Comprehensive list of dutasteride side effects -- pls. add

[mattam]

Hi,

I am about to take plunge in to dutasteride (started finasteride with good results, then start losing again...)

I would like to take a list of all dutasteride side effects. Would appreciate if you can add your experiences OR links to scientific study that may point to the danger to dutasteride

These are potential danger to dutasteride I have compiled from reading through articles/threads. Pls. add comment or provide link to scientific studies related to these:

1) dutasteride is dangerous b/c it blocks nearly all DHT

Debunked?: Castrated men, eunuch, castrati, post-ops transexual-- whatever u call them, live relatively healthy long-lives. They of course lack sexual functiong (b/c of lack of Testosterone). However, they all completely lacks DHT.

2) dutasteride is dangerous b/c it blocks 5-AR Type I

Debunked?: dutasteride is supposed to be a "specific and competitive" inhibitor. Therefore, this means that it would bind to only 5-AR TypeI (and II) and nothing else. It would also mean that it should only inhibit 5-AR TypeI from binding to testosterone and nothing else (if 5-AR I does other function)

3) dutasteride is dangerous b/c it binds to 5-AR Type I, which is found in brain cells

Debunked?: Only found article that found 5AR I in "rat" brain cells. Would appreciate if anyone has link showing 5AR-I in "human" brain cells...

Debunked?: This would only be dangerous if 2) fails

4) dutasteride is dangerous b/c no one can account of how 50% of it is metabolizes

Debunked?: This is one of the comments from the forum...havn't seen articles on this....

5) dutasteride is dangerous b/c of long half-life

Debunked?: I supposed this could be an issue if you need to get dutasteride out of your system quickly

6) dutasteride is dangerous b/c it blocks all DHT but leaving Testosterone intact (in fact Testosterone actually increases.... see GSK product info). If there's a relationship between DHT and T regulation, this maybe an issue

Debunked? If this is an issue, Finasteride would run into the same issue (but to a lesser degree).

Would be interesting to see how people with 5AR deficiency (i.e. born w/ ambiguous genitalia) fare in other health areas (as this is essentially their issue -- full Testosterone but lacking DHT).

 

[Bismarck]

5aR does also convert progesterone to allopregnanolone (neurosteroid). This could explain the mental sides.

 

[Slartibartfast]

Hi Bis, any idea as to what the expected result of altering neurosteroid levels would be?

 

[drinkrum]

5aR does also convert progesterone to allopregnanolone (neurosteroid). This could explain the mental sides.

Huh? Progesterone (and its metabolites) is an inhibitor of 5-alpha reductase! Confer: http://www.greenjournal.org/cgi/content ... t/78/1/103

You may be thinking of "progesterone 5 alpha-reductase", which is a different animal.

D.

 

[drinkrum]

Would be interesting to see how people with 5AR deficiency (i.e. born w/ ambiguous genitalia) fare in other health areas (as this is essentially their issue -- full Testosterone but lacking DHT).

The people that are born with 5-AR deficiency (5-ARD) lack only the Type II isozyme. They show normal activity of the Type I isozyme, so they still produce some DHT as long testosterone is available.

Here is a link: http://www.emedicine.com/ped/topic1980.htm

D.

 

[Bismarck]

5aR does also convert progesterone to allopregnanolone (neurosteroid). This could explain the mental sides.

Huh? Progesterone (and its metabolites) is an inhibitor of 5-alpha reductase! Confer: http://www.greenjournal.org/cgi/content ... t/78/1/103

You may be thinking of "progesterone 5 alpha-reductase", which is a different animal.

D.

Sure.
I searched for allopregnanolone, it is
3-alpha-hydroxy-5-alpha-pregnan-20-one.
Therefore it seems evident to mo that 5aR plays a role in the conversion ( and a hydrogenase).
I think the name implies that allopregnanolone is a progesteron (4-pregnan-3,20-dion) metabolite (at least indirectly). The fact that allopregnalone is a 5aR inhibtor doesn't contradict this.

bis

 

[drinkrum]

5aR does also convert progesterone to allopregnanolone (neurosteroid). This could explain the mental sides.

Huh? Progesterone (and its metabolites) is an inhibitor of 5-alpha reductase! Confer: http://www.greenjournal.org/cgi/content ... t/78/1/103

You may be thinking of "progesterone 5 alpha-reductase", which is a different animal.

D.

Sure.
I searched for allopregnanolone, it is
3-alpha-hydroxy-5-alpha-pregnan-20-one.
Therefore it seems evident to mo that 5aR plays a role in the conversion ( and a hydrogenase).
I think the name implies that allopregnanolone is a progesteron (4-pregnan-3,20-dion) metabolite (at least indirectly). The fact that allopregnalone is a 5aR inhibtor doesn't contradict this.

bis

Right, finasteride _does_ block the reduction of progesterone to allopregnanolone.

