It has long been held that testosterone is the root of all evil – probably true for most wars, and possibly true for the development of prostate cancer. Oft times, lecturers on prostate cancer will cite sketchy data on eunuchs not developing prostate cancer. When you try to actually find data supporting this statement, it is very difficult indeed. On the other hand, men born with a genetic defect in 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone do seem to be protected from developing prostate cancer (of course they don’t have prostates either !). Adding to the confusion surrounding this issue is the recurring finding that men with lower levels of testosterone who DO develop prostate cancer seem to have higher Gleason scores and in some cases more advance stage implying worse cancer outcomes.
So what would be the result of blocking the enzyme that converts T to DHT (which has 10 times the affinity for the androgen receptor) in preventing prostate cancer? This hypothesis was tested in two large randomized trials. I have reviewed the PCPT trial elsewhere in this blog. The REDUCE trial also looked at blocking the enzyme with dutasteride (Avodart, another 5 alpha-reductase inhibitor or 5-ARI) in men who had psa values of 2.5-10 and a previous negative biopsy. Both trials showed a reduction in the development of prostate cancer, but a disturbing increase in the few men with higher grade tumors. These findings led to an FDA warning about increased risk for high grade cancers that has been very controversial.
Another way to look at this controversy would be to simply evaluate what happens to men in terms of prostate cancer outcomes, not simply whether a certain grade or incidence of prostate cancer develops. In a current article in JAMA, Canadian investigators evaluated nearly 14,000 patients who were diagnosed with prostate cancer during the decade of 1999-2009 and compared the outcomes of men who were or were not taking a 5-ARI prior to their diagnosis. Using two separate mathematical models, they found no difference in prostate specific or overall mortality in the two groups.
In an accompanying editorial by Drs. Figg and Thompson (two highly regarded experts in this area), the question of whether one should consider using 5-ARI’s to prevent prostate cancer is further discussed. Their conclusion is as follows:
“The role of 5-ARIs as chemopreventive agents for prostate cancer remains uncertain. On the one hand, reduction of low-grade tumor incidence is unlikely to translate to a reduction in prostate cancer mortality; on the other hand, such a reduction could reduce disease overdetection and overtreatment, a serious concern that led the US Preventive Services Task Force to recommend against PSA screening.10 The study by Azoulay et al8 suggests that 5-ARI use is unlikely to increase prostate cancer mortality in men receiving them for BPH, reassuring those men on the symptom relief they may provide.”
Given these data and the discussion by the experts in the field, I would still recommend that sons of men with prostate cancer strongly consider taking 5-ARI’s, even though they may not reduce the chances of developing a lethal cancer. It seems reassuring that they will not have a worse outcome in all likelihood. Prevention of a low grade cancer and the morbidity from treatment seems a worthy goal to me (never mind the possibility of decreasing urinary obstructive -BPH- symptoms and reducing baldness). Whether it would help them not drive like idiots, attack their siblings at family gatherings, or say offensive things to their sisters is an entirely other matter. Happy Passover/Easter to those of you hosting such individuals!