bipolar androgen therapy

[nuc1111]

does anyone have experience with this? how did it work?

[Tall_Allen]

Seems to extend time to failure with Xtandi, but so far, no increase is survival.

[pjoshea13]

I have used testosterone [T] in one way or another for 17 of the 18 years since diagnosis.

I was influenced by a hypothesis that appeared in a journal in the early 1990's. The author thought that when a patient on ADT became 'refractory' he should restore T. Cells that could not adapt would die; cells that could adapt would then respond to ADT. The cycle might perhaps be repeated indefinitely.

I was leery of doing a 12-18 month stint of ADT. I decided that I would do no more than 3 months - & then do 3 months of T. I repeated that cycle for years & remained hormone sensitive.

3 years ago (after 15 years) I decided to try BAT. Denmeade's 28 day cycle did not work for me. I tinkered with it & decided that one should never get the next T shot until T has returned to the previous lever or lower. That's what I'm doing.

T acts as 'reset'. I see it as something that should start with ADT - definitely not delayed until CRPC.

There was no BAT when I began my 3 months ADT / 3 months T program, but I view that as BAT now. The concept of BAT, as Isee it, is tha a periodic shot of T provides a jolt that sets the clock back. And maybe, if Denmeade figures out a protocol, CRPC can be delayed indefinitely.

-Patrick

[nuc1111 in reply to pjoshea13]

Patrick-can't you enough--Ed

[CurrentSEO in reply to pjoshea13]

Patrick, Thank you for continuous wealth of information that is coming from you.

Would you mind to clarify few things please:

- Why you switch from rotating testosterone and ADT to BAT?

- Was your PSA always increasing while you were rotating and was on testosterone 3 months?

- Have you had mets (if yes, lymph nodes only or bones too) when you started ADT and testosterone 3 months rotation?

- As you were doing rotation of ADT with testosterone for 15 years when oral ADT was not available, it is understandable why you might have chosen 3 months ADT injections. However as now Orgovyx is available and also Abirateron, Xtandi, Erleada, Nubeqa that most likely can be used instead of standard ADT to rotate with testosterone injections would you also do you rotation 3 months ADT and 3 months Testosterone ... or if you were starting it now you would use not fixed time frame (3 months in your case before) but certain PSA percentage drop/rise?

- BAT as I understand is when you continuously on ADT and periodically shoot testosterone while you are still on ADT. Do you think that this way is more effective than rotation of ADT with Testosterone injections?

- How do you decide how long to stay in castrate state and how long in high testosterone phase while on your current BAT?

Sorry for so many questions. Thank you!

[pjoshea13 in reply to CurrentSEO]

When I was diagnosed, my doctor wasn't a fan of the imaging options of the time & I didn't bring the subject up intil I had pain that might be due to bone mets. A simple bone scan showed a large lesion at L5, but no other. That lesion could not have caused the pain. It took a year to find someone who would zap an oligometastatic met when there was no pain. In that time, the lesion had hardly grown, so I think it had been there a while.

The radio-oncologist who treated me was reluctant. He said that there was no evidence that treatment would improve survival.

When I was tinkering with BAT 5 years later, I developed pain that could be due to bone mets. Another bone scan revealed a large lesion at T6. Again, it could not explain the pain. The same radiologist zapped T6. I asked him why he immediately offered to zap it when he was so reluctant to zap L5. He said "How could I not?" He hadn't expected me to be alive after 5 years.

Months went by & the pain lingered. He sent me to a spine guy who said that my spine was in good shape for my age (thank you vitamin K2?) The pain was likely due to cancer. He wanted a scan but insurance would not approve it.

The bone scan hadn't shown anything, but the radiologist asked for another. Insurance will pay for any number of those. This showed a pin-prick of white at S1. By the time I got to see that, I had modified my BAT protocol & the pain was much diminished.

The radiologist asked me whan I wanted to do. I had begun to tire of the whack-a-mole approach & I didn't expect an oligometastaic cure, so I said that I rather liked having S1 as my canary in the mineshaft. I would save radiation for when S1 really needed it.

You say: "BAT as I understand is when you continuously on ADT and periodically shoot testosterone while you are still on ADT."

