Hair Loss Management with PRP at AGA and Hair Transplants

 
Hair Loss Management with PRP at AGA and Hair Transplants
Hair Loss Management with PRP at AGA and Hair
                        Transplants
Introduction:

Androgenetic alopecia (AGA) is the most common form of hair loss. It can affect not only
men but also women (1). Prevalence increases with age, affecting up to 80% of men and 40%
of women (2). AGA can lead to a considerable impairment of the quality of life up to
depression (3). Therefore, early intervention and management of AGA with evidence-based
medicine (EBM) is of great importance (4.5). Autologous Platelet-Rich plasma (PRP) has
recently been used for AGA. However, the market has grown faster than the research for this
promising technology and there are still many open questions.

Objective: Development of a recommendation for an evidence-based management of AGA
with PRP and as an addition to hair transplants.

Recommendation on how to proceed with consultation and diagnosis
Before a possible treatment of hair loss with PRP, its cause must be clarified exactly. Because
PRP is not a meaningful therapy for everyone or any kind of hair loss. The temporal and
schematic course of the hair loss, possible stress-inducing events in the last 3 to 6 months as
well as current blood values must be examined.

       No therapy should be carried out without sufficient diagnostics!!!!

Often it is only a case of diffuse hair loss (teleogenic effluvium) in which more hair falls out
over the whole head than usual. Hair loss can be an indication of an existing disease or the
result of a traumatic event that occurred shortly before. If the cause of the hair loss disappears,
in this case the hair also starts to grow again, i.e. the hair grows even without the use of PRP
(6).

Procedure in case of diffuse hair loss: clarify cause, remove trigger and wait and see

If you have recently changed a medication that may affect your hair metabolism, you will also
need to wait and see.

A dermatoscopic examination of the scalp is mandatory and a trichsoscan (Fig. 1,2) would be
desirable.
Over 90% of patients are diagnosed with AGA (1). This form of hair loss is hereditary and is
mostly of hormonal origin and follows a pattern which is classified according to Norwood (7)
in men as NW I - VII and in women as Ludwig (8) LW I - III (Fig.3).

Currently, topical minoxidil and oral finasteride are the only drugs approved by the Food and
Drug Administration (FDA) for the treatment of AGA (Fig. 4).
Currently available therapies are sometimes considered to have limited efficacy, which is why
it is very important to find new therapies such as PRP for this pathology (9).
Hair Loss Management with PRP at AGA and Hair Transplants
Therapy management by AGA

AGA therapy management should be evidence-based to ensure the best possible consultation
and treatment. In practice, this means integrating individual clinical expertise with the best
available external evidence (10), taking into account the patient's values and wishes (Fig. 5).

The EBM is based on 3 pillars

- individual clinical experience
- current status of clinical research (Table 3-S3 Guideline)
- Values and wishes of the patient

In order to be able to make a recommendation for the various therapeutic approaches of AGA
treatment according to the best EBM principles, an evidence level was assigned to each
therapy per se. A low level corresponds to a high evidence level, a high level to a low
evidence level (Table 1).

The level of evidence is determined by the fact that each study is assigned a quality level (A1
= randomized double-blind studies with high quality to D = expert opinion with low quality).
The quality grades of all studies belonging to a therapy scheme are then combined into an
evidence level (Table 2) (4.5).

The resulting evidence levels of the various therapy approaches for AGA are listed in Table 3
and serve as guideline S3 (11) for orientation in the recommendation for the management of
AGA therapy. This primarily takes into account their level of evidence, the therapy results to
be expected, the practicability for physician and patient as well as the compliance of the
patient. Together, the 3 pillars of EBM should decide which individualized therapy is best
suited for the patient (Table 3).

New recommendation of the S3 Guideline and current therapy approaches today and in
the future for the AGA.

