Diffuser44
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http://www.hairlosshelp.com/forums/messageview.cfm?catid=10&threadid=85335
Hi,
My name is Alex Miller and I am studying biology -> specialization track: neurology and neurological sciences. I have been referred to this website by a good friend of mine who was using Propecia (Finasteride 1 mg) for 9 years. He never had any sexual side effects or other problems during this time. But about two month ago, he started having problems with cognitive function, forgetfulness, slurring of speech and depression. He went to several doctors and in the end a neurologist told him, that these effects come from the propecia. He then stopped using it and told me that if I have some time left, I should look into the matter. He started researching too and found this forum, where he said people named this side effect "brain fog". Unfortunately, I just don't have the time to read through this forum.
Before starting the research, I already knew that 5-alpha-reductase (5AR) has important functions in the central nervous system (CNS). So inhibiting it (by finasteride) might induce some side effects there. I will not address the possible sexual side effects but only the neurological ones. I will explain to you all what I have come up with so far. And guys: this is not looking good at all.
First of all, 5AR exists in two different isozymes: 5AR type 1 (5AR1) and 5AR type 2 (5AR2). 5AR1 is present mainly in the brain, muscle, liver and in sebaceous glands. 5AR2 is referred to as the "peripheral 5AR" since it is present mainly in the prostate, seminal vesicles, liver and hair follicles. Finasteride is a specific type 2 inhibitor and doesn't inhibit 5AR1 in significant amounts. But here comes something that not many people know: 5AR type 2 is also expressed in very significant amounts in spinal chord motor neurons, actually in similar amounts found in the prostate (Poletti et al. 2003) and could have (damn it!: WILL have) an effect there. What kind of effect this is, will be explained soon.
Something else, that many people don't know: Both isozymes of 5AR have more functions than just Testosterone (T) -> Dihydrotestosterone (DHT) conversion. They do the following conversions:
1. Testosterone -> Dihydrotestosterone
2. Progesterone -> Dihydroprogesterone
3. Deoxycorticosterone -> Dihydrodeoxycorticosterone
The latter two conversions are also inhibited by finasteride and so the production of neuroactive steroids is inhibited, since their metabolic pathway continues like this:
Dihydroprogesterone -> Tetrahydroprogesterone or also called Allopregnanolone.
Dihydrodeoxycorticosterone -> tetrahydrodeoxycorticosterone
These converions are catalyzed by an enzyme called 3-alpha hydroxysteroid dehydrogenase (3-alpha HSD).
You can read about these neuroactive steroids on wikipedia in order to get a rough idea about them:
Tetrahydrodeoxycorticosterone
Allopregnanolone
Altough it states there, that Tetrahydrodeoxycorticosterone is synthesized by 5AR1 in the brain, this is only partially true since, as explained above 5AR2 is also present in the CNS namely in the motor neurons of the spinal chord.
Now we come to the REAL concern: The inhibition of Allpregnanolone production. Altough Allopregnanolone can be produced in the brain by 5AR1, the CNS is also dependent on peripheral 5AR2. I quote from "Implications of neuroimaging for the treatment of epilepsy":
"Allopregnanolone formed in peripheral tissues readily enters the brain where it acts to enhance activation of GABA. A receptors" (William H. Theodore, MD; Clinical Epilepsy Section NIH Bethesda, MD).
Now to repeat again: Finasteride definitely inhibits allopregnanolone production in spinal chord motor neurons where mainly 5AR2 is present and also reduces allopregnanolone levels in the brain and other parts of the CNS since these parts are dependent on peripheral 5AR2 conversion of progesterone to dihydroprogesterone which is then converted to allopregnanolone by 3-alpha HSD.
The question is what the result of long-term allopregnanolone depletion is. Before you have to understand what the myelin-sheath of neurons is. The axon of neurones (both, peripheral neurons and neurons in the CNS) are surrounded by an electrically insulating layer: the myelin sheath. This is vital for fast and efficient impulse propagation on the neurons. I don't want to go into details here. Fact is: Allopregnanolone has vital function in the myelination of neurons as seen in the following studies:
When you read these, you'll see that the metabolic pathway of progesterone (inhibited by finasteride...) is vital for myelination and other functions in the CNS. In fact there are dozens of studies about the effects of progesterone metabolism and allopregnanolone on myelination.
1. Progestins and antiprogestins: mechanisms of action, neuroprotection and myelination (Link)
2. Progesterone: Therapeutic opportunities for neuroprotection and myelin repair (Link)
Quote: "Progesterone and its metabolites promote the viability of neurons in the brain and spinal cord. ".
