No Such Thing as a Free Lunch

In an ideal world, we'd only need to swallow a risk-free, side effect-free, interaction-free pill just once and never have to worry again about whatever condition we were treating.  To date, we're not even close to reaching that goal.  There is no such thing as a free lunch.  

We can provide up 10 years worth of protection against tetanus, diphtheria, and pertussis but this requires an injection.  Screening colonoscopy is recommended starting at 50 years of age in low risk patients, but there is still a small but real risk of perforation.  The statins are extremely powerful at lowering cholesterol but at the risk of myalgias and liver irritation.

For those men suffering from lower urinary tract symptoms of benign prostate hyperplasia (BPH) despite alpha blockers (which themselves have been associated with an increase risk of heart failure), 5 alpha reductase inhibitors (5ARI) have been a God-send, shrinking the prostate (and thus, PSA) by 50% within 6 months and generally improving their quality of life.  This class, as exemplified by finasteride & dutasteride, works by inhibiting the conversion of testosterone (T) into dihydrotestosterone (DHT).  Therefore, testosterone is forced down the metabolic pathway towards estradiol (E2), which accounts for the 5ARI's known risk of gynecomastia, erectile dysfunction & loss of libido, all from having too much E2.  Imagine a seesaw with testosterone as the fulcrum and DHT & E2 balanced on opposite sides before starting a 5ARI.  Upon starting either finasteride or dutasteride, the seesaw is thrown out of balance as T is converted into more E2 and less DHT.

This much we've known for a while.  We've also theorized that by shrinking the prostate, we might be able to prevent prostate cancer, which then lead to the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, both of which did demonstrate an overall 23-25% reduction in prostate cancer.  However, the flip side is that both trials also demonstrated an increase risk of high grade prostate cancers.  After PCPT and before REDUCE, we tried to explain this by any number of statistical models.  However, with both studies arriving at the same conclusion, the FDA's advisory panel denied the claim for chemoprophylaxis last December after concluding that one additional case of high-grade prostate cancer would be diagnosed for ever 150-200 health men treated long-term with a 5ARI.

The FDA has left open the option to continue to treat men with symptomatic BPH and/or hair loss with 5ARIs.  But last month, the FDA updated the Warnings & Precautions section with the above discussion & concerns as noted in this week's NEJM (thanks to Dr. Peter G's keen eyes).  It's now up to us to deliberate whether the risk is worth the benefit in this specific situation for each individual we see.  It would be all too easy if we could foretell the future but unfortunately, my crystal ball is at the repair shop.  For now, we'll need to discuss/warn our patients who need something besides an alpha blocker to treat their BPH.  Remember, there's no such thing as a free lunch.  And there are no risk free, side effect free, interaction free medications.