Abstract
Objectives:
Androgenetic alopecia (AGA) is the most common cause of hair loss in men and women, affecting about 30% of men and 15% of women at 30 years and 80% and 48% at 70 years, respectively. This study aims to assess the effectiveness of growth factor cocktail therapy including fibroblast growth factor 9 (FGF9) (Cellcurin) in men and women with AGA.
Materials and Methods:
This is a single-center randomized controlled trial, conducted with 10 men and 10 women with AGA. Eight men participated in the therapeutic group and two men in the control group. Eight women participated in the therapeutic group and two women in the control group. All were classified by sex, age, duration, and degrees of progression of AGA. The study obtained approval from the Research Ethics Committee (REC) of the Federal University of Uberlandia at approval number: 36918620.8.0000.5152. Six microneedling sessions were performed with an electromedical pen with an interval of 15 days between sessions. In the therapeutic group, sterile injectable Cellcurin was used and, in the control group, injectable sterile minoxidil 5 mg/ml 2 ml, both through the drug delivery system. Trichoscopic photos were taken before and after 12 weeks in the frontal and vertex regions. Descriptive statistics were performed using the t-test with the IBM SPSS-25 software.
Results:
Men and women showed an expressive and significant increase in the amount of hair per cm2 after Cellcurin therapy, as well as an increase in the amount of terminal hair, vellus hair, sum of the terminal hair diameters, and mean of the terminal hair diameters in both regions, frontal and vertex.
Conclusions:
In this study, we demonstrated that the use of Cellcurin in the treatment of AGA in men and women is associated with an increase in the amount of hair per cm2, in the amount of terminal hair per cm2, in the amount of vellus hair per cm2, in the number obtained by the sum of the terminal hair diameters per cm2, as well as an increase in the mean diameter of the terminal hairs.
Keywords: Alopecia, androgenetic alopecia, fibroblast growth factors, growth factors
INTRODUCTION
Androgenetic alopecia (AGA) is the most common cause of hair loss in men and women and can impact the psychological and social activities of affected individuals, thereby reducing their quality of life.[1,2]
The hair loss in AGA occurs in genetically susceptible individuals caused by the effects of androgens such as testosterone and its most potent derivative dihydrotestosterone (DHT). About 30% of Caucasian men are affected at age 30 and 80% are affected by age 70.[3] In women, the involvement is about 15% at 30 years and 48% at 70 years.[4] Testosterone is converted by the cytoplasmic enzyme 5α-reductase into DHT, which is the most active form, leading to a progressive miniaturization of genetically susceptible terminal hair follicles (thick, long, pigmented, and medullated) and to conversion into miniaturized hair follicles (thinner than terminal follicle, about half or less of its thickness) and vellus hair follicles (extremely thin, small, usually not medullated). The miniaturization distribution pattern is bitemporal and vertex, following the AGA classification proposed by Hamilton in 1951 and later improved by Norwood with the creation of the Hamilton–Norwood classification in 1975.[1,5] It is a polygenic and hereditary disease.[6] Several cytokines, growth factors, hormones, neuropeptides, and enzymes are involved in the normal hair cycle, and it is hypothesized that these substances may be involved in the pathogenesis of AGA.[7] Usually, the most common AGA treatments are topical minoxidil, oral finasteride, and hair transplant.[8] AGA treatments do not only depend on effectiveness but also on applicability, risks, and costs.[9]
Recently, new adjuvant therapies are emerging for AGA such as platelet-rich plasma, stem cell therapies, photobiostimulation therapy, and growth factor cocktail (GFC) therapy. GFC therapy is safe for AGA and can be used topically or in association with microneedling. Microneedling creates microperforations in the scalp with the intention of produce controled microlesions to release growth factors and facilitate the release of medications in the scalp.[10] Lee et al., 2012, reported the therapeutic efficacy of GFC in association with microneedling over a period of 5 weeks.[11] Ro et al., 2016, reported positive results over a 3-month treatment period, with hair density and hair thickness values increased by 21.4% and 5.3%, respectively.[12] Of the total 18 patients who participated in the study, 12 showed results with a >15% increase in hair density. There did not appear to be any differences between the genders. The importance of fibroblast growth factor 9 (FGF9) in hair follicle regeneration was previously reported by Gay et al., 2013.[13]
The hair follows a specific cycle composed of three phases: anagen, catagen, and telogen, related to growth, transition, and rest, respectively.[14] A variety of growth factors and signaling molecules are involved in each phase. Hair follicles in the anagen phase contain various growth factors such as insulin-like growth factor type 1 (IGF-1), epidermal growth factor, FGFs, and the factor platelet-derived growth factor.[15]
Cellcurin (PnP Biopharm, Seoul, Korea), used in this study, is composed of basic FGF (2.5 μg/ml), vascular endothelial growth factor (2.5 μg/ml), factor 2 of keratinocyte growth (KGF-2, 2.5 μg/ml), stem cell factor (2.5 μg/ml), IGF-1 (1.25 μg/ml), growth factor 9 fibroblast (FGF9, 2.5 μg/ml), superoxide dismutase 1 (SOD-1, 5 μg/ml), and noggin peptide (10 μg/ml).
