Comparative efficacy of topical minoxidil alone against combination of topical minoxidil and platelet rich plasma in women with female pattern hair loss—A pilot, open randomised trial

   Abstract 


Background: Female pattern hair loss (FPHL) affects a significant proportion of population and poses a major therapeutic challenge. Aims and Objectives: To compare the efficacy and safety profile of combination of topical minoxidil 2% plus platelet rich plasma (PRP) (group 1) and topical minoxidil 2% solution alone (group 2) in women having FPHL. Materials and Methods: 26 females with FPHL were randomised into two treatment groups. They were evaluated for increase in hair density, reduction in hair pull test (HPT), patient satisfaction score (PSS) and side effects. Results: Mean change of 34.92 ± 8.39 hairs/cm2 in group 1 (P < 0.001) and 31.21 ± 8.30 hair/cm2 in group 2 (P < 0.001) was seen. 16.7% and 28.6% patients in Group 1 and 2, respectively, had PSS of highly satisfied. The reduction in HPT was significant with P = 0.0123 (group 1) and P = 0.0128 (group 2). There was no statistically significant difference between the two groups. No major side effects were reported. Conclusion: Minoxidil—PRP combination therapy is an effective modality for FPHL but is not superior to topical 2% minoxidil therapy alone. PRP is a promising option in patients with minoxidil related compliance issues.

Keywords: Female pattern hair loss, hair fall, minoxidil, platelet rich plasma


How to cite this article:
Agarwal A, Mendiratta V. Comparative efficacy of topical minoxidil alone against combination of topical minoxidil and platelet rich plasma in women with female pattern hair loss—A pilot, open randomised trial. Indian J Dermatol 2023;68:121
How to cite this URL:
Agarwal A, Mendiratta V. Comparative efficacy of topical minoxidil alone against combination of topical minoxidil and platelet rich plasma in women with female pattern hair loss—A pilot, open randomised trial. Indian J Dermatol [serial online] 2023 [cited 2023 Apr 1];68:121. Available from: 
https://www.e-ijd.org/text.asp?2023/68/1/121/373037    Introduction Top

Female pattern hair loss (FPHL) refers to a progressive decline in hair fibre production by scalp hair follicles and their eventual miniaturisation.[1] The most common pattern of hair loss seen in women is diffuse reduction of hair density over the crown, with complete or near complete preservation of the frontal hairline.[2] Olsen also observed the so called 'Christmas tree pattern', with widening of the central parting line most noticeably in the mid frontal scalp. He pointed out that the hair loss in women is often not confined to the crown but may extend ear to ear.[3]

FPHL affects a sizeable proportion of the population and advances with age and menopause. It can occur at any age after puberty; however, women approach for treatment mostly between 24 and 40 years of age. There is a second peak at menopause, between 50-60 years of age.[4],[5] In a study conducted in South India, FPHL accounted for 15.3% of diffuse hair loss in women. A positive family history is noted in half of the patients, with no difference in the age of onset of FPHL in patients with positive or negative family history.[6]

Women who seek medical advice for their hair loss experience more negative body image feelings, social anxiety, poorer self-esteem and adverse psychosocial well-being than control subjects with non-visible skin disease, as well as dissatisfaction with their hair.[6],[7]

A variety of treatment modalities are available for FPHL like topical minoxidil (FDA approved), oral anti androgens such as cyproterone acetate, spironolactone, finasteride or flutamide and surgical options like hair transplantation.[8],[9],[10],[11] But these treatment options are associated with their own set of side effects, such as minoxidil leads to local irritation, hypertrichosis of temples, clinical regression to a pre-treatment state on discontinuation of treatment to pre-treatment state and requires daily application indefinitely.[12],[13] Also anti-androgens can lead to feminisation of a male foetus (cyproterone acetate), hepatotoxicity (high dose flutamide) and teratogenicity in premenopausal women (finasteride).[14],[15]

Platelet-rich plasma (PRP) is a treatment modality that has gained popularity for FPHL over the years due to its autologous nature, minimal invasiveness, absence of major side effects, better compliance and more affordability compared to hair restoration surgery. It is an autologous concentration of platelets in a small volume of plasma with platelet concentrations 4 to 7 times baseline.

