Testosterone propionate supposedly the best ester?

FunkOdyssey said:

Yep, that will do it. Welcome to the club!

Click to expand...

Just looked it up again, thought it's only sexual problems.


The core symptoms of PSSD, they write, are “genital anesthesia, loss of pleasure derived from genital stimulation, pleasure-less or weak orgasms (anhedonic orgasm), decreased sex drive, erectile dysfunction (ED), premature ejaculation, diminished vaginal lubrication, and diminished tactile sensitivity of nipples.” Additionally, according to their comprehensive review, “accumulated data of numerous case-reports suggest…non-sexual symptoms of PSSD, including anhedonia, apathy, and blunted affect.” These need inclusion in subsequent studies.

For me it's the non-sexual symptoms.
I think that's why I need this absurd amount of TU.
Will try to modify my protocol by reducing TU and adding proviron, maybe that's less of a hair killer for me.
Assumption: brain does not properly convert T to DHT, or something along that line.

I cannot remember if you fellows tried proviron and whether it did move the needle?

P.S. I'm now completely off SSRI.

Seagal said:

I cannot remember if you fellows tried proviron and whether it did move the needle?

Click to expand...

Proviron is too strongly anti-estrogenic for me and makes me feel like crap. Better results with actual DHT in my case or even masteron.

I just read this article Post-Finasteride Syndrome And Post-Ssri Sexual Dysfunction: Two Clinical Conditions Apparently Distant, But Very Close
I think there is nothing directly practically useful for us in the current state of this neuroendocrinology research.
There are two interesting aspects:
the link of gut microbiome - neurotransmitters - sex steroids (neuroactive steroids) which reminded me of your experience with the diet changes (carnivore+).
And the similarities between PFS and PSSD (DHT)

Forty2 said:

I started off on 40mg every 3.5 days, then experimented with 50mg every 3.5 days for a short time.
I definitely felt better on the lower dose. If I were to experiment again, I'd try 35mg test enanthate every 3 days along with 350iu hCG.
Did you guys who took accutane in your teenage years look very young in the face before starting TRT? I'm pretty sure that low testosterone for many years has a preservation effect on the face. When I was 30 I looked 20 and when I was 40 I looked about 28, despite my skin being very dry.

Click to expand...

Yes, though I’ve been on TRT for 8 years and don’t think it’s changed my face any in that regard.

Seagal said:

Just looked it up again, thought it's only sexual problems.

Sexual Dysfunction May Continue Even After SSRIs Are Ended

Post-SSRI sexual dysfunction is a medical condition that persists after antidepressants are discontinued. A field review says that it causes “substantial and prolonged suffering.”

www.psychologytoday.com

The core symptoms of PSSD, they write, are “genital anesthesia, loss of pleasure derived from genital stimulation, pleasure-less or weak orgasms (anhedonic orgasm), decreased sex drive, erectile dysfunction (ED), premature ejaculation, diminished vaginal lubrication, and diminished tactile sensitivity of nipples.” Additionally, according to their comprehensive review, “accumulated data of numerous case-reports suggest…non-sexual symptoms of PSSD, including anhedonia, apathy, and blunted affect.” These need inclusion in subsequent studies.

For me it's the non-sexual symptoms.
I think that's why I need this absurd amount of TU.
Will try to modify my protocol by reducing TU and adding proviron, maybe that's less of a hair killer for me.
Assumption: brain does not properly convert T to DHT, or something along that line.

I cannot remember if you fellows tried proviron and whether it did move the needle?

P.S. I'm now completely off SSRI.

Click to expand...

I've been off Prozac and Accutane for 30 years, yet I still have genital anaesthesia, weak orgasms, low libido and general apathy.
I've been completely gaslighted by doctors who all say that the side effects go away soon after quitting both drugs.

FunkOdyssey said:

Proviron is too strongly anti-estrogenic for me and makes me feel like crap. Better results with actual DHT in my case or even masteron.

Click to expand...

