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04/06/2010

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Male28

Dear Dr Jacobs

Thanks for that very interesting summary of the post-finasteride problem.

I'm experiencing what you describe: wide-ranging symptoms of hypogonadism that remain 18 months after stopping finasteride.

As with many in this situation, the real puzzle is that raising serum T to the top of the range in a controlled way (in my case, first with Tamoxifen and then with Androgel) does not alleviate symptoms. It seems that the heart of the post-finasteride condition is, for many men at least, a kind of androgen resistance.

You mention that if a man has developed a resistance to androgens, this would be "treated in a different manner". The problem currently has my endo stumpted: do you have any insights on potential treatment that might help?

Thanks.

John

Dr. Jacobs - Thank you for speaking up on this issue. It appears finasteride sharply reduces the 5 alpha reductase Type 2 enzyme (5AR2) in some men far more than others, and for some of those who are strongly effected the 5 alpha reductase Type 2 enzyme levels do not return to anywhere near normal levels after cessation of the drug. This is seen in post finateride sufferers nearly psuedohermaphrodite levels of the 5AR2 final breakdown product 3a androstanediol glucuronide (and are backed up by low levels of 5beta to 5alpha metabolite ratios in urine analysis)/

The neuroendocrine pathways effected by 5AR2 include more than just the basic synthesis of DHT (indeed, some post finasteride sufferers have average DHT levels presumably via the 5AR1 pathway). The 5AR2 enzyme is also responsible for transforming progesterone into the important neurotransmitter allopregnanalone. This lack for transformation is indicated by many post finasteride men who show frequent high levels of progesterone, and may play a role in the "brain fog" and lack of libido. I would be curious as to your opinion on this last point, and would encourage you to test both progesterone and 3 alpha androstanediol glucuronide in your patients.

Thanks again for discussing this critical issue.

needhelp28

Dr Jacobs -

You describe the treatment bringing the testosterone up to normal levels and treating with an anti-estrogen. How long would you do this for? I can see how the treatment would be adjusted until the symptoms disappeared. But how can this be designed so it is a cure rather than a permanent HRT? I understand that blocking the aromatase enzyme then you force the 5aR to synthesize the Testosterone effectively to DHT. How can we keep this from stopping once the testosterone or AI was discontinued? How long would you run this for and then taper off?

Dave

Dr. Jacobs

Again, many thanks for writing about this serious issue. It is way overdue that this life ruining problem starts getting attention in the medical community.

Referring to the previous poster (John), it is very unfortunate that certain individuals are going about spreading false information about this problem. There currently is no proof that 5AR2 deficiency has anything to do with these side effects. If the problem were that simple, supplementing DHT (i.e. Andractim) would alleviate the problem in every case, which unfortunately isn’t true.

Even though a few men seem to benefit from supplementing DHT, many have made the experience that increasing androgens by any means (Clomid, TRT, DHT, etc.) makes the symptoms worse.

This clearly indicates that the problem is more complex than simple 5AR2 deficiency and more akin to an active resistance of the body against androgens. Misguided androgen receptor autoregulation mechanisms, which silence the AR signal, is a more likely possibility which must be considered.

3a-Androstanediol Glucuronide (3a-diol-G) is a metabolite of the enzyme 3a-HSD, which is responsible for maintaining androgen homeostasis at the cellular level. Given that 3a-HSD is probably induced by AR gene expression, a lack thereof, due to silencing of the AR signal, would equally lead to low 3a-HSD throughput. This would also result in low 3a-diol-G levels. 3a-HSD additionally plays a central role in the synthesis of key neurosteroids. Hence a downregulation of this important enzyme would better explain “brain fog” and depression rather than low progesterone levels would, which many patients don’t even have.

So let’s stick with the facts and not start potentially damaging treatments based on misleading information. The only way we are going to progress in this issue is by getting science involved and not by making wild claims in the Internet.

JN

I hope to contribute to this interesting debate. We need to further this productive discussion.

May I introduce myself as a medical doctor in Australia, although initially from England. I am a sufferer of Finasteride side effects for the last 9 years, and have pursued several treatment options.

