Platelet-Rich Plasma in Androgenetic Alopecia: Is It Really Worth the Hype?

ABSTRACT

Introduction:

Androgenetic alopecia (AGA) is defined as progressive, patterned hair loss that occurs as a result of androgen-mediated conversion of terminal hairs to vellus hairs. By the age of 60 years, 45% of men and 35% of women develop AGA. The Hamilton–Norwood scale is used to assess the extent and severity of AGA and classify the stages of male pattern hair loss in men, whereas the Ludwig scale is preferred for women. Currently, U.S. Food and Drug Administration-approved treatments for AGA include oral finasteride and topical minoxidil. Due to the limited number of effective therapies for AGA, platelet-rich plasma (PRP) has become an effective alternative treatment. A number of studies on PRP have shown promising results, leading to increased hair density and thickness with minimal or no side effects.

Aims:

We aim to study the safety, efficacy, and side effects of PRP therapy in patients of AGA and to study demographic data in the form of age, sex, age of onset of hair loss, and grade of AGA in patients.

Materials and Methods:

Fifty patients, 38 males and 12 females, with AGA were enrolled in the study. PRP was prepared using a double-spin method. Upon activation, PRP was injected in the involved areas of scalp once every 2 weeks for 6 months. Follow-up photos were taken every 3 months.

Results:

At 6 months, majority of the patients (45%) were unsatisfied and showed no change in hair growth after PRP therapy and few patients were lost in follow-up. Adverse effects were minimal and no long-term serious adverse effects were noted.

Conclusion:

We conclude from the results in our study that PRP therapy is not significantly effective in treatment of AGA. There is a need to develop standard protocols with regard to total length of PRP therapy and spacing between the two sessions of PRP for AGA.

INTRODUCTION

Androgenetic alopecia (AGA) is a type of hair loss characterized by a nonscarring progressive miniaturization of the hair follicles with shortening of the anagen phase. It occurs in genetically predisposed individuals, usually in a specific pattern distribution, hence it is sometimes also known as “pattern hair loss” or “common balding.”[1] In men, it is predominantly due to a combination of both genetic predisposition and the effect of androgens, hence the term AGA is often applied. In females, the better term for AGA is “female pattern alopecia” or “female pattern hair loss.”

In some people, especially women, hair loss can affect the self-esteem by affecting personal attractiveness and may even lead to depression.[2,3,4] A number of products have been proposed as hair loss therapies, most of them being over-the-counter products. Drug therapies specifically approved by the Food and Drug Administration (FDA) for treating AGA are limited to minoxidil and finasteride, and both can be used either alone or combined together.[5] Due to the limited number of effective therapies for AGA, continuous search goes on for other modalities and platelet-rich plasma (PRP) has emerged as an effective alternative treatment.

It is an autologous preparation of plasma containing a supraphysiological concentration of platelets.[6] The regenerative potential of PRP depends on the levels of growth factors (GFs) released upon activation.[7,8] Main GFs involved are platelet-derived GF (PDGF), transforming GF (TGF), vascular endothelial GF, epidermal GF, fibroblast GF, and insulin-like GF with their isoforms.[5,9,10,11] GFs appear to act in the bulge area of the follicle, where they bind to their respective receptors located in the stem cells. Primitive stem cells of ectodermal origin and germinative cells of mesenchymal origin are found in the bulge area and the dermal papilla, respectively. Interactions between these two kinds of cells as well as with binding GFs (PDGF, TGF-b, and vascular endothelial growth factor) activate the proliferative phase of the hair, giving rise to the future follicular unit.[12] PRP also modulates angiogenesis and enhances blood flow around the hair follicles, thus improving the cutaneous ischemic conditions.

Objectives

We conducted the present study to note the efficacy as well as safety profile of PRP therapy in patients with androgenic alopecia. Any untoward events or side effects, if any, were also noted.

MATERIALS AND METHODS

This was a prospective study conducted in a tertiary care hospital in western India as a part of postgraduate research thesis and has been approved by the state university. Fifty patients of AGA were enrolled in our study for PRP therapy on the basis of inclusion and exclusion criteria from August 2017 till August 2019 after taking written informed consent.

Inclusion and exclusion criteria

Both male and female patients with age between 20 and 50 years, who were off treatment both oral and topical for the last 30 days, and having AGA Grade 3–5 (Norwood–Hamilton pattern) in male and Grade 2–3 (Ludwig classification) in female were enrolled in the study. Patients with AGA of all other grades, other types of alopecia, age <20 or >50 years, patients with platelet count <1.5 lakhs or history of any bleeding tendency/disorders/anticoagulant medication, keloidal tendency, or having any active infections at the local site were excluded from the study.

