Prostaglandin D2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia

Sci Transl Med. 2012 Mar 21;4(126):126ra34.
Prostaglandin D2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia.
Garza LA, Liu Y, Yang Z, Alagesan B, Lawson JA, Norberg SM, Loy DE, Zhao T, Blatt HB, Stanton DC, Carrasco L, Ahluwalia G, Fischer SM, Fitzgerald GA, Cotsarelis G.

Department of Dermatology, Kligman Laboratories, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet, the mechanisms for decreased hair growth in this disorder are unclear. We show that prostaglandin D(2) synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D(2) (PGD(2)), is similarly elevated in bald scalp. During normal follicle cycling in mice, Ptgds and PGD(2) levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD(2) inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD(2) receptor G protein (heterotrimeric guanine nucleotide)-coupled receptor 44 (GPR44), but not the PGD(2) receptor 1 (PTGDR). Furthermore, we find that a transgenic mouse, K14-Ptgs2, which targets prostaglandin-endoperoxide synthase 2 expression to the skin, demonstrates elevated levels of PGD(2) in the skin and develops alopecia, follicular miniaturization, and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD(2) as an inhibitor of hair growth in AGA and suggest the PGD(2)-GPR44 pathway as a potential target for treatment.

Quercetin and Omega-3 fatty acids (such as krill oil) will make this less of an issue.

Related information:

J Affect Disord. 2012 May;138(3):479-84. Epub 2012 Feb 26.
Differential expression of prostaglandin D2 synthase (PTGDS) in patients with attention deficit-hyperactivity disorder and bipolar disorder.
Marín-Méndez JJ, Patiño-García A, Segura V, Ortuño F, Gálvez MD, Soutullo CA.

Department of Psychiatry, University Clinic of Navarra, Pamplona, Spain.

BACKGROUND:
As marker genes for bipolar disorder (BP) and attention deficit hyperactivity disorder (ADHD) are not fully identified, we carried out a complete genome analysis to search for genes differentially expressed in ADHD and BP.
MATERIALS AND METHODS:
We recruited 39 patients (30 ADHD, 9 BP), aged 7 to 23years. For evaluation of the psychiatric diagnosis, we used a semi-structured interview based on the K-SADS-PL (DSM-IV). RNA was extracted from peripheral blood and analyzed with the GeneChip® Human Genome U133-Plus 2.0 (Affymetrix). For the validation of differentially expressed genes, real-time PCR was used.
RESULTS:
Hybridization and subsequent statistical analysis found 502 probe-sets with significant differences in expression in ADHD and BP patients. Of these, 82 had highly significant differences. Neuregulin (NRG1), cathepsins B and D (CTSB, CTSD) and prostaglandin-D2-synthase (PTGDS) were chosen for semi-quantitative mRNA determination. The expression of PTGDS was statistically increased in ADHD relative to BP patients (p=0.01). We found no such differential expression with NRG1, CTSB and CTSD genes (p>0.05).
CONCLUSIONS:
The gene coding for PTGDS was found to be more expressed in patients with ADHD relative to patients with BP, indicating a possible link with the differential etiology of ADHD. The experimental approach we have used is, at least in part, validated by the detection of proteins directly concerned with brain functions, and shows a possible way forward for studies of the connection between brain function genes and psychiatric disorders.
LIMITATIONS:
Confirmation of our findings requires a larger sample of patients with clearly-defined phenotypes.

Would this require mega dosing of quercetin or krill? What about astaxanthin itself?

Also, is there a topical option? I read some good initial reports with topical quercetin, but it stains really badly.

It's basically the Omega-3 fatty acids that help (not the astaxanthin).

http://www.ncbi.nlm.nih.gov/pubmed/10457118

CausticSymmetry wrote:It's basically the Omega-3 fatty acids that help (not the astaxanthin).

http://www.ncbi.nlm.nih.gov/pubmed/10457118

Gotcha, thanks

This article (link below) by Chris Masterjohn, is an interesting counterpoint to diminishing PGD2 (and AA's role worth noting) by increasing dosage of of Omega-3s; essentially we need very little Omega-3 intake - if diet and lifestyle are in balance. In fact, high dose Omega-3 is probably detrimental (unless for specific therapeutic use)

Reading between the lines... needing to high dose Omega-3 to balance out PGD2 would also perhaps suggest that something is wrong with one's diet/lifestyle -- or does the study's implications extend beyond that?