D.

 

[Bismarck]

5aR does also convert progesterone to allopregnanolone (neurosteroid). This could explain the mental sides.

Huh? Progesterone (and its metabolites) is an inhibitor of 5-alpha reductase! Confer: http://www.greenjournal.org/cgi/content ... t/78/1/103

You may be thinking of "progesterone 5 alpha-reductase", which is a different animal.

D.

Sure.
I searched for allopregnanolone, it is
3-alpha-hydroxy-5-alpha-pregnan-20-one.
Therefore it seems evident to mo that 5aR plays a role in the conversion ( and a hydrogenase).
I think the name implies that allopregnanolone is a progesteron (4-pregnan-3,20-dion) metabolite (at least indirectly). The fact that allopregnalone is a 5aR inhibtor doesn't contradict this.

bis

Right, finasteride _does_ block the reduction of progesterone to allopregnanolone. There is evidence that finasteride can be used to control seizures, in this regard.

D.

Nice. So what's the problem ?

 

[Bismarck]

Hi Bis, any idea as to what the expected result of altering neurosteroid levels would be?

We concluded that 5aR inhibitors like Finasteride and Dutasteride decrease allopregnanolone levels in the brain tissue. Allopregnanolone has neuroprotective effects - this does not necessarily imply you are more likely to develop Alzheimer, Parkinson, ....
I think epidemiological studies in 40 years could say "The risk for developing neurodegnerative disease XYZ was significantly higher for people taking 5aR inhibitors in their life" or not.

Here's another üpost from kofi on alt.baldspot:

Prolonged inhibition of 5alpha-reductase (both isoenzymes) results in a
decrease in inhibitory GABA currents. It remains to be seen how lower
doses of less specific 5ar inhibitors like finasteride work. In any
event, this makes 5AR blockers questionable for age-related memory
disorders, neuropathies, chronic pain conditions and other failures of
GABA inhibition like epilepsy.



Neuropharmacology. 2003 Jan;44(1):49-55. Related Articles, Links
Click here to read
On the putative physiological role of allopregnanolone on GABA(A)
receptor function.

Puia G, Mienville JM, Matsumoto K, Takahata H, Watanabe H, Costa E,
Guidotti A.

The Psychiatric Institute, Department of Psychiatry, University of
Illinois at Chicago, 1601 W. Taylor St. MC912, Chicago, IL 60612, USA.

To obtain definitive evidence for a physiological allosteric
modulatory role for endogenous brain ALLO on GABA(A) receptor function,
we studied GABA(A) receptor activity under conditions in which the
concentration of endogenous brain ALLO was decreased by about 80% for
longer than 5 h following the administration of SKF 105111-
17beta-17-[bis (1methylethyl) amino carbonyl]
androstane-3,5-diene-3-carboxylic acid (SKF), a potent inhibitor of
5alpha-reductases Type I and II. We used the in situ patch-clamp
technique to record GABA-evoked currents and spontaneous inhibitory
postsynaptic currents (sIPSCs) from pyramidal neurons in neocortical
slices of vehicle- or SKF-treated mice. The potency, but not the
efficacy, of exogenously applied GABA was decreased in slices from mice
treated with SKF. When neocortical slices were treated in vitro for 3 h
with 10 microM SKF, ALLO was also reduced (25-30%) and in addition, the
GABA dose-response curve was shifted to the right; however this shift
was not as marked as the shift in the slices obtained from mice treated
with SKF, in keeping with the smaller decrease of the ALLO content in
these slices. Furthermore, direct application of ALLO to these slices
shifted the dose-response curve of GABA back toward a non-SKF treated
profile. We then analyzed GABAergic sIPSCs in neocortical slices
obtained from vehicle or SKF-treated mice. Mean decay time and charge
transfer were significantly reduced by SKF treatment. The decay of
sIPSCs was best fitted by two exponentials, but only the fast component
was decreased in the SKF group. Direct application of ALLO (100 nM)
normalizes the sIPSC kinetics in slices from ALLO depleted mice. No
changes were detected in the amplitude or frequency of sIPSCs. These
data demonstrate that endogenous ALLO physiologically regulates
spontaneously induced Cl(-) current by acting on a specific recognition
site, which is probably located on GABA(A) receptors (a receptor on a
receptor), thereby prolonging inhibitory currents by facilitating
conformational transition of the GABA-gated Cl(-) channel to an open
state.

PMID: 12559121 [PubMed - indexed for MEDLINE]

 

[Bismarck]

Just found sth with the search function.
This was written by gourmetstylewellness.com member AJB on Jun 03, 2002 :

I've been using finasteride (proscar cut into roughtly 1.25mg quarters) now for about four to five months. I can't tell yet if it is helping my hair, which is not suprising given this short duration.