The diagnosis of AGA was established on the basis of a detailed medical history and clinical and trichoscopic examination when required. Assessment of severity was done on the basis of Norwood–Hamilton scale in males and Ludwig scale in females. In patients who were using minoxidil lotion before PRP therapy, a wash-off period of 3 months was given before starting the therapy.

Laboratory investigations such as complete blood count and serum T3, T4, and TSH were done to exclude other causes of hair loss such as anemia, poor nutrition, and thyroid disorder. Serum HIV and serum HBsAg were done in all patients prior to starting the treatment. Photographic documentation was done at the time of enrollment and at every 3-month follow-up visit. Following informed consent, PRP was injected in the involved area of scalp once in every 2 weeks for 6 months. The whole procedure was done under strict aseptic conditions. The procedure for preparation of PRP is depicted in Figure 1.

Figure 1.

Preparation of platelet-rich plasma

Topical anesthesia (eutectic mixture of lidocaine and prilocaine) was applied to the recipient area 45 min prior to procedure. Before injecting PRP, the scalp was cleaned with betadine and spirit. Multiple small injections were given over the treatment area, 1 cm apart in a linear pattern. 0.1 ml/cm² PRP was injected in the affected areas of scalp per sitting, and maximum 5.28 ml PRP was injected in scalp per sitting. The procedure was carried similarly once in every 2 weeks for 6 months.

Response to treatment was assessed in two ways – investigator’s assessment and patient’s satisfaction. For investigator’s assessment, standardized global photographs of the patients were taken, following which paired baseline and posttreatment photographs were reviewed and assessed with standard 7-point assessment scale as very poor, fair, below average, average, above average, good, and excellent. Patients’ satisfaction was assessed by standard Likert’s scale for subjective satisfaction which ranged from highly unsatisfied, unsatisfied, undecided, satisfied, and highly satisfied. We also observed and noted any adverse effects during the follow-up visits.

RESULTS

One hundred patients were enrolled in this study by consecutive enrollment. Fifty patients were excluded on the basis of the exclusion criteria and fifty patients were given PRP therapy. Among these 50 patients, 14 (28%) patients were in the age group between 26 and 30 years (mean age: 32 years). Thirty-eight patients were males and 12 were females (M: F = 3.1:1). The most common grade of AGA among included males was Norwood–Hamilton Grade 3 (n = 14). In the female patients, Ludwig Grades 2 and 3 were seen equally in 6 patients belonging to each grade. Family history of AGA was positive in 64% (n = 32) of the patients in our study. Most of the patients (28%; n = 14) reported onset of hair loss between 20 and 24 years, followed by onset between 25 and 29 years (24%; n = 12). Three patients reported an early age of onset of hair loss (15–19 years) and six patients had hair loss which started between 40 and 44 years. The mean age of onset of hair loss was 29.5 years [Table 1].

Table 1.

Clinical and demographic data of patients (n=50)

Patient characteristics	Number of patients (%)
Gender distribution
Male	38
Female	12
Grade of AGA (Males - Hamilton-Norwood) (n=38)
3	14
4	13
5	11
Grade of AGA (Females - Ludwig) (n=12)
2	6
3	6
Age of onset of hair loss (years)
15-19	3 (6)
20-24	14 (28)
25-29	12 (24)
30-34	7 (14)
35-39	8 (16)
40-44	6 (12)
Family history of AGA
Present	32 (64)
Absent	18 (36)
Previous treatment
Present	28 (56)
Absent	22 (44)

AGA - Androgenetic alopecia

Most patients (n = 28) had taken some treatment previously in the form of topical minoxidil lotion and/or herbal oils. Most of the patients had baseline platelet count between 2.6 and 3.5 lakhs, and the mean baseline platelet count was 2.5 lakhs/cumm. The platelet count in PRP was between 9.6 and 11.5 lakhs in most of the patients (40%). The mean platelet count in PRP was 8.4 lakhs/cumm [Table 2].

Table 2.

Platelet count in platelet-rich plasma

Platelet count (L)	Number of patients, n (%)
5.5-7.5	18 (36)
7.6-9.5	12 (24)
9.6-11.5	20 (40)

Out of 50 patients, 36 followed up at 3 months while 14 patients were lost to follow-up for various reasons. Out of these 36 patients, only 30 patients followed up at 6 months and 6 were lost to follow-up. Hence, out of 50 patients, only 30 completed the study till 6 months [Figure 2]. A maximum number of sittings were 12 in 6 months taken by 60% of the patients.

Figure 2.

Follow-up of patients in our study

All patients had adverse effects in the form of transient erythema, immediately after injecting PRP therapy. Eighteen patients reported a mild headache and pain persisting for few hours after the injections.

Subjective assessment of patient’s satisfaction with treatment by PRP therapy was assessed by standard Likert’s scale of subjective assessment, in which majority of the patients 19 (45%) were unsatisfied with the PRP therapy and only 8 patients found it satisfactory [Figure 3].