http://www.westonaprice.org/know-your-fats/precious-yet-perilous

Many authors consider EPA an “anti-inflammatory” essential fatty acid, but its “anti-inflammatory” activity is a result of its ability to interfere with arachidonic acid metabolism. The conversion of arachidonic acid to PGE2 in immune cells is an important initiator of inflammation, but it also turns on the genes necessary for the synthesis of compounds that resolve inflammation, some of which are derived from arachidonic acid and others of which are derived from DHA.52 Providing sufficient DHA to allow the synthesis of the full spectrum of inflammation-resolving compounds is a nutritional approach to inflammation. Providing high doses of EPA that interfere with arachidonic acid metabolism, however, is a pharmacological approach, and it is likely to have many adverse consequences.

Our bodies use the same enzymes to convert EPA to DHA as they use to convert ALA to DHA or linoleic acid to arachidonic acid. The same conditions that reduce the requirement for arachidonic acid and DHA are likely to increase a person’s tolerance for EPA. A diet that excludes refined sugar and rancid vegetable oil, is low in total PUFA content, is adequate in protein and total energy, and is rich in vitamin B6, biotin, calcium, magnesium, and fresh, whole foods abundant in natural antioxidants should not carry any risk of arachidonic acid deficiency when moderate amounts of EPA are consumed. Liberal amounts of egg yolks and liver providing preformed arachidonic acid would provide extra insurance against damage by EPA. Under these conditions, it would be safe to consume cod liver oil—valuable for its abundant provision of DHA, vitamin A and vitamin D—in spite of its EPA content.

CS,
Is it your opinion that high doses of Omega- 3 could minimize PGD2?
If so, what do you consider a sufficient dosage?
Also what do you think of this omega-3 from LEF?
http://www.lef.org/Vitamins-Supplements/Item01482/Super-Omega-3-EPA-DHA-with-Sesame-Lignans-Olive-Fruit-Extract.html
Are there any other supplements you know of that may reduce PGD2?

Also I have heard that aspirin (salicylic acid) could also minimize PGD2.
What are your thoughts about taking an aspirin a day and also applying aspirin power to one's scalp possibly mixed with shampoo or perhaps some type of topical mix?
http://www.amazon.com/Aspirin-Powder-1-lb/dp/B003GC8LAA/ref=cm_cr_pr_pb_t

Thank you in advance for you help

I believe the best way to deal with PGD2 is taking Quercetin. Quercetin does other things besides PGD2, in fact I take it for another reason entirely (Cortisol management mostly). http://tinyurl.com/dxzak76

It would be a mistake to take aspirin and especially Erythromycin because of the side effects.
Aspirin is not as safe as it is believed.

I agree that AA is not really an issue unless there is an imbalance such as those already mentioned.
I take krill oil for mostly other reasons (hair related).

Long story short, lots of fish oil is not that desirable. Please read this thread for more information:

https://immortalhair.forumotion.com/t4431-new-paradigm-shift-peo-s-not-efa-s

thanks CS!
I searched the net for quercetin and hair loss I saw something that worried me..

"The problem is that when quercitin is given to rats along with finasteride, their serum levels of DHT go right back up, so quercitin must interefere with finasteride."

also saw this:
http://joe.endocrinology-journals.org/content/181/3/493.full.pdf

Is there any truth to this in your opinion?

Also, whats your take on aspirin topically?

MiamiSteve wrote:thanks CS!
I searched the net for quercetin and hair loss I saw something that worried me..

"The problem is that when quercitin is given to rats along with finasteride, their serum levels of DHT go right back up, so quercitin must interefere with finasteride."

also saw this:
http://joe.endocrinology-journals.org/content/181/3/493.full.pdf

Is there any truth to this in your opinion?

Also, whats your take on aspirin topically?

It's not a concern to me. In fact, when asked similar questions I worry more about damage of the petrochemical poisons being taken. Lowering DHT in the manner by which finasteride does is a totally undesired effect.

You might note that the prostate weight reduction was even more significant when Quercetin was added, despite the DHT increase. Finasteride (as Proscar) was originally intended as a prostate enlargement drug.

If the prostate weight were to have increased with Quercetin, that would be a concern, however just the opposite occurred. Moreover, Quercetin helps tackle something far worse than DHT.

