I came across an article that talk about Androgen Deprivation therapy in prostate cancer patients. This is different than finasteride but some of the mechanisms might be similar.
Here is the link to the article: theoncologist.alphamedpress.org/ … ll/9/3/295
The part that caught my attention is that there are different types of prostate cells. Some are androgen dependent and others are independent. When androgens are deprived the depended cells die off and are replaced by the independent cells.
“Prostate epithelium is made up of three different types of cells. The largest portion is secretory epithelial cells. Others are basal epithelial cells and endocrine-paracrine cells. Normal secretory epithelial cells require androgens to survive, while basal cells can endure without them. Basal cells are understood to be the stem cells of the prostate, or cells that generate secretory epithelial cells [12, 13]. Only epithelial cells undergo apoptosis upon androgen withdrawal and not basal or stromal cells [14]. The clonal selection hypothesis relates to the selective survival of preexisting androgen-independent cells within the tumor by hormonal deprivation [15]. These clonal cells are thought to be poorly differentiated and akin to basal or stem cells.”
This might explain why after ceasing treatment we do not get better.
The article also talks about reactivation of the androgen receptors. Does anyone know anything about that? Has anyone tried it?
"Acquisition of an effectual circumvention where steroid hormone receptors are activated without a ligand. Three growth factors—insulin-like growth factor, keratinocyte growth factor, and epidermal growth factor—have been shown to activate receptor tyrosine kinases (RTKs) [17]. After RTKs are activated, the androgen receptor is phosphorylated by either protein kinase B (Akt) or mitogen-activated protein kinase, resulting in ligand-independent androgen receptor activation [19]. "
very vey interesting,in my opinion this way is one of the most importantway togheter with the 5AR2 deficit …
infact also if we could have the enzyme 5AR2 working we could have a problem on the androgen receptor or about cells that are androgen depending … but if it should be our case,how can we restore it? … i think pumping for long time an higher testosterone level in pour body .
There are at least a couple of theories in this thread which interest me. I would like to know which theory at the androgen receptors you tend to believe is true. Also, is it in our interest to have tests done like Chams for AR? I suppose it would cause some interested physicians or researchers to take note and initiate research on this problem if nothing else.
I have lost no hair since I quit finasteride back in January. My un-erect corpus cavernosa remain smaller than my former penis. I suppose many of you have the same symptoms in these two areas. I often think that the unresponsiveness or weakness of response in my genital area is caused by the AR ‘problem.’ It’s as if they’re only half functioning and thus the sum body of the penis, for example, is only half responsive. Thus the sum tissue there responds slowly and is rarely ever truly “hard.”
Looking back, do you think you would have chosen to quit FIN gradually instead of suddenly? Do you think it may have helped to prevent the supposed androgen receptors problem?
Yes. For all the arguments about supposed genetic predisposition to this I bet this forum would be practically empty had everyone weened off slowly. Perhaps this is why Merck said you should always consult you doctor before quitting in thier recent statement to Swedish TV.
Pretty bold statement. After 4-5 days being off FIN abruptly in January 09, I read some postings on this site about weening off FIN but I didn’t adopt the method or read the entirety of that theory/thread.
bad decision after bad decision…
I have a feeling that those two to three weeks following my FIN usage were the most destructive and perhaps the reason why these problems have never ceased.
I would like to give you an update from my interactions with the scientific community.
Looking up and trying to contact scientists around the world has been a pretty intensive and sometimes demoralizing task. Obviously, not all were interested in talking with me (often because they thought that our problem was not relevant to what they were doing). Some were also very surprised to be contacted by some guy from outside of their “circle”. In order to give me a chance of having an intelligent conversation with these people I have spent many months reading all kinds of scientific publications (mainly on pubmed), which I though had relevance to our problem (including many of the excellent links provided by mew and other members of this forum). Each time I came across a term which I didn’t understand, I looked it up. I am currently also following courses on Biochemistry and Molecular Biology at Berkley University (over the Internet). I can strongly recommend this for anyone (with sufficient time) who is interested in getting more background on how we function at the molecular level (which I believe is highly relevant to our problem, I’ll talk about this further on). In addition, a well known cell biology scientist and relative of mine, has been giving me personal guidance during the whole process.
