Normal hair loss (alopecia)

Common baldness (syn.: androgenetic alopecia, androgenic baldness, androgenic alopecia)

Hair change, which begins before birth, occurs throughout a person's life. Humans are not the only primates in which baldness is a natural phenomenon associated with sexual maturity. Minor baldness develops in adult orangutans, chimpanzees, and tailless macaques, with the latter having the greatest similarity to that in humans.

Conventional baldness may be noticeable in healthy men by age 17 and in healthy women by age 25-30. During baldness, terminal hairs become thinner, shorter, and less pigmented. The reduction in follicle size is accompanied by a shortening of the anagen phase and an increase in the number of hairs in the telogen phase.

N. Orentreich named this type of baldness “androgenic” in 1960, emphasizing the leading role of the effect of androgens on androgen-dependent hair follicles.

Androgenetic alopecia is often incorrectly referred to as male pattern baldness, which leads to its unreasonably rare diagnosis in women, especially when assessing the early manifestations of alopecia, since the pattern of hair loss in women is different than in men.

The nature of hair loss in normal baldness

The first, and still significant, classification of types of common baldness belongs to the American doctor J. Hamilton (1951). Having examined more than 500 people of both sexes aged 20 to 79 years, the author identified 8 types of baldness.

There is no baldness in the parietal area	Type I	Hair preserved;
	Type IA	the frontal hairline recedes, the forehead becomes higher
	Type II	bald spots on both sides of the temples;
	Type III	borderline;
	Type IV	deep frontotemporal baldness. There is usually also a receding hairline along the midline of the forehead. In older people, this degree of hair loss in the frontotemporal region may be combined with thinning hair on the crown
There is baldness in the parietal area	Type V	enlarged frontal-temporal bald spots and pronounced baldness of the crown;
	Type VI and VIA	increased hair loss in both areas, which gradually merge;
	Type VII	an increase in the frontal-temporal and parietal baldness zones, separated only by a line of sparse hair;
	Type VIII	complete fusion of these areas of baldness.

J. Hamilton described the progression from the normal prepubertal hair growth pattern (type I) to type II, which develops after puberty in 96% of men and 79% of women. Types V-VIII baldness is characteristic of 58% of men over 50 years of age, with progression to 70 years. It was later noted that men in whom baldness in the parietal region forms before the age of 55 are more likely to suffer from coronary artery disease.

In women, types V-VIII baldness do not occur. In 25% of women by the age of 50, type IV baldness develops. In some women with type II baldness, hair growth is restored to normal (type I) during menopause. Although these types of baldness sometimes occur in women, androgenic alopecia in women is often diffuse. In this regard, to assess common baldness in women, it is more convenient to use the classification of E. Ludwig (1977), who identified three types of alopecia.

• Type (stage) I: Noticeable, oval-shaped diffuse thinning of hair in the frontal-parietal region, along the anterior hairline, hair density is unchanged.
• Type (stage) II: More noticeable diffuse thinning of hair in the specified area.
• Type (stage) III: Almost complete or total baldness of the specified area. The hair surrounding the bald area is preserved, but its diameter is reduced.

The types (stages) of baldness identified by J. Hamilton and E. Ludwig are certainly not a method for measuring the degree of hair loss, but they are convenient for practical work, in particular, when evaluating the results of clinical trials. In surgical correction of baldness, the generally accepted standard is the Norwood classification (1975), which is a modified Hamilton classification.

The change from prepubertal hair growth to adult hair growth is significant. The extent and speed of these changes are determined by genetic predisposition and the level of sex hormones in both sexes. The role of living conditions, nutrition, the state of the nervous system and other factors influencing the aging process and hair loss cannot be ruled out.

The discovery of the role of androgens in the pathogenesis of common baldness has given rise to the idea that balding men are more sexually active. However, this assertion lacks scientific substantiation. No connection has been found between hair loss on the head and thick hair growth on the trunk and limbs.

