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This won’t be a long blog, but since I anticipate lots of news this week regarding an article that was published a few days ago, I thought I would provide a “heads up” to my prostate cancer “groupies”. What makes the news and becomes “viral” is interesting and I haven’t had the opportunity to watch the sequence up close personally before. My wife is a pediatric infectious disease expert with specific interest in Kawasaki Disease. As you most likely have seen in the news over the past few days, SARS CoV2 now seems to trigger a KD type of illness in children. This became apparent a little over a week ago with calls flying back and forth from around the world among her friends, notably because Michael Levin, from London had seen some cases and sounded the alarm among the international colleagues. So, from “insider info” to public alarm seems to take about a week.
As you know from faithfully reading this blog, I predicted that men on androgen deprivation therapy might be protected from SARS CoV2 about 6 weeks ago and that physicians/scientists with access to large databases would be able to show this. And, true to the prediction, this past week an article appeared showing just that. I have summarized the data for you on this slide:
It will be interesting to see this get picked up and “sensationalized” by the media over the coming days. And it is already underway. I am aware of a conference call with the CDC and another being hosted by the Prostate Cancer Foundation this coming week. So consider yourselves forewarned! CNN, FOX, ABC, etc. etc. will be all over it…
Now, as I also predicted, I would bet that there will be prospective studies looking at ADT as a form of therapy for COVID19 starting soon (if not already underway). My favorite design would be with the approved agent, remdesivir in a randomized prosepective trial. Male patients sick enough to be admitted to a hospital would all receive remdesivir, and 1/2 would receive ADT in the form of an anti-androgen (e.g. enzalutamide, apalutamide or darolutamide) or a single injection of a month of a GnRH analog like degarelix (Firmagon), or the androgen synthesis blocker abiraterone/prednisone (Zytiga). I would hope that this kind of approach could help men (and maybe even women) fight the virus by blocking TMPRSS2 as I previously showed you in the graphic on the original blog. Now YOU are the insiders!
PS, I think that another approach could be starting everyone in a nursing home “under attack” could be starting all the occupants on finasteride. Blocks DHT production from T and is very well tolerated in the pcpt trial. Lower DHT -> lower TMPRSS2 -> lower viral replication.
prost8blog 
Hi Dr. Glode, Thanks for your blog! I’m curious to know if you think this effect is due to low testosterone or some other action of the drugs? Also, what puts the 37,161 men in that column? Are they the men who are cured from prostate cancer (for the most part)? Who else could they be?
Thanks, Marty Magid
Yes, the hypothesis would be that lack of T results in lower levels of TMPRSS2 which is required for viral entry (and processing) – see my previous blog for details. As I understand the study, the 37,161 men were in a database as having prostate cancer but not being on ADT. I don’t think they would be other cancer patients or non-PCa patients. Possibly cured? Maybe surgical or radiation therapy patients with or without rising PSA. Cured or not… What would be interesting, of course, would be to know the T levels in each group.
Logically, one would first determine the variation of expression levels of TMPRSS2 in the pulmonary epithelium of men versus women since it is in that epithelium that the virus evidently enters. Theoretically men could have higher levels of TMPRST2 in the AR but not the pulmonary epithelium . Second, does ADT down regulate TMPRST2 in that location as we know it does in the AR .
You are correct, and I think that is being looked at. The regulation of AR and TMPRSS2 could be very different in different tissues. My understanding is that there is a mouse study showing less regulation in pulmonary epithelium. One of our researchers at CU is looking into the regulation in human pulmonary epithelial cells. I would expect a plethora of papers coming out on the subject. What about genetic differences between African Americans and other groups? And the kids at risk for KD in London seem to be disproportionately from AA and Caribean backgrounds. Further, the “east coast” viral strain may be different from the west coast/China strain. So many unknowns!!
I’d like to know if men on androgen deprivation therapy are protected from Covid by the ADT drugs, or is it the low testosterone which is protective?
Also. when you look at the data in the study, there are 5,273 men on ADT and 37,161 not on ADT. I asked the author if the men not on ADT included those considered cured and she said she didn’t know. I don’t see any other way to have that many prostate cancer patients who are undergoing treatment that does not include ADT.
I would need to re-read the details of the study. However, if you ask a large database to “show me all the men with a diagnosis of prostate cancer” and then from that group, “separate into those on ADT and those not on ADT, my thought is that the majority would not be on ADT. They would be men who were treated, cured and watching their psa’s, remaining in “biochemical remission”.
Hello Dr Glode.
Since being on ADT fro a year in association with eSRT, I have started to pay attention to researchers looking at how long the testosterone-lowering effects of these medications last, and was surprised to see that it is only recently that papers have been appearing claiming to be the first to track post-ADT carefully. Anyway, my point is that an episode of ADT, depending on age and pre-ADT T level, seems to suppress T for a long time (many months at a minimum). So presumably in that 37k patients there would be quite a few who would have been T-suppressed, even if they were not actually on ADT at the time. Of course, if you were looking for a quick hit treatment for covid men, without the tail T effect, I presume you would opt for abiraterone or enzalutamide, and just block the T rather that stop its production.
Interesting stuff!
Stuart Fysh
There would definitely be some men with low T, which might make the differences even more impressive if you threw them out of the 37k group. The right way to do it of course would be to segregate a bunch of men into quartiles of testosterone, or perhaps compare only men with “castrate T” (usually defined as 250-300/dL). Meanwhile, the vast majority of men with a diagnosis of “prostate cancer” in a database have probably never been on ADT at all, so their T would most likely not be affected in the way you are thinking. Abi would stop synthesis, lead to high LH and quick rebound. Enz might be more complicated, as would a 1 month degarelix injection (with a tail). Then there is the issue of drug-drug interactions and abi and enz might affect antiviral drug metabolism, so it would require careful planning and measurements – never mind the benchmarks you set out for such a study (survival, time in hospital, time in ICU, time on respirator, viral loads, inflammatory markers, coagg markers, etc etc)
How about casodex monotherapy in this application? It’s far less expensive than the newer anti-androgens, and pretty ’clean’ as to AE’s, especially if 50 mg is sufficient to afford protection. Of course, duration would need to be limited to 12 months for men at risk of mutation to agonist.
It could be given en masse to all men over the age of 70 in assisted-living or nursing care residences. It also might help their PSA’s.
Interesting idea. Finasteride could be used in such a way as well. Both would be likely to be fairly non-toxic, although the issues of bone loss, frailty, and sarcopenia would be there. Neither would be as potent as the other ADT agents of course. We have used low dose flutamide in “step up” therapy in the past – even weaker than full dose casodex. Not sure there would be any mutations outside of the genetic instability found in cancer. Thx for the comment!
Dr. Glode, I think you’ll find this interesting and maybe can offer an explanation:
Remembering a day in March when I had a one-day fever of 100.6, and about 8 days later my wife felt poorly, but no fever, we both got an Antibody Test last Thursday in Avon. Hers came back POSITIVE. Mine came back NEGATIVE. Did my ADT inhibit me from being infected? Bob Louthan PS: I’m secretly hoping these results won’t cause you to recommend a longer stay on ADT…..
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VERY interesting. I think the antibody test(s) are pretty unreliable, but who knows. Maybe you had a lesser infection (which might make sense biologically if the ADT suppresses viral replication) and lower antibody titer as a result. Sounds like you were probably both infected to me, but WHO KNOWS. ADT for the masses??? (would also stop wars, and perhaps keep AR-7 carrying citizens out of state capitols?)