That is easily misunderstood - "continuous" is not a requirement. I use old-fashion Diethylstilbestrol [DES], which is an oral estrogen. I started out with 1mg and had increased it to 2mg when S1 was found. I had also increased the cycle to two months.

I take a DES vacation when I inject T - 7 days, which I will increas to 10 in the next cycle. A week of T above 1,000 ng/dL is just a blip compared to 3 months. I hardly notice the benefit.

Why did I switch? I thought that rapid cycling might be better.

-Patrick

[CurrentSEO in reply to pjoshea13]

Thank you Patrick, a lot to think about

[George71 in reply to pjoshea13]

Hi Patrick,

As you know I have been doing a T variant protocol . I'm on Avadart daily and taking T- cyp injections weekly no ADT or estrogen patches yet.

My concern is -- how can I stop T injections and get my T to produce naturally again now that I have been on T injections so long? I don't want to go to low or no T for many months till my body starts back making it naturally.

Any suggestions? My PSA is anywhere from 1.05 to 2.12 -- depending on what my T is when I go get the blood draw....ie. a low T of 200 on one occasion PSA 1.05) and a high of over 3000 (PSA 2.45) -- last draw T was 605 and PSA 2,12

I am working on the idea that trying to reduce PSA to undetectable is what actually brings on the CRPC -- so I just try to keep the PSA from rising or doubling in less that a year or 18 months..

So far I am 6 years post surgery -- with nothing but Avadart and trying to keep T at a fluctuating range -- between super high and then down to normal range every month or so. I don't think the fluctuating T has helped or hurt from what I can tell. That is why I think I will go back to natural until PSA doubling time increases and then I will do the estrogen patch and super T in 3 month cycles like you are doing (and zap any visible mets as they show up). .

I don't want to stay at super low T very long -- while waiting for my body to start making it again on its own. Any thoughts ?

[pjoshea13 in reply to George71]

George,

I don't know what periodic T-cyp does to regular T production, or how long T takes to recover and if recovery is to the previous (natural) high.

You could titrate T-cyp down to a dose that gives you a max T of ~1,000 ng/dL (normal high - no more 3,000 ng/dL). Let your body adjust to that. Then perhaps slowly reduce T-cyp further & try to assess if/how your narural production is responding.

At diagnosis, most men don't have normal-high T - due to age & the effects of PCa. Do you know what your level was? I always assume that we need a little help to get T into the 650-1,000 range.

-Patrick

[George71 in reply to pjoshea13]

My T was around 450 to 500 prior to starting T injections to reach super high T to cause double strand breaks in cancer cells. I stopped injections for a month and my T dropped to under 200. It has a similar effect as BAT without the ADT... (T went from over 2000 to under 200 by just suspending the T shots -- I was taking anywhere from 1/3 cc to 3/4 cc per week -- then stopped entirely for one month. Then came concerned that staying off could lead to months of very low (almost castrate level) which is what I am trying to avoid... I think evidence shows that that is what brings on CRPC.

[Hidden in reply to pjoshea13]

How quickly does your T go castrate after starting DES? I used patches for ADT in 2019 and my T did not go castrate until 5 weeks in.

[pjoshea13 in reply to Hidden]

I can't really say, since T-cyp lingers. I suspect that I am at castrate levels in the last half of the second month.

[Hidden in reply to pjoshea13]

Probably.

Half life elimination

[MateoBeach in reply to pjoshea13]

That is a good protocol. I also found that T-cyp does not clear in 14 days as standard 28 day BAT suggests. Found I need 3 to 4 weeks to clear and now using Relugolix then for my 30 days off period. Will consider extending it perhaps to 60 days.

[Hidden in reply to MateoBeach]

I planned to use Relugolix as you do, but my insurance denied coverage. So I use Lupron continuously.

T-Cyp has about a 1-week half-life so shouldn't get very low until maybe 4-5 weeks in. That is problematic and I found that Androgel, dosed properly, gets my T to > 1800 ng/dl and then clears in less than a week (1-day half-life). I tested out both the hi and the low many times.

On my 7th month of modified BAT. I'm HSPC. The last PSA was zero (standard scale).