In result I have managed to get into contact with a number of scientists, which are involved in research in the following areas:
Androgen Insensitivity Syndrome (AIS)
DNA methylation
Androgen receptors
Endocrine disruptors
Muscle dystrophy
High end genomic functional studies (including gene expression)
I have had the chance to have some very interesting conversations with these specialists and would like to provide a short summary of the information that I managed to gather.
First of all, the fact that finasteride can cause long lasting symptoms, like the ones described in this forum, was news to all of these people. This clearly confirms that one of the biggest problems this group is currently facing is a complete lack of awareness, even within the scientific community. Our problem is completely off of the map. Hence the first objective that I have been pursuing is to build interest for a case report. Even this has so far proved to be extremely difficult. Androgen receptor related research basically falls into two main categories: Prostate cancer and AIS. We don’t fit either. In order to define a new category, we first need to get this problem onto the map. We can achieve this if someone is willing to do a case report. Only then can we hope for further investigation into our problem.
The other difficulty we are faced with, and one scientist even told me this, is that our problem is not sufficiently dramatic. We have neither a very large affected population nor are the side effects (on average) sufficiently dramatic to catch immediate and widespread attention. Our 1200 members from the forum pale in comparison to the 190’000 new prostate cancer cases each year (alone in the United States). Out of these cases, almost 30’000 die each year. Never mind that for some us it may seem more attractive to die from prostate cancer than to deal with these side effects indefinitely and not having a universally clear diagnosis. Indeed, the most severely affected amongst us are truly in a serious health condition (I consider myself as part of this group).
According to the specialists which have examined me, the severity and duration of my side effects can only be explained by a problem at the molecular level - most likely at the level of the androgen receptor. I fully agree with them and would also say that the more “simple” theories going around on this site, even though easier to understand, just don’t cut it when it comes to explaining side effects such as life threatening depression, extensive damage to penile structure or massive muscle wasting.
Accordingly, my interaction with basic scientists was focused on the androgen receptor theory (including related signaling pathways) and not things like the prostate, pituitary or whatever. I also chose the people I contacted based on what they have published in the fields of the androgen receptor, AIS, prostate cancer, epigenetic and gene regulation mechanisms, 5AR and other closely related fields.
This is what I have learned from talking with these scientists:
Both the scientist specialized on the androgen receptor and the scientist specialized on endocrine disruptors deemed it to be plausible that our side effects are caused by some form of androgen receptor malfunction.
The AR specialist told me that the androgen receptor was extremely complex and that over 200 known proteins interact with it, either silencing or enhancing gene expression. Science currently only partially understands how it all plays together.
We know that mechanisms of self-regulation at the protein level exist, but don’t understand their feedback system. It seems that proteins, such as the androgen receptor, have some mechanism of self-regulation (at the protein level) which are probably based on genetically/epigenetically defined set points. In other words, the receptor has a perception of what the “right” level of gene expression is supposed to be. If this level is exceeded, it shuts down. This regulation happens through various mechanisms of gene regulation (dna methylation, other proteins, post translational modification, etc.).
One possible explanation of our problem could be, that this set point somehow got messed up by lowering DHT levels. It could also be that our bodies are overproducing some protein involved in gene silencing of the androgen receptor.
