Hair is an important part of the human body and one of the main fashion details. It has been a status symbol throughout history, up to the present day. Hair loss and hair loss represent a minor health problem when looking at the patient’s physical health, however, it significantly affects the quality of his life, as it causes a feeling of inferiority. Research shows that people with alopecia, especially women, have a higher incidence of psychiatric disorders such as social phobia, anxiety and depression.
The problem of hair loss affects both men and women, and given that the causes can be numerous, it presents a major challenge for healthcare professionals in search of the cause, but also an effective solution to this problem. Various factors can lead to hair loss or alopecia, including genetic predisposition, medications, systemic diseases, trauma, diet, endocrine and psychological abnormalities.
Hair growth phases
Under normal circumstances, the biological processes that involve hair growth and shedding are in balance. Each hair goes through a repeated cycle of active growth and rest, and the duration of each cycle varies among individuals. The average person has about 100,000 hairs, all in different stages of the growth cycle.
There are three main phases of hair growth: anagen (growth phase), catagen (transitional phase), and telogen (resting phase). The anagen phase lasts on average from two to seven years, the catagen phase about two weeks, and the telogen phase about three months. About 84% of the scalp is in the anagen phase, 1 to 2% in the catagen phase, and 10 to 15% in the telogen phase.
The anagen phase is the stage where there is intense mitotic division in the matrix area of the hair, as well as keratinization and shaping of a complex cylindrical formation that constantly grows. During this phase, hair never falls out spontaneously, and when plucked, pain is felt. The anagen phase is a stage of active growth where the follicle reaches its maximum length and volume. The catagen phase refers to the period of involution. In this phase, cells undergo apoptosis and hair stops growing and the follicle retracts. The telogen phase represents a dormant stage where there is a marked decrease in the proliferation and biochemical activity of the hair follicle. These cycles constantly alternate.
Unlike animals, the phases of hair growth in humans are not synchronized. Animals lose their hair all at once, while in humans some hairs fall out while others grow at the same time. There are circumstances in which transient synchronization of hair growth is possible in humans when hair falls out more intensely. Harmless and expected hair loss is that which usually occurs in spring or autumn, as well as hair loss after childbirth or during breastfeeding. This is physiological hair loss caused by scalp renewal. Concern should be raised if such hair loss is caused by other factors such as endocrine disorders, infectious diseases, surgical procedures, psychological trauma or taking certain medications.
Increased hair loss is termed effluvium, while alopecia is noticeable hair loss or baldness. Effluvium is always diffuse and most often transient in nature. By removing the factors that caused the increased hair loss, its regrowth and appearance are normalized. Alopecia can be focal or diffuse in nature, and removing its cause does not always result in hair regrowth.
Causes of hair loss
Telogen effluvium is one of the most common causes of alopecia. It is a form of non-scarring alopecia characterized by diffuse, often acute hair loss. Factors such as traumatic events, and physiological or emotional stress can lead to it. Numerous medications such as beta-blockers, retinoids, anticoagulants, propylthiouracil and carbamazepine are associated with this condition.
Endocrine imbalance
Male androgenic alopecia is the most common form of hair loss in men. It affects 30-50% of the male population by the age of 50. About 38% of women who have a problem with hair loss also have elevated levels of androgens. Key features of this condition are changes in the development of the hair cycle and inflammation. The length of the anagen phase decreases with each cycle, while the telogen phase remains constant or lengthens, and eventually, the anagen phase becomes so short that the growing hair cannot achieve sufficient length. Thyroid disorders such as hyperthyroidism and hypothyroidism can lead to alopecia.
Hormonal hair loss
The most common form of hair loss in women is hormonally conditioned. Increased hair loss occurs equally with a lack of female sex hormones – estrogen, as well as with an excess of male sex hormones – testosterone. Diffuse hair loss after childbirth and in postmenopause occurs due to decreased levels of estrogen. Lack of estrogen inhibits the induction of hair growth, so initially the ratio between growing hairs and falling hairs changes. With the synchronization of hair growth towards the end of pregnancy, hair grows rapidly and flourishes, so the proportion of hairs in the growth phase is about 80 to 85%. After childbirth, the situation reverses, and due to the absence of menstruation and lack of estrogen, the proportion of hairs in the growth phase drops to only 25 to 30%. That is why many women complain about increased hair loss after childbirth. There is actually no problem here, because with the onset of a normal menstrual cycle after childbirth, the level of estrogen normalizes, and with it normal hair growth.
Increased hair loss in postmenopause is also a condition that occurs due to a lack of estrogen. In this case, the situation can be improved by systemic or local hormone therapy, and the effect depends on its duration.
In addition to a lack of estrogen, an excess of the male sex hormone testosterone can be responsible for hair loss in women. However, there are cases where there is no increased concentration of testosterone in the blood. The main cause of this is an inherited increased sensitivity of the hair root to dihydrotestosterone, an active metabolite of testosterone, which inhibits hair growth and development until the complete disappearance of the hair and its root. The result in both cases is so-called androgenic, i.e. male type baldness or alopecia.
