New therapeutic options for androgenetic alopecia

This paper summarizes the current state of knowledge regarding androgenetic alopecia. The focus is on the therapy options photobiostimulation with LED light (830 nm), platelet-rich plasma (PRP) and mesotherapy.

Alopecia is a long-standing problem, accordingly many therapies are established and known. These can not always meet expectations and besides, just recently reports of side effects, especially of finasteride, have become more frequent. Are there new treatment methods and can they be recommended to patients with a clear conscience? In the field of lifestyle products in particular, the demands on safety and sustainability are exceptionally high.

In this brief overview, the focus is on constitutional hair loss, i.e. androgenetic alopecia. However, if it seems appropriate, there will be a sidelong look at other hair root disorders. Photobiostimulation with LED light of wavelength 830 nm (“near Infrared”), PRP (Platelet Rich Plasma) and mesotherapy with various injection solutions are discussed in detail.

In this article, these three therapies will be presented with their scientific background, for the explanation of the procedure the author refers to specific publications. The printing of before and after pictures is expressly waived.

Etiology of androgenetic alopecia

In men, it is now well established that the increased activity of 5α-reductase is responsible for the increase in local dihydrotestosterone (DHT) levels. DHT is responsible for the miniaturization of the follicle and inhibits cell proliferation in the papilla as well as the local production of VEGF (“Vascular Endothelial Growth Factor”). In addition, there is a genetically programmed increased sensitivity of the receptor to DHT in different areas of the scalp. In women, estrogens have a beneficial effect on diffuse hair loss, probably through the antiandrogenic effect, the increase of VEGF, and a proliferative stimulus on the papilla. Thyroid hormones also promote the productivity of the follicle. In addition to the above intrinsic (genetic) factors, several extrinsic factors play a role (oxidative and emotional stress, UVA and UVB rays, tobacco use) [1].

What does the hair follicle need in the growth phase?

In the germinative phase, it needs growth factors, iron, zinc, proteins and vitamins. In addition to keratin and melanin, it also produces a large number of hormones, neurotransmitters, neuropeptides and growth factors. Furthermore, radical scavengers, especially glutathione, are of great importance because they provide antioxidant protection. This substance, consisting of three amino acids, decreases with age. This decline, among other factors, is responsible for various degenerative changes at the follicle, including graying of the hair [2].

Knowledge of the above factors is of great importance for the therapy of androgenetic alopecia, but also other diseases of the hair follicle including diffuse telogen effluvium.

Photobiostimulation with LED light (830 nm)

The use of electromagnetic waves has been routine in medicine since the 1960s. In dermatology, lasers are used for a variety of different indications; usually for destruction in the broadest sense, for example, to destroy hair follicles in cases of unwanted hair growth. LED light is used for activation, photobiostimulation or modulation, for example to stimulate hair growth. Here, the wavelength of 830 nm, i.e., close to the infrared range, is suitable and particularly well studied [3].

LED light differs from laser light in many respects: it is less energetic, neither monochromatic nor coherent, and also non-collimated and non-polarized. Only recently has it become possible to produce “quasi-monochromatic” light with low divergence and sufficiently high and stable energy yield. We do not refer to the application of LED light as “low-level laser” therapy, but correctly as “low-level light” therapy.

The indication spectrum of this wavelength of 830 nm alone is broad and includes:

Alopecia
Wound healing on skin, soft tissues and bones
Pain management
Improvement of cerebral blood flow
Photorejuvenation
Photoactivation of transepidermally delivered products including stem cell material and “Platelet-rich Plasma” (PRP)
adjunctive therapy after invasive therapies on the skin such as peelings, ablative lasers and photodynamic therapy (PDT)

Another indication for this wavelength is the treatment of inflammation. In our practice, a total of three devices run many hours a day. We use it to treat acne, rosacea, burns and atopic eczema. We have also had good results with insatiable itching, post-operative swelling and even jellyfish lesions. Other wavelengths (e.g., 415 nm, 447 nm, 633 nm) also have many different indications due to their shallower penetration depth and other biological effects, but will deliberately not be discussed here.

In this article, we will only talk about LED light with 830 nm wavelength and its various effects [4]:

Improvement of nerve conduction and capillary blood flow
Proliferation of fibroblasts and keratinocytes, stimulation of macrophage activity in the production of growth factors (FGF = “fibroblast growth factor”).
Improvement of collagen and elastin synthesis
Degranulation of mast cells, release of cytokines, chemokines and trophic factors.
Increase in the production of RNA/DNA, enzymes and superoxide dismutase (SOD) as an effective radical scavenger.
Pain control via the opiate and non-opiate track (endorphins, dynorphins, and enkephalins).

Many of these processes are familiar to us from “platelet-rich plasma”. In androgenetic alopecia, mainly the first three effects are relevant, in alopecia areata and inflammatory alopecias all mechanisms except pain control.

We offer our alopecia patients a series of eight treatments, initially at weekly intervals, then with intervals of two and four weeks. Depending on the findings and response, maintenance treatments are then given at 3-6 month intervals. The results after 8 exposures are impressive and in individual patients the success is persistent. Unfortunately, there are few randomized studies of long-term outcomes.

Platelet Rich Plasma (PRP)

The use of this method has long been successfully established in accident and sports medicine, and dermatologists use it to treat wrinkles and scars. A Cochrane review on the treatment of chronic wounds with PRP [5] found positive results, which is not surprising because platelets play a central role in wound healing via the release of growth factors, among other factors.