I have experienced few if any sexual side effects, except that maybe I'm not as consistently horny as I used to be. That isn't entirely a bad thing. However, despite the intact sex life, I must admit I've felt a bit more moody on it than I used to feel. I thought maybe it was just my imagination, but then one night I went to a party and had a couple beers. I don't drink very often and my tolerance is not all that high these days. I was suprised to notice that I didn't really feel drunk. I had two more beers. At this point I should have had a lampshade on my head, but instead I felt only slightly buzzed. Another night I went out to eat with my girlfriend and, after a couple drinks, felt next to nothing. At least, I didn't feel that kind of relaxing high that alcohol can give you. All I felt was a bit red in the face.

I didn't think much of it at the time, but on a hunch, I got on the internet, wondering if finasteride might affect the way EtOH is metabolized or something.

Much to my suprise, I did find a connection between finasteride and alcohol. It would appear that alchohol causes an increase in the production of a "neurosteroid" called allopregnanolone. Allopregnanolone binds to a certain receptor in your brain, the GABA(A) receptor. GABA(A) is a receptor for a neurotransmitter called GABA (short for gamma aminobutyric acid). GABA is one of the major inhibitory neurotransmitters, and is implicated in many anxiety disorders and depression. Certain anti-anxiety drugs like valium bind to GABA's recpetor too. Allopregnanolone is an "allosteric enhancer" of the GABA(A) receptor. That means it helps the receptor do it's job better. Specifically, it intensifies the effects of GABA by making it much easier for GABA to "turn on" the receptor. So, when you drink alcohol, more allopregnanolone gets produced, GABA is thus made more potent, and you feel relaxed and happy.

Here's the deal: Allopregnanolone is a metabolite of progesterone. Guess what is one of the enzymes responsible for converting progesterone to allopregnanolone: Yep, 5-alpha reductase. In other words, just like it inhibits the conversion of testosterone to DHT, finasteride blocks the conversion of progesterone to allopregnanolone.

It gets worse: Just before menstruation, the levels of progesterone in a woman's body drop dramatically. This leads to a corresponding drop in allopregnanolone, which leads to...PMS! That's right, one of the reasons women get moody and anxious before they get their period is because they're experienceing allopregnanolone withdrawl. Contrary to what many think, men also make progesterone, and men also depend on allopregnanolone for the proper functioning of GABA in their brains.

Needless to say, I have been doing a lot of reading about this, and I'm a bit alarmed. I knew going into it that finasteride could maybe effect erections or my sex drive, but nobody said it could make me depressed or anxious too. But there is clear scientific evidence out there that finasteride can have some profound effects on the way your brain works. Most specifically, it will effect the way your brain reacts to stress: stress causes increases in the production of allopregnanolone, and allopregnanolone production in the cerebral cortex is greatly inhibited by finasteride. Some people are even considering giving finasteride to alcoholics to help them get off the sauce: Since finasteride deprives you of the relaxing reward of drinking, there's less of an incentive to drink!

I work as a biologist. The studies on this subject have been published in some very reputable journals, like The Proceedings of the National Academy of Sciences, The Journal of Neuroscience, Brain Research, etc.

Just follow this link:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

Type in the blank "finasteride" and "allopregnanolone" and see what you turn up. Scientists use finasteride as a tool in the lab to study behavior in rats, like their response to alcohol or stress. Loss of allopregnanolone even makes rats more prone to seizures when treated with certain drugs. I'm not making any of this up.

My feelings upon reading all this stuff: Oh f**k! I really don't know what I should do at this point. My emotional state has only been mildly affected, I would say, and I can't really say I've experienced any significant impact on my life. But the fact is, this drug does more than just just stop you from losing your hair (maybe). It turns out there are a lot of steroid hormones in your body, and many of them are converted by 5-alpha reductase. All of these hormones have a purpose, and I just have to wonder what the long-term effects of monkeying around with them might be. If all finasteride did was inhibit DHT, I probably could ignore it, since my sex life is fine. But I'm not so sure any of us should ignore some of its other effects. We should at least be fully informed as to what this drug does to our bodies.

So, what do you all think?

 

[drinkrum]

Yeah, I echo his feelings. But I wonder if there is any significant impact at the 1 mg level.

D.

 

[Bismarck]

Yeah, I echo his feelings. But I wonder if there is any significant impact at the 1 mg level.

D.

Well, the few 5aR-I enzymes in the brain tissue are not affected by finasteride, so I hope the best. :?

 

[Mindfull]

5aR does also convert progesterone to allopregnanolone (neurosteroid). This could explain the mental sides.

which type of 5-AR ... type I or type II?!

 

[Bismarck]

5aR does also convert progesterone to allopregnanolone (neurosteroid). This could explain the mental sides.

which type of 5-AR ... type I or type II?!

I think both.