With reference to John's comments, I have a 3 Adiol G level at a pseudohermaphroditic level, even on high dose Testosterone therapy (250/wk).

Particular features to note:

- Very high dose T therapy is generally believed to improve both psychological and physical symptoms, particularly when combined with E2 management. It did in me.
- Addition of DHT (ie, Andractim) relieves symptoms further, yet even at high doses, not fully.

Theories:

- AR malfunctioning
- Transdermal DHT application is not an optimal mode of DHT replacement due to cutaneous formation of DHT metabolites.

With reference to Dave's comments:

Dave, John mentioned 'high progesterone levels', not low.
Furthermore, would you agree that overriding a defunct enzyme (be it 3a HSD or Type 2 5AR) by appropriate replacement of both of their products; 3 Adiol G, would induce symptomatic relief? Or do you theorise the AR is simply dysfunctional?


Should anyone wish to contact me directly for further discussion, my email is finasteridedoctor@yahoo.com.

Let the discussion continue.

I am A Fighter

Dear Dr Jacobs

Thank you for posting this. I am still suffering from severe hypogonadol symptoms from Finasteride 12 months after I quit the drug. I believe the problem is being caused by 5AR2 levels that never recovered. Since I have normal total testosterone, free testosterone and DHT levels I believe that 5AR1 increased to compensate for the low 5AR2 during the finasteride treatment and that this has persisted post quitting. I believe that DHT metabolised in the body has different functions depending on whether it was metabolized by 5AR1 or 5AR2 either due to the site where this conversion happens or alternatively how the body reacts to the different byproducts. Why would the body have two chemicals that perform exactly the same function? I have had numerous times when I felt i was recovering but then my body reacted in some way and I crashed shortly afterwards. I believe that this is because 5AR2 started increasing, without 5AR1 decreasing and the body reacted to the increase in DHT by down regulating 5AR2 activity. A possible solution to this may ironically be to use Duasteride to inhibit both 5AR1 and 5AR2, (since there is no drug that targets 5AR1 exclusively) and then to stop the treatment and wait for 5AR2 and 5AR1 levels to find their own optimal balance again. This treatment though carries considerable risks and should only be considered once it has conclusively been determined that low 5AR2 levels are the underlying cause of this problem.

Please let me know your thoughts on this theory.

arjmd

I have been dwelling on the fact that that the exposure of DHT in any given tissue is dependent on the balance between reductase and oxidase enzymes that drive DHT to 3-alpha DIOL and 3-alpha DIOL to DHT, a reversible reaction, and that disorders in this metabolic pathway may factor into the mechanism by which finasteride can bring androgen-related disorders. I am still wrapping my mind around this challenging problem.

arjmd

As for the issue of allopregnenolone, this neurosteroid is extremely potent at the GABA-A chloride ionophore and causes GABA, a main inhibitory neurotransmitter in the brain, to remain on its receptor longer, bringing increased anxiolytic and anti-seizure effects.

JN

Dr Jacob's, I would be very interested to hear your opinions regarding the following thread, specifically the excellent entry by 'Alex Miller' regarding the reduction by 300% of allopregnanolone in a trial of 20 subjects on finasteride for 4 months.

http://www.propeciahelp.com/forum/viewtopic.php?f=24&p=22847#p22847


Here is the direct link to the recent trial, conducted in Czech Republic, 2009. As you are a neuroendocrinologist, this could interest you greatly.

http://www.lf1.cuni.cz/Data/Files/PragueMedicalReport/pmr_110_2009_03/pmr2009a0025.pdf

Many thanks Dr Jacobs.

cole lewis

hi i have been struggling with partial ejaculatory incompetence ( a decrease in sensation in orgasm with semen that seeps out instead of spurts). I was only on propecia for 2 and half months and have had these side effects for almost 4 years. Do you know what could be causing these unpleasurable orgasms i have tried several hormone therapies but nothing has helped my hormone levels are all in normal range. There is a small cyst that showed up in a prostate ultrasound that i had but that is it the doctors said that the cyst has nothing to do with my situation.