[MateoBeach in reply to Hidden]

Thanks for pointing that out. It fits with what I’m finding coming off T-cyp. Don’t want to waste my expensive month on Relugolix. Maybe I will use androgel for the last week or two of high T cycles. 🤔

[Hidden in reply to MateoBeach]

You could also try substituting T-cypionate with T-proprionate. Prop has a 3 day half-life. I inject it slowly in my glutes and only 100 mg at a time with a 25 guage. No pain at all. Prop is a short ester so it can hurt if you do a lot and do it fast.

I do 100 mg of T-prop every other day for the first week and then 175 mg of Androgel for the second. (in practice I vary the high cycle length and low cycle length and adjust the prop and gel accordingly)

I used to have a little joint pain. NPP (Nandrolone Phenylpropionate) is great for joint pain - collagen growth, bone growth, and muscle growth. I use 200 mg/week for the first week or so. You can get NPP with an Rx. No pain from this injection and joint pain goes away. Supposedly joint pain gets even less over time. I love the stuff.

[j-o-h-n]

BAT? Man, you can find tons of info regarding that subject in our online database....just do a search....from your home page. Stay well....

Good luck, Good Health and Good Humor.

j-o-h-n Friday 03/18/2022 3:52 PM EST

[Hidden in reply to j-o-h-n]

youtube.com/watch?v=EZ9ymE2...(Not working as expected?)

[Hidden]

I am HSPC but my PSA was rising and went up to 0.17. So I pulled the trigger on BAT. I modified it. My PSA goes to 0.2 on every high T phase, and zero on every low T phase (<0.1).

My MO loves the results and tells me to keep on keeping on.

ABAT Program

To address possible sub-optimal issues with the standard BAT therapy I designed ABAT (adaptive BAT). It is more complicated than a standard BAT program. There aren’t any trials on ABAT so feel free to modify it or add a couple of the ABAT components to your standard BAT program. If I were going to make one change in standard BAT, I would apply Androgel for 1 week instead of using testosterone cypionate.

The maximum allowed PSA (X) is up to the individual. Based on my status I choose X = 0.05.

The maximum allowed PSA to determine termination (Y) during ABAT is up to the individual. Because my PSA during the lead-in phase was zero, I choose Y = 4.

• Step 1. Lead-in ADT

1. Lead-in ADT drugs/therapies

1. Firmagon or another ADT therapy (e.g., Relugolix or Orgovyx or an orchiectomy).

2. Estrogen patches (0.05 mg/day). This is a low dose estrogen replacement.

3. Cabergoline to reduce prolactin (0.25 mg twice weekly).

4. Optional: Zytiga (either 1000 mg on an empty stomach or 250 mg with a low-fat meal). Zytiga is used to prevent cancer cells from manufacturing testosterone.

5. Optional: Prednisone (10 mg/day split into two doses). Zytiga depletes steroid production so 10 mg of prednisone a day is used to supplement.

2. Start a lead-in ADT phase and continue until PSA is less than X. If it has not dropped below X within 6 months, consult your MO or move on to a different therapy.

• Step 2. ABAT

1. ABAT Cycle drugs (example 56-day cycle)

1. 1. We need some way to reduce the body’s internally produced testosterone to zero or close to it. Some options are Firmagon, Relugolix, and Lupron. Estrogen will be replaced during the HT portion of ABAT via aromatase activity and during the LT portion of ABAT via the estrogen patch. Estrogen replacement negates many of the harmful side effects of Firmagon.

2. HT:

1. Day 1-56: 0.25 mg twice weekly cabergoline to reduce prolactin.

2. Day 1-7: Apply 8 pumps a day of 1.82% Androgel. Each pump is 1.25 g of gel). Note that you could also use three or four 5 g packets of 1% Cernos gel a day.

3. Day 1: Take an AI. I take a 2.5 mg tablet of letrozole. Anastrozole or exemestane might be preferable but they give me insomnia and bloating. The AI should be in your system for the first week.

5. Optional: Day 1: Inject 200-400 mg nandrolone phenylpropionate (NPP)1.

3. LT:

1. Day 14-49: Apply estrogen patches (delivering 0.05 mg/day). I use Climara.

2. Optional: Day 8-14: take 50 mg/day bicalutamide. This is optional. Bicalutamide will inactivate most of your residual testosterone from the Androgel. This is optional because even without using bicalutamide, the testosterone gel will be cleared within 4 or 5 days.