Microneedling, also known as percutaneous induction of collagen with needles, is a minimally invasive procedure that uses extremely thin needles, typically 0.5–1.5 mm in length, to puncture the stratum corneum (epidermis) and the papillary dermis. These created microlesions stimulate growth factors that induce collagen production and elastin formation in the dermis. The epidermis remains relatively intact, thus helping to avoid adverse effects. The indications for microneedling therapy have grown significantly and have become a more widely used treatment in dermatology. Microneedling can also be used to increase the release of transdermal drugs (drug delivery).[16]
MATERIALS AND METHODS
This single-center randomized controlled clinical trial was conducted in a city in the southeastern countryside of Brazil, with approximately 140,000 inhabitants. The city is a reference for other 10 cities in the Alto Paranaiba microregion, with a total of 425,801 population. The Research Ethics Committee (CEP) of the Federal University of Uberlandia approved this study, and all participants signed a free and informed consent form (CAAE 36918620.8.0000.5152). It was accomplished in an appropriate, individualized private clinic, with all the necessary materials and comfort to the participants. Participants were invited to participate in the study voluntarily.
We obtained a convenience sample of men and women with AGA from the local community. The sample size calculation using a two-tailed model, with average effect size (0.75), alpha of 0.05, statistical power of the test of 0.8, and estimated loss of 25% (G*Power 3.1.9.7 Franz Faul, 2020, Universität Kiel, Germany), resulted in 20 participants for the therapeutic intervention group with injectable Cellcurin. However, we used 80% of the 20 participants (16 participants), due to the limited amount of Cellcurin available to do the study. The number of 16 participants was acceptable, considering that this number is within the minimum number of estimated loss of the sample calculation. The control group was composed of 40% of the number of participants in the intervention group, resulting in 4 patients. The Cellcurin injectable group was randomly composed of 8 men and 8 women and the control group of 2 men and 2 women also randomly composed.
The inclusion criteria for the present study were as follows: active AGA, male patients with baldness classification between IIa and V of Hamilton–Norwood, and females with baldness classification between I-2, I-3, I-4, II-1, and II-2 of Ludwig–Savin. The age for both sexes will be between 18 and 60 years old. All races and ethnicities were included.
The diagnosis of AGA and its classification were performed by inspecting the hair and scalp of the participants with a noncicatricial pattern of alopecia in a typical pattern of distribution. Trichoscopy was used in the diagnosis,[3,17] characterized by heterogeneity in the thickness of the hair shaft of at least 20%, more than 10% of vellus hair, a greater number of follicular units with only 1 shaft, yellow dots, peripilar signal, empty follicles, honeycomb pattern pigmentation, and prevalence of these changes in the frontal and vertex areas when compared to the occipital area.
The exclusion criteria for the present study were illiterate patients, pregnant women, or breastfeeding. Start of another therapeutic option such as minoxidil, finasteride (or any other 5-alpha-reductase inhibitor), medications with anti-androgenic properties (acetate cyproterone, spironolactone, ketoconazole, flutamide, bicalutamide), topical estrogen, progesterone, tamoxifen, anabolic steroids, drugs that can cause hypertrichosis (cyclosporine, diazoxide, phenytoin, psoralens), oral corticosteroids (inhaled was allowed), lithium, phenothiazines, Serenoa repens (saw palmetto), anticoagulants (warfarin, heparin), isotretinoin. Patients with a history of cancer, keloid, immunodeficiency, vitiligo, psoriasis, lichen planus, solar keratosis, and rosacea.
Six microneedling sessions were performed with a portable electromedical pen (Alur Derma Pen), registered at the National Health Surveillance Agency (ANVISA-81676079002), with disposable Alur Derma 9 needle cartridges, 31G needles with 0.5 mm depth, speed from 9000 to 10,000 times/min, with an interval of 15 days between sessions, totaling a period of 12 weeks. In the microneedling sessions, Cellcurin was used through the drug delivery system, which consists of the application (dripping) of the therapeutic product simultaneously with the microneedling, aiming at improving penetration and therapeutic function, following the dilution recommended by the manufacturer of 5 ml of 0.9% saline solution.
The control group also received 6 microneedling sessions using 0.5% minoxidil (5 mg/ml) 2 ml for injection, also by dripping, manufactured by the Centro Paulista laboratory (São Paulo, SP, Brazil).
The sessions and data collections were carried out between November 2020 and February 2021. The recruitment period was 2 weeks in October 2020. To minimize the risk of identification, randomized codes were applied to each participant.
