NPP (nandrolone phenylpropionate - nandrolone is legal. It is perhaps the healthiest anabolic steroid, arguably better for us than TRT). We have to use an underlaying ADT and we should be able to use Zytiga also. We can not use an ARSI such as Darolutamide or this will not work.
This is very experimental. We might be able to reverse cachexia and build muscle in what is primarily an ADT state. We will have to use ADT (e.g. Orgovyx) and we could use Zytiga if we want – double hormone blockade. Then inject 250 mg of NPP every 10 days. The average anabolic action should be higher than what a 60+-year-old man has naturally. Roughly half the days we’ll be at an androgenic “castrate” level (single-digit androgenic action decaying close to zero). We'll build bone mass, and muscle mass, and improve joint health, and NPP's effects on lipids are neutral or positive (reduce bad LDL cholesterol and increase good HDL cholesterol).
Some rational:
Dihydronandrolone, the 5α‐reduced metabolite of nandrolone, is substantially less potent than DHT in terms of androgen receptor activation. Research comparing their relative androgenic activities indicates that DHN exhibits roughly 20–30% of the potency of DHT. In other words, DHN is approximately 70–80% weaker than DHT. This lower potency is attributed to DHN’s reduced binding affinity for the androgen receptor and differences in its molecular structure compared to DHT.
This significant difference in androgenic strength is one reason why nandrolone (and its metabolites like DHN) tends to have a lower incidence of androgenic side effects (such as severe acne, aggressive behavior, or significant hair loss) compared to testosterone-derived androgens, even though it still exerts anabolic effects useful for certain clinical applications.
References: In vitro binding studies and androgenicity assessments have established these relative potencies, with nandrolone’s androgenic rating often cited around 0.3 (relative to testosterone = 1.0), whereas DHT is typically rated at about 2–3. Thus, the 5α-reduced metabolite DHN shows markedly lower activity compared to DHT.
Abiraterone (Zytiga) specifically targets the CYP17A1 enzyme, which is key for androgen synthesis from cholesterol. It does not inhibit the 5α-reductase enzyme that converts nandrolone to its 5α-reduced metabolite (often referred to as dihydronandrolone or DHN), nor does it directly interfere with DHN’s ability to activate androgen receptors. In essence, while Zytiga lowers overall androgen production upstream, it does not block the conversion of nandrolone to DHN or DHN’s AR activity. Abiraterone (Zytiga) works by inhibiting CYP17A1, thereby reducing the production of endogenous androgens from the adrenal glands. If you administer exogenous testosterone—as in bipolar androgen therapy—it bypasses the need for endogenous production. Abiraterone does not block the conversion of testosterone to dihydrotestosterone (DHT), which is mediated by 5α-reductase, nor does it interfere with the binding of testosterone or DHT to androgen receptors. Therefore, when you pump in exogenous testosterone, Zytiga does not significantly impact testosterone or DHT levels, their action on androgen receptors, or the muscle hypertrophy that these hormones promote.
In general, estrogen receptor B (ERb) is protective and receptor A (ERa) is oncogenic (bad).
Nandrolone relative binding affinity ERa = 0.01, ERb = 0.23
Nandrolone absolute binding affinity (ki) ERa 765 ERb 53.
So it requires a high concentration to bind most of ERa. Much lower to bind ERb.
I use a Nandrolone ester during high testosterone phases for joint and bone and muscle health. Perhaps the ERa/ERb agonism is another reason to take it?
One negative is that this doesn't do much for libido. For that we would need to use Androgel once a week. Same drugs (ADT and Zytiga optional. Daro could be used on a few days).
NPP is definitely the best compound for the combination of joint health, muscle building and strength while mitigating androgenic side effects. You might really be on to something here. Its effects on ERa/ERb and how it works with Zytiga are good to know. Thank you for your research on this.
I’ve often wondered if a TP/NPP combo would be as effective for PBAT as TP alone. There would definitely be even greater QOL benefits with the combo.
When it comes to SARMS do they also work better when using zytiga vs using Nubeqa ? And can they still be effective while on Nubeqa.
It’s great to see you and the incredible work you do back. Thank you
Sure. I'm fascinated with this field. Not many people really understand what we are going through. Who the heck wants to be frail? QOL is darned important and just gets more important to me as I get older.
