Statin use and mortality risk in men on ADT.

[pca2004]

New ADT study from Hong Kong (1).

"A total of 4920 patients were included, consisting of 2578 statin users and 2342 non-users (mean age 76.1 ± 8.2 years). Over a mean follow-up period of 4.2 ± 3.3 years, it was observed that statin users had significantly lower risks of both PCa-related mortality (weighted hazard ratio [wHR] 0.56 ...and all-cause mortality (wHR 0.57 ...), regardless of the type of ADT used.

... Notably, these associations were more pronounced among patients with less advanced PCa, as indicated by the absence of androgen receptor antagonist or chemotherapy usage"

imo the direct effects of statins on PCa cells are:

i) a reduction in the VLDL-cholesterol available for uptake, & ...

ii) inhibition of cholesterol generation within the cells.

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/381...

[GreenStreet]

Thanks very interesting. I finally went on Atorvastatin about 6 weeks ago

[Maxone73 in reply to GreenStreet]

How much per day?

[GreenStreet in reply to Maxone73]

20 mg

[cujoe]

pca2004 et al - I've long felt that the myriad influences of cholesterol are instrumental in understanding and controlling PCa. For anyone wanting to get a better understanding of the role of cholesterol and the various processes involved in the creation of the steroid hormones that rule our lives - and cancers, this 15 minute video from the Catalyst University YouTube site is excellent. Note also that the superb graphic used in the video can be found at the Wiki page titled, "Steroidogenic enzyme". (also linked)

Catalyst Univ - Steroidogenesis | The Biosynthesis of Steroids from Cholesterol

youtube.com/watch?v=TJf62Om...(Not working as expected?)

Steroidogenic enzyme

en.wikipedia.org/wiki/Stero...

Learn more to live longer - & Stay S&W, while you do both,

Ciao - cujoe

[Don_1213]

Thanks for this - I had mentioned in another thread the synergistic effect of combining statins and metformin on PCa. Just out of curiosity, I did a really primitive search of metformin and statin on the NHS website.. to my surprise many papers came up covering a wide range of types of cancer (breast, brain, pancreatic, etc...) indicating a positive effect of this combination.

The search can be replicated: pubmed.ncbi.nlm.nih.gov/?te...

Some interesting reading. I wonder if the researchers in all these different cancer fields are talking to each other and if anyone has actually tried doing research on the "why" this works (in the hope of making a breakthrough treatment..)

Good stuff - I have to come back to this tomorrow - it's too late now to head down the rabbit hole, but it looks like a really interesting hole to go down.

[lcfcpolo in reply to Don_1213]

The Care Oncology Clinic protocol includes Metformin and Atorvastatin. Appx £320 per quarter. It's worth asking your GP if he or she will prescribe.

[maley2711]

So, you believe that cholesterol "feeds" PCa???? Is there an association between LDL and or HDL and PCa mortality...we know that is tru for OS!!!!!! But PCA survival?

[pca2004 in reply to maley2711]

Cholesterol does not "feed" PCa.

It has been known for 100+ years that solid tumor cells accumulate excess cholesterol. PCa is no exception.

PCa will generate cholesterol when circulating levels are low. However, PCa will even generate cholesterol when circulating levels are not low. This is particularly true for lethal disease.

VLDL-cholesterol [VLDL-C] is readily taken up by PCa cells. When testosterone is high-normal, the cholesterol profile has very little VLDL-C. While on ADT, much of the LDL-C is VLDL-C.

Although non-PCa solid cancer cells accumulate cholesterol, there is an added threat in PCa cells - cholesterol is the starting point for steroidogenesis. PCa cells may generate androgen if necessary.

Statins can reduce circulating cholesterol, but they can also prevent cholesterol generation in cancer cells.

Liver generation aside, the lipophilic statins are best for cancer cell uptake.

