Baldness: Theory and practice of treatment, part 2

Even the prostate has tonsils

Vizavi, Habr

The second article on baldness, its causes and methods of treatment will be devoted to prostaglandins – signaling proteins, which, among other things, are involved in the regulation of both hair growth and baldness processes.

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

The relationship between prostaglandins and the development of androgenic alopecia (AHA) was discovered only in 2012, by a group of doctors at the Perelman School of Medicine at the University of Pennsylvania. How did you open it? It's very simple – a tissue biopsy was performed in the AHA zones (frontotemporal and parietal areas of the scalp, they are the most susceptible to AHA) and a comparative analysis between men who had AHA and healthy volunteers. It would seem that an absolutely obvious study (and far from the first such one) showed that in bald men the amount of prostaglandin D2 (hereinafter PGD2), as well as its metabolite 15-dPGJ2, is significantly higher in the AHA zones, and prostaglandin E2 (hereinafter PGE2), on the contrary, is less.

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

The answer to the second part of the question is simple – yes, nothing to do with it.

Prostaglandins are synthesized in almost all types of tissues, and they owe their name to the fact that they were first isolated from seminal fluid and named after the prostate gland (Latin glandula prostatica).

By the nature of their effect 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 of cell growth, effects on hormones, menstrual cycle (in women), etc.

All prostaglandins are synthesized by binding cyclooxygenase enzymes of both types (hereinafter COX1, COX2) and omega-6 fatty acids.

As you might have guessed, there are 2 types of COG.

COG 1: Activity and synthesis are relatively constant and continuous.

COX2: 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 "harmful to hair" PGD2 and "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 amount of prostaglandins PGD2 and PGE2 in the scalp of AHA-prone and healthy men is the cause, and not the consequence of the disease, an experiment was conducted on mice.

For this purpose, "ordinary" laboratory mice (Wild-type) and specially bred (K14-Ptgs2 line) mice with increased COX2 secretion (as a result, with an increased amount of PGD2 and other prostaglandins) were used.

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

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

How to treat?

As already mentioned at the beginning of the post, prostaglandins can be used as a substitute for minoxidil-finasteride therapy (in case of individual intolerance) so it is with her.

Blocking PGD2 (more precisely, the GPR44 receptor that PGD2 binds to)

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

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

At the moment, it is impossible to judge the side effects of the original drugs because there are no official data or results of taking them by patients (although the setipiprant has passed the safety testing stage).

According to the reports of users of Chinese "generics", when taking drugs from early batches, some users experienced the following side effects (which many associate with an insufficient degree of purification of the drug):

• Dry skin, eyes.
• Deterioration of sleep quality\ sleep disturbance.

Fevipiprant (Fevipiprant) The principle of action is similar to setipiprant, but it is being developed and tested (it is also at the stage of clinical trials by the FDA) for the treatment of asthma.
According to numerous claims, it is more effective than setipiprant, with a lower effective dosage and a longer half-life. However, clinical tests on the effectiveness of fevipiprant have not yet been published, so it is impossible to accept such statements as something more than rumors. Also available to order from the Chinese.

Ramatroban (Ramatroban \ Baynas JP) Another GRP44 inhibitor, its development was discontinued before it was put on the market.
Also available on the Chinese market in the form of a lotion, according to voluntary testers, the drug proved to be quite effective, but again, nothing can be said for sure without clinical results.

Stimulating hair growth with prostaglandins

This can be called a kind of analogue of minoxidil

PGE2
Available for purchase in pure form on sale for research purposes, and, of course, in the Chinese market. It has no official recommendations for use, unofficially – it is used externally in a dosage of 1 mg / ml once a day (a rather low dosage is due to the high price).

PGF2a (Cloprostenol\Cloprostenol) Synthetic analog of prostaglandin PGF2a, sold in veterinary stores by various manufacturers.
It has no official recommendations for use, unofficially it is used externally at a dosage of 0.1mg /ml once a day. Ricinoleic acid (castor oil)
Ricinoleic acid (the source of which is castor oil) activates 2 of the 4 receptors responsible for binding to PGE2. It is used both orally – in a dosage of 1 ml 2 days (castor oil also serves as a laxative, so it is strongly recommended not to exceed the "safe" dosage in order to avoid incidents), and externally, often in the form of a mixture with 10-30% dimexide (it is added to improve oil permeability). It is worth noting that dimexide is a rather aggressive drug and its tolerability is individual, so the dosage should be selected carefully and gradually in order to avoid irritation or even burns. The application time for external use is 1-2 hours (if dimexide is present in the solution).

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