george

Dear Dr.Jacobs,

Have you noticed anything about osteoporosis and low bone mass density through your search? Is it possible to cause osteoporosis in men for example in his 30'es years old?
or is it just a coincidence, and irrelevant from finasteride?

thanks

G

Why am i on a completely different path from most people that believe that finasteride just alters the enzyme conversion ratios and the HPG system?? This theory of low rate of T to DHT conversion is far more complex than what most research papers state. Noone gets into understanding the firing output of GnRH neurons, the fact that LH/FSH remain unaltered despite a very low GnRH output and the direct connections between the hypothalamus and the testes. More over there is very little information regarding what happens inside the testis(intraluminal T, DHT, CRF etc etc) after using finasteride and what alterations take place in the protein synthesizing mechanisms over there. Most post finasteride users have testicular shape and size changes and low levels of testicular inflammation. Some can not recover their testicular sizes despite using HcG or SERMs. Needless to say that the HPA is also affected to a great degree after finasteride use, and this contributes mostly to the brain fog, low energy, concentration issues and many more. We need a more overall aproach and not just what 5ar2 does to the sex steroids. Other steroid levels are also vastly affected.
What sort of changes take place, after those sex steroids are affected for quite a while, in higher brain centers.
Many of us have wasted enormous amount of time collecting data regarding our absolute hormonal values but noone really approaches the way those systems (HPG, HPTA) feedback and how their sensitivities are altered

JN

My new theory: Reverse T3 syndrome.

JN

Mr Andrew Pemberton

After taking generic finasteride [PROSCALPIN] for 16 days at 1 mg per day I quit 4 days ago.I now have insomnia.Is this irreversible or will it pass?

Robert

Dr. Jacob
Like others here, I have been affected by the use of propecia. I have had blood test done, but like others, it's hard to figure everything out.It may help if we had a pre propecia baseline of our levels to compare to. That's when the thought hit me. I have a identical twin brother. I know not everything would be the same, but would it make sense to have him do a hormonal blood workup and kinda use that as a baseline for myself?

arjmd

Robert:
I doubt very much if your twin brother's lab measures will tell you anything about yours.

kevin

Dr Jacobs, Thank you for writing this article. I have quit using propecia a year and a half ago, but the horrible side effects have persisted.

I hope your article can bring awareness that this drug has potential long term damaging consequences to a man's health.

Norbert

Hello Dr. Jacobs,

Thanks for writing this. I´m suffering form propecia with brainfog for about two years now. I felt sooo depressed. I thought about sucide many times. Years of my life are wasted. Its time to get the whole thing in public.

very best wishes
Norbert Emmert ( germany)

frank

Hello Dr Jacobs,

Would arimidex kill two birds with one stone - raise Testosterone and at the same time lower estrogen - this assuming that E was slightly elevated in a patient and his T was low normal?
Thus there would be no need to boost T?

Thanks


Jon

This is by far the best article I have seen on finasteride side effects.
I stopped taking Finasteride about 3 months ago after taking it for hair loss for 5 years. The main thing I have noticed is that my errections are much harder and my sex drive has gone through the roof! Also my ejaculations are much larger. However, I have been feeling very depressed and unable to concentrate on anything and can't think straight at all. I had no idea why I was feeling like this but after reading DR Jacobs article I think I know why. My advise to anyone thinking about taking the drug is DON'T DO IT! Losing hair is not as bad as feeling suicidal! I would rather be bald and able, mentally and sexually than the way I feel right now. Does anyone know if this will pass or am I doomed?

Joni119

Yes! My sex life is back!!! I have received the order and I am extremely pleased with the service and the pills. I had previously been paying a very high price through prescriptions from my local GP. I am now able to order online without hassle and delivery has been within the stated period. I came to be extremely happy with the service and the product. I will absolutely place any and all future orders through this site canadianrx-drugs.com/?ref_id=3915

Joe

I can't pretend to understand all the medical science contained in Dr Jacobs blog above, but I'm glad that this condition is attracting the attention it deserves. I'm just coming to terms with the fact that I am suffering from finasteride side effects and thought it appropriate to share my own story.

