Does Setipiprant Need To Be Used With An Anti-androgen?

[mowingdown]

How long were you on finasteride for? And you crashed after quitting or while still on it?

I crashed while on it. I tried to power through but it was quickly apparent that things were just getting worse. I got off as fast as possible and I luckily didn't see a greater crash, but it took over a year to get back to baseline. I'm thankful I'm at where I was pre-finasteride, but it was a really trying year. On the plus side, I know exactly what to look for when delving into these other drugs in terms of side effects. At the first sign of them, I'm out. This Lyphar Setipiprant I received is extremely questionable considering the brain fog I've had for the first 3 days. It seems it's either very impure, or they are cutting it with an anti-androgen. I'm thinking I may send it off to get tested, because by all accounts, Seti shouldn't be producing these side effects.

 

[strandman]

I crashed while on it. I tried to power through but it was quickly apparent that things were just getting worse. I got off as fast as possible and I luckily didn't see a greater crash, but it took over a year to get back to baseline. I'm thankful I'm at where I was pre-finasteride, but it was a really trying year. On the plus side, I know exactly what to look for when delving into these other drugs in terms of side effects. At the first sign of them, I'm out. This Lyphar Setipiprant I received is extremely questionable considering the brain fog I've had for the first 3 days. It seems it's either very impure, or they are cutting it with an anti-androgen. I'm thinking I may send it off to get tested, because by all accounts, Seti shouldn't be producing these side effects.

That’s unfortunate to hear about Lyphar. I was planning to order a large quantity of seti from them soon. I probably won’t now.

 

[IdealForehead]

I crashed while on it. I tried to power through but it was quickly apparent that things were just getting worse. I got off as fast as possible and I luckily didn't see a greater crash, but it took over a year to get back to baseline. I'm thankful I'm at where I was pre-finasteride, but it was a really trying year. On the plus side, I know exactly what to look for when delving into these other drugs in terms of side effects. At the first sign of them, I'm out. This Lyphar Setipiprant I received is extremely questionable considering the brain fog I've had for the first 3 days. It seems it's either very impure, or they are cutting it with an anti-androgen. I'm thinking I may send it off to get tested, because by all accounts, Seti shouldn't be producing these side effects.

I would be very careful about trying to guess what side effects seti should or shouldn't be producing.

PGD synthetase, the enzyme that creates PGD2, is most highly abundant in rat brains and spinal cords. There is dramatically more of it in the brain and spine than anywhere else in the body:

It's expressed pretty evenly throughout every area of the brain:

What does all this PGD2 do in the brain? No one knows.

Furthermore, the very same receptor that seti blocks is involved in mood related functions of rats:

CRTH2, a prostaglandin D2 receptor, mediates depression-related behavior in mice.

Depression is a complex neuropsychiatric disorder with an unclear molecular etiology. Inflammatory cytokines and molecular intermediates (including prostaglandins) are suggested to be involved in depression; however, the roles of prostaglandins and their respective receptors are largely unknown in depression. Using genetic and pharmacological approaches, we show here that chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2), a second receptor for prostaglandin D2 (PGD2), mediates depression-related behavior in mice. CRTH2-deficient (CRTH2(-/-)) mice showed antidepressant-like activity in a chronic corticosterone treatment-induced depression. Consistent with this observation, the pharmacological inhibition of CRTH2 via the clinically available drug ramatroban also rescued abnormal social interaction and depression-related behavior in well-established models, including chronic corticosterone-, lipopolysaccharide-, and tumor-induced pathologically relevant depression models. Importantly, chronic stress via corticosterone treatment increased mRNA levels in PGD2-producing enzymes, such as cyclooxygenase-2 and lipocalin-type PGD2 synthase, in the brain. Furthermore, the activity of the hippocampal noradrenergic system but not the dopaminergic or serotonergic systems was increased in CRTH2(-/-) mice. Together with the observation that untreated CRTH2(-/-) mice showed antidepressant-like activity in the forced swim test, these results provide evidence that central CRTH2-mediated signaling is critically involved in depression-related behavior.

https://www.ncbi.nlm.nih.gov/pubmed/25698598
​

In that study, they found mice that don't have this receptor for PGD2 were protected against depression. What will blocking it do to human moods?