The activated platelets act as source of multiple growth factors like epidermal growth factor, vascular endothelial growth factor, platelet derived growth factor and transforming growth factor. Together they have shown to promote proliferation of dermal papillae and prolongation of anagen phase of hair cycle.

Most studies have showed platelet rich plasma to be an attractive option with next to no side effects but primarily in males. Till date no head to head trial exists comparing minoxidil and PRP therapy combinations to topical minoxidil alone in females with patterned baldness. There is no consensus regarding frequency, dosage and number of PRP sessions either.[5]

   Materials and Methods Top

Study design and subjects

This was a single centre-based open labelled randomised pilot study conducted over a two year period from November 2019 to October 2021, approved by the Institutional Ethics Committee conducted at Department of Dermatology, Venereology and Leprosy. All patients provided with a written informed consent before participation in the study. 26 patients of FPHL (12 in Group 1 and 14 in Group 2) were enrolled and the study was registered on 18 June 2020 under the number CTRI/2020/06/025969. Inclusion criteria comprised of females between 18 and 55 years with a diagnosis of FPHL established on the basis of clinical and trichoscopic examination, belonging to Ludwig grade 1-3. Exclusion criteria included females with endocrinological disorders, platelet disorders, bleeding disorders, malignancy, keloidal tendency, active scalp infection, positive viral markers (HIV 1 and 2, Hepatitis B and Hepatitis C), history of minoxidil intake in past 6 months, history of hair transplant, intake of drugs causing hair loss and pregnant or lactating women.

Randomisation technique

Variable block size randomisation (2, 4 or 6) was done using computer generated randomisation sequence by a person not involved in the study. Sealed opaque envelopes containing group codes were prepared. Envelopes were sequentially numbered and kept in order according to their serial number. Envelopes were opened at the time of randomisation and the patients were allocated to their respective groups, PRP+topical minoxidil combination group (group 1) and topical minoxidil alone group (group 2).

Platelet rich plasma preparation

To prepare PRP approximately, 17 ml of blood was taken from a peripheral vein into an acid citrate dextrose (ACD) vial. The sample was centrifuged with a 'light spin' first, where it separated into different blood components according to their specific gravity. The red blood cells formed the bottom most layer followed by WBC forming the middle layer and platelets form the top most layer. The top most plasma containing platelets was separated gently using pipette and transferred for second 'heavy-spin' so as to further concentrate platelets at the bottom making a pellet with platelet poor plasma (PPP) above. The majority of the PPP, approximately 3/4th was discarded and the end product consisting mostly of PRP was resuspended in remaining plasma.

Study intervention

Ludwig score, hair pull test [Table 1] and trichoscopic evaluation was done for all recruited patients at baseline, 4th, 8th, 12th, 16th and 24th week. Autologous PRP suspension (1-3 ml) was injected intradermally as per the dimensions of the affected area. Group 1 was injected with 0.1 ml of PRP at an interval of 1 cm (as per the standard departmental protocol) at monthly interval for four sessions and were assessed for outcome measures 2 months after last session. A scalp vibrator was used to alleviate pain during the procedure. They were instructed to apply 1 ml of 2% minoxidil solution twice daily. Patients in group 2 were instructed to apply only 1 ml minoxidil solution, twice daily. Global photography of the recipient area was done in the frontal, temporal and the vertex views keeping fixed, preselected settings of the digital camera (LUMIX, DMCGF3K, digital camera, Panasonic) at baseline and for the final evaluation at 24 weeks.

Table 1: Baseline demographic and clinical details of patients in Group 1 and Group 2.

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Methodology

Our study hypothesis was that combination of topical minoxidil 2% plus PRP was more effective as compared to topical minoxidil 2% solution alone in women with FPHL. Our primary objective was to compare the efficacy of topical minoxidil 2% solution alone and combination of topical minoxidil 2% plus PRP therapy by measuring patient satisfaction score in women having female pattern hair loss. Secondary objective was to compare the increase in hair density in the two groups and to assess the side effect profile of the two regimens.

Given the pilot nature of the study the sample size was calculated based on study with similar but not same comparison groups.[16] Our primary outcome was comparative assessment of the proportion of patients with patient satisfaction score >6. Secondary outcome included comparative assessment of the mean change in hair density, proportion of patients showing improved hair density on global photography, negative hair pull test and side effects in the two groups [Figure 3].