 

[Mindfull]

Just found sth with the search function.
This was written by gourmetstylewellness.com member AJB on Jun 03, 2002 :

I've been using finasteride (proscar cut into roughtly 1.25mg quarters) now for about four to five months. I can't tell yet if it is helping my hair, which is not suprising given this short duration.

I have experienced few if any sexual side effects, except that maybe I'm not as consistently horny as I used to be. That isn't entirely a bad thing. However, despite the intact sex life, I must admit I've felt a bit more moody on it than I used to feel. I thought maybe it was just my imagination, but then one night I went to a party and had a couple beers. I don't drink very often and my tolerance is not all that high these days. I was suprised to notice that I didn't really feel drunk. I had two more beers. At this point I should have had a lampshade on my head, but instead I felt only slightly buzzed. Another night I went out to eat with my girlfriend and, after a couple drinks, felt next to nothing. At least, I didn't feel that kind of relaxing high that alcohol can give you. All I felt was a bit red in the face.

I didn't think much of it at the time, but on a hunch, I got on the internet, wondering if finasteride might affect the way EtOH is metabolized or something.

Much to my suprise, I did find a connection between finasteride and alcohol. It would appear that alchohol causes an increase in the production of a "neurosteroid" called allopregnanolone. Allopregnanolone binds to a certain receptor in your brain, the GABA(A) receptor. GABA(A) is a receptor for a neurotransmitter called GABA (short for gamma aminobutyric acid). GABA is one of the major inhibitory neurotransmitters, and is implicated in many anxiety disorders and depression. Certain anti-anxiety drugs like valium bind to GABA's recpetor too. Allopregnanolone is an "allosteric enhancer" of the GABA(A) receptor. That means it helps the receptor do it's job better. Specifically, it intensifies the effects of GABA by making it much easier for GABA to "turn on" the receptor. So, when you drink alcohol, more allopregnanolone gets produced, GABA is thus made more potent, and you feel relaxed and happy.

Here's the deal: Allopregnanolone is a metabolite of progesterone. Guess what is one of the enzymes responsible for converting progesterone to allopregnanolone: Yep, 5-alpha reductase. In other words, just like it inhibits the conversion of testosterone to DHT, finasteride blocks the conversion of progesterone to allopregnanolone.

It gets worse: Just before menstruation, the levels of progesterone in a woman's body drop dramatically. This leads to a corresponding drop in allopregnanolone, which leads to...PMS! That's right, one of the reasons women get moody and anxious before they get their period is because they're experienceing allopregnanolone withdrawl. Contrary to what many think, men also make progesterone, and men also depend on allopregnanolone for the proper functioning of GABA in their brains.

Needless to say, I have been doing a lot of reading about this, and I'm a bit alarmed. I knew going into it that finasteride could maybe effect erections or my sex drive, but nobody said it could make me depressed or anxious too. But there is clear scientific evidence out there that finasteride can have some profound effects on the way your brain works. Most specifically, it will effect the way your brain reacts to stress: stress causes increases in the production of allopregnanolone, and allopregnanolone production in the cerebral cortex is greatly inhibited by finasteride. Some people are even considering giving finasteride to alcoholics to help them get off the sauce: Since finasteride deprives you of the relaxing reward of drinking, there's less of an incentive to drink!

I work as a biologist. The studies on this subject have been published in some very reputable journals, like The Proceedings of the National Academy of Sciences, The Journal of Neuroscience, Brain Research, etc.

Just follow this link:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

Type in the blank "finasteride" and "allopregnanolone" and see what you turn up. Scientists use finasteride as a tool in the lab to study behavior in rats, like their response to alcohol or stress. Loss of allopregnanolone even makes rats more prone to seizures when treated with certain drugs. I'm not making any of this up.

My feelings upon reading all this stuff: Oh f**k! I really don't know what I should do at this point. My emotional state has only been mildly affected, I would say, and I can't really say I've experienced any significant impact on my life. But the fact is, this drug does more than just just stop you from losing your hair (maybe). It turns out there are a lot of steroid hormones in your body, and many of them are converted by 5-alpha reductase. All of these hormones have a purpose, and I just have to wonder what the long-term effects of monkeying around with them might be. If all finasteride did was inhibit DHT, I probably could ignore it, since my sex life is fine. But I'm not so sure any of us should ignore some of its other effects. We should at least be fully informed as to what this drug does to our bodies.

So, what do you all think?

yes, I read this one as well a year ago ... I even tried to contact member ½ year ago to get a possible update, but did not get a reply. But again, the description above would seem plausible if we were talking about 5-AR I which is present in the human brain cells, but I am unaware that the same can be said about 5-AR II (which is inhibited by finasteride). This member obviously knows something about the topic - maybe he read about 5-AR I (inhibited by dutasteride only) and made it apply to his own symptoms which however may have been caused by something different than finasteride since finasteride does not interact with neural activity ... (?).