This is such an incredibly experimental compound and pathway to manipulate. The truth is you really have absolutely no idea what you're doing to your brain with it.

I think these compounds would be easier to rationalize if they were topical. But seti makes a terrible topical from what I understand. I've heard fevi makes a better topical. Is that true? If so, why aren't people trying to do that instead? Why nuke the PGD2 in your brain with massive oral doses?

 

[westonci]

Several people have claimed that setipiprant gave them full maintenance without the need for any anti-androgens involved. What is your opinion on this? Does anyone here use Seti with or without an AA? What has your experience been? I’m very interested in high dose oral seti for complete maintenance as there are little to no sides, especially sexual ones. Thanks for any information provided.

https://i.imgur.com/m8otWQI.png

Think of this: finasteride in the end has the same effect of seti but does it in a different way. finasteride blocks conversion of DHT, less DHT attaches to follicle so then downstream there is less PGD2 which attacks the follicle. Seti works by competing with PGD2 at the receptor so there is less PGD2 attacking the follicle. In the end both result in less PGD2 hurting the follicle.

It's an established fact that for finasteride results are completely different for everyone. Some get maintenance, some get a little regrowth, some get crazy regrowth, and some don't get anything at all. Since as I said before in the end both end up reducing PGD2 I can't see why seti couldnt have a range of results for users like finasteride does.

 

[westonci]

I would be very careful about trying to guess what side effects seti should or shouldn't be producing.

PGD synthetase, the enzyme that creates PGD2, is most highly abundant in rat brains and spinal cords. There is dramatically more of it in the brain and spine than anywhere else in the body:

View attachment 85843

It's expressed pretty evenly throughout every area of the brain:

View attachment 85844


What does all this PGD2 do in the brain? No one knows.

Furthermore, the very same receptor that seti blocks is involved in mood related functions of rats:

CRTH2, a prostaglandin D2 receptor, mediates depression-related behavior in mice.

Depression is a complex neuropsychiatric disorder with an unclear molecular etiology. Inflammatory cytokines and molecular intermediates (including prostaglandins) are suggested to be involved in depression; however, the roles of prostaglandins and their respective receptors are largely unknown in depression. Using genetic and pharmacological approaches, we show here that chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2), a second receptor for prostaglandin D2 (PGD2), mediates depression-related behavior in mice. CRTH2-deficient (CRTH2(-/-)) mice showed antidepressant-like activity in a chronic corticosterone treatment-induced depression. Consistent with this observation, the pharmacological inhibition of CRTH2 via the clinically available drug ramatroban also rescued abnormal social interaction and depression-related behavior in well-established models, including chronic corticosterone-, lipopolysaccharide-, and tumor-induced pathologically relevant depression models. Importantly, chronic stress via corticosterone treatment increased mRNA levels in PGD2-producing enzymes, such as cyclooxygenase-2 and lipocalin-type PGD2 synthase, in the brain. Furthermore, the activity of the hippocampal noradrenergic system but not the dopaminergic or serotonergic systems was increased in CRTH2(-/-) mice. Together with the observation that untreated CRTH2(-/-) mice showed antidepressant-like activity in the forced swim test, these results provide evidence that central CRTH2-mediated signaling is critically involved in depression-related behavior.

https://www.ncbi.nlm.nih.gov/pubmed/25698598
​

In that study, they found mice that don't have this receptor for PGD2 were protected against depression. What will blocking it do to human moods?

This is such an incredibly experimental compound and pathway to manipulate. The truth is you really have absolutely no idea what you're doing to your brain with it.

