**2. Mesotherapy in alopecia treatment**

#### **2.1. Introduction**

Mesotherapy is a noninvasive technique in which active substances are delivered just below the epidermis via superficial microinjections. Various substances including vitamins, medications, plant extracts, and other bioactive compounds including vasodilators, finasteride, and minoxidil can be injected intradermally or subcutaneously to reach the target tissues in mesotherapy [4].

There is evidence regarding the clinical efficacy of mesotherapy in the treatment of thermal burns, local pain, local fat contouring, and skin aging [5–8].

Although evidence‐based studies regarding the efficacy of mesotherapy in different types of alopecia are lacking, in recent years, mesotherapy is increasingly being used in the treatment of telogen effluvium, androgenetic alopecia, and alopecia areata [9–11].

#### **2.2. Method**

Before starting hair mesotherapy, informed consent should be taken from the patient. After cleaning the scalp with antiseptic solution, the substances can be given by intraepidermal, papular, nappage, or point‐by‐point technique. In hair mesotherapy usually 4–6 mm, 27–32 G special mesotherapy needles are applied a depth of 4–6 mm about 1–2 cm apart. Although superficial intradermal technique is most commonly used, nappage technique can also be used manually or by mesotherapy gun. Hair mesotherapy can also be applied by using mesoroller device [9–11]. Each session lasts for 10–30 min [9]. There is no standardized protocol for the frequency of sessions and it depends on the decision of the applier and the indication it is done for. Hair mesotherapy is commonly applied at intervals of 1–4 weeks [10, 11]. Frequently accepted schedule is once a week for the initial weeks then with longer intervals and maintenance treatment in every 2–3 months [12]. Some clinics prefer to apply mesotherapy once in two weeks for at least 10 sessions and then once a month for 5 months [10].

#### **2.3. Mechanism of action**

Although the exact mechanism how the mesotherapy works is not known, several theories have been speculated. According to Pistor, skin may be a point for stimulation which is triggered by mesotherapy that sends inhibitory signals reaching to the lateral medullary center of the spinal cord. These inhibitory signals have been suggested to be either produced by the needling itself or the pharmacologic substances given during mesotherapy. The negative signals are suggested to restore the pathologic mechanisms causing alopecia [13]. The target tissue of hair mesotherapy is mostly the dermis including the circulatory, neuronal, and immune component. Also, epidermis and subcutaneous tissue are affected by the procedure of diffusion of substances. According to mesodermic theory, mesotherapy acts on the tissues derived from mesoderm including capillary and venous spaces, neuronal components, and immune cells of the skin [13, 14]. Another explanation is the third circulation theory that, after blood (first) and the lymphatic (second) circulation, interstitial compartment between skin cells are considered as the third space of circulation. Mesotherapy is suggested to target the interstitial compartment that the substances administered via mesotherapy diffuse through interstitial compartment to the deep target tissues without being rapidly washed out by vessels [13].

The aim of hair mesotherapy is to restore the abnormal physiology causing alopecia by stimulating various biological responses via injecting the active substances into scalp. Additionally, mechanical stimulation by needling itself creates a biologic response that is expected to stimulate mesodermal changes [10, 15]. Hair mesotherapy offers the prevention of hair loss, activation of new hair growth, and the improvement in the quality of existing hair. By hair mesotherapy, local microcirculation is increased, which improves the environment of hair follicle for better growth. Additionally, nutritional supply is provided to the hair follicle and the excess of dihydrotestosterone (DHT) is suggested to be neutralized [16].

#### **2.4. Solutions and substances**

Various cosmetic procedures are being applied for different types of alopecia including mesotherapy, microneedling, platelet‐rich plasma (PRP), low‐level light therapy, and stem‐cell

In this chapter, the above‐mentioned cosmetic treatments for alopecia are briefly described.

