From what we already know about Post Finasteride Syndrome (PFS) certain things can be reasonably assumed. What I am referring to when I came to some of these conclusions is not in any way abstract or “new” to this forum. I have spoken in detail with Awor about the research and have been told specifically not to publically share many details. From what he has told me and with the evidence we already have here on propeciahelp.com, certain extrapolations about what is occurring within our bodies can be made.
From what I know about what was found in Italy the problem is itself not centered in our androgen receptors. However there was a clue as to the potential problem found at the androgen receptor, that clue without going into much detail… that something is “altering” or “blocking” specific androgenic cellular functions. Now the current projects over there are to figure out exactly what is going on, on the cellular/genetic levels to determine exactly where the problem is at. Part of this effort is the genome expression study where the goal is to: “Determine gene expression profile at a full genome level and identify potentially deregulated pathways.”
Now the point of this study is specifically to identify where the problem is occurring in regards to what has been down regulated. With the two follow up studies related to what is causing it on the epigenetic level and the proteomic study trying to find what is going on, on the very base level of how this disease is affecting our androgenic cellular functions.
I am going to jump ahead here and using what data we already have available propose an assumption about what exactly has occurred with us.
For years now we have known factually that many of us are coming back low 3-Adiol-G (a DHT metabolite specifically metabolized in DHT sensitive tissues), as well as from the Rhien Labs urine panels that everyone who has had it tested has come back with low 5-Alpha Reductase metabolites there as well.
Now before anyone even says anything about it, when I discuss this on the phone with anyone not “up” on the way DHT works in our bodies this is what they always say: “Well why do most of us all have normal DHT levels when we get blood work done though?” This is simple to explain really if these people would do a bit of in-depth research into DHT. DHT is very “site specific” in nature about how it acts on the androgen receptor. Most research you will find says that DHT actually enhances the androgenic effects of testosterone in the tissues where it is metabolized. Further reading on DHT and 3-Adiol-G will reveal that 3-Adiol-G is the marker for intra-cellular (tissue) DHT activity, thus blood Serum DHT tests ARE NOT accurate predictors of overall DHT metabolism.
And what is PFS? PFS is for the most part a very site specific disease. We have sexual, mental and physical side effects. DHT being site specific in nature is obviously not being metabolized in the correct places. Also (and Awor has already alluded to this finding) it is likely to assume that Allopregnanlone metabolism has also been disrupted in our (or some of our) brains. Now while testosterone maybe the most prominent and well recognized male hormone, DHT is 3-10X more potent in its binding to the androgen receptor, and as I previously mentioned research has shown DHT to be a “force multiplier” for testosterone. Thus DHT has a POWERFUL effect on sexual function.
Sexual Sides:
Genital shrinkage
Loss of libido
Erectile dysfunction
Reduced ejaculate volume
Reduced fertility
Orgasm disorders
Penile numbness
Sexual organ tissue alterations
Mental Sides:
Depression
Insomnia
Anxiety
Muscle twitching
Physical sides (common):
Digestive issues
Liver pain (potentially caused by issues with bile production, thus why lower fat diets seem to help people)
Bloating
Enlarged Spleen (not many people have had this looked at but I’m willing to bet it’s something many of us have)
Muscle wastage (probably caused by low testosterone in response to the body trying to maintain homeostasis in reaction to disturbed androgen metabolism)
Skin issues (dry skin, reduced sweating, reduced acne)
Since DHT is relatively site specific in its action, we can know that 5-Alpha Reductase enzyme is also relatively site specific in nature. Look at the physical locations in our bodies of our issues; the sexual organs, the brain (nervous system), the skin, the liver. What do these places in our bodies have in common? Simply that 5-Alpha Reductase acts heavily on hormones in these areas to either produce DHT, Allopregnanlone, THDOC as well as bile production.
With all this taken into consideration, that we now can quite clearly see that not only is 5-Alpha Reductase (2) enzyme activity reduced by observing data already available on propeciahelp, but also that this is most likely occurring because of issues at the androgen receptor and epigenetic level.
Thus is it not unreasonable to gather from this that the sharp rise in DHT in our bodies post finasteride cessation caused an “auto-regulatory response” from our own bodies thereby down-regulating the expression of SRD5A. I’m leaving out a lot in this statement but everything up until the point of me stating SRD5A being down-regulated has already been essentially proven.
What does this mean for us? I’m not sure but the next study inline over in Italy is the: “Full genome gene expression in penile tissue”
What I am saying is that it seems highly likely, based on the above that this study will yield results showing altered gene expression of the SRD5A gene. Once again, none of this is novel and much of it has been stated in bits and pieces before by others and myself. Nearly two years ago I when first learned I had PFS I came to similar conclusions just based on my own side effects and what I knew about 5-AR2’s role in biological functions. Now with our evidence and current findings it seems that much more likely the issue IS in-fact 5AR and that it (PFS) is being sustained by a down regulated SRD5A gene.