Trichoscopic photos were taken before the interventions (T0) and after 12 weeks (T1) under 10, 20, and 70 times augmentation in the frontal and vertex regions of the scalp. The parameters analyzed were the amount of hair per cm2; amount of terminal hair per cm2; ratio between the number of terminal hairs and vellus hairs; number of terminal hairs divided into thin, medium, and thick, considering thicknesses between 31 and 60, 61 and 80 μm, and above of 80, respectively; sum of the total diameter of the terminal hair; and the mean terminal hair diameter of the participants. A DermLite DL4 dermatoscope, manufactured by 3Gen LLC, Orange County, California, USA, was used coupled through an adapter specific to the Samsung Galaxy S8 Plus camera.
The software TrichoSciencePro © v. 1.7TE for the analysis of hair and scalp was used to evaluate the dimensions of the parameters analyzed in the study.
Descriptive statistics were used to characterize the indicators (frequency, percentage, mean, and standard deviation [SD]). The comparison of the indicators was performed using the t-test (means) of paired samples. Data were analyzed using IBM Statistical Package for Social Sciences software version 25 (Armonk, NY, USA: IBM Corp) and Microsoft Excel 2019 software.
RESULTS
All participants of the 20 recruited (8 women and 8 men in the therapeutic group and 2 women and 2 men in the control group) completed the study.
In the therapeutic group, men had a mean age of 38.1 years (SD = 8.75) and an average duration of 13.2 years (SD = 6.06), 37.5% had Grade III of Norwood–Hamilton, and 25% had Grade V. Women had an average age of 33.1 years (SD = 10.57) and an average duration of 9.6 years (SD = 6.52) and 25% had Grades 1-2, I-3, and II-1 of the Savin Classification Scale.
The women group showed an increase in the amount of hair per cm2 of 86.96% in the frontal area, with 82.5 hairs/cm2 at baseline to 154.25 hairs/cm2 after treatment (P=0.004). In the vertex area showed an increase of 59.52%, from 94.5 hairs/cm2 to 150.75 hairs/cm2 (P=0.016). They showed an increase in the number of terminal hairs per cm2 of 46.07% in the frontal area, with 47.75 terminal hairs/cm2 at the beginning to 69.75 terminal hairs/cm2 after the treatment (P=0.001) and 19.67% of increase in the vertex area, with an initial count of 62.25 terminal hairs/cm2 to 74.5 terminal hairs/cm2 after the treatment (P=0.049). Regarding the amount of vellus hair, the women group showed an increase of 143.16% in the frontal region, with 34.75 vellus hairs/cm2 at the beginning to 84.5 vellus hairs/cm2 after Cellcurin therapy (P=0.011) and 136.43% of increase in the vertex region, with an initial count of 32.25 vellus hairs/cm2 to 76.25 vellus hairs/cm2 after the treatment (P=0.020). The sum of terminal hair diameters per cm2 increased by 61.93% in the frontal region, jumping from 3055μm to 4947 μm (P<0.001) and increased 42.97% in the vertex region, with values of 1908μm at the beginning to 2728μm after treatment (P=0.001). The average diameter of terminal hairs in the frontal region increased by 13.57%, with an average of 62.6μm before the treatment to 71.1μm after Cellcurin therapy (P=0.010). The vertex area showed an increase of 19.67%, with 61.5μm initially and 73, 6μm after treatment (P=0.001). The detailed results are described in Tables 1, 2 and Chart 1.
Table 1.
Hair analysis of the frontal region of women before and after therapy with injectable Cellcurin
| Parameter | Mean (SD) | t | df | P* | 95% CI | |
|---|---|---|---|---|---|---|
|
| ||||||
| T0 | T1 | |||||
| Hairs (per cm2) | 82.5 (32.68) | 154.25 (65.17) | −4.255 | 7 | 0.004 | −111.62-−31.87 |
| Terminal (per cm2) | 47.75 (23.18) | 69.75 (21.49) | −6.068 | 7 | 0.001 | −30.57-−13.42 |
| Vellus (per cm2) | 34.75 (15.37) | 84.5 (47.78) | −3.448 | 7 | 0.011 | −83.86-−15.63 |
| Terminal/vellus | 1.86 (1.62) | 1.32 (1.35) | 2.756 | 7 | 0.028 | 0.15-2.00 |
| Thin terminal | 17.75 (7.88) | 22 (10.84) | −1.726 | 7 | 0.128 | −10.07-1.57 |
| Mean terminal | 17 (9.91) | 16.75 (9.49) | 0.088 | 7 | 0.932 | −6.46-6.96 |
| Thick terminal | 13 (10.19) | 31 (15.56) | −5.165 | 7 | 0.001 | −26.23-−9.76 |
| Total terminal diameter (μm) | 3055 (839.7) | 4947 (806.8) | −8.372 | 7 | <0.001 | −2427.02-−1357.98 |
| Mean terminal diameter (μm) | 62.6 (5.1) | 71.1 (10.1) | −3.534 | 7 | 0.010 | −14.19-−2.81 |
*Test of paired samples. t: t-value, df: Degrees of freedom, T0: Before therapy, T1: After 6 sessions of Cellcurin, SD: Standard deviation, CI: Confidence interval
Table 2.
