Androgenetic alopecia

While the exact step-processes of AGA aren’t yet determined, there is general consensus on two contributing factors: genetics and androgens (i.e., male hormones).

AGA has an undisputed genetic component, with one study measuring a 2.5-fold increased risk of developing pattern hair loss in men whose fathers had pattern hair loss, as compared to those whose fathers didn’t (Chumlea et al., 2004). Moreover, women affected by AGA often report having other family members affected by the same condition (Ramos et al., 2015).

Genetic studies of this disease have brought to the fore the role of inheritance. In this regard, a recent analysis of published AGA genetic studies revealed a new association of AGA and rs7349332 located in the intron region of WNT10A, suggesting the involvement of WNT signaling in the etiology of AGA. In a German case-control study of AGA, it was shown that one of the reasons for the genetic risk of developing AGA is a pronounced polygenic component. This fact likely reflects the complexity of the biological pathways associated with AGA.

However, the exact genes involved in androgenic alopecia have not yet been discovered. The "commonly suspected" gene on the "androgen side" in this case is the androgen receptor (AR) gene, which is located on the X chromosome, which may explain maternal transmission of AGA. It is still unclear which genes other than AR are responsible for AGA. Patients should be aware that current genetic testing relies on variations in the AR gene, while the actual onset of androgenetic alopecia is caused by polygenic involvement of other genes or epigenetic mechanisms.

Scientists are still trying to uncover which polymorphisms may prompt individual susceptibility to AGA. Particular focus is on genes that code for androgen receptors (more on this soon).

In the body, nearly all DHT is created when unbound testosterone comes into contact with the enzyme 5-alpha reductase. This enzyme binds to free testosterone and then changes testosterone’s structure into DHT.

There are different types of 5-alpha reductase, and most types correspond to a specific tissue or region in which the enzyme expresses (i.e., the skin, brain, prostate, etc.).

When it comes to AGA, the type II 5-alpha reductase is most heavily implicated.

This is because:
(1) type II 5-alpha reductase is greatly expressed in scalp tissues, and
(2) men with a gene mutation who cannot produce type II 5-alpha reductase never go bald (Adachi et al., 1970).

Moreover, drugs that inhibit the type II 5-alpha reductase enzyme (i.e., finasteride) help to improve pattern hair loss in men.

Together, these findings implicate DHT and the type II 5-alpha reductase enzyme in AGA. But there’s at least one more androgenic factor involved in the onset and progression of pattern hair loss: that of androgen receptors.

When free testosterone comes into contact with type II 5-alpha reductase and converts into DHT, that DHT needs a place to bind to a cell. Once DHT is bound to a cell, this hormone can begin to influence that cell’s functionality.

Androgen receptors are where DHT binds to cells. They’re considered cellular “landing pads” – a place for male hormones to attach, so that they can begin to change cellular behavior.

That means that for (most) scalp DHT to form, we need:
(1) free testosterone,
(2) type II 5-alpha reductase, and
(3) an androgen receptor.

This is why androgen receptors are a major focus of AGA research: without androgen receptors, DHT cannot bind to scalp cells and influence their functionality.

DHT is still involved, but there’s debate over its degree of involvement.

Some studies have demonstrated that both men and women have elevated levels of 5α-reductase in the frontal hair follicles (Orme et al, 1999, Sawaya et al., 1997). This suggests that DHT may play a role in at least some female AGA cases.

At the same time, case studies have demonstrated female pattern hair loss can occur in women who are androgen-deprived, meaning they lack the ability to produce any male hormones at all (Orme et al., 1999).

While some have argued that these instances are just cases of mistaken identity (i.e., not AGA), others have used these findings as starting points to explore other aspects of AGA – and what the DHT-genetic sensitivity argument might not be telling us.

A new wave of AGA research is focusing more so on non-androgenic factors that might influence hair follicle functionality.

In 2014, excitement was generated over prostaglandin D2 and its potential connection to pattern hair loss. Prostaglandin D2 is a fatty acid derivative that, theoretically, can express as a result of androgenic activity (i.e., DHT) (Nieves et al., 2014).

Prostaglandin D2 was once found to be elevated in balding scalp regions and even impede hair lengthening. However, follow-up studies have shown conflicting findings – suggesting that prostaglandin D2 might be less involved in AGA than initially believed (Villarreal-Villarreal et al., 2019).

