Prolactin & Cabergoline.

[pjoshea13]

New study blow [1].

Some who have read my zinc posts might remember Costello & Franklin. They seem to have been at it for ever (the first of 109 joint papers was in 1977). Their focus has been citrate & zinc in the prostate.

Anyway, here is an anecdotal case of a man with CRPC who:

"was treated with cabergoline [2] (dopamine agonist) treatment, which decreased the plasma prolactin 88%; by inhibiting the pituitary production of prolactin. The subsequent PET scan (positron emission tomography) revealed the absence of malignancy; and the CTC (circulating tumor cells) decreased from count=5.4 to count=0."

No doubt, you know Cabergoline for its "recreational use in reducing or eliminating the male refractory period, thereby allowing men to experience multiple ejaculatory orgasms in rapid succession". Those were the days!

I have often thought of tackling the PCa-Prolactin literature. There are, after all, 899 PubMed hits. But that's part of the problem. Even so, why is a hormone associated with breast feeding important in PCa? My most recent attempt was last year when I read a just-published paper by Costello & Franklin [3]:

"Especially relevant is the major metabolic function of production of high levels of citrate by the peripheral zone acinar epithelial cells. Citrate production, along with growth and proliferation by these cells, is regulated by co-existing testosterone and prolactin signaling pathways; and by the oncogenic down-regulation of ZIP1 transporter/zinc/citrate in the development of malignancy."

They conclude that "both testosterone ablation and prolactin ablation are required to prevent and/or abort terminal hormone-dependent prostate cancer."

They have been working up to this & it now looks as though they have proof of concept. However, I'd like to know if other CRPC cases were involved & what their experiences were.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/312...

Mathews J Case Rep. 2019;4(1). pii: 42. Epub 2019 May 8.

A Novel Patient Case Report to Show the Successful Termination of Untreatable Androgen-independent Prostate Cancer: Treatment with Cabergoline (Dopamine agonist).

Costello LC1, Franklin RB1, Yu GW2.

Author information

Abstract

INTRODUCTION:

Testosterone promotes the initial development of androgen-dependent prostate cancer. This is the basis for androgen ablation treatment, which attenuates, but does not terminate, the malignancy. Instead, it leads to prolactin-dependent malignancy; in which patient death generally occurs within 5 years. This report describes the novel treatment of a patient; which terminated androgen-independent prostate cancer.

RESULTS:

Patient "XY" was diagnosed with prostate malignancy and metastases. He received hormonal androgen ablation treatment, chemotherapy, and radiation treatment. He developed androgen-independent prostate cancer; with expected death in 2-3 years. He was treated with cabergoline (dopamine agonist) treatment, which decreased the plasma prolactin 88%; by inhibiting the pituitary production of prolactin. The subsequent PET scan (positron emission tomography) revealed the absence of malignancy; and the CTC (circulating tumor cells) decreased from count=5.4 to count=0.

DISCUSSION:

The cause of androgen-independent malignancy has been unknown, and an effective chemotherapy did not exist. The activities of normal and malignant prostate cells are regulated primarily by testosterone. When testosterone availability diminishes; prolactin regulation is manifested. This is represented when androgen ablation results in the development of prolactin-dependent malignancy. An effective chemotherapy would be targeted to eliminate the plasma prolactin-manifestation of the androgen-independent malignancy.

CONCLUSIONS:

This report of a novel chemotherapy for androgen-independent malignancy corroborates our understanding of the implications of prolactin in its development and treatment. There are about 165,000 cases/year with 25,000 deaths/year in the U.S.; and 1.0 million cases/year with 260,000 deaths/year worldwide. Those patients with androgen-independent prostate cancer can now employ this cabergoline treatment to prevent or terminate this deadly type of prostate cancer.

KEYWORDS:

Advanced Prostate Cancer; Androgen-Independent Malignancy; Cabergoline Treatment; Case Report

PMID: 31211288

[2] en.wikipedia.org/wiki/Caber...

[3] ncbi.nlm.nih.gov/pmc/articl...

Conclusions

Although the importance of testosterone in the development and maintenance of the prostate gland has been well recognized; its major metabolic/functional role of prostate citrate production has been ignored by most contemporary clinicians and biomedical investigators.

The importance of prolactin in the development and maintenance of the prostate gland has received little attention; and its well-established role in prostate citrate production has been completely ignored.