While minoxidil and finasteride have been the only evidence-based therapies for AGA in
recent decades, further developments with new approaches have progressed in recent years.
Figure 6 shows the main components of AGA pathogenesis and current and future therapeutic
approaches (12). Very much correspondingly, the topical
25% finasteride solution (13), which, like the topical androgen receptor blocker Clascoterone
(14), is still in the preclinical study phase. For the efficacy of prostaglandin (PGE2 and PGF2)
analogues and PDG2 antagonists (15) the result of an ongoing study (16) has yet to be
determined. For other approaches such as JAK inhibitors (17), stem cell therapy (18),
mesotherapy (19) and carboxytherapy (20), there is currently no sufficient scientific evidence
of efficacy. Currently, only low-level laser therapy (LLLT) (evidence level 2) and PRP
(evidence level 3) meet the criteria of the S3 guideline in order to be recommended for AGA
management alongside minoxidil and finasteride. Evidence level 3 in PRP was achieved
through two studies evaluating the efficacy of PRP in male and female patients with AGA,
both with evidence level C and meeting inclusion criteria for the guideline (21,22,23).
However, there is currently no standard procedure for PRP, no standardized techniques or kits
for isolation and activation, and no standardized protocols for dosage and frequency of
injections. There is also uncertainty about the combination with other substances and cells. It
Hair Loss Management with PRP at AGA and Hair Transplants
is therefore difficult to objectively assess the impact of PRP on AGA in order to achieve a
higher level of evidence in the long term.

Postulated effect of PRP

The platelets enriched in PRP produce growth factors that positively influence proliferation,
survival and differentiation of many different cells. This also seems to be true for hair follicle
cells. The higher the number of platelets, the higher the concentration of growth factors. The
most important growth factors involved in hair follicle formation are probably vascular
endothelial growth factor (VEGF), epidermal growth factor (EGF), insulin-related growth
factor (IGF)-1 and fibroblast growth factors (FGFs) (24,25).
AGA results from the shortening of the anagen phase and extension of the telogen phase
which results in follicle miniaturization. The injection of activated PRP into mice was shown
to reverse this process with an increased anagen telogen rate and a larger number of hair
follicles in the anagen phase (26) (Fig.7).
A similar conclusion was reached by Li and colleagues (2012) who found that activated PRP
stimulates the proliferation of human DP cells, promotes the survival of hair follicle cells
through its anti-apoptotic effects (Akt) on dermal papilla (DP) cells and can stimulate hair
growth by prolonging the anagen phase of the hair cycle (27) (Fig.8). The most likely
mechanisms of action are the triggering of various signalling cascades including the β-
Catenin (BC) pathway, the extracellular signal-regulated kinase (ERK) cascade and the
protein kinase B (Akt) cascade, which positively affect cell survival, proliferation and
differentiation (28).

Activate or not activate?

Growth factors are usually physiologically present in an inactive form. It should not be
debated whether these factors have to be activated in order to achieve an effect.

The important question is "how and when to activate".

Options include calcium chloride, bovine thrombin, mechanical (e.g. ultrasound, etc.) or
autologous thrombin serum. In a recently published study by Inslaco, a significantly improved
Hair mass index for activation with 20Hz ultrasound of 48% was found compared to 25% in
the calcium chloride control group. There was also an increased hair density (57% compared
to 33%) and a larger hair diameter (10% compared to the initial level of 0%) (29) But also
other activation methods such as extracellular matrix (Acell), autologous lipocytes or fat stem
cells can achieve good results.