Interestingly, evidence is accumulating that in addition androgenic activity, retinoid receptors and the PPAR pathway are intimately tied to hair follicle miniaturization – and may even explain why some women develop AGA despite having normal scalp DHT levels (Siu-Yin Ho et al., 2019).

AGA is a continuous, protracted process, rather than a series of distinct disease phases, and each patient is characterized by a wide range of different features. With the progression of AGA, it behaves similarly to the process of tissue aging - in the hair follicles, as in other organs, the proportion of cells that carry only a structural function increases, sutures, constrictions, scars are formed, sclerosis occurs - an increased development of connective tissue components, which leads to a weakening of specific functions, thinning and hair loss

The shift of the frontal growth line back and baldness of the crown are the main signs of male androgenetic alopecia. In addition, areas of alopecia can merge into a single whole, as a result of which only a border of normal hair growth remains on the sides and on the back of the head of the scalp.
AGA can occur both in men and women, but it manifests differently between the two sexes.

In men, classic pattern balding appears as:

• Recession of the hairline at the temples
• Loss of hair at the vertex (crown)

AGA in women progresses more slowly, its severity is less, and shows a greater variety of responses to therapy.

There are three distinct patterns of AGA in women:

• diffuse thinning of the crown area while maintaining the frontal hairline (Ludwig model);
• thinning and spreading to the central part of the scalp in violation of the frontal hairline (Christmas tree model);
• thinning associated with bitemporal bald patches (Hamilton model) is more common in menopausal women and in women with hyperandrogenism.

In rare cases, extremely severe androgenetic alopecia or its early onset may be a symptom of a complex genetic disorder, such as:

• trichorinophalangeal syndrome;
• progeria;
• Laron syndrome;
• and myotonic dystrophy of Kurshman-Steinert-Batten.

Androgenetic alopecia, the clinical signs of which appear between the ages of 10 and 20 years, is called premature or early baldness. In children before puberty, the disease, both in boys and girls, manifests itself exclusively as female pattern baldness.

The differential diagnosis for congenital hair loss includes:
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• simple hypotrichosis;
• and ectodermal dysplasia (with concomitant physical/mental retardation, sweating, nail and tooth abnormalities).

Determining the severity of androgenetic alopecia is challenging.

The top row shows four drawings carved on the walls of a primitive cave. It took about 30,000 years to classify the pattern of male hair loss shown in the bottom row. At present, various classification methods have been developed and modified.

Until recently, the Hamilton-Norwood classification (1951-1975) for men and the Ludwig classification (1977) for women, emphasizing gender heterogeneity, were the generally accepted standard.

There was a need to improve existing classifications, as a result of which a universal classification was created in 2007. In 2007 Lee et al. proposed a basic and specific (BASP) classification system, which is an improved version of the Norwood-Hamilton classification, includes four basic types (L, M, C, U) and two specific types (F and V).

Anatomical regions of the scalp (a). The BAsic and SPecific classification systems (b). Four BAsic types (L, M, C and U) and two SPecific types (frontal [F] and vertex [V]). L, no recession is observed in the frontotemporal region; M, recession in the frontotemporal hairline is more obvious than the mid-anterior hairline; C, recession in the mid-anterior hairline is more obvious than the frontotemporal hairline; U, the anterior hairline recedes to the vertex forming a horseshoe shape.

Figure: Areas of the scalp. F-Frontal / M - Mid frontal / T-Temple / V-Vertex

The new pattern hair loss classification is a universal tool used for both men and women: the basic and specific (BASP) classification.

It can be used to evaluate both the further degree of hair loss and the response to therapy. By improving on the shortcomings of existing classifications, it is easy to remember and easier to apply in a clinical setting. The Norwood-Hamilton classification does not take into account some specific types of baldness, such as female pattern hair loss.

In addition, the Ludwig scale cannot be used to classify male pattern baldness in women. BASP classifies all types of hair loss regardless of gender or race.

AGA has specific features that distinguish it from other types of hair loss.

For starters, it primarily affects hair at the top part of the scalp – above the galea aponeurotica (the dense fibrous membrane that stretches across the top of the scalp).

Secondly, scalp regions affected by AGA show three defining characteristics of the condition:

1. Hair follicle miniaturization
2. Increased telogen:anagen hairs
3. Shortened anagen cycling

Each of these phases are covered below.