Heredity and baldness

The enormous frequency of common baldness makes it difficult to determine the mode of inheritance. The current state of knowledge suggests a lack of genetic homogeneity.

Some authors distinguish between normal baldness in men with early (before 30 years) and late (over 50 years) onset. It has been established that in both cases baldness is inherited and depends on androgenic stimulation of hair follicles.

It has been suggested that baldness is determined by a single pair of sex-specific factors. According to this hypothesis, normal baldness occurs in both sexes with the BB genotype and in men with the Bv genotype. Women with the Bv genotype and men and women with the bb genotype are not predisposed to baldness.

When studying the immediate relatives of women with normal baldness, it was found that a similar process occurred in 54% of men and

25% of women over 30 years of age. It has been suggested that common baldness develops in heterozygous women. In men, this process is due to either a dominant type of inheritance with increased penetrance, or there is a multifactorial nature of inheritance.

The identification of a biochemical marker of baldness may help clarify the type of inheritance. Thus, 2 groups of young men with different activity of the enzyme 17b-hydroxysteroid in the scalp have already been established. In families of patients with high activity of this enzyme, many relatives suffered from pronounced baldness. On the contrary, low activity of the enzyme is associated with the preservation of hair. Research in this promising direction continues.

The connection between seborrhea and common baldness

The connection between increased sebum secretion and regular baldness has been noted for a long time and is reflected in the frequent use of the term "seborrheic alopecia" as a synonym for regular baldness. The function of the sebaceous glands, like androgen-dependent hair follicles, is under the control of androgens. Androgens cause an increase in the size of the sebaceous glands and the amount of excreted sebum, which was proven when testosterone was prescribed to boys in the prepubertal period. Testosterone prescription to adult men did not have a similar effect, since, probably, during puberty, the sebaceous glands are maximally stimulated by endogenous androgens at their normal level. In addition to testosterone, other androgens also stimulate sebum production in men: dehydroepiandrosterone and androstenedione. Androsterone does not have a similar effect. However, gravimetric studies of sebum production on the bald scalp compared to other areas of the scalp, as well as compared to these parameters in non-balding subjects, did not reveal significant differences.

In women, sebum production increases even with a slight increase in the level of circulating androgens. It is generally accepted that normal, or androgenic, alopecia in women is part of the hyperandrogenism syndrome, which, in addition to seborrhea and alopecia, also includes acne and hirsutism. However, the severity of each of these manifestations can vary widely.

Frequent hair washing, recommended by many cosmetologists, does reduce hair loss over the next 24 hours, but this is explained by the removal of hair at the end of the telogen phase during washing.

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How does baldness develop?

Changes begin with focal perivascular basophilic degeneration of the lower third of the connective tissue sheath of the hair follicle in the anagen phase. Later, a perifollicular lymphohistiocytic infiltrate forms at the level of the sebaceous gland excretory duct. Destruction of the connective tissue sheath causes irreversibility of hair loss. Multinucleated giant cells surrounding hair fragments are found in approximately 1/3 of biopsies. Most follicles in the area of the formed bald spot are short and reduced in size. It should be mentioned that horizontal sections of the biopsy are more convenient for morphometric analysis.

Under the influence of ultraviolet rays, degenerative changes in the skin develop in areas deprived of hair protection.

Modern research methods have shown that the onset of baldness is accompanied by a decrease in blood flow. Unlike the richly vascularized normal follicle, the vessels surrounding the root of the vellus hair are few in number and tortuous, and are difficult to detect. It remains unclear whether the decrease in blood flow is primary or secondary to baldness. It has been suggested that the same factors are responsible for changes in both the vessels and follicles.

In normal baldness, there is a shortening of the anagen phase of the hair cycle and, accordingly, an increase in the number of hairs in the telogen phase, which can be determined by the trichogram in the frontal-parietal region long before baldness becomes obvious.

Miniaturization of hair follicles results in a decrease in the diameter of the hairs they produce, sometimes 10-fold (to 0.01 mm instead of 0.1 mm), which is more pronounced in women than in men. Some follicles are late in entering the anagen phase after hair loss, and the mouths of such follicles appear empty.