Mesotherapy is a noninvasive technique in which active substances are delivered just below the epidermis via superficial microinjections. Various substances including vitamins, medications, plant extracts, and other bioactive compounds including vasodilators, finasteride, and minoxidil can be injected intradermally or subcutaneously to reach the target tissues in mesotherapy [4]. There is evidence regarding the clinical efficacy of mesotherapy in the treatment of thermal

Although evidence‐based studies regarding the efficacy of mesotherapy in different types of alopecia are lacking, in recent years, mesotherapy is increasingly being used in the treatment

Before starting hair mesotherapy, informed consent should be taken from the patient. After cleaning the scalp with antiseptic solution, the substances can be given by intraepidermal, papular, nappage, or point‐by‐point technique. In hair mesotherapy usually 4–6 mm, 27–32 G special mesotherapy needles are applied a depth of 4–6 mm about 1–2 cm apart. Although superficial intradermal technique is most commonly used, nappage technique can also be used manually or by mesotherapy gun. Hair mesotherapy can also be applied by using mesoroller device [9–11]. Each session lasts for 10–30 min [9]. There is no standardized protocol for the frequency of sessions and it depends on the decision of the applier and the indication it is done for. Hair mesotherapy is commonly applied at intervals of 1–4 weeks [10, 11]. Frequently accepted schedule is once a week for the initial weeks then with longer intervals and maintenance treatment in every 2–3 months [12]. Some clinics prefer to apply mesotherapy once in two weeks for at least 10 ses-

Although the exact mechanism how the mesotherapy works is not known, several theories have been speculated. According to Pistor, skin may be a point for stimulation which is triggered by mesotherapy that sends inhibitory signals reaching to the lateral medullary center of the spinal cord. These inhibitory signals have been suggested to be either produced by the needling itself or the pharmacologic substances given during mesotherapy. The negative signals are suggested to restore the pathologic mechanisms causing alopecia [13]. The

therapy with variable outcomes [2, 3].

**2.1. Introduction**

318 Hair and Scalp Disorders

**2.2. Method**

**2. Mesotherapy in alopecia treatment**

sions and then once a month for 5 months [10].

**2.3. Mechanism of action**

burns, local pain, local fat contouring, and skin aging [5–8].

of telogen effluvium, androgenetic alopecia, and alopecia areata [9–11].

There is no standardized formulation used in hair mesotherapy and the various ingredients can be given depending on the indication. Generally, cocktails containing mixture of different ingredients used in hair mesotherapy and they can be applied in alternation depending on the clinical response. It is important to remember that there may be interactions between the injected substances that interfere with the efficacy. However, there is no definite protocol for the compounds and the concentrations [9–11, 15]. Commonly used substances in hair mesotherapy include minoxidil, finasteride, dutasteride, biotin, tretinoin, pantothenic acid, pyridoxine, procaine, dexpanthenol, azelaic acid, T3/T4, and other vitamins and minerals [9–12]. These compounds have different biologic effects. Especially, buflomedil, minoxidil, finasteride, dutasteride, biotin, vitamins, and organic silicium are proposed to stimulate new hair growth [10]. Many of these substances have vasodilator effect. The main effects of the commonly used substances in hair mesotherapy are as follows:

Buflomedil is an α‐2 receptor antagonist and a weak calcium channel blocker. It has vasodilatory effect [10, 17]. Minoxidil also has vasodilatory effect. It is the only drug that is proven to increase hair growth by prolonging the anagen phase [10, 11]. Some authors do not use minoxidil more than 1/2 cc in the cocktail since it may be painful for the patient [10]. Procaine is a well known anesthetic that provides patient comfort. It has vasodilator activity and enhances the absorption of other drugs [10, 11]. Ginkgo biloba increases perifollicular blood flow. It also has antiedema and antioxidant effect. It contains diterpene which inhibits platelet activating factor and decreases platelet aggregation [10, 11]. Conjoctyl (organic silicium, salicylate of monometilsilanotriol) has an antioxidant and vasodilatory effect [10]. Dexpanthenol (Vitamin B5) is involved in the hair development. It is converted into pantothenic acid which is a precursor for the synthesis of coenzyme A, important in the carbohydrate metabolism [10, 11]. Biotin acts as a coenzyme and growth factor. It has a role in the carboxylation and fatty acid metabolism [10, 11]. Vitamin C acts as an antioxidant and helps in collagen production [18]. Vitamin A (retinoic acid) has a regulatory role in the growth of epidermal cells and keratinization process. It induces dermal fibroblastic activity and collagen production [18]. Pyridoxine (Vitamin B6) stimulates hair growth and augments the effects of zinc [11]. Cobalt, copper, lithium, magnesium, manganese, phosphorus, selenium, sulphur, and zinc can be used as trace elements [10]. Zinc acts as a 5‐α reductase inhibitor [11]. Recently intradermal injection of copper has been suggested to be beneficial in AGA most likely by balancing the steroid‐converting enzyme activity, enhancing the anagen phase of hair cycle, simultaneous transition to the telogen phase, and stimulation of the proliferation of dermal papilla cells [19]. Finasteride is an inhibitor of 5‐α reductase enzyme and selectively interfere with the androgen activity on skin [18]. Dutasteride is a second generation 5‐α reductase inhibitor. While finasteride inhibits type II enzyme, dutasteride inhibits both type I and type II [18]. Heparin and heparin‐like mesoglycan acts as vasodilator [11]. X adene contains vitamin B complex and increases blood flow [11]. Azelaic acid inhibits 5‐α reductase activity [11]. Calcitonin and cyproterone acetate can also be used in hair mesotherapy [10].

