Long term finasteride use and staying on top of prostate

[corza000]

I’ve been on finasteride for over 10 years now. It has been great for my hair during this time. I haven’t really lost any noticeable ground in this time and I initially had some grow back.

I remember reading a while back the impact finasteride can have on prostate, prostate cancer etc. It seemed mixed at the time. Given I’ve been on the medication for some time now is there something I can ask the doctor to check just to be on top of any risks? Is there a blood test worth doing to ensure finasteride isn’t having any negative impacts such as on the prostate.

I have no health concerns but I want to be proactive.

thanks

 

[BetaBoy]

By all means ask your doctor but the claim that finasteride may increase the rate of high gleason prostate cancers were recently (2019) retracted by the authors who originally raised the alarm after reviewing long term (~18 years) patient data.

 

[Regan]

I think a bigger risk of long-term finasteride use is probably the effects of allopregnanolone depletion on long-term brain health. Cognitive decline, risk of Alzheimer's and so forth. We can't really do trials on that stuff because we're talking about effects that unfold over many years, but it seems likely that cutting allopregnanolone should worsen age-related cognitive decline.

 

[Regan]

In terms of what you can do to mitigate cognitive decline, you can check your genes, as we know quite well which genes are risk-factors for Alzheimer's, for example. You could then look into lifestyle interventions that reduce cognitive decline risks. In the opinion of this random dude on the internet, the book The Mindspan Diet is pretty good. The book has also been endorsed by people like George Church, who is probably more credible than me. Also, he has great hair for a man in his late 60s, which of course makes everything he says more credible than if he were a bald dude.

 

[losingbattle88]

In terms of what you can do to mitigate cognitive decline, you can check your genes, as we know quite well which genes are risk-factors for Alzheimer's, for example. You could then look into lifestyle interventions that reduce cognitive decline risks. In the opinion of this random dude on the internet, the book The Mindspan Diet is pretty good. The book has also been endorsed by people like George Church, who is probably more credible than me. Also, he has great hair for a man in his late 60s, which of course makes everything he says more credible than if he were a bald dude.

Dutasteride fuks your brain even more. Betaboy gonna suffer lol.

 

[corza000]

In terms of what you can do to mitigate cognitive decline, you can check your genes, as we know quite well which genes are risk-factors for Alzheimer's, for example. You could then look into lifestyle interventions that reduce cognitive decline risks. In the opinion of this random dude on the internet, the book The Mindspan Diet is pretty good. The book has also been endorsed by people like George Church, who is probably more credible than me. Also, he has great hair for a man in his late 60s, which of course makes everything he says more credible than if he were a bald dude.

Thanks Regan. That is alarming the possible impacts on brain health. Is there not a test that can be done to check allopregnanolone levels? I haven’t noticed cognitive decline but then again I’m in my mid 30s. I just get the odd bouts of anxiety but always have. Hence why I’m investigating this (in a current bout of anxiety). Finasteride has been so good for me and I hope I don’t have to drop it but I don’t want to rob my future health.

 

[corza000]

By all means ask your doctor but the claim that finasteride may increase the rate of high gleason prostate cancers were recently (2019) retracted by the authors who originally raised the alarm after reviewing long term (~18 years) patient data.

Very good to know thank you. Now I just need to work out how to be on top of these newly discovered potential issues!

 

[DominoEffect]

I’ve been on finasteride for over 10 years now. It has been great for my hair during this time. I haven’t really lost any noticeable ground in this time and I initially had some grow back.

I remember reading a while back the impact finasteride can have on prostate, prostate cancer etc. It seemed mixed at the time. Given I’ve been on the medication for some time now is there something I can ask the doctor to check just to be on top of any risks? Is there a blood test worth doing to ensure finasteride isn’t having any negative impacts such as on the prostate.

I have no health concerns but I want to be proactive.

thanks

I thought finasteride prevented prostate cancer.

 

[DominoEffect]

The potential involvement of cholinergic system in finasteride induced cognitive dysfunction

Neurosteroids are known to exert diverse functions in the brain. 5α-reductase (5α-R), a rate-limiting enzyme involved in the biosynthesis of neuroster…

www.sciencedirect.com

here it says there's no linking finasteride with alzheimers/ dimentia.

 

[Regan]

The potential involvement of cholinergic system in finasteride induced cognitive dysfunction

Neurosteroids are known to exert diverse functions in the brain. 5α-reductase (5α-R), a rate-limiting enzyme involved in the biosynthesis of neuroster…

www.sciencedirect.com

here it says there's no linking finasteride with alzheimers/ dimentia.

Where does it say that? As far as I can tell this paper is a rat experiment where they have found that feeding finasteride to rats induces cognitive deficits.

