Finasteride caused Androgen Insensitivity or altered Gene Expression?

General Discussion
#121

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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#122

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.

#123

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?

#124

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…

#125

Whalen,

My interpretation to that problem is low 3 adiol G. Does TRT bump your 3 adiol G up?

#126

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.

#127

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

#128

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?

#129

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.

#130

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.

#131

Mine weren’t.

#132

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.

#133

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:

viewtopic.php?f=3&t=371

#134

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

#135

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)

#136

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.

#137

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.

  1. 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.

  2. 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."

#138

This seemingly reactivates the VDR - perhaps that could trigger something with the androgen receptor?
mpkb.org/home/pathogenesis/vitamind/metabolism

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#139

Makes sense. I want to try and address both LH and FSH cuz they are very low. I guess it’s worth a shot. By the way i have all the symptoms of PFS sufferer having taken Finasteride, some more severe than others. I know Clomid has mixed results but since my issues don’t seem to corrolate with my testosterone levels (prolactin and SHBG are in good range as well) but mostly LH and FSH that are at complete bottom of the range, might be worth a shot with clomid ? To trick/reeducate brain on how to release proper levels of LH… Would clomid affect FSH at all ? I know it affects mostly LH but i really would like it if my FSH is also kickstarted since FSH is even lower.

#141

This is a very long and very complicated thread but as far as I understand it deals with matters that go the core of what PFS might be and how to potentially test for it. As far as I understand, the steps required to make progress in figuring out this disease, as laid out by @awor in this thread, is to test for gene expression.

The thread was started 10 years ago. Have we gained any more information about the issues discussed in this thread since then?

I would like to ask anyone who might have knowledge about this if they are aware of any tangible progress having been made in the cost/ease of testing for gene expression? Surely it must have become easier to run such tests in the past decade?

I know there are already various research efforts under way, but I think it is important to have an idea about this: how costly would it be to test a single subject for the relevant gene expression?

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