Thanks again CS,
sorry if I sound ignorant, but to summarize, would you think its okay, and even beneficial to use Quercetin and finasteride together?
Would there be any negative impact on the workings of finasteride as I have been having small success with it, even though it may be starting to lose its impact. (which is why i would like to add to my regiment)

Also any thoughts on applying aspirin powder topically with shampoo or in a topical leave on mix?

Swelling would constrict blood flow Would it not? These condensed notes would make a lot of sense.

Humoral Immunity (human immune system)

Trigger the phagocytosis of Antigen-Antibody complex B-cells humoral immunity The antibodies can cluster around and cover up a toxin or virus, which inactivates toxins/virus Activate complement System Membrane attack complex You create a hole in the foreign cell of the bacteria in the cell membrane, water rushes in and burst (lyse) the cell Chemotaxis of Leukocytes Chemicals released that tells the white blood cells to come to the infection area Stimulation of phagocytosis in the macrophages and neutrophils (neutrophils have lysosome) Mast cell release Histamines, more white blood cells come to fight infection. Prostoglandin concentration also increase causing swelling to increase Histamine and prostaglandin are regulated by positive feedback

MiamiSteve wrote:Thanks again CS,
sorry if I sound ignorant, but to summarize, would you think its okay, and even beneficial to use Quercetin and finasteride together?
Would there be any negative impact on the workings of finasteride as I have been having small success with it, even though it may be starting to lose its impact. (which is why i would like to add to my regiment)

Also any thoughts on applying aspirin powder topically with shampoo or in a topical leave on mix?

Here's a two part answer: Finasteride can irrevocably alter the endocrine system, however some users can tolerate it much better than others. If you feel confident that it has not hurt you so far, you could continue and evaluate its effects with Quercetin.

The overall problem however, is that PGD2 and DHT are not the sole causative factors. They are only an effect from something else. In fact, if the thyroid is normal (on a cellular level, which is not verified with standard blood tests), DHT is not even inflammatory.

If someone where to catalog this forums topics every few months, many would find the startling difference and variation on topics concerning what is the most important factor for hair growth or stopping loss.

Would focus on the bigger picture than just one of the potential triggers.

Topical aspirin might not be as bad (however I am not 100% certain. Also, there are many natural things that can help reduce PGD2.

Concerning this, an elevation of PGD2 is simply a symptom of an imbalance in adrenals. Quercetin is an effective treatment for this while balancing them out.

MiamiSteve wrote:
Also any thoughts on applying aspirin powder topically with shampoo or in a topical leave on mix?

You would be better off with topical salicylic acid, this chemical being the active moiety in aspirin (aspirin=acetylated salicylic acid). There are plenty of topicals containing salicylic acid, but I guess you would need something fairly concentrated like a "peeling solution" for it to be effective.

the full paper

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319975/

a discussion with Cotsarelis about some of this

http://www.aad.org/dermatology-world/monthly-archives/2012/june/can-blocking-pgd2-prevent-androgenetic-alopecia-

By Abby Van Voorhees, MD, June 01, 2012

In this month’s Acta Eruditorum column, Physician Editor Abby S. Van Voorhees, MD, talks with George Cotsarelis, MD, about his recent Science Translational Medicine article, “Prostaglandin D2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia.”

Dr. Van Voorhees: What have we known about androgenetic alopecia (AGA) up until your most recent findings?

Dr. Cotsarelis: We know a lot about AGA from studies a long time ago, in the ’50s, by Dr. James Hamilton. He was the first one to coin the term androgenetic alopecia. He noticed that men who had been castrated before puberty never went bald, and realized that baldness was androgen-dependent. He did some experiments where he gave men who had been castrated testosterone; the ones who had a family history of baldness started to go bald, so that was how he identified the genetic component. He originally called it androchronogenetic alopecia because you needed androgens, time, and genetics. We’ve known it’s androgen-dependent since then.

Next we learned more from studies by Imperato-McGinley, who studied families in the Dominican Republic who were pseudo-hermaphrodites — they were born looking like girls, with female genitals, and then at puberty they virilized, developing musculature, lower voices, and hair, and would actually develop a penis and could be fertile if they had their undescended testes surgically corrected. They were found to have a deficiency of type-2 5- reductase, the enzyme that converts testosterone into dihydrotestosterone. This was when we understood the importance of dihydrotestosterone in the process. Of course that’s what finasteride blocks; Merck developed that drug based on those studies.