Regardless of associations of circulating VLDL-C, LDL-C & HDL-C with PCa & OS -survival, we should be concerned as to what is actually happening in PCa cells. Blood tests may not reflect cancer cell reality.

Note that ultimately, it is pressure from therapies that induce PCa cells to generate androgens. e.g. Abi exerts more pressure than Lupron.

[maley2711 in reply to pca2004]

You appear to be one of the most prolific post/study contributors during your approx one year tenure on this forum. You have probably mentioned this already......but what is/was your professional background that led to such information/knowledge about cancer biology?

[pca2004 in reply to maley2711]

Maxone73 is way more prolific.

I used to design & build systems. I retired at age 52, so when I had a (failed) RP at age 56 (20 years ago), & (failed) salvage radiation, I had the time, experience & motivation to quickly dig through PubMed for anything that might keep me alive.

These days I sift through the 3 dozen papers that are added each day. Typically, a few will interest me, but perhaps not the group. It would be nice if there was something meaty to post each day - something that would set off a big discussion - but the literature tends to be more obscure these days.

I prefer to post on research that is actionable: involving supplements, meds that one may easily get (like statins) and diet-related topics.

[Maxone73 in reply to pca2004]

thanks! I am still in “scared like hell” mode, that’s why I am so up to date 😀😀

[Soumen79]

There is a trial named PEACE 4 led by Karim Fizazi exploring statin and metformin, results expected in late 2023, early 2024.

[Maxone73 in reply to Soumen79]

Statin and aspirin from what I read, still very interesting!

[Don_1213 in reply to Maxone73]

There is some trial involving all 3 - and preliminary results from it (IIRC) were excellent news. And good thing - I take all 3..

[Maxone73 in reply to Don_1213]

send me the link if you can!

[kainasar]

Hi Patrick. Thanks for another helpful analysis. Would be useful to know if any supplement is a lipophilic statin.

[cujoe in reply to kainasar]

kainasar - Patrick is having trouble posting or replying (Thanks Bethishere??!!! BTW, where did you get authorization to restrict member privileges at FPC?) He asked me to forward this reply for him - which I am more than happy to do:

I sometimes read: "My doctor recommended" StatinX.

If StatinX is hydrophilic, it may be that the doctor is thinking in terms of cholesterol produced by the liver.

However, with advanced PCa, we want to stop cancer cell production. Lipophilic statins are best for PCa uptake.

"Drugs can be classified as hydrophilic or lipophilic depending on their ability to dissolve in water or in lipid-containing media. The predominantly lipophilic statins (simvastatin, fluvastatin, pitavastatin, lovastatin and atorvastatin) can easily enter cells, whereas hydrophilic statins (rosuvastatin and pravastatin) present greater hepatoselectivity.":

ncbi.nlm.nih.gov/pmc/articl...

-Patrick

[cigafred in reply to cujoe]

Who or what is "Bethishere"? Sad how one of the most, if not the most, helpful poster encounters this stuff.

[cujoe in reply to cigafred]

cigafred - Agree 100%. I don't know of any uncourteous/unhelpful comment or post ever made by Patrick during his long history at HU. See this for where/who/what "?" is:

healthunlocked.com/advanced...

healthunlocked.com/user/Bet...

I am also restricted at APC and am thus unable to use the search function to find the 1213 Posts & 4872 Replies he made there.

United we stand (& survive). Divided we fall (& lose our friends)! Stay safe and well!

Ciao - cujoe

[cigafred in reply to cujoe]

Thanks. Especially strange given Patrick's following establishment sources whereas the administrator's bio includes "interested in alternative and complementary medicine."

[cujoe in reply to cigafred]

Not to mention having 9 posts (half of which were just solicitations for donations) and 9 replies vs Patrick's "always informative" 1213 Posts & 4872 Replies. Who is more likely to be qualified as a forum admin? . . . no need to reply, as the answer is obvious.

[kainasar in reply to cujoe]

Thanks Cujoe and Patrick.