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Thursday, May 5, 2022

Sex! Drugs! (or just another correlation/causality example)

How did I not hear about this sooner? Maybe I just wasn't paying attention, but one would think that this would have been headline news.

Five months ago, research came out showing an association between Viagra (sildenafil) and Alzheimer's: "sildenafil users were 69% less likely to develop Alzheimer’s over a six-year period than non-users". 

The full paper is behind a paywall, but you can read the abstract. The most important line is this: 

"The association between sildenafil use and decreased incidence of AD does not establish causality, which will require a randomized controlled trial."

As much as some want to giggle about Viagra, this is an interesting statistical problem. Think about how one would structure a controlled trial.

Remember - sildenafil is prescribed for two reasons:

  • Sex (erectile dysfunction)
  • High blood pressure (pulmonary arterial hypertension)
Could we even do a randomized controlled trial with men in these groups? That's tricky. Even with informed consent, is it ethical to randomly withhold medical treatment known to help with either of these conditions? 

A ethical trial would require a group of men old enough to be at risk for Alzheimer's and with neither medical condition. They would volunteer to be randomly assigned to sildenafil or a placebo. In a double-blind study, neither they nor their direct researchers would know who was receiving the real drug. 

It's Viagra. How long do you think it would take before the men figured out which group they were in?

This leaves us with problems.
  1. It would be unethical to do a trial with men who have a medical need for sildenafil.
  2. It would be nearly impossible to maintain double-blind status for any length of time.
I don't have a solution but I have a suggestion for where research could start. Since sildenafil is prescribed for two different conditions, the existing data should be separated by medical condition. Then the Alzheimer's incidence could be compared between those two conditions.**

Suppose that those treated for erectile dysfunction had lower incidence of Alzheimer's than those treated for hypertension. That could imply that it's not the sildenafil itself, but the increased frequency of sex that helps prevent Alzheimer's. Many men would cheer for that.

Then suppose the opposite. What if the data showed that those treated for hypertension had lower incidence than those treated for erectile dysfunction. Would that imply that too much sex could increase the risk of Alzheimer's? Now most men wouldn't cheer as much.

What if there's no difference in Alzheimer's incidence? That's evidence in favor of sildenafil causing decreased Alzheimer's, but it's still far from proof. Maybe sildenafil allows both groups to exercise more. Maybe it's ... just about anything. 

This is why medical research is hard. There are usually ethical issues and it's difficult to maintain double-blind status for any treatment that has well-known side effects.

**It's possible that this separation was done in the study. Since it's behind a paywall, I can't check but the abstract doesn't mention it.

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