It also seems to be clear that receptor signaling pathways can “permanently” change under hormonal influence (or lack thereof). A good example of this are LNCaP prostate cancer cells. When deprived of androgens through androgen ablation therapy (which notably includes finasteride), the signaling pathways somehow changes to allow the cells to further grow, even with very low levels of androgens. In many ways this is the exact opposite to what seems to have happened to us. Instead of becoming super sensitive, our receptor/pathways have become super insensitive. This analogy was noted by the androgen receptor specialist. Another good example of this is tamoxifen resistance. Estrogen receptors (ERbeta) in breast cells, when treated with tamoxifen, eventually start perceiving tamoxifen as an agonist instead of an antagonist. I personally have experienced this. I have been on tamoxifen since about 2 years now. Initially, this treatment helped to reduce my breast pain. Since about 6 months, tamoxifen actually increases my pain level. In other words, tamoxifen started being perceived as an estrogen at the breast (ER) receptor level.
From talking with these scientists, it is also very clear that our problem is way beyond the current envelope of basic science. Trying to explain what has happened to us is about as daunting as trying to explain the exact mechanism as to why prostate cancer cells become super sensitive to androgens once deprived thereof. Billions of dollars have been invested into this sole question since over 20 years and we still don’t have real answers. Asking for a research solution to our problem is currently like asking for a cure for cancer. We’ll get there someday, but I doubt it will be in a time frame which is still relevant to us. On the other hand, a breakthrough in understanding the underlying mechanisms behind signaling path changes, in prostate cancer cells for example, could also improve the chances of explaining our problem (this was noted by two of the scientists that I have talked with). Molecular tools and diagnostic equipment are advancing at an incredible speed. Discoveries often lead to further discoveries in a snowball fashion. It remains hard to tell, what advances will be possible in what time frames.
Even though a potential cure currently seems out of reach, it is quite realistic that we can actually prove or disprove the androgen receptor theory and what has happened to us. Gene expression studies are becoming increasingly accessible with a unit cost of around 700USD for materials (multiply that by at least 40 individuals and add salaries/time of specialists and we are still talking six digits). Of course, you still need the scientist that can design the test and interpret test results correctly. On the other hand, given the complex nature of protein interaction at the signaling level, it is not said that our problem can be reproduced in a lab environment (in vitro). Also, if our problem is related to some form of post translational modification (chemical modification protein after its translation), a gene expression study isn’t going to reveal this either. But such a scenario is provable as well, although more complex (statement from lab scientist specialized on executing such studies).
The bottom line to all this is: Our problem is likely to be at the molecular level, an area which is still relatively poorly understood by basic science. In order to get our problem onto the map (an get research going), we need to get something published. As far as I can tell, it is not realistic that a cure will be found to our problem within a useful time frame – even once research has started. However, it is realistic that our bodies can heal themselves (at least in some cases). We must support our bodies the best we can in the process. Given the assumption of this problem, it is also not realistic that a simple doctor has any real chance of helping us. A regular doctor (as opposed to a scientist) is governed by the boundaries of basic science. Even worse, he/she is governed by commercialized solutions (i.e. pharma products) resulting from basic science. So if the basic scientists are still trying to figure out what’s going on at the molecular level, we can’t expect a simple doctor to be able to solve this. Most of us that have been to see various “specialists”, without real results to show for, probably have realized this.
To end on a positive note, and I have said this before: Our biggest asset is nature and this forum. We have people trying all kinds of things. Sometimes deceivingly simple things can help. We must condense and build on this knowledge in order to assist our self-healing powers.
In the mean time I am slotted to see another scientist who specializes on nutritional aspects of muscle wasting. I also plan on doing further testing of urine metabolites and will continue to try out various treatments. I will continue to do anything I can to support awareness for our cause in the science community. In particular, I am hoping that we will achieve some form of publication in 2010. I’ll keep you updated on any interesting developments.
Wishing everyone a successful self-healing process.
First, I just wanted to preface such comments that this is all still hypothetical. Regardless, such conversations with specialists certainly help shed additional light on where the problem areas might be, if it were proven to be true via in-depth testing by scientists. Thanks for all the time and effort you have invested thus far to present this additional information.
