Judging by one of the recently published articles, the topic of baldness is still quite interesting for the local public, and therefore I decided to write a couple of posts about the disease itself and its treatment methods (to be more precise, not exactly treatment, because the means for permanently solving the problem the market has not yet, it is about stopping the development and return of lost hair).
In the first post there will be a description of the disease itself (no matter how strange it sounds, but most people, even those confronted with
AHA , do not understand the nature of the disease), then how does it begin, and the actual treatment methods based on blocking
DHT and androgenic receptors, despite the fact that such an approach has been rather obsolete in the last 10 years, it is still more than effective.
So what is the AHA?
This is a gradual decrease and degradation of the hair follicle - the organ that "creates" the hair. As a result of degradation, with time pigmentation and thickness of the hair decreases, and healthy hair turns into plump.
Contrary to popular belief, hair loss does not lead to baldness, and even the opposite - it is absolutely natural. Unlike for example nails, hair does not grow constantly but in cycles, the last stage of a hair growth cycle is its loss. After this stage, the cycle begins again, and with it the new hair grows. That's just when the AHA hair growth phase is reduced, which in turn leads to a reduction in the amount of hair on the scalp at any point in time.
Hair growth cycle
The growth and development of the hair occurs in a strictly cyclical order: the growth phase (anagen), the degradation phase (catagen), the resting phase (telogen).
In case of successful completion of the entire cycle of hair grows in its original form after the completion of the last two phases. In addition to the growth of the hair itself, in the anagen phase, important parts of the epithelial follicle also develop the keratinocytes of the hair matrix - located around the follicle show the highest activity in this phase of growth. Also in this phase, newly formed hair undergoes pigmentation (Paus and Cotsarelis, 1999).
During the next phase — catagen, the follicle goes to controlled degradation — an increase in programmed cell death (apoptosis) in most follicular keratinocytes, cessation of pigment secretion, substantial extracellular matrix reorganization, and reduction of follicles (Paus and Cotsarelis, 1999).
During telogen, the hair comes to a dead state, but it is firmly held in the bulbous base of the follicle until it finally falls out (usually during washing, combing or other mechanical effects). It has not yet been established whether the final loss of dead hair (teloptos) is also an active, controlled growth phase, or just a passive consequence of the regrowth of a new hair in the follicle (Paus and Cotsarelis, 1999; Pierard-Franchimont and Pierard, 2001).
There are large differences between these phases, depending on the location of the hair on the body, the duration of the anagen also changes and determines the type of hair and its length (Paus and Cotsarelis, 1999). On the scalp, the hair is in the anagen phase for 2-7 years, and the duration of the telogen is about 100 days, which means the ratio of hair in anagen and telogen is about 9 to 1. Most of the number of new hair on the scalp corresponds to the amount of hair that has been dropped and is about 100 per day, thereby maintaining full scalp coverage.
It should be understood that this is a very conditional figure, in order to determine the "normal" amount of lost hair, you need to know both the amount of hair on the head (which varies depending on gender, race, and hair color), and the duration of the telogen phase, and in general, the formula will look like this: number of hair * 0.1 / telogen phase duration in days.
In the terminal stage of degradation, the follicle does not "die off" and continues to function, however, the hair produced by it is too thin and short and is almost not visible visually. Over time, the hair growth shaft is closed by connective tissue (Histological examination of scalp biopsy results in miniaturization of terminal hair often associated with lymphocytic infiltration and, ultimately, fibrosis (Jaworsky et al., 1992; Whiting, 1993)). This phase can be considered the "point of no return" for the pharmacological treatment of AHA.
Causes of the occurrence and development of the AHA.
The cause of AHA is considered to be the genetic "increased" sensitivity of hair follicles on a specific area of the scalp to androgens . Studies of men without testicular androgens have shown that testosterone or its metabolites are the primary cause of the development of AHA. Men who had been deprived of the testicles before the end of puberty were never exposed to AHA, and the development of AHA was triggered by the injection of testosterone to castrated men (Kaufman, 1996). The same data is valid for people who have changed sex.
Nevertheless, even the almost complete elimination of androgens only stops the development of AHA, but does not return the follicles to normal appearance, which suggests that in addition to the androgenic effect, other processes take part in the development of AHA.
Despite the fact that any androgen is involved in the development of AGA (as all androgens are associated with the same AR receptor), DHT has the greatest influence.
It also shows the so-called "Dihydrotestosterone paradox", in which DHT causes body hair to grow, but at the same time falls on the head. The degree of affinity with the AR receptor DHT is 2-3 times greater than testosterone and 5 times the duration of communication with the receptor (Grino PB, Griffin JE, Wilson JD 1990).
DHT is synthesized directly in the target tissues (in our case we are talking about the skin), by linking testosterone synthesized in the testicles with the enzyme 5-alpha reductase.
It should also be noted that there are three types of 5-alpha reductase, with each of them testosterone forms DHT.
And here is another paradox, type I is most common in the skin, including the scalp, on the other hand, type II is more common in the follicle directly (Hoffmann R, Happle R. 1999)
How to treat ?
!!! IMPORTANT!!!