There are three types of hairs:

1. Lanugo hair. Fine long hair covering the foetus. Shed about 1 month before birth unless born prematurely. May reappear sometimes in severe malnutrition and anorexia nervosa.
2. Vellus hair. Fine, short unmedullated hair covering much of the body surface. They replace the lanugo hair just before birth.
3. Thick, pigmented hairs are called terminal hairs. Terminal hairs on the top of the head and in the beard, axillary, and bubic areas are influenced by androgenes.
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Figure: Schematic with possible dermal cellular mechanisms modulating a vellus-terminal transition. Increased influx into the dermal papilla (DP) during the telogen-anagen transition would trigger a large step change that would take a vellus hair to terminal state in one cycle. Comparatively, reduced DP cell efflux during catagen would over time result in a gradual increase in DP size assuming that influx of hfDSCs remains unchanged. Alternatively, both of these mechanisms may be required to act in tandem with one another to achieve a reversal of male pattern baldness

All hair follicles are replaced at different rates by the normal process of hair cycling. Hair growth alternates between phases of activity and rest.
1. Anagen Phase: The growth period, called the anagen phase, lasts for two to six years. During this time, the follicle is long and deep and produces thick, well-pigmented hair, the hair shaft is actively growing inside the follicle, with rapidly dividing new cells being supplied by the dermal papilla. About 90% of all scalp hairs are in the anagen phase at a given time.

2. Catagen Phase: Anagen is followed by a brief transition phase known as the catagen phase, which lasts 1–2 weeks. This is also called the degradation phase and is a transitional phase where the hair follicle pulls away from the dermal papilla. During this time, the base of the follicle shrivels. Since the hair follicle is no longer being supplied with the new cells from the dermal papilla, the hair stops growing. This stage is brief, usually lasting several days.

3. Telogen Phase: The resting period, or telogen phase, follows catagen and lasts for three months. In this phase, the shrunken follicle retains the hair fibre. Following the telogen phase, the next anagen phase begins, and the old hair is dislodged and falls out to make room for new hair to begin growing in its place. Since the hair follicle is no longer being supplied with the new cells from the dermal papilla, the hair stops growing. This lasts about 3-4 months.

(4). Exogen (shedding) phase: Exogen is a phase independent of the main hair follicle cycle where the club hair is actively shed from the old bulge. Exogen refers to the state of the club hair rather than the hair follicle.

(5). Kenogen (latent lag) phase: Kenogen is not observed in all hair follicles; however, frequency and duration increases in scalp follicles of individuals with AGA. It refers to a lag phase, or a follicle in telogen which has lost its club hair (exogen) prior to re-entry into anagen.

Hair follicles are the foundation on which healthy strands of hair are grown. It is the follicle that supplies the root of the hair with the oxygen, nutrients, and support needed to flourish during the anagen phase. The follicle also plays a vital role in supporting hair as it transitions through the catagen phase. During telogen phase, the hair follicle rests in preparation for new hair growth.

Though much is still being discovered about the root causes of hair loss, research shows that many hair loss conditions are associated with certain conditions that impair hair follicle health and function. To illustrate, consider:

• Telogen effluvium (stress-related hair loss) occurs after a stressful event causes enough trauma to “shock” the follicles into an inactive state. The hair loss condition receives its name from the telogen phase in which follicles become stuck.
• Androgentic alopecia (pattern baldness) is correlated with high levels of DHT (the androgen dihydrotestosterone) on the scalp. DHT is thought to penetrate the scalp and cause hair follicle miniaturization, a phenomenon in which follicles become smaller and eventually incapable of supporting a healthy hair growth cycle.

The development of AGA is based on gender homogeneity, which is associated with the genetic characteristics of androgen metabolism in the hair follicle.
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Male pattern hair loss is an inherited condition, caused by a genetically determined sensitivity to the effects of dihydrotestosterone (DHT) in some areas of the scalp. DHT is believed to shorten the growth, or anagen, phase of the hair cycle, from a usual duration of 3–6 years to just weeks or months. Follicle miniaturization is unique to AGA. It is a process by which AGA-affected hair follicles progressively get smaller until they produce fewer hairs. The hairs that are left may transition into fine, wispy hairs – known as vellus hairs.