Dr. Van Voorhees: What is the mechanism that accounts for the miniaturization of hair?

Dr. Cotsarelis: We know that inhibiting the testosterone pathway slows down the miniaturization of the follicle. Jaworsky, Kligman, and Murphy had a paper 20 years ago showing that half the time there is also inflammation around the hair follicle, which led to some thought that maybe inflammatory cells including mast cells were contributing to hair loss. Studies and case reports of transgender operations where men become women and receive high doses of estrogen show that a scalp that was almost completely bald can have, after castration and high estrogen supplementation, a tremendous amount of hair growth.

The overall feeling is that the follicles can be thought of as being in three states. Either they’re terminal, and they’re large, or they’re miniaturized, and they’re small, and the hair they’re creating is microscopic, or they’re in between, called indeterminate. It’s thought that follicles reach a point where they’re producing a hair so small that at that point the chance of reversing that follicle is small. There seems to be a point of no return with respect to androgen removal; even if you castrate someone who’s bald he won’t regrow all his hair. If you give him estrogen, too, he might.

Dr. Van Voorhees: Do resting stem cells remain in AGA? Do current medications used to treat AGA help us understand this process? What did this research demonstrate about the mechanism of AGA?

Dr. Cotsarelis: About a year ago Luis Garza, MD, did another study in my lab and looked at the stem cells in balding scalps of men undergoing transplants. He got tissue from the donor site and the recipient site and he actually quantitated the number of hair follicle stem cells using flow cytometry, a very accurate cutting-edge technique for quantitating the number of stem cells. And he showed that the percentage of stem cells was very similar in both areas. So the stem cells were still there even in the balding scalp where the follicles were miniaturizing.

However, he did find a population of cells that was markedly diminished in the balding scalp, and those resembled progenitor cells, the immediate progeny of stem cells. At that point we thought there must be either a lack of an activator of the stem cells preventing them from proliferating and doing their job and making hair, or maybe an inhibitor present. Using microarrays of bald and non-bald scalp in the same people, we looked at all 30,000 genes to see whether their expression levels were increased or decreased in the bald scalp. One of the genes that was markedly elevated in the bald scalp was PTGDS, prostaglandin D2 synthase.

We collaborated with Garret FitzGerald, MD, who’s an expert in prostaglandins and has done a lot of work with the COX-2 inhibitor he’s the one who actually showed that the COX-2 inhibitors have dangerous side effects. We gave him tissue from balding and non-bald scalp and he looked at the levels of PGD2 with mass spectrometry and showed that the PGD2 levels were quite high in the bald scalp. That was still just a correlation showing that there were higher levels of the genes and the lipid products in the bald scalp — we didn’t really know functionally whether that meant anything.

So then Luis worked with mouse models to assess the function of PGD2. Luis applied the PGD2 and another breakdown product, PGJ2, topically to the back of a mouse and he showed that hair growth slowed. Next, we collaborated with another group that was good at growing human hair follicles in culture. They showed that PGD2 in the culture media slowed down hair growth. So now we had functional evidence that prostaglandins played a role in hair growth. Luis also looked in the mouse, which has a better-defined hair cycle than humans because all of the hairs tend to be in the same stage whereas humans have mixtures of hair follicles in different stages of growth. In that model we showed that PGD2 started to go up during the end of the growing phase and was highest at catagen, the stage of regression. That, again, was good correlative evidence that PGD2 was inhibiting hair growth and even in a spontaneous hair cycle played a role in controlling hair growth.

There was a mouse that was made in the ’90s by Sue Fisher, who studies skin cancer; it’s a transgenic mouse that makes the COX-2 enzyme in the skin, so you drive COX-2 gene expression with keratin K14 promoters. It’s up higher in the pathway so if you overexpress COX-2 you get increases in PGD2 and also PGE2. E2 and F2 are actually known to promote hair growth — bimatoprost (Latisse) is an F2 analog. We looked at levels of D2 in that mouse, which develops alopecia, and they were sky high. E2 was also higher than the control but D2 levels were much higher. What’s amazing is if you looked at that mouse’s skin histologically the hair follicles were miniaturized and the sebaceous glands were enlarged, just like in androgenetic alopecia.