Statistical analysis

Descriptive statistics was elaborated in the form of means/standard deviations. Group comparisons for continuously distributed data were made using independent sample 't' test when comparing two groups. Chi-squared test was used for group comparisons for categorical data. Linear correlation between two continuous variables was explored using Pearson's correlation (if the data were normally distributed) and Spearman's correlation (for non-normally distributed data). Statistical significance was kept at P < 0.05.

   Results Top

Clinical efficacy

The mean increase in total hair density at [Table 2] 24th week showed statistically significant change in hair density for both the groups, with mean change of 34.92 ± 8.39 hairs/cm2 in group 1 (P < 0.001) and 31.21 ± 8.30 hair/cm2 in group 2 (P < 0.001) [Figure 1] and [Figure 2]; however, no significant difference was seen between the two groups (P = 0.241). Patient satisfaction score (PSS) of majority of patients, 10 (83.3%) in group 1 and 10 (71.4%) patients in group 2 showed PSS of moderately satisfied (PSS-4-6), while 2 (16.7%) patients in Group 1 and 4 (28.6%) patients in Group 2 had a PSS of highly satisfied (PSS: 7-10). There was no statistically significant difference between the PSS of the two groups (P = 0.652). Baseline Hair Pull Test (HPT) was positive in 9 (75.0%) patients of Group 1 and 8 (57.1%) patients of Group 2. At the end of 24 weeks, there was statistically significant reduction in positivity of HPT in both groups with only 2 (16.67%) patients in Group 1 (P = 0.0123) and 1 (7.14%) patient in Group 2 (P = 0.0128) having a positive HPT. There was no statistically significant difference between the two groups in terms of HPT at the end of 24 weeks (P > 0.05). Overall, mean platelet count was 2.27 ± 0.68 lac/ml, with a mean of 2.43 ± 0.65 lakh/ml for Group 1 and 2.13 ± 0.70 lac/ml in Group 2. A positive correlation was seen between mean platelet count and change in hair density at 24 weeks in group 1 (P = 0.049).

Figure 1: Dermoscopic image at baseline (L) and 24th week (R) of the patients of FPHL in group 2

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Figure 2: Global images at baseline (L) and 24th week (R) of a patient of FPHL in group 2

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Adverse effects

The most common side effect in Group 1 was pain [Table 3] at the time of PRP injections seen in 12 (100%) patients which resolved on its own in a few hours which was followed by itching over scalp experienced by 4 (33.3%) patients post minoxidil application. The most only side effect in Group 2 was of itching seen in 8 (57.1%) patients. 6 (42.9%) patients in group 2 experienced no side effects.

   Discussion Top

This study demonstrated that PRP in combination with topical minoxidil was effective in women who received four treatment sessions at 4 weekly intervals (P < 0.001), with a mean change in hair density of 34.92 hair/cm2 and 31.21 hair/cm2 for group 1 and group 2, respectively. However, it did not have any superiority over topical minoxidil therapy given in isolation (P > 0.05). Being a pilot study there was unavailability of any study with the same treatment groups as ours but in a study by Bruce et al. conducted in 2019, an RCT comparing PRP to topical minoxidil foam for treatment of AGA in females in which 20 women with AGA received topical minoxidil and injectable PRP for 12 weeks each in a randomised crossover design with an 8 week washout between treatments, it was found that after minoxidil therapy there was more significant increase in hair density count (P < 0.001), wrt PRP therapy (P = 0.002). Thus, it was concluded that PRP is an effective treatment for hair regrowth in female AGA, although not as effective as minoxidil.[17] In a double blind, placebo controlled study on the use of PRP in women with female AGA by Puig et al. the effect of PRP with that of saline placebo was compared, with the end points being hair count, hair mass index (HMI) and patient opinion survey responses. In this study, HMI or hair count was not increased statistically significantly between the study and placebo groups and PRP failed to demonstrate any statistically significant improvement in HMI or hair count in women with FPHL.[18] These studies had findings similar to ours. In a comprehensive systematic review and meta-analysis by Zhou et al., it was concluded that PRP was an excellent therapy for FPHL, although efficacy with minoxidil was not compared in this study.[19]

