I received the following emails from an anonymous user, and have posted the correspondence for us all. [/i]
I have been reading this forum for insight as to the cause of finasteride induced hypogonadal hypogonadism. The studies in OTHER STUDIES section are very informative.
Lets start with the facts:
all of the men had normal sexual function prior to the finasteride treatment, and DHT is responsible for prostate growth
studies show DHT is responsible for NO synthesis and release, and erectile function – you posted this in other studies 11/02/06:
finesteride halts gene expression mRNA synthesis of 5AR in the prostrate and the anterior pituitary — see study on DHT and GnRh regulation (you posted this on 12/27/06 in OTHER STUDIES): propeciahelp.com/forum/viewtopic.php?t=171
4)finesteride decrease weight of prostate and PROBABLY the anterior pituitary too – see same study: propeciahelp.com/forum/viewtopic.php?t=171
5)finesteride doubled the concentration of testosterone in the prostate. The author states these changes probably occur in the anterior pituitary as well… really read this study! Page 1041, exp. 2, 2nd paragraph, 9th line — endo.endojournals.org/cgi/reprint/139/3/1038.pdf
- somehow after finesteride treatment men get fixed in a state where the pituitary is insensitive to low testosterone
Now here is my theory:
Since finesteride raised testosterone levels in the prostate, and the author extrapolates this to the anterior pituitary as well, then finesteride shrinks the 5AR producing part of the pituitary.
This halts the conversion of testosterone to DHT within the pituitary.
This raises the concentration of testosterone in the pituitary and maybe even the hypothalamus.
As a result, the pituitary thinks the serum testosterone is high or normal, so no more LH is secreted.
So now we have testosterone backed up (elevated) in the pituitary and the finesteride user has a fixed state of pituitary insensitivity to low serum testosterone!
This would lead to the variability between finesteride users depending how low their 5AR concentration is in the pituitary.
Next, the prostate has lost its ability to make DHT due to same mechanism – so you get impotence.
You may argue that most post finesteride users can make DHT, but the key here is testosterone levels in the prostate and pituitary are raised.
My theory is the 5AR1 in the skin and other organs synthesizes the remaining DHT, but the pituitary and prostate contain 5AR2 which has been downregulated by finesteride – so the finesteride user becomes hypogonadal and has a prostate and erectile tissue that does not release NO… that is why TRT doesnt really help.
Also, this theory explains why clomid may raise testosterone, because although the pituitary is still sensitive to low estrogen it is the lack of 5AR2 in the prostate and pituitary that must be raised.
*** Now here is the CURE! ***
Look at dynaaminen’s post 3/30/07: propeciahelp.com/forum/viewt … ight=#1702
DHT positively upregulates the gene expression of 5AR in the prostate, and probably in the pituitary. These rats were given 1mg/kg dht for 4 days and their prostates size grew more than double, and their 5AR activity was raised about half as much as testosterone (but test raised it 20 times).
so, this would explain why ex finasteride users can get better on their own – the more DHT they make, they slowly reverse the process. They increase 5AR in the pituitary so more testosterone converts to DHT in the pituitary, and the pituitary testosterone level drops and LH goes gradualyy up. The same thing happens in the prostate and erectile tissue, so problems resolve.
But what if some supraphysiologic dose of DHT is given for four days and all of the 5AR is is permanantly increased in the pituitary and prostate? The man would be cured.
This is my proposal, send this email to MEW and discuss with him and keep me anonymous. We then should approach Dr. Shippen to design a treatment protocol using DHT at supraphysiologic dosages for a short time. He can recruit many of the sufferers and do some trials and gather data to fine tune the dose and schedule.
This way everyone is treated for this under a physician’s care and when people come out of the woodwork and get cured, then people will come forward and get this drug off the market.
I have already googled use of DHT in hypogonadism… it doesnt seem to be as negative on the pituitary, so maybe you need HCG or clomid or maybe nothing. There is Intramuscular, transdermal and sublingual – sublingual seems to drop off quick, so there’s little effect on the HPTA but it can create a significant plasma rise and possible stimulate prostate and pituitary 5AR mRNA repair.
This email is not meant to medical advice and is only for discussion with a licensed physician. This is the only theory that fits all the observations and is consistant with the effects of finasteride. I am very optimistic. I will not post and will only communicate with you or mew.