Second, just to play devil’s advocate for a second – we have had a few members on this site who have reported TRT has had a noticeably positive effect on their libido, erections, penile size etc. How could this be possible, if in fact AR gene expression had been altered? I’m still trying to understand why certain guys report feeling great improvements on treatments, while others do not report much change at all. Similarly, we have a user with elevated Prolactin who brought it under control via dopamine agonist treatment, which he reports has cleared up his sexual side effects tremendously. This does not tie directly into the AR gene expression theory, yet he was able to significantly improve via therapy targetting a hormonal imbalance.
Third, how does the AR theory account for the common post-Finasteride drop in Testosterone levels? For a lot of guys here who have yet to try treatments to boost Testosterone or ultimately TRT, perhaps they are now running on a lower level than they had been before Finasteride, which may make all the difference if they were able to increase their T. Then again, we’ve had reports of guys not feeling much of an improvement despite elevated T levels, and Dr. Crisler himself mentioning it often takes supraphysiological levels of Testosterone to evoke the desired response in post-Fin sufferers… which is puzzling (and could tie into the AR gene expression theory).
Fourth, chams mentioned in his tests, he got tested for AR gene deletion and gene mutation via an analysis of the entire coding region from genital tissue (where 5AR2 was being inhibited by Finasteride), the results of which came back normal: propeciahelp.com/forum/viewt … 2984#12984 . If this is the case (normal results), what does that imply about the AR gene expression theory? Or, do such tests not even factor into the gene expression side of things?
Finally, in my recent conversation with a molecular biochemist (on the phone), he mentioned the body is a remarkable machine and is capable of self-repair under many circumstances, that the body is constantly changing, and if AR signalling pathways were altered via Finasteride, the possibility exists they could also potentially be “unaltered” in the future… hopefully somehow on their own due to proper environmental conditions, or via some form of treatment that targets the exact cause.
The basic jist of his message was one of hope and staying positive despite our current situation (which he believes in), and his agreement that getting a published report on our syndrome in peer-reviewed journals will be the first step in gaining the necessary medical awareness to investigate things further. To that end, I will provide further updates once I have more news to share about this exact possibility (published report).
With enough medical and media awareness, published reports and scientific investigation, we will certainly be on the way to finding the root cause of our syndrome and potentially, a cure (although there is no timeframe on such a thing, at this stage). In the meantime, it seems in certain cases regimens and treatments which target the various hormonal imbalances we have been left with post-drug can have a positive effect, and help reduce or alleviate some or many of the symptoms we continue to experience. That in of itself is certainly a positive. While our lives have been altered by use of this drug, we must accept that this has happened, adjust, and try to stay positive despite the obstacles we have had to, and continue to, overcome… while fighting to get the proper medical and media awareness this syndrome so desperately needs, to spur further interest in our cause.
1)It would be ideal to live in a place where the diet is more varied (than the typical American or Canadian diet for example), where the protein and sugar sources come from numerous flora and fauna. In N. America, it’s rare to get the variety I have in mind and I have experienced in Asia.
digression on the topic:
Unless you are wealthy and have access to imported tropical fruits, fresh seafood, quality yogurt, grains, etc… AND you willing cycle through all of these choices regularly, you will not, typically, living in North America, expose yourself to the variety of proteins a person can consume in India or SE Asia–for example. The resilience of a person eating the variety of fresh foods and cooked foods of Asia is much greater (minus chemicals and WITH regular exercise and sunlight).
I believe that the balance and normal function can be restored.
Mew,
can you refer me to this particular user’s thread(s) please?
“we have a user with elevated Prolactin who brought it under control via dopamine agonist treatment, which he reports has cleared up his sexual side effects tremendously. This does not tie directly into the AR gene expression theory, yet he was able to significantly improve via therapy targetting a hormonal imbalance.”
Both Mew and Awor are on the right course as they’re trying to increase awareness of the problems we face post-FIN. Just for this problem to be published ONE TIME in a peer-reviewed medical journal by a doctor with the right background and reputation could be enough to initiate necessary research that will ultimately find the ‘key’ to this problem.