It should be noted that all the drugs listed below are strictly prohibited not only for use but also for any contacts to women and men under 25 years of age. The slightest dose of any of them can lead to an incurable pathology of the development of the fetus in a pregnant woman and disrupt the formation of muscularity in men (depending on age).
The FDA currently recognizes only two drugs recommended for the treatment of AHA, it is Finasteride and Minoxidil.
Blocking the conversion of testosterone to DHT
The oldest clinically proven way to fight AGA is to block reductase enzymes so that they cannot convert testosterone to DHT in target tissues.
As mentioned above, even complete elimination of androgens does not restore hair by itself, and here, the goal of anti-DHT therapy is to stop the progression of the disease, other drugs or methods must return the hair. Although of course in the early stages of AGA, it is enough to block DHT or androgenic scalp receptors in many cases in order to return the hair, simply due to the cellular regeneration of the follicles.
- Finasteride - is aimed at reducing the level of DHT in the body, by blocking 5-alpha reductase type II and type III, the FDA recommended dosage is 1 mg daily oral. The drug is generally well tolerated, with a half-life of only 6-8 hours.
About side effectsThere are many reports of all kinds of side effects of finasteride, ranging from impotence to dementia.
Sometimes it seems that when starting it, some people blame any of their diseases on it, while others do not experience any side effects after a decade of regular use.
Side effects are well described by reference.
In addition to preoral administration, finatseride can be used externally.According to the information that was previously published by Hasson & Wong, the use of finasteride outwardly did not cause any side effects even in those patients who they reported during oral admission, the effectiveness of the tolerance was quite obvious . A month ago, a page describing finasteride for external use was removed, and the order page was locked with a password.
Some manufacturers of minoxidil-containing lotions are also added to finasteride.
At the moment, Polichem is conducting clinical trials of its own form of finasteride for external use.
- Dutasteride has the same principle as finasteride, but the effectiveness of blocking reductase of all types is higher; it also blocks type I reductase, which finasteride does not affect. Side effects are similar to finasteride, but with a slightly higher (1-5%) probability. The half-life is several orders of magnitude higher than that of finasteride and is 5-6 weeks.
Dutasteride is not effectively used externally, but it can be used for mesoinjections containingDutasteride is not applied externally in view of molecular weight too large for free penetration through the skin. However, if you use the injection method of delivery (for example - mesotherapy), studies show improvements and even stated about the lack of side effects.
Androgen receptor blocking
As the name implies, the meaning of this therapy is simply to prevent the activation of the androgen receptors on the scalp. Since the receptor as a whole is blocked, rather than an individual hormone activating it, in theory such therapy should be several times more effective than blocking DHT and have less chance of side effects.
There are no official data on half-life, but judging by the dosages in clinical trials, both drugs are recommended to be used twice a day, 1 ml in 5% concentration.
- RU58841 (PSK 3841), a drug that was developed to treat acne and AHA, is used exclusively externally, in the form of a lotion, entering the systemic circulation can cause side effects similar to dutasteride, the drug was researched and developed more than 20 years ago; People 1. 2. The results of which the company (according to their comments) was sufficient, but it never officially entered the market (no official reasons were announced,
but there are several versions1) That, according to the results of clinical studies in humans, the effectiveness was insufficient.
2) That this is due to the expiration of the duration of the monopoly patents on the drug, which makes it commercially failure and its testing - unprofitable).
In this case, the drug is made in many private laboratories and is used on their own, a typical dosage is 5%
- CB-03-01 (Breezula) The principle of the drug is similar to RU, according to users who used both drugs - there was no difference in effectiveness. Currently undergoing clinical testing in Europe at concentrations of 1% and 5% for the treatment of acne and AGA, respectively. According to the results of double-blind testing, Breezula showed a better effect than minoxidil, and a lack of systemic side effects. The drug is also sold by third-party chemical companies despite the fact that a commercial launch is scheduled only next year.
Other preparations
In fact, they are not very relevant here, since in fact they are not related to DGT or to the AHA as a whole, but it would be even more inappropriate to write about them in other articles.
- Minoxidil , the second drug approved by the FDA for the treatment of AGA. Essentially, it is not a cure for AGA, but rather a rather effective stimulator of hair growth, any hair and healthy, and damaged, on the scalp, on the body, everywhere. Minoxidil is effective only in the sulphate form to which it is transferred by the enzyme - sulphur transferase, this is the main reason that the effect of it does not manifest itself in all and the effectiveness also differs. There is also an active compound, Minoxidil Sulfate, which is not required for Sulfur Transferase.
It is worth mentioning that there is a huge number of fakes on the market (Ukraine is especially distinguished here, where all the shops are inundated with some kind of drug based on the minoxidi N compound unknown to science) and it is better to pay several orders for delivery in proven Western stores.
The use is the same as with previous preparations - outwardly, 1 ml of 5% p-ra twice a day. - Ketoconazole containing shampoos , in contrast to popular opinion, does not affect DHT (and they cannot with this method of application, too high molecular weight, a solution of water and surfactant is a very bad delivery method). Nevertheless, it effectively suppresses pathogenic microflora, reducing inflammatory processes and improving the delivery of topical preparations.
I think this is enough for the first post, if the topic is interesting, I will continue with more modern means and approaches.