PSS is a subjective tool for assessment of treatment efficacy which is influenced by increase in hair density and side effects perceived by the patient. The PSS was divided into four categories of dissatisfied (<1), less satisfied (1-3), moderately satisfied (4-6) and highly satisfied (7-10). Majority of patients, 10 from each group belonged to the moderately satisfied category with a mean of 5.75 for group 1 and that of 6.07 for group 2. No statistically significant difference was seen between Group 1 and Group 2 in terms of PSS. At the end of the 6 months, all the patients from both the groups were motivated to continue their treatment and recommend it to others which further points towards effectiveness of both the treatments. In an RCT comparing PRP to topical minoxidil foam for treatment of AGA in women, it was concluded that although PRP was not as effective as minoxidil for hair regrowth in female AGA, the improved quality of life responses after PRP, suggested overall greater degree of satisfaction which could be attributed to a placebo like effect, where patients' outlooks were positively affected by receiving a new and promising treatment for hair loss.[17] No statistically significant difference in PSS of the two groups in our study could be attributed to the presence of minoxidil related side effects and compliance-related issues as minoxidil was the common denominator in both the groups.

Hair pull test, also known as the Sabouraud's sign, is used to reveal an increase in the number of telogen hair. Unlike alopecia areata and telogen effluvium, where in positive hair pull test is seen diffusely, in case of FPHL it is seen only in the involved areas.[20],[21] In our study, 75% patients in group A and 57.1% patients in group B had positive hair pull test in the beginning of the study. 77.78% patients in group A and 87.5% patients in group B had changed to a negative HPT at the end of 24 weeks. In a study by Tawfik et al., a randomised placebo controlled study to see the effect of autologous-activated PRP in 30 females with FPHL found that all the patients had a positive hair pull test at the baseline which turned negative in PRP injected areas in 83% patients, this change in the HPT was similar to our study.[22]

Our study demonstrated that the most common side effect in group 1 was temporary and localised scalp pain/discomfort seen in 100% patients followed by itching seen in 33.3% patients. In group 2, the most common side effect was tolerable itching, seen in 57.1% patients. The side effects were of mild severity which neither affected the compliance nor caused anyone to drop out of the study. In a study by Bruce et al.,[17] a pilot RCT comparing PRP to topical minoxidil in females with FPHL, no adverse effects were seen in minoxidil receiving groups; however, the PRP treatment was associated with pain/discomfort or bruising seen in 4 (21.1%) patients.

The primary limitation of this study was its small sample size, although justifiable for a pilot study.

   Conclusions Top

PRP + 2% Minoxidil combination didn't show any superiority to 2% minoxidil therapy and required the patient to undergo a painful procedure every month. PRP therapy is costlier, equipment dependent, has long processing time, requires patient work up and is not available to all. Thus, we recommend topical 2% minoxidil therapy alone over PRP + minoxidil combination. However, PRP is an effective therapy, specially, in patients with high platelet count and can be recommended in those having compliance related issues or not being able to tolerate minoxidil induced pruritus. Our study was the first to compare PRP + 2% minoxidil combination with 2% minoxidil alone for FPHL. Further studies are required to confirm our findings.