 

[Bismarck]

Just found sth with the search function.
This was written by gourmetstylewellness.com member AJB on Jun 03, 2002 :

I've been using finasteride (proscar cut into roughtly 1.25mg quarters) now for about four to five months. I can't tell yet if it is helping my hair, which is not suprising given this short duration.

I have experienced few if any sexual side effects, except that maybe I'm not as consistently horny as I used to be. That isn't entirely a bad thing. However, despite the intact sex life, I must admit I've felt a bit more moody on it than I used to feel. I thought maybe it was just my imagination, but then one night I went to a party and had a couple beers. I don't drink very often and my tolerance is not all that high these days. I was suprised to notice that I didn't really feel drunk. I had two more beers. At this point I should have had a lampshade on my head, but instead I felt only slightly buzzed. Another night I went out to eat with my girlfriend and, after a couple drinks, felt next to nothing. At least, I didn't feel that kind of relaxing high that alcohol can give you. All I felt was a bit red in the face.

I didn't think much of it at the time, but on a hunch, I got on the internet, wondering if finasteride might affect the way EtOH is metabolized or something.

Much to my suprise, I did find a connection between finasteride and alcohol. It would appear that alchohol causes an increase in the production of a "neurosteroid" called allopregnanolone. Allopregnanolone binds to a certain receptor in your brain, the GABA(A) receptor. GABA(A) is a receptor for a neurotransmitter called GABA (short for gamma aminobutyric acid). GABA is one of the major inhibitory neurotransmitters, and is implicated in many anxiety disorders and depression. Certain anti-anxiety drugs like valium bind to GABA's recpetor too. Allopregnanolone is an "allosteric enhancer" of the GABA(A) receptor. That means it helps the receptor do it's job better. Specifically, it intensifies the effects of GABA by making it much easier for GABA to "turn on" the receptor. So, when you drink alcohol, more allopregnanolone gets produced, GABA is thus made more potent, and you feel relaxed and happy.

Here's the deal: Allopregnanolone is a metabolite of progesterone. Guess what is one of the enzymes responsible for converting progesterone to allopregnanolone: Yep, 5-alpha reductase. In other words, just like it inhibits the conversion of testosterone to DHT, finasteride blocks the conversion of progesterone to allopregnanolone.

It gets worse: Just before menstruation, the levels of progesterone in a woman's body drop dramatically. This leads to a corresponding drop in allopregnanolone, which leads to...PMS! That's right, one of the reasons women get moody and anxious before they get their period is because they're experienceing allopregnanolone withdrawl. Contrary to what many think, men also make progesterone, and men also depend on allopregnanolone for the proper functioning of GABA in their brains.

Needless to say, I have been doing a lot of reading about this, and I'm a bit alarmed. I knew going into it that finasteride could maybe effect erections or my sex drive, but nobody said it could make me depressed or anxious too. But there is clear scientific evidence out there that finasteride can have some profound effects on the way your brain works. Most specifically, it will effect the way your brain reacts to stress: stress causes increases in the production of allopregnanolone, and allopregnanolone production in the cerebral cortex is greatly inhibited by finasteride. Some people are even considering giving finasteride to alcoholics to help them get off the sauce: Since finasteride deprives you of the relaxing reward of drinking, there's less of an incentive to drink!

I work as a biologist. The studies on this subject have been published in some very reputable journals, like The Proceedings of the National Academy of Sciences, The Journal of Neuroscience, Brain Research, etc.

Just follow this link:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

Type in the blank "finasteride" and "allopregnanolone" and see what you turn up. Scientists use finasteride as a tool in the lab to study behavior in rats, like their response to alcohol or stress. Loss of allopregnanolone even makes rats more prone to seizures when treated with certain drugs. I'm not making any of this up.

My feelings upon reading all this stuff: Oh f**k! I really don't know what I should do at this point. My emotional state has only been mildly affected, I would say, and I can't really say I've experienced any significant impact on my life. But the fact is, this drug does more than just just stop you from losing your hair (maybe). It turns out there are a lot of steroid hormones in your body, and many of them are converted by 5-alpha reductase. All of these hormones have a purpose, and I just have to wonder what the long-term effects of monkeying around with them might be. If all finasteride did was inhibit DHT, I probably could ignore it, since my sex life is fine. But I'm not so sure any of us should ignore some of its other effects. We should at least be fully informed as to what this drug does to our bodies.

So, what do you all think?

yes, I read this one as well a year ago ... I even tried to contact member ½ year ago to get a possible update, but did not get a reply. But again, the description above would seem plausible if we were talking about 5-AR I which is present in the human brain cells, but I am unaware that the same can be said about 5-AR II (which is inhibited by finasteride). This member obviously knows something about the topic - maybe he read about 5-AR I (inhibited by dutasteride only) and made it apply to his own symptoms which however may have been caused by something different than finasteride since finasteride does not interact with neural activity ... (?).