Thus, the contemporary understanding and views of the hormonal regulation of the prostate gland, and the implications in hormone- dependent malignancy are questionable and likely to be untenable. This new concept recognizes and incorporates the compelling evidence of co-existing testosterone and prolactin roles in the regulation of the prostate gland; along with our concept of the oncogenic development of prostate malignancy. This relationship should be incorporated for the prevention and treatment of hormone- dependent malignancy. Studies with appropriate animal models and clinical trials are now needed to establish the plausibility of this concept. The eradication of hormone-dependent untreatable terminal PCa is achievable.

[pjoshea13]

Blood test:

lifeextension.com/Vitamins-...

[johnscats]

hi read your findings do you have to have crpc for this to work and what is the dose

[pjoshea13 in reply to johnscats]

John,

I think they are simply saying that prolactin should be inhibited while on ADT.

But see the Gus Gold post.

-Patrick

[johnscats in reply to pjoshea13]

thanks i get it now john

[gusgold]

I have taken Cabergoline and Zinc Citrate for years and have had Zero results. Dr Strum had hundreds of guys on this with no positive results

[pjoshea13 in reply to gusgold]

Hi Gus,

You wrote: "for years" & "hundreds of guys". Why do you think Dr. Strum persisted if there was no evidence of benefit?

-Patrick

[pjoshea13 in reply to pjoshea13]

... & what was the dose?

Did Strum monitor prolactin levels? Was there a target?

-Patrick

[pjoshea13 in reply to pjoshea13]

Gus & others,

There is a reference to Strum below: -Patrick

”

Medical Oncologist Stephen Strum remarks: “If the fasting prolactin is 5.0 or higher, start Dostinex (cabergoline) at 0.25 mg every Monday, Wednesday, and Friday. A month later recheck the prolactin level.”

"

theprostateadvocate.com/pdf...

[Sisira in reply to pjoshea13]

Patrick,

Couple of years ago after seeing this remark by Dr.Stephen Strum, I checked my Prolactin level. My blood report read as follows:

Prolactin - Male Result : 213.12 mIU/L Ref. Range : 70 - 410

Even at that time I couldn't understand what this 5.0 was.

Could you please specify the units for 5.0 ?

Thanks

Sisira

[pjoshea13 in reply to Sisira]

Sisira,

The units are probably ng/mL.

"The reference range for prolactin in males is 2-18 ng/mL." [1].

The conversion factor is 21, so your result was ~10 ng/mL.

-Patrick

[1] emedicine.medscape.com/arti...

[Sisira in reply to pjoshea13]

Hi Patrick,

Thanks for your conversion of my prolactin level.

Wow! what a great new treatment. Rarely you can hear something like this when everything fails near the grave yard! "Those patients with androgen-independent prostate cancer can now employ this cabergoline treatment to prevent or terminate this deadly type of prostate cancer"!!!

I have a long way to go since I have been enjoying a very stable remission for more than 4 years now with my PSA unchanged at 0.008ng/ml since diagnosis in March 2015 ( PSA 9.7 ) and my aggressive initial treatment followed in April of the same year.

I will certainly use this cabergoline treatment in case I confront an androgen-independent situation.

All of us benefit immensely by your findings and thank you very much again.

Sisira

[pjoshea13 in reply to Sisira]

Hi Sisira,

Had blood drawn at the end of my BAT month. Prolactin was 11.1.

Today, who knows?, since T has been more than restored.

Also, here is an interesting observation about T & blood pressure. My BP was 120/80 for decades. Perhaps a little higher in a doctor's office. Recently, the first number (systolic) has been in the high 130s. I was in my doctor's office this morning. The way I was feeling I assumed that the reading would be high. Instead, it was 110/60.

I need to keep track of future readings, but I'm assuming that the high BP occurs when I am castrate.

But:

[1] 1988 - "Systolic and diastolic blood pressure inversely correlated with testosterone levels"

[2] 2004 - "The results of the present study are consistent with the hypothesis that lower levels of testosterone in men are associated with higher blood pressure, left ventricular mass, and left ventricular hypertrophy."

[3] 2011 - "These results show that low male TT concentrations are predictive of hypertension, suggesting TT as a potential biomarker of increased cardiovascular risk."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/337...

[2] ncbi.nlm.nih.gov/pubmed/147...

[3] ncbi.nlm.nih.gov/pubmed/210...

[Sisira in reply to pjoshea13]

Hello Patrick, Thanks for the message.