Hair analysis of the vertex region of women before and after therapy with injectable Cellcurin
| Parameter | Mean (SD) | t | df | P* | 95% CI | |
|---|---|---|---|---|---|---|
|
| ||||||
| T0 | T1 | |||||
| Hairs (per cm2) | 94.5 (23.36) | 150.75 (53.06) | −3.136 | 7 | 0.016 | −98.66-−13.83 |
| Terminal (per cm2) | 62.25 (18.74) | 74.5 (14.09) | −2.374 | 7 | 0.049 | −24.45-−0.04 |
| Vellus (per cm2) | 32.25 (10.49) | 76.25 (46.5) | −3.002 | 7 | 0.020 | −78.66-−9.33 |
| Terminal/vellus | 2.11 (0.80) | 1.74 (1.44) | 0.942 | 7 | 0.378 | −1.12-2.61 |
| Thin terminal | 23.75 (13.99) | 19.25 (11.31) | 1.158 | 7 | 0.285 | −4.69-13.69 |
| Mean terminal | 25.75 (7.66) | 20 (6.84) | 1.665 | 7 | 0.140 | −2.41-13.91 |
| Thick terminal | 12.75 (8.74) | 35.25 (12.91) | −6.979 | 7 | <0.001 | −30.12-−14.87 |
| Total terminal diameter (μm) | 1908 (592.5) | 2728 (537.4) | −5.824 | 7 | 0.001 | −2305.82-−974.18 |
| Mean terminal diameter (μm) | 61.5 (4.8) | 73.6 (7.7) | −5.775 | 7 | 0.001 | −17.09-−7.16 |
*Test of paired samples. t: t-value, df: Degrees of freedom, T0: Before therapy, T1: After 6 sessions of Cellcurin, SD: Standard deviation, CI: Confidence interval
Chart 1.
Cellcurin before and after in the frontal and vertex regions in women
The men group showed an increase in the amount of hair per cm2 of 46.72% in the frontal area, with 91.5 hairs/cm2 at baseline to 134 hairs/cm2 after treatment (P=0.049) and an increase of 50.80% in the vertex region, from 77.25 hairs/cm2 to 116.5 hairs/cm2 (P=0.036). They showed an increase in the number of terminal hairs per cm2 of 47.39% in the frontal area, with 48 terminal hairs/cm2 at the beginning to 70.75 terminal hairs/cm2 after treatment (P=0.014) and 49.47% of increase in the vertex area, with an initial count of 47.5 terminal hairs/cm2 to 71 terminal hairs/cm2 after the treatment (P=0.001). Regarding the amount of vellus hair, the men group showed an increase of 45.97% in the frontal region, with 43.5 vellus hairs/cm2 at the beginning to 63.5 vellus hairs/cm2 after Cellcurin therapy, but it did not present statistical significance (P=0.206). The vertex region showed an increase of 52.94%, with an initial count of 29.75 vellus hairs/cm2 to 45.5 vellus hairs/cm2 after treatment (P=0.247). The sum of terminal hair diameters per cm2 increased by 65.52% in the frontal area, jumping from 3072μm to 5085μm (P=0.003) and increased 69.97% in the vertex area, with values of 3027μm at the beginning to 5145μm after treatment (P<0.001). The average diameter of terminal hairs in the frontal area increased by 13.76%, with an average of 62.5μm before the treatment to 71.1μm after Cellcurin therapy (P=0.015). The vertex area showed an increase of 15.67%, initially with 61.9μm of mean diameter to 71,6μm after treatment (P=0.008). The detailed results are described in Tables 3, 4 and Chart 2.
Table 3.
Hair analysis of the frontal region of men before and after therapy with injectable Cellcurin
| Parameter | Mean (SD) | t | df | P* | 95% CI | |
|---|---|---|---|---|---|---|
|
| ||||||
| T0 | T1 | |||||
| Hairs (per cm2) | 91.5 (20.58) | 134.25 (66.56) | −2.382 | 7 | 0.049 | −85.18-−0.31 |
| Terminal (per cm2) | 48 (20) | 70.75 (22.49) | −3.255 | 7 | 0.014 | −39.27-−6.22 |
| Vellus (per cm2) | 43.5 (21.95) | 63.5 (54.06) | −1.395 | 7 | 0.206 | −53.90-13.90 |
| Terminal/vellus | 1.47 (1.01) | 2.44 (2.21) | −1.431 | 7 | 0.196 | −2.57-0.63 |
| Thin terminal | 16 (5.55) | 20.25 (13.70) | −0.747 | 7 | 0.479 | −17.69-9.19 |
| Mean terminal | 19.25 (13.13) | 21 (10.19) | −0.336 | 7 | 0.746 | −14.05-10.55 |
| Thick terminal | 12.75 (8.06) | 29.5 (17.42) | −3.216 | 7 | 0.015 | −29.06-−4.43 |
| Total terminal diameter (μm) | 3072 (1380.2) | 5085 (1826.6) | 4.512 | 7 | 0.003 | −3067.22-957.78 |
| Mean terminal diameter (μm) | 62.5 (5) | 71.1 (8.5) | −3.212 | 7 | 0.015 | −14.98-−2.27 |
*Test of paired samples. t: t-value, df: Degrees of freedom, T0: Before therapy, T1: After 6 sessions of Cellcurin, SD: Standard deviation, CI: Confidence interval
Table 4.