I don't think so:

I didn't think much of it at the time, but on a hunch, I got on the internet, wondering if finasteride might affect the way EtOH is metabolized or something.

Furthermore dutasteride wasn't really an issue at this time.

bis

 

[Mindfull]

Just found sth with the search function.
This was written by gourmetstylewellness.com member AJB on Jun 03, 2002 :

I've been using finasteride (proscar cut into roughtly 1.25mg quarters) now for about four to five months. I can't tell yet if it is helping my hair, which is not suprising given this short duration.

I have experienced few if any sexual side effects, except that maybe I'm not as consistently horny as I used to be. That isn't entirely a bad thing. However, despite the intact sex life, I must admit I've felt a bit more moody on it than I used to feel. I thought maybe it was just my imagination, but then one night I went to a party and had a couple beers. I don't drink very often and my tolerance is not all that high these days. I was suprised to notice that I didn't really feel drunk. I had two more beers. At this point I should have had a lampshade on my head, but instead I felt only slightly buzzed. Another night I went out to eat with my girlfriend and, after a couple drinks, felt next to nothing. At least, I didn't feel that kind of relaxing high that alcohol can give you. All I felt was a bit red in the face.

I didn't think much of it at the time, but on a hunch, I got on the internet, wondering if finasteride might affect the way EtOH is metabolized or something.

Much to my suprise, I did find a connection between finasteride and alcohol. It would appear that alchohol causes an increase in the production of a "neurosteroid" called allopregnanolone. Allopregnanolone binds to a certain receptor in your brain, the GABA(A) receptor. GABA(A) is a receptor for a neurotransmitter called GABA (short for gamma aminobutyric acid). GABA is one of the major inhibitory neurotransmitters, and is implicated in many anxiety disorders and depression. Certain anti-anxiety drugs like valium bind to GABA's recpetor too. Allopregnanolone is an "allosteric enhancer" of the GABA(A) receptor. That means it helps the receptor do it's job better. Specifically, it intensifies the effects of GABA by making it much easier for GABA to "turn on" the receptor. So, when you drink alcohol, more allopregnanolone gets produced, GABA is thus made more potent, and you feel relaxed and happy.

Here's the deal: Allopregnanolone is a metabolite of progesterone. Guess what is one of the enzymes responsible for converting progesterone to allopregnanolone: Yep, 5-alpha reductase. In other words, just like it inhibits the conversion of testosterone to DHT, finasteride blocks the conversion of progesterone to allopregnanolone.

It gets worse: Just before menstruation, the levels of progesterone in a woman's body drop dramatically. This leads to a corresponding drop in allopregnanolone, which leads to...PMS! That's right, one of the reasons women get moody and anxious before they get their period is because they're experienceing allopregnanolone withdrawl. Contrary to what many think, men also make progesterone, and men also depend on allopregnanolone for the proper functioning of GABA in their brains.

Needless to say, I have been doing a lot of reading about this, and I'm a bit alarmed. I knew going into it that finasteride could maybe effect erections or my sex drive, but nobody said it could make me depressed or anxious too. But there is clear scientific evidence out there that finasteride can have some profound effects on the way your brain works. Most specifically, it will effect the way your brain reacts to stress: stress causes increases in the production of allopregnanolone, and allopregnanolone production in the cerebral cortex is greatly inhibited by finasteride. Some people are even considering giving finasteride to alcoholics to help them get off the sauce: Since finasteride deprives you of the relaxing reward of drinking, there's less of an incentive to drink!

I work as a biologist. The studies on this subject have been published in some very reputable journals, like The Proceedings of the National Academy of Sciences, The Journal of Neuroscience, Brain Research, etc.

Just follow this link:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

Type in the blank "finasteride" and "allopregnanolone" and see what you turn up. Scientists use finasteride as a tool in the lab to study behavior in rats, like their response to alcohol or stress. Loss of allopregnanolone even makes rats more prone to seizures when treated with certain drugs. I'm not making any of this up.

My feelings upon reading all this stuff: Oh f**k! I really don't know what I should do at this point. My emotional state has only been mildly affected, I would say, and I can't really say I've experienced any significant impact on my life. But the fact is, this drug does more than just just stop you from losing your hair (maybe). It turns out there are a lot of steroid hormones in your body, and many of them are converted by 5-alpha reductase. All of these hormones have a purpose, and I just have to wonder what the long-term effects of monkeying around with them might be. If all finasteride did was inhibit DHT, I probably could ignore it, since my sex life is fine. But I'm not so sure any of us should ignore some of its other effects. We should at least be fully informed as to what this drug does to our bodies.