Pathogenesis of common alopecia (hair loss)

The role of androgens in the development of common baldness is now widely recognized.

The hypothesis of the androgenic nature of baldness seems to be quite reasonable, since it allows us to explain a number of clinical observations: the presence of baldness in humans and other primates; the presence of the disease in men and women; the combination of baldness in both sexes with seborrhea and acne, and in some women with hirsutism; the location of baldness zones on the scalp.

J. Hamilton demonstrated the absence of baldness in eunuchs and in castrated adult men. Testosterone administration caused baldness only in genetically predisposed subjects. After testosterone was discontinued, the progression of baldness ceased, but hair growth did not resume.

The hypothesis of hypersecretion of testicular or adrenal androgens in balding men has not been confirmed. Thanks to modern methods of determining free and bound androgens, it has been shown that normal androgen levels are sufficient for the occurrence of baldness in genetically predisposed men.

In women, the situation is different; the degree of hair loss depends in part on the level of circulating androgens. Up to 48% of women with diffuse alopecia suffer from polycystic ovary syndrome; hair loss on the scalp in such patients is often combined with seborrhea, acne and hirsutism. The maximum changes in hair growth occur after menopause, when the level of estrogens falls, but the "androgen supply" remains. During menopause, androgens cause hair loss only in genetically predisposed women. With a less pronounced genetic predisposition, baldness develops only with increased production of androgens or taking medications with androgen-like action (for example, progestrogens as oral contraceptives; anabolic steroids, which are often taken by female athletes). At the same time, in some women, even a sharp increase in androgen levels does not cause any significant baldness, although the manifestation of hirsutism always occurs in such cases.

Since the establishment of the leading role of androgens in the development of common baldness, the efforts of many scientists have been focused on uncovering the mechanism of their action. The brilliant results of transplanting hair follicle-containing autografts from the occipital region to the baldness zone have convincingly demonstrated that each hair follicle has a genetic program that determines its reaction to androgens (androgen-sensitive and androgen-resistant follicles).

The effect of androgens on hair follicles varies in different areas of the body. Thus, androgens stimulate beard growth, pubic hair growth, axillary hair growth, chest hair growth, and, conversely, slow down hair growth on the head in the area of androgen-sensitive follicles in genetically predisposed individuals. Hair growth is controlled by different hormones: testosterone (T) stimulates pubic and axillary hair growth; dihydrotestosterone (DHT) causes beard growth and regular baldness on the scalp.

The occurrence of common baldness is determined by two key factors: the presence of androgen receptors and the activity of androgen-converting enzymes (5-alpha-reductase types I and II, aromatase and 17-hydroxysteroid dehydrogenase) in different areas of the scalp.

It has been established that in the frontoparietal region in men the level of androgen receptors is 1.5 times higher than in the occipital region. The presence of androgen receptors has been demonstrated in the culture of dermal papilla cells taken from the scalp of both balding and non-balding subjects, and is also indirectly confirmed by the good effect of antiandrogens in diffuse alopecia in women. These receptors have not been detected in the cells of the matrix and the outer root sheath of the hair follicle.

The second key factor in the pathogenesis of common alopecia is a change in the balance of enzymes involved in androgen metabolism. 5a-reductase catalyzes the conversion of T into its more active metabolite, DTS. Although type I 5a-reductase dominates in scalp tissue extracts, type II of this enzyme has also been found in the hair sheath and dermal papilla. Moreover, individuals with congenital deficiency of type II 5a-reductase are not known to suffer from common alopecia. The DTS receptor complex has a high affinity for nuclear chromatin receptors, and their contact triggers the process of hair follicle growth inhibition and its gradual miniaturization.

While 5a-reductase promotes the conversion of T to DTS, the enzyme aromatase converts androstenedione to estrone and T to estradiol. Thus, both enzymes play a role in the development of common hair loss.