What is it about Proviron that makes it strongly anti estrogenic?
I thought it was because it's a DHT derivative?
Therefore I'm surprised that straight DHT didn't make you feel even worse.
Btw have you noticed hair loss from the DHT?

Forty2 said:

What is it about Proviron that makes it strongly estrogenic

Click to expand...

Anti-estrogenic. Unlike DHT, proviron binds to the aromatase enzyme and actually lowers serum E2. Neither DHT nor masteron do the same. DHT can interfere with E2's activation of gene transcription and has an anti-estrogenic effect that way, but Proviron inhibiting aromatase takes the anti-E effect to the next level (too much for me).

Forty2 said:

Btw have you noticed hair loss from the DHT?

Click to expand...

No. I think like the prostate, DHT in skin tissue is mostly derived from local conversion from testosterone and has not much relationship with serum DHT. I think Keith Nichols is right on this one (serum DHT is not very meaningful for androgen-sensitive tissues). In other words, high free T, or low E2, or especially the combination, is more likely to cause your hair to fall out than high DHT.

FunkOdyssey said:

Anti-estrogenic. Unlike DHT, proviron binds to the aromatase enzyme and actually lowers serum E2. Neither DHT nor masteron do the same. DHT can interfere with E2's activation of gene transcription and has an anti-estrogenic effect that way, but Proviron inhibiting aromatase takes the anti-E effect to the next level (too much for me).


No. I think like the prostate, DHT in skin tissue is mostly derived from local conversion from testosterone and has not much relationship with serum DHT. I think Keith Nichols is right on this one (serum DHT is not very meaningful for androgen-sensitive tissues). In other words, high free T, or low E2, or especially the combination, is more likely to cause your hair to fall out than high DHT.

Click to expand...

How much proviron did you take?

Seagal said:

How much proviron did you take?

Click to expand...

12.5 mg twice daily.

Forty2 said:

I've been off Prozac and Accutane for 30 years, yet I still have genital anaesthesia, weak orgasms, low libido and general apathy.
I've been completely gaslighted by doctors who all say that the side effects go away soon after quitting both drugs.

Click to expand...

Are you using Minoxidil? It can also affect androgens.
I suspected it but there was no scientific evidence, just because it wasn't researched.

Seagal said:

Are you using Minoxidil? It can also affect androgens.
I suspected it but there was no scientific evidence, just because it wasn't researched.

Click to expand...

Cortex was saying recently that he sees minoxidil causing PFS-like issues.

Maybe these are the major 'environmental' changes (SSRIs, Fina, Minox etc) in the past decades.

FunkOdyssey said:

... Unlike DHT, proviron binds to the aromatase enzyme and actually lowers serum E2. Neither DHT nor masteron do the same. DHT can interfere with E2's activation of gene transcription and has an anti-estrogenic effect that way, but Proviron inhibiting aromatase takes the anti-E effect to the next level (too much for me).
...

Click to expand...

Do you have a reference for this claimed distinction, or is it more a matter of degree? I believe DHT is also capable of aromatase-inhibition, and can act as a competitive antagonist of the estrogen receptor.

Cataceous said:

Do you have a reference for this claimed distinction, or is it more a matter of degree? I believe DHT is also capable of aromatase-inhibition, and can act as a competitive antagonist of the estrogen receptor.

Natural 21M Very Low E2 Relative to T With Symptoms

Hello all, I'm at my wits end regarding low E2 symptoms which have been going on for at least 3 years, but have worsened: frequent urination (feels like I can't empty my bladder; underwear is always soaked), constipation, dry mouth, achy joints, complete loss of libido, ED. The blood test I took...

www.excelmale.com

Click to expand...

"In addition, mesterolone has a high binding affinity for the enzyme aromatase that converts other steroids into estrogen (Brueggemeier,1994), even though it does not undergo ring aromatization to estrogen (El-Sadr et al.,1990). It is likely that mesterolone prevents the conversion of other steroids, especially testosterone, to estrogen by blocking the binding site of aromatase enzyme."