I don't think you have reasons to worry about your BP. Most of the time my BP remains around 110/70 and some times 120/80. I am sure you know the bad increases and decreases for any action to be taken. Further I have no worry at all since my Lipid Profile and HbA1C reports are perfect when checked periodically. The only blood marker which troubled me about 5 years back was the PSA @ 9.7ng/ml leading to this lifetime threat although I have been in very stable remission since my initial treatment. There can be interesting connections between T levels and BP for the researchers since hormones are involved in various checks and balances in biological functions of the body. Thanks to you we have the opportunity to learn about such things quite frequently by reading your posts.

BTW both of us are almost in the same range as far as the Prolactin levels are concerned. What do you mean by your " BAT month" ? Are you undergoing the Bipolar Androgen Therapy at present for your PCa ?

Best Regards

Sisira

[pjoshea13 in reply to Sisira]

Sisira,

My BAT:

- T cypionate injected on 1st of each month

- 1 mg DES each day 8th to 31st of each month

-Patrick

[Sisira in reply to pjoshea13]

PAT, Why do you call it BAT? Curious to know.

Sisira

[pjoshea13 in reply to Sisira]

Sisira,

I'm just giving credit to Sam Denmeade at Johns Hopkins:

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

"Adaptive auto-regulation of androgen receptor provides a paradigm shifting rationale for bipolar androgen therapy (BAT) for castrate resistant human prostate cancer."

Others here have used the term.

My version of BAT is a little different, but the length of the cycle he uses is key (I do monthly - it's easier than 28 days for me):

ncbi.nlm.nih.gov/pubmed/292...

"Bipolar androgen therapy in men with metastatic castration-resistant prostate cancer after progression on enzalutamide: an open-label, phase 2, multicohort study."

-Patrick

[Sisira in reply to pjoshea13]

Yes Patrick. It is the same BAT most of us have learned as a novel and out of the box treatment when virtually everything else fails. Of course since you are an expert you can play different strokes with your BAT !

Sisira

[MateoBeach in reply to pjoshea13]

Regarding your modified BAT Patrick. I thought you were doing 3 months on then 3 months off it?As I have learned in my own mBAT, TT levels will never fall to castrate at the end of a month after 400 mg T-cypionate. It has an effective 8 day half life.

I’m order to go on my castrate cycles, currently one month, I have to stop the T-cyp 4 weeks before and switch to androgel topical 150 mg/day for the last few weeks of high T. Then when I stop that I become clearly castrate one week later. And until then, any ADT makes no difference, of course. Start my month of orgovyx then.

Denmeade, Morgentaler and Schweitzer never actually had their patients truly castrate in their BAT trials. (!) Paul

[pjoshea13 in reply to MateoBeach]

Hi Paul,

This thread is 3 years old. For years I used T for 3 months & ADT for 3 months.

But about 3 years ago, I decided to try a single T-cyp dose followed by as much ADT as needed to bring PSA back to baseline.

-Patrick

Alas, Gus Gold is no longer with us.

[gusgold in reply to pjoshea13]

Pat,

we are talking maybe 10 years and most Onco's do not use Cabergoline...if there were really good results wouldn't it be a mainstream treatment by now

[pjoshea13 in reply to gusgold]

Gus,

Yes, but perhaps Cabergoline slows down the cancer? Perhaps it is a useful add-on, like Metformin?

"maybe 10 years" ago! You have done better than many - can you be sure that Cabergoline didn't help?

How many in the 'mainstream' know anything about prolactin?

According to Dr. Myers, most oncologists are so focussed on T, they don't even check DHT.

-Patrick

[gusgold in reply to pjoshea13]

Pat,

you may be right...I started using Cabergoline when Dr. Strum said PCa can use Prolactin as a back door when on ADT.

Gus

[MateoBeach in reply to pjoshea13]

Now commenting and questions about the prolactin/cabergoline/Zn which I have been carefully noting since you brought this to my attention. The case report only peaks that. I did try adding zinc supplement along

With topical clioquinol, but very questionable absorption. Also take quercetin. Then realized this can only follow a passive Zn gradient and not produce high intercellular levels in absence of active Zip1 transport.

Still very interested in using Cabergoline. Already FDA approved and available. Thought I would save it until CR emerges. But now wonder if it might have some efficacy while HS?

Seems it would be fairly easy to do a small proof of concept trial, an open label series esp in mCRPC to see what might be there. Paul

[jimbob99999]

This is actually quite interesting. Thanks for sharing. I found this article too which recommends a dual strategy that includes Cabergoline and Clioquinol. It suggests doses and is apparently approved by the FDA.

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

[Graham49]

Could this be a link to oestrogen, which presumably is also involved with lactation?

[pjoshea13 in reply to Graham49]

Graham,

For men treated via ADT, testosterone [T] (the source of estradiol [E2] in men, by aromatization of T) should be too low for E2 to be a player.

