Researchers have suggested that men who take the erectile dysfunction pill Viagra – and similar medications – are 18% less likely to develop the most common form of dementia years later than those who went without the drugs.
They said the effect was strongest in men with the most prescriptions, with scientists finding a 44% lower risk of Alzheimer’s in those who received 21 to 50 prescriptions of the pills over the course of their study.
While the findings are striking, the observational study cannot determine whether Viagra and similar pills protect against Alzheimer’s or whether men who are already less prone to the condition are simply more likely to use the tablets, reports The Guardian.
“We can’t say that the drugs are responsible, but this does give us food for thought on how we move into the future,” said lead author Dr Ruth Brauer at University College London.
“We now need a proper clinical trial to look at the effects of these drugs on Alzheimer’s in women as well as men.”
Brauer and her colleagues analysed medical records for more than 260 000 men who were diagnosed with erectile dysfunction, but who had no evidence of memory or thinking problems.
More than half were taking PDE5 inhibitor drugs, including sildenafil (sold as Viagra), avanafil, vardenafil and tadalafil. The men were followed for an average of five years to record any new cases of Alzheimer’s.
Around 55m people worldwide have dementia, mostly due to Alzheimer’s.
New drugs that clear aberrant proteins from the brain have shown promise for slowing down the disease, but the effects of the medicines appear marginal.
Viagra was originally developed to treat angina and high blood pressure, but when Welsh miners who took part in a trial in Merthyr Tydfil remarked on its unexpected night-time side-effects, the drug became a multibillion dollar erectile dysfunction pill.
PDE5 inhibitors work by relaxing veins and arteries, allowing blood to flow more freely. Studies in animals show that this improves blood flow in the brain, which may help protect against Alzheimer’s.
Further work has shown that PDE5 inhibitors raise levels of a compound called cGMP, which may also help to protect brain cells.
There are other possible explanations for the findings, which were published in the journal Neurology.
Because the information is not recorded reliably in medical records, the researchers were unable to account for differing levels of physical and sexual activity among the men.
It may be that the most physically and sexually active men, who had a low risk of developing Alzheimer’s, were most likely to use Viagra or similar pills.
Previous studies into Viagra and Alzheimer’s have found contradictory effects. In 2021, researchers at the Cleveland Clinic in Ohio reported a 69% lower risk of Alzheimer’s among Viagra users, while a Harvard study in 2021 found no protective effect in patients with pulmonary hypertension.
If PDE5 inhibitors do protect against Alzheimer’s, the drugs would be expected to work in women as well as men. “We think it would be very worthwhile to run a trial in a wide group of people,” Brauer said.
“This is a significant development, as repurposing existing drugs for the prevention of dementia is a promising strategy to stop dementia from developing in the first place,” said Dr Ivan Koychev, a senior clinical researcher at the University of Oxford.
But he warned that it would be difficult to run a blinded placebo-controlled trial, where neither doctors nor patients know who receives which, given the prominent effects of the drugs.
Dr Madhav Thambisetty, a senior investigator at the US National Institute on Ageing, whose 2021 study found no protective effect of Viagra, said there is always a risk of unmeasured factors, such as the quality of people’s sleep or how well they control their diabetes, producing false results.
He also questioned the plausibility of a drug like sildenafil, which is only used when needed in patients with erectile dysfunction, altering the course of a chronic, progressive neurodegenerative disease.
“While sildenafil is known to reach the brain from blood, can its levels in the brain be maintained at high enough concentrations over a sustained period of time that may be required to alter the trajectory of Alzheimer’s disease?” he said.
“This is an important question to consider for drugs like sildenafil that are only used ‘as needed’ in comparison to drugs that are used every day or multiple times a day over a prolonged period of time.”
Study details
Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease: A Cohort Study
Matthew Adesuyan, Yogini Jani, Dana Alsugeir, Robert Howard, Chengsheng Ju, Li Wei.
Published in Neurology on 27 February 2024
Abstract
Background and Objectives
Repurposing phosphodiesterase type 5 inhibitors (PDE5Is) as drugs for Alzheimer disease (AD) risk reduction has shown promise based on animal studies. However, evidence in humans remains inconclusive. Therefore, we conducted a cohort study to evaluate the association between PDE5I initiation compared with nonuse and the risk of developing AD in men with erectile dysfunction (ED).
Methods
Using electronic health records from IQVIA Medical Research Data UK (formerly known as the THIN database), we identified men aged ≥40 years with a new diagnosis of ED between 2000 and 2017. Individuals with a previous diagnosis of dementia, cognitive impairment, confusion, or prescription for dementia symptoms were excluded. The occurrence of incident AD was identified using diagnostic read codes. To minimize immortal-time bias, PDE5I initiation was treated as a time-varying exposure variable. Potential confounders were adjusted using inverse probability of treatment weighting based on propensity scores. Cox proportional hazard models were used to estimate the adjusted hazard ratio (HR) with 95% CIs. A secondary analysis explored the association between AD and the cumulative number of PDE5I prescriptions. Sensitivity analyses included lag (delay) periods of 1 and 3 years after cohort entry to address the prodromal stage of AD.
Results
The study included 269,725 men, with 1,119 newly diagnosed with AD during a median follow-up of 5.1 (interquartile range 2.9–8.9) years. The adjusted HR in PDE5I initiators compared with non-use was 0.82 (95% CI 0.72–0.93). The associated risk of AD decreased in individuals issued >20 prescriptions: HR 0.56 (95% CI 0.43–0.73) for 21–50 prescriptions and HR 0.65 (95% CI 0.49–0.87) for >50 prescriptions. Sensitivity analysis with a 1-year lag period supported the primary findings (HR 0.82, 95% CI 0.72–0.94), but the results differed with the inclusion of a 3-year lag period (HR 0.93, 95% CI 0.80–1.08).
Discussion
PDE5I initiation in men with ED was associated with a lower risk of AD, particularly in those most frequently issued prescriptions. The differences between primary and sensitivity analyses highlight the need to explore the optimal lag period. To enhance the generalizability of our findings, a randomized controlled trial including both sexes and exploring various PDE5I doses would be beneficial to confirm the association between PDE5I and AD.
See more from MedicalBrief archives:
Viagra as a candidate drug for Alzheimerʼs disease — US prescription analysis
Pfizer is looking for another ‘Viagra’
Up to half of men under 50 suffer from erectile dysfunction