Hair analysis of the vertex region of men before and after therapy with injectable Cellcurin
| Parameter | Mean (SD) | t | df | P* | 95% CI | |
|---|---|---|---|---|---|---|
|
| ||||||
| T0 | T1 | |||||
| Hairs (per cm2) | 77.25 (22.47) | 116.5 (62.85) | −2.596 | 7 | 0.036 | −74.99-−3.50 |
| Terminal (per cm2) | 47.5 (15.70) | 71 (20.31) | −5.480 | 7 | 0.001 | −33.64-−13.35 |
| Vellus (per cm2) | 29.75 (14.39) | 45.5 (44.21) | −1.263 | 7 | 0.247 | −45.23-13.73 |
| Terminal/vellus | 2.02 (1.29) | 3.53 (4.14) | −1.156 | 7 | 0.286 | −9.18-3.15 |
| Thin terminal | 19.25 (6.34) | 22.75 (8.81) | −0.669 | 7 | 0.525 | −15.87-8.87 |
| Mean terminal | 13.5 (11.64) | 16.75 (5.23) | −0.843 | 7 | 0.427 | −12.36-5.86 |
| Thick terminal | 14.75 (15.11) | 31.5 (16.06) | −7.292 | 7 | <0.001 | −22.18-−11.31 |
| Total terminal diameter (μm) | 3027 (1346) | 5145 (1722.2) | −8.873 | 7 | <0.001 | −2681.8-−1553.2 |
| Mean terminal diameter (μm) | 61.9 (11.8) | 71.6 (7.8) | −3.623 | 7 | 0.008 | −16.11-−3.39 |
*Test of paired samples. t: t-value, df: Degrees of freedom, T0: Before therapy, T1: After 6 sessions of Cellcurin, SD: Standard deviation, CI: Confidence interval
Chart 2.
Cellcurin before and after in the frontal and vertex regions in men
In the men control group, the mean age was 43.5 years (SD = 19.09). The average duration of AGA was 19.5 years (SD = 10.6). The Norwood-Hamilton classification was III vertex and IV. In the women group the mean age of 33.5 years (SD = 7.77). The average duration of AGA was 5.5 years (SD = 0.7). The Savin classification was I-2 and I-3.
Control group women using injectable minoxidil therapy showed a 1.6% reduction in the amount of hair per cm2, from 127 to 125 in the frontal region, but it did not reach statistical significance, with P = 0.960, and a reduction of 23.07% in the vertex region, from 182 to 140 (P = 0.030). They showed an increase in the amount of terminal hair per cm2 in the frontal region of 20.68%, from 58 to 70, but it did not reach statistical significance (P = 0.500), and a reduction in the vertex region of 1.3% with an initial count of 72 and 71 afterward, also without statistical significance (P = 0.500). Regarding the amount of vellus hair, they showed a reduction of 20.28%, with 69 at the beginning and 55 after the therapy with minoxidil in the frontal region, not reaching statistical significance P = 0.700, and a reduction of 37.27% in the vertex region with an initial count of 110 and a posterior count of 69 (P = 0.016). The changes in the values of the sum of the diameters of terminal hairs per cm2 and the mean diameter of the terminal hair in the frontal and vertex regions were not statistically significant, with an increase of 18.50% in the frontal area, initially with 3890μm/cm2 and after treatment with 4720μm/cm2 (P=0.304) and an increase of 3.36% in the vertex area, with values of 4750μm/cm2 and 4910μm/cm2 (P=0.156). The mean diameter of terminal hair in the frontal region increased by 3.03%, with an average of 66 μm before and 68 μm after (P = 0.823) and in the vertex region 6.10%, with values of 65.5 μm before and 69.5 μm after. The detailed results are described in Tables 5 and 6.
Table 5.
Hair analysis of the frontal region of women in the control group before and after therapy with injectable minoxidil
| Parameter | Mean (SD) | t | df | P* | 95% CI | |
|---|---|---|---|---|---|---|
|
| ||||||
| T0 | T1 | |||||
| Hairs (per cm2) | 127 (7.07) | 125 (52.32) | 0.063 | 1 | 0.960 | −404.59-408.59 |
| Terminal (per cm2) | 58 (14.14) | 70 (31.11) | −1.000 | 1 | 0.500 | −164.47-70.23 |
| Vellus (per cm2) | 69 (7.07) | 55 (21.21) | 0.700 | 1 | 0.611 | −240.12-268.12 |
| Terminal/vellus | 0.85 (0.28) | 1.25 (0.07) | −2.667 | 1 | 0.228 | −2.30-3.01 |
| Thin terminal | 11 (7.07) | 14 (11.31) | −0.231 | 1 | 0.856 | −168.18-162.18 |
| Mean terminal | 29 (1.41) | 30 (8.48) | −0.200 | 1 | 0.874 | −64.53-62.53 |
| Thick terminal | 18 (19.79) | 26 (11.31) | −1.333 | 1 | 0.410 | −42.11-68.23 |
| Total terminal diameter (μm) | 3890 (1400) | 4720 (2008.1) | −1.930 | 1 | 0.304 | −6293.6-4633.6 |
| Mean terminal diameter (μm) | 66 (8.4) | 68 (1.4) | −0.286 | 1 | 0.823 | −90.9-86.9 |
*Test of paired samples. t: t-value, df: Degrees of freedom, T0: Before therapy, T1: After 6 sessions of minoxidil, SD: Standard deviation, CI: Confidence interval
Table 6.
