OC buy

[Swooping]

Maybe, maybe not. I have seen lots of threads about how RU has crazy ups and downs, and I think any receptor blocker has the capacity to upregulate that receptor and really make it more sensitive. Until I see research that tells me why this wouldn't happen, then Im not convinced. You could be right, but Ive yet to hear from one guy who says that RU has saved his hair in the long run, like many years. Im also skeptical of the fact that it was never approved, and Im thinking it was maybe due to the possibility that it doesn't do anyone any good. Word from the people who researched it, or positive reviews from anyone long term would ease my mind a lot.

But so far I see a lot of people who did great on it, only to shed massive amounts when they stopped or somewhere along their treatment.

What you think doesn't really matter. It isn't scientifically proven. Do you see that finasteride upregulates or makes the 5 alpha reductase 2 enzyme more sensitive over time? No it doesn't, because that would mean DHT levels would increase again and you would need to increase the dosage. And obviously people are going to shed when they stop RU, you need to use it continuously just as with finasteride.

You already project the PGD2 angle as it's going to be the best maintenance treatment which will be side effect free though. Based on what? On 3-4 guys on a forum who claim so? Some people didn't notice anything at all, I saw also some claims of OC bringing up insomnia and breathlessness, what about that?

Anyway it's a good thing you are proactive. Let's hope the PGD2 angle will indeed be "fruitful".

[KO1]

Swooping - is there any advantage, apart from side effects, to inhibit CRTH2 directly versus inhibiting DHT? Since PGD2 is downstream of the androgen pathway, shouldn't fin already be taking care of this?


What is interesting to me is that in the original Cots/Garza study, they looked closely at PGD2, they noted that mice that express PGD2 bald, but they never actually tried an inhibitor on one of those mice. However, Kythera is saying that pgd2 inhibitors did reverse miniaturization in in vitro follicles.

[Hairismylife]

No need to argue. Use both RU and OC. This should halt hairloss completely.

[Swooping]

Swooping - is there any advantage, apart from side effects, to inhibit CRTH2 directly versus inhibiting DHT? Since PGD2 is downstream of the androgen pathway, shouldn't fin already be taking care of this?


What is interesting to me is that in the original Cots/Garza study, they looked closely at PGD2, they noted that mice that express PGD2 bald, but they never actually tried an inhibitor on one of those mice. However, Kythera is saying that pgd2 inhibitors did reverse miniaturization in in vitro follicles.

Good point. Androgens are a prerequisite for AGA obviously. I don't think there is any advantage though as you mention because it lays downstream. If we castrate someone, that person is AGA free. Meaning that even if PGD2 would stay overexpressed in a castrated person it doesn't matter. Cause we see from evidence that AGA doesn't progress in a castrated person.

However in the hypothesis that PGD2 would stay overexpressed in a castrated person in the scalp, calibrating these levels could reverse miniaturization. This is obviously a hypothesis that is plausible. If you ask my opinion it is highly damn unlikely though. It's just too simple for me.

If you look at the model here above Garza argues that PTGDS the enzyme responsible for PGD2 synthase is directly hormone driven in the scalp. Therefore they think that the PGD2 angle is a big player and functions highly upstream of the cascade. I don't think so and would argue that it would lay more downstream.

However using compounds can also yield for cross-talk between pathways which can be interesting. It's complex. Garza for example states that PGE2 is known to be a procarcogenic signal and refers to literature. I read those studies and indeed in many tissue PGE2 can have impact on other pathways which I think for example are interesting. For example he refers to this one; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759608/.

In this study we investigated the mechanisms by which PGE2 stimulates murine keratinocyte proliferation using in vitro and in vivo models. Our data suggest the mechanisms involve PGE2-induced phosphorylation of EGFR and activation of Ras-MAPKs, PI3-K/Akt and cAMP/PKA signaling pathways. Furthermore, our data revealed that PGE2 increased binding of CREB, NF-κB and AP-1 to the promoters of cyclin D1 and VEGF.

Hyperactivated AKT can for example promote cell profileration by downregulating P27 and upregulating cyclin d1 as you can read in the study. Upregation of cyclin d1 can yield to possibly other reactions like downregulation of P53. It is these players that can have way a bigger impact in my opinion. Using estrogen can upregulate cyclin d1 also for example and has impact on the MAPK pathways too etc.

Nonetheless a full cure in a drug form would be a miracle in my opinion, highly unlikely for a pretty long time time seeing the implications in AGA.

[Hairismylife]

Good point. Androgens are a prerequisite for AGA obviously. I don't think there is any advantage though as you mention because it lays downstream. If we castrate someone, that person is AGA free. Meaning that even if PGD2 would stay overexpressed in a castrated person it doesn't matter. Cause we see from evidence that AGA doesn't progress in a castrated person.

However in the hypothesis that PGD2 would stay overexpressed in a castrated person in the scalp, calibrating these levels could reverse miniaturization. This is obviously a hypothesis that is plausible. If you ask my opinion it is highly damn unlikely though. It's just too simple for me.

If you look at the model here above Garza argues that PTGDS the enzyme responsible for PGD2 synthase is directly hormone driven in the scalp. Therefore they think that the PGD2 angle is a big player and functions highly upstream of the cascade. I don't think so and would argue that it would lay more downstream.

