The Overlooked Problem of Drug-Receptor Desensitization

General Discussion
#1

The desensitization of androgen receptors could well be the explanation of our problems.

Quote from Bio Balance Homepage:

Bio Balance is a biomedical research company dedicated to improving drug safety through a better understanding of drug-receptor interactions.

If androgen receptors aren’t sensitive to androgens anymore we won’t show much/any reaction in response to these hormones (DHT, Testosterone), even if they are abundantly present in our bodies. That equates to the same problems as if you wouldn’t have any androgens in your body at all.

If androgen receptors become desensitized, any part of our body which is dependent on androgens (brain/cns, prostate, penile tissue, libido, muscle, facial collagen tissue, etc.) will not function correctly anymore.

Here is an interesting article on receptor desensitization and drug safety:

http://www.bio-balance.com/DrugSafety.htm

And background reading on androgen receptor function:

http://www.endotext.org/male/male3/male3.pdf

Permanent sexual side effects from SSRI’s are tentatively being linked to receptor desensitization.

#2

I’m don’t think it touches everone of us.

I very rarely (maybe once per week in avg.) have some moments, that for about 5 to 10 minutes I feel 100% ok. And then it suddently passes out.

I don’t think that I get correct sensitivity for few minutes and then it goes away into desensitive state for another few days.

#3

I believe there is something to this theory. Evidence of Fin affecting the AR has already been seen here.

Additionally, if we are to believe that the inhibition of DHT production caused a lasting crash due to excessive T, there is obviously reason to expect our system to exhibit changes (prostate/penile shrinkage, muscle wastage, etc), due to the un-natural hormonal environment, right?

Your train of thought puts forth my curiosity of, what would cause permanent/long-lasting desensitization of the AR? In pursuit of more information on the Androgen Receptor, I encountered cases known as “Kennedy Disease” and “Spinal & bulbar muscular atrophy” which both describe symptoms that many people here have experienced, however, these conditions specifically are linked to genetic mutations of the Androgen Receptor.

I suppose if our hormonal balance were normal and we still were not benefiting from it, the desensitization of the AR would be the main culprit (can’t say certainly since I’m no expert on the AR), but this seems to be a more multi-faceted problem, marked by our inability to produce the level of hormones which we once did.

Judging from the study referenced first, I think it’s right to say that in most cases, there is a downregulation in AR function which is probably not repaired post-finasteride, thusly requiring further examination in patients like us.

Just my two cents.

#4

I’m scared to say that there might be some basis to this. Could some of us have a predisposition to this and fin triggered it? Pure guessing, but many of the symptoms match these and those of post-SSRI-sufferers’.

#5

The core problem that is affecting all of us is probably the same. It doesn’t make rational sense that Propecia has just gone about destroying random parts of our bodies - different parts for everyone. There has got to be a common denominator to this.

It also is counter-productive to pursue 30 different theories at the same time because we don’t have the necessary resources for that. We need to work out what the most likely candidate could be and focus on getting to the bottom of this.

Why can’t it be that receptors work better some days and worse on others?

Quote from Bio Balances

Just the words “equilibium”, “interaction” and “probability” are hints enough that receptor sensitivity is a very complex and dynamic issue.

The interesting question to pursue is “what interaction would be required to arrive at a new state of equilibrium”?

I have contacted these guys to see if there is any chance that they could somehow help explain what happened to us.

#6

Peres, you stated:

Richard Lanzara, Ph.D. is a legit researcher and has articles published in reputable scientific journals (links on his site)… thus I have no reason to disbelieve the below.

Just more food for thought, for the Androgen Receptor desensitization theory…

bio-balance.com/DrugSafety.htm

#7

If androgen receptor mutation/desensitization has occured (though based on most people’s hormones here, we do not have elevated LH/T, a hallmark of androgen resistance)… why would TRT not work?

Treatment options for AR mutation ( propeciahelp.com/forum/viewtopic.php?t=1417 ) involve massive doses of androgen to overcome the defect… but in certain cases there is little improvement felt (similar to how some guys on TRT post-Fin feel little improvement).

The million dollar question would then be, why do some men respond to such treatment and others do not… in the end, it probably all boils down to genetics – especially considering these two pieces of research highlighting Finasteride’s mechanisms of action are more effective in certain men vs others, and that future drug treatment protocols with 5AR inhibitors should involve genotyping BEFORE commencing treatment, to determine drug choice/efficacy.

propeciahelp.com/forum/viewtopic.php?t=1406
propeciahelp.com/forum/viewtopic.php?t=1407

That said, I wouldn’t be surprised if all of us share a common genetic marker/allele/mutation(?) involving either the androgen receptor or 5AR2 enzyme that caused us to respond in the way we did. But without a study involving us “sufferers”, we’d never know… or, if everyone here had genetic testing done and shared the info to look for commonalities.