#32

I believe you are incorrect regarding finasteride/dutasteride not affecting neurosteroids. In rats neurosteroid levels are definitively impacted. There’s also rather strong evidence in humans. Please see Melcangi R.C., Santi D., Spezzano R., Grimoldi M., Tabacchi T., Fusco M.L. Neuroactive steroid levels and psychiatric and andrological features in post-finasteride patients. J Steroid Biochem Mol Biol. 2017;171:229–235.

Also Motofei I.G., Rowland D.L., Tampa M., Sarbu M.I., Mitran M.I., Mitran C.I. Finasteride and androgenic alopecia; from therapeutic options to medical implications. J Dermatolog Treat.

The latter study showed decreased P4, DHP, THP, as well as reductions in CSF DHT and T.

Alteration of neurosteroids fits with the not uncommon side effects of depression, sexual dysfunction, and apathy associated with 5-AR blockade.

5-AR blockade also decreases dopaminergic transmission in the brain and inhibits neurogenesis in the hippocampus in rat models.

Please see:
The post-finasteride syndrome: possible etiological mechanisms and symptoms. Leliefeld, et al. 2023.

The above review has an excellent explanation regarding the lipophilic nature of dutasteride/finasteride. Easy access across the blood barrier and inhibition of 5-AR1/AR2 which are both present in the brain. Also provides references regarding alteration of neurosteroids in humans and how these alterations can remain permanent despite d/c of the drug in both humans and rodents.

Metabolically we have evidence for insulin resistance, increased adiposity, bone loss, muscle loss, and reduced clearance of glucocorticoids. I can provide additional references at your preference.

Majority of the above are studies looking at PFS (post finasteride syndrome) which I fully admit the exact etiology is unknown. Nonetheless the studies provide ample evidence of the deleterious effects of 5-AR blockade with the potential for some of these effects to be permanent.

On the contrary, I’m not aware of any evidence that these drugs prolong human longevity or health span and the reduction in Gleason 6 prostate CA is of questionable clinical benefit given the standard of care for this type of prostate cancer is simply active surveillance.

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#33

Cialis is available in 2.5mg and 5mg in the US.

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#34

Humans are not rats. In humans, finasteride is a selective 5ar2 inhibitor while the brain predominantly contains 5ar1. Dutasteride may inhibit brain neurosteroids but despite that, the side effect profile appears to be the same as finasteride.

In the present study, we were able to provide strong biochemical evidence for the predominant, if not exclusive, activity of the 5α-reductase type 1 isozyme in the human brain by determining the inhibitor sensitivity of the in vitro reaction ( Figs. 1–3123). We could demonstrate the presence of 5α-reductase and colocalized 3α-HSD in the brain tissue biopsies of all patients under investigation

Finasteride is a potent inhibitor of human 5α-reductase type 2 (with an IC50 value of approximately 5 nmol/L) and a poor inhibitor of the type 1 isoform (with an IC50 value of approximately 500 nmol/L).

Characterization of the 5α-Reductase-3α-Hydroxysteroid Dehydrogenase Complex in the Human Brain1 | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic (oup.com)

Regarding post-finasteride syndrome, in 2022 the FDA did not find a causal connection between finasteride and persistent side effects.

The US Food and Drug Administration (FDA) had advised that the PFS petition “does not provide reasonable evidence” of a link to suicide, but in August 2022 added suicidal ideation (SI) and behaviour to the adverse reactions listed for finasteride. According to the FDA statement, the PFS petition “does not provide reasonable evidence” of a causal link between finasteride and persistent SD, depression, or suicide.

US Food and Drug Administration Warning Regarding Finasteride and Suicidal Ideation: What Should Urologists Know? - ScienceDirect

#35

Humans are not rats. In humans, finasteride is a selective 5ar2 inhibitor while the brain predominantly contains 5ar1. Dutasteride may inhibit brain neurosteroids but despite that, the side effect profile appears to be the same as finasteride.

You completely ignored the references I provided showing definitive changes in neurosteroids in both humans and rats.

Dutasteride seems like a no bainer for hair, prostate and skin health. Plus it stacks well with tadalafil for additional prostate protection and zero risk of side effects.

Your original post mentions dutasteride as a “no brainer” which is incongruent with your argument above regarding isoforms of 5-AR in the brain. Dutasteride inhibits AR1 and 2 so you are most definitely altering brain neurosteroids. This is also seen with Finasteride (despite AR2 selectivety) in the human studies I provided.

Regarding post-finasteride syndrome, in 2022 the FDA did not find a causal connection between finasteride and persistent side effects.

They didn’t find a connection, but they added suicidal ideation and behavioral changes to the side effect profile. They also recommend mental health screening prior to drug initiation.

I’ll let you interpret that as you wish.

You haven’t provided any evidence that neurosteroids aren’t affected by 5-AR blockade. Contrarily, I have provided animal and human evidence of the effect along with numerous other potential deleterious effects. I’m also interested in the proposed longevity/healthspan benefits as I see none?

I have no concern with you wanting to be on the medication as you have apparently researched it to your satisfaction, but representing it as a “no brainer” and “zero risk of side effects” on a public forum to people who may seek out the medication without fully understanding the potential risk involved is questionable.

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#36

The study/ies in question were done on people who allegedly suffered from PFS. They took blood samples from them and supposedly found changes that differed from “normal” human parameters. But since this was neither a randomized, placebo-controlled trial nor a in-vitro study done on human tissue, causality is impossible to prove. Selection bias is also a huge issue.

They didn’t find a connection, but they added suicidal ideation and behavioral changes to the side effect profile. They also recommend mental health screening prior to drug initiation.

