Friday, April 13, 2012

Caught Between A Rock And A Hard Place - Part 5

Just over a year ago, I pointed out a study linking use of 5 alpha reductase inhibitors (5ARIs) to adverse side effects that persisted even after discontinuing the medication.  As a quick review, these two 5ARIs, finasteride & dutasteride, by inhibiting the conversion of testosterone (T) into dihydrotesterone (DHT), are used to shrink the prostate, while the former also has an indication in male pattern hair loss.  However, in doing so, this can potentially push the metabolism of T towards estradiol (E2), high levels of which could account for loss of libido, erectile dysfunction, and ejaculation & orgasmic disorders.  Issues w/semen quality have also been reported with finasteride.

Earlier this week, the Food & Drug Administration announced a label change for finasteride, in both strengths, indicating that the above noted side effects could persist even after discontinuation of the medication.  So what are we to do as physicians & patients?  I posit that we do nothing different than what we've always done - which is to say we need to have an ongoing & open dialogue about risk vs benefits at each & every visit.  I counsel my residents to review their patients' medication list and engage them in conversation to determine whether a medication is (still) needed and if the benefits are worth the (theoretical) risk.

Even in the same person, this equation may change over time, such that a medication needed earlier may no longer be needed now.  For instance, I find that many patients are discharged from the hospital on proton pump inhibitors started as prophylaxis against stress ulcers.  The patients continue to take their medications dutifully even though they have no history of gastroesophageal reflux or peptic ulcer disease and now run an increase risk of community acquired pneumonia, osteoporotic fracture, cardiac dysrhythmia, and/or C. difficile diarrhea.  As I've noted many times in the past, there's no such thing as a free lunch.

But back to the current issue at hand: finasteride & dutasteride are reasonable drugs to take if you have symptomatic enlargement of your prostate.  And smaller doses of the former are an option for those suffering from hair loss and don't care for the Telly Savalas look.  So there's definitely benefit to be gained if desired.  And what of the risks?  In the their announcement, the FDA quoted a 3.8% risk of side effects in those men taking finasteride compared to 2.1% of those randomized to placebo.  So while one could claim 50% greater relative risk, the overall risk is still quite small, unless you're one of the 3.8%, in which case, who cares about the remaining 96.2%, especially if your side effects persist long after discontinuation.

While I don't like the pharmaceutical domino effect, I suppose we could consider checking both DHT & E2, and perhaps even add an aromatase inhibitor to stop the conversion of T into E2 in an attempt to mitigate said persistent 5ARI side effects.  Let's just pray there are no side effects from the aromatase inhibitor.  The bigger problem for us physicians?  This single topic (ignoring the potential increase risk of high grade prostate cancer associated w/5ARIs) will probably require more than 15 minutes to cover to the patient's understanding (and most likely spill over into future appointments as more questions come up).  As always, choose wisely!



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