Supported by anecdotal information on both sides: proviron reducing serum E2 on lab tests, DHT having no effect. There's no better place to look for DHT's lack of impact on serum E2 than scrotal cream users - they've got all the E2 you'd expect given their T levels.

Anyone can run this experiment at home now that we have publicly vetted sources for DHT products.

FunkOdyssey said:

https://anatomypubs.onlinelibrary.wiley.com/doi/10.1002/ar.22439#bib8

"In addition, mesterolone has a high binding affinity for the enzyme aromatase that converts other steroids into estrogen (Brueggemeier,1994), even though it does not undergo ring aromatization to estrogen (El-Sadr et al.,1990). It is likely that mesterolone prevents the conversion of other steroids, especially testosterone, to estrogen by blocking the binding site of aromatase enzyme."
...

Click to expand...

I do not see mesterolone mentioned in the underlying reference. Is there another name for it aside from the ones listed in Wikipedia? The last sentence is speculation. Is there some direct evidence in the literature?

Anecdotes aside, is there any reason to believe that DHT does not act similarly, albeit with less potency?

Of course similar. This miniscule molecule modifications and related functional changes are fascinating.

It seems to act similarly to the metenolone metabolites. You cannot expect to have many research papers on those topics. Bro science based on large samples is reliable to predict outcomes, the explanations have been sometimes wrong.

Best up to date source could be Nichols related publication on exogenous DHT.

Cataceous said:

I do not see mesterolone mentioned in the underlying reference. Is there another name for it aside from the ones listed in Wikipedia?

Click to expand...

Maybe? I don't know.

Cataceous said:

The last sentence is speculation. Is there some direct evidence in the literature?

Click to expand...

Not that I can find.

Cataceous said:

Anecdotes aside, is there any reason to believe that DHT does not act similarly, albeit with less potency?

Click to expand...

If we put the anecdotes aside, we're left with very little in terms of useful information. The few studies that exist on the topic may be misleading or irrelevant - for example: FSH-induced aromatase activity in porcine granulosa cells: non-competitive inhibition by non-aromatizable androgens

"The addition of 5 alpha-dihydrotestosterone (DHT) into cultures of FSH-stimulated cells during the induction period resulted in a definite dose-dependent inhibition (30-70%) of the aromatase activity expressed in the test period. This inhibitory action, of the mixed non-competitive type, is characterized by a decrease in the apparent Vmax and an increase in the Km value, suggestive of an androgen inhibition of FSH-stimulated aromatase synthesis. This inhibition was also shown by the other 5 alpha- and 5 beta-reduced androgens: 5 beta-androstanedione was the most effective, while DHT was the least. Other steroids such as pregnenolone and progesterone were inhibitory, but testosterone and diethylstilboestrol were stimulatory. "

If we conduct the experiment in ourselves where DHT is an independent variable that we manipulate with exogenous DHT, and we observe no effect on serum E2, that is infinitely more useful to know than how much aromatase is synthesized in an FSH-stimulated porcine granulosa cell. Same thing with proviron, if we do observe a reduction in serum E2 (which cannot be explained by and is disproportionately higher than the reduction of SHBG).

Primobolan is well known for a powerful serum E2 reducing effect, often crashing E2 in users that don't pair it with sufficient testosterone. There is no explanation for this effect in the medical literature. Recently, some fungal metabolites of metenolone were discovered which act as suicidal aromatase inhibitors, but it is unknown whether these metabolites form in the human body. Yet, tens of thousands of men have observed E2 reduction with primobolan and this occurs so reliably that it is accepted as fact by the bodybuilding community.

FunkOdyssey said:

... Same thing with proviron, if we do observe a reduction in serum E2 (which cannot be explained by and is disproportionately higher than the reduction of SHBG).
...

Click to expand...