Figure 3.

Patients’ subjective assessment after PRP therapy

Investigator’s assessment was done by the standardized 7-point scale. Majority of the patients did not show any change at the end of 3 months (72.2%) and even after 6 months (33.3%). Mild improvement, in terms of reduction in hair loss, was seen in 22.2% and 26.6% of the patients at the end of 3 and 6 months, respectively. No patient showed excellent improvement at the end of 3 months, and only ten patients out of thirty had excellent improvement after PRP therapy at the end of 6 months [Figure 4a and b].

Figure 4.

(A) Observer’s assessment after PRP therapy (B) Observer’s assessment. a, b, c – Excellent improvement; d, e, f – Moderate improvement; g, h, I – No improvement

DISCUSSION

AGA is considered to be the most common type of baldness in men.[13] Prevalence of AGA is considered to be the highest in Caucasians, around 30% for men in the age group of 30–39 years and 40% for men in 40–49 years and 50% for men in 50–59 years.[13] In the Indian context, a prevalence of AGA in males aged 30–50 years has been reported to be slightly higher (58%)[14] as compared to Chinese (21.3%) and Korean (14.1%) populations.[15] Epidemiological studies of AGA in women are few. One study showed Hamilton–Norwood Grade II pattern as the most common presentation in Indian population,[16] while another study showed type II and III as being the most common presentation.[17]

Despite being the most common hair disorder, a satisfactory treatment for AGA still eludes the medical fraternity. FDA-approved drug therapies include finasteride and minoxidil.[18,19,20] Due to the limited number of effective therapies for AGA, newer options are being explored continuously and PRP has emerged as an effective alternative treatment.

A lot of research has already been done on its role in other specialties such as orthopedics and gynecology, and nowadays, it is being researched as an effective therapeutic modality in a variety of diseases in dermatology as well as for esthetics. It is an emerging modality of treatment in conditions such as AGA, alopecia areata, acne scars, skin rejuvenation, nonhealing wound ulcers, striae atrophicans, lipodermatosclerosis, and lichen sclerosus.

The mean age of patients in our study was 32 years (20–46 years) which is more than that reported by foreign authors.[21,22] In Indian studies, both lesser mean age (28.5 years)[23] and a comparable value (30.5 years) have been seen.[24] The mean age of onset of hair loss was 29 years in the study which was much higher than that seen by Verma et al.[23]

A standard method for preparing the PRP is lacking, hence different methods are used by the authors worldwide. PRP can be prepared by manual double-spin technique as well as with the help of automated devices. In our study, we prepared the PRP by manual double-spin technique (1^st spin at 1500 rpm for 15 min and 2^nd spin at 2500 rpm for 5 min) which is similar to use by other Indian authors also.[23,25] The single-spin method has been used mainly by foreign authors.[21,22,26] The volume of blood to be drawn for preparation of PRP has also varied between 18 and 35 ml in most studies,[22,23,25,26] and we used 16 ml of blood to prepare the PRP. Schiavone et al.[21] used a much higher volume of blood (60 ml) for preparing the PRP in their study, as they estimated that a higher volume of whole blood (40–120 ml) is necessary to inject an adequate volume (5 ml–15 ml) of PRP in the scalp. Many activators such as calcium chloride, calcium gluconate, and platelet-releasing factors have been used by various authors, but we did not use any of these [Table 3].

Table 3.

Comparison of various studies showing mode of platelet-rich plasma preparation, activator used, time and rotation of centrifugation, blood volume used, and volume of platelet-rich plasma gained

First author	Mode of preparation	Activator used	Centrifugation	Time of centrifugation (min)	Blood volume (ml)	PRP volume (ml)
Schiavone et al., 2014[21]	Single spin at baseline Double spin at 3 months	No	Not mentioned	Not mentioned	60 40	6-8
Khatu et al., 2014[25]	Manual double spin	Calcium chloride (1:9 ratio)	1500 rpm 2500 rpm	6 15	20	2-3
Alves and Grimalt, 2016[22]	Single-spin method	Calcium chloride (10%, 0.15 ml)	460 g	8	18	3
Anitua et al., 2017[26]	Single-spin method	PRGF activator	580 rpm	8	18	3-4
Verma et al., 2019[23]	Manual double spin	Calcium gluconate	1100-1500 g	5-10	25-35	6-8
Present study	Manual double spin	No	1500 2500	15 5	16	2-3