So, what do you all think?

yes, I read this one as well a year ago ... I even tried to contact member ½ year ago to get a possible update, but did not get a reply. But again, the description above would seem plausible if we were talking about 5-AR I which is present in the human brain cells, but I am unaware that the same can be said about 5-AR II (which is inhibited by finasteride). This member obviously knows something about the topic - maybe he read about 5-AR I (inhibited by dutasteride only) and made it apply to his own symptoms which however may have been caused by something different than finasteride since finasteride does not interact with neural activity ... (?).

I don't think so:
[quote:8d14a]I didn't think much of it at the time, but on a hunch, I got on the internet, wondering if finasteride might affect the way EtOH is metabolized or something.

Furthermore dutasteride wasn't really an issue at this time.

bis[/quote:8d14a]

Still, its all essential to be clear about whether 5-AR II is also present in the brain. If not - then this member is anticipating severe neurobiological side effects that will not occur from taking finasteride. You say that dutasteride was not an issue. Maybe it wasnt a commercial issue, but surely 5-AR type I has been clinically investigated long before the development ofAvodart, so it has not been difficult to find studies describing its positive or negative effects in the brain. Im too tired to find out whether the links above refer to 5-AR type II or I. BUt please let us know

It would be nice to know if 5-AR type II could indeed be responsible for what this member has described

 

[Bismarck]

Just found sth with the search function.
This was written by gourmetstylewellness.com member AJB on Jun 03, 2002 :

I've been using finasteride (proscar cut into roughtly 1.25mg quarters) now for about four to five months. I can't tell yet if it is helping my hair, which is not suprising given this short duration.

I have experienced few if any sexual side effects, except that maybe I'm not as consistently horny as I used to be. That isn't entirely a bad thing. However, despite the intact sex life, I must admit I've felt a bit more moody on it than I used to feel. I thought maybe it was just my imagination, but then one night I went to a party and had a couple beers. I don't drink very often and my tolerance is not all that high these days. I was suprised to notice that I didn't really feel drunk. I had two more beers. At this point I should have had a lampshade on my head, but instead I felt only slightly buzzed. Another night I went out to eat with my girlfriend and, after a couple drinks, felt next to nothing. At least, I didn't feel that kind of relaxing high that alcohol can give you. All I felt was a bit red in the face.

I didn't think much of it at the time, but on a hunch, I got on the internet, wondering if finasteride might affect the way EtOH is metabolized or something.

Much to my suprise, I did find a connection between finasteride and alcohol. It would appear that alchohol causes an increase in the production of a "neurosteroid" called allopregnanolone. Allopregnanolone binds to a certain receptor in your brain, the GABA(A) receptor. GABA(A) is a receptor for a neurotransmitter called GABA (short for gamma aminobutyric acid). GABA is one of the major inhibitory neurotransmitters, and is implicated in many anxiety disorders and depression. Certain anti-anxiety drugs like valium bind to GABA's recpetor too. Allopregnanolone is an "allosteric enhancer" of the GABA(A) receptor. That means it helps the receptor do it's job better. Specifically, it intensifies the effects of GABA by making it much easier for GABA to "turn on" the receptor. So, when you drink alcohol, more allopregnanolone gets produced, GABA is thus made more potent, and you feel relaxed and happy.

Here's the deal: Allopregnanolone is a metabolite of progesterone. Guess what is one of the enzymes responsible for converting progesterone to allopregnanolone: Yep, 5-alpha reductase. In other words, just like it inhibits the conversion of testosterone to DHT, finasteride blocks the conversion of progesterone to allopregnanolone.

It gets worse: Just before menstruation, the levels of progesterone in a woman's body drop dramatically. This leads to a corresponding drop in allopregnanolone, which leads to...PMS! That's right, one of the reasons women get moody and anxious before they get their period is because they're experienceing allopregnanolone withdrawl. Contrary to what many think, men also make progesterone, and men also depend on allopregnanolone for the proper functioning of GABA in their brains.

Needless to say, I have been doing a lot of reading about this, and I'm a bit alarmed. I knew going into it that finasteride could maybe effect erections or my sex drive, but nobody said it could make me depressed or anxious too. But there is clear scientific evidence out there that finasteride can have some profound effects on the way your brain works. Most specifically, it will effect the way your brain reacts to stress: stress causes increases in the production of allopregnanolone, and allopregnanolone production in the cerebral cortex is greatly inhibited by finasteride. Some people are even considering giving finasteride to alcoholics to help them get off the sauce: Since finasteride deprives you of the relaxing reward of drinking, there's less of an incentive to drink!

I work as a biologist. The studies on this subject have been published in some very reputable journals, like The Proceedings of the National Academy of Sciences, The Journal of Neuroscience, Brain Research, etc.

Just follow this link:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

Type in the blank "finasteride" and "allopregnanolone" and see what you turn up. Scientists use finasteride as a tool in the lab to study behavior in rats, like their response to alcohol or stress. Loss of allopregnanolone even makes rats more prone to seizures when treated with certain drugs. I'm not making any of this up.