It’s probably a good idea to keep hypochondrics from taking finasteride, dutasteride, ssri, accutane, statins, ozempic or any of the other drugs that are unjustifiedly villified by online grifters.

You haven’t provided any evidence that neurosteroids aren’t affected by 5-AR blockade.

I did. My study done on human brain simples offers a direct mechanistic evidence of finasteride not affecting brain neurosteroid production in humans. Unless you can find a randomized, placebo-controlled study of people with finasteride suffering from a higher incidence of mental side effects compared to placebo, this study is much stronger evidence than anything you have provided.

and “zero risk of side effects” on a public forum to people who may seek out the medication without fully understanding the potential risk involved is questionable.

I made that statement in the context of stacking dutasteride with tadalafil.

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#37

Guys - the issues around Dutasteride and Finasteride have been debated ad nauseam in this other thread, no need to re-debate them. Anyone interested in this discussion, please see here: Opinion about Finasteride and DHT

related: Can I take dutasteride with rapamycin - #5 by RapAdmin

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#38

I’ll digress at the request of admin, but if anyone is interested there’s a 2009 paper showing alteration of several hormones/neurosteroids pre-/post- finasteride in BPH patients. Duskova is the author.

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#39

I will stop posting about it too after clarifying the study you mentioned.
@RapAdmin If you are moving my post, please also move @Shady’s post.

You are refering to Finasteride treatment and neuroactive steroid formation - PubMed (nih.gov)

Which haircafe discusses in the following video, stating that serum allopregnanolone levels do not (necessarily) correlate with brain allopregnanolone levels.

The reason finasteride decreases serum allopregnanolone levels is very likely due to its inhibition of spine (and other) allopregnanolone production which is indeed affected by a selective 5ar2 inhibitor.

Allopregnanolone: An overview on its synthesis and effects - PMC (nih.gov)

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#40

@RPS, I started walking in a weighted vest several years ago and honestly feel like it’s one of the best things I’ve done for my body composition.

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#41

That’s great! I just paid $29.87 for 90 Tadalafil, 5mg with GoodRx. CostPlus would be ~$9.50 cheaper for the 90 days.

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#42

In the end, I decided to try Telmisartan first before Tadalafil (I couldn’t find a reasonable price from a reputable supplier in India, and I don’t want to deal with US prescriptions).

I’ll start at a dose of 20 mg of Telmisartan daily and then move up to 40 mg. My BP is in the 106-128 SBP range, so to be optimal, it can be a bit lower, and I do like the extra insulin sensitivity and mitochondrial boost it provides. Also, the price was quite reasonable at:

Telmisartan 40mg Tablet= 1.5 USD for 10 tablets (Sun Pharma)

Is there any reason I should not add this med to my longevity stack?

#43

Here’s a shortlist of medications often associated with promoting longevity:

  1. Rapamycin: A drug with anti-aging properties, showing promise in extending lifespan in various studies, though still under research.
  2. Metformin: Commonly used to treat type 2 diabetes, it shows promise in extending lifespan and delaying age-related diseases.
  3. Statins: Prescribed to lower cholesterol levels and reduce the risk of heart disease, potentially contributing to longevity.
  4. ACE Inhibitors: Medications used to treat high blood pressure and heart failure, with potential benefits for longevity and cardiovascular health.
  5. Resveratrol: Found in red wine and grapes, it’s believed to have anti-aging effects and promote longevity.

Always consult with a healthcare professional before starting any new medication or supplement regimen, especially for longevity purposes.

#44

I am not myself persuaded that Metformin should be on that list, nor Resveratrol. I think there is some evidence that they should not be.

Statins maybe. I have no idea about ACE inhibitors. (I was prescribed one about 20 years ago and stopped taking it after a few months).

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#45

Statins have shown promising results in reducing cardiovascular risk, which is linked to longevity, but their overall impact on lifespan is still debated. ACE inhibitors, like any medication, have potential benefits and risks that should be carefully considered based on individual health circumstances.
I understand your concern regarding the inclusion of Metformin and Resveratrol on the list. It’s essential to acknowledge that opinions on these medications’ efficacy for longevity vary among people.

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#46

@Elena did you use ChatGPT (or other Ai bot) for this? Resveratrol has been disproven many times by scientists, the only person really pushing it still is David Sinclair. If you are still positive on resveratrol, you may want to view this video: https://youtu.be/jOE7VsjuFP8?si=_E11cGX0WBED8K_q&t=450

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#47

I would argue that Metformin should definitely be on that list – for pre-diabetic and diabetic individuals. Getting your blood sugar into the ideal range should do wonders for longevity.

Unfortunately, I would argue that most older folk in the Western world are more likely to be pre-diabetic or diabetic than not. Therefore, it is a longevity drug for most.

However, empagliflozin would be even better.

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#48

I will agree only for pre-diabetic and diabetic individuals. Hence I do not think it is a general pro longevity drug even if many people may benefit from it.

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#49

I’m sure this is of no help!, but there is also something about telmisartan that can be supportive to kidneys. Perhaps this is only in those with existing disease.

Why do I know this? My cat has just been put on this for his kidney disease, and fwiw, my cat has better doctors than I do.

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#50

FWIW: I love metformin, but can only take 500mg/day because it causes a stomach gripe, in me, at higher levels. I will be switching to a timed-release version.
I agree with others that the resveratrol hype turned out to be untrue.
Metformin has been on several lists of compounds synergistic with rapamycin in prolonging life.

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#51

Despie me posting that warning on the risks of combining supplements, I have continued missing out on this. The allure of the great promise of each supp has been too great. I try to narrow my list but am there at around 15. Hope to work through each one for combination and side effects. Writing this to strengthen my resolve.

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