Restoring androgen sensitivity with epigenetic modulators

#21

I could be mistaken, but I think the case of father and son is that they where both susceptible to PFS. I think they both took propecia and then both got PFS.

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#22

does anyone have anymore details about this father and son? i hadnt heard about this

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#23

No, I’m talking about a mother who reported the underdevelopment of her son’s male characteristics (namely his genitals) and the father has PFS. But yes I have also heard of at least one father/son case who both took Fin and wound up with PFS. My cousin also has PFS sides. Two different issues. It’s been pretty clear there is some genetic predisposition for a while. Hopefully as the studies get funded and progress they’ll get a handle on which genetic links are at play.

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#24

I remember that and just checked it. The husband was ON the drug so he didn’t have PFS per se, and the woman just seemed a bit hysterical about her son having a small penis, even though a pediatrician said it was normal. I found her attitude a bit crass and maybe she doesn’t know that small dicks run in her side of the family or something.

There are a couple of cases I recall of PFS guys having boys and no mention of anything untoward.

What sides does your cousin still have boston? If he’s told you…

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#25

There have been many incidences of guys who have had PFS for years and their wives/girlfriends don’t acknoledge it’s a real condition either. We were all told our penises were just fine too even though we knew they’d been shrunk by 50% by Fin. I’m not trying to be alarmist but there does seem to be alot of evidence out there that epigenetic modifications can be inherited.

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#26

Not all epigenetic modifications will be inherited.

NYscientist any updates?

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#27

NYScientist, I wish you were around here more often as you provide a lot of insight into our problem. I was looking into AR expression modulation and prostate cancer and came across the articles below. What are your thoughts?

Genistein down-regulates androgen receptor by modulating HDAC6-Hsp90 chaperone function.
ncbi.nlm.nih.gov/pubmed/18852123

Fulvestrant (ICI 182,780) down-regulates androgen receptor expression and diminishes androgenic responses in LNCaP human prostate cancer cells.
ncbi.nlm.nih.gov/pubmed/16818513

The curcumin analog ca27 down-regulates androgen receptor through an oxidative stress mediated mechanism in human prostate cancer cells.
ncbi.nlm.nih.gov/pubmed/21796654

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#28

NYscientist,

Any further insights from you on our condition?

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#29

Airborne,

How is your baby doing now? wish and hope, he/she is doing good without any PFS mess inherited.

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#30

Hi All,

It’s been a while and hope you are all doing well. I haven’t been on the forum for a bit and wanted to give an update on a little trial I did using sulforaphane that has yielded some interesting results. First off, I want to give a disclaimer that this is my own personal experience and it is likely that other people will not have the same experience as me. That said, I have experienced a noticeable improvement across a number of factors, in some areas more and some areas less.

I decided to try sulforaphane because you can get it without a prescription and I was able to find a very high quality dietary supplement. The product I used was BroccoProtect made by a company called Designs for Health. Here is a link to a place that sells it, although there are cheaper places to find it on the internet as well:
vnfnutrition.com/phpshop/index.p … OgodUBoAUQ

I picked this version because after doing some research I found that it was manufactured to a very high standard and had the highest concentration of sulforaphane of any of the other supplements out there. In fact, some of the other similar broccoli extract products claiming to have sulforaphane had only 0.2% of the amount of sulforaphane as BroccoProtect. I mention this to stress that supplements are highly variable in quality and you need to make sure you are getting what you pay for.

Being that one capsule of BroccoProtect has 50mg and sulforaphane has a short half-life, I started off talking 4 capsules a day for a week (one at 8am, 1pm, 6pm, and 11pm). When I was confident I could tolerate this and wasn’t having any negative side effects I increased this to 1.-2 capsules at each of those time points eventually reaching 2 capsules (8 capsules in a day). After doing this for two weeks total I didn’t experience any improvement so decided to take a break.

During this time I reviewed the papers I referenced at the start of this thread, and realized that they typically just did a short treatment upfront, and this was sufficient to confer a persisting effect of resensitization to hormone. I thought that maybe it wasn’t as important to maintain steady state levels of sulforaphane, but rather to reach a concentration high enough for the compound to reach therapeutic levels and cause an acetylation event to occur. So I switched my strategy to instead take a larger single dose instead of multiple doses over an extended period of time. Warning: as with any pharmaceutical product, taking higher than the recommended dose can be very dangerous I started off with a single dose of 8 capsules at one time (400mg sulforaphane total) which I felt comfortable doing because I had already reached 8 capsules in one day spread out without significant side effects. After this single dose I stopped and observed. I didn’t notice anything right away. A few weeks later I took 10 capsules. Again I didn’t notice any immediate objective differences but after a couple weeks I started to notice a few changes:

  • Noctural erections started coming back. Whereas previous I would rarely get erections when I went to sleep I started to get them again sporadically. Certainly not to pre-fin levels but much more than previously
  • Erection quality began to improve. This is probably this biggest noticeable change. Post fin I would say I was around 50-60% of the stiffness of pre-fin–when I did get erections they were softer and more difficult to maintain. Now I would say I am at about 80-90%, occasionally reaching close to 100% on good days–and they last for longer.
  • Watery semen–this was also greatly reduced and I would say it is about 60-70% of what I would consider normal
  • Morning erections are more consistent
  • Spontaneous erections are also more frequent. Pre-fin I would get spontaneous erections ~5-8x a day. Post-fin it was virtually 0. I would estimate now I’m at 2-3.