I took Propecia for only three weeks last October (2009). After only a week I noticed a change in my ability to achieve an erection. Initially I wasn't concerned, the information leaflet that came with the pills explained that this wasn't unusual. However after three weeks I decided that the risk just wasn't worth it - I hated the feeling of not being sexually normal. So I stopped taking them. My sex drive and ability to achieve an erection soon returned to normal and I briefed a big sigh of relief. However, this proved to be a temporary reprieve - something that I understand isn't unusual. By mid December - some six weeks after i'd stopped taking it, I started to notice problems again. These problems have remained to a greater or lesser extent to the present day. The symptoms are: difficulty in achieving and maintaining an erection, loss of sex drive, difficulty in achieving orgasm and shrinkage of penis. Unsurprisingly, this has made me feel extremely depressed at times. At times I have felt suicidal. I have recently met a wonderful girl. Without wanting to sound corny, she is the best thing that has happened to me, beautiful and loving. Instead of relishing and enjoying every moment of this new relationship, the sexual side of the relationship is a constant matter of anxiety. I am secretly taking viagra to be able to perform. Ironically she tells me what a great lover i am. Inside though, i want to cry, as I feel like a fake. And worse, I am not enjoying it as I know I should be. To make matters worse, she is very sexual and I'm not sure how long I can lie a lie. But i'm terrified that if I tell her, she'll leave me. She's exactly the kind of woman i'd have given my right arm for previously. I can't tell you how much I long be normal again. I'd give anything not to have been so vain as to have taken pills to stop hair loss. I'd happily shave all my hair off now to retrieve my previous healthy libido.

Reading the various posts on this site, what really worries me is the number of men who have been suffering from finasteride side effects for a number of years. Can anyone tell me if there are reports of men who return to normal after a while? It feels like there are those who return to normal almost immediately, and those who never regain their previous state. Is that the case? I'd love to have something positive to cling to.

polymath

Dear Dr. Jacob

Thanks for posting this.

I'll tell my experience.

I dosed finasterid(1mg) total 45 days and stopped 5 days ago.
(and I stopped 5 day ago but still under suffering.)

I experienced very similar posted symptoms.
-Brain fog
( very uncomfortable and slow thinking )
- Very Extreme Anxiety and Panic Attacks
( I guess Brain fog makes this symptoms. )
and more.. I experienced
-'sleep apnea'
( fall asleep after 30min ~ 1hour, Feel strangle and moved under unconsciousness. I recognized my movement after by my room CCTV )
-'a little hand tremor'
( It likes brain fog's thinking uncomfortable ).

I deeply regret what I used finasteride.
and Although stopped 5 days finasteride, I still under suffering by these horrible side effects.

I just want to return to before I used finasteride.

It devastated my life.


Charles

Oh, Lord! I'm getting quite scared!
I've been having the feeling lately that something wasn't right regarding the interaction of my Proscar (Finasteride) and my libidinal energy. Today, I started to scan for the literature online, and found this (and other) sites. I realize that my urologist hasn't been keeping up on current trends. I have low sex drive, low energy, and have a growth on one of my testicles (which was assessed through ultrasound as "a common occurrence" and not cause for concern). My urologist told me that Finasteride would drastically reduce my chances of prostate cancer, and would shrink the size of the prostate. The price to be paid, he said, would be the drug's limiting of testosterone production, and possibly a drop in sex drive. I was told that a "stent" was the only alternative to the restricted urine flow that an enlarged prostate was causing. That was two years ago. As of today's reading here and elsewhere, I am stopping taking this drug, and will seek other advice. I would also appreciate more advice at this site. What are the long-term implications for me with having taken this Finasteride for over two years? I live in Canada, where medicine is socialized, and where (in my experience) many physicians seem to think that a universal health care system equals a diminished duty of care regarding explanation of effects, and reduces the need for periodic active follow-up on their patients! Must I do all my own research, as I would if I were thinking about buying a certain model of automobile??? Advice, please!

Vasilis K

Hi to all

I have a box of propecia beside me in order to treat hairloss and i dont know what to do.I am 33 years old and i was wondering if there is a safe way to treat hairloss .your opininions .thanx

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