Hormones and hair condition
2019-12-11
In anti-aging medicine, much attention is paid to hormone replacement therapy. The gradual reduction and imbalance of hormones is associated with the aging process. Let's understand the hormones that affect hair.
Yulia Ovcharenko, Associate Professor of the Department of Dermatovenereology of the Kharkov Medical Academy of Postgraduate Education (KMAPO), Head of the Institute of Trichology Clinic, Member of the Board of the European Society for Hair Research (Ukraine)
Anti-aging medicine is concerned with the discovery and use of treatments aimed at modifying, weakening or slowing down the diseases that progress with age. Among many methods, experts pay great attention to hormone replacement therapy, based on the assumption that the gradual reduction and imbalance of hormones with age are closely related to the aging process. In both sexes, levels of the growth hormones melatonin, dehydroepiandrosterone (DHEA) and its sulfate form DHEAS peak in the third decade of life and then gradually decline. In addition, men experience a continuous decrease in the production of biologically active free testosterone by approximately 1% per year. An abrupt cessation of sex hormone production is not typical for men, unlike women [1].
Target organs, which include skin and hair, signal these involutional changes. The hair follicle (HF) is a constantly changing organ capable of regenerating new and different hair under hormonal regulation, ensuring that hair type matches the season, age or gender, and is thus not only the most important marker of aging, but also a stigma that characterizes endocrine and somatic status.
And with the identification of hormones as an important factor in the hair growth cycle, new therapeutic options have emerged to influence hair growth through the regulation of hormonal influences.
Among the hormones that influence the condition of hair, the most important are androgens, estrogens, thyroid and parathyroid hormones, prolactin, corticosteroids, growth hormone and melatonin [2]. In this publication, we propose to consider in more detail these clinically important and sometimes paradoxical interactions.
Effect of androgens on hair growth
Androgens are the main regulator of human hair growth, with paradoxical differences in follicular responses depending on location on the body: from stimulating the beard, for example, to stopping hair growth on the scalp, but without any effect on the eyelashes. At the same time, in different zones of hair growth on the head, the sensitivity of the VF to androgens is determined: in the area of the crown and crown it is increased, which leads to a slow progression of miniaturization processes; in the occipital region, the VFs are insensitive to the action of androgens. Transplanted follicles retain this variety of reactions, and this fact underlies corrective cosmetic surgeries for androgenetic alopecia (AGA) [3].
One of the first signs of puberty is the gradual replacement of the finest vellus hairs by larger, pigmented intermediate hairs on the pubis and later in the armpits, eventually producing larger, darker terminal hairs. These changes occur in parallel with the pubertal increase in androgens in the blood plasma, which occurs earlier in girls than in boys. The same metamorphoses occur in many other parts of the body in young men, leading to the growth of a beard, pubic hair, the appearance of hair on the chest and an increase in their amount on the limbs - by these signs it is easy to distinguish an adult man. Beard growth increases sharply during puberty and continues to increase until approximately 35–40 years of age, with terminal hair on the chest or ear canals not appearing until several years after puberty. However, androgens have no obvious effect on many of the follicles that produce terminal hair in childhood, such as the eyelashes, or many of the follicles of the scalp. Paradoxically, in individuals with a genetic predisposition, androgens promote the gradual transformation of large terminal follicles of the head into vellus follicles, causing AGA. Apart from the role of androgens, the exact mechanisms of these responses within the hair follicle are not fully understood, although it is clear that these responses are individual in nature and depend on the location of the follicle on the body site [4].
Steroid hormones regulate cell growth, differentiation and metabolism. Disorders of the adrenal glands can lead to both increased glucocorticoid activity and insufficient activity, excessive androgen activity or insufficient.
Increased androgen activity is expressed in early puberty in children and virilization in women, while in men it is asymptomatic. Excess androgens can result from many different conditions of both the adrenal glands and the ovaries. These include congenital adrenal hyperplasia, or adrenogenital syndromes, adrenal tumors, Cushing's syndrome, polycystic and ovarian tumors, as well as other neoplasms not related to the adrenal glands and ovaries. Dermatological signs of virilization include, among others, hirsutism and AGA. Rapid onset of signs of virilization, DHEAS levels greater than 600 ng/L, and free testosterone levels greater than 200 ng/L suggest the presence of an androgen-producing tumor. Adrenogenital syndromes are the result of genetically determined disorders of cortisol synthesis. Increased production of ACTH, causing increased stimulation of the adrenal glands, in combination with blockade of the cortisol pathway leads to the accumulation of adrenal androgens, causing virilization in women. Partial 21-hydroxylase deficiency can manifest as hirsutism, even in older women.