Hair analysis of the vertex region of women in the control group before and after therapy with injectable minoxidil
| Parameter | Mean (SD) | t | df | P* | 95% CI | |
|---|---|---|---|---|---|---|
|
| ||||||
| T0 | T1 | |||||
| Hairs (per cm2) | 182 (5.65) | 140 (2.82) | 21.000 | 1 | 0.030 | 16.58-67.41 |
| Terminal (per cm2) | 72 (19.79) | 71 (21.21) | 1.000 | 1 | 0.500 | −11.70-13.70 |
| Vellus (per cm2) | 110 (25.45) | 69 (24.04) | 41.000 | 1 | 0.016 | 28.29-53.70 |
| Terminal/vellus | 0.69 (0.33) | 1.15 (0.70) | −1.769 | 1 | 0.328 | −3.76-2.84 |
| Thin terminal | 15 (4.24) | 20 (2.82) | −1.000 | 1 | 0.500 | −68.53-58.53 |
| Mean terminal | 38 (2.82) | 24 (14.14) | 1.750 | 1 | 0.330 | −87.64-115.64 |
| Thick terminal | 19 (12.72) | 27 (9.89) | −4.000 | 1 | 0.156 | −33.41-17.41 |
| Total terminal diameter (μm) | 4750 (1456.6) | 4910 (1513.2) | −4.000 | 1 | 0.156 | −668.2-348.2 |
| Mean terminal diameter (μm) | 65.5 (2.1) | 69.5 (0.7) | −4.000 | 1 | 0.156 | −16.7-8.7 |
*Test of paired samples. t: t-value, df: Degrees of freedom, T0: Before therapy, T1: After 6 sessions of minoxidil, SD: Standard deviation, CI: Confidence interval
The men in the control group showed a reduction in the amount of hair per cm2 of 23.12% in the frontal area, from 147 hairs/cm2 to 113 hairs/cm2, however, it was not possible to calculate the t-test because the SD of the difference was zero. The vertex area showed an increase of 7.69%, at the beginning with 104 hairs/cm2 to 112 hairs/cm2 afterward, with no statistical significance (P=0.705). The men in the control group presented an increase in the amount of terminal hair per cm2 in the frontal region of 7.35%, with 68 terminal hairs/cm2 at the beginning to 73 terminal hairs/cm2 after the treatment, but it did not show statistical significance (P=0.126). The vertex region showed an increase of 10.41% with an initial count of 48 terminal hairs/cm2 to 53 terminal hairs/cm2 after the treatment, also with no statistical significance (P=0.344). Regarding the amount of vellus hair, they showed a reduction of 49.36% in the frontal region, with 79 vellus hairs/cm2 at the beginning to 40 vellus hair/cm2 after the therapy with minoxidil (P=0.016). The vertex region showed an increase of 5.35%, with 56 vellus hairs/cm2 at baseline to 59 vellus hairs/cm2, with no statistical significance (P=0.856). The changes in the values of the sum of the diameters and the average diameter of the terminal hair in the frontal and vertex regions were not statistically significant, with an increase of 9.06% in the frontal region, initially with 4080 μm and later with 4450 μm (P = 0.378), and 9.45% in the vertex region, with values of 2960 and 3240 μm (P = 0.258). The mean diameter of terminal hair in the frontal region increased by 0.8%, with an average of 59.5 μm before and 60 μm after (P = 0.874), and in the vertex region, it decreased by 5.78%, with values of 60.5 μm before and 57 μm after. The detailed results are described in Tables 7 and 8. Chart 3 compares the average capillary diameters before and after in men and women by region and therapy.
Table 7.