PRP Protocol - Techniques to be considered

Different PRP protocols differ significantly in preparation and execution. It is recommended
to use platelet concentrations 1.5 to 4 times higher than the physiological level. Giusti et al.
showed that the optimal platelet concentration to promote angiogenesis in human endothelial
cells is 1.5 million / µl and that higher concentrations may be worse (30). The literature
recommends one PRP session per month for 3 to 4 months and a subsequent maintenance
interval of 3 to 6 months. Injection of PRP into a subdermal layer at a depth of approximately
3 to 4 mm may allow diffusion into connective tissue and subdermal space, allowing PRP to
reach the base of the hair follicle and DP cells without damaging the vessels and nerves below
and parallel to the skin surface (31) (Fig.9).
Hair Loss Management with PRP at AGA and Hair Transplants
Effect of PRP on hair transplants

Hair transplants (Fig.10), 11) not only obviously improve the current hair condition, but as a
recently published study could show, also the quality of life and even health (32) (Fig.12).
PRP as adjuvant therapy shows an improved result in wound healing as well as in the growth
rate of transplanted follicles. In 2006, Übel and his colleagues published their first paper on
the use of PRP as an additional therapy for hair transplantation. They were able to show a
significant difference in the transplant density of the scalp previously treated with PRP
compared to the untreated control area: on average the transplant density in the scalp treated
with PRP was 18.7 follicular units (FUT) per cm 2 compared to 16.4 FUTs per cm2 in the
untreated scalp (33) Garg et al. This study also showed a significant influence on the quantity
and quality of hair growth when PRP was injected into the prefabricated slits during hair
transplantation (34). Some advocate PRP as the optimal holding solution for transplants
compared to NaCl solution (35), but there is still no evidence for this.
Since PRP promotes wound healing (36), it should also be recommended for use in the
extraction area, as healthy hair can also be injured here, which can be reduced by PRP. PRP
stimulates the formation of new blood vessels, scarring is reduced and the regeneration of
grafts traumatised by transplantation is improved, which can ultimately lead to an improved
growth rate of implanted grafts.

Conclusion (Fig.13)

Although hair loss is very common in both men and women, FDA approved drug treatments
are currently limited to Minoxidil and Finasteride. PRP is a promising new option to bridge
the gap between medical and surgical options for AGA. Animal models suggest that PRP
promotes hair growth, and several clinical studies have shown that PRP is effective in
androgenetic alopecia in a variety of settings, including maintaining hair density. Also, its
supportive effect as an adjuvant during and after hair transplantation is significant. Further
controlled studies with quantifiable measures of treatment success are now needed to confirm
these results.
Hair Loss Management with PRP at AGA and Hair Transplants
Table 1: Evidence level (1-4)

 1       Studies with evidence level 1 or studies with predominantly consistent results with
         evidence level A2
 2       studies Level of evidence A2 or studies with predominantly consistent results with
         Level of evidence B
 3       studies with evidence level B or studies with predominantly consistent results
         evidence level C
 4       Little or no standardized evidence
Source: Kant et al. 2018

The evidence level takes into account the methodological quality of the studies (evidence
levels) and the interim consistency of the results. 

Table 2: Evidence evaluation (grades A1..D)

 A1      A1 Meta-analysis comprising at least one randomised clinical trial with evidence
         of grade A2 with consistent results from different studies.
 A2      Randomized, double-blind, high quality, comparative clinical trials (e.g., sampling,
         patient involvement flowchart, ITT analysis, sufficient size).
 B       Randomised, lower quality clinical trials or other comparable studies (non-
         randomised, cohort or case-control studies)
 C       Non-comparable studies
 D       expert opinion
Source: Kant et al. 2018

The methodological quality of each study included in the evidence-based analysis was defined
in degrees by the quality of the evidence according to the following scheme ( A1..D).