 

[Feelsbadman.jpg]

I think a bigger risk of long-term finasteride use is probably the effects of allopregnanolone depletion on long-term brain health. Cognitive decline, risk of Alzheimer's and so forth. We can't really do trials on that stuff because we're talking about effects that unfold over many years, but it seems likely that cutting allopregnanolone should worsen age-related cognitive decline.

Dutasteride fuks your brain even more. Betaboy gonna suffer lol.

Do you have any studies to support this? All research I've seen points to the opposite.

Dutasteride protects against Parkinson's disease.

The 5α-reductase inhibitor Dutasteride but not Finasteride protects dopamine neurons in the MPTP mouse model of Parkinson's disease - PubMed

Finasteride and Dutasteride are 5α-reductase inhibitors used in the clinic to treat endocrine conditions and were recently found to modulate brain dopamine (DA) neurotransmission and motor behavior. We investigated if Finasteride and Dutasteride have a neuroprotective effect in...

pubmed.ncbi.nlm.nih.gov

Alzheimer's and Parkinson's have overlaps that suggest a common pathogenic disease mechanism.

Alzheimer's disease and Parkinson's disease: distinct entities or extremes of a spectrum of neurodegeneration? - PubMed

Alzheimer's disease (AD) and Parkinson's disease (PD) are generally considered to be separate and distinct disease entities. However, a considerable amount of evidence demonstrates that these disorders share common clinical and neuropathologic features and that overlap between the two conditions...

pubmed.ncbi.nlm.nih.gov

Myelin and Dutasteride

Oligodendrocytes create new myelin. DHT inhibits Oligodendrocytes in male and female rats. Progesterone increases Oligodendrocytes,
https://onlinelibrary.wiley.com/doi/10.1002/jnr.21943

Progesterone’s beneficial affect on Oligodendrocytes and myelination is due to activation of the progesterone receptor. Since allopregnanolone, a 5 alpha reduced metabolite of progesterone, binds to the GABA-A receptor, it is reasonable to conclude that inhibiting 5AR would not interfere with myelination and may even enhance it due to increased Progesterone levels.
https://www.ncbi.nlm.nih.gov/pmc/ar...erentiation into myelinating oligodendrocytes.

In the brain, allopregnanolone is thought to have no affect on progesterone receptors but instead acts as a positive modulator of the GABA-A receptor.
https://www.sciencedirect.com/topic...n, allopregnanolone is,of the GABA-A receptor.

 

[Regan]

Do you have any studies to support this? All research I've seen points to the opposite.

Dutasteride protects against Parkinson's disease.

The 5α-reductase inhibitor Dutasteride but not Finasteride protects dopamine neurons in the MPTP mouse model of Parkinson's disease - PubMed

Finasteride and Dutasteride are 5α-reductase inhibitors used in the clinic to treat endocrine conditions and were recently found to modulate brain dopamine (DA) neurotransmission and motor behavior. We investigated if Finasteride and Dutasteride have a neuroprotective effect in...

pubmed.ncbi.nlm.nih.gov

Alzheimer's and Parkinson's have overlaps that suggest a common pathogenic disease mechanism.

Alzheimer's disease and Parkinson's disease: distinct entities or extremes of a spectrum of neurodegeneration? - PubMed

Alzheimer's disease (AD) and Parkinson's disease (PD) are generally considered to be separate and distinct disease entities. However, a considerable amount of evidence demonstrates that these disorders share common clinical and neuropathologic features and that overlap between the two conditions...

pubmed.ncbi.nlm.nih.gov

Myelin and Dutasteride

Oligodendrocytes create new myelin. DHT inhibits Oligodendrocytes in male and female rats. Progesterone increases Oligodendrocytes,
https://onlinelibrary.wiley.com/doi/10.1002/jnr.21943

Progesterone’s beneficial affect on Oligodendrocytes and myelination is due to activation of the progesterone receptor. Since allopregnanolone, a 5 alpha reduced metabolite of progesterone, binds to the GABA-A receptor, it is reasonable to conclude that inhibiting 5AR would not interfere with myelination and may even enhance it due to increased Progesterone levels.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237628/#:~:text=Taken together, these results indicate,their differentiation into myelinating oligodendrocytes.

In the brain, allopregnanolone is thought to have no affect on progesterone receptors but instead acts as a positive modulator of the GABA-A receptor.
https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/allopregnanolone#:~:text=Sex Hormones, Mood, and Cognition&text=In the brain, allopregnanolone is,of the GABA-A receptor.

Hello FBM,

thanks for the studies, that is interesting!

