Glaucoma turned up 22% more often in men prescribed tadalafil, sold as Cialis

Men who took tadalafil — sold as Cialis — long-term for urinary symptoms caused by an enlarged prostate were 22% more likely to develop glaucoma than matched men who never used a PDE5 inhibitor, according to a multinational cohort study in the British Journal of Ophthalmology. Investigators led by Yun Hsia analyzed 73,854 men aged 40 or older in the TriNetX Analytics Network, matching 36,927 tadalafil users against 36,927 non-users for up to five years of follow-up. The increase concentrated in two specific conditions — primary open-angle glaucoma and ocular hypertension — rather than glaucoma broadly, and Hsia’s team said the pattern supports closer eye monitoring for men on long-term tadalafil therapy who carry other glaucoma risk factors.

Tadalafil is a long-acting PDE5 inhibitor the Food and Drug Administration approved for erectile dysfunction in 2003 and, in 2011, for treating the urinary symptoms of benign prostatic hyperplasia, a use now backed by more than a decade of clinical data. Its mechanism relaxes smooth muscle by blocking the breakdown of cyclic guanosine monophosphate, improving urinary flow in men with an enlarged prostate — the same signaling pathway researchers now suspect also touches the eye’s drainage system.

TriNetX Data Tracked 73,854 Men for Up to Five Years

The team used the TriNetX federated health research network to identify men aged 40 and older with a history of lower urinary tract symptoms between 2012 and 2022, excluding anyone with a prior glaucoma diagnosis, then matched tadalafil users one-to-one against non-users on age, race, comorbidities, kidney function and other medications. Over that follow-up, tadalafil use carried a 22% higher likelihood of developing glaucoma, a result that held up across sensitivity analyses built specifically to rule out early, pre-existing disease being mistaken for a new one caused by the drug.

The Risk Concentrated in Two Glaucoma Subtypes

Broken down by subtype, primary open-angle glaucoma carried a hazard ratio of 1.33 and ocular hypertension a hazard ratio of 1.32, while no significant association turned up for normal-tension glaucoma or angle-closure glaucoma. Tadalafil users were also 33% more likely to be started on glaucoma treatment during follow-up, a proxy the Ophthalmology Times account of the study says the authors used to capture clinically meaningful disease rather than a diagnosis code alone. Five-year cumulative incidence came out to 3.93% among tadalafil users against 3.16% among non-users, a modest absolute gap even though the relative increase is what produced the 22% figure.

A Nitric Oxide Pathway May Link the Drug to Eye Pressure

PDE5 inhibitors act on the nitric oxide-cGMP signaling pathway increasingly recognized as a regulator of eye pressure: nitric oxide stimulates an enzyme that generates cGMP, relaxing the trabecular meshwork cells that govern how fluid drains out of the eye. That same pathway is now the target of newer glaucoma medications built around nitric oxide donors, a sign of how sensitive eye-fluid drainage is to shifts in cGMP signaling. The study itself did not measure intraocular pressure directly, so whether chronic PDE5 inhibition actually disrupts that balance over years of use remains unconfirmed rather than established.

The elevated risk held up across several sensitivity analyses, including lag times of one, three and six months built in specifically to reduce the chance that early diagnoses reflected undetected disease that predated the drug rather than a true effect of it. The association also stayed consistent across subgroups, including men older than 50, White patients, and patients carrying different levels of other health conditions, which argues against the result being an artifact of any single subgroup driving the whole finding.

Researchers Say Monitoring, Not a Prescribing Change, Is the Takeaway

Hsia’s team frames the results as supporting ophthalmic monitoring rather than a change in how urologists prescribe tadalafil, noting that the study’s retrospective, claims-based design cannot rule out residual confounding. Men prescribed tadalafil for urinary symptoms may simply see doctors more often than non-users, which raises the odds that an incidental glaucoma finding gets recorded regardless of the drug itself.

For men older than 50 or carrying other glaucoma risk factors such as family history or thin central corneas, the findings, published in the British Journal of Ophthalmology, are a reasonable prompt to keep up with routine comprehensive eye exams rather than a reason to stop the medication. Tadalafil already carries a separate, better-established ophthalmic warning — a rare optic nerve event called NAION — that the study’s authors say is mechanistically distinct from the glaucoma signal and should not be confused with it.

Urologists and primary care clinicians who prescribe tadalafil for urinary symptoms may also want to ask patients directly about their eye care history and glaucoma risk factors during treatment, looping in an ophthalmologist when those risk factors are present rather than waiting for a routine screening interval to catch a problem on its own. That advice applies specifically to the long-term, daily-dose regimen used for enlarged-prostate symptoms, not necessarily to the lower, on-demand doses men take intermittently for erectile dysfunction, since the cohort excluded that use pattern entirely.

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This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.