I've been using NPP with pBAT almost since the day I started. To be safe and minimize any interference I inject the NPP 12 hours or so after I do my first TP injection. Most of the DNA DSBs will be created in the first 12 hours so this seems a little safer to me. I also increase my T a little over 2000 to compensate. I should figure out how much I need. Wouldn't be hard to do. Good grunt work for ChatGPT.
I think real SARMs need some AR activation to work well. I could be wrong on that though. Some of the fake ones (e.g. Cardarine) should work as well with the ARs blocked as with them open. (Nubeqa blocks them - Zytiga doesn't)
I've tried a SARM (Rad-140) with ADT and it didn't seem like it did much for me. That's not very scientific.
So perhaps a good program would be TP, a day or so later NPP, then more TP to keep the T level above (x). Then SARMs while your T is high. Then maybe Zytiga and a low dose of Rad. A few mg seems safe (for me at least). I had to go to 100mg a day before my PSA started shooting up. Or perhaps Nubeqa and some Cardarine. I need to check Cardarine out more. The few times I've used it my HDLs improved. And I lost a little more fat than usual. Not definitive by a long shot though.
Lots of experiments and lots of research to do. I'll be posting.
Cardarine doesn't need the ARs to work. But there are some backdoor pathways that cancer might exploit during ADT if Cardarine is present. Really hypothetical. But still a possibility.
I think its very safe to use 10mg a day of Cardarine during hi T. And 10 mg of Rad or Ostarine.
Then during ADT 5 mg of Rad per day "should" be okay.
Thank you. Your knowledge is incredible. What is your opinion of sarm s4. Its main component is bicalutamide and has some anti prostate cancer properties and excellent bone density effects. Supposed to be a little better than ostarine but a lot of people stay away because of potential for temporary vision side effects.
Anyway I started Nubeqa with the intentions that it would be better for PBAT. So that’s what’s next. NPP would be a better addition to high T than any sarm. Do you think a combination of TP and NPP (there is a definite synergy between the two compounds for physical performance and quality of life) would still create the double strand breaks the same as TP alone? And would the addition of oliparib be as beneficial with the combo as it would be with TP alone. Thanks again
I'll look into s4. I've used it before but I dont remember why. I'll let you know tomorrow. What you just wrote is interesting and has me wanting to research it.
I think Nubeqa is the best ARSI for pBAT. Olaparib shouldn't be affected by NPP. A little maybe but not much.
I need to look into Zytiga also. If we can use it, awesome!
There are also many other sarms that were designed for prostate cancer patients. OPK 88004, GSK2881078, FL442, S42, ,MK4541 etc etc. It’s interesting that OPK 88004 isn’t offered by any sarms sites. In clinical trials it had superior muscle gain and fat loss results t for prostate cancer patients.
Your posts also make wonder if both zytiga and nubeqa have both worked effectively for a patient and he hasn’t failed either., would a schedule that alternates the two be effective for delaying resistance to them. They would each kill a different type of resistant pca. Especially if the person has already had a positive response to treatment breaks.
Kinda like this: Adaptive Zytiga, BAT with multiple timeframes and intermittent high T pulses, PARP inhibitors, Immune therapy, and possibly radioligand therapy. Experimental but I have this as a backup plan anyway. I can measure PSA and do scans and get an idea of what might be working (if anything).
Or this? Another backup plan.
16. Zytiga/NPP/darolutamide rechallenge after testosterone recovery from BAT.
This should be a good anabolic therapy. Muscle, bone, joints, and RBC should all benefit. Libido won’t. It might be possible to block intracellular DHT with dutasteride and then use a low dose of transdermal testosterone gel to increase membrane androgen receptor activity.
• A 2015 study included etoposide for CRPC. Post BAT, testosterone levels were allowed to recover and four men were rechallenged with Zytiga. Response rates to this small sample were good. Delay was 4+ months.
• TOP2 inhibitors such as etoposide can sometimes restore sensitivity to Zytiga according to a 2022 study.
• Researchers speculate that intratumoral testosterone doesn’t wash out immediately and this prevents Zytiga’s reduced testosterone biosynthesis from having an appreciable effect.
• One of these might be responsible for the Zytiga results. Or perhaps the study was simply too small to draw any conclusions.