3. Optional: Day 8-49: take 1-5 mg/day finasteride. This is optional. It lowers DHT but DHT should be close to zero in the LT phase.

4. Optional: Day 8-49: 250 mg Zytiga with a low-fat meal (approximately 300 calories with less than 2 grams from fat – 12 ounces of pomegranate juice with an ounce of soy or whey protein satisfies this). When taking Zytiga, corticosteroid replacement is necessary and typically this is done by taking 10 mg of prednisone each day split into two doses. Zytiga takes about 2 days to reduce testosterone. This is optional. Zytiga reduces the small amount of testosterone made by the adrenals and cancer cells. Note that you could also take 1000 mg of Zytiga on an empty stomach.

5. Optional: Day 8-49: A moderate to high dose statin. Statins reduce the small amount of testosterone made by the adrenals. I would take Atorvastatin. Atorvastatin gives me insomnia, so I take Lovastatin. They are both lipophilic and might be more therapeutic than hydrophilic statins. This is optional. Some research indicates that a statin might help control cancer during the LT phase. Note that I also take 500 mg of metformin per day as well as 300 mg of EGCG, 300 mg of curcumin, 60 mg of melatonin before bed, and a 81 mg of aspirin before bed.

6. Optional: Day 8-49: 10 mg/day Rad-140.

2. The first ABAT cycle length is a minimum of 6 weeks but no longer than 12 weeks.

3. Continue the cycle until PSA is undetectable or is less than (X).

4. If greater than X at the lowest point, discontinue ABAT and determine next therapy. It might be desired to do 6 cycles of a static BAT (BAT with 4-week cycle lengths). This might re-sensitize cancer to Xtandi. If already Xtandi sensitive perhaps a 6-month stint of Xtandi, 6 cycles of static BAT, another 6 months of Xtandi, etc. Other options might be ADT or radiation, or an adaptive Zytiga or Xtandi approach. Adaptive approach: if PSA > 10 then start Zytiga (or Xtandi). When PSA drops below 4, discontinue AR drug. When PSA recovers and exceeds 10 restart AR drug. Continue until PSA will not go below (Y) within 4 months (Gattenby?). Or RBAT which is explained below.

• Example:

1. Lead-in phase, PSA target 0.05 (X).

2. Hypothetical result: PSA dropped to 0.0 so start cycle #1.

3. Start Cycle#1 (minimum cycle length – 4 weeks, maximum = 12 weeks). Increase X to 1.15*.05 = .058 to allow for slow cancer growth.

a. Start HT phase. Continue for 1 week.

b. Continue cycle#1 until PSA is undetectable or less than 0.058 (X).

c. Hypothetical result: PSA dropped to 0.02 during week 8. Note that if PSA had not dropped below 0.058 (X) by the end of the 12th week I would have ended ABAT and sought another therapy instead.

4. Start Cycle#2 (predicted length = 8 weeks). Increase X to 1.15*.058 = 0.067 to allow for slow cancer growth.

a. Start HT phase. Continue for 1 week.

b. Start LT phase.

c. Hypothetical result: PSA dropped to 0.02 during week 7.

5. Start Cycle#3 (predicted length = 7 weeks). Increase X to 1.15*.067 = 0.077 to allow for slow cancer growth.

a. Start HT phase. Continue for 1 week.

b. Start LT phase.

c. Hypothetical result: PSA dropped to 0.07 during week 6.

6. Start Cycle#4 (predicted length = 6 weeks). Increase X to 1.15*.077 = 0.089 to allow for slow cancer growth

a. Start HT phase. Continue for 1 week.

b. Start LT phase.

c. Hypothetical result: PSA dropped to 0.08 during week 6.

7. Start Cycle#4 (predicted length = 6 weeks). Increase X to 1.15*.089 = 0.102 to allow for slow cancer growth

a. Start HT phase. Continue for 1 week.

b. Start LT phase.

c. Hypothetical result: PSA dropped to 0.07 during week 6.