Oh damn it! Didn't we say just before, that the motor neurons of the spinal chord expresses mainly 5AR type 2 (inhibited by finasteride)? So there will be a negative effect of myelination there for sure!
2. Allopregnanolone treatment, both as a single injection or repetitively, delays demyelination and enhances survival of niemann-pick C mice (Link)
3. There is also a study of Goumari et al. (didn't find it on the net) that shows the function of allorpegnanolone in myelination. Quote: "... allopregnanolone accelerated myelination ..." (Ghoumari et al. 2003b)
Alright. Let's see what the effects of demyelination are: Read Myelin . The most worrying effect is again demyelination of the motor neurons of the spinal chord which will be the effect of long term finasteride use:
"Sub-acute combined degeneration of the spinal cord secondary to pernicious anaemia can lead to anything from slight peripheral nerve damage to severe damage to the central nervous system affecting speech, balance and cognitive awareness. When myelin degrades, conduction of signals along the nerve can be impaired or lost and the nerve eventually withers."
Do you see those symptoms? Speech is affected, balance and cognitive awareness. This is exactly what you call brain fog here. The question is wheter this effect is reversable if you take finasteride for years. I certainly hope so for my friend altough, you know, neurogegeneration can really be irreversible.
It has to be said, that these effects are of LONG-TERM use but probably WILL eventually happen after years of finasteride use.
Now, I don't want to scare any one of you. I just want to give my input as a student of neurological sciences. Is it worth for you hair? My friend definitely regrets taking it.
Please ask if you have any questions but I don't know if I have the time to answer them.
Have a nice day.
- - - Updated - - -
My reponse to the above post. I used to get brain orgasms. Spine tingle sensations also known as auto sensory merridian response. Since taking finasteride I no longer get them. I do however get goosebumps from the same exposure. But just goosebumps. Its lacking that cool rush tingle from my scalp down my spine. It was seriously the most intense most euphoric feeling I had ever felt. I think given the information from the above post it is very possible that finasteride has prevented my ability to be able to experience these sensations again. I haven't given them up yet though. I think there is hope that over time I will get these back. I just won't be taking finasteride because I'm thinking that was the culprit that impaired me from getting them.
If you are one of the few people that do experience ASMR's and know how great that feeling is. Do yourself a favor and don't take finasteride. However if you are currently taking finasteride and still get ASMR's, let me know! It would be a relief to know I didn't screw myself out of getting them to try to save my stupid hair.
Hi,
My name is Alex Miller and I am studying biology -> specialization track: neurology and neurological sciences. I have been referred to this website by a good friend of mine who was using Propecia (Finasteride 1 mg) for 9 years. He never had any sexual side effects or other problems during this time. But about two month ago, he started having problems with cognitive function, forgetfulness, slurring of speech and depression. He went to several doctors and in the end a neurologist told him, that these effects come from the propecia. He then stopped using it and told me that if I have some time left, I should look into the matter. He started researching too and found this forum, where he said people named this side effect "brain fog". Unfortunately, I just don't have the time to read through this forum.
Before starting the research, I already knew that 5-alpha-reductase (5AR) has important functions in the central nervous system (CNS). So inhibiting it (by finasteride) might induce some side effects there. I will not address the possible sexual side effects but only the neurological ones. I will explain to you all what I have come up with so far. And guys: this is not looking good at all.
First of all, 5AR exists in two different isozymes: 5AR type 1 (5AR1) and 5AR type 2 (5AR2). 5AR1 is present mainly in the brain, muscle, liver and in sebaceous glands. 5AR2 is referred to as the "peripheral 5AR" since it is present mainly in the prostate, seminal vesicles, liver and hair follicles. Finasteride is a specific type 2 inhibitor and doesn't inhibit 5AR1 in significant amounts. But here comes something that not many people know: 5AR type 2 is also expressed in very significant amounts in spinal chord motor neurons, actually in similar amounts found in the prostate (Poletti et al. 2003) and could have (damn it!: WILL have) an effect there. What kind of effect this is, will be explained soon.
Something else, that many people don't know: Both isozymes of 5AR have more functions than just Testosterone (T) -> Dihydrotestosterone (DHT) conversion. They do the following conversions:
1. Testosterone -> Dihydrotestosterone
2. Progesterone -> Dihydroprogesterone
3. Deoxycorticosterone -> Dihydrodeoxycorticosterone
The latter two conversions are also inhibited by finasteride and so the production of neuroactive steroids is inhibited, since their metabolic pathway continues like this:
Dihydroprogesterone -> Tetrahydroprogesterone or also called Allopregnanolone.
Dihydrodeoxycorticosterone -> tetrahydrodeoxycorticosterone
These converions are catalyzed by an enzyme called 3-alpha hydroxysteroid dehydrogenase (3-alpha HSD).