A test trichogram should be performed one year after to evaluate the clinical efficacy of hair mesotherapy. Additionally, mesotherapy injection technique has been suggested to decrease the pain and provide the distribution of drug more evenly during intralesional corticosteroid therapy for AA [20]. Shulaia et al. have reported successful results in AA patients treated with mesotherapy using nicotinic acid, vitamin C, pentoxifylline, and trace elements (Zn, Se, and placentex) over a period of 28 weeks [21].

#### **2.5. Contraindications and side effects**

The contraindications of hair mesotherapy are as follows: allergy to the substances used in mesotherapy, diabetes, liver, renal and cardiac failure, pregnancy, lactation, use of medication for anticoagulation, infection, or lesion on the area [11, 22]. Side effects of hair mesotherapy are edema, bruising, itching, pain, and headache [10, 23]. Also, side effects related to the systemic absorption of substances may be observed [11]. Contrarily, alopecia has been reported as a side effect following hair mesotherapy. In one case report, one patient developed cicatricial alopecia after heparinoid vasodilator mesoglycan and reversible alopecia has occurred in the second patient due to homoeopathic agents [24]. Additionally, cutaneous infections caused by nontuberculous mycobacteria have been observed after mesotherapy. Although these infections are mostly reported after mesotherapy for lipolysis, physicians should keep in mind that they can be seen after hair mesotherapy [11, 25–27]. Moreover, multifocal scalp abscesses with subcutaneous fat necrosis and scarring alopecia have been reported as a complication of hair mesotherapy. This complication has been attributed to the improper application technique [28]. Recently, frontal edema due to %5 minoxidil solution after hair mesotherapy has been reported [29].

#### **2.6. Evidence for efficacy**

into pantothenic acid which is a precursor for the synthesis of coenzyme A, important in the carbohydrate metabolism [10, 11]. Biotin acts as a coenzyme and growth factor. It has a role in the carboxylation and fatty acid metabolism [10, 11]. Vitamin C acts as an antioxidant and helps in collagen production [18]. Vitamin A (retinoic acid) has a regulatory role in the growth of epidermal cells and keratinization process. It induces dermal fibroblastic activity and collagen production [18]. Pyridoxine (Vitamin B6) stimulates hair growth and augments the effects of zinc [11]. Cobalt, copper, lithium, magnesium, manganese, phosphorus, selenium, sulphur, and zinc can be used as trace elements [10]. Zinc acts as a 5‐α reductase inhibitor [11]. Recently intradermal injection of copper has been suggested to be beneficial in AGA most likely by balancing the steroid‐converting enzyme activity, enhancing the anagen phase of hair cycle, simultaneous transition to the telogen phase, and stimulation of the proliferation of dermal papilla cells [19]. Finasteride is an inhibitor of 5‐α reductase enzyme and selectively interfere with the androgen activity on skin [18]. Dutasteride is a second generation 5‐α reductase inhibitor. While finasteride inhibits type II enzyme, dutasteride inhibits both type I and type II [18]. Heparin and heparin‐like mesoglycan acts as vasodilator [11]. X adene contains vitamin B complex and increases blood flow [11]. Azelaic acid inhibits 5‐α reductase activity [11]. Calcitonin and cyproterone acetate can also be used

A test trichogram should be performed one year after to evaluate the clinical efficacy of hair mesotherapy. Additionally, mesotherapy injection technique has been suggested to decrease the pain and provide the distribution of drug more evenly during intralesional corticosteroid therapy for AA [20]. Shulaia et al. have reported successful results in AA patients treated with mesotherapy using nicotinic acid, vitamin C, pentoxifylline, and trace elements (Zn, Se, and