2. Start Cycle#5 (predicted length = 6 weeks). Increase X to 1.15*.102 = 0.117 to allow for slow cancer growth

a. Start HT phase. Continue for 1 week.

b. Start LT phase.

c. Hypothetical result: PSA only dropped to 0.15 by the end of week 12.

d. This is greater than X so end ABAT and go to the next therapy.

Notes:

1. These are optional and are included only for muscle building/bone loss mitigation.

2. SARMs and AAS might reduce HDL cholesterol, increase LDL cholesterol, and negatively affect liver enzymes. This needs to be monitored. In my experience, HDL cholesterol is the only one that is severely affected.

Tests

Monthly:

PSA, CBC, CMP, Lipids, Testosterone, Estradiol. Note that PSA should be measured after week 3 in each cycle.

As desired: PSMA PET scans.

A graphical depiction of the end of the ADT Lead-in and the first four ABAT cycles:

Figure 3 ABAT

Optional drugs are plotted with dashed lines.

References

1. Home | Medical society dedicated to testosterone deficiency (hypogonadism) and its treatment androgensociety.org/

2. Summary of modified BAT programs liebertpub.com/doi/epdf/10....

3. 5ARIs perhaps not beneficial jme.bioscientifica.com/down...

4. Zytiga with 5ARIs urotoday.com/center-of-exce...

5. Metformin for ADT phase ncbi.nlm.nih.gov/pmc/articl...

6. Statins lower intracellular testosterone healio.com/news/endocrinolo...

7. Use of high-dose estrogens for ADT

a. ncbi.nlm.nih.gov/labs/pmc/a...

b. cancernetwork.com/view/estr...

c. pubmed.ncbi.nlm.nih.gov/126...

d. nature.com/articles/ncponc0602

e. bjui-journals.onlinelibrary...

f. ncbi.nlm.nih.gov/labs/pmc/a...

8. Low estrogen replacement for ADT

a. erc.bioscientifica.com/view...

b. Con: pubmed.ncbi.nlm.nih.gov/177...

9. Use of reduction of estrogens, therapy for Pca ar.iiarjournals.org/content...

10. Mathematical modeling of prostate cancer progression in response to androgen ablation therapy | PNAS pnas.org/content/108/49/19701

11. Sci-Hub | Strategies for Testosterone Therapy in Men with Metastatic Prostate Cancer in Clinical Practice: Introducing Modified Bipolar Androgen Therapy. Androgens: Clinical Research and Therapeutics, 1(1), 76–84 | 10.1089/andro.2020.0009 sci-hub.se/10.1089/andro.20...

12. FSH lower is better? urotoday.com/conference-hig...

13. Statins pubmed.ncbi.nlm.nih.gov/350...

14. Finasteride upregulates expression of androgen receptor in hyperplastic prostate and LNCaP cells: Implications for chemoprevention of prostate cancer - Hsieh - 2011 - The Prostate - Wiley Online Library onlinelibrary.wiley.com/doi...

[MateoBeach in reply to Hidden]

Wow! Thank you for documenting your program so meticulously.

[Hidden in reply to MateoBeach]

I have to document. If I don't I forget what to do

[Wassersug in reply to Hidden]

Dear Hidden,

That is a remarkable program. You have done a heck of a lot of research.

What I don't understand is why you feel that your identity should be "hidden." I believe that it adds to credibility, when those in-the-know identify themselves in this discussion group.

Is there a reason why you feel that you must be hidden?

Richard Wassersug, PhD

[CAMPSOUPS in reply to Wassersug]

Our forum states that "hidden" occurs by way of the user closing their account however I have a feeling or more than a feeling that "hidden" also can occur and does when a user is admonished for not following the rules of the forum X amount of times and finally is removed becoming "hidden".

[Grumpyswife in reply to CAMPSOUPS]

I have always wondered about the “hidden” status thinking maybe the person had been harassed for their posts or something.

Five or so years ago there was a person named Raoul who posted a lot about Lutetium. He had it in Germany I believe before anyone else on here. He was very vocal about it. I think he became “hidden”. Then gradually disappeared from here. Maybe others recall him.

[cigafred in reply to Hidden]

Wow me too. Lots to ponder here.

[Hidden in reply to cigafred]

Graphical depiction

BAT