#21

Shit. Thank you for this.

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#22

ā€œTamsulosinā€
I am not promoting tamsulosin and I am always looking for the best meds to take.
Millions of men are taking tamsulosin.

ā€œEstimate: If we conservatively estimate that tamsulosin is prescribed to about 20-30% of men with BPH, this would translate to approximately 120 million to 180 million men worldwide taking tamsulosin for BPH.ā€

I have been taking tamsulosin for 25+ years with no negative side effects that I am aware of.

Alfuzosin might be the better choice. Next time I visit my PCP I will ask him about changing.
(For those who donā€™t want or canā€™t get a prescription, it is still another cheap drug available from India.)

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#23

I wonder why that paper didnā€™t do any comparisons with silodosin?

Also, couldnā€™t the lower ORs of the other alpha blockers just mean that tamsulosin has no neuroprotective action while the others do, as opposed to tamsulosin actually having a negative effect.

There is a major advantage to the more selective alpha blockers like tamsulosin and silodosin. Theyā€™re much less likely to have an effect on blood pressure and cause dizziness/syncope, which can have very dangerous/deadly sequelae, especially for the elderly (broken hips, head injuries, etc).

#24

The issue with long-term neurotoxicity is that itā€™s hard (if not impossible) to detect in typical clinical trials on humans and on animal or cell models as 1/ they take years if not decades to develop and 2/ our models for these diseases arenā€™t great.

So itā€™s only with well done emulated trials / longitudinal studies that we can detect signals pointing to detrimental or protective effects. The data started being collected in the 2000s-2010s so itā€™s only now that we can measure the long-term effects. Thatā€™s why weā€™re starting to discover many unexpected effects of existing drugs (whether positive like for telmisartan or negative for tamsulosin).

So here we have more than 3 papers
by different research teams from different research institutions in various countries published in the worldā€™s best journals all concluding that alternatives to tamsulosin should be preferred. Given that these alternatives are well studied and safe, thatā€™s more than enough for me to conclude.

Iā€™ll check. It might not be used often enough to detect signals.

Youā€™re correct: dutasteride and finasteride had the same ORs for AD and PD as tamsulosin so itā€™s probably alpha blockers and tadalafil being neuroprotective than tamsulosin being neurotoxic. However all drugs had a lower all cause mortality than tamsulosin. Thatā€™s actually the most concerning finding.

This recent meta analysis suggests tamsulosin is NOT safer than terazosin: Terazosin / doxazosin / alfuzosin may protect against dementia with Lewy bodies - #18 by adssx

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#25

@Davin8r actually check the table: they looked at silodosin and it is as bad as tamsulosin.

#26

Another older paper found a +15% lifespan extension on worms with doxazosin: A pharmacological network for lifespan extension in Caenorhabditis elegans 2013

Iā€™ll discuss with Ora Biomedical to reproduce these findings and also test alfuzosin as the study on humans found an even lower death rate among its users.

Doxazosin also identified as potentially neuroprotective in this other paper: Drug repurposing for neurodegenerative diseases using Zebrafish behavioral profiles 2024

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#27

So terazosin seems the overall winner with fairly low risk of side effects yet max potential neuroprotection.

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#28

Terazosin or tadalafil. Although ideally weā€™d like research papers to look at a composite event such as ā€œdeath or AD or PDā€. Terazosin might seem better at neuroprotection than alfuzosin because alfuzosin patients donā€™t die, live longer and therefore are more likely to be diagnosed with PD or AD?

#29

I meant within the alpha-blocker meds. One could take both terazosin and tadalafil together, since they have different mechanisms of action, as long as blood pressure and side effects are manageable.

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#30

As theyā€™re both approved for BPH, based on this paper alone why would one prefer terazosin to tadalafil? (just curious, based on mechanistic understanding, terazosin looks better to me)

#31

Based on a quick literature review, apparently tadalafil works just as well as alpha blockers for BPH and has the added benefit of improving sexual dysfunction. However, this was not my experience at all when I had BPH because tadalafil did absolutely nothing for my urinary symptoms while alpha blockers helped quite a bit (for a while, until symptoms got bad enough for surgical fix). This was also the ā€œreal worldā€ experience of every urologist I saw over the years (alpha blockers>>tadalafil).

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#32

Interesting so the comparison of tadalafil to alpha blockers in the above paper might be misleading. If what you say is true then urologists would probably prescribe alpha blockers to patients with more advanced BPH and tadalafil to those with mild BPH and/or erectile dysfunction.

So one more point for terazosinā€¦

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#33

I donā€™t know. Not sure how to explain or trust my ā€œn of 1ā€ experience in the context of the actual published experimental studies:

And of course, maybe the urologists I saw over the years were just sticking with old prescribing habits rather than keeping up with the data.

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#34

First article from Egypt: not high quality. Second one says ā€œTadalafil is superior to tamsulosin in treating LUTS suggestive of BPH when associated with erectile dysfunction (ED).ā€

Do we have high quality meta reviews or large trials comparing tadalafil vs tamsulosin vs terazosin for BPH?

#35

The 2023 American guidelines and 2024 European guidelines seem to consider that alpha blockers and tadalafil are equivalent and could or even should be combined :man_shrugging:

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#36

I asked a Parkinsonā€™s disease researcher their view on tadalafil. They think that (contrary to terazosin) the case of PDE5 inhibitors as neuroprotective is not very compelling:

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#37

Another paper (by the same Iowa team already cited above) pointing towards low-dose terazosin being better than high dose: A model for stimulation of enzyme activity by a competitive inhibitor based on the interaction of terazosin and phosphoglycerate kinase 1 2024

At low concentrations, TZ binding circumvents slow product release and increases the rate of enzymatic phosphotransfer. However, at high concentrations, TZ inhibits PGK1 activity. The model explains stimulation of enzyme activity by a competitive inhibitor and the biphasic doseā€“response relationship for TZ and PGK1 activity. By providing a plausible mechanism for interactions between TZ and PGK1, these findings may aid development of TZ or other agents as potential therapeutics for neurodegenerative diseases.
This model also has practical implications. First, the model supports the conclusion that TZ enhancement of PGK1 activity and the biphasic doseā€“response relationship are inherent properties of the interaction between the enzyme and TZ. Second, by providing a plausible mechanism for the biphasic TZ doseā€“response observed in cells and animals, it highlights that in vivo dosing will require careful attention to beneficially enhance energy metabolism. Thus, clinical testing of TZ as an agent that may slow or prevent neurodegeneration may require knowledge of the relationship between the blood TZ concentration and the position on the TZ doseā€“response. Pilot data suggest that measurements of the effect of TZ on ATP levels in blood or the brain might suffice (9). Third, as a potential therapeutic for neurodegenerative disease, TZ has the limitation that it also inhibits Ī±l-adrenergic receptors and can thus predispose to orthostatic hypotension (25). Development of novel agents that stimulate PGK1 activity but lack Ī±l-adrenergic receptor antagonism will benefit from the understanding provided by this model. Thus, this work may provide a foundation for additional experimentation and development.

#38

I found this article on terazosin interesting;

I use tadalafil 5mg for Ā²BPH prevention and it gives me a systolic BP of 100. If I had a higher value, I would consider adding low dose terazosin

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#39

Do we have data on the use of tadalafil for BPH prevention? Is it better than terazosin? Could a low dose combination be the best (1 mg terazosin + 1 mg tadalafil?)

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#40

As far as I know, there is no data for prevention, but there is some data for relieving the symptoms (LUTS).

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