Hypercortisolism, or Cushing's syndrome, is a sign of increased secretion of cortisol by the adrenal glands due to some cause. Most often, this condition is iatrogenic due to the use of glucocorticosteroids (GCS), but similar signs are present in patients with endogenous hypercortisolism, due to production of adrenocorticotropic hormone (ACTH) by the pituitary gland (Cushing's disease), with adrenal tumors, or with ectopic ACTH production. Hypertension and weight gain are early manifestations of the disease, typical skin symptoms include redistribution of fat, obesity with deposits in the trunk area, moon-shaped face and thin arms, skin atrophy, which quickly bruises, pigmented hypertrichosis of the face, general increase in lanugo hair and alopecia. These phenomena may initially be dismissed as secondary to normal skin aging.
Insufficient androgen activity can lead to decreased sex drive, loss of muscle tone, dry skin, and decreased vital energy. The development of androgen deficiency after puberty is characterized by the presence of slowly growing pubic hair, since the maintenance of already formed pubic hair is less dependent on androgens than their production.
Addison's disease is a chronic insufficiency of the adrenal cortex. The most striking dermatological sign is an increase in skin pigmentation; hair may also become darker [1].
Menopause and hair condition
During menopause, the ovaries stop producing hormones that control reproduction and can affect sexual behavior. A decrease in the level of circulating estrogen affects the entire chain of a woman’s reproductive function - from the brain to the skin. The typical age for menopause is between 45 and 55 years. Postmenopausal women face dermatological problems such as atrophy, dryness, itching, loss of skin elasticity and flexibility, increased skin trauma, dry hair and alopecia [5]. It is now generally accepted that these phenomena are caused by low estrogen levels.
Clinical evidence of the effect of estrogens on hair growth has been obtained by observing the effects of pregnancy, taking hormonal medications that affect estrogen metabolism, and menopause on hair condition. During the second half of pregnancy, the proportion of anagen hair increases from 85 to 95% [6], while the proportion of hair with a large shaft diameter is also higher than in women of the same age who are not preparing for motherhood. After childbirth, the follicles rapidly transition from the extended anagen phase to the catagen and then telogen phases, followed by increased hair loss noticeable after 1–4 months (postpartum effluvium). The increased hair loss observed in many women between 2 weeks and 3 to 4 months after stopping oral contraceptives is similar to the hair loss typically seen after childbirth. Birth control pills or hormone replacement therapy with progestogens that have androgenic activity (norethisterone, levonorgestrel, tibolone) are more likely to cause generalized baldness in genetically predisposed women. It has been suggested that with a genetic predisposition, the ratio of estrogen to androgens may be a provoking factor for hair loss in women [7]. This also corresponds to hair loss provoked in predisposed women by treatment with aromatase inhibitors for breast cancer [8]. Finally, postmenopausal women show an increased tendency to experience male pattern hair loss [9].
Estrogens certainly have important functions in many parts of the human skin, including the epidermis, dermis, vasculature, hair follicle, and sebaceous and sweat glands, which play a significant role in skin aging, pigmentation, hair growth and sebum production. [10]. In addition to altering gene transcription through estrogen-responsive elements, 17-beta-estradiol (E2) also alters androgen metabolism in the pilosebation complex, which itself exhibits marked aromatase activity, a key enzyme in the conversion of androgens to E2. Thus, the hair follicle is both a target for estrogens and their source. Estrogens have been found to influence hair follicle growth and cyclicity by binding to locally expressed high-affinity estrogen receptors (ERs). The discovery of a second intracellular estrogen receptor (ERbeta), which performs cellular functions that differ from the classical estrogen receptor (ERalpha), as well as the identification of membrane estrogen receptors in the hair follicle have become areas that are subject to further research to understand the mechanism of action of estrogen on hair growth [11].
Effect of thyroid-stimulating hormones
Thyroid hormones influence the growth and differentiation of many tissues and the overall energy expenditure of the body, the circulation of many substrates, vitamins and other hormones. The activity of the thyroid gland influences oxygen consumption, protein synthesis and mitosis and is therefore of great importance for hair formation and growth. Expression of the thyroid hormone receptor beta-1 has been demonstrated in the human hair follicle. Triiodothyronine has been shown to significantly increase the survival rate of human hair in vitro [12]. The effect of thyroid hormone activity on hair is most noticeable when there is a deficiency or excess. Schell et al. [13], who for the first time analyzed DNA using flow cytometry, demonstrated the influence of thyroid hormones on the in vivo dynamics of the cell cycle of human hair follicles of the scalp. Clinically, the effects of thyroid disease on hair are nonspecific, but associated symptoms and signs of thyroid hormone deficiency or excess can provide important clues to the diagnosis of thyroid disease.