A few women present with male pattern hair loss because they have excessive levels of androgens as well as genetic predisposition. These women also tend to suffer from acne, irregular menses and excessive facial and body hair. These symptoms are characteristic of polycystic ovarian syndrome (PCOS) although the majority of women with PCOS do not experience hair loss. Less often, congenital adrenal hyperplasia may be responsible. In women, as a rule, a large role is played by a decrease in the activity of aromatase, which converts ovarian testosterone circulating in the blood into 17 beta-estradiol. Females that are losing their hair with age are more likely to present with female pattern hair loss, in which hormone tests are normal. 

An increase in the local concentration of DHT leads to a progressive contraction of the anaphase due to a longer telogen phase and is accompanied by a progressive miniaturization of the HF. Miniaturization of the HF occurs due to relatively sharp reductions in the number of cells in the dermal papilla and dermal membrane. Accompanied by:

• reduction in the absolute number of HF,
• a decrease in the anaphase period,
• rod diameter,
• as well as an increase in the duration of the kenogen phase.

While the causes and step-processes of hair follicle miniaturization are still debated, this process is often accompanied by histological (i.e. structural) changes – particularly to the tissues surrounding these hair follicles.

In fact, researchers believe these structural changes help to explain why pattern hair loss is a progressive condition – as they limit miniaturized hair follicles’ capabilities of returning back to full-size. They are:

1. Dermal sheath thickening
2. Perifollicular fibrosis and perifollicular inflammation
3.  Oxidative stress
4.  The loss of connection between the levator pilus muscle and the follicular unit
5.  The replacement the levator pilus muscle by adipose tissue
6.  Increased telogen:anagen ratio
7.  Shortened anagen cycling

All of these histological changes can be considered forms of scarring.

In addition to androgen-dependent changes in the pathogenesis of AGA, the involvement of follicular microinflammation with the formation of fibrosis provoked by the presence of bacterial flora, toxins and oxidative stress has been proven.

According to the obtained data, inflammatory markers such as fibrinogen, C-reactive protein and lipoprotein (a) acted as risk factors for cardiovascular diseases in AGA. AGA has also been shown to be associated with increased arterial stiffness, even in asymptomatic young adults.

While complex genetic inheritance and age of the individual are major risk factors in AGA development, on a cellular level, the initiation of an inflammatory condition in the follicle microenvironment is considered the central event, with contributory mechanisms, including abnormal signal transduction (the wingless-type integration site pathway), high levels of apoptosis, and oxidative stress.

DHT, a major factor causing hair loss in AGA, has been found to act downstream by inducing the production of interleukin- (IL-) 6 and transforming growth factor- (TGF-) β2 by dermal papilla cells (DPCs), thus suppressing hair growth and premature onset of the catagen phase.

Figure: Progressive miniaturization within follicular units (FUs). Initially, multiple compound follicular units are found across the scalp comprising a primary follicle and multiple secondary follicles. Miniaturization occurs initially in the secondary follicles, leading to a reduction in hair density but no visible baldness. Baldness occurs when the entire follicular unit is miniaturized. As hairs miniaturize, there is progressive loss of contact between the APM and outer root sheath of the follicle at the level of the bulge. Loss of contact between the APM and ORS predicts irreversibility of miniaturization. In AGA, there appears to be a hierarchy of androgen sensitivity within FUs, the persisting terminal hairs represent primary follicle within the FU and that the miniaturized follicles that lose contact with the AP represent the secondary follicles.

Beyond hair follicle miniaturization, the second defining characteristic of AGA is an increase in telogen versus anagen hairs.

Telogen and anagen are terms used to describe specific stages of the hair cycle.

The hair cycle is the natural, ever-repeating cycle of regeneration and degeneration of hair follicles. A hair grows, stops growing, and eventually falls out – at which point a new hair follicle reforms and a new hair starts growing again. In human scalps, these hair cycles last between two to seven years.

In non-balding scalps, 80-85% of scalp hairs are in their growth (anagen) phase, 1-2% have stopped growing and are in their resting (catagen) phase, and 10-15% have already fallen out and entered their shedding (telogen) phase.

In healthy scalps, this cycle repeats indefinitely. Thus, many hair loss disorders can sometimes be identified by measuring the number of shedding versus growing hairs – and then comparing that ratio to what is seen in normal scalps. If the ratio is high, this suggests abnormal hair loss. If it’s low, this suggests normal, healthy hair.

This is the telogen:anagen ratio.

