It is an unfortunate fact of life that, male and female alike, we lose hair and/or have thinner hair as we age. The American Hair Loss Association states that two-thirds of men over 35 years of age show signs of hair loss (American Hair Loss Association, 2010). Although occurring more in men, hair loss also affects women, usually in their 50s and 60s. Every day, some hair is lost—while in the shower, brushing hair or drying or styling. In this chapter, the author will explain the reasons for hair loss and demonstrate how platelet-rich plasma is an extremely useful and highly successful treatment for this common problem.
Normal versus abnormal hair loss
On average, normal hair loss is under 100 hairs per day; and these are normally replaced by new, thicker hair, so the loss does not tend to be noticeable.
However, in the evolution of male and female pattern baldness, there tends to be a more definite manifestation of loss. As this is more obvious than generalised hair thinning, patients are increasingly looking for non-surgical ways to stimulate hair growth.
With age, hair becomes thinner (intermediate or miniaturised hair), and the growth cycle is not as successful at replacing the lost hairs. However, hair loss can be linked to other factors in addition to the ageing process, including stress, illness, hormonal changes, side effects of some medications or even excessive hair styling such as hair extensions.
Hair structure
Hair is a complex structure, made up of various different cells and chemicals. The hair root sits below the surface of the skin within a hair follicle, which is completely enclosed within connective tissue, acting as the hair production unit. Made up of different epithelial cells, the core of any hair follicle is the hair fibre.
Keratin—the key part of hair fibre—is a chain of amino acids that forms the cytoskeleton of all epidermal cells. Research has proven that the durability and resistance of hair fibre to degradation under environmental stress stems from the high amount of sulphur that comes from the amino acid, cysteine—in the hair fibre. The sulphur in the cysteine molecules in adjacent keratin proteins binds to form disulphide chemical bonds, which are very strong and very difficult to break.
These cells are in contact with the dermal papilla, situated at the base of the hair follicle. The bloodstream feeds the dermal papilla by carrying nutrients to produce new hair and plays a vital role in promoting and maintaining hair growth.
Hair growth cycle
In normal circumstances, hair growth in each hair follicle follows a cycle made up of three main phases: anagen (growing), catagen (transition or rapid involution) and telogen (resting). Further information can be seen in Figure 1.
Figure 1. The anagen, catagen, telogen (resting and shedding) and early anagen phases of the hair growth cycle
Normally, this hair production cycle continues throughout a person's life. However, other factors may affect and prevent hair production by aberrant hair follicle cycling and changes in the hair follicle morphology, sometimes leading to the hair follicle being destroyed.
Platelet-rich plasma, a high concentration of blood platelets in a small volume of plasma injected into the scalp, is attracting new interest
Under the dermal papilla's influence, differentiation of the epidermal cells during the anagen stage produces a hair fibre and associated products. Inadequate stimulation to the dermal papilla cell results in the growth of the hair fibre and root sheaths stopping. The dermal papilla can become isolated in the dermis and the hair fibre can easily be pulled out, leading to hair loss.
Dihydrotestosterone and hair loss
Testosterone acts directly on many tissues; however, some of its least desirable effects do not occur until it is converted into another androgen—in the case of this article, dihydrotestosterone (DHT).
DHT is a specific hormone responsible for male and female pattern baldness, as a result of changes in its metabolism. An old diuretic (spironolactone) appears to be a competitive inhibitor of DHT receptor binding (also used to treat acne).
DHT acts on the skin (sometimes producing acne) and on the hair follicles. It is responsible for the hair on a man's chest, but can often remove it from the scalp. DHT also stimulates the growth of prostate cells, which grow normally in adolescence, but can contribute to benign prostatic hyperplasia in many older men.
Back to basics
New interest in preventing and/or treating both hair loss and baldness has occurred with the use of platelet-rich plasma (PRP) on the scalp.
PRP is a high concentration of blood platelets in a small volume of plasma and, more precisely, according to Marx et al, who published the first study on PRP in the late 1990s, the platelet's concentration should be at least double the concentration in the native blood (Marx et al, 1998).
However, PRP is not a new discovery. In 1953, two researchers, Rita Levi-Montalcini and Stanley Cohen, discovered the two first growth factors in the plasma (epidermal and neural growth factors), and were subsequently awarded a Nobel Prize in 1986 by the Nobel Assembly at the Karolinska Institute.