This paper for example discusses research linking allopregnanolone and neurodegeneration, and provides evidence that dysregulation of allopregnanolone plays a role in the pathophysiology of Alzheimer's:

Allopregnanolone Levels are Reduced in Temporal Cortex in Patients with Alzheimer’s Disease Compared to Cognitively Intact Control Subjects - PMC (nih.gov)

Afaict there is a phase 2 trial planned for 2023 where allopregnanolone will be used as anti-Alzheimer's therapy:

Allopregnanolone Regenerative Therapeutic for Mild Alzheimer's Disease - Full Text View - ClinicalTrials.gov

After reading more on this topic, I have become more uncertain about the net effect of 5AR inhbition on neurodegeneration, because estrogen seems to have neuroprotective effects and is raised by 5AR blockers.

 

[BetaBoy]

Dutasteride fuks your brain even more. Betaboy gonna suffer lol.

5 years in and ain't brain dead just yet but yeah I don't buy into any of the current 5ar-gaba-steroid fear fad/hype. I mean if dutatsteride/finasteride is actually having any antagonistic/negative modulatory affects on GABAA shouldn't we all be experiencing sides consistent with synthetic GABAA antagonists (gabazine, bicuculline) like epilepsy and convulsions and they are supposedly weakly competitive for the receptor.

 

[losingbattle88]

5 years in and ain't brain dead just yet but yeah I don't buy into any of the current 5ar-gaba-steroid fear fad/hype. I mean if dutatsteride/finasteride is actually having any antagonistic/negative modulatory affects on GABAA shouldn't we all be experiencing sides consistent with synthetic GABAA antagonists (gabazine, bicuculline) like epilepsy and convulsions and they are supposedly weakly competitive for the receptor.

It was a joke friend.

5 years in and ain't brain dead just yet but yeah I don't buy into any of the current 5ar-gaba-steroid fear fad/hype. I mean if dutatsteride/finasteride is actually having any antagonistic/negative modulatory affects on GABAA shouldn't we all be experiencing sides consistent with synthetic GABAA antagonists (gabazine, bicuculline) like epilepsy and convulsions and they are supposedly weakly competitive for the receptor.

Ru bottom or top or vers?

 

[Feelsbadman.jpg]

Hello FBM,

thanks for the studies, that is interesting!

This paper for example discusses research linking allopregnanolone and neurodegeneration, and provides evidence that dysregulation of allopregnanolone plays a role in the pathophysiology of Alzheimer's:

Allopregnanolone Levels are Reduced in Temporal Cortex in Patients with Alzheimer’s Disease Compared to Cognitively Intact Control Subjects - PMC (nih.gov)

Dosage of Finasteride used on mice in this study:

Pretreatment with finasteride (50-300 mg/kg, i.p.) produced a dose-dependent (ED50, 146 mg/kg) reversal of the protective effects of progesterone (2 x ED50 dose = 188 mg/kg). That's also way more than was used in the Parkinson's mouse study.

For a 65 kg human, this is 3250 mg - 19500 mg. It was also administered intraperitoneally (injection into abdomen) not orally.

Whenever possible, we should look at human studies as rat/mice results often don't translate to human very well.

This study follows allopregnanolone levels in women taking dutasteride.

5α-Reductase Inhibition Prevents the Luteal Phase Increase in Plasma Allopregnanolone Levels and Mitigates Symptoms in Women with Premenstrual Dysphoric Disorder

Changes in neurosteroid levels during the luteal phase of the menstrual cycle may precipitate affective symptoms. To test this hypothesis, we stabilized neurosteroid levels by administering the 5α-reductase inhibitor dutasteride to block conversion ...

www.ncbi.nlm.nih.gov

Changes in neurosteroid levels during the luteal phase of the menstrual cycle may precipitate affective symptoms. To test this hypothesis, we stabilized neurosteroid levels by administering the 5α-reductase inhibitor dutasteride to block conversion of progesterone to its neurosteroid metabolite allopregnanolone in women with premenstrual dysphoric disorder (PMDD) and in asymptomatic control women. Sixteen women with prospectively confirmed PMDD and 16 control women participated in one of two separate randomized, double-blind, placebo-controlled, cross-over trials, each lasting three menstrual cycles. After one menstrual cycle of single-blind placebo, participants were randomized to receive, for the next two menstrual cycles, either double-blind placebo or dutasteride (low-dose 0.5 mg/day in the first eight PMDD and eight control women or high-dose 2.5 mg/day in the second group of women). All women completed the daily rating form (DRF) and were evaluated in clinic during the follicular and luteal phases of each menstrual cycle. Main outcome measures were the DRF symptoms of irritability, sadness, and anxiety. Analyses were performed with SAS PROC MIXED. In the low-dose group, no significant effect of dutasteride on PMDD symptoms was observed compared with placebo (ie, symptom cyclicity maintained), and plasma allopregnanolone levels increased in women with PMDD from follicular to the luteal phases, suggesting the absence of effect of the low-dose dutasteride on 5α-reductase. In contrast, the high-dose group experienced a statistically significant reduction in several core PMDD symptoms (ie, irritability, sadness, anxiety, food cravings, and bloating) on dutasteride compared with placebo. Dutasteride had no effect on mood in controls. Stabilization of allopregnanolone levels from the follicular to the luteal phase of the menstrual cycle by blocking the conversion of progesterone to its 5α-reduced neurosteroid metabolite mitigates symptoms in PMDD. These data provide preliminary support for the pathophysiologic relevance of neurosteroids in this condition.