It might be possible to quantify this, though it gets complicated. Here are a couple of the elements—chime in with any others you can think of: the androgenic action of mesterolone leads to reduced production of SHBG and lower levels; mesterolone's strong binding potential for SHBG displaces testosterone and estradiol, effectively further reducing SHBG. This latter can lead to "a reduction in [total] serum E2 (which cannot be explained by and is disproportionately higher than the reduction of SHBG)." The question then is, how can you be sure this is not the phenomenon being observed, as opposed to aromatase inhibition? The observations with DHT fit in this scenario because DHT has a much lower binding affinity for SHBG than does mesterolone.

The key point is that real and effective reductions in SHBG do not affect the free hormone levels at steady state. Thus the way to resolve this issue is to accurately measure free estradiol at baseline and while using mesterolone. A decrease in free estradiol could be reflective of lowered production via aromatase inhibition.

Cataceous said:

Here are a couple of the elements—chime in with any others you can think of: the androgenic action of mesterolone leads to reduced production of SHBG and lower levels; mesterolone's strong binding potential for SHBG displaces testosterone and estradiol, effectively further reducing SHBG.

Click to expand...

I think what you are saying here is that beyond the reduction of total E2 that will be caused by SHBG reduction, there will be a further reduction of total E2 because of the SHBG that remains, less E2 will be bound to it due to displacement by proviron. This latter effect then could produce a reduction of total E2 that is disproportionately greater than the reduction of SHBG level. Am I following you correctly?

In that case, I'm not sure how you would discriminate between SHBG-displacement versus aromatase inhibition. Maybe the magnitude of the effect would be a clue? Aromatase inhibition is able to reduce E2 to the low single digits in men who aren't taking hCG when taken too far. I would expect the SHBG displacement effect to be minor by comparison.

Cataceous said:

The key point is that real and effective reductions in SHBG do not affect the free hormone levels at steady state. Thus the way to resolve this issue is to accurately measure free estradiol at baseline and while using mesterolone. A decrease in free estradiol could be reflective of lowered production via aromatase inhibition.

Click to expand...

You would need to measure free E2 directly though, as any calculation that relies on SHBG would have its accuracy compromised by the proviron displacement effect. Is this testing available?

FunkOdyssey said:

I think what you are saying here is that beyond the reduction of total E2 that will be caused by SHBG reduction, there will be a further reduction of total E2 because of the SHBG that remains, less E2 will be bound to it due to displacement by proviron. This latter effect then could produce a reduction of total E2 that is disproportionately greater than the reduction of SHBG level. Am I following you correctly?
...

Click to expand...

Yes. Mesterolone-bound SHBG is effectively missing with respect to estradiol, yet it is still counted when SHBG is measured.

FunkOdyssey said:

...
In that case, I'm not sure how you would discriminate between SHBG-displacement versus aromatase inhibition. Maybe the magnitude of the effect would be a clue? Aromatase inhibition is able to reduce E2 to the low single digits in men who aren't taking hCG when taken too far. I would expect the SHBG displacement effect to be minor by comparison.
...

Click to expand...

This would be strongly dependent on the dose and strength of the compound doing the aromatase inhibiting, which is exactly what's in question here. As for estradiol's displacement from SHBG, using Wiki's numbers, mesterolone's affinity for SHBG could be as much as 88 times greater than estradiol's. That's suggestive of a significant effect, depending on the dose/relative concentrations.

FunkOdyssey said:

...
You would need to measure free E2 directly though, as any calculation that relies on SHBG would have its accuracy compromised by the proviron displacement effect. Is this testing available?

Click to expand...

This is why I said "measure". There is a nice spreadsheet around for calculating free estradiol using the Multi-Ligand Model. But as you imply, it would need to be modified to make use of the concentration and binding affinities of mesterolone. I'm suspecting that serum mesterolone is an uncommon test, so the calculation is impractical. However, it would be useful for getting some idea of the magnitudes involved. In any case, free estradiol testing is available. @Gman86 shared a nice collection of data that correspond well to the calculated values.