Abbreviations

ACD = Acid citrate dextrose

AGA = androgenetic alopecia

HMI = Hair mass index

FPHL = Female pattern hair loss

PPP = Platelet poor plasma

PRP = Platelet rich plasma

PSS = Patient satisfaction score

RCT = Randomised control trial

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

   References Top
1.Kabir Y, Goh C. Androgenetic alopecia: Update on epidemiology, pathophysiology, and treatment. J Egyptian Women's Dermatologic Soc 2013;10:107-16.  Back to cited text no. 1
    2.Birch MP, Lalla SC, Messenger AG. Female pattern hair loss. Clin Exp Dermatol 2002;27:383-8.  Back to cited text no. 2
    3.Hébert JM, Rosenquist T, Götz J, Martin GR. FGF5 as a regulator of the hair growth cycle: Evidence from targeted and spontaneous mutations. Cell 1994;78:1017-25.  Back to cited text no. 3
    4.Olsen EA. Female pattern hair loss. J Am Acad Dermatol 2001;45(Supplement):S70-80.  Back to cited text no. 4
    5.Keaney T. Emerging therapies for androgenetic alopecia. J Drugs Dermatol 2015;14:1036-40.  Back to cited text no. 5
    6.Singal A, Sonthalia S, Verma P. Female pattern hair loss. Indian J Dermatol Venereol Leprol 2013;79:626-40.  Back to cited text no. 6
[PUBMED]  [Full text]  7.Ravikiran SP, Syrti C, T S. An epidemiological study of female pattern hair loss at a referral centre in south India. Indian J Clin Exp Dermatol 2016;2:106-10.  Back to cited text no. 7
    8.Rose J, Stormshak F, Oldfield J, Adair J. Induction of winter fur growth in mink (Mustela vison) with melatonin. J Anim Sci 1984;58:57-61.  Back to cited text no. 8
    9.Garza LA, Liu Y, Yang Z, Alagesan B, Lawson JA, Norberg SM, et al. Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. Sci Transl Med 2012;4:126ra34.  Back to cited text no. 9
    10.Trüeb RM. Molecular mechanisms of androgenetic alopecia. Exp Gerontol 2002;37:981-90.  Back to cited text no. 10
    11.Milner Y, Sudnik J, Filippi M, Kizoulis M, Kashgarian M, Stenn K. Exogen, shedding phase of the hair growth cycle: Characterization of a mouse model. J Invest Dermatol 2002;119:639-44.  Back to cited text no. 11
    12.Kishimoto J, Ehama R, Ge Y, Kobayashi T, Nishiyama T, Detmar M, et al. In vivo detection of human vascular endothelial growth factor promoter activity in transgenic mouse skin. Am J Pathol 2000;157:103-10.  Back to cited text no. 12
    13.Kishimoto J, Burgeson RE, Morgan BA. Wnt signaling maintains the hair-inducing activity of the dermal papilla. Genes Dev 2000;14:1181-5.  Back to cited text no. 13
    14.Stenn KS, Paus R. Controls of hair follicle cycling. Physiol Rev 2001;81:449-94.  Back to cited text no. 14
    15.Randall VA, Jenner TJ, Hibberts NA, De Oliveira IO, Vafaee T. Stem cell factor/cKit signalling in normal and androgenetic alopecia hair follicles. J Endocrinol 2008;197:11-23.  Back to cited text no. 15
    16.Verma K, Tegta GR, Verma G, Gupta M, Negi A, Sharma R. A study to compare the efficacy of platelet-rich plasma and minoxidil therapy for the treatment of androgenetic alopecia. Int J Trichology 2019;11:68-79.  Back to cited text no. 16
    17.Bruce AJ, Pincelli TP, Heckman MG, Desmond CM, Arthurs JR, Diehl NN, et al. A randomized, controlled pilot trial comparing platelet-rich plasma to topical minoxidil foam for treatment of androgenic alopecia in women. Dermatol Surg 2020;46:826-32.  Back to cited text no. 17
    18.Puig CJ, Reese R, Peters M. Double-blind, placebo-controlled pilot study on the use of platelet-rich plasma in women with female androgenetic alopecia. Dermatol Surg 2016;42:1243-7.  Back to cited text no. 18
    19.Zhou S, Qi F, Gong Y, Zhang C, Zhao S, Yang X, et al. Platelet-rich plasma in female androgenic alopecia: A comprehensive systematic review and meta-analysis. Front Pharmacol 2021;12:726.  Back to cited text no. 19
    20.Gupta AK, Foley KA. 5% minoxidil: Treatment for female pattern hair loss. Skin Therapy Lett 2014;19:5-7.  Back to cited text no. 20
    21.Goren A, Shapiro J, Roberts J, McCoy J, Desai N, Zarrab Z, et al. Clinical utility and validity of minoxidil response testing in androgenetic alopecia. Dermatol Ther 2015;28:13-6.  Back to cited text no. 21
    22.Tawfik AA, Osman MAR. The effect of autologous activated platelet-rich plasma injection on female pattern hair loss: A randomized placebo-controlled study. J Cosmet Dermatol 2018;17:47-53.  Back to cited text no. 22
    
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