When studying the metabolism of androgens in the scalp, increased activity of 5-reductase was found in bald spots. In men, the activity of 5a-reductase in the skin of the frontal region is 2 times higher than in the occipital region; aromatase activity in both areas is minimal. In women, the activity of 5a-reductase in the frontal-parietal region is also 2 times higher, but the total amount of this enzyme in women is half that of men. Aromatase activity in the scalp of women is higher than in men. Preservation of the anterior hairline in most women with normal baldness is apparently explained by high activity of aromatase, which converts androgens to estrogens. The latter are known to have an antiandrogenic effect due to their ability to increase the level of proteins that bind sex hormones. Intensive hair loss in men is associated with low aromatase activity and, accordingly, with increased production of DTS.

Some steroid enzymes (3alpha-, 3beta-, 17beta-hydroxysteroids) have the ability to convert weak androgens, such as dehydroepiandrosterone, into more potent androgens that have different tissue targets. The concentration of these enzymes in balding and non-balding areas of the head is the same, but their specific activity in the frontal region is significantly higher than in the occipital region, and in men this indicator is significantly higher than in women.

It is also known that prescribing growth hormone to men with a deficiency of this hormone increases the risk of androgenic alopecia. This effect is explained either by direct stimulation of androgen receptors by insulin-like growth factor-1, or by this factor acting indirectly, activating 5a-reductase and, accordingly, accelerating the conversion of T to DTS. The function of proteins that bind sex hormones is poorly understood. It has been suggested that high levels of these proteins make T less accessible for metabolic processes, reducing the risk of baldness.

The influence of cytokines and growth factors on the hair loss process should also be taken into account. Accumulating data indicate an important role for the regulation of cytokine, growth factor and antioxin gene expression during hair cycle initiation. Attempts are being made to identify key molecules of cyclic hair growth activity. It is planned to study the changes caused by these substances during their interaction with hair follicle cells at the subcellular and nuclear levels.

Symptoms of baldness

The main clinical sign common to both men and women is the replacement of terminal hair with thinner, shorter and less pigmented hair. The reduction in the size of hair follicles is accompanied by a shortening of the anagen phase and, accordingly, an increase in the number of hairs in the telogen phase. With each hair cycle, the size of the follicle decreases and the cycle time shortens. Clinically, this is manifested by an increase in hair loss in the telogen phase, which forces the patient to consult a doctor.

In men, the process of baldness begins with a change in the frontotemporal hairline; it recedes from the sides, forming the so-called "professor's angles", the forehead becomes higher. It is noted that changes in the frontal hairline do not occur in men with familial pseudohermaphroditism associated with 5a-reductase deficiency. As alopecia progresses, the hair in the pre- and postauricular areas changes texture - it resembles a beard (moustache). Bitemporal bald spots gradually deepen, hair thinning appears, and then a bald spot in the parietal region. In some men, vellus hair is preserved in the parietal region for a long time. The rate of progression and the pattern of normal baldness are determined by genetic factors, but the influence of unfavorable environmental factors cannot be ruled out. It is characteristic that with normal baldness, hair is completely preserved in the lateral and posterior parts of the scalp (in the form of a horseshoe). The sequence of hair loss in men is described in detail by J. Hamilton.

In women, the frontal hairline usually does not change, there is a diffuse thinning of hair in the frontal-parietal area. Thinner and vellus hair is "scattered" among normal hair. A widening of the central parting is typical. This type of baldness is often described as "chronic diffuse alopecia". Sometimes there is partial baldness of the parietal area, but diffuse alopecia is much more typical. E. Ludwig described the consistent change in clinical manifestations of baldness "according to the female pattern". Changes in the pattern of hair growth occur in all women after puberty. The rate of these changes is very slow, but it increases after the onset of menopause. It is known that progesterone-dominant contraceptives increase hair loss. Women with rapid progression of common baldness, as well as women with a gradual onset of alopecia combined with dysmenorrhea, hirsutism and acne, need a thorough examination to identify the cause of hyperandrogenism.