Hair analysis of the frontal region of men in the control group before and after therapy with injectable minoxidil
| Parameter | Mean (SD) | t | df | P* | 95% CI | |
|---|---|---|---|---|---|---|
|
| ||||||
| T0 | T1 | |||||
| Hairs (per cm2) | 147 (26.87) | 113 (26.87) | † | 1 | 0.126 | −17.70-7.70 |
| Terminal (per cm2) | 68 (19.79) | 73 (21.21) | −5.000 | 1 | 0.016 | 26.29-51.70 |
| Vellus (per cm2) | 79 (7.07) | 40 (5.65) | 39.000 | 1 | 0.047 | −3.67-−0.12 |
| Terminal/vellus | 0.85 (0.17) | 1.80 (0.27) | −13.571 | 1 | 0.656 | −66.53-60.53 |
| Thin terminal | 31 (1.41) | 34 (5.65) | −0.600 | 1 | 0.205 | −9.70-15.70 |
| Mean terminal | 27 (15.55) | 24 (16.97) | 3.000 | 1 | 0.500 | −68.53-58.53 |
| Thick terminal | 10 (2.82) | 15 (9.89) | −1.000 | 1 | 0.378 | −3546.5-2806.5 |
| Total terminal diameter (μm) | 4080 (1329.3) | 4450 (1682.9) | −1.480 | 1 | 0.874 | −32.2-31.2 |
| Mean terminal diameter (μm) | 59.5 (2.1) | 60 (5.6) | −0.200 | 1 | 0.126 | −17.70-7.70 |
*Test of paired samples. t: t-value, df: Degrees of freedom, T0: Before therapy, T1: After 6 sessions of minoxidil, SD: Standard deviation, CI: Confidence interval
Table 8.
Hair analysis of the vertex region of men in the control group before and after therapy with injectable minoxidil
| Parameter | Mean (SD) | t | df | P* | 95% CI | |
|---|---|---|---|---|---|---|
|
| ||||||
| T0 | T1 | |||||
| Hairs (per cm2) | 104 (45.25) | 112 (22.62) | −0.500 | 1 | 0.705 | −211.29-195.29 |
| Terminal (per cm2) | 48 (36.76) | 53 (32.52) | −1.667 | 1 | 0.344 | −43.11-33.11 |
| Vellus (per cm2) | 56 (8.48) | 59 (9.89) | −0.231 | 1 | 0.856 | −168.18-162.18 |
| Terminal/vellus | 0.81 (0.53) | 0.95 (0.71) | −1.077 | 1 | 0.476 | −1.79-1.51 |
| Thin terminal | 20 (11.31) | 22 (2.82) | −0.200 | 1 | 0.874 | −129.06-125.06 |
| Mean terminal | 16 (14.14) | 22 (22.62) | −1.000 | 1 | 0.500 | −82.23-70.23 |
| Thick terminal | 12 (11.31) | 9 (12.72) | 3.000 | 1 | 0.205 | −9.70-15.70 |
| Total terminal diameter (μm) | 2960 (2375.8) | 3240 (2545.5) | −2.333 | 1 | 0.258 | −1804.7-1244.7 |
| Mean terminal diameter (μm) | 60.5 (3.5) | 57 (12.7) | 0.538 | 1 | 0.686 | −79-86 |
*Test of paired samples. t: t-value, df: Degrees of freedom, T0: Before therapy, T1: After 6 sessions of minoxidil, SD: Standard deviation, CI: Confidence interval
Chart 3.
Mean hair diameter before and after Cellcurin and minoxidil in men and women by region
There was a positive change in 5 women and 3 men, with a reduction of one score on the Savin and Norwood–Hamilton Scales, respectively. The other participants showed no change in the degree of alopecia.
DISCUSSION
In this study, we observed significant increases in the parameters evaluated before and after Cellcurin therapy in men and women with statistical significance. Unlike the results found in the study by Ro et al.[12] in 2016, our study showed greater increases in hair density and thickness than those previously found, as well as differences between genders.
In the analysis of men, we observed greater increases in the vertex region when compared to the frontal region, in the parameters of the amount of hair per cm2, the amount of terminal hair per cm2, the amount of vellus hair per cm2, the sum of the diameters of the terminal hair per cm2, and the average of the diameters of terminal hair. The increases of hairs per cm2 in the frontal region in men were 46.72% against 50.8% in the vertex. In the frontal region, the terminal hairs per cm2 showed an increase of 47.39%, and in the vertex an increase of 49,47%. The vellus hairs/cm2 in the frontal region present an increase of 45.97% and in the vertex area an increase of 52,94%. The sum of the diameter of terminal hairs shafts per cm2 in the frontal region showed an increase of 65.52% and in the vertex region an increase of 69,97%. The mean diameter of terminal hairs in the frontal region presented an increase of 13.76% an in the vertex region an increase of 15,67%. Although in the analysis of the amount of vellus hair in both the frontal and vertex regions, we did not observe statistical significance. Chart 4 shows these increases.
Chart 4.
Increase among Cellcurin and minoxidil by region in men
In women who used Cellcurin therapy, we observed greater increases in the frontal region of most of the parameters observed when compared to the increases observed in the vertex region, differently from men. The mean diameter of terminal hair followed that observed in men, with greater increases in the vertex. The count of hair per cm2 in the frontal region increased 86.96% after therapy with Cellcurin and presented an increase of 59.52% in the vertex region. The amount of terminal hair increased by 46.07% compared to 19.67% in the vertex region. The amount of vellus hair in the frontal region grew by an impressive 143.16% in relation to the amount prior to therapy and an increase of 136.43% in the vertex region, which, although smaller than in the frontal region, is also an impressive growth. The sum of terminal hair diameters increased by 61.93% in the frontal region and 42.97% in the vertex region. The average diameter of terminal hair showed a smaller growth in the frontal region of 13.57% when compared to the growth observed in the vertex region of 19.67%. All parameters were statistically significant. Chart 5 visually demonstrates these increases.