Finally, in genetic experiments done in collaboration with FitzGerald, we applied D2 to mice that lacked two different receptors that D2 binds to. The DP-1 knockout mouse had suppressed hair growth. The DP-2 (or GPR44) knockout mouse did not have inhibited hair growth.

Dr. Van Voorhees: Does this research open up possible avenues for treatment approaches that have not yet been considered? Are there currently drugs under development which might be utilized?

Dr. Cotsarelis: This work suggested that D2 was working through the GPR44 receptor to inhibit hair growth. It turns out that there are compounds under development by a number of companies to inhibit this receptor. They are being developed for asthma and allergic rhinitis. PGD2 causes bronchoconstriction — when you inhibit its receptor you relax smooth muscle so it helps with lung disorders. No one is developing a topical formulation, but we think if you did, it would be a potential treatment for alopecia.

Dr. Van Voorhees: Do you expect female pattern hair loss to have the same pathologic mechanism?

Dr. Cotsarelis: The only evidence we have is that when you take hair follicles from women, put them in the culture medium, and add D2, it inhibits their hair growth as well. But we haven’t studied women with female pattern hair loss to see if D2 is elevated there as well. The problem is that women who get hair transplants don’t have the donor scalp removed like men do; the grafts go in between existing hair follicles. The role of PGD2 in female pattern hair loss is an important question to address.

Dr. Van Voorhees: Should this allow for reversal of previously lost hairs or do you expect that it will only play a role in retaining hairs that have not yet miniaturized?

Dr. Cotsarelis: We don’t know. Like anything you’d have to test a large number of people to see how they respond. We don’t know if people who are already completely bald will regrow hair. We do know that the stem cells are present in men who are balding so if this is indeed the inhibitor preventing stem cells from making progenitor cells, there’s a possibility this would help there as well.

Dr. Van Voorhees: Why do you think there’s that threshold where miniaturization becomes non-reversible?

Dr. Cotsarelis: That’s an interesting question. There might be other genes downstream of testosterone playing a role. We already know that if you inhibit testosterone that hair doesn’t revert once it’s completely miniaturized. The fate of the hair follicle is determined very early on during development; there’s patterning, that’s why you have follicles responding to androgens on the top of the scalp and in the beard area in completely different ways. Androgen receptors are set up very early in development; I think the more we understand about that patterning the more we’ll likely be able to figure out what’s going on with hair loss.



Dr. Cotsarelis is chairman and Milton B. Hartzell Professor in the department of dermatology at the University of Pennsylvania. His article was published in Science Translational Medicine, Vol. 4, Issue 126, p. 126ra34.doi:10.1126/scitranslmed.3003122.

Dr. Cotsarelis: This work suggested that D2 was working through the GPR44 receptor to inhibit hair growth. It turns out that there are compounds under development by a number of companies to inhibit this receptor. They are being developed for asthma and allergic rhinitis. PGD2 causes bronchoconstriction — when you inhibit its receptor you relax smooth muscle so it helps with lung disorders. No one is developing a topical formulation, but we think if you did, it would be a potential treatment for alopecia.

This begs the obvious question: Who is going to be the first man to spray asthma inhalers on his head? Seriously though... Is anyone following these drugs and when they are scheduled to come to market?

people are already crushing asthma pills and dissolving them and putting them on their heads

LawOfThelema wrote:people are already crushing asthma pills and dissolving them and putting them on their heads

As funny as that sounds, I'm intrigued. Do you happen to have a link to this?

That article written in June 2012 says, " It turns out that there are compounds under development by a number of companies to inhibit this receptor. They are being developed for asthma and allergic rhinitis."

By what mechanism are these asthma pills that people are crushing hoped to work? I'm assuming they aren't the same compounds mentioned above?

i think receptor antagonists... blocking the receptor

zyrtec is one, and OC000459... looking at zyrtec, i dont think it blocks the right receptor but i could be wrong... i know ppl are using it tho.

This thread is very depressing. Why? Well, the last I checked it's a natural oriented forum and 2nd, these poisons that block inflammatory pathways are necessary functions that even when attempted to deliver locally still present systemic risks.

How about a few natural ways to deal with this that are probably no less effective? Also PGD2 is not everything...I wish it were, but it's just another piece of the puzzle. If I were to guess, it likely acts as a compensatory mechanism for lack of oxygen. This is basic on the fact that elevation of PGD2 is associated with ischemia.

