I’ve been lurking BB forums keeping tabs on this drug along with users experiences with it. In all of the studies I’ve read and accounts of people using it, never have I heard it explained like you are trying to here. I think you may have the wrong idea about this compound. It has an affinity for muscle tissue, but barely anything noticlable in the brain, prostate and genitals, possibly because it’s NOT aromatised. Hence Body Builders don’t “feel” juiced in their heads, but when they go to lift, the stamina and stregnth are there. It is compared to being on cycle without feeling on cycle. 5AR isn’t part of the equation here…
Whilst this study has been conducted on frogs i believe it does have relevance to this theory. This is a very recent study so it may be worth getting into contact with the researchers to discuss the implications of their findings. (Published in General and Comparative Endocrinology Volume 166, Issue 2, Pages 217-442 (1 April 2010)
ncbi.nlm.nih.gov/pubmed/19917284
Fadrozole and finasteride exposures modulate sex steroid- and thyroid hormone-related gene expression in Silurana (Xenopus) tropicalis early larval development.
Exposures to fadrozole (an aromatase inhibitor; 0.5, 1.0 and 2.0 microM) and finasteride (a putative 5-reductase inhibitor; 25, 50 and 100 microM) were designed to assess the consequences of inhibiting these enzymes on gene expression in early amphibian larval development. Exposed embryos showed changes in both enzyme activities and sex steroid- and thyroid hormone-related gene expression.
Finasteride treatment inhibited srd5 beta (activity and mRNA), decreased cyp19 mRNA and activity levels and increased estrogen receptor alpha mRNA. Both treatments altered the expression of deiodinases (thyroid hormone metabolizing enzymes). We conclude that cyp19 and srd5 beta are active in early embryogenesis and larval development in Silurana tropicalis and their inhibition affected transcription of genes associated with the thyroid and reproductive axes.
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I believe this is infact the same study but possibly published in a different paper.
ncbi.nlm.nih.gov/pubmed/20130388
The aromatase inhibitor fadrozole and the 5-reductase inhibitor finasteride affect gonadal differentiation and gene expression in the frog Silurana tropicalis.
We conclude that chemically induced intersex animals display different gene expression profiles than non-exposed animals and that, although morphologically similar, intersex animals produced by different chemicals have different endocrine pathophysiologies.
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The more i read about this the more i’m convinced that epigenetic changes are the key to this whole thing.
I think that we need to get in contact with epigeneticists and try to convince them to take interest in our case.
With all my experience with Androgen replacement therapies(TRT,Masteron,HGH etc) I notice that the amazing effects fade after a few weeks.This is scary because it points to a deeper problem…receptor densensitivity.
But here is what confuses me…the sexual boost fades but I continue to maintain and grow lots of muscle,have oily facial skin,hair loss,acne on back and shoulders,aggresion etc.
So what’s going on here?Why does the libido fade but all the other effects remain.My understanding of this is that all effects should fade.Is it possible that only the receptors in the genital area are desensitized?
viewtopic.php?f=5&t=3901&p=24587&hilit=deacetylase#p24587
Read that threat on HDAC inhibitors…I’m going to try Sodim butyrate…This maybe VERY Helpful in order for us to get better…
On your end whalen, you just started the 400mg of TRT, why not give it a few months to see if you feel better…It may take awhile for your body to recognize it on a cellular level…
Whalen,
My interpretation to that problem is low 3 adiol G. Does TRT bump your 3 adiol G up?
CorrioVip…yes my Adiol-G was rock bottom(3.4 ng/ml) back before I started the high dose Test.The blood test is very expensive(over $800) so I never did it again…yet.
Man… I think anyone who lives in Canada and is seriously afflicted with this condition needs to move to the states or see an American doc. Adiol g test are free with insurance here
Hey Golf I’m willing to do just about anything at this point including a trip anywhere…If blood work is so readily available then why aren’t more of us posting frequent blood updates?
i guess not everyone loves to share there personal blood work, but the fact is if you have full time employment in the states they do usually pay for blood work.
Are you referring to insurance coverage. Don’t you need a doctor’s permission for blood tests before insurance will cover them? Doctor’s are very resistant to authorize the full gammut of tests on the short list.
Mine weren’t.