I think these compounds would be easier to rationalize if they were topical. But seti makes a terrible topical from what I understand. I've heard fevi makes a better topical. Is that true? If so, why aren't people trying to do that instead? Why nuke the PGD2 in your brain with massive oral doses?

Here is a more recent study on CRTH2

https://www.docdroid.net/qAxmyM7/1-s20-s1098882317300151-main.pdf#page=5

 

[IdealForehead]

Here is a more recent study on CRTH2

https://www.docdroid.net/qAxmyM7/1-s20-s1098882317300151-main.pdf#page=5

The "Nervous system" section of that article was glaringly empty of any meaningful content, which is not any fault of the author, but just highlights what I'm saying. We know the enzyme that makes PGD2 at least in rats is massively made in the brain and spinal cord. More than any other tissue of the body. But why? What is all that PGD2 doing in there?

It's an interesting puzzle but I don't think we have enough science to put it together yet.

 

[HairSuit]

The "Nervous system" section of that article was glaringly empty of any meaningful content, which is not any fault of the author, but just highlights what I'm saying. We know the enzyme that makes PGD2 at least in rats is massively made in the brain and spinal cord. More than any other tissue of the body. But why? What is all that PGD2 doing in there?

It's an interesting puzzle but I don't think we have enough science to put it together yet.

@IdealForehead, foregive my ignorance, but doesn’t Ceti work on the PGD2 angle as well? You’ve peaked my interest with Seti. I have used it successfully for three months and had great maintenance from it, but I also don’t want to run into the same situation as I did with finasteride, down the road. It’s been a nightmare. Why are you so against Seti, yet pro Cetirizine, if they both work on the same angle?

 

[IdealForehead]

@IdealForehead, foregive my ignorance, but doesn’t Ceti work on the PGD2 angle as well? You’ve peaked my interest with Seti. I have used it successfully for three months and had great maintenance from it, but I also don’t want to run into the same situation as I did with finasteride, down the road. It’s been a nightmare. Why are you so against Seti, yet pro Cetirizine, if they both work on the same angle?

Cetirizine does not work on PGD2 directly. ItI is a h1 histamine receptor antagonist. The first such antihistamine was developed in 1933! We have had dozens of antihistamines with plenty of long term safety data. Antihistamines have been around longer than many of our grandparents.

But in fact it is partly due to the long term risks of antihistamines that i comment on the potential brain risks of PGD2 inhibition. Long term antihistamines use, particularly with the older generations of antihistamines, is linked to dementia:

https://lifespa.com/long-term-use-of-antihistamines-linked-to-dementia/

Now desloratadine which i use is a much cleaner antihistamine with a likely lower risk but it is probably still there. I also use it topically in small doses which should reduce the risk further.

By contrast these PGD2 blockers are brand new, have completely unknown long term neurological effects, and are required to be taken in massive oral doses to work on the hair. I'm not exactly "against" them. I'm just pointing these elements out and saying be aware you are guinea pigging yourself for a completely unknown type of drug here with unknown brain risks if you hop on this early.

Assuming it's perfectly safe because "its not finasteride" and "finasteride is poison" is not necessarily going to be correct long term. At least we already have decades of data on finasteride.

 

[jared garnith]

I would be very careful about trying to guess what side effects seti should or shouldn't be producing.

PGD synthetase, the enzyme that creates PGD2, is most highly abundant in rat brains and spinal cords. There is dramatically more of it in the brain and spine than anywhere else in the body:

View attachment 85843

It's expressed pretty evenly throughout every area of the brain:

View attachment 85844


What does all this PGD2 do in the brain? No one knows.

Furthermore, the very same receptor that seti blocks is involved in mood related functions of rats:

CRTH2, a prostaglandin D2 receptor, mediates depression-related behavior in mice.

