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Platelet Rich Plasma – hype or fact?

PRP has been around for a while. The product is actually fairly simple: take some blood from the patient, and spin it down until you have the plasma with all the platelets in it, and inject it into the affected areas of scalp.

Proposed rationale behind the use of Platelet rich plasma (PRP) in hair loss

Platelet rich plasma (PRP)is concentrated blood plasma which contains approximately three to five times the number of platelets found in normal circulating blood.PRP contains > 20 growth factors including platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor (TGF) and other bioactive proteins that aid in wound healing.

The few studies that have been conducted on PRP and hair loss have shown that it appears to have positive effects on hair growth. It is proposed that PRP inducesdermal papilla cell proliferation in vitro, induces angiogenesis via VEGF, and up-regulates Wnt-signaling proteins and beta catenin, all of which appear to haveimportant roles in hair follicle activation.

All this is at present merely a hypothesis.

But does PRP really work?

You need to look at randomized controlled trials (RCTs) for something like this, and particularly ones that compare it to a placebo. The lack of a placebo can be confusing and lead to incorrect conclusions. One must understand that clinical trials are designed to specifically evaluate both efficacy and safety endpoints.The clearest inferences can be drawn from a double blind randomized controlled study where the investigator and patient bias is eliminated and the active treatment is compared to a placebo or a standard drug. Also the methods of assessment have primarily relied on patient satisfaction, global photography and trichoscopy. Addition of cross-sectional trichometry to assessment methods would give further information on its efficacy.

One of the studies published in 2012 (https://www.ncbi.nlm.nih.gov/pubmed/22455565) and another published in 2015 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622412/) mention upregulation of the growth factors but the benefits are seen to drop after a few months after the last treatment and more importantly there being no control group it is difficult to give the entire credit of improvement to PRP.

Another study published in 2016 (https://www.ncbi.nlm.nih.gov/pubmed/27761085) mentions improvement in percentages. When reports come out that you get more than75% growth at 6 months, what does that mean? How has the author quantified this percentage. There is no talk about the final result in both groups and whether there was a difference at the end of one year as that is the time one sees 90% growth in most cases after hair transplantation. Merely getting early growth does not mean that the ultimate outcomes are better with the PRP group as compared to the non PRP group.

We, at Hairrevive have been one of the chief investigators ofa prospective, multicentric, open label, randomized, bio-interventional, phase i/ii pilot study to evaluate the safety and efficacy of autologous human platelet lysate (HPL) (a variant of PRP where the platelets are broken down to release the growth factors. HPL has almost five times the concentration of growth factors as compared to HPL) for treatment of androgenetic alopecia (AGA)(http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=4375&EncHid=&userName=human%20platelet%20lysate). The study did not show any consistent benefits in improving hair loss in patients of MPHL when compared to standard treatments of using minoxidil and finasteride.

The reason for increased demand for PRP treatment seen today

The search for a minimally invasive solution to improve the status of hair loss in men and women with no adverse effects is what most patients want. In this scenario, PRP appears to be a novel and promising treatment. Most of the studies of PRP mention patient satisfaction as one of the criteria for efficacy of the treatment.  In a clinical trial (https://www.ncbi.nlm.nih.gov/pubmed/27608205) though the doctors did not find any statistically significant improvement in the hair mass index (HMI) or hair counts, but in the same study patient feedback suggested a better therapeutic outcome. Likewise patients who consult us for hair loss and who had previously received PRP treatments grudgingly agreed that there was no real improvement in their hair loss issue but most of them said that their hair fall had slowed down.

The reason patients feel like this is because of “placebo effect” (a beneficial effect produced by a placebo drug or treatment, which cannot be attributed to the properties of the placebo itself, and must therefore be due to the patient’s belief in that treatment)

PRP actually meets the requirements of an ideal placebo.

Patients get stronger placebo effects because:

  1. Response to placebo is irrespective of IQ of the patient thus possibly affecting all patients.
  2. The degree of response is determined by what the patients are told about the treatments by the doctor and their expectations. Widespread propaganda by the doctors and clinics, alike, calling PRP treatments ‘high tech’ and ‘natural’. Usually these qualities are mutually exclusive but they are applied unfailingly to PRP.
  3. The route of delivery –injections. When treatments involve injections, patients feel that these are more powerful than topicals or pills(needling is one of the most powerful routes of delivery, especially when performed repeatedly in injection cycles)

Why PRP may be more hype than science (at least at present)?

Pattern hair loss is known to progress with age, and is caused by the effect of androgens (male hormones) on hair follicles in genetically susceptible individuals. It is a genetic condition for which there is no definite cure.

Most currently used and approved treatments need daily dosing. In such a scenario it is difficult to look at a treatment which requires a few interventions at monthly intervals. Most reports mention the end points of study at 6 months. Whether more treatments would be needed and if so – How many? How often?

  1. PRP does not address any of the main reasons for hair fall (namely the androgens or the genes) and hence it can have only a marginal and temporary effect. Growth factors delivered in the scalp will be metabolized and one does not know how long the benefits of a single treatment will last. As a result there is no standardized treatment schedule.
  2. Male pattern baldness is the result of premature entry into catagen due to androgens. At the initiation, dihydrotestosterone (DHT) stimulates synthesis of transforming growth factor-beta2 (TGF-beta2) in dermal papilla cells. TGF-beta2 suppresses proliferation of epithelial cells and stimulates synthesis of certain caspases. PRP contains TGF-Beta in high concentrations. The role of this growth factor in PRP treatments has never been explained. In fact studies have used TGF-B inhibitors along with PRP in some of the orthopedic studies -(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332503/) to overcome this anti proliferative effect of TGF B.
  3. Most studies from Orthopedics have shown no benefits in treatments of various disorders of ankle, knee and shoulder (https://www.ncbi.nlm.nih.gov/pubmed/21602565https://www.ncbi.nlm.nih.gov/pubmed/19288080). Studies from dental field have also revealed similar outcomes. If benefit has been demonstrated it is marginal and is seen in studies with small sample size of short duration.
  4. Clinics and doctors who promote PRP will tell you there is good evidence that PRP works, but they are cherry picking from a few studies that worked out in their favor one way or another. A few positive studies never mean much; unless they are good quality studies with a larger sample size and an optimum period of evaluation.

Looking at the recent papers published, we are uncertain as to the science behind these treatments. It seems like a broad statement to say that gene transcription is stimulated and stem cells are stimulated. Some of the studies performed in vitro (in the lab) on dermal papilla cells. The changes seen in these cells may not be replicated in in vivo (in the patient scenario) so one cannot make that assumption. Moreover there is no consensus on the concentrations of platelets to use, depth of the injection, amount per injection, type of PRP, type of delivery system, distance from one injection to another, interval between two injections etc.

There are significant scientific lacunae in our understanding of PRP. As with any new treatments the pioneers push the limits of science and often do not follow proper methods. But subsequent studies do test the conclusions before it becomes a part of the mainstream treatment. Where PRP is concerned, that has not happened.  What is alarming is that most doctors are recommending this treatment without truly assessing the efficacy and safety, indicating a conflict of interest and profit motive.

Reiterating how doctors (and the public) don’t just overestimate the benefits (as described above), but they also underestimate the harms. Offering treatments like PRP without proof and making money on each treatment taints those who are doing it. Worst of all, it makes doctors look gullible and it shows how doctors can practice without scientifically evaluating the available evidence. Unfortunately the results from published studies are so varied that it is difficult to accept PRP as a standard treatment.

As practitioners of evidence based medicine we choose not to offer these treatments to our patients till there is a strong evidence of efficacy from good controlled studies.

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