In terms of things that did not change, I did not notice a big difference in libido. If it is increased, it is only by an incremental amount. I would still estimate that my libido is about 1/2 of what it was pre-fin.

Side effects: at the higher dose I definitely started to notice some stomach discomfort, a lot of gas, and mild diarrhea. I also noticed myself feeling hot and a bit restless. When I took the pills with food, it definitely helped the stomach discomfort but the gas and diarrhea still occurred.

I waited a while to report this since I wanted to make sure it wasn’t just a fluke. But the effects have persisted for about two months now. Again, I want to add a disclaimer that my experience will likely be different from others and may be due to reasons completely unrelated to sulforaphane. But at the same time, I wanted to share my experience.

Since the 10 capsule dose, I have also tried 12 capsules and 15 capsules, but I haven’t noticed any more benefit yet. For many drugs they have a therapeutic range, when you get outside the range by going too high you don’t get any additional benefit, and sometimes you may get the opposite intended effect. For this reason I am going to try going back to a 10 capsule dose once more.

If the effects persist, and if other people experience the same thing, I may consider posting it over in recoveries or another part of the forum. For now though just wanted to give an interim update on my experience.

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#31

Very interesting. Do you recommend that others try it out to see if we get similar results?

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#32

In reading this over, I wondered if the substance nyscientist used is able to cross the BBB or not. From what I understand about this theory, certain areas of the body have been affected while others have not. This explains the variability of symptoms. In nyscientist’s case, he did see some positives from his treatment but had very little effect on libido. Could this possibly be because the substance he was using doesnt have the capability of affecting the epigenome of brain cells, which seems particularly important when dealing with libido loss or anhedonia in general? If that’s the case, it might be necessary to use a number of different substances to affect all the different areas of the body that have been altered.

…which brings us back again to ghb as a possibly successful treatment option because of it’s ability to cross the BBB.

ncbi.nlm.nih.gov/m/pubmed/19427877/

Regardless, this is exciting that you’ve seen some success with this treatment, especially since so much of our efforts are connected with this theory. Thanks

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#33

I would recommend other people try this treatment with the caveat that they start at a low dose and they be extremely careful about monitoring for negative side effects (e.g., allergic reactions). Other than that, and aside from the fact that it’s a bit expensive and causes some gas, I don’t see a reason not to try it. At the very least, everyone can always use an extra serving of broccoli! hehe

mehhhh, I think that’s a really good observation and you may be correct. Another possibility is that different HDAC inhibitors modulate different sets of genes. Sulforaphane, the active ingredient, may thus only affect the genes regulating physiological response but not affect those which regulate psychological response. Nevertheless, if other people try this and it works, we could hypothesize that there are other HDAC inhibitors which may address the psychological aspect.

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#34

Swanson’s is dirt cheap. And Swansons always has high-rated products, testing their products at independent labs. swansonvitamins.com/swanson … 0-veg-caps

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#35

this contain only 0.4%

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#36

Does this explain why some were having success with the broccoli treatment?

Personally the only time I felt something approaching normality sexually was a couple of days into first trying that, when I woke up without fatigue and had a strong erection and libido, as well as generally feeling good mentally. This was early after the crash period as well when things were a lot worse.

I also remember the user ‘way’ who had long term bad sexual sides had a recovery period too. viewtopic.php?f=6&t=373

I think previously positive effects were thought to be from ‘reducing estrogen’ or whatever rather than some cellular mechanism.

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#37

Reducing estrogen…hmmm that sounds it would have some positive affect on our condition. Why do you think after the crash there is seemingly not a mechanism in our body that would protect us from estrogenic effects?

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#38

Just thought I’d post this study I found. Thought it was interesting for the GHB/gene modulation discussion. Basically, it highlighted the impact of one “acute” dosage of GHB on gene expression in the hippocampus and frontal cortex. They identified over 200 genes that were altered after administration.

m.physiolgenomics.physiology.org … /146.short

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#39

NY Scientist: this sounds most promising, thanks for posting how you are doing. Are you planning on taking sulforaphane long term, or weaning yourself off?

Thanks, and do keep us updated.

Davey

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So there is a cure for AR overexpression?!
#40

I’m interested in potentially trying this, but I’m unclear on the dosage. Is the idea to take 8 capsules together daily? Or just to do it once every few weeks?

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