Hypothyroidism results from a deficiency of thyroid hormones. It most often occurs due to chronic autoimmune thyroiditis (Hashimoto's disease) or iatrogenic ablation of the thyroid gland (sodium iodide-131 treatment or surgical thyroidectomy). Hypothyroidism occurs approximately ten times more often in women than in men, and is especially common between the ages of 40 and 60 years. Patients have dry, rough skin, and in severe cases the condition may resemble ichthyosis. The skin of the face is swollen, with an increased number of wrinkles, the face may have an “empty”, monotonous expression. Hair becomes dull, coarse and brittle, and diffuse alopecia with thinning of the lateral eyebrows may occur. The rate of hair growth slows down, and the proportion of telogen hair increases. Alopecia is characterized by a gradual onset. In genetically predisposed individuals, prolonged hypothyroidism may be accompanied by AGA. The proposed mechanism is due to an increase in free androgens in plasma [1].
Hyperthyroidism is caused by excess circulating thyroid hormones. The most common cause of hyperthyroidism today is Graves' disease, with an estimated prevalence of 5.9% in the population of patients aged 60 years and older. This is an autoimmune disease that affects women much more often than men. The most common symptoms of hyperthyroidism are systemic rather than cutaneous and are caused by a hypermetabolic state known as thyrotoxicosis. However, diffuse hair loss is observed in 20–40% of cases, and axillary hair loss in 60% [14]. The severity of alopecia does not correlate with the severity of thyrotoxicosis. The hair itself is fine, soft, straight and, it is claimed, cannot be permed.
It should be borne in mind that the cause of hair loss can be drugs for the treatment of thyroid diseases or drugs that interfere with thyroid metabolism: carbimazole, thiamazole, methylthiouracil, propylthiouracil, iodine, levothyroxine, lithium and amiodarone [2].
Hypoparathyroidism is most commonly observed in the geriatric population following inadvertent removal of the parathyroid glands during thyroid surgery or radical neck excision for cancer. Patients experience episodes of hypocalcemia with tetany. Hair thinning or complete loss may occur. The nails often develop horizontal indentations (Bo's lines) that appear at the base of the nails approximately three weeks after a tetanic attack. Decay of tooth enamel may be misinterpreted as poor oral hygiene, especially in older adults [1].
Prolactin and hair loss
Prolactin is a lactotropic hormone from the anterior pituitary gland, which stimulates the growth of the mammary gland, leads to lactation and the emergence of the instinct to care for offspring (including in males). Secretion of prolactin occurs in accordance with the circadian rhythm through mediator substances in the hypothalamus, prolactin-releasing hormone (PRH+), prolactin-releasing inhibitory hormone (PRIN–), dopamine (–).
Clinically, hyperprolactinemia is manifested by a symptom complex of galactorrhea-amenorrhea with hair loss, galactorrhea (in 30–60%), menstrual cycle abnormalities, secondary amenorrhea, seborrhea, acne and hirsutism. The interactions between prolactin and hair growth are complex, with prolactin affecting the hair follicle not only directly, but also indirectly, through an increase in the content of paraandrogens in the adrenal cortex. Consequently, hyperprolactinemia can cause not only diffuse telogen hair loss, but also AGA and hirsutism [15]. Schmidt's work indicates a possible influence of prolactin on AGA in women [16].
The importance of growth hormone
Growth hormone, or somatotropin, is also important for hair, which is obvious from clinical observation of conditions with increased or decreased levels of it. If the growth factor receptor has changed due to mutations, the cells are less responsive to somatotropin. This condition is called growth hormone resistance, or Laron syndrome. In addition to proportional dwarfism, which manifests itself in childhood, this syndrome is characterized by hypotrichosis, premature alopecia and hair shaft abnormalities [17]. In this case, the effect of GH is manifested indirectly; it binds to the growth hormone receptor, which is a transcription factor and increases the expression of insulin-dependent growth factor 1 (IGF-1). IGF-1 is a growth factor that is structurally similar to insulin and, as a growth factor, influences cell growth and differentiation. IGF-1 also plays a role in the development of hair follicles and hair growth. Itami and Inui discovered that IGF-1 is produced in the hair papillae of the dermis. Since the presence of messenger RNA of the IGF-1 receptor in keratinocytes has been proven, it is assumed that IGF-1 from dermal hair papilla fibroblasts is capable of inducing hair growth by stimulating the proliferation of keratinocytes of hair follicles [12]. With acromegaly, on the contrary, hypertrichosis develops [2].
