solothesensei

Supplement Ecommerce/R&D Chaotic good, all things biz and biochem

[solothesensei @solothesensei]

Confident in the prescience of this prediction -

Dihydrotestosterone and its esters will gain mainstream popularity in the next 10 years

[solothesensei @solothesensei]

There are 3 uses for E2 cypionate in men:

1. Running it with a net anti-estrogenic stack to prevent low E2 symptoms (improves dopamine and serotonin signalling)

2. Correcting crashed E2 caused by Adex/Asin/primo etc

3. PFS (highly advanced, stacked with DHTE)

[exp @0xexpt]

Anyone played with estradiol cypionate in the case of over-suppression OR fine-tuning for focus/dopamine?

cc @solothesensei

[solothesensei @solothesensei]

@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 @solothesensei]

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 💪

[solothesensei @solothesensei]

@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

[solothesensei @solothesensei]

@bowtiedcrake Pretty good, 25% EBITDA

[solothesensei @solothesensei]

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

[solothesensei @solothesensei]

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

[solothesensei @solothesensei]

@markusssss91 E2C>E2V>E2 cream

[solothesensei @solothesensei]

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

[solothesensei @solothesensei]

@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

[solothesensei @solothesensei]

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.

[Zedzies @Zedzies]

Early TRT leads to accelerated thymic involution and reduced longevity. Not a good idea to start this stuff at too young of an age. Guys doing T in their 20's are in for a rude awakening.

[solothesensei @solothesensei]

@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 @solothesensei]

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”

[solothesensei @solothesensei]

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

[solothesensei @solothesensei]

@EagleTwoRomeo Under my supervision, yes there were several

[solothesensei @solothesensei]

@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 @solothesensei]

@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 @solothesensei]

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 @solothesensei]

@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 @solothesensei]

@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?