solothesensei

Confident in the prescience of this prediction - Dihydrotestosterone and its esters will gain mainstream popularity in the next 10 years

@curebaldyhage I recommend neither Prog, Preg nor DHEA for PFS If you follow my thesis that PFS is an epigenetic AR hyperupregulation causing an excessive AR:ER activation ratio causing low E2 symptoms All 3 of the above neurosteroids worsen the AR:ER activation ratio in that state

@solothesensei How do you explain this? He took Progesterone, Pregnenolone and DHEA but he crashed severely. He got muscle loss, insomnia, brain fog, anhedonia and height loss.

Over the past year I have healed many mild PFS cases and improved baselines for serious ones. I’m now ready to share my learnings, so this will be a huge post on what PFS is, and what I believe to be the cure for it. PFS is basically 2 concurrent issues: 1. Downregulated 5AR 2. Overexpressed ARs (read that again) Issue 1 is a no-brainer, everyone knows it. PFS guys often have a T:DHT well above 15-20 (sometimes even 30-40). Obvious sign of low 5AR. Low 5AR means low DHT and low allopregnanolone, AKA constant anxiety and loss of cognitive function But here’s the weird part. If low 5AR was the issue, wouldn’t DHT Enanthate instantly solve that? No, it never did. Almost everyone who injected DHT Enanthate solo felt WORSE even though it upregulates 5AR and supplies the missing DHT. Issue 2 explains the rest. Ever realized PFS symptoms almost completely overlap with low estrogen symptoms? I always had a sneaking suspicion it was a receptor issue causing low estrogenic signalling I just never knew if it was underexpressed ERs or overexpressed ARs I have now confirmed it is the latter, but this is probably another post on its own. In any case, the actionable for low estrogenic signalling was the same. I was the first person to prescribe Estradiol Cypionate for PFS cases and it worked amazingly. In 100% of cases, increasing estrogenicity caused a directional improvement (see my previous post on this). Many guys felt respite they had not felt in years. A few mild cases were even healed at this point. But because E2 upregulates SHBG, this exogenous E2 eventually became mostly SHBG-bound Effectively becoming inactive and causing relapses in serious cases.. This is where I would pull the trump card: DHTE + E2C combo From my earlier experiments with DHT Enanthate I knew there was an estrogenic range (around 50-200mg/week, varies between individuals) (Note: DHTE’s estrogenic range appears ONLY when serum E2 is relatively high) I initially believed this was due to DHT’s conversion to estrogenic 3b-androstanediol, but now believe SHBG reduction is the main reason. Exogenous DHT massively increases free E2 (even if it reduces total serum E2) via two mechanisms: A. Reducing SHBG thus directly increasing free E2 B. Having 17x the binding affinity to SHBG (compared to E2), so most remaining SHBG would bind to DHT, liberating even more free E2 Hence, having DHTE in the estrogenic range basically solves Issue 1 (low 5AR) and Issue 2 (overexpressed ARs) For serious PFS cases, this protocol led to the best and most prolonged benefits: - DHTE: 50-200mg/week - E2C: Up to 5-8mg/week Often it would not be a complete cure, but they reported significant improvements in their baseline states after coming off. I believe anyone with PFS should look deeply into this therapeutic modality. After all, the original epigenetic trigger was nuking a critical hormone to 1/5th its usual level. It only makes sense to fix PFS by applying the same epigenetic force in the same magnitude but inverse direction (5x) More serious cases might look into combining the above with Valproate to further “catalyse” the epigenetic reversal (once the correct magnitude and direction is applied) I consider this my biggest and possibly final contribution to the PFS mystery and thank everyone who worked with me to reach these insights. To all PFS folks: Do not lose hope, and all the best 💪

@bowtiedcrake As someone who has incorporated, hired and operated in the Philippines, their banking system is completely wack Enormous effort just to setup a bank account Banks nickel-and-diming on transfer fees Abhorrent FX payments infrastructure

TIL that Philippines blocks access to IBKR and other international brokerages, but has the US S&P500 inside wrappers called "feeder funds" you can buy from PH banks with high fees (e.g. 1.5%) Parasitic oligopolies lmao But all said and done, probably what I'm gonna tell relatives to buy from now on, and where I'll keep excess pesos I'm actually skeptical on getting older relatives from buying BTC because self-custody is hard and data leaks from local exchanges are real.

@bowtiedcrake Pretty good, 25% EBITDA

@solothesensei Returns beats SPX?

@ASvanevik The banks are retarded especially with FX transfers. Huge fan of Aspire, Wise, Airwallex etc

Everything in Singapore is modern and efficient. Except the banks. Wow.

