Tadalafil: A PDE-5 Inhibitor for Life?

Tadalafil:

A PDE-5 Inhibitor for Life?

PDF Version for Printing: Tadalafil: A PDE-5 Inhibitor for Life?

New research shows tadalafil may reduce the risks of heart attack, stroke, and even dementia.

Tadalafil (brand name Cialis) is best known for treating erectile dysfunction (ED) and benign prostatic hyperplasia (BPH). But a groundbreaking 2025 study published in The American Journal of Medicine reveals that this medication may offer much more—extending benefits to the heart, brain, and overall longevity.

Study Overview: Millions of Men, Meaningful and Profound Outcomes

Researchers from the University of Texas Medical Branch (UTMB) analyzed health data from over 50 million U.S. men using the TriNetX database. They followed patients over three years who were diagnosed with Erectile Dysfunction (ED) or lower urinary tract symptoms (LUTS), comparing those who used tadalafil versus those who didn’t take any PDE-5 inhibitors. In just 3 years of follow-up, they were able to find the following:

Key Results at a Glance, All for Tadalafil 5mg Daily (with or without food)

  • 38% lower all-cause mortality in ED, 61% lower in LUTS!!!
  • 33% reduction in heart attacks in ED, 29% lower in LUTS.
  • 29% reduction in strokes in ED, 41% lower in LUTS.
  • 26% lower risk of blood clots in ED, 36% lower in LUTS.
  • 31% less likely to develop dementia in ED, 48% lower in LUTS.

The unusual finding here is that men with LUTS had significantly more benefits than the ED patients, despite ED being a well-known indicator of cardiovascular risk. This is presumably due to men taking tadalafil for LUTS being more consistently than those for ED. Sildenafil (Viagra) was also reviewed in this study and had fewer benefits, consistently, presumably due to its short half-life, than tadalafil.

Can you imagine how many drug ads you would have seen by now if tadalafil was still on patent as Cialis!

Why Does This Happen?

Tadalafil works by enhancing nitric oxide–cGMP signaling in blood vessels, which improves circulation and reduces vascular inflammation. It also helps increase the availability of endothelial progenitor cells, your body’s natural blood vessel repair team.

This means tadalafil’s effects go far beyond the pelvic region. It improves the entirety of your vascular system through improved microcirculatory flow, an anti-inflammatory action and by improving repair through enhanced endothelial progenitor cells.

What This Means for Patients

If you’re already using tadalafil for ED or urinary symptoms, these findings suggest you may also be protecting your heart and brain. For men with cardiovascular or cognitive risk factors, tadalafil might be a helpful part of a broader preventive strategy—under medical supervision.

Important: Tadalafil is not for everyone. It must be avoided if you use nitrates.  Always consult your healthcare provider before starting or continuing any medication.

What About Women?

Unfortunately, there is no reliable data to confirm that women have the same cardiovascular and mortality benefits. I have no reason to suspect it won’t. It has a mild benefit in terms of sexual arousal in women. This is a review that summarizes the minimal research on Female Sexual Disorder: https://www.researchgate.net/publication/316196780_

Conclusions:

For all men or women older than 40, daily tadalafil should become a part of the conversation with you and your health care provider. If I had a family history of dementia and/or had one or two of the ApoE4 alleles, I would consider daily tadalafil. If I had a family history of CAD and/or a positive CAC (Coronary Artery Calcium) score, I would consider daily 5mg tadalafil. Furthermore, via Cost Plus Pharmacy it costs $9 for a 90-day supply, plus $5 shipping.

Did I mention, that although this was a case controlled observational study, and not prospective, double-blinded trial, there was a 61% reduction in all-cause mortality in men over 40 with LUTS in only a 3-year observational trial. I started tadalafil two weeks ago, and as the studies show there are no significant side effects (and as a 62 y/o man I am peeing better than I have in quite some time).

Reference:
Anderson JP, Byrd JB, Buras MR, et al. Association of Phosphodiesterase-5 Inhibitor Use With Mortality and Morbidity in Men With Erectile Dysfunction or Lower Urinary Tract Symptoms. Am J Med. 2025 Mar;138(3):441–448.e3. doi:10.1016/j.amjmed.2024.10.039 (https://pubmed.ncbi.nlm.nih.gov/39532245/)

 

Your Journey to Health and Healing,

Gary E. Foresman, MD

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