In normal scalps, there is generally one telogen hair for every 12 anagen hairs, or a 1:12 ratio.

However, in men with AGA, the telogen:anagen ratio can exceed 1:4 (or 25%). In women, this ratio often exceeds 2:5 (or 40%).

During pregnancy, estrogen levels are increased, which lengthens the hair growth phase and lessens the shedding phase, resulting in a thicker than normal head of hair. After pregnancy (postpartum), estrogen levels fall, resulting in an increased shedding/resting phase (telogen). This also results in less hair in the growth phase (anagen). Postpartum hair loss is temporary and normal, with hair growth cycles normalizing six months to a year after pregnancy and restoring your hair to pre-pregnancy thickness.

If DHT is elevated in balding scalps of most men (and some women), what causes DHT to increase in these regions? This is one question researchers are still trying to answer.

One small-scale study indicates that whole-body DHT may not be the culprit – or that AGA patients don’t seem to have elevated serum DHT versus controls (Urysiak-Czubatka et al., 2014). This gives the impression that elevated DHT in balding scalp tissue is likely a local issue, and not a systemic problem.

So, then, what causes DHT to increase in scalp tissues, specifically? Elevated 5α-reductase activity has been implicated, which explains the ability of 5α-reductase inhibitors like finasteride to halt the progression of AGA (English, 2018). However, finasteride treatment doesn’t fully reverse AGA; it generally just stop its progression.

Findings that AGA is not associated with polymorphisms in the 5α-reductase genes suggest that this enzymatic upregulation is unrelated to genetic predisposition (Ellis et al., 1998). This indicates a possible environmental factor. This assumption is supported by studies showing that in genetically identical twins, one twin can bald faster than his counterpart – despite both twins having the same sets of genes (Nyholt et al., 2003).

Although research is sparse regarding environmental factors influencing 5α-reductase activity, there are some clues.

In women with PCOS, insulin resistance is related to increased 5α-reductase activity, possibly explaining why pattern hair loss is often a feature of the disorder (Wu et al., 2017). Male AGA is also associated with insulin resistance, however, whether this is a result of enhanced enzyme activity is unclear (González-González et al., 2009).

But again, no research team has discovered a definitive answer to this question.

No one is sure. The closest answers we have (so far) come from DHT and its link to a signaling protein called transforming growth factor beta 1 (TGF-β1).

Follicular miniaturization, as well as dermal sheath thickening and perifollicular fibrosis, are key features of AGA. In vitro studies strongly implicate the role of a growth factor, TGF-β1, in these processes (Yoo et al., 2006).

One of TGF-β1’s primary roles in the body is promoting both wound healing and the deposition of fibrous scar tissue (Pakyari et al., 2013). Thus, elevated TGF-β1 activity is likely involved in AGA follicle miniaturization and may even contribute to the process.

TGF-β1 expression can be triggered by the binding of androgens – like DHT – to androgen receptors, and in a potentially dose-dependent manner (Yoo et al., 2006). TGF-β1 may also enhance androgen activity through an androgen co-activator, Hic-5, that allows androgens like DHT to more effectively influence gene expression, like TGF-β1, within cells (Dabiri et al., 2008).

Essentially, increased androgen activity enhances TGF-β1 expression, and TGF-β1 exacerbates androgen activity. This feedback loop creates a vicious cycle that may underpin AGA progression.

Genetically-determined increased androgen receptor expression in AGA tissue contributes to this upregulated androgen activity, but this genetic component alone isn’t enough to dictate AGA progression (Nyholt et al., 2003).

This begs the question: in AGA, what causes androgen activity to increase?

If activity is dictated by androgen availability in the hair follicle, the rate of DHT conversion by 5α-reductase (which is controlled by the number of 5α-reductase enzymes and their activity), and the involvement of co-activators, then what, beyond genetics, could trigger any one of these factors?

Future research will hopefully begin to answer these questions.

DHT is linked to hair loss in AGA scalps. But ironically, this same hormone also enhances facial and body hair growth (Thornton et al.,1993). This occurs in spite of a 3-5 times higher 5α-reductase activity in beard follicles.

Given androgens and their negative impact on hair growth in the scalp, one would assume that elevated 5α-reductase activity would result in beard hair loss, not growth. But, this isn’t true for either case. Why might this be?