My feelings upon reading all this stuff: Oh f**k! I really don't know what I should do at this point. My emotional state has only been mildly affected, I would say, and I can't really say I've experienced any significant impact on my life. But the fact is, this drug does more than just just stop you from losing your hair (maybe). It turns out there are a lot of steroid hormones in your body, and many of them are converted by 5-alpha reductase. All of these hormones have a purpose, and I just have to wonder what the long-term effects of monkeying around with them might be. If all finasteride did was inhibit DHT, I probably could ignore it, since my sex life is fine. But I'm not so sure any of us should ignore some of its other effects. We should at least be fully informed as to what this drug does to our bodies.

So, what do you all think?

yes, I read this one as well a year ago ... I even tried to contact member ½ year ago to get a possible update, but did not get a reply. But again, the description above would seem plausible if we were talking about 5-AR I which is present in the human brain cells, but I am unaware that the same can be said about 5-AR II (which is inhibited by finasteride). This member obviously knows something about the topic - maybe he read about 5-AR I (inhibited by dutasteride only) and made it apply to his own symptoms which however may have been caused by something different than finasteride since finasteride does not interact with neural activity ... (?).

I don't think so:
[quote:07b5c]I didn't think much of it at the time, but on a hunch, I got on the internet, wondering if finasteride might affect the way EtOH is metabolized or something.

Furthermore dutasteride wasn't really an issue at this time.

bis

Still, its all essential to be clear about whether 5-AR II is also present in the brain. If not - then this member is anticipating severe neurobiological side effects that will not occur from taking finasteride. You say that dutasteride was not an issue. Maybe it wasnt a commercial issue, but surely 5-AR type I has been clinically investigated long before the development ofAvodart, so it would be difficult to find studies describing its positive or negative effects in the brain.

It would be nice to know if 5-AR type II could indeed be responsible for what this member has described[/quote:07b5c]

Type II is not present in the brain. But allopregnanolone is metabolized by the type II in the blood and reaches the brain.

 

[Slartibartfast]

Bis - thanks for the two posts on the previous page, the first one was of particular interest. Could this decrease in allopregnanolone levels be responsible for the side effect that I noted in a November '04 post on my story thread? Namely:

The light-headedness began within two weeks of changing to a daily dose. Typically it would be noticeable 2.5 to 3 hours after dosing and persist for the next several hours - with its intensity fading during this period. This was a tolerable side effect but, sometime round the 6 week mark, it was replaced with a non-specific headache.
A dull, nagging, affair reminiscent of one from a very, very, mild hangover or, indeed, slight dehydration, which also kicked in about 3 hours after swallowing the dutasteride.....after a week of this the headaches had subsided and I was back to that good old feeling of light-headedness.

Up until two weeks ago that effect remained fairly constant but I then noticed that both its duration and intensity were diminishing and today, after 101 daily doses, I experienced no noticeable side effects after taking Dutasteride.

Now assuming this was all a consequence of my taking Dutasteride why, after getting progressively more severe as the drug's level increased in my system, would this side effect then fade to nothing - starting from approximately the point at which dutasteride's serum concentration peaked? And should the cessation of said side effect be viewed as a positive for longer-term Dutasteride usage?

Answers on a postcard to the usual address, please.

Slarti

 

[drinkrum]

Bis - thanks for the two posts on the previous page, the first one was of particular interest. Could this decrease in allopregnanolone levels be responsible for the side effect that I noted in a November '04 post on my story thread? Namely:

The light-headedness began within two weeks of changing to a daily dose. Typically it would be noticeable 2.5 to 3 hours after dosing and persist for the next several hours - with its intensity fading during this period. This was a tolerable side effect but, sometime round the 6 week mark, it was replaced with a non-specific headache.
A dull, nagging, affair reminiscent of one from a very, very, mild hangover or, indeed, slight dehydration, which also kicked in about 3 hours after swallowing the dutasteride.....after a week of this the headaches had subsided and I was back to that good old feeling of light-headedness.

Up until two weeks ago that effect remained fairly constant but I then noticed that both its duration and intensity were diminishing and today, after 101 daily doses, I experienced no noticeable side effects after taking Dutasteride.

Now assuming this was all a consequence of my taking Dutasteride why, after getting progressively more severe as the drug's level increased in my system, would this side effect then fade to nothing - starting from approximately the point at which dutasteride's serum concentration peaked? And should the cessation of said side effect be viewed as a positive for longer-term Dutasteride usage?

Answers on a postcard to the usual address, please.

Slarti

The body adjusts. With finasteride, at least, the first couple of weeks are marked by elevated testosterone, etc. but in the long-term, levels return to baseline. I am not sure about dutasteride, but finasteride at the 1 mg/day level is not supposed to interfere with the HPTA (hypothalamus-pituitary-testes axis), which regulates the body's androgen production.

D.