You can read about these neuroactive steroids on wikipedia in order to get a rough idea about them:
Tetrahydrodeoxycorticosterone
Allopregnanolone
Altough it states there, that Tetrahydrodeoxycorticosterone is synthesized by 5AR1 in the brain, this is only partially true since, as explained above 5AR2 is also present in the CNS namely in the motor neurons of the spinal chord.
Now we come to the REAL concern: The inhibition of Allpregnanolone production. Altough Allopregnanolone can be produced in the brain by 5AR1, the CNS is also dependent on peripheral 5AR2. I quote from "Implications of neuroimaging for the treatment of epilepsy":
"Allopregnanolone formed in peripheral tissues readily enters the brain where it acts to enhance activation of GABA. A receptors" (William H. Theodore, MD; Clinical Epilepsy Section NIH Bethesda, MD).
Now to repeat again: Finasteride definitely inhibits allopregnanolone production in spinal chord motor neurons where mainly 5AR2 is present and also reduces allopregnanolone levels in the brain and other parts of the CNS since these parts are dependent on peripheral 5AR2 conversion of progesterone to dihydroprogesterone which is then converted to allopregnanolone by 3-alpha HSD.
The question is what the result of long-term allopregnanolone depletion is. Before you have to understand what the myelin-sheath of neurons is. The axon of neurones (both, peripheral neurons and neurons in the CNS) are surrounded by an electrically insulating layer: the myelin sheath. This is vital for fast and efficient impulse propagation on the neurons. I don't want to go into details here. Fact is: Allopregnanolone has vital function in the myelination of neurons as seen in the following studies:
When you read these, you'll see that the metabolic pathway of progesterone (inhibited by finasteride...) is vital for myelination and other functions in the CNS. In fact there are dozens of studies about the effects of progesterone metabolism and allopregnanolone on myelination.
1. Progestins and antiprogestins: mechanisms of action, neuroprotection and myelination (Link)
2. Progesterone: Therapeutic opportunities for neuroprotection and myelin repair (Link)
Quote: "Progesterone and its metabolites promote the viability of neurons in the brain and spinal cord. ".
Oh damn it! Didn't we say just before, that the motor neurons of the spinal chord expresses mainly 5AR type 2 (inhibited by finasteride)? So there will be a negative effect of myelination there for sure!
2. Allopregnanolone treatment, both as a single injection or repetitively, delays demyelination and enhances survival of niemann-pick C mice (Link)
3. There is also a study of Goumari et al. (didn't find it on the net) that shows the function of allorpegnanolone in myelination. Quote: "... allopregnanolone accelerated myelination ..." (Ghoumari et al. 2003b)
Alright. Let's see what the effects of demyelination are: Read Myelin . The most worrying effect is again demyelination of the motor neurons of the spinal chord which will be the effect of long term finasteride use:
"Sub-acute combined degeneration of the spinal cord secondary to pernicious anaemia can lead to anything from slight peripheral nerve damage to severe damage to the central nervous system affecting speech, balance and cognitive awareness. When myelin degrades, conduction of signals along the nerve can be impaired or lost and the nerve eventually withers."
Do you see those symptoms? Speech is affected, balance and cognitive awareness. This is exactly what you call brain fog here. The question is wheter this effect is reversable if you take finasteride for years. I certainly hope so for my friend altough, you know, neurogegeneration can really be irreversible.
It has to be said, that these effects are of LONG-TERM use but probably WILL eventually happen after years of finasteride use.
Now, I don't want to scare any one of you. I just want to give my input as a student of neurological sciences. Is it worth for you hair? My friend definitely regrets taking it.
Please ask if you have any questions but I don't know if I have the time to answer them.
Have a nice day.
- - - Updated - - -
My reponse to the above post. I used to get brain orgasms. Spine tingle sensations also known as auto sensory merridian response. Since taking finasteride I no longer get them. I do however get goosebumps from the same exposure. But just goosebumps. Its lacking that cool rush tingle from my scalp down my spine. It was seriously the most intense most euphoric feeling I had ever felt. I think given the information from the above post it is very possible that finasteride has prevented my ability to be able to experience these sensations again. I haven't given them up yet though. I think there is hope that over time I will get these back. I just won't be taking finasteride because I'm thinking that was the culprit that impaired me from getting them.
If you are one of the few people that do experience ASMR's and know how great that feeling is. Do yourself a favor and don't take finasteride. However if you are currently taking finasteride and still get ASMR's, let me know! It would be a relief to know I didn't screw myself out of getting them to try to save my stupid hair.