@hoeflatoor I wrote this letter to Indranee yesterday, the stats in it may be helpful for your essay

We are dying. I will put out an essay detailing the eventual collapse of our nation on the level of Citrini soon. LKY, give me strength to do what you could not...

@markusssss91 E2C>E2V>E2 cream

@solothesensei I noticed slight improvements using huge doses of estriol cream. Should estradiol valerate work or does it need to be cypianate?

Anyone with PFS who takes exogenous E2 for the first time finally feels alive again after months/years of suffering It’s not an instant cure but a step in the right direction. It’s the last thing you’d expect from a condition associated with low 5AR/DHT

@PGC1a_RB @Zedzies Blunting definitely but net overall? Just a surface observation but moms simply age faster than non-moms, yet is entirely worth it

@Zedzies @solothesensei Pregnancy also increases maternal IGF-1 too, so that blunts some of the induced thymic involution as well, doesn't it?

Pregnancy dramatically increases thymic involution too. Even more so with multiple kids. Are we going to say it’s “not a good idea”? At some point we must all trade lifespan for actually living the life we want.

@AbudBakri Sure 100% but you get my broader point. Even if the pregnancy was net thymic involutionary it would still be entirely worth it for most if not all mothers

@solothesensei Not the full story Breast feeding leads to thymic regrowth 1+ years of breast feeding > pregnancy involution

I’ve written about this, that’s because PFS is not just a 5AR shutdown but also an AR overexpression. The latter “crowds out” ERs so every PFS person has low E2 symptoms. From this study: “Androgen receptor expression was significantly higher in study patients compared to controls”

I don’t think PFS is just a simple 5AR shutdown. If it were only that, the body knows how to restore those enzymes. PFS often reveals underlying dysfunction that was already there. Hormonal intervention can help, but it’s rarely enough on its own. If someone keeps the same negative inputs : compulsive habits, social isolation, no sunlight, poor diet, bad body composition … etc. They’re going to feel the PFS no matter what hormones they add. You can’t out-supplement a system that’s still under chronic stress.

Ray Peat on PFS : « That particular problem, the finasteride syndrome, or the post-traumatic stress disorder, for example, they forget what the problem is. What they’re doing in their life … and if they can get the sense of excitement and play as a governing principle of their activities, and start imagining the constructive, anti-inflammatory, energy-restoring things, rather than trying to work out the thousands of details of what particular substance would be most effective »

@WrongXbt @EagleTwoRomeo Serious cases no but baselines were improved after coming off therapy

@solothesensei @EagleTwoRomeo Healed?

@EagleTwoRomeo Under my supervision, yes there were several

@solothesensei Has anyone done this routine start to finish before?

@EagleTwoRomeo Yes, why is why at some point I introduce DHTE in a way that would complement the E2 None of it is intended to be long-term

@solothesensei So I’m guessing that phase two of this project is to introduce androgens? The plan is not to have this guy on e the rest of this life?

@EagleTwoRomeo Correct. Often serum E2 is mid-high but estrogenic signalling is low-zero Simple example: If you run testosterone at 500mg/week but crash your E2 to 0 with letrozole you are functionally and emotionally neutered

@solothesensei To be clear, they weren’t deficient in estrogen, but you believe an over abundance of AR made whatever estrogen they had ineffective? What’s an example of androgens needing estrogen to work?

They are low in both androgenic and estrogenic signalling But there is a correct starting point in fixing this. Androgens can’t work without estrogens, but estrogens can work without androgens That’s why increasing estrogenicity is the starting point, but I never said it was the end point

@solothesensei You’re correct I misread your previous post. Would you agree with the symptoms of PFS are also similar to low androgens? The risk I see is that someone with PFS has deficiency of androgens, adding additional estrogen could make things worse Were they deficient in estrogen?

@EagleTwoRomeo You are conflating 5AR with AR 5AR = 5-alpha reductase AR = Androgen receptor PFS is both a shortage of 5AR and an overexpression of AR Literally every PFS symptom is the same with low E2. Anhedonia, inability to get a pump, inability to feel, the list goes on

@solothesensei Are you saying that some with PFS can have an overload of 5AR steroids or just overactive 5AR enzyme? What symptoms overlap?

@EagleTwoRomeo That’s because low 5AR is only one of the two issues. The second issue is AR overexpression causing low estrogenic signalling. Ever realized PFS symptoms completely overlap with low E2 symptoms?

@solothesensei I’m open to learning more, but it seems like a stretch that the solution to a lack of 5AR steroids is estrogen

@Oleg_Bowtied I have, but for purposes of sleep topical allopregnanolone is better

@solothesensei Have you tried topical progesterone? I’ve tried allop injections and topical and it didn’t do much of anything for me but the topical progesterone that metabolizes to allop gets me chilled out and tired and ready to sleep