PRP is acquired when we ‘spin’ the blood from the patient, and three different fractions are obtained (depending on the weight):
- The lowest one, located at the bottom, is composed of the red cells (heavier)
- The PRP (rich in platelets)
- The platelet-poor plasma (PPP) on top.
Is platelet-rich plasma the correct name?
When doing research online (Pubmed, Wiley, Google Scholar and Medline), PRP is referred to in various ways: platelet leukocyte gel, platelet-rich plasma gel, platelet concentrate, plasma-rich fibrin and blood plasma therapy.
The names are not really important but preparations could—and should—differ, depending on the indication. More important are the latest discoveries.
The importance of growth factors
Once PRP is injected into the dermal layer, the activated platelets will release growth factors. The most important growth factors for hair are detailed below.
Platelet-derived growth factor
There are four possible isoforms of platelet-derived growth factor (PDGF). It stimulates the growth of dermal mesenchyme. PDGF signals are involved in both epidermis follicle interaction and the dermal mesenchyme interaction needed to form hair canals and the growth of dermal mesenchyme (Amgar and Bouhanna, 2013).
However, PDGF mainly acts as a conductor and upregulates the effects of other growth factors.
Transforming growth factor
Transforming growth factor beta (TGF-β) is a superfamily of growth and differentiating factors. TGF-β stimulates angiogenesis and chondrogenesis, the production of fibronectin, glycosaminoglycans and collagen in connective tissue.
Vascular endothelial growth factor
Vascular endothelial growth factor (VEGF) is essential for many angiogenic processes.
In 2001, Yano et al identified VEGF as a significant mediator of hair follicle growth, which was the first evidence demonstrating that improved follicle vascularisation promotes hair growth, as well as increasing follicle and hair size.
Furthermore, a 2007 study by Rinaldi et al demonstrated, in a trial of 104 patients receiving hair transplants by means of confocal microscopy, that VEGF up-stimulation through adenosine receptors induces noteworthy changes in the average diameter of the scalp's perifollicular vessels.
Epidermal growth factor
Epidermal growth factor (EGF) stimulates mitosis on epithelial cells and fibroblasts and improves the ratio of anagen. It inhibits the entry in the catagen phase, thereby promoting the anagen phase. EGF signals also control the orientation and elongation of follicles.
Fibroblast growth factor
Fibroblast growth factor (FGF) stimulates the proliferation and differentiation of keratinocytes and endothelial cells and is a member of the multifunctional fibroblast growth factor family.
» Platelet-rich plasma appears to prolong the anagen (growing) phase of the hair cycle through increased exposure of fibroblast growth factor 7 (FGF-7), as well as increasing the probability of cell survival by inhibiting apoptosisd «
Angiogenesis is also enhanced through endothelial cell stimulation to undergo mitosis and migration (Anitua et al, 2012).
Neural growth factor
Neural growth factor (NGF) slows down apoptosis and stimulates hair growth (Amgar and Bouhanna, 2015).
Keratinocyte growth factor
Keratinocyte growth factor (KGF) is a recent discovery and is an important endogenous mediator of hair follicle growth and development.
International studies on platelet-rich plasma
Uebel et al (2006) demonstrated that storing hair grafts in PRP can improve graft survival, increase hair density and stimulate the growth of transplanted follicular units.
Following this, Li et al (2012) published their results on the use of PRP as a potential therapeutic tool for promoting hair growth, and Takikawa et al (2011) proved that PRP improved the density of hair at 12 weeks, writing: ‘Activated PRP increased the proliferation of DP (dermal papilla) cells and stimulated extracellular signal-regulated kinase (ERK) and Akt signalling. Fibroblast growth factor 7 (FGF-7) and beta-catenin, which are potent stimuli for hair growth, were upregulated in DP cells. The injection of mice with activated PRP induced faster telogen-to-anagen transition than was seen on control mice’ (Takikawa et al, 2011).
In their 2009 study, following PRP treatment, Greco and Brandt observed an increase in hair density of 18.8% at 3 months and 29% at 9 months. Newer research confirmed their work, showing in vitro that PRP increases the proliferation of dermal papillae cells and activates the signalling pathways extracellular signal-regulated-kinase and Akt.4 (Trink et al, 2013). Additionally, fibroblast growth factor-7 and beta catenin, both factors of hair follicle growth, were also stimulated.