Alopecia areata

Focal (nesting) alopecia is characterized by the appearance of single or multiple rounded bald patches of varying sizes, which can be located both on the surface of the head and in the area of the eyebrows, eyelashes or on the beard. As the disease progresses, the surface area of such foci becomes larger, they can also connect with each other and take on an arbitrary shape. With complete hair loss, baldness is considered total. If hair disappears from the surface of the body, we are talking about universal baldness. Focal alopecia progresses quite quickly, but often hair growth resumes on its own. However, in about thirty percent of cases, the disease can take a cyclical form with periodic alternation of hair loss and renewal. The main factors that provoke the development of focal alopecia include problems with the immune system, hereditary predisposition, the negative impact of stress and environmental factors, traumatic and acute pathologies. In most cases, focal alopecia is treated with corticosteroids, which are included in various creams, tablets, and injection solutions. It is also possible to use drugs that enhance the production of corticosteroids in the body. But it should be noted that such drugs can only promote hair growth in the affected areas and are not able to affect the causes of the disease and prevent the reappearance of bald spots.

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Baldness in men

Baldness in men is often androgenetic. The causes of this disease are associated with genetic predisposition. The male hormone testosterone begins to have a destructive effect on the hair follicles, as a result of which the hair weakens, becomes thinner, shorter and loses color, bald spots appear on the head. Years after the development of androgenetic alopecia, the follicles completely lose the ability to form hair. Baldness in men can be associated with prolonged stress situations, which result in narrowing of the blood vessels of the scalp, which causes a lack of nutrition in the hair roots and hair loss. Some medications, such as aspirin, diuretics, antidepressants can cause side effects in the form of hair loss. In diseases of the endocrine system, baldness can be localized in the eyebrows, forehead or back of the head. Hair first dries out, becomes dull, becomes thin and sparse, and then falls out completely. There is also an opinion that nicotine addiction, which increases the production of estrogens in the body and disrupts blood flow in the skin, can also provoke the risk of developing baldness.

Baldness in women

Baldness in women can be associated with the following reasons:

• Damage to hair follicles due to repeated excessive pulling or harsh plucking of hair, such as from careless brushing.
• Too frequent use of a hair dryer, curling iron, straightening iron, cosmetics, which leads to weakening and thinning of hair and further hair loss.
• Malfunction of the ovaries and adrenal glands, hormonal imbalances in the body.
• Intoxication, infectious pathologies.
• Cicatricial changes in the skin caused by injuries, neoplasms, severe infections.

To diagnose the causes of baldness, a hair trichogram is performed and a blood test is taken. With the help of a trichogram, the condition of not only the hair itself is examined, but also the hair follicle, bulb, bursa, etc., and the ratio of hair growth at different stages is determined. Women are more susceptible to diffuse baldness than men, which is characterized by an intensive process of hair loss. Often, after eliminating the cause of diffuse baldness, the hair is able to recover within three to nine months, since the hair follicles do not die and continue to function.

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Baldness in children

In infants, baldness can be observed in the forehead and back of the head and is often associated with constant friction of the baby's head against the pillow, since in infancy the baby spends most of the time in a lying position. Hormonal changes that occur in the first year of the baby's life can also cause hair loss. In older children, hair loss can be caused by damage to the hair shaft, which can occur with constant strong pulling of the hair, as well as chemical exposure. A phenomenon such as trichotillomania, when a child intensely and often involuntarily pulls his hair, can also cause hair loss. This phenomenon can be caused by neurotic conditions, the diagnosis and treatment of which should be carried out by a qualified specialist. Among the causes of baldness in children, a disease such as ringworm is often encountered, which occurs as a result of damage to the scalp, as well as eyelashes and eyebrows by a fungal infection. The lesions in such cases are usually round or oval, the hair becomes brittle and subsequently falls out. Treatment is usually carried out with antifungal drugs, as an auxiliary means it is possible to use the shampoo "Nizoral" for two months. The shampoo is used twice a week, and for prevention purposes - once every fourteen days. After applying to the scalp, the shampoo is left on the hair for about five minutes, then washed off with water.

