So, there has been a lot of conversation about cognitive decline on hormone therapy.
So first of all, how does that show up to patients? Does it show— like, if you see cognitive
decline, does it show up right away? And is there anything that they can do to mitigate that issue?
Yeah, the the studies that document cognitive decline from testosterone deprivation
are not particularly high-quality studies. They come from databases,
and what they don't look at is whether this "cognitive decline" is reversible
or not and that's not— they can't tease it out from the studies that have been done,
and there are men that comment that their, you know, their memory for words is not as sharp
and, of course, fatigue that comes especially in the men that don't exercise that reduces
mental endurance and causes cognitive decline. In my experience, these effects are 100% reversible
when the hormone treatment is stopped. The specter of long-term permanent mental damage from
testosterone deprivation I think is completely unfounded. I think that as long as people are on
testosterone deprivation they're going to need to take compensatory measures to stay strong
and maybe cut their schedule back a little bit if they've got a high-intensity executive position;
they may not be able to function at 100 percent, but maybe they can function at 80%
just because they don't have the same endurance. I think the sad thing is that in the studies that
have been published there's this implication that this is a harbinger of Alzheimer's disease or or
that people are going to go into some sort of spiraling decline that will continue the rest of
their lives, and that's just—in my opinion—not true. It's a reversible effect. Now, some men
have to stay on hormone treatment the rest of their lives. They have advanced cancers
and this treatment's keeping them alive, and so they therefore will have to deal
with these lingering reductions in performance from low testosterone,
and there are ways to to work around these things, but it's not a progressive thing anymore,
you know— aging is progressive; these people are getting older.
Some of them will have cognitive issues unrelated to their low testosterone and if someone was very
borderline in terms of their cognitive function before starting hormonal therapy you could see how
the further loss of testosterone could exacerbate their pre-existing problems. So it's not to
minimize the fact that performance can be enhanced with testosterone. In the athletic world there's
a lot of use of testosterone surreptitiously to improve mental and physical performance,
and it does; it's a wonderful thing, and when you move remove it there is some reduction in an
individual's capacity to perform various different tasks. The outline of what we're talking about
is that, and one thing I wanted to emphasize, is it doesn't cause any destruction of brain tissue,
but it does temporarily reduce performance and it can be restored when the testosterone comes back.
Thank you for clarifying that. I think we see a lot of headlines that come up with hormone therapy
and Alzheimer's and all of these issues, and PCRI gets inundated with phone calls when these types
of headlines come out. One thing based off of what you said— so it sounds like because it's a lack of
testosterone, it's true the lack of cognitive decline would be true for first generation
and second generation hormone therapy? I know the patients ask if there's a difference
between those two, but because they're taking the testosterone out, it's across the board the same?
Yes, so let's talk about three generations of hormone treatment. So, what's traditionally
being called second-generation, let's call that third-generation, we're talking about
Xtandi, Zytiga, Nubeqa, and Erleada, and these remarkable medicines can shut down the
synthesis of testosterone inside of cancer cells— breakthrough medicines, extending life, doing
marvels in many ways, and if you compare that to the second-generation, medicines like Orgovyx,
Firmagon, Lupron, Trelstar, those shut down testosterone production and the testicles,
and so the difference between someone being on a second-generation and a
third-generation or both in terms of reduction of testosterone in the system is very trivial;
there's very little difference, and so if you add Zytiga or Xtandi to Lupron or Orgovyx, you'll get
pretty much the same degree of side effects, the same degree of testosterone reduction.
If there are differences, they're subtle. But first-generation hormone blockade with medications
such as Casodex, which allows testosterone to stay in the bloodstream induces fewer and milder side
effects and many men function quite well with that. It's not as effective as the second and
third-generation medications, but it's a nice alternative, especially for more elderly men
who we need to control the cancer but we're not as urgently concerned about, you know, giving
them 25 years of life expectancy, if say, they're already in their 80s or 90s. So, I think it might
be more helpful to be thinking in terms of first, second, and third generation. First-generation,
mild Casodex; second and third-generation, whether you do them individually as second or third, or
in combination, second and third, the side effects are going to be about the same.
Why would urologists or doctors in general not put patients on Casodex first as a primary? I
see a lot of people go straight to Lupron so what are the numbers that
they're seeing or anything that causes them to go straight to Lupron versus starting Casodex?
Well, men that are diagnosed with prostate cancer in their 50s, 60s, maybe early 70s, the primary
goal is to cure them, and the cure rates are going to be superior if you use more powerful
hormone treatment. So, when the goal is to cure somebody, then you want to use optimal therapy.
Sometimes we even give a little chemotherapy, certainly radiation is considered standard,
surgery, these sorts of things are to get rid of the cancer once and for all,
and the advantage is not only ensuring normal longevity and survival, but also
that the treatment would be one and done— that they don't have the cancer come creeping back
in the future. The impact on quality of life, even if they live a normal life expectancy,
the impact of quality of life of having to have their testosterone taken away again
is very significant. So it may be worth going within a more intense upfront hormone treatment
to optimize cure rates for more younger individuals and then the additional side
effects, then would be worth the fact that you can get cured or have a higher cure rate.
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