Low Level Laser Therapy in Treatment of Androgenic Alopecia

ABSTRACT

Alopecia is a common disease affecting more than half of the world population. Alopecia exists in different types. One of the common types of Alopecia diseases is the Androgenic Alopecia. A recent research has shown this type of Alopecia disease to have been affected approximately fifty-one percent of the total number of males of between the ages of forty and seventy-five years. This type of alopecia is more common in females who are above the age of sixty-five years. Despite the widespread of this disease, much has not been done regarding identifying the possible drugs for treating the disease. Currently, there are only two possible medications that have been scientifically approved to cure this disease. These medications include finasteride and minoxidil (1).Another possible form of medication that has been proposed for the treatment of this disease has been the case of hair transplanting. This treatment entails the transplanting of hair from a person who is not affected by the person who is affected by the disease. This research paper tries to evidence the effectiveness of using the low-level laser therapy commonly abbreviated as LLLT as a possible treatment for Androgenetic alopecia. Moreover, the paper is going to discuss the other possible mechanisms for the treatment of the hair loss. Despite the new possible treatment options available for treatment of different types of hair loss, there is a need for the invention of more efficient management and treatment options that are less costly, environmentally friendly and most importantly human consumption friendly. Due to the recent evaluation that low-level laser therapy stimulated hair growth, (2), this research paper reviewed the current possible evidence on the effects of the use of low-level laser therapy. Evidence –supported approach has been employed with much focus directed towards randomized controlled studies. The evidence-supported approach critically evaluates the effects of low-level laser therapy taking all the possible factors into consideration. Some earlier studies had shown that the use of low-level laser therapy stimulates hair growth. in research carried out when mice were treated with chemotherapy which was induced by the alopecia and also the other type of alopecia called alopecia areata (2). The researchers hypothesized that the primary mechanism of treating Androgenetic alopecia as the stimulation of the epidermal stem cells. The epidermal stem cells are located in the hair follicle. These epidermal stem cells make the hair follicle to bulge and shift them into the antigen phase (11). This is because hair growth in both men and women appears to be both efficient and much safer. INTRODUCTION A lot of information has been generated concerning the use of laser technology in the treatment of diseases. It is well known that the use of red or near infrared light promotes the mechanism of tissue repairing while the use of low-intensity light which is called low-level laser therapy abbreviated as LLLT stimulates cell activities within the body of an organism. Since the discovery of laser in the mid of the nineteenth century, tremendous interests have been made towards its use in the treatment of diseases. The recent discovery has shown that, apart from a low-level laser, AGA can be treated by the alpha-reductase inhibitor finasteride and the antihypertensive minoxidil (1). However, low-level laser technology is commonly used because it not only treats AGA but also used for the cases of transplantation in the surgical medicine. However, the use of low-level laser technology is faced with a number of drawbacks. These drawbacks include limited effectiveness in use of a low-level laser, cases of unwanted side effects, and the high cost of utilization of this technology (11) hence making it not readily available to many people. Androgenetic Alopecia (AGA) has been commonly recognized to have a high negative impact on the patients’ life. As such, this contributes to the adverse effects and thus affecting the quality of life and their psychological setting (1). According to the research carried out by Monck et al, (2014, 405), it is revealed that a number of women affected by the Androgenetic Alopecia reported being discontented with the idea of the appearance and concern about the loss of hair on their head. Moreover, these women are also about the fear of other people noticing their loss of hair. The emotional aspects of these women have been ranked high. This includes self-consciousness, embarrassment and also the feeling of being not able to control and stop the act of them losing hair. The patients’ expectations should be put into consideration when anticipating when to use these devices in the treatment of Androgenetic Alopecia (11).The following photographs show the condition of AGA that occurs in a large population.

LITERATURE REVIEW

1. Hair and types of Hair loss

Human hair is considered to be one of the fastest growing body tissues. The hair follicle, which is one of the features that give mammals a unique characteristic, mainly represents a cell-rich stem, prototypic neuroectodermal-