Alopecia areata and platelet-rich plasma
Alopecia areata (AA) is the most common condition to cause inflammation-induced hair loss. It is characterised by patches of hair loss and baldness, which can progress to a complete loss of hair from the scalp (alopecia totalis), or, in the most severe cases, from the whole body (alopecia universalis) (Trink et al, 2013). Often, patients can be young, and so, the burden is significant, as is the effect on the self-esteem and quality of life (Trink et al, 2013).
AA is an organ-specific autoimmune disease, which stems from the loss of the hair follicle's ‘immune privilege’ (Trink et al, 2013). As a result, most therapies are immunosuppressive.
In Singh's 2015 paper, he discusses his experience of using PRP on chronic AA, with 20 patients who had had 2 unsuccessful years of various forms of therapy. They were treated with PRP alone, without any side effects and with good preliminary results. The study showed a relapse in just one case, and no side effects in any of the 20 treated patients (Singh, 2015).
Male pattern baldness surgery
The second indication for improving male pattern baldness is surgery or hair transplant surgery. PRP has multiple uses when used in conjunction with hair transplants. It can be used to strengthen a poor donor area, improve graft survival and to minimise the post-operative side effects.
Furthermore, injecting PRP into the patient's scalp increases vascularisation to the transplanted follicular units, therefore improving the yield and density of non-transplanted hair.
Androgenic alopecia and platelet-rich plasma
The most common form of male or female pattern baldness is androgenic alopecia (AGA). PRP therapy has been found to be a more effective treatment than minoxidil (one of the most prescribed topical drugs for hair loss), and is a highly effective treatment option for hair loss, with a high patient review rating.
The growth factors from the injected PRP are released and locally activated. They stimulate the angiogenesis near the hair root so that the supply of oxygen and nutrients through the blood is re-established. The growth factors decrease the length of the hair follicle's rest period, meaning that the growth phase is longer. As a treatment for hair loss, PRP is a treatment regimen, rather than a one-off procedure.
AGA is characterised by miniaturisation of the hair follicles, which progressively leads to a reduction of the scalp's hair density as a result of terminal hairs being converted into vellus hairs (Stevens et al, 2018).
In men, this condition is generally known as male pattern baldness, but it can also affect women and is defined as a common, chronic and progressive form of hair loss. It affects up to 80% of Caucasian men and 40% of Caucasian women (Gkini et al, 2014). Although it may start at puberty, its frequency increases with age.
Finding a satisfactory treatment
Various products have been recommended as hair loss therapies. Despite these, AGA remains the most common hair disorder without satisfactory treatment as a result of low patient compliance and satisfaction rates, as well as various adverse effects (Gkini et al, 2014).
Various studies have shown the positive effects of PRP on AGA. In 2019, Starace et al investigated the efficacy, tolerability and clinical improvement of PRP for the treatment of female AGA. The results showed that, after 24 weeks, the median relative percentage change for hair density was mostly positive (Starace et al, 2019). After 12 weeks, in the frontal area, the medium hair diameter showed a substantial increase. After 24 weeks, the vellus relative change showed a decrease, particularly in the front and the central area, while for the vertex, the decrease was mainly visible at the end (Starace et al, 2019). No adverse events were reported. The authors concluded by saying that PRP injections positively affect hair density and improve hair diameter (Starace et al, 2019).
In Egypt, Tawfik and Osman (2018) evaluated the efficacy and safety of autologous platelet-rich plasma in the treatment of female pattern hair loss. Some 30 female patients with female pattern hair loss were randomly assigned to receive autologous PRP injection into a particular part of the scalp, while another area was injected with a placebo. The treatments occurred weekly for a maximum total of four sessions. Six months after the last treatment, patients were followed up regarding the results, which were assessed subjectively and objectively (Tawfik and Osman, 2018).
In relation to both hair density and hair thickness as measured by a folliscope, there was a statistically significant difference (P<.005) in the results when comparing the areas injected with PRP versus the placebo areas. Pictures taken of the patients after the study showed substantially improved hair volume and quality, as well as expressing a high overall patient satisfaction with the areas injected with PRP. The authors of this study concluded that PRP injections are an alternative treatment for female pattern hair loss with a low cost-to-benefit ratio (Tawfik and Osman, 2018).
Uebel studied 23 patients and compared two areas of hair transplant, with or without PRP, in the root of the grafts (Uebel, 2005). Two areas (2.5 cm2) were marked on the scalp and each planted with 20 grafts/cm2. After 1 year, the area implanted with the PRP-enriched grafts demonstrated a higher follicle units survival rate and density.