When the level of testosterone is actually elevated, appropriate (anti) hormonal therapy is applied. Prior to this, it is necessary to exclude adrenal gland diseases and tumors that produce male sex hormones. In male-type baldness without elevated levels of testosterone, local preparations based on thymus, minoxidil and aminexil are used.
Androgenic hair loss can also occur in girls and women and is very often a consequence of hormonal imbalance within the polycystic ovary syndrome (PCOS). It is characterized by increased hair loss, absence of ovulation, irregular menstrual cycles, increased body weight and acne. Treatment of PCOS is carried out by teamwork of gynaecologists, endocrinologists and dermatologists. A complete gynaecological, endocrinological and dermatological examination is necessary.
Hair loss and breakage due to poor care
Although hair is very resilient, excessive bleaching, frequent hair colour changes, permanent dyes or frequent use of hair straighteners can damage the hair and cause it to break. These procedures do not directly cause hair loss, but breaking near the root leads to short and split hairs.
Hair loss due to vitamin deficiency
Hair growth requires a balanced diet rich in vitamins. Unbalanced diets and rapid diets can lead to temporary hair loss. Hair is healthiest with a balanced diet that includes fruits, vegetables, proteins, whole grains, nuts and high-unsaturated fatty acids. If the diet is not optimal, it is necessary to supplement vitamins and minerals important for hair growth by taking special dietary supplements.
Hair loss due to infection or poor immune system
Hair loss can also be a consequence of infection. In this case, it is most often a focal hair loss or alopecia areata. Such foci can exist in larger numbers or an isolated focus can appear, not only on the scalp but also on other parts of the body. This type of hair loss is mediated by immunological mechanisms and very often represents a reaction to an inflammatory focus in the body, but can also be associated with stress.
Sometimes deep bacterial and fungal infections of the scalp skin, as well as some autoimmune skin diseases such as scleroderma, lupus and sarcoidosis, can cause permanent loss of hair roots. Clinical manifestations in addition to hair loss are the appearance of a scar on the affected part of the body. Since there are no more hair follicles on that part of the scalp, because it was destroyed by an inflammatory process, there is no possibility for its regrowth.
Hair loss as a result of COVID affects both women and men, and more and more patients have noticed that this unpleasant side effect lasts up to 6 months after recovery.
Hair loss caused by trauma or telogen effluvium is a type of alopecia, i.e. hair loss caused by traumatic events such as serious illnesses, injuries or surgical procedures, stress or physiological shock to the body. Since COVID-19 is not exclusively respiratory, but a systemic disease often accompanied by high fever, it can act on the body as one of the mentioned stressors that cause increased hair loss. When the body is endangered and “thrown” out of balance, the body directs most of its energy towards vital functions and puts everything else “on hold”, including hair growth. Hair loss usually normalizes 6-12 months after recovery.
Treatment
In the treatment of male androgenic alopecia, local minoxidil is used. It can partially prevent further baldness but requires continuous use to maintain the effect. Minoxidil is a vasodilator that was originally used to treat hypertension. Its side effect is hypertrichosis, which limited its use, especially in women. Its unwanted side effect has become an indication for the treatment of alopecia.
In Croatia, it is available without a prescription as a 2% and 5% solution. As a 2% solution, minoxidil is indicated for the treatment of androgenic alopecia in men and women aged 18 to 65 years, and a 5% solution is indicated for the treatment of androgenic alopecia in men aged 18 to 65 years.
The response to treatment with this drug is very variable, and its onset of action as well as the degree of hair regrowth can vary among individuals. The minoxidil solution contains inactive ingredients including water, ethanol and propylene glycol which are used as carriers to increase solubility. Propylene glycol facilitates drug delivery to the hair follicle, but due to frequent local irritations induced by this ingredient, formulations of solutions without it have been developed, in the form of minoxidil foam.
Minoxidil shortens the telogen phase and opens potassium channels causing hyperpolarization of the cell membrane thus allowing more oxygen and nutrients to the follicles. It is also a vasodilator that increases blood flow to the scalp. The most common side effects of the solution are itching and irritation associated with propylene glycol in the formulation. Side effects associated with the use of minoxidil foam are headache, dyspnea, dermatitis and itching.
Aminexil is a trade name for kopeksil which is known as 2,4-diaminopyrimidine-3-N-oxide. It represents a modified form of minoxidil without side effects. It is a new patented compound that stimulates human keratin fibres, thus stopping hair loss. It helps reduce hair loss without changing collagen structure and maintains tissue elasticity around hair roots. In preparations, it is found as 1.5% aminexil which reduces accelerated aging of roots by fighting the fibrosis process. It is often combined with niacinamide and pyridoxine to enhance its effect.
Role of micronutrients
Micronutrients such as vitamins and minerals play an important, but not entirely clear role in the normal development of hair follicles. In general, vitamins, minerals and proteins are considered essential for healthy hair growth.
Niacinamide (nicotinamide, nicotinic acid amide, vitamin PP, vitamin B3) is often used in shampoos and ampoules against hair loss. Niacinamide is the active form of vitamin B3 and a component of the nicotinamide adenine dinucleotide NAD coenzyme, through which it is involved in a wide range of biological processes including energy production, synthesis of fatty acids, cholesterol and steroids. It is a non-toxic compound that is quickly absorbed through the skin and widely distributed throughout the body, and is excreted through the urinary system.
