure in the lung's blood vessels. Patients were randomly assigned tadalafil, targeting 40 mg daily, or placebo. A supply problem stopped the trial after 125 participants had enrolled, against a planned 372. It found no benefit on the combined measure of hospitalisation for heart failure or death (PubMed).

The authors also reported higher mortality with tadalafil, although the estimate was highly uncertain because of the small sample. This finding concerns a specific heart patient population and a different dose from daily urological use. It prevents cardiovascular protection from being treated as a universal property of the molecule (PubMed).

The favourable large follow-up studies and this negative trial answer different questions. Research needs to establish which patients might benefit, at what exposure, and on which clinical outcome. Better blood flow alone cannot answer those three questions.

What is missing for longevity use

No dose is validated for extending life in a healthy person. Borrowing a dose authorised for another indication does not resolve that lack of evidence. Current findings justify longer trials with outcomes specified in advance: cardiovascular events, independence, cognition and mortality. Trials must also document withdrawals and adverse effects.

The known risks already matter. Headache, flushing, digestive problems and dizziness are among sildenafil's adverse effects. Visual disturbances are also described. Tadalafil can cause muscle or back pain (EMA) (EMA).

Where a medical indication exists, the decision rests on its expected benefit, medical history and other medicines being taken. The longevity hypothesis should not attach an additional promise to a useful prescription. Progress would come from a trial showing that vascular improvements preserve function over time or prevent clinical events. That connection between mechanism and outcomes people experience remains to be established.

Frequently asked questions

Is daily tadalafil proven to extend life?#[ + ]

No published trial identified in this review demonstrates longer life in healthy adults. Daily use for certain medical indications does not constitute a validated longevity protocol. The associations observed in medical records justify dedicated trials.

Is tadalafil better than sildenafil for longevity?#[ + ]

Tadalafil stays in the body for longer. Some medical record studies associate it with better outcomes, but patients and patterns of use may differ. No comparison assigning treatment at random demonstrates that tadalafil is better at extending life.

Do these medicines prevent Alzheimer's disease?#[ + ]

Follow-up studies give conflicting results. Trials of blood flow to the brain mainly measure physiological effects. ETLAS-2 found no overall cognitive benefit after three months. Alzheimer's prevention remains a hypothesis to test.

Do the findings also apply to women?#[ + ]

The large mortality studies involve almost exclusively men, often receiving care for erectile dysfunction. Some brain trials include small numbers of women with a defined vascular condition. These data cannot establish a general benefit for women.

Which interactions should people know about?#[ + ]

Combining these medicines with nitrates, poppers or riociguat is contraindicated because blood pressure may fall dangerously. Other medicines can affect tolerability or drug exposure. A doctor or pharmacist should review everything being taken.

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