Table 3: Current recommendation for the management of AGA according to S3 Guideline
1/2018

 Therapy             Eviden     Evidence    evidence      Safet practicabil      practicabil
                     ce level   prevent     condition     y     ity              ity
                                progressi   improvem            patient          doctor
                                on          ent

 Men

 Finasteride 1mg     1          +++         ++            +++     ++++           ++

 Dutasteride         1          +++         +++           ++      ++++           ++
 0,5mg
 Minoxidil 5%        1          +++         ++            +++     +/++           +++
                                                          +
 Hair                2          -           +++           ++      + interv.      +
 transplantation
 with/without adj.                                                +++longter
 therapy                                                          m
Hair Loss Management with PRP at AGA and Hair Transplants
LLLT (Low-level 2              +/-   +/-   +     +/-        +
Laser Therapie)
PRP             3              +/-   +/-   +     +/-        +

Women

Minoxidil 2%         1         +++   ++    +++   +          +++
Lsg.                                       +
Minoxidil 5%
Schaum
Hormones oral        3         +     +     +     +++        ++
Hyperandrogenis
mus
Hormones oral        3         +/-   +/-   +     +++        ++
normal
Hormones
Hair                 4         -     ++    ++    +          +
transplantation                                  Eingriff
with/without adj.                                +++
therapy                                          Langzeit
LLLT (Low-level      2         +/-   +/-   ++    +++        +++
Laser Therapie)
PRP ( Platelet-      3         +/-   +/-   1     +/-        +
Rich Plasma)
Overall rating       -         +/-   +     ++    +++        ++++
                     niedrig                                hoch

Quelle: Kanti et al. 2018
Hair Loss Management with PRP at AGA and Hair Transplants
Figure 1: Trichoscan before PRP treatment

Bestimmt die Haaranzahl, deren Dichte und die Rate der Haare in der Ruhephase
(Telogenrate)
Hair Loss Management with PRP at AGA and Hair Transplants
Figure 2: Trichoscan 6 months after 4 x PRP treatments

Total number of hairs, hair density and number of growing hairs are significantly improved.

Figure 3: Classification of the AGA according to Norwood and Ludwig.

Quelle: Norwood, 1975, Ludwig, 1977
Hair Loss Management with PRP at AGA and Hair Transplants
Figure 4: Previous FDA approved medication

©Bruce Reith
                                                                         Quelle: Autor

While in the last 3 decades only 2 substances, Minoxidil and Finasteride, were the only
substances of choice at AGA, new and improved therapies have developed rapidly in the last
6 years.
Multiple drug treatments as well as cell therapeutics or medical devices are still in preclinical
development or clinical trials. However, these could soon come onto the market.
Hair Loss Management with PRP at AGA and Hair Transplants
Figure 5: Triad of Eivdenzbased Medicine (EbM)

Quelle: Autor
Figure 6: Pathogenesis and therapeutic approaches in AGA.

Quelle: Gua H. et al. 2017

The main components of AGA pathogenesis are genetically susceptible hair follicles, the
conversion of dihydrotestosterone (DHT) in the skin from circulating androgens, accumulated
DHT-inducible suppressors of hair follicle growth, micro-inflammations and cell aging, some
of which are caused by androgen-mediated DNA damage.
Current and future treatment strategies include reducing local DHT production, targeting
androgen-regulated factors in follicular epithelial cells and dermal papilla cells, improving
perifollicular vascular supply, controlling microscopic follicular inflammation, and possibly
controlling connective tissue remodelling by balancing protease/antiprotease systems.
Figure 7: Effect of PRP on hair growth cycle

©Bruce Reith

Dermal papilla cells: Regulate the development and growth of hair follicles and is considered
a reservoir of multipotent stem cells.
Figure 8: Mechanical model of the PRP effect on the dermal papilla cells

Quelle: Autor

Activated PRP stimulates hair growth by promoting vascularization and angiogenesis, and
encourages hair follicles to enter and extend the anagen phase of the growth cycle. The
process is achieved by increased activation of β-Catenin (BC), extracellular signaling
regulated kinase (ERK) and protein kinase B (Akt) signaling pathways mediated by growth
factors, leading to the necessary cell proliferation and differentiation. Akt also
simultaneously prevents apoptosis A
Figure 9: Main protocol PRP in 4 steps

