Why we are predisposed to PFS

General Discussion
#4

In addition to an AI like Letrozole, I suggest Calcium-D-Glucarate (instead of DIM or I3C).

Calcium D Glucarate – Assists phase 2 estrogen metabolism. In one study, calcium-d-glucarate was able to reduce the number of estrogen receptors by 48 percent. It’s also been shown to lower serum estrogen levels by 23 percent.

Walaszek Z, Hanausek-Walaszek M, Minto JP,Webb TE. Dietary glucarate as anti-promoter of7,12-dimethylbenz[a]anthracene-induced mammary
tumorigenesis. Carcinogenesis1986;7:1463-146
altmedrev.com/publications/7/4/336.pdf

–

Sulforaphane - This could also be helpful (although by itself no cure). It stimulates phase 2 estrogen detoxification.
drnibber.com/the-liver-and-h … foraphane/

In phase 1, estrogens are broken down (hydroxylated) into the following metabolites…
a. 2-estrogens | These are less potent than the estrogens (estradiol, estrone, and estratriol)
b. 4-estrogens | These are MORE potent than the estrogens
c. 16-estrogens | These are MORE potent than the estrogens

So in effect, our estrogens are hydroxylating (phase 1) into more potent estrogen metabolites. In a normal person, phase 2 would methylate (and glucarate) the metabolites and excrete them. In our cases, phase 2 is not occurring so the more potent metabolites are building up and dominant.

Finasteride and Accutane can cause methylation issues on their own. So they can cause PFS on their own. You do not HAVE to have the genetic methylation mutations to get PFS. However, having the mutations makes you EXTREMELY susceptible to PFS.

#5

Can Arimidex not be used as alternative to Letrozole ?

#6

Fantastic. Thank you for posting this.

I just started on 0.5 mg of Arimidex yesterday and 10 mg shots of testosterone propionate. Would be nice to see some positive results from it.

#7

Bullshit. Its clearly gut parasites and candida. Or a wizard. Nah seriously this is fantastic guys, one of the more plausible theories I’ve seen here. Great work from some seriously smart fellas.

#8

How would this theory account for the recovery/crash cycle most PFS experience after stopping Fin?

#9

I kinda saw it the same way a person with CFS experiences crashes and respite from their symptoms. An explanation would be cool though.

#10

Thank you for the attempts to make some sense out of this mess. Methylation is definitely involved, and it’s cool you’re making links between droits research and JQDs experiments.

Although I believe your reasoning is sound, I’m having trouble applying it to my own experience – my DHT has always been normal or normal/high. I’ve never had high E either.

#11

I should point out that I think this estrogen/estrogen metabolites part is the main explanation for the sexual and genital symptoms of PFS, but poor methylation itself can also cause many of the other issues related to PFS, especially the cognitive and energy symptoms. CFS is a hallmark in poor methylation status and a lot of PFSers have CFS as well as sexual/genital PFS symtptoms.

I think it can. It just seems like with Letro people are able to find their dosage schedule better. Letro also is better at increasing your natural test.

This is 100% conjecture, but I would assume the DHT coming back online is killing off the estrogen and the withdraw of Finasteride/Accutane itself temporarily takes a little burdon off the mehtylation system. This holds for a few days/weeks, until the estrogen is able to re-supply and create the methylation burdon again. Again 100% conjecture.

I think this theory explains the fact that (1) some people get PFS after take 1 single pill and (2) a lot of people crashed after some sort of environmental stressor (i.e. night of poor sleep, out drinking/drugs the night before, infections, job/relationship stress, etc).

Same situation here. My DHT has been normal/high in 8/10 of my labs. I do not trust my labs for estrogen though…or at least think they fit my biochemisty. I think the DHT aspect is part of the issue (as obviously low androgens has its symptoms), but the hidden estrogens and estrgoen metabolites (which are more potent) and the poor methylation status are the aspect that make PFS unique to something like CFS or andropause (low testosterone).

#12

Davey, you should post that to my thread to update your progress, also, 0.5mg of arimidex is a very big joke for PFS and exogenous testosterone. you are going to need much more than that, I really suggest you get letrozole, everyone I have spoken to (myself included) seems to require it eventually.
Try taking 1mg of Arimidex at a time, the estrogen with PFS from test can be sobering, it is going to be hard the first money, but worth it as your DHT builds up. A month into this and I haven’t needed any AI for almost 2 days! You have to start with high doses which makes arimidex not very practical.
Def 0.5mg will not work, I took that dose pre PFS, I hate to tell you how much arimidex I was taking on prop, but it was a lot, many times a day, to keep prop working, so that was why I switched to Letro. Everyone is different, but when you feel any estrogen symptoms, take more arimidex.

#13

I second that. You’ll need more.

#14

I’ve read people from the methylation forums who have gone through “crashes” who have not taken finasteride. It could be related to methylation being screwy as well.

Regarding the methylation problem, do we have results from the “general public” who have successfully recovered from PFS or who have not had symptoms, or even just an average person in general? Although these are “mutations” and more rare according to the literature, I think we need to see what the average person has in regards to mutations if these are truly rare or not. The methylation community is so all over the place and it’s all so new, many people have differing opinions on everything. Many people on the meythlation forums seem to have similar mutation problems (referring to the fact that EVERYONE seems to have some mutations, which seems odd, you would think some people would have NO mutations if they are indeed rare)

#15

Skeptical of this. DNA methylation is very trendy right now, and is used as a catch all for every undiagnosed condition.

That said I am interested and have purchased 23andme. What do I do with the results?

#16

I have seen two PFS individuals with estrogen metabolites tested and it actually showed the opposite of what we would expect with this theory, so as of now it does not look correct.

This is different than the DNA methylation theory.

#17

Opposite how? Are you saying that the methylation cycle is impaired but that estrogen is metabolizing properly?

#18

From what I have gathered…

We would expect 16- and 4-metabolites to be high and 2-metabolites to be low, but its actually the complete opposite…I have not have time yet to research into this more so I may be wrong still.

#19

The above labs were when the individual was well into the methylation trestment protocol, so its possible that that accounts for the unexpected values, although they did not feel a substantial improvement.

#20

Did this research ever lead you to any improvements?

#21

I find this all very interesting. I don’t know my full 23andme panel yet but I know I have low COMT activity. The COMT enzyme is responsible for metabolizing estrogen via methylation, as well as neurotransmitters. This would be neuro-estrogen as @moonman1 points out.

#22

I also have the cyp1b1 which has to do with estrogen if I understand correctly as well

#23

Interestingly, in the revival of this topic, I looked up Methylation, and a site the made some recommendations to overcome demethylation, they seemed incredibly similar to the suggestions others had to improve PFS symptoms.

At this point, the advice doesn’t seem to hurt, but without additional serious science and research, it doesn’t bring us closer to understanding root cause or a remedy.