The contraindications of hair mesotherapy are as follows: allergy to the substances used in mesotherapy, diabetes, liver, renal and cardiac failure, pregnancy, lactation, use of medication for anticoagulation, infection, or lesion on the area [11, 22]. Side effects of hair mesotherapy are edema, bruising, itching, pain, and headache [10, 23]. Also, side effects related to the systemic absorption of substances may be observed [11]. Contrarily, alopecia has been reported as a side effect following hair mesotherapy. In one case report, one patient developed cicatricial alopecia after heparinoid vasodilator mesoglycan and reversible alopecia has occurred in the second patient due to homoeopathic agents [24]. Additionally, cutaneous infections caused by nontuberculous mycobacteria have been observed after mesotherapy. Although these infections are mostly reported after mesotherapy for lipolysis, physicians should keep in mind that they can be seen after hair mesotherapy [11, 25–27]. Moreover, multifocal scalp abscesses with subcutaneous fat necrosis and scarring alopecia have been reported as a complication of hair mesotherapy. This complication has been attributed to the improper application technique [28]. Recently, frontal edema due to %5 minoxidil solution after hair mesotherapy has been

in hair mesotherapy [10].

320 Hair and Scalp Disorders

reported [29].

placentex) over a period of 28 weeks [21].

**2.5. Contraindications and side effects**

Unfortunately, there is scanty scientific data on the role of mesotherapy in the treatment of alopecia. Abdallah et al. have found hair mesotherapy more effective than placebo in 28 male AGA patients by using a dutasteride containing solution (dutasteride 5 mg, D‐panthenol 500 mg, biotin 20 mg, and pyridoxine 200 mg) after 11 weeks of treatment. They also observed a negative correlation between the duration of AGA and response to treatment which is suggested to be associated with the replacement of terminal hair follicles with epithelial remnants of telogen follicles [30]. In another study, 90 male AGA patients were divided into three groups as group A (30 patients) receiving pure dutasteride, group B (30 patients) receiving dutasteride containing solution (dutasteride 5 mg, dexpanthenol 500 mg, biotin 20 mg, and pyridoxine 200 mg), and group C (30 patients) receiving saline. According to the results, there was no statistically significant difference between groups, however, dutasteride containing solution was found to be superior according to trichogram results [31]. Ozdoğan et al. have treated 15 male and 8 female AGA patients with mesotherapy using 2% minoxidil, biotin, dexpanthenol, herbal complex, and procaine once a week. Hair mesotherapy was found to be significantly effective in the improvement of hair quantity and hair thickness after 10 weeks [32]. A mesotherapy solution containing dutasteride 0.5 mg, biotin 20 mg, pyridoxin 200 mg, and D‐panthenol 500 mg was used in 86 female AGA patients and the results were compared with control group receiving saline solution. A decrease in hair loss and improvement in both photographic assessment and hair density after 12 sessions were observed [23]. Topical application of minoxidil 2% (30 patients) was compared with the intraepidermal injection of the drug (30 patients) on 60 females with FPHL and it was concluded that the mesotherapeutic application of minoxidil revealed significantly better results compared to topical application of the drug in both self assessment and trichogram tests [33]. Freund et al. have treated 40 male AGA patients with mesotherapy using botulinum toxin. They have applied two injections at 24‐week intervals after a 12 weeks period without treatment. After 48 weeks of first injection, statistically significant increase in mean hair counts was observed. They suggested that botulinum toxin relaxes the scalp muscles and reduces the pressure on the perforating vessels resulting in the increase of blood flow and oxygen concentration. Furthermore, they reported that there is an increased oxygenation of the scalp so the hair follicles may be associated with enhanced conversion of testosterone to estradiol which favors high oxygen concentrations [34].

Recently, in a systematic review, two unpublished trials (NCT01655108, EUCTR2013‐002740‐85‐ ES) have been reported on the efficacy of mesotherapy for the treatment of FPHL. First trial (54 patients) has compared the application of minoxidil 0.5% (27 patients) with saline 0.9% (27 patients) using mesotherapy technique. Although the study is ongoing, the results regarding the increase in hair volume and decrease in the extent of hair loss were better in minoxidil group. The second was a randomized, double‐blind, and placebo‐controlled clinical trial evaluating the efficacy of plasma rich in growth factors (PRGF‐Endoret) on 24 male and female AGA patients by comparing with saline solution. The results of the study are awaiting publication [35].