Quelle: Autor
Figure 10: Hair transplantation Strip method- FUT

Quelle: Autor
Figure 11: Single removal - FUE

A hair transplant is a surgical procedure that transplants hair follicles from the scalp, which is
resistant to hair loss, to bald or sparse areas.
The hair follicles are removed either with strips (FUT) (Fig.10) or individually (FUE)
(Fig.11), preserved in a holding solution and then implanted into the slits prefabricated by the
doctor.
Figure 12: Influence of hair transplantation on quality of life and health

 Verbessern Haartransplantationen die geistige und körperliche Gesundheit?
Reith Bruce, MD, PhD., Mojto Viliam, MD, PhD, Kottman Tanja, MD.
Medizinischer Direktor bei medical hair & esthetic (Munich,Germany) / Medizinischer Direktor Haarzenrum Bodenseeklink (Lindau, Deutschland )
Kontakt: brucereith@me.com

Ausschluß: COI; Keine; Off-Label Usage; Keine.
                                                                          RESULTS                                                                                                                                                                                            5) AQoL-8D Resultat
Einleitung                                                                1) Kein signifikanter Unterschied in der Alters- und Ge-                                                                                                                                                                                          AQoL 8D Werte pro
Das Haar ist ein wesenlicher Bestandteil unserer Erscheinung.                schlechtsverteilung zw. Prä- und postoperativer Gruppe:                                                                                                                                                                                        Dimension prä- (n=188)
Zahlreiche Studien zeigten die negative Auswirkungen des Haar-               Durchschnittsalter 37.0 ± 12.1 Jahre und 88.7% männlich                                                                                                                                                                                        versus postoperativer
                                                                                                                                                                                                                                                                                                                            Gruppe (n=129)
ausfalls auf das Wohlbefinden und die Lebensqualität. Darüber                im Vergleich zu 36.9 ± 11.8 Jahre und 88.5% männlich.
hinaus wurde ein Zusammenhang mit psychischen Problemen                   2) 96.6% sagten, dass die Transplantation ihr Leben positiv ver-                                                                                                                                                                                  Die AQoL 8D Werte waren in
(z.B. geringes Selbstvertrauen) und Depressionen beobachtet.              änderte und 97.7% würden sich wieder operieren lassen (n=213).
                                                                                                                                                                                                                                                                                                                            allen 8 Dimensionen der prä-
                                                                                                                                                                                                                                                                                                                            opertiven Gruppe signifikant
                                                                          3) Auswirkung von schönen Haaren auf……                                                                                                                                                                                                            höher (p< 0,001) imVergleich
Studienziel                                                                                                                                                                                                                                                                                                                 zur postoperativen Gruppe
                                                                                                                       100
Diese Studie untersuchte die Auswirkungen einer Haartrans-
                                                                           Patienten mit hoher Punktzahl (% )

                                                                                                                                                                                                                                              Pic: www.worth1000.de
plantation auf die psychische Gesundheit im infolge des Haar-                                                          80

ausfalls und auf die allgemeine Lebensqualität.                                                                        60
                                                                                                                                                                                                                                                                             6) BDI-II Resultat