Here are some drug free options to block dihydrotestosterone:

• Dong Quai
• Red Clover
• Black Cohosh
• Saw Palmetto
• Pumpkin Seed Oil
• Green Tea

Essential oils:

• Lavender
• Rosemary
• Peppermint

Minoxidil is a universal drug available on the domestic market with a wide spectrum of action.

Minoxidil, a piperidine pyrimidine derivative, an arteriolar vasodilator that activates potassium channels, is catalyzed in NKV by minoxidil sulfotransferase to minoxidil sulfate, an active metabolite that is presumably:

• stimulates hair follicles
• increases blood flow
• activates the expression of mRNA of endothelial vascular growth factor in the cells of the dermal papilla, providing an anti-apoptotic effect,
• prolongs anagen,
• leads to a reduction in telogen follicles and an increase in the size of the HF,
• demonstrated an immunoregulatory effect due to an inhibitory effect on T-lymphocytes.

A test is being developed to determine response to minoxidil. The issue of "predictability" of treatment with minoxidil is very relevant, because only 40% of patients can boast of regrowth of hair. At the same time, to evaluate the effectiveness of therapy, one has to wait from 3 to 6 months, all this time taking the medicine “for nothing”. The researchers tried to use the determination of sulfotransferase activity in hair follicles to diagnose the effect of minoxidil earlier.
The essence of the new test is based on the following observations. Minoxidil is converted to minoxidil sulfate in the scalp by the action of the SULT1A1 enzyme. It is assumed that the activity of SULT1A1 in hair follicles correlates with the effectiveness of the drug.
Thus, the use of a sulfotransferase test will help to exclude up to 95% of patients who are resistant to therapy.

Promising results in the treatment of male AGA are dutasteride, which is used by many dermatologists, despite the fact that the drug is approved for the treatment of this condition only in Korea. Dutasteride has a similar safety profile to finasteride.

Gübelin Harcha et al. in 2014 published the results of a large randomized controlled trial comparing the efficacy of different doses of dutasteride and 1 mg finasteride versus placebo. The authors found that compared with 1 mg of finasteride, the efficacy of taking 0.5 mg of dutasteride was significantly higher. These results further supported the superior efficacy of dutasteride (versus 5 mg finasteride) in increasing hair growth from Olsen's previous randomized controlled trial (Olsen et al. (2006)).

Scientists from Switzerland, taking care of the safety of AGA treatment, have developed a new patented product P-3074, which is a 0.25% finasteride lotion for topical use. In clinical testing, it reduces the concentration of dihydrotestosterone in the scalp by 40% more than oral finasteride. Topical preparations with a combination of minoxidil and finasteride are of interest.

The described powerful antioxidant properties of melatonin allow us to consider it as a possible option to counteract oxidative stress associated with involutional hair thinning in AGA and as a preventive measure in graying.

Recently, topical preparations of melatonin have entered the European market as an anti-aging cosmetic product. Topical melatonin has been shown to suppress UV-induced erythema threshold and also increases the proportion of anagen hair in women with AGA.

These data are supported by the results of a double-blind, placebo-controlled pilot study in which topical application of 1 ml of an alcoholic solution of melatonin 0.1% in women with AGA and diffuse alopecia resulted in a significant increase in anagen hair after six months of application compared with placebo.

Alternatives to minoxidil include cyproterone acetate, spironolactone, and flutamide.

It promotes re-growth in alopecia area by exerting an immunosuppressive effect. Hydrocortisone acetate (25mg/ml) and triamcinolone acetonide (5-10 mg/ml), betamethasone dipropionate 0.05% and fluocinolone acetonide (0.2%) are commonly used.

Currently, the efficacy and safety of minoxidil 2% and 5% twice daily solution for the treatment of AGA is of the highest level of evidence.
The results of the use of pharmacological agents approved for the treatment of other diseases, such as oral antiandrogens, are controversial.
If drug therapy is ineffective, surgical treatment is recommended, although in this case there is a high variability of results.
Several promising methods have recently been proposed.

In the absence of an established optimum concentration level, the currently used PRP preparation method achieves an enrichment of 300-700% (typically over 1,000,000 platelets/µl).

The possible effect of PRP on hair growth has been studied since 2012 in in vitro and in vivo studies in mice.