Melatonin in hair activity
Originally discovered as a neurohormone produced and released by the pineal gland during circadian rhythms [18], melatonin regulates various physiological processes—seasonal biorhythms and daily sleep-wake cycles—and influences the aging process [19]. However, what is most noteworthy about melatonin is its protective and antiapoptotic effects, which can ensure the functional integrity of non-tumor cells due to its strong antioxidant properties and ability to actively scavenge free radicals [20, 21]. The described powerful antioxidant properties of melatonin (N-acetyl-5-methoxytryptamine) allow us to consider it as a possible option for counteracting oxidative stress associated with general hair loss, as well as AGA, and as a preventive measure for graying [22].
According to recent data, numerous peripheral organs are not only the target of the biological activity of melatonin, but also a simultaneous site of extrapineal melatonin synthesis, regulation and metabolism. Human skin has been shown to possess a melatonergic enzyme system that fully expresses the specific enzymes required for melatonin biosynthesis. In addition, keratinocytes, melanocytes, and fibroblasts have functional melatonin receptors that are involved in phenotypic effects such as cell proliferation and differentiation. An active melatonergic antioxidant system has been identified in the skin, which protects against damage caused by ultraviolet (UV) rays.
Like the skin, human follicles synthesize melatonin and express its receptors, and effects on the hair growth cycle have also been observed [23].
Hormonal treatment to combat signs of aging
The Women's Health Initiative's Menopause and Hormone Replacement Therapy Study [24] led many women to have negative attitudes toward systemic estrogen replacement therapy. A study of topical estrogen supplementation with E2 or its stereoisomer 17-alpha-estradiol (alpha-tradiol) reported only some therapeutic effect [25].
Using anti-aging hormone treatments containing recombinant human GH, Edmund Chein of the Palm Springs Life Extension Institute reported improvements in hair thickness and texture in 38% of patients, as well as isolated cases of darkening. hair and improving their growth [26].
In individuals with androgenetic alopecia, hormonal therapy with androgens, androgen precursors (DHEA), or androgenic progestins (norethisterone, levonorgestrel, tibolone) may cause hair loss.
Blocking the activation of androgen receptors with antiandrogens is a useful approach in theory, but impractical in practice, since antiandrogens block all androgen actions, leading to unacceptable side effects on the expression of masculine characteristics in men and possible feminization of the male fetus in a pregnant woman. However, cyproterone acetate, a progestogenic antiandrogen indicated for hirsutism and acne [27], is also used for AGA in women, usually in combination with estrogen as an oral contraceptive for premenopausal women. This treatment method stabilizes the progression of the condition. In the USA, spironolactone, an aldosterone antagonist with moderate antiandrogenic effects, is often used [28].
The most successful modern therapeutic agent for the treatment of AGA in men is oral finasteride, a type II 5α-reductase inhibitor that blocks the conversion of testosterone to 5α-dihydrotestosterone [29]. Finasteride, developed to treat benign prostatic hypertrophy, slows the progression of typical hair loss; it is also beneficial for older men. It is unknown whether the inhibitor acts centrally or within the follicles, since plasma 5α-dihydrotestosterone levels are reduced [30]. Unfortunately, finasteride is not effective in postmenopausal women [31], and its use in premenopausal women is limited, similar to antiandrogens. Recently, a short-term trial of dutasteride, a dual inhibitor of 5α-reductase types I and II, demonstrated similar and possibly superior effects [32].
Melatonin, a major secretion product of the pineal gland, is known to modulate hair growth and pigmentation, presumably serving as a key neuroendocrine regulator that links hair phenotype and function to photoperiod-dependent changes in the environment and reproductive status. Recently, it has been demonstrated that important melatonin synthesis occurs in human anagen scalp hair follicles (outside the pineal gland), in which melatonin, through inactivation of apoptosis, may functionally participate in the regulation of the growth cycle. A double-blind, randomized, placebo-controlled study was conducted to examine the effects of topical melatonin on hair growth and hair loss in 40 healthy women complaining of hair loss. A 0.1% melatonin solution or a placebo solution was applied to the scalp once a day for six months, and a trichogram was performed. This pilot study was the first to demonstrate the effects of topical melatonin on hair growth in humans in vivo. The principle of action is presumably to activate the anagen phase. Since melatonin has the additional properties of a free radical scavenger and an activator of DNA repair, the anagen hair follicle, characterized by high metabolic and proliferative activity, can use in loco melatonin synthesis as its own cytoprotective strategy [20, 21, 23].
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First published in Les Nouvelles Esthetiques 2015/№2