• If the reason is the delay, that can be added in after BAT to allow testosterone to recover. And perhaps short darolutamide cycles can be inserted into the Zytiga treatment.
S4 is intriguing but I think Rad might be a better bet during ADT (not sure about SPT). Much higher anabolic:androgenic ratio (supposedly). 90:1.
From what I've found so far, S4 (like Rad) needs active ARs to work. That eliminates Nubeqa. I'm looking into orgovyx and Zytiga. Should still work with them? Need lower doses though. Maybe too low so Rad... I've used lots of Rad over the last 4 years so feel comfortable with it. Lots of data. Takes 100 mg/day to start affecting my PSA. PSA is just a marker and I don't know what say 10 mg of Rad would do today. I'll think I'll be finding out in the next 6 months.
Some of our reasoning is sad. So S4 causes cancer. I'm sure you've heard that. Well, that stupid study was in rats given 40 mg/day (human equivalent) for 2 years! Yeah, so by that "logic" water causes you to explode. Hey, watch what happens when someone drinks 10 gallons of water a day for 2 years. 100% death rate. Lesson: don't drink water.
And S4 trials were halted because of vision issues. Digging in, the vision problems were "a slight yellow tint at night". As expected, the "vision problems" went away when S4 was stopped.
Infuriates me. Tell me the truth. Do reasonable human doses on reasonable schedules cause cancer? How much is the difference? Significant? I'm all ears. But don't to lie to me. Deca internet and government horrors are even more disingenuous.
OPK-88004 is a non‐steroidal selective androgen receptor modulator that acts in a tissue-selective manner. In muscle and bone, it behaves as an AR agonist—stimulating anabolic effects—while in the prostate it functions as an antagonist, thereby lowering prostate-specific antigen (PSA) levels1. Unlike testosterone, it is not converted to dihydrotestosterone (DHT) by 5α-reductase, thus avoiding excessive androgen stimulation in prostate tissue2. By binding with high affinity but displaying partial agonist activity, OPK-88004 competes with endogenous androgens, leading to anabolic benefits (increased lean mass and bone density) while protecting the prostate. In contrast, agents like nandrolone phenylpropionate (NPP) and testosterone are full agonists with less tissue selectivity. Cardarine is a PPARδ agonist—not an AR ligand—enhancing fatty acid oxidation and endurance8, and YK-11 is a steroidal SARM with potential myostatin inhibition but no human clinical data.
One might speculate that its anabolic to androgenic ratio could range anywhere from 10:1 to perhaps 1000:1, that remains entirely hypothetical without direct comparative research. This research has not been done.
________________________________________
2. Research & Studies
Clinical research on OPK-88004 includes Phase 1 trials showing a long elimination half-life (~27 hours) and acceptable oral bioavailability. A Phase 2 randomized trial in older men with a history of prostate cancer and hypogonadism (using doses of 1, 5, and 15 mg) demonstrated dose-dependent increases in lean body mass with concomitant reductions in fat mass and PSA. A separate trial in benign prostatic hyperplasia (BPH) noted transient liver enzyme elevations at higher doses (15–25 mg). In contrast, nandrolone (NPP) has been studied primarily in contexts like HIV/AIDS wasting and dialysis-related muscle loss, demonstrating anabolic efficacy yet with risks such as HPT-axis suppression and virilization. Testosterone replacement therapy benefits are well documented in large-scale RCTs, whereas Cardarine and YK-11 suffer from limited human data.
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3. Overall Quality of Evidence
For OPK-88004, the evidence is promising but limited to Phase 1/2 studies with moderate sample sizes and short follow-up periods. Its anabolic effects have been reliably demonstrated; however, long-term functional and safety data remain pending. Nandrolone and testosterone are supported by decades of clinical use, though testosterone’s non-selective AR activation may pose greater prostate risks. Cardarine and YK-11 lack robust human data.
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4. Conclusion
OPK-88004 shows potential as a tissue-selective anabolic agent—capable of increasing muscle and bone mass without stimulating the prostate—in older men, including those with PCa or on ADT. While testosterone remains the gold standard for hormone replacement, OPK-88004 might serve as a safer alternative where androgenic risks are a concern. Nevertheless, more extensive and longer-term clinical trials are needed to confirm its benefits and safety profile compared with established agents like nandrolone, testosterone, and even experimental compounds such as Cardarine and YK-11.