The actual mechanisms of action on the hair follicle remain controversial: PRP in vitro activates the proliferation of dermal papilla cells and prevents apoptosis, which provokes an increase in the expression level of Akt and Bcl-2. In addition, PRP is involved in the formation of the hair epithelium and the differentiation of stem cells into hair follicle cells. An increase in FGR-7 expression leads to an extension of the anagen phase in the hair growth cycle.

The published results of only a small number of clinical trials of the effectiveness of PRP for hair growth cannot be considered objective. Of the 14 trials included in the systematic review by Gkini et al., only 2 trials in women were evaluated according to the principles of evidence-based medicine.

Lasers and light therapy devices use monochromatic light sources with a wavelength of 600 to 1400 nm in the red/infrared region of the spectrum.

The use of low-intensity laser therapy (LLT), in particular, represents a new approach to the treatment of certain hair diseases, including androgenetic alopecia. Despite the lack of a clear understanding of the mechanism of action, laser therapy stimulates the re-transition of telogen hair follicles into the anagen phase, increases the duration of the anaphase by stimulating epidermal stem cells in the region of the hair follicle bulge, and prevents the premature onset of the catagen phase.

In addition, this type of therapy has been found to regulate the anti-inflammatory and immunological response.

In 2011, the US Food and Drug Administration (FDA) approved the use of the Hairmax Lasercomb R laser comb for the treatment of female AGA, but there are no published results from studies of its effectiveness in women.

Despite numerous studies, more data are needed to develop a standardized treatment procedure, including the optimal wavelength, degree of coherence, and dosimetric parameters.

The safety and possible efficacy of LILT as a treatment option for patients with AGA who are unresponsive or intolerant to standard therapy should be confirmed in further clinical trials.

A recent study examined the efficacy of topical injections of dutasteride in the treatment of female pattern hair loss in 126 patients. A combination of 0.5 mg of dutasteride, 20 mg of biotin, 200 mg of pyridoxine and 500 mg of D-panthenol in a 2 ml solution was injected into the crown area intradermally by mesotherapy. The injections were repeated weekly for 8 weeks, then every 2 weeks for 4 weeks, at the 16th week the last session was performed.

It was found that 18 weeks after the start of treatment (compared to the control group treated with saline), this method had a positive effect on hair growth in women with PVAT. At the 18th week, 62.8% of patients showed photographic improvement, an increase in hair diameter and a decrease in their loss.

Prostaglandin analogues (PGAs), such as latanoprost and bimatoprost, are topical agents for the treatment of glaucoma and intraocular hypertension. Later it was found that these substances promote the growth and pigmentation of eyelashes. The mechanism of action that promotes hair regrowth is presumably the stimulation of the dermal papilla, leading to the activation of the transition of telogen hair into the anagen phase.

To date, there are no data on the use of APG for the treatment of female AGA.

The use of bimatoprost 0.03% scalp injections once a week for 12 weeks and then every other week for 4 weeks in a 59-year-old female patient with PVAT was unsuccessful.

Based on the proposed effect on the release of platelet-derived growth factors, stem cell activation, and overexpression of genes associated with hair growth, microneedling therapy has been proposed as a new treatment for AGA.

A randomized trial of 100 men with mild to moderate AGA showed that the combined use of dermaroller and minoxidil 5% lotion in promoting hair growth was significantly superior to that of minoxidil alone.

Despite these promising results, the use of this method in the treatment of AGA needs to be confirmed in clinical trials.

If standard treatments fail to improve hair loss, hair transplantation may be considered as a treatment option. This still effective procedure must be performed by an experienced surgeon, during which individual hair follicles are transplanted from a donor site, but unlike men, in women, due to the diffuse nature of hair loss, the area of \u200b\u200bthe site is very limited.

Among the complications of the operation: temporary hair loss after transplantation, infections, pain and failure of the transplant.

Hair transplantation is performed by various methods, one of such methods is PL-FUT
longitudinal partial follicular unit transplantation.

The new method consists in partial longitudinal extraction of a follicular unit, which can be used as a complete follicular unit to form a fully differentiated hair follicle. The partial follicular unit remaining in the dermis at the donor site can survive and form a hair.

Modern areas of research and future methods of therapeutic intervention are:

• stem cells of follicular origin,
• as well as technologies for cultivating hair follicle tissues.

Accurate identification and effective delivery of the appropriate defense and trigger mechanisms that will stimulate the activation of quiescent stem cells can make the prevention and reversal of hair loss a reality.