Another point is that anti-asthma medications can (if it reaches systemically) can prevent necessary inflammation, ultimately preventing repair.

So what knocks down PGD2 without placing serious risk to health? GLA (Gamma Linolenic Acid)

On top of that GLA inhibits DHT up to 80%...however, like PGD2, DHT is not everything either.

CS, in the Greek hair loss forum, members are using topical zyrtec and they have great results. I'm still away from that, because i'm afraid the side effects after applying this thing every day to my scalp for a long long time.
So, GLA is it better than quercetin for manage pgd2 or equal?
What's your opinion for topical usage of borage oil, because i don't like the additional of extra omega 6 in my diet.
http://www.iherb.com/Health-From-The-Sun-Borage-Liquid-Gold-2-fl-oz-59-ml/5297

CausticSymmetry wrote:

On top of that GLA inhibits DHT up to 80%...however, like PGD2, DHT is not everything either.

And it does this when taken orally?

CausticSymmetry wrote:This thread is very depressing. Why? Well, the last I checked it's a natural oriented forum and 2nd, these poisons that block inflammatory pathways are necessary functions that even when attempted to deliver locally still present systemic risks.

How about a few natural ways to deal with this that are probably no less effective? Also PGD2 is not everything...I wish it were, but it's just another piece of the puzzle. If I were to guess, it likely acts as a compensatory mechanism for lack of oxygen. This is basic on the fact that elevation of PGD2 is associated with ischemia.

Another point is that anti-asthma medications can (if it reaches systemically) can prevent necessary inflammation, ultimately preventing repair.

So what knocks down PGD2 without placing serious risk to health? GLA (Gamma Linolenic Acid)

On top of that GLA inhibits DHT up to 80%...however, like PGD2, DHT is not everything either.

But for people like me, who has a root canal in the front tooth (which isn't the ideal spot for a partial), has had surgery resulting in screws and bolts in the head, someone stuck in between male and female, who is on Spiro to be more "adrogynous" - which messes with "optimal" hormonal balance in itself... DHT, PGD2, etc are the only things I feel I can concentrate on that will make a difference. If low T means inflammation I'm screwed, I may have naturally high T, but not on Spiro. In fact when on fin, my T levels sky rocketed and my DHT levels plummeted yet my hair got worse, fast! I can try to be as healthy as I can, clear out my heavy metals, balance my thyroid/adrenals, eat super healthy (raw foods, low carbs, lots of vits) but I'll still always have implants affecting my auto-immune system and likely be on some sort of testosterone lowering medication for partial-feminizing effects, causing stress and chaos in my body. Unless I have it all wrong, and this low T / root canal stuff isn't the end of the world.

Good post CS/Law.

Do you guys think that PGD2 elevation in the scalp is downstream of the DHT pathway or is this a separate and novel pathway that attacks the hair follicle?

CS do you believe that Scalp PGD2 dis-regulation is associated with Systemic Prostaglandin Dis-regulation?

I also noticed in the Cotsarelis interview:
"Studies and case reports of transgender operations where men become women and receive high doses of estrogen show that a scalp that was almost completely bald can have, after castration and high estrogen supplementation, a tremendous amount of hair growth." ->
You mentioned this before Law & that comment forced me to jump off the Ray Peat/ Danny Roddy solution to hair loss

Also:
"Garret FitzGerald, MD, who’s an expert in prostaglandins and has done a lot of work with the COX-2 inhibitor he’s the one who actually showed that the COX-2 inhibitors have dangerous side effects."
Also Makes me second guess Ray Peat's Aspirin a day recommendation.

I think Ray Peat's idea of using aspirin is foolish. At least it becomes a greater risk as we age. Also, aspirin resistance is real and increases the risk of death.

PDG2 is complex and it's really unknown at this point how safe it would be to block it using as a direct antagonist.
In this link, it discusses this as acting as both a pro and anti-inflammatory agent.

http://www.hindawi.com/journals/mi/2012/503128/

There are a number of ways to naturally attenuate PGD2 without blocking it directly.
However, addressing the real reason for its elevation is probably far more important.
It is certainly possible that oral pathology is a link.

Perhaps the safest way to address this, at least in theory is to populate the intestinal microbiota.
Because a favorable good to pathogenic bacteria ratio stands a strong chance to handle problems
in many areas affected by those with elevated PGD2.