Awor,
I do not understand why you believe that the altered Gene Expression theory explains muscle wastage. 5AR is not expressed in the muscle tissue; thus, while on or after quitting finasteride, muscle cells do not perceive any change. While the theory explains the subsequent insensitivity to androgens of tissues in which 5AR is expressed, it fails here, I believe. How exactly would the androgen receptors in the muscle cells “know” that they should downregulate? I am not aware of any mechanism by which the body sends this information intracellularly.
And you are? Considering this is your first post, please fill out the Member Story template and post yours in that section please, so we can get acquainted with your history:
This article gives an excellent account of Androgen Receptors.
http://jcem.endojournals.org/cgi/content/full/88/9/4043
Expression and Degradation of Androgen Receptor: Mechanism and Clinical Implication
Awor,
First of all, thanks for serving as guinea pig for your Procaine treatment and congrats for your success so far. The androgen resistance theory exaplins most facts and experiences collected in the years. I have a question though: how does this theory explain the temporary improvement in sexual functions that some people experience after messing with their neurotransmitters? (dopamine in particular)
I would think that, if our androgen receptors are dead, then increasing dopamine would only increase motivation and possibly libido, but wouldn’t help with erections or with penis shrinkage – or, am I wrong?
These people, on the other hand, say that sexual function is back to 100%:
http://www.propeciahelp.com/forum/viewtopic.php?f=23&t=4231
http://www.propeciahelp.com/forum/viewtopic.php?f=5&t=4352
http://www.propeciahelp.com/forum/viewtopic.php?f=3&t=1247&start=60(he took Phenibut)
It seems that the theory of epigenetic changes at a cellular level is inescapable for those suffering from post-finasteride syndrome. Considering the universal symptoms are a lack of apparent androgen mediated gene expression and low levels of Vitamin D it is interesting to note the relationship many academics and doctors have made between Androgen Receptors (AR) and Vitamin D Receptors (VDR).
Androgen-receptor coregulators mediate the suppressive effect of androgen signals on vitamin D receptor activity http://www.ingentaconnect.com/content/hum/endo/2005/00000026/00000001/art00001http://www.urmc.rochester.edu/george-whipple-lab/professors-investigators/documents/HJT-13.pdf
Interactions Between Vitamin D and Androgen Receptor Signaling in Prostate Cancer Cells
prevention.cancer.gov/files/news-events/20070507-8-weigel.ppt (see slide 13 for example)
Interactions between the androgen and vitamin D axes in early stage prostate cancer http://gradworks.umi.com/14/49/1449377.html
Its pretty complicated stuff. Both AR and VDR share regulatory proteins; en.wikipedia.org/wiki/Androgen_receptor#Interactions , although the true number of proteins that interact with each is unknown. (Many of these proteins effect gene expression through histone acetylation and deacetylation not methylation.)
Anyway, if one receptor can indirectly effect the other through certain proteins and coregulators that interact with both, it stands to reason that the only answer to what has happened to many of us is an epigenetic change at a basic level to the way our bodies now work.
Found this on the Post SSRI Sexual Dysfunction group, regarding a possible gentic study on sufferers by one of the members. Seems less complex than the full genome sequencing awor was suggesting but thought it might be of interest:
"It would in possible in theory to determine which genetic variations are linked to PSSD. This could potentially help us identify the genes involved. I don’t think any major research institute will do such a study on their own for some time.
I have discovered that it may be possible for me to do a GWAS (Genome Wide Association Study) with Do It Yourself Genomics diygenomics.org/participate.php . I do not have enough training YET to do this but I am currently working on genomics research and learning more everyday. This group will help citizen groups to set up studies of their own. It essentially could help us to do the research ourselves.
If we were to do this I would need many PSSD suffers to get themselves genotyped. I have got myself genotyped. It currently costs $200 with 23andMe (23andMe.com) . You would then have to volunteer your data for the study.
I see two things potentially coming out of it.
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We may learn what genes are responsible for PSSD symptoms. This could possibly help explain the disorder and MAY (I really cannot know) eventually help lead to treatments.
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It may allow us to determine the genetic basis such that others would not take SSRIs if they were prone to developing PSSD.
Right now I don’t need commitment from anyone. I just want to see if there are even close to enough people interested. We would need at least 100, probably more people to participate for it to be effective."
This seemingly reactivates the VDR - perhaps that could trigger something with the androgen receptor?
mpkb.org/home/pathogenesis/vitamind/metabolism
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