After two months of .5 mg of dutasteride a day, allopregnanolone leves were still inreasing which means 5AR1 was not being inhibited in brain to any significant extent. I believe dutasteride at .5 mg ED reaches 60% of steady state levels after 1 month and 90% of steady state after 3 months. It seems unlikely that 5AR1 levels in the brain are impacted that much by the standard dose of .5 mg. Now at 2.5mg, it clearly does.

 

[BetaBoy]

It was a joke friend.

Really? I had no idea..

Ru bottom or top or vers?

I have no preference, the more degenerate the better.

 

[notoriousone]

Dosage of Finasteride used on mice in this study:

Pretreatment with finasteride (50-300 mg/kg, i.p.) produced a dose-dependent (ED50, 146 mg/kg) reversal of the protective effects of progesterone (2 x ED50 dose = 188 mg/kg). That's also way more than was used in the Parkinson's mouse study.

For a 65 kg human, this is 3250 mg - 19500 mg. It was also administered intraperitoneally (injection into abdomen) not orally.

Whenever possible, we should look at human studies as rat/mice results often don't translate to human very well.

This study follows allopregnanolone levels in women taking dutasteride.

5α-Reductase Inhibition Prevents the Luteal Phase Increase in Plasma Allopregnanolone Levels and Mitigates Symptoms in Women with Premenstrual Dysphoric Disorder

Changes in neurosteroid levels during the luteal phase of the menstrual cycle may precipitate affective symptoms. To test this hypothesis, we stabilized neurosteroid levels by administering the 5α-reductase inhibitor dutasteride to block conversion ...

www.ncbi.nlm.nih.gov

After two months of .5 mg of dutasteride a day, allopregnanolone leves were still inreasing which means 5AR1 was not being inhibited in brain to any significant extent. I believe dutasteride at .5 mg ED reaches 60% of steady state levels after 1 month and 90% of steady state after 3 months. It seems unlikely that 5AR1 levels in the brain are impacted that much by the standard dose of .5 mg. Now at 2.5mg, it clearly does.

This is fascinating.

As someone who got significant depression, anxiety, brain fog on .25mg of finasteride for 1 week (sides lasted 2.5 weeks), this might be a solution as I never suffered from any other side effect. I also tried Mozzarella et al .1mg topically (no reduction in serum DHT: https://sci-hub.se/https://doi.org/10.3109/09546639709160517) and got brain fog to a lesser degree. However, I concurrently did blood work and found no reduction in DHT with this method.

As far as I am aware dutasteride has a dose dependent half life. Which I thought meant if the amount circulating in the blood begins to go up over time regardless of dose, it will end up having the same net outcome over time whether it's .5mg or 2.5mg.

Would you assume that alloP is directly related to the brain fog?

 

[Mr. Slap Head]

Dutasteride fuks your brain even more. Betaboy gonna suffer lol.

He’s on incel regimen lol

 

[Feelsbadman.jpg]

As far as I am aware dutasteride has a dose dependent half life. Which I thought meant if the amount circulating in the blood begins to go up over time regardless of dose, it will end up having the same net outcome over time whether it's .5mg or 2.5mg.

No that's not correct. Steady state levels are the level of drug concentration in serum that a particular dosage schedule of said drug approaches but never reaches. It's a limit (calculus). Your body is constantly eliminating the drug. The elimination rate and the accumulation rate reach an equilibrium that gives an ever decreasing rate of accumulation that approaches a limit, the steady state drug level(Think about trying to walk from one side of a room to the other but each step you take is half the distance of the previous. You would approach the other side of the room, but never reach it.) This means that a .5 mg a day dosing schedule will never approach the steady state level of 2.5 mg a day.

Would you assume that alloP is directly related to the brain fog?

No, there is no research that shows this to my knowledge. The study I quoted shows that the 5AR1 reduction in the brain at .5 mg a day most likely minimal. This may even be beneficial, hence the patents for dutasteride as a preventative therapy for Parkinson's.

 

[Mr. Slap Head]

On top? You a topper? @losingbattle88