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Diagnosis of baldness

Diagnosis of common male pattern baldness is based on the following criteria:

• the onset of hair loss during puberty
• the nature of changes in hair growth (symmetrical bitemporal bald spots, thinning hair in the frontal-parietal region)
• hair miniaturization (reduction of its diameter and length)
• anamnestic data on the presence of common baldness in the patient's relatives

In general, the same criteria are used to diagnose common baldness in women. The only exception is the nature of the change in hair growth: the front line of hair growth does not change, there is diffuse thinning of hair in the frontal-parietal region, and the central parting widens.

When collecting anamnesis from women, it is necessary to pay attention to recent pregnancy, taking contraceptives, and endocrine system disorders. The following may indicate endocrine pathology:

• dysmenorrhea
• infertility
• seborrhea and acne
• hirsutism
• obesity

Women with hair loss combined with any of the above symptoms require a thorough examination to identify the cause of hyperandrogenism (polycystic ovary syndrome, late-onset congenital adrenal hyperplasia). In some patients, despite the clinically distinct hyperandrogenism syndrome (seborrhea, acne, hirsutism, diffuse alopecia), no endocrine pathology can be identified. In such cases, peripheral hyperandrogenism is likely to occur against the background of normal serum androgen levels.

When diagnosing common baldness, one should not forget about other possible causes of hair loss. Most often, common baldness can be combined with chronic telogen effluvium, as a result of which the symptoms of common baldness become more noticeable. In these cases, patients of both sexes need additional laboratory examination, including a clinical blood test, determination of the level of iron, thyroxine and thyroid-stimulating hormone in the blood serum, etc.

One of the objective methods of diagnosing common baldness is a trichogram - a method of microscopic examination of removed hair, which allows one to get an idea of the ratio of hair in the anagen and telogen phases. To obtain reliable research results, the following conditions must be met:

1. Remove at least 50 hairs, as the standard deviation is too large with a small number of hairs.
2. Hair should not be washed for a week before the examination to avoid premature removal of hairs approaching the end of the telogen phase; otherwise, the percentage of hairs in this phase is artificially reduced.
3. Hair should be removed with a sharp movement, as this causes less damage to the hair roots than with slow traction.

The bulbs of the removed hairs are stained with 4-dimethyl-aminocinnamaldehydе (DACA), selectively regulating with citrine, which contains) only in the inner root sheath. Hair bulbs in the telogen phase, deprived of the inner sheath, are not stained with DACA and look small, unpigmented and rounded (club). Hair in the anagen phase is characterized by elongated pigmented bulbs, surrounded by an inner root sheath, which DACA stains bright red.

In normal baldness, the trichogram of hair taken from the frontal-parietal region reveals an increased number of hairs in the telogen phase and, accordingly, a decrease in the anagen/telogen index (normally 9:1); dystrophic hair is also encountered. In the temporal and occipital regions, the trichogram is normal.

Histological examination is not used as a diagnostic method.

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How to stop baldness?

To accurately answer the question of how to stop baldness, you need to undergo a preliminary examination to identify the causes of hair loss. In the treatment of androgenetic alopecia, such drugs as minoxidil and finasteride (recommended for use by men) are considered effective. Minoxidil is able to influence the structure and activity of hair follicle cells, slowing down hair loss and stimulating their growth. The drug is applied to dry scalp with a special applicator, avoiding contact with other areas of the skin, use this product no more than twice a day, one milliliter at a time. Within four hours after applying the drug, the head should not be wetted. Minoxidil is contraindicated for children, as well as people with individual intolerance to the components included in the drug. It is prohibited to apply such a product to damaged skin, for example, with sunburn. Minoxidil is ineffective if the baldness was caused by taking any medications, poor diet, or excessive pulling of the hair into a bun. In order to stop baldness, a method such as hair transplantation can be used. Hair follicles from the occipital and lateral segments of the head are transferred to the bald spots. After such a transplant, the follicles continue to function normally and produce healthy hair.