Chart 5.
Increase among Cellcurin and minoxidil by region in women
We can see in Figure 1 the frontal trichoscopy of two men (a and b) before and after therapy with Cellcurin injectable and in Figure 2 the vertex trichoscopy of these same men. In Figure 3 we observe frontal trichoscopy of two women (a and b) before and after therapy with Cellcurin and in Figure 4 the vertex trichoscopy of these same women. In the Figure 5 we see Global photography of the two men (a and b) before and after therapy with Cellcurin injectable. In The Figure 6 the global photography of the two women (a and b) before and after therapy with Cellcurin injectable.
Figure 1.
(a and b) Frontal trichoscopy before and after therapy with Cellcurin injectable in men
Figure 2.
(a and b) Vertex trichoscopy before and after therapy with Cellcurin injectable in men
Figure 3.
(a and b) Frontal trichoscopy before and after therapy with Cellcurin injectable in women
Figure 4.
(a and b) Vertex trichoscopy before and after therapy with Cellcurin injectable in women
Figure 5.
Global photography before and after therapy with Cellcurin injectable in men
Figure 6.
Global photography before and after therapy with Cellcurin injectable in women
In the control group of men, although we observed a reduction in the amount of hair per cm2 in the frontal region of 23.12%, a reduction in the amount of vellus/cm2 and smaller increases in the other parameters when compared to those observed in the group of men who used Cellcurin. In the frontal region, the count of terminal hairs per cm2 increased by 7.35% and in the vertex region by 10.41%. The amount of hair per cm2 increased by 7.69% in the vertex region and the amount of vellus increase of 5.35% also in the vertex. The sum of terminal hair diameters increased by 9.06% in the frontal region and 9.45% in the vertex. The mean diameters of terminal hair showed an increase of 0.8% in the frontal region and 5.78% in the vertex. Statistical significance was achieved only in the parameter vellus per cm2 in the frontal region and is probably related to the small sample of the male control group. Chart 4 shows the changes observed in the male control group.
In the control group of women, we also observed less expressive increases compared to the Cellcurin group, as well as reductions in the number of hairs per cm2 in the frontal region of 1.6% and in the vertex region of 23.07% and reduction in the amount of vellus per cm2 of 20.28% in the frontal region and 37.27% in the vertex region. We observed an increase of terminal hairs per cm2 in the frontal region of 20.68%. The sum of terminal hairs diameter in frontal region presented an increase of 18,5% and in the vertex region an increase of 3,36%. The mean diameter of terminal hair increased by 3.03% in the frontal region and 6.1% in the vertex region. Chart 5 shows changes observed in the female control group.
The reduction in the parameters observed in the control group may be related to the shedding presented in the 1st weeks of the beginning of the use of minoxidil, and apparently, they are due to the vellus, although we must have a larger sample to obtain the statistical significance of the parameters observed.
In the Cellcurin group, we observed a large increase in the sum of the diameters of the terminal hair, greater in the group of men, which shows an important increase in the thickness of the terminal hair. In the group of women, we observed a very expressive increase in the amount of vellus hair per cm2, greater than that observed in the group of men, although the growth in the male group cannot be disregarded. The growth in the number of terminal hairs per cm2, as well as the sum of the diameters of terminal hairs, was smaller in women when compared to men.
Considering that AGA is a chronic, genetic, and progressive disease[18] and the first line of treatment proposed to be an ongoing maintenance treatment to sustain growth,[17] treatment with GFC solution could be continued at 2-week intervals for as long as necessary, although more studies are needed to assess the need and frequency of additional applications and maintenance of treatment with GFC solution in patients with AGA.
CONCLUSIONS
In this study, we demonstrated that the use of Cellcurin in the treatment of AGA in men and women is associated with an increase in the amount of hair per cm2, an increase in the amount of terminal hair per cm2, an increase in the amount of vellus hair per cm2, an increase in the number obtained by adding the diameters of the terminal hairs per cm2, as well as an increase in the average diameter of the terminal hairs in the frontal and vertex regions.
This study adds important results to those obtained in the South Korean studies and reaffirms Cellcurin as a new effective and safe option for the treatment of AGA in men and women, with extremely positive and statistically significant results, greater than those obtained in previous studies and demonstrating important differences between genders.
Another important characteristic that we must take into account in this study and that can help to explain the greater increase in hair growth and the differences observed between genders in relation to previous studies carried out in Asians, is that the sample was constituted by Brazilian participants, with characteristics own racial differences. The extremely positive results are indicative that Cellcurin has a good therapeutic response to AGA in men and women in our population.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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