Mew, although I don’t think I’m following your argument about TRT causing improvement–which you’ve used to suggest a counter-argument to Awor’s AR theory-- how does the efficacy of TRT indicate that there is a flaw in the AR theory? In my simple view, I’m considering it necessary to stimulate the flesh with high levels of testosterone because the threshold was raised (the intervention of FIN) too high for ‘normal’ levels of androgens to create the ‘normal’ response.
So considering these comments, it would appear the androgen receptors are working correctly in these men (?), in order for TRT to exert its effects… although, it could be because some of them are using supraphysiological dosages, similar to what Crisler reported as sometimes necessary amongst post-fin users to exert T’s effects properly.
Yes, that could also be a possibility. I’m sure Awor can clarify the possible reasons for these users’ responses, and your thoughts, further within the context of the AR gene expression theory.
if you’ve seen any information on the effects of long-term fasting (food deprivation) on androgen levels (pertaining to one possible way of androgen deprivation), please tell me.
I’ve thought about a long fast before which could help reset the balance, but I’ve not yet executed it. At the same time, I have a feeling that due to my own unrelated health problems, doing such a thing might only improve one area (the prostate, reproductive system, etc.) but not the brain (dopamine).
I’m not sure about the cases mentined being valid for the severe cases of post-propecia syndrome.
‘Troubledfinuser’ never had a problem with erections while ‘dmartinez’ was gradually recovering prior to prolactin reducing treatment, never had chronic ed and tissue changes/shrinkage. ‘Postfinsufferer’ likewise had good T levels and seemingly no bad ed. The user ‘jairus’ had the more typical symptoms and tried similar supraphysiological treatment seemingly without success.
The ‘dustin’ example may prove more reliable with more updates.
I think a big issue is the crash. Many men seem to get into trouble without this (very) brief ‘recovery’ period and perhaps they respond better to treatment. I don’t think JN ‘crashed’ and he at least seemed to get a decent physical if non-sexual response to TRT Something has gone wrong for the others but I don’t know what.
surprisingly, the seemingly unhelpful endocrinologist I saw two weeks ago may have order a test for prolactin levels. If so, it was simply done on a blood sample. I’m wondering if this may show anything.
Yes it is. Like I said in my post I focused my discussion with the scientists on the androgen receptor theory, because I believe that it does the best job at explaining what happened to us. Having said that, we also touched the possibility of 5AR not functioning correctly anymore. At first sight, it seems to be the obvious thing to look at considering that finasteride inhibits 5AR. More on that later.
Unfortunately, all of our theories will remain such until we can prove something in a lab.
You’re right, and I should have stressed that more in my post. Three scientists told me this as well. Our bodies are incredible machines, which can compensate for and repair just about anything. The point I was trying to get across was this: If we are hoping that if everybody chips in 50 bucks and we hire a scientist to solve our problem, we’ll most likely be disappointed.
The power of healing is within us. Deceivingly simple ideas like juicing/diet/herbs/lifestyle etc. can help promote these powers. Believing in ourselves and giving our bodies the time and support they need seems to be a more promising route to me.
This does not mean that we must give up all hope in science. All of the scientists confirmed to me that developments can all of the sudden go very quickly after perhaps years of achieving no results. It’s not a linear business where input leads to continuous output. One of the areas I have been looking into is full genome sequencing. This technology basically lets us analyze the full 3 billion base pairs of the human genome (which includes dna and tons of epigenetic information). This allows for a genetic comparison between “us” and the “other” guys (who don’t have a problem with finasteride), without knowing where to start looking. Once we find out what “sticks out” in our genetic information, scientists could then determine what functions in our body are encoded by these genes - basically attacking the problem from the other end. Currently, such tests cost around $100’000 a pop. This cost is expected to be reduced to under 10K within the next couple of years (< 5 years). We’re in the midst of a molecular tool revolution at the moment.