                                                                                                                       40                                                                                                                                                                                                   BDI-II-Gesamtpunktzahl in
Material und Methoden                                                                                                                                                                                                                                                                                                       der prä- und postoperativen
Ø Studiendesign: retrospektive 2 Zenter Kohortenstudie                                                                 20                                                                                                                                                                                                   Behandlungsgruppe
Ø 130 Pateinten mit erblichem bedingten Haarausfall welche                                                              0                                                                                                                                                                                                   Die Differenz zwischen dem
  eine Transplantation 9 -36 Monate vor Einschluss erhielten                                                                  Se
                                                                                                                                 lb                  At tr                        Mä           Ge
                                                                                                                                                                                                  sun
                                                                                                                                                                                                           “ Mein volles Haar hat mir zum Erfolg
                                                                                                                                                                                                                                                                                                                            Mittelwert von 9,58 ± 9,45
                                                                                                                                      st v                    akt                We nnlic                        alsSchauspieler geholfen”
Ø 194 Geschlechts- und Altersgleiche Patienten die sich noch                                                                              e   rtr
                                                                                                                                                    aue
                                                                                                                                                                    ivit
                                                                                                                                                                         ä   t
                                                                                                                                                                                   ibli hke
                                                                                                                                                                                       chk it /
                                                                                                                                                                                                     dh
                                                                                                                                                                                                       eit
                                                                                                                                                                                                                     (George Clooney)                                                                                       der präoperativen und 3,31
                                                                                                                                                          n                               e it                                                                                                                              ± 5,33 der postoperativen
  keiner Haartransplantation unterzogen haben                                                                                                                                                                                                                                                                               Patienten ist statistisch
                                                                           Prozentsatz der Patienten, die auf die Frage nach der Wirkung von schönen Haar eine
Ø Alle Patienten füllten 3 Umfragen aus: (1) Autorenfragebogen             hohe Wichtigkeit (4,5 or 6 on 6-point Likert scale) angegeben haben (n=401)                                                                                                                                                                      signifikant (p 20)
                                                                                  Patienten mit hoher Punktzahl (% )

Ø 83 weitere Pilotstudienpatienten haben den vom Auto erstel-                                                                                                                                                                                                               Minimale Depression   9 - 13    16,6%   6,3%    wurden bei 18,2% der prä-

                                                                                                                                                                                                                                                   Pic: www.worth1000.de
                                                                                                                        80
  lten Fragebogen ausgefüllt (in Analyse mit einbezogen).                                                                                                                                                                                                                                                                   operativen Patienten fest-
                                                                                                                                                                                                                                                                            Milde Depression      14 - 19   4,8%    4,7%
                                                                                                                        60                                                                                                                                                                                                  gestellt, verglichen mit 2,4%
                                                                                                                                                                                                                                                                            Mittelschwere Depr    20 - 28   11,2%   1,6%    der postoperativen Patienten.
                                                                                                                        40                                                                                                                                                  Schwere Depression    29 - 63   7,0%    0,8%

                                                                                                                        20                                                                                                                                                 Fazit
                                                                                                                                                                                                             “ mit den Haaren verliert man auch                            Ø Erfolgreiche Haartransplantationen haben einen signifikant
                                                                                                                         0                                                                                          sein Selbstvertrauen”
                                                                                                                             Selb                    Ane         Part           Beru                                                                                           positiven Einfluß auf die geistige Gesundheit und verbessern
                                                                                                                                 stw                und rkenn         nerw          f
                                                                                                                                     e                  Bek ung            ahl
                                                                                                                                          rt
                                                                                                                                                           ann im F                                                                                                            das Wohlbefinden und die allg.Lebensqualität des Pateinten.
                                                                                                                                                              ten     re
                                                                                                                                                                 kre unde
                                                                                                                                                                    is       s-                                                                                            Ø Haartransplantationen sind nicht nur rein kosmetische Ein-
                                                                          Patientenanteil, die bei der Befragung zu den Auswirkungen des Haarusfall eine hohe                                                                                                                  griffe sondern auch medizinische notwendige Behandlungen
   Quelle : Richardson, J.
                                                                          Bedueutung (4,5 or 6 on 6-point Likert scale) angegeben haben (n=401)                                                                                                                                welche ebenso bedeutend für die Gesundheit sind.
Figure 13: Current recommendation for AGA

Quelle:Autor
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Kontakt

Dr.Bruce Reith, (MD, PhD)
Chefarzt Medical Hair& Esthetic
Brunnstrasse 11
80331 München
Chefarzt Haarklinik Bodenseeklinik
Graf-Lennart-Bernadotte-Str. 1
DE 88131 Lindau / Bodensee

Email: Brucereith@me.com
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