Baldness: Theory and practice of treatment, part 2 "Even the prostate has tonsils, prostaglandins"

The second article on baldness ( part one ), the causes and methods of treatment, will be devoted to prostaglandins - signaling molecules that, among other things, are also implicated in the regulation of both hair growth and baldness processes.

The use of prostaglandins, or drugs blocking them, is a fairly new (and experimental) form of treatment in the fight against baldness, which can be an alternative to minoxidil-finasteride therapy and addition to it.

The relationship between prostaglandins and the development of AHA was discovered only in 2012, by a group of doctors at the Perelman School of Medicine at the University of Pennsylvania. How to open? It is very simple - we performed a tissue biopsy in the AGA zones (the frontal-temporal and parietal areas of the scalp, they are most susceptible to AGA) and a comparative analysis between men who have had AGA and healthy individuals, it would seem an absolutely obvious study (and not the first such), showed that in bald men the amount of prostaglandin D2 (hereinafter PGD2) is significantly higher in the AGA zones, and the opposite of prostaglandin E2 (hereinafter PGE2).

Prostaglandins, what is it and what does glands and prostate have to do with it?

By the nature of their effects on tissues, prostaglandins are similar to hormones - they are able to bind to their corresponding receptors (DP1-2, EP1-4, FP, IP1-2) and cause a response: control cell growth, effects on hormones, the menstrual cycle (in women), etc.

All prostaglandins are synthesized by linking the cyclooxygenase enzymes of both types (hereafter, TSOG1, TSOG2) and omega-6 fatty acids.

As it was already possible to guess, there are 2 types of COX:
TSOG1: Activity and synthesis are relatively constant and continuous.
TSOG2: Activated, relatively speaking, as a response to certain external factors, for example, is one of the factors controlling inflammatory reactions. Also, the synthesis of COX2 can be increased by the prostaglandins themselves, which are synthesized from it.

And here it is, another paradox - both the "harmful to the hair" PGD2 and the "useful" PGE2 are synthesized from the same "sources."

Testing the theory of the effect of PGD2 on hair growth

In order to check whether the difference in the number of PGD2 and PGE2 prostaglandins in the scalp in AGA-prone and healthy men is the cause and not the result of the disease, mice were tested.

For this purpose, “ordinary” laboratory mice were used and mice with increased secretion of TSOG2 were specially bred (as a result of which, an increased amount of PGD2 and other prostaglandins).

The results of the experiment clearly show not only the effect of prostaglandins on the condition of the hair, but also the fact that although the level of PGE2 (as well as the “beneficial for hair” PGF2a) increased along with the level of PGD2, while the disproportion is observed and the level of PGD2 is much higher than PGE2, AHA is observed.

Also, the theory was tested on explanted human hair bulbs.
After 7 days, the length of hair grown in culture with the addition of PGD2 was 62 (+ - 5)% less than the length of hair from the control group, hair treated with 15-dPGJ (PGD2 metabolite) completely stopped its growth .

How to treat ?

As already mentioned at the beginning of the fast, prostaglandins can be used instead of minoxidil-finasteride therapy (in the case of individual intolerance) and with it.

PGD2 blocking (more specifically, the GPR44 receptor to which PGD2 binds)

It should be understood that the blocking of PGD2 is not intended to return you lost hair, but rather to stop the development of AHA (by analogy with finasteride).

• Setipprant (Setipiprant) - A selective inhibitor of the GRP44 receptor.
  Currently in phase III clinical trials (in humans) at the FDA. The drug is tested specifically for the treatment of AHA, and after completing clinical trials (if successful, of course) will become the third drug approved by the FDA for the treatment of AHA. The recommended dosage is 1 g orally (although in theory the molecular weight allows it to be used externally as part of lotions) for 2 days (ie, every 12 hours). Although the drug has not officially entered the market, it has been available for purchase from Chinese farm companies for several years. Perhaps its main drawback at the moment is its price, 1g costs $ 4-5.

• Fevipiprant - By the principle of action it is similar to setipiprant, however it is being developed and tested (it is also at the stage of FDA clinical trials) for the treatment of asthma. According to numerous statements, it is more effective than setipiprant, with a lower effective dosage and longer half-life. However, clinical tests on the effectiveness of feipranta have not yet been published, so it is impossible to accept such statements as anything more than rumors. Also available to order with the Chinese.
• Ramatroban (Ramatroban \ Baynas JP) - Another GRP44 inhibitor, its development was discontinued before being released to the market. Also available in the Chinese market in the form of a lotion, according to reports of voluntary testers, the drug proved to be quite effective, but again, nothing can be asserted without clinical results.

Stimulating hair growth with prostaglandins

What can be called a peculiar analogue of Minoxidil

• PGE2 - Available for purchase in pure form for sale for research purposes, and of course in the Chinese market. He has no official recommendations for use, unofficially - it is used externally at a dosage of 1 mg / ml once a day (rather low dosage is due to the high price).
• PGF2a (Kloprostenol \ Cloprostenol) - A synthetic analogue of prostaglandin PGF2a, sold in veterinary stores, various manufacturers. He has no official recommendations for use, informally - it is used externally at a dosage of 0.1 mg / ml once a day.
• Ricinoleic acid (Castor oil) - ricinoleic acid (the source of which is Castor oil) activates 2 of 4 receptors responsible for binding to PGE2.
  Used orally - at a dosage of 1 ml of 2x day (castor oil also serves as a laxative so it is strongly not recommended to exceed the "safe" dosage in order to avoid incidents). So outwardly, often in the form of a mixture with 10-30% Dimexidum (it is added to improve the permeability of the oil, it is worth noting that Dimexidum is quite an aggressive drug and its tolerance is individual, so the dosage should be chosen carefully and gradually to avoid irritation or even burns). The time of application for external use is 1-2 hours (if there is dimexide in the solution).