Depression is a complex neuropsychiatric disorder with an unclear molecular etiology. Inflammatory cytokines and molecular intermediates (including prostaglandins) are suggested to be involved in depression; however, the roles of prostaglandins and their respective receptors are largely unknown in depression. Using genetic and pharmacological approaches, we show here that chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2), a second receptor for prostaglandin D2 (PGD2), mediates depression-related behavior in mice. CRTH2-deficient (CRTH2(-/-)) mice showed antidepressant-like activity in a chronic corticosterone treatment-induced depression. Consistent with this observation, the pharmacological inhibition of CRTH2 via the clinically available drug ramatroban also rescued abnormal social interaction and depression-related behavior in well-established models, including chronic corticosterone-, lipopolysaccharide-, and tumor-induced pathologically relevant depression models. Importantly, chronic stress via corticosterone treatment increased mRNA levels in PGD2-producing enzymes, such as cyclooxygenase-2 and lipocalin-type PGD2 synthase, in the brain. Furthermore, the activity of the hippocampal noradrenergic system but not the dopaminergic or serotonergic systems was increased in CRTH2(-/-) mice. Together with the observation that untreated CRTH2(-/-) mice showed antidepressant-like activity in the forced swim test, these results provide evidence that central CRTH2-mediated signaling is critically involved in depression-related behavior.

https://www.ncbi.nlm.nih.gov/pubmed/25698598
​

In that study, they found mice that don't have this receptor for PGD2 were protected against depression. What will blocking it do to human moods?

This is such an incredibly experimental compound and pathway to manipulate. The truth is you really have absolutely no idea what you're doing to your brain with it.

I think these compounds would be easier to rationalize if they were topical. But seti makes a terrible topical from what I understand. I've heard fevi makes a better topical. Is that true? If so, why aren't people trying to do that instead? Why nuke the PGD2 in your brain with massive oral doses?

why does seti make a terrible topical?

 

[Afro_Vacancy]

@IdealForehead is running a scientific clinic, as usual.

An old poster here who also had quite a lot of scientific knowledge of hairloss was @Swoop. He departed sometime back. He too was skeptical of the prostaglandin angle but for different reasons. IIRC, he said that many drugs which had been PGD2 antagonists had been tested over prior decades for different purposes, and that hair growth did not get reported as a side effect, which is a common path to use-discovery for lots of other drugs. Thus, the expected benefit is modest at best. He rejected the angle that PGD2 damage was downstream of finasteride and that it would this yield the same benefits with fewer side effects. He also pointed out that just because bald men have more PGD2 doesn't mean that the PGD2 is what kills hair -- an obvious point that is missed by most people.

Quite a few people tried seti on these boards. There was a huge thread a while back. For the most part they reported either no effect, decrease in itch (a good sign?), and insomnia. I think that the insomnia is a really bad sign. I trust those reports, and if decreased itch and insomnia don't get reported in the clinical trial I will have less respect for them.

The prostaglandin theory popular on the internet makes a testable prediction: that people on seti should derive no additional benefit from adding in finasteride. We should know within a year or two if that's the case.

 

[Arrade]

I took .25 for 2 days then .1 for 2 days then stopped yesterday. I know it’s not much of a wean but I really did not want to take it anymore. I’m confident that because I was only on it for two months and barely experienced any side effects in that period, that I won’t crash. I purchased a month’s supply of Clomid and Tamoxifen just in case. Do you still think I should get back on and slowly wean instead, maybe 0.1mg per day for awhile?

Have you used tamoxifen before? It's really toxic to brain cells, it acts like an estrogen agonist, which is why some people get mental sides to the point of being suicidal. PCT drugs are chemo drugs that cause chemo brain, personally I would ride it out naturally
If you're worried about libido try a decent horny goat weed, it actually works

 

[strandman]

Have you used tamoxifen before? It's really toxic to brain cells, it acts like an estrogen agonist, which is why some people get mental sides to the point of being suicidal. PCT drugs are chemo drugs that cause chemo brain, personally I would ride it out naturally
If you're worried about libido try a decent horny goat weed, it actually works

Oh thanks I didn’t know that. I’m not gonna use it now

 

[westonci]

The prostaglandin theory popular on the internet makes a testable prediction: that people on seti should derive no additional benefit from adding in finasteride. We should know within a year or two if that's the case.