MY (Mew’s) REPLY:
Thank you for your email. First of all, who are you, what is your background/education, etc? What is your history with the drug, are you a sufferer yourself? If not, what got you interested in trying to solve this puzzle? How long have you been reading the forum? And why are you unwilling to post and share your theory with others on the forum? I think it would be very helpful for others to read and comment on your message.
I re-read through the studies and yes, you are correct in that the pituitary expresses 5AR – thus use of Finasteride probably did inhibit 5AR/DHT activity in the brain.
Much like your theory about the pituitary no longer “seeing” low testosterone, I also speculated that perhaps we have undergone some form of pituitary desensitization due to downregulated and burnt out pituitary LHRH receptors thanks to Fin’s constant upregulation of Testosterone/LH – as discussed here (my 4th post down) propeciahelp.com/forum/viewtopic.php?t=258 . I’m not sure, but I thought I read somewhere that Tamoxifen and/or Clomid can resensitize the pituitary to Gonadotrophs (GnRH).
As for DHT treatment, haven’t heard of any concrete cases of recovery, although Dynaaminen mentions one guy from the old Yahoo forum in his post. It would appear DHT treatment is analogous to TRT, in that it will likely surpress T production and other hormones, as noted here:
“Serum concentrations of LH, FSH, E2, T, and SHBG decreased significantly during DHT treatment.”
According to the above statement, taking external DHT will surpress T production. Strangely enough, the above study parallels the experience for those of us who ended up with low T after quitting the drug – ie, perhaps our rebounding DHT to skyhigh levels, very quickly after stopping Finasteride could have signalled the pituitary to decrease LH, and thus T, since the Pituitary sensed a high level of DHT in the body and lowered T to compensate.
However, there are guys who have high DHT serum levels after Finasteride (albeit serum DHT is apparently not entirely accurate, one should measure its metabolite 3 -diol-G, aka 3a-androstanediol glucuronide via 24 urine panel, as well as androsterone/etiocholanolone (A/B) ratio in urine as a measure of 5a-reductase activity – see propeciahelp.com/forum/viewtopic.php?t=761)… and they still have issues.
Also, here is a former Finasteride users (Josh and John) who underwent DHT cream treatment under the care of Shippen, who did not have success:
Josh’s final story is here:
So I’m not sure if DHT treatment is the answer, but what do I know.
One thing is for sure, without doctors to discuss this with, like Dr. Shippen or others, we will never find out.
Look forward to your response, and hope you will post on the site.
ANONYMOUS EMAIL #2:
I continue to read the posts.
You have again posted another article dec 18 showing dht increases 5ar activity: propeciahelp.com/forum/viewtopic.php?p=4698
Also 1/3/08, Majkellos states Propecia destroys 5ar activity and you refer him to dynamin post – propeciahelp.com/forum/viewtopic.php?t=1079
I assume my input is not credible to you since you did not respond to my last email. I Assure i am a medical doctor. I read your last email to me.
Your logic is flawed in that you assume normal DHT in post-Fin users means 5AR is normal. They may be synthesizing dht from 5AR1 in skin and liver. My theory is 5ar2 gene expression is damaged. 5AR2 is in the brain and prostate.
Based on those studies I quoted in my first email, 5AR2 is in pituitary and prostate and that is where the damage is. The other study I quoted in my first email showed high doses of dht increased 5ar activity in the pituitary.
Also, you referred me to a man who took DHT ( propeciahelp.com/forum/viewtopic.php?t=262 ) and cited him as an example of DHT as a failure – BUT, if you read his post, he states DHT gave him excellent erections and he wished he could continue the DHT. Also, you cited DHT as a form of TRT – I never suggested DHT as TRT. The DHT is treatment to the damaged 5AR2.
You correctly cited DHT as TRT decreasing gonadotropins, so here is my solution:
High DHT once a week to activate the 5AR2 in brain
This will decrease testosterone in the pituitary and reverse the sensitivity of anterior pituitary to low testosterone, and restore 5AR2 activity in the prostate to increase NO (nitric oxide) synthesis and erectile function.
Both DHT and NO will restore libido, as once a week DHT will not shut down gonadotropins.