-Patrick

[Graham49 in reply to pjoshea13]

Thanks Patrick

[Jdbnord]

sammamish

[pjoshea13 in reply to Jdbnord]

Thanks. -Patrick

[Kevinski65]

Tell me, does degarilix interfer with pituitary hormones? If so would it be better than Lupron?

[Break60]

My RO had me on cabergoline for years. My prolactin was extremely low as a result. Seeing no obvious benefits I stopped taking it about nine months ago. Maybe I was wrong?

[Hidden in reply to Break60]

Any side effects of taking cabergoline?

[Break60 in reply to Hidden]

I don’t recall any but I was on ADT3 metformin, etc so who knows? I would google it to find out. It’s expensive as hell . The list price is $55 per tiny tablet and you take 3 a week.

[Hidden in reply to Break60]

really expensive! Maybe there are other prolactin inhibitors less expensive and less toxic. Do you know how much was in a pill?

[Hidden in reply to Hidden]

In this case ncbi.nlm.nih.gov/pmc/articl... it was only 0.5mg 2X week

[Break60 in reply to Hidden]

.5 mg sounds right. I’m away and don’t have access to my bottle of pills. I know Snuffy Meyers recommendation was three per week . I cut back to two per week before I stopped taking them when my prolactin was practically nil. There’s a u tube video by Dr Meyers on cabergoline. Google it.

[tallguy2]

Thanks for posting this. Tall_Allen what is your take on Cabergoline? I know that Phase III trials are a long way off.

[pjoshea13 in reply to tallguy2]

No PCa studies yet, but som interest for BCa:

clinicaltrials.gov/ct2/show...

-Patrick

[Break60 in reply to pjoshea13]

PCa and Bca have many similarities, no?

[pjoshea13 in reply to Break60]

Some parallels - but some big differences, of course. -Patrick

[Break60 in reply to tallguy2]

I know Snuff Meyers believes it stops high prolactin another source of PCa. Cabergolinedrove my prolactin down to like 95% below normal levels. After stopping it it now is in normal range. I test it whenever I test Psa T lipids E2 etc.

[Captain_Dave]

I believe resveratrol can lower prolactin.

ncbi.nlm.nih.gov/pubmed/221...

[pjoshea13 in reply to Captain_Dave]

Thanks! -Patrick

[kainasar]

I would be interested in what vitex users have to say about prolactin reduction.

[Rilu]

Dear fighting partners,

With the issue of prolactin an important question arises because of my great ignorance. It costs us a lot for a doctor to prescribe medication outside of the cancer treatment and our oncologist does not want to leave conventional treatments, so we can only go to supplementation. I have read that vitamin B6 considerably reduces prolactic levels, but instead in some post in this group I have also read that it is better not to take vit b6. At the same time I have found some study that, while they advise against taking folate and vit b12 for prostate cancer, vit b6 is not contraindicated, on the contrary.

I have also read some post in which the MO advises for neuropathy to take high doses of vit b6.

I'm having a mess.

I bought vit b6 and now after reading everything, I don't know if it's convenient or not. Is anyone taking vit B6 and has not had an increase in psa or disease associated with its consumption? What dose do you take? Is it not advisable to take it?

Thanks a lot!!

researchgate.net/publicatio...

reuters.com/article/us-vita...

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

[pjoshea13 in reply to Rilu]

Vitamin B6 does not concern me in the way that folate/folic acid & B12 do. If B6 has an effect on your prolactin level, please let us know (as a new topic).

I am using this, but I'm not sure how it is affecting prolactin:

swansonvitamins.com/now-foo...

-Patrick

[Rilu in reply to pjoshea13]

Thks Patrik, i'll do

[Hidden]

Hello Patrick! Did Dopa-Mucuna bring your prolactin down? How were your levels before and after? Do you take 1 capsule per day or more? It should not make any difference for T while on ADT, right?

[pjoshea13 in reply to Hidden]

My level was higher!

6/2019 - 11.1 ng/mL (4.0-15.2).

10/2019 - 13.7 ng/mL

But I would need more data before writing it off.

I used 2 caps with my early morning coffee. Perhaps I should take another 2 caps before bed.

Re: "... right?". Right.

-Patrick

[Hidden in reply to pjoshea13]

So these levels are after taking L-Dopa? it's in the normal range.

[pjoshea13 in reply to Hidden]

I was hoping for low-normal (or lower).

[Hidden in reply to pjoshea13]

Related to DES?