I disagree, for those that dont mind taking finasteride or dutasteride, adding seti would work syngergistically. Your blocking PGD2 from being made via finasteride as well as blocking the receptor that PGD2 attaches to (CRTH2) with Seti

Again lets wait untill June to confirm. Dont expect much growth from Seti, its more for maintenance.

 

[IdealForehead]

why does seti make a terrible topical?

Perhaps actually it doesn't. In truth I don't know, since we have no studies on it. We have threads on this site from guys that started using seti topically since 2016. Over two years now. I don't know how many people have continued to use it or had long term success. We don't see many people posting about it. Most of the seti supporters at least on this site seem to be moving into the "it needs to be taken orally to really work" camp. Which could be telling about the topical vs. oral routes. Maybe topical was too difficult to get success with.

Partly this may be that seti has poor solubility in most agents. This means it requires unusual solvents to get good solutions. For example, "here is vehicle that can hold 5% seti: 50% ethanol, 30% polysorbate 80, 20% Dimethyl Isosorbide (DMI) and just a drop of DMSO." (ref)

50% ethanol is way too much in my opinion - this level of alcohol in any vehicle can be potentially toxic directly to the skin and hair. I try to keep alcohol at 30% or less. I am also not keen on DMSO as it is anti-collagen, but a drop is no big deal. Perhaps there are better solutions that can be made still than this - it's not something I've researched.

If I were forced to become a seti/fevi guinea pig, I would absolutely prefer to do it topically than orally. I think these drugs, if they work, make more sense topically than orally. There is no reason to intentionally interfere with all the PGD2 in the brain. At least with topical, you can use less, and hopefully focus it at the scalp. (Same reason I use daro and desloratadine topically.)

 

[jared garnith]

Thanks for the thoughtful

Perhaps actually it doesn't. In truth I don't know, since we have no studies on it. We have threads on this site from guys that started using seti topically since 2016. Over two years now. I don't know how many people have continued to use it or had long term success. We don't see many people posting about it. Most of the seti supporters at least on this site seem to be moving into the "it needs to be taken orally to really work" camp. Which could be telling about the topical vs. oral routes. Maybe topical was too difficult to get success with.

Partly this may be that seti has poor solubility in most agents. This means it requires unusual solvents to get good solutions. For example, "here is vehicle that can hold 5% seti: 50% ethanol, 30% polysorbate 80, 20% Dimethyl Isosorbide (DMI) and just a drop of DMSO." (ref)

50% ethanol is way too much in my opinion - this level of alcohol in any vehicle can be potentially toxic directly to the skin and hair. I try to keep alcohol at 30% or less. I am also not keen on DMSO as it is anti-collagen, but a drop is no big deal. Perhaps there are better solutions that can be made still than this - it's not something I've researched.

If I were forced to become a seti/fevi guinea pig, I would absolutely prefer to do it topically than orally. I think these drugs, if they work, make more sense topically than orally. There is no reason to intentionally interfere with all the PGD2 in the brain. At least with topical, you can use less, and hopefully focus it at the scalp. (Same reason I use daro and desloratadine topically.)

Thanks for the thoughtful response, I think I'm going to go on the topical seti route as I'm running out of options and I hear salted seti is much more easily mixed in a vehicle and people are putting it in stemox, so maybe the results didn't come out too pleasing since the solutions then were at around 5% and I've heard some people using around 30% who have had some succes , still I am a bit weary since it seems like most chemicals in our body are here for a reason of course and play roles in processes we might not even be aware of yet.