The answer to this is likely to be quite simple. Even though we are all suffering from the same basic problem, the variation even amongst us is probably still relatively large. In other words, we are not all the same. It is obvious from reading the member stories that we are also not all affected to the same degree. The less affected amongst us are primarily suffering from some degree of ED. I can very well imagine that this group has got sufficient remaining androgen sensitivity to allow for TRT to improve their symptoms. My sensitivity is probably pretty close to zero. But even I sometimes get a little benefit from TRT (sometimes I also get the contrary). In other words, androgen insensitivity has many shades of gray, it’s not all simply black or white, on or off. If you read through the AIS literature, you will notice this as well (Btw. I am NOT saying that we have AIS, this is just an analogy to a remotely similar problem)
I had this testing done as well, except with normal skin tissue, but the results where the same. Let me quickly clarify what we mean by gene expression, receptors, etc. and how it all ties together (hi level):
Sequencing the genetic code of the androgen receptor, in order to check it for known defects, does NOT tell us anything about what happens at the other end of the machinery. We even know that the receptor is functioning correctly in both cases (chams and me). BUT you can only tell if something is coming out the other end by quantifying the output (gene expression). The scientists are telling me that it is in the machinery (signaling path) that things can easily go wrong (remodeling of signaling paths, etc.). Various mechanisms of gene regulation can play a role here (as described in my last post).
While on the subject, let me use this model to explain why my specialists and myself believe that the problem is somewhere “downstream” from the receptor. Let’s run through what we know about each variable in the equation:
Let’s start with the output: In the most serious cases we’ve got massive penile shrinkage and massive muscle wasting. These are both hallmark androgen dependent tissues. Then we’ve got ED, loss of aggressivity, prostate, etc. Also well know to be androgen dependent. So we are clearly missing out on androgenic action. In other words we are lacking “output” (gene expression).
Ligand/Hormone: Some of us have a lot, some too little. It doesn’t matter. In the best case you can inject an insane amount of Testosterone and get some improvement. In the worst case the same amount won’t do anything. In any case I am still waiting to hear from a guy that has 100% solved the problem through TRT. So it can’t be the hormones.
What about DHT, maybe we’ve got too little or from the wrong enzyme or whatever. Permanent damage to 5AR is actually not a bad theory. But it has a major shortcoming that pretty much rule it out: It doesn’t explain muscle wasting. DHT is not required to build or maintain muscle mass.
This is demonstrated in male pseudohermaphroditism due to congenital 5-AR deficiency. When puberty occurs, the testosterone levels of these individuals raise normally, although their DHT levels remain very low. Despite this, their musculature develops normally like that of other male adults. There are about 3-4 other arguments which further support this and are scientifically backed (joe.endocrinology-journals.org/c … t/170/1/27).
If this is not convincing enough, try supplementing it (I have).
So in my opinion and with current medical knowledge, we can pretty much rule out hormones. But what about all the other hormones? Well, I haven’t found any scientific litterature which explains why androgenic tissue dies because of a dis balance of other (non-androgenic) hormones. Maybe someone can correct me on this. What about hormones that could have a gene silencing effect (regulation) on the androgen receptor? That’s possible. But then we would be talking about something hitting the machinery. Or take a hormone like prolactin. You can explain ED with it, but not muscle wasting. The key is to find a theory which explains everything for everybody. It can’t just work for isolated symptoms or for certain members. In other words, a lot of things can potentially explain ED. If you try combining ED, depression, muscle wasting and penile shrinkage (just to name a few), the number of options gets real small real quick.
Receptor: As stated above, Chams and me had them tested. They work. This for me is sufficient evidence to rule out the receptors.
What we have got left is the machinery. The piece in between that is still partially a scientific mystery. A machine 1000 times more complicated than a missile guidance system. What are the odds?