However using compounds can also yield for cross-talk between pathways which can be interesting. It's complex. Garza for example states that PGE2 is known to be a procarcogenic signal and refers to literature. I read those studies and indeed in many tissue PGE2 can have impact on other pathways which I think for example are interesting. For example he refers to this one; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759608/.



Hyperactivated AKT can for example promote cell profileration by downregulating P27 and upregulating cyclin d1 as you can read in the study. Upregation of cyclin d1 can yield to possibly other reactions like downregulation of P53. It is these players that can have way a bigger impact in my opinion. Using estrogen can upregulate cyclin d1 also for example and has impact on the MAPK pathways too etc.

Nonetheless a full cure in a drug form would be a miracle in my opinion, highly unlikely for quite some time seeing the implications in AGA.

I have this question also.
Basically blocking upstream or downstream makes not so much difference.
However I would use both RU and OC, I do think this would work great.
And can lower RU dose to a much safer concentration say2%.

[nave13579]

I would rather address the downstream problem as opposed to upstream, allowing more natural processes in my body to remain unblocked and functional.

[Hairismylife]

I would rather address the downstream problem as opposed to upstream, allowing more natural processes in my body to remain unblocked and functional.

Add some antiandrogen at very low dose.
Mpb need to be attacked in all angles!

[KO1]

Good points. I definitely think we need to add PGE2 concurrently with seti, and it will magnify pgd2 inhibition. What's more, pge2 is already available in drug form.

[sdsurfin]

I would rather address the downstream problem as opposed to upstream, allowing more natural processes in my body to remain unblocked and functional.

Exactly. Downstream means more specific. Also OC and setipip do not reduce PGD2 the way fin reduces DHT. they block a very specific receptor in the follicle, and there is still the same amount of PGD2 floating around interacting with the other receptors in your body. People don't seem to understand that. This is hands down a less invasive approach, and one that avoids ****ing with crucial hormonal balances, Which is why A billion dollar drug company is investing to bring this to market. I don't need to say anything more than that. If they did not see a superiority to finasteride then they would not be researching it and developing it.

Also swooping I don't think you understand how these drugs differ in their mechanism. Fin does not block any receptors, it inhibits an enzyme. This action is not linked to upregulation. In contrast, when you block a receptor site, this often results in the creation of more receptors on a cell. Look up beta blockers. I'm not saying RU definitely up regulates androgen receptors, but the possibility is there.

I really don't want to argue about anti-androgens. In my experience they all give me side effects, and are tied to hormonal pathways that are just too important for my health and identity as a man to **** with. If you want to roll those dice, go ahead.

My goal is to bring to market an option that has top scientists behind, it, that has PROVEN safety as opposed to RU, and that at least has very strong anecdotal evidence of success at halting loss. Breathlessness is something that every person with anxiety experiences, and neither that or insomnia really scare me, especially if they are mild. The worst that can happen is you get those sides and decide to stop. The worst that can happen on fin is that you get sides and they never go away. I personally know people who this has happened to. For me the choice is simple.

[Swooping]

Also swooping I don't think you understand how these drugs differ in their mechanism. Fin does not block any receptors, it inhibits an enzyme. This action is not linked to upregulation. In contrast, when you block a receptor site, this often results in the creation of more receptors on a cell. Look up beta blockers. I'm not saying RU definitely up regulates androgen receptors, but the possibility is there.

I really don't want to argue about anti-androgens. In my experience they all give me side effects, and are tied to hormonal pathways that are just too important for my health and identity as a man to **** with. If you want to roll those dice, go ahead.

My goal is to bring to market an option that has top scientists behind, it, that has PROVEN safety as opposed to RU, and that at least has very strong anecdotal evidence of success at halting loss. Breathlessness is something that every person with anxiety experiences, and neither that or insomnia really scare me, especially if they are mild. The worst that can happen is you get those sides and decide to stop. The worst that can happen on fin is that you get sides and they never go away. I personally know people who this has happened to. For me the choice is simple.

Nope, it can happen with enzymes too a classical example of this is upregulation of cytochrome P450 enzymes. There is zero reasoning to believe that a anti-androgen causes upregulation of AR or AR sensitivity. It could possible but would be the other way around and it would resolve on discontinuation.

Even with beta blockers you are not correct because if they would upregulate that would mean you would to continuously increase your dosage , making the medicine ineffective over a while. Yes you can't abruptly stop from a (high) dosage of them. This is called physical dependence and has nothing to do with upregulation of these receptors; http://en.wikipedia.org/wiki/Physical_dependence. GABA drugs are a primary example of this like alcohol and benzodiazepines

Drugs that cause physical dependence; blood pressure medications, including beta blockers such as propanolol and alpha-adrenergic agonists such as clonidine[18][19]

Top scientists, yeah that's true. But I only see Cotsarelis and Garza being convinced and even Garza acknowledges that many questions marks are to be solved and that possibly PGD2 isn't a major important pathway (http://www.ncbi.nlm.nih.gov/pubmed/24521203).

Nonetheless I'm interested in how everything will unfold regarding this pgd2 angle.