Proscar/Avodart for prevention? The confusing tale of testosterone.

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!

11 Comments

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11 responses to “Proscar/Avodart for prevention? The confusing tale of testosterone.

  1. David Lacey

    Dr. Glode, Apart from prescribing 5-ARIs, would you consider recommending a whole plant food low fat diet? See link below. Thanks, David Lacey

    http://www.forksoverknives.com/science-says-about-diet-and-cancer/

    • Generally a low fat, high soy diet is what we should all be doing, and I definitely recommend it to prostate cancer patients. It would make sense for their first degree relatives as well.

  2. Dan

    Dr Glode,
    Thanks for the post!
    I was dxed in June of 2006 , as stage 4, gs 10, lymph and bone mets to distant sites, I have been through casodex, nilandron, estradiol patches all with zolodex and Avodart, and zytiga and now xtandi ,both with Avodart, I never had a receding hairline and neither has any of the males in my Family. So all I can say was that it may have been something that worked well for me. Unfortunately my last psa doubled from 23 to 40 in 3 months,They used to say that Avodart reduces your psa falsely by 50%, Is this still true in my case. I wish I could convince my local to try Cytozan, but perhaps I will be able to use that with your paper to do during off periods of intermittent chemo. what do you think of Luekine in the intermittent chemo app, since I have used up the zytiga and xtandi which for the last 18 months I have done in combo.

  3. David Stevens

    Dr. Glode: thank you very much for this informative post. I look forward to your talk on the subject of testosterone on June 9th. (I am particularly intrigued right now because my PSA has gone down twice in the last six months, even though I am a Gleason 9. 1.15 to 1.05 to 1.00. Tiny drops but drops none the less.)

  4. Forgot to add that my PSA drop is not caused by any treatment since I am not in treatment right now – just watching.

  5. Dr. Glode: regarding your mention of soy in the diet – – do you have guidelines for how much soy on a daily basis and in what form? Tofu, soy protein powder, edamame, or…..?? Thanks.

    • I am not sure there is an answer to “how much soy”. In one Ohio State study, subjects took 25gm soy powder daily plus lycopene and they measured the blood components to show genestine etc. went up. In that study there was some slowing of psa, for whatever it’s worth. I’ve heard other lectures discuss the differences between getting “soy” from tofu vs powder vs soy milk, etc. and there are significant differences in composition, absorption, etc.

  6. Amy Fries

    Hi—Did you want us to repost on AC? If so, we will copyedit and send it back for your review.
    Thanks.
    Amy

  7. Howard Rachlin

    Dr. Glode: My son is 43 and his PSA has not been a problem. I had my prostate removed in 2003 and was fine until it doubled within a year in 2009. At your suggestion I underwent ADT in conjunction with radiation which took care of things until a doubling in the last 12 months. Would you suggest that my son begin taking Avodart now at his age?

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