Vitamin B6 (pyridoxine hydrochloride) is one of the active ingredients in shampoos and ampoules against hair loss. It comes in combination with niacinamide as an addition to aminexil to enhance its effect on hair. Vitamin B6 functions as a nutrient for the hair root and helps in creating beautiful, shiny, stronger and thicker hair.
L-arginine is a semi-essential amino acid that participates in many important functions in the human body. As a precursor to nitric oxide, it plays an important role in hair growth because its vasodilatory effect favors its growth by opening potassium channels and improving the supply of nutrients to hair follicles.
Vitamin E is a lipid-soluble antioxidant that neutralizes free radicals in the skin, hair and body. Vitamin E can reduce hair loss, improve scalp health and circulation, and give shine to hair. Foods that naturally contain vitamin E are wheat germ oil, unrefined sunflower oil, sunflower seeds, almonds, peanuts, beets, cabbage, spinach, pumpkin, avocado.
Zinc is a key cofactor for several metalloenzymes and transcription factors. The required daily intake is 8-10 mg and is usually met by a normal diet. Deficiency can lead to telogen effluvium, the growth of thin white and brittle hair. Zinc catalyzes more than a hundred different reactions and helps strengthen the immune system and resistance to infections. It is essential for cell growth and helps maintain normal hormone levels in the blood, especially testosterone, so its effect on hair metabolism is observed from this aspect. It stimulates thyroid function whose reduced function affects hair loss. Zinc should be taken with copper to establish mineral balance in the body. Zinc stimulates protein synthesis and cell division, thus renewing hair strands.
Copper is part of the melanin pigment that gives color to hair and skin. It also participates in collagen synthesis, a protein that builds bones, skin and hair.
Selenium with zinc further stimulates healthy hair growth. It has an antioxidant role that prevents damage caused by free radicals. It is an important component of glutathione peroxidase. Its deficiency is most common in regions where the soil is poor in selenium and in patients on parenteral nutrition. Deficiency can lead to hypopigmentation of hair and skin. The recommended daily intake for adults is 55 μg.
Cystine is a non-essential dimeric amino acid containing two cysteine molecules covalently linked by a disulfide bond. It has been found in large amounts in immune system cells, connective tissues, skin, digestive enzymes and hair. Skin and hair contain about 10-14% cystine in their composition, and its role in hair is to connect keratin chains through disulfide bonds. Keratin is the main protein in nails, skin and hair. Cystine is also important for collagen formation.
Vitamin C participates in collagen and elastin synthesis as well as keratin fiber bonding. Therefore a diet with sufficient amounts of vitamin C is very important for healthy hair.
Biotin or vitamin H is a carboxylase cofactor in mitochondria. Its deficiency is rare because it is synthesized by bacteria in the digestive tract but has been observed in congenital or acquired deficiency of biotinidase or carboxylase or in patients on parenteral nutrition.
References:
1 Lanjewar, A., Maurya, S., Sharma, D. andGaur, A. 2020. Review on Hair Problem and its Solution. Journal of Drug Delivery and Therapeutics. 10, 3-s (Jun. 2020), 322-329. https://doi.org/10.22270/jddt.v10i3-s.4066.
2 Phillips TG, Slomiany WP, Allison R. Hair Loss: Common Causes and Treatment. Am FamPhysician. 2017 Sep 15;96(6):371-378. PMID:28925637.
3 Orasan MS, Roman II, Coneac A, Muresan A, Orasan RI. Hair loss and regeneration performed on animal models. Clujul Med. 2016;89(3):327-334. doi:10.15386/cjmed-583
4 Lin RL, Garibyan L, Kimball AB, Drake LA. Systemic causes of hair loss. Ann Med. 2016 Sep;48(6):393-402. doi: 10.1080/07853890.2016.1180426. Epub 2016 May 5. PMID: 27145919.
5 Schneider MR, Schmidt-Ullrich R, Paus R. The hair follicle as a dynamic miniorgan. Curr Biol. 2009 Feb 10;19(3):R132-42. doi: 10.1016/j.cub.2008.12.005. PMID: 19211055.
6 Shapiro J, Wiseman M, Lui H. Practical management of hair loss. CanFamPhysician. 2000 Jul;46:1469-77. PMID: 10925761; PMCID:PMC2144852
7 Park AM, Khan S, Rawnsley J. Hair Biology: Growth and Pigmentation. Facial Plast Surg Clin North Am. 2018 Nov;26(4):415-424. doi:10.1016/j.fsc.2018.06.003. Epub 2018 Aug 16. PMID: 30213423.
8 Available at:: Anatomska struktura kose https://svijet-kose.hr/anatomska-struktura-kose/ accessed 17.05.2021.
9 Available at:: Zanki Zelić A. Vlasi – ukras na tijelu http://www.inpharma.hr/index.php/news/1809/18/Vlasi-ukras-na-tijelu accessed 26.06.2021.
