to the lost
Member
- Reaction score
- 0
Hi everybody,
so i am eager to see what everybody else thinks and hope to lear somethnig new
p.s. english is not my mother-language, so expect typos
sorry for long thread, could not get shorter
NOTE: some of the actual studies on the finasteride and neurosteroids are on page 2
I was looking on the mechanism of action of finasteride, and I found something discouraging/problematic. First of I am NOT a doctor or a neuro-scientist, so this is for me kind of a “hard-to-understand” subject, but I did reasearch. And please don’t accuse me of anything (I am neither for or against finasteride: in my previous thred – those who read it, know – that I am starting to have hair loss problems, but I am not on finasteride yet, but I would like to be if it is safe).
Ok, let’s start:
1.) finasteride inhibits T to DHT conversion, which means less of DHT in your body (by 5α reductase I and II, but as i understand type II more)
2.) please look at the picture http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2006.00053.x/pdf (page 55, picture 1)
It says: “[FONT=&]use of a 5[/FONT] α[FONT=&] -reductase inhibitor can be considered a[/FONT]
[FONT=&]blockade of the rate-limiting step to the two-step production of neuroactive steroid metabolites”
[/FONT]
[/FONT]
[FONT=&]So the 5[/FONT] α reductase inhibitor (like finesteride) can block production of certain neurosteroids (if I understand picture correctly) like DHT (you also get less androstanediol, because it is metabolite from DHT and there is less DHT in body); DHP (get also less allopregnanolone or short THP, same reason just from progesterone) and DHDOC (get also less THDOC).
did i understand that right? (it block all reductase metabolites, not just androstanediol)
did i understand that right? (it block all reductase metabolites, not just androstanediol)
3.) p 58 says: “[FONT=&]Given this finding, there has been speculation that finasteride[/FONT]
[FONT=&]might be useful to inhibit progesterone metabolism, and the concomitant synthesis of[/FONT]
[FONT=&]neuroactive steroids in the brain”
[/FONT]
[/FONT]
p. 60 has this conclusion:”[FONT=&] In summary, preclinical studies with[/FONT]
[FONT=&]finasteride and other drugs that alter 3[/FONT] α[FONT=&],5[/FONT] α[FONT=&] -THP biosynthesis support a role for endogenous[/FONT]
[FONT=&]3[/FONT][FONT=&]á[/FONT][FONT=&],5[/FONT][FONT=&]á[/FONT][FONT=&]-THP in maintaining normal GABAergic brain function, and suggest that alterations[/FONT]
[FONT=&]in endogenous 3[/FONT][FONT=&]á[/FONT][FONT=&],5[/FONT][FONT=&]á[/FONT][FONT=&]-THP levels could contribute to symptoms of anxiety and[/FONT]
[FONT=&]depression”
[/FONT]
[/FONT]
[FONT=&]p.61: “In male mice, finasteride reduced the anticonvulsant effects of progesterone and[/FONT]
[FONT=&]fluoxetine, both of which increase 3[/FONT] α[FONT=&],5[/FONT] α[FONT=&] -THP levels (discussed above),”[/FONT]
[FONT=&]if I understand this correctly finasteride (in male mice) reduces progesterone (and subsequently also lover THP)[/FONT]
[FONT=&]p. 62: “…one can surmise[/FONT]
[FONT=&]that finasteride would decrease levels of androsterone and etiocholanolone” (remember the picture on page 55)
[/FONT]
[/FONT]
[FONT=&]4.) so my worry is, that finasteride “mess-up” the brain neurosteroids. And those are rather important: “[/FONT]Neurosteroids are brain chemicals. Unlike most of the body's potent steroids, which are made in the sex glands, neurosteroids are only synthesized in the brain. Neurosteroids are known to be involved in behavior, stress, memory, depression, anxiety, aging of the brain, and neurodegenerative diseases” (http://scienceblog.com/community/older/1999/A/199900072.html)
Like THP (allopregnanolog) it deficit is found in some neurological disorders (not sure if there is causation): Allopregnanolone aids neurogenesis and has been found to reverse neuron proliferative deficit and cognitive deficits in mouse model of Alzheimer's disease (http://en.wikipedia.org/wiki/Tetrahydroprogesterone).
biosynthesis of allopregnanolone starts with the converting of progesterone into 5α-dihydroprogesterone by 5α-reductase type I. After that, 3α-hydroxysteroid oxidoreductase isoenzymes (also referred to as 3α-hydroxysteroid dehydrogenase) converts this intermediate into allopregnanolone. Anxiety and depression are common side effects of 5α-reductase inhibitors such as finasteride and dutasteride, and they are believed to be caused, in part, by the prevention of the endogenous production of allopregnanolone.
So my fear is NOT erectile dysfunction, depression or anxiety, but the neurological damage. Is this a real concern? Can somebody explain this more in detail? I think they should do some test for that too (OR AT LEAST ONE, there is literrally none existent)..
5.) and if somebody read my previous post, you know I had my hormones tested (drug free ofc). I have pretty low testosterone, and free test (lower part of reference rage but still in the reference range) but more importantly low DHT (like extremely low 3x less than minimal reference range).
And I had few “interesting” symptoms for past year – dizziness (feeling drunk for past 6 months, it stopped in November – had MRI and CT scans, came negative), depression and anxiety, now it started low libido and no morning wood. And I think I could correlate those with low DHT. Will see what my doctor says
p.s. english is not my mother-language, so expect typos
sorry for long thread, could not get shorter
NOTE: some of the actual studies on the finasteride and neurosteroids are on page 2