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Finasteride reduces the amount of a neurosteroid called Allopregnanolone in the blood markedly, this is a fact, see table. (1). This is because the Allopregnanolone is formed by the 5a-reductase enzyme acting on 5α-dihydroprogesterone. Finasteride's whole mechanism of action is to inhibit this enzyme and thus reduce DHT. However, in doing so, not only is DHT reduced, but so are the formation of critical neurosteroids, including but not limited to Allopregnanolone.
This is a serious concern, as Allopregnanolone has been shown to affect Alzheimer's disease pathology, namely Amyloid-beta deposition in pre-clinical Alzheimer's disease models (2). Moreover, the level of Allopregnanolone is reduced in the brains of AD patients, this is to say, the neurosteroid plays some role in this area (2).
Alzheimer's disease is the result of (amyloid-beta) building up over decades (FACT). This subsequently leads to the development of tau tangles in the brain, which is ultimately what causes the death of neurons and AD (FACT) . So essentially, the build-up of Amyloid beta triggers tau tangles which causes Alzheimers, if you were to prevent amyloid from building up in the brain in the first place the disease pathology wouldn't be able to take place in theory. Finasteride lowers the amount of Allopregnanolone as shown in this study, and numerous others, and thus the brain will be more prone to the build up of amyloid-beta and subsequently AD decades down the line. This could all have a big cumulative effect, as I stated, the disease takes decades before symptoms show up, the changes in the brain are still occurring, it is not like one day a person just wakes up with AD, it is the culmination of many years of pathological proteins (amyloid-beta and tau) building up in the brain (FACT). Each day one takes Allopregnanolone they are impairing their bodies ability to get rid of toxic amyloid-beta from the brain. OK, maybe that is fine for a short while, but multiply this effect over many years / decades and you might have a problem, especially if you are genetically at risk. Those who carry the APOE4 allele for example showed that Allopregnanolone had an even more significant effect in reducing atrophy of the hippocampus (2), around 25% of you reading this will carry at least 1 copy of the APOE4 allele (frequency in white population - FACT), this is higher in other races.
Lastly, this doesn't even take into account the other neurosteroids that Fin suppresses, and who knows how they might further be protecting the brain but in ways we don't know about, so far we know about allo.
This is ultimately what has disuaded me from taking finasteride, but maybe this is a risk you are willing to take, life is all about managing risks.
TLDR: Allopregnanolone protects brain against amyloid-beta which causes Alzheimer's disease, Finasteride nukes allopregnanolone, and thus the brain is more likely to develop amyloid-beta and AD, especially in those at risk. Imagine impairing this neurosteroid for years of finasteride use, and thus years of suboptimal amyloid-beta clearance.
(1) https://www.researchgate.net/public...e_treatment_and_neuroactive_steroid_formation
(2) https://www.alzforum.org/therapeutics/allopregnanolone
This is a serious concern, as Allopregnanolone has been shown to affect Alzheimer's disease pathology, namely Amyloid-beta deposition in pre-clinical Alzheimer's disease models (2). Moreover, the level of Allopregnanolone is reduced in the brains of AD patients, this is to say, the neurosteroid plays some role in this area (2).
Alzheimer's disease is the result of (amyloid-beta) building up over decades (FACT). This subsequently leads to the development of tau tangles in the brain, which is ultimately what causes the death of neurons and AD (FACT) . So essentially, the build-up of Amyloid beta triggers tau tangles which causes Alzheimers, if you were to prevent amyloid from building up in the brain in the first place the disease pathology wouldn't be able to take place in theory. Finasteride lowers the amount of Allopregnanolone as shown in this study, and numerous others, and thus the brain will be more prone to the build up of amyloid-beta and subsequently AD decades down the line. This could all have a big cumulative effect, as I stated, the disease takes decades before symptoms show up, the changes in the brain are still occurring, it is not like one day a person just wakes up with AD, it is the culmination of many years of pathological proteins (amyloid-beta and tau) building up in the brain (FACT). Each day one takes Allopregnanolone they are impairing their bodies ability to get rid of toxic amyloid-beta from the brain. OK, maybe that is fine for a short while, but multiply this effect over many years / decades and you might have a problem, especially if you are genetically at risk. Those who carry the APOE4 allele for example showed that Allopregnanolone had an even more significant effect in reducing atrophy of the hippocampus (2), around 25% of you reading this will carry at least 1 copy of the APOE4 allele (frequency in white population - FACT), this is higher in other races.
Lastly, this doesn't even take into account the other neurosteroids that Fin suppresses, and who knows how they might further be protecting the brain but in ways we don't know about, so far we know about allo.
This is ultimately what has disuaded me from taking finasteride, but maybe this is a risk you are willing to take, life is all about managing risks.
TLDR: Allopregnanolone protects brain against amyloid-beta which causes Alzheimer's disease, Finasteride nukes allopregnanolone, and thus the brain is more likely to develop amyloid-beta and AD, especially in those at risk. Imagine impairing this neurosteroid for years of finasteride use, and thus years of suboptimal amyloid-beta clearance.
(1) https://www.researchgate.net/public...e_treatment_and_neuroactive_steroid_formation
(2) https://www.alzforum.org/therapeutics/allopregnanolone