 

[talesofdahustle]

I’m using Zhe Chems. From everything I’ve read, it shouldn’t cause brain fog, the same way that finasteride does, as it shouldn’t affect the hormone profile, but who knows. I had persisting brain fog from finasteride already, so..... the whole chicken or the egg argument comes into play.

@strandman i haven’t tried those yet. Been following some stuff on another website. It seems like what finasteride does in our bodies that it messes with progesterone receptors amongst a bunch of other things, which cascades into brain and sexual hormones. Trying to avoid anymore drugs to fix it. Going to do a bunch of liver flushes and fasting. Did a hair test to try and get my minerals and nutrients back in balance. Hoping that helps. Did clinic have a positive effect for you?

hackstasis gbold arl hair test ?

 

[jonnywalker93]

Just my two cents here as this is the first proper discussion about seti brain fog.

From my own experience I can tell that Seti makes you feel completely zoned out. Oral intake turned out to be accompanied by heavy brain fog during the day. Felt like my brain gets squeezed and a weird numb feeling occurred over the day. I ordered mine from Lyphar. I then tried topical seti from Kane and even that gave me headaches and slight brain fog after only one application.

Totally agree with IdealForehead on this issue, just because it's not Finasteride and there are studies that do not show these mental side effects, it doesn't mean that they are impossible to get. Don't want to be negative here (I would accept the risk and continue with seti if the side effects weren't there), but you need to look at these new drugs from every angle....

Currently, I am contemplating trying cet or deslo to see how I respond to these kind of drugs. Waiting for my H&W topical finasteride, but not very confident that it will help me...

 

[Nextjohns]

Just my two cents here as this is the first proper discussion about seti brain fog.

From my own experience I can tell that Seti makes you feel completely zoned out. Oral intake turned out to be accompanied by heavy brain fog during the day. Felt like my brain gets squeezed and a weird numb feeling occurred over the day. I ordered mine from Lyphar. I then tried topical seti from Kane and even that gave me headaches and slight brain fog after only one application.

Totally agree with IdealForehead on this issue, just because it's not Finasteride and there are studies that do not show these mental side effects, it doesn't mean that they are impossible to get. Don't want to be negative here (I would accept the risk and continue with seti if the side effects weren't there), but you need to look at these new drugs from every angle....

Currently, I am contemplating trying cet or deslo to see how I respond to these kind of drugs. Waiting for my H&W topical finasteride, but not very confident that it will help me...

How much are you taking? I'm getting no sides at 400mg a day. I take it at 5-6pm though. So maybe I'm sleeping through it lol.

Finesteride literally made me forget things, among other sides I eventually had to stop it before it crashed me.

 

[allthegains]

Just my two cents here as this is the first proper discussion about seti brain fog.

From my own experience I can tell that Seti makes you feel completely zoned out. Oral intake turned out to be accompanied by heavy brain fog during the day. Felt like my brain gets squeezed and a weird numb feeling occurred over the day. I ordered mine from Lyphar. I then tried topical seti from Kane and even that gave me headaches and slight brain fog after only one application.

Totally agree with IdealForehead on this issue, just because it's not Finasteride and there are studies that do not show these mental side effects, it doesn't mean that they are impossible to get. Don't want to be negative here (I would accept the risk and continue with seti if the side effects weren't there), but you need to look at these new drugs from every angle....

Currently, I am contemplating trying cet or deslo to see how I respond to these kind of drugs. Waiting for my H&W topical finasteride, but not very confident that it will help me...

wow, this is extremely discouraging.

Could it be that this is something related to Lyphar's SETI? I haven't seen anyone using Zhechem's SETI report these side effects. And I know 3 guys in a private group using it

 

[jonnywalker93]

wow, this is extremely discouraging.

Could it be that this is something related to Lyphar's SETI? I haven't seen anyone using Zhechem's SETI report these side effects. And I know 3 guys in a private group using it

I applied kane's seti topically and it gave me similar sides...