Remember, we are not trying to replace DHT – we are trying to restore 5AR2 activity. If it takes months, so what! Nobody is getting better with any other therapy so by now most are patient.
Again, note the dose of proviron that guy John used ( groups.google.ca/group/alt.suppo … b2017722b1 ) and time period, and was he cured? I suspect transdermal Testosterone once a week would also raise DHT pretty well.
Again none of the above is meant as medical advice… rather it is an idea to be presented to a medical doctor such as Dr. Shippen to review and refine it to be safe and effective under his care.
My (Mew’s) 2nd reply:
Thank you for the reply. Your input IS credible to me, and I DID respond to your last email – hence you referencing the points I made in it (other guys trying DHT etc). Did you send an email after that? If so, I did not receive it.
You mention you are a medical doctor – from where, what country/hospital etc? What is your name/contact info? Do you have a profile on the web?
Funny that you should mention 5AR1 can make up for lack of 5AR2 via producing DHT – I actually came across a study that mentioned this was possible.
Thus, DHT values should not necessarily be taken at face values, since it may come from 5AR1. Yes, you are correct in that one guy’s story, he mentions the DHT shot helped him feel great, unsure why he would not continue.
I did however misinterpret your comments of a shourt course of DHT as a form of TRT… I understand your theory in more detail now, so thanks for explaining further.
Can I ask you a favor? Can you post the theories (both emails) you have sent me on the forum? Or would you prefer I do that and cite you as a user who has been privately messaging me this info?
I would love to present such theories to Dr Shippen, however I am not scheduled to see him. However, if your theory were on the forum, others who are going to see him might have a chance to get his feedback.
Thanks for the followup, let me know.
MY (Mew’s) 3rd email:
One last thing,
I went through the old Yahoo Group and found some posts by Dr. Crisler.
Here is what he said:
[i]Be forewarned–if you supplement DHT, then you reduce testosterone
production. Has to happen. I do not think that will help.
Dr. John Crisler, DO[/i]
[i]Yes. The DHT is highly suppressive of the HPTA. Thus LH, and subsequently T (and E) levels will drop.
Dr. John Crisler, DO[/i]
[i]"There are a couple of fundamental problems with these comments. When DHT is lowered, estrogens are elevated, de facto. Thus T levels go down, due to estrogenic inhibition at the HP.
There is no evidence that finasteride “destroys the 5-AR gene”, as the assays many of you have produced demonstrate healthy DHT levels status post Propecia cessation.
“Chronic high T elevation” does not cause liver toxicity—at least not at the levels we are dealing with here. In fact, the body is MUCHG healthier at the upper quartile of physiological range.
When Free T levels go down, LH production goes up, and this re-establishes baseline levels.[/i]
Dr. John Crisler, DO[/i]
ANONYMOUS EMAIL #3
I would prefer not to post.You actually seem to be doing a great job finding the articles. Let me help you analyze the data. You can post my analysis as your own.
The key to my theory is propecia downregulates 5AR2 activity in the pituitary and genatalia leading to permanent hypogonadal hypogonadism.
This guy ( propeciahelp.com/forum/viewtopic.php?t=2261 )who used proviron is successfully treating himself by using TRT and HCG to maintain his testicular function. The proviron is DHT, which he uses to free up his testosterone, DHT and lower his E2. This should work, but it will not cure him because he is not upregulating the 5ar2 activity in his pituitary.
To do this properly one must NOT suppress the pituitary… this is the difficult part because this is uncharted territory.
All of this is based on the articles I already cited, to do this correctly one would have to do this under a physicians care. As you may have noticed I am not properly posting my cited articles and this is because i am a very busy physician and family man.
I propose you help me put together a proper letter with the proper articles referenced with footnotes and I will present the theory and general treatment to Dr. Shippen, and we will ask him to produce a treatment protocol, and hopefully he can start treating several patients and develop an efficacious treatment program.
ANONYMOUS EMAIL #4
Have you come across any way to stop floaters with anti estrogens?
MY (Mew’s) 4th reply:
None that I know of. In fact, Clomid can induce floaters.
Regarding your previous msg and constructing a theory with footnotes, when I have some more time I will look into this.
You mention you are a physician, where are you located, what is your name, office address, phone number etc?
No further contact at this time.