How platelet-rich plasma works
PRP appears to prolong the anagen (growing) phase of the hair cycle through increased exposure of fibroblast growth factor 7 (FGF-7), as well as increasing the probability of cell survival by inhibiting apoptosis (associated with increased Bcl-2 protein levels as well as activated Akt signalling). It also appears to increase the perifollicular vascular plexus, through the increase of two major growth hormone levels (VEGF and PDGF), which increase the microvascularisation potential.
It seems that activated PRP promotes differentiation of stem cells into hair follicle cells through the upregulation of transcriptional activity of beta-catenin (Gkini et al, 2014). In vitro, it demonstrated a proliferation of dermal papilla cells and an increase of dermal papilla cell growth by activating ERK signalling.
Gkini et al (2014) published the results of their study on PRP injections for treating AGA throughout a 1-year period.
The study included 20 patients (18 men and two women), with a mean age of 34 years (24–72). Among the male patients, according to the Hamilton-Norwood scale, five patients had type II AGA, eight from type III, four from type IV and one from type V alopecia. Both women suffered from grade I AGA, according to the Ludwig scale. The advancement of both male and female pattern hair loss can be seen in Figure 2. Six of the patients had previously sought medical help for their hair loss, and they had been treated with topical minoxidil lotion 5%. Since the beginning of the PRP treatment (over 6 months), the patients were not taking any medication, and none had undergone hair transplantation.
Figure 2. Male and female pattern baldness
In terms of patient satisfaction, 85% of the participants reported an improvement in the quality and thickness of their hair, with a mean result rating of 7.1 on a linear analogue scale of 1–10 (1 = no result, 10 = best result), and 65% reported an increase in hair density. Six months into the treatment, 100% of patients wanted a booster session, while, at the conclusion of the study (1 year), 75% needed or wanted one.
The male patients with grade II–III alopecia (according to the Norwood-Hamilton scale) had better results compared to patients with more advanced alopecia, and both of the female patients were satisfied with the results. Furthermore, patients who had vellus hair had better results, as PRP appeared to act on the hair's diameter and caused thin hair to become thicker.
A final study
As seen so far, the role of PRP for the treatment of hair loss has been well demonstrated. Activated autologous PRP can increase the production of dermal papilla cells by upregulating FGF-7 and β-catenin, as well as extracellular signal-related kinase (ERK) and Akt signalling. Due to the secretion of VEGF by the keratinocytes of the outer root sheath and fibroblasts of the dermal papilla, anagen-associated angiogenesis is one of the most important factors in active hair growth.
Cervelli et al (2014) detailed how PRP can be used to treat AA. The results demonstrated a substantial increase treatment area's mean hair count after 3 months (3 months versus pre-treatment). In the treatment area, there was a mean increase of 18.0 hairs, compared to baseline, while the control area had a mean decrease of 2.0 hairs (control versus treatment; P < 0.0001. Furthermore, the authors showed that there was a significant improvement in terminal hair density (27.0 ± 15.3—the number of hairs/cm2) in the area treated, compared to the baseline (Cervelli et al, 2014).
Conclusion
The growth of normal and pathological dermal structures can be influenced by increased secretion of VEGF. PRP has been shown to improve cutaneous ischemic conditions and to increase vascular structures around hair follicles. Many of the current treatment modalities for pattern hair loss have been shown to modulate angiogenesis and enhance bloodflow.
PRP injections are demonstrated to be an effective treatment of AGA and AA in both men and women, with a high patient satisfaction rate and without any significant adverse effects.
All the study protocols, despite the fact that they vary slightly, show good and even better results than all other treatments used previously (minoxidil, finasterine, corticosteroids, etc), but they all rely on at least three sessions (each 1 month apart) with a top-up/booster 1 year later.
Key points
- The way that the plasma is prepared is very important and the result depends on the total volume of blood/plasma harvested and the speed (RPM) at which the centrifuge will spin
- Several studies have looked at the effectiveness of platelet-rich plasma as a treatment for hair loss and/or thinning. Results have shown that it is more effective than minoxidil (one of the most prescribed topical drugs for hair loss) and produces high patient satisfaction scores
- Platelet-rich plasma is not a one-off treatment, rather, it is a treatment regimen.
CPD reflective questions
- How is platelet-rich plasma defined?
- Aside from growth factors, what else can be found in plasma?