Knowing that growth factors also play such an important role in hair growth, it made sense to use platelet-rich plasma against alopecia as well. When platelets leave the vessels due to trauma, for example during surgical procedures or after centrifugation and accumulation by injection into the tissue, they are endogenously activated by dermal collagen and release the contents of their granules. Growth factors, such as PDGF (“platelet-derived growth factor”), TGF-β (“transforming growth factor beta”), VEGF (“vascular endothelial growth factor”) and IGF-1 (“insulin-like growth factor 1”) are released primarily from the α-granules, and other biogenic amines, such as histamine, are released from the so-called “dense” granules. PRP stimulates the differentiation of stem cells into hair follicle cells in the bulge region, prolongs the anagen phase, and stimulates angiogenesis in the perifollicular vascular plexus via VEGF and PDGF.

Numerous studies with different designs are available, some with half-side treatment. The centrifuged plasma is injected directly into the scalp, usually 3-4×, initially at 2-4 week intervals, then maintenance treatments are given at alternate intervals, for example every six months. The studies show an improvement in hair density of about 12%, with stopping hair loss also recorded as a success. In our practice, we always perform an exposure with our 830 nm LED light for photobiostimulation after each PRP injection. This is also perceived as very pleasant by patients because of the calming and pain-relieving effect. According to Hu et al. [6], monotherapy with PRP is inferior to first-line therapies with minoxidil and 5α-reductase inhibitors, but may improve their outcomes in combination. A study evaluating this treatment is pending.

Against alopecia areata, PRP was evaluated against triamcinolone acetonide intracutaneously and placebo in a randomized double-blind trial on 45 patients, with the other side of the scalp left untreated in each case [7]. PRP was significantly superior to triamcinolone and placebo. The number of dystrophic hairs decreased particularly under PRP, a marker for cell proliferation (Ki-67) was significantly increased, and even itching and paresthesia were reduced. No side effects occurred.

In conclusion, treatment with platelet-rich plasma for androgenetic alopecia and alopecia areata is an autologous, well-tolerated, low-risk therapeutic approach that is certainly worth waiting for long-term observations.

Mesotherapy

Mesotherapy is a minimally invasive injection method in which active ingredients are applied directly and in low doses specifically to the sites where they are to act [8]. By diffusion, the active ingredients also reach deeper regions, but usually not the circulation, since the connective tissue and in it the matrix ensure metabolization of the active ingredients. Initially, mesotherapy was used in pain medicine; in dermatology, other indications besides hair loss are the treatment of skin aging, cellulite and striae distensae.

Like PRP, mesotherapy has few side effects and is safe. Active ingredient cocktails are used with substances that are important for the function of the hair follicle (see above), or protect it from harmful influences: for example, dexpanthenol, biotin, vitamin C, hyaluronic acid, vitamins, glutathione as an antioxidant and iron gluconate and saw palmetto extract as antiandrogens. The goal is not only to prolong the anagen phase and decrease the telogen phase, but the cytoprotective and antioxidant molecules should also have anti-inflammatory and anti-fibrosing effects. Medications such as minoxidil, hormones or reductase inhibitors are not used. Knoll [9] reports in a recent pilot study on treatment with a cocktail containing hyaluronic acid and glutathione, among others. Ten patients were treated in combination with photobiostimulation, in all of them a stop of hair loss after one month, appearance of new hair with improvement of density, volume, hair quality and even repigmentation in the further course could be observed. Ideally, she says, six treatments at one-week intervals are sufficient, followed by a transition period of three sessions at two-week intervals followed by maintenance therapies on an alternating schedule. The global success rate is about 80%, he said. Other authors are not convinced by this method [10]. Its use in other types of alopecia is worth trying when other treatments are not an option.

Take-Home Messages

There are three new procedures for the treatment of androgenetic alopecia.
Among these, LED light therapy is a particularly compelling choice as a non-invasive, side-effect-free and inexpensive treatment that is also and especially suitable as an accompaniment to established therapies (minoxidil, reductase inhibitors) as well as platelet-rich plasma (PRP).
The mechanisms of action of LED light therapy overlap in several respects with those of PRP, for example concerning growth and angiogenesis factors, etc. However, treatment with PRP is much more complex than light therapy and, according to the current state of studies, is also probably insufficient as monotherapy.
Mesotherapy differs from the other therapeutic techniques in that non-medicated concentrates of active ingredients are injected. In approach, this is comparable to oral nutritional supplements and has its justification as an alternative for patients who want a safe treatment with few side effects.
All of the above methods can also be used on a trial basis for inflammatory alopecia and alopecia areata. However, studies on long-term results and application strategies are still pending.

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Arck PC, et al: Towards a “free radical theory of graying: melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress-induced tissue damage”. FASEB J 2006; 20: 1567-1569.
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Martinez-Zapata MJ, et al: Autologous platelet-rich plasma for treating chronic wounds. Cochrane Database Syst Rev 2012; 10: CD006899.
Hu R, et al: Combined treatment with oral finasteride and topical minoxidil in male androgenetic alopecia: a randomized and comparative study in Chinese patients. Dermatol Ther 2015; 28(5): 303-308. doi: 10.1111/dth.12246. epub 2015 Jun 2.
Trink A, et al: A randomized, double-blind, placebo- and active-controlled, half-head study to evaluate the effects of platelet rich plasma on alopecia areata. Br J Dermatol 2013; 169: 690-694.
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