Just imagine if a scientist finds a solid explanation to our problem one day. All the theories collapse in themselves. What are we going to talk about then in this forum? It’s going to get real boring around here at some point!
I am hoping to start covering the nutritional side of things with a scientist/doctor in about 1-2 months. I’ll report back on this interesting subject as soon as I find out more.
Good luck. Seeing as Doctors are still telling their patients to follow the food pyramid as a healthy way to live, your going to have a tough time finding a Dotor who know’s anything about nutrition.
Scary thing is, even nutrionists have it all wrong.
My recent urine panel showed high corticosteroids. It turns out that high levels of cortisol cause muscle wastage. It is possible that 5-a-rase is no longer working correctly. As you can see from my test results it is not since I have low 5a-THF/THF ratios, low adiol-G, etc. It is interesting that 5-alpha-reductase also metabolizes cortisol and cortisone into 5a-tetrahydrocortisol and 5a-tetrahydrocortisol. So if cortisol is no longer being metabolized by 5ar, leaving it to circulate it will cause muscle wastage. If you want studies on this I can provide them as I have access to a good medical database that I have been using. Also, check out Cushing’s syndrome if you are interested on the effects of high cortisol.
Yes, I and many others did not experience muscle atrophy while on Finasteride – only after quitting, when our Testosterone levels crashed. It is well known that Testosterone is the primary anabolic agent responsible for muscle mass and tissue growth.
From the study you highlighted, I found the following passage of interest which supports your statement:
First of all, according to scientific litterature, it is the androgen/estrogen balance that regulates the feedback mechanism for gonadotropin production (FSH/LH):
Assuming that the androgen receptor/pathway is not functioning correctly, this would cause the body to think that the estrogen/androgen ratio is higher than it actually is. This would also lead to a down-regulation of LH/FSH production.
In many areas, androgens offset estrogens. This is also clear with the many gyno cases that we are seeing in this forum, despite sometimes normal estrogen levels. I, for example, have normal-low estrogens. Nevertheless, I am developing gyno. That most certainly is because the estrogenic action in the breast cells is not offset by androgenic action any longer. In other words, if the androgen receptors/pathways are not functioning right, you get exactly the same result like if you didn’t have any androgens in your body. Actually, it’s worse. If you you have androgens but the receptors don’t react to them, you still end up with androgens aromatizing to estrogens, giving you all the unwanted estrogenic effects like bloating, gyno, etc. In a situation without androgens, you at least would not have much estrogens floating around either. Having normal estrogen levels without any androgen action to offset them is what is causing me this horrible pain in the breast/nipple area.
Some further research led me to a very interesting study, which was published only two days ago. Here is the punch line:
In other words, without the presence of AR (androgen receptors), FSH does not have the same positive effect on Leydig cell number like it normally does. As we know, Leydig cells are the ones that produce testosterone. If you have less Leydig cells, you logically get less testosterone production. This would also correlate with some guys reporting their balls “shrinking”.
In my opinion, both above cited articles provide strong grounds for explaining why lacking androgen receptor gene expression could lead to a reduction in testosterone production.
In my opinion it is like a cascade, a domino effect.
I believe our main problems are Pituitary suppression + 5arII deficiency. All the other problems/symptoms derive from this.
Example:
5arII deficiency consequences:
Elevated Cortisol due to lack of further conversion to 5a tetrahydrocortisol
Reduced 3 adiol G as it is not converting from Dht through 5arII
Cascade effect:
muscle wastage (caused by excess cortisol)
death of androgen dependent tissues in some men (caused by lack of Androstenadiol Glucoronide combined with low DHT, and low T). So, if one of the three hormones is still somewhat high, your body is able to keep the androgen dependent tissues alive.
We have to remember we will not find an exact pattern on everybody’s symptoms since the drug affects everyone differenttly. So far, the only patterns we found in everybody were a low LH and FSH (which indicate pituitary suppression) and a low 3 adiol G number in everyone who tested it, which indicates 5arII deficiency.