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5. Common Side Effects
In clinical trials, OPK-88004 caused a dose-dependent reduction in HDL cholesterol (approximately 13–18 mg/dL at 5–15 mg) with minimal effects on LDL and total cholesterol. Higher doses in the BPH trial were associated with transient liver enzyme elevations. In contrast, nandrolone is known for HPT-axis suppression, potential virilization (especially in women). Cardarine’s short-term use is generally well tolerated. YK-11 remains unproven in human studies but is presumed to share steroid-like side effects such as testosterone suppression.
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6. DNA Damage & Double-Strand Breaks (DSBs)
OPK-88004 has not been shown to induce DNA damage or double-strand breaks. Its AR modulation is designed to confer anabolic benefits without overstimulating the receptor to levels that impair DNA repair. In contrast, therapies like Bipolar Androgen Therapy (BAT) rely on supraphysiologic testosterone levels to induce DSBs in prostate cancer cells. Given that OPK-88004 operates as a partial agonist/antagonist, it does not reach the threshold required to cause such DNA damage. Accordingly, it does not appear to synergize with BAT. There is no evidence that OPK-88004 enhances DNA-damaging treatments such as PARP inhibitors or radioligand therapy.
Yeah. It’s kind of crazy(infuriating) why some compounds that would be very helpful to all prostate cancer patients are just brushed aside while others that are debilitating and really don’t offer that much to OS are pushed in SOC. I guess we both know the answer to that question , but it doesn’t really accomplish anything to address it. We also know we have to keep doing our own research that is enhanced with our ability to get more factual and unbiased information. There are some really resourceful and smart patients like yourself and John who has followed your lead and have paved the way for the rest of us. It’s obvious to me what I have to.
They did a clinical trial at a well renowned cancer hospital where OPK 88004 was used on patients with non recurrent pca. All patients had an increase in muscle mass and a decrease in fat and psa. And they weren’t actually excercising. If that isn’t positive results I don’t know what is. But they failed it because it didn’t increase libido. (It wasn’t designed or expected to) and it didn’t increase stair climbing ability. (How could it if the patients weren’t actively doing cardio) . I was actually a former patient at that hospital and asked my oncologist about the compound and his response was “That it failed in clinical trial “ simple and easy response but it didn’t sound like a failure from my point of view
How do you incorporate NPP in your high T phase of PBAT? Is it used throughout the high T phase or in pulses ? This is a great compound and definitely works great when combined with TP. I wonder since it’s not bio identical like TP would it interfere with the action that creates double strand breaks? It’s binding affinity to ERb and not ERa makes it very appealing in addition to all the QOL benefits that are superior when combined with TP than TP has on it’s own
It interferes. I use its AR affinity, its estimate of 5ar conversion to DHN, and its weak action to calculate its theoretical negation of DHT. Then I give a big buffer because I am probably off. I use my SHBG and lean body weight to estimate my DHT concentration in the PCa cells. It's all programmed now so I can enter the amount(s) of NPP and the day(s) and the amount(s) of TP and the day(s). I should arrive at the practical DHT level. I'm typically about triple what is supposedly needed (clinical trials). Mostly because of my very low SHBG (15-25 vs. a mean of 50 nmol/L for a 60-year-old man). The real reason I take it is for muscle and joint health. As you mention though, it does have the ERb and ERa binding positive.
And to be extra cautious, I take it about a day after my first injection. By then most of the damage should be done. I'm inclined to wonder if the longer pulses are even needed for DNA DSBs. But they might be for some cell types (looking into the studies, most cell types only need high T for hours or a few days, but at least one needs weeks for optimal destruction).
By the way, I'm doing rBAT pulses for the next month - hours or a couple of days of high T. Every time I've done them my PSA has dropped (except once - when I did SBRT). PSA isn't cancer and I only have data on 13 of them. 12-1 sounds good but maybe it's like the Phoenix Suns this year. Ouch!
NPP needs active ARs to work it's joint and muscle magic. So, that part is a waste during ADT phase. But it has a good ERb/ERa ratio. I'm not aware of any clinical trials that I can use for an ERb/ERa proof so I tend not to take it during ADT. Might be good. But it might not.
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