PRP - Platelet-rich plasma; PRGF - Plasma rich in growth factor

The relation between platelet concentration in the PRP and clinical benefits is still an unexplored and under investigation territory. In our study, majority (54%) of the patients had platelet counts between 2.5 and 3.5 lakhs at the baseline and 9.6–11.5 lakhs in the PRP. The mean platelet count was 2.57 lakhs at the baseline, and in majority (40%) of the patients, the mean platelet count in PRP was four times of the baseline. Verma et al. also observed similar platelet counts at the baseline and in the PRP.[23] However, few authors have observed a lesser platelet count also in the PRP in their studies.[22,26] Schiavone et al. suggested in their study that a threefold to fivefold increase in platelet concentration over baseline would be effective and target the follicular stem cells successfully.[21]

As any grievous adverse reactions have not been reported till date, PRP has already become an attractive off-label treatment alternative. No major adverse effects were reported in our study also after the PRP therapy. Majority of the patients had pain at injection sites, headache, and transient erythema after therapy which were short lived and did not require any intervention.

Although PRP therapy has been used for over a decade now in treatment of AGA, no standard protocols are there regarding the preparation method, number of sessions, or the interval between the two sessions. In the present study, PRP was given at 2-week interval for 6 months and effect of PRP therapy was evaluated by global photography and patient satisfaction score. In addition to these methods, other studies have used phototrichogram and hair pull test also in the evaluation of hair growth.[23,25] Concerns have been there regarding global photography and patient satisfaction score being subjective and hence exposed to some bias. However, as global photography is now accepted for monitoring improvement even during clinical trials for biologics in psoriasis, these concerns may not be completely justified.

Many studies have demonstrated the effectiveness of PRP therapy for AGA, but there are only a few studies that have given a negative result after PRP therapy, similar to the present study.[27,28] Most of the patients in our study were unsatisfied with the treatment due to no satisfactory improvement in the form of hair growth and having pain and headache after PRP therapy. On global photography also, majority of the patients showed no change at 3 months and 6 months [Table 4].

Table 4.

Comparison of various studies with the present study in form of treatment protocols, evaluation methods, and results of various studies

Study	Sample size	Sessions	Interval between sessions	Follow-up	Evaluation methods	Results
Schiavone et al.,2014[21]	64	2	3 months	6 months	Hair count and hair thickness using Jaeschke 15-Point Scale rating of clinical change	Visible improvement in hair thickness and count after 6 months of PRP treatment 40.6% of the study participants reached moderate level of improvement
Khatu et al.,2014[25]	11	4	2 weeks	3 months	Global photographs, phototrichogram, Patient’s Assessment Scale	81.81% of the patients achieved a negative pull test at 12-week mean gain of 22.09 follicular units/cm2 moderate improvement in hair volume and coverage
Alves and Grimalt 2016[22]	25	3	1 month	6 months	Phototrichogram and global photography	Significant improvements were detected hair density PRP-treated areas versus placebo-treated area (P<0.05) at 3 and 6 months
Anitua et al.,2017[26]	19	5	1 month for first 4 sessions; final session 7 months after start point	1 year	Computerized phototrichogram, global photographs, patient self- satisfaction score	Significant improvement in hair density, diameter, and telogen to vellus hair ratio Most patients had noticeable decrease in hair loss and noticeable improvement in hair quality and appearance
Verma et al.,2019[23]	40	4	1 month	6 months	Global photographs, hair pull test, patient satisfaction score	Better outcome in PRP group as compared to minoxidil group. In 75% of the patients, hair pull test was negative in PRP group compared to 42.8% in minoxidil group. 6.56±1.09 in PRP group versus 4.85±1.46 (P=0.001)
This study	50	12	2 weeks	6 months	Patient satisfaction score Global photographs	Most of the patients unsatisfied and no notifiable hair growth at 6 months Few patients had mild-to-moderate improvement in hair growth after 3 and 6 months

PRP - Platelet-rich plasma

In Indian literature, studies have used minoxidil along with PRP and have achieved significant results. We used PRP as a monotherapy and failed to achieve good results, despite following the procedure similar to the other Indian studies. We have also described in detail our protocol of PRP preparation and application, thus making our results easily reproducible.

Limitations

Our study has the limitation of not being a randomized, double-blind, controlled trial, and potential bias might be present. We did not use phototrichogram or trichogram to assess the hair growth in our studies, but the global photographic assessment, which we did, is considered a good tool.

CONCLUSION

Although PRP therapy is considered for the treatment of AGA due to less side effects, easy reproducibility, and cost-effectiveness, our study did not show any major improvement in hair growth with PRP therapy. Patients’ and observer’s assessment scores were low. Hence, our study showed that PRP has little value as monotherapy. It may be used as an adjuvant with other agents such as minoxidil and finasteride in AGA. Further research is warranted to define standard protocols for preparing PRP and its application in AGA. Standardized evaluation methods should be decided as it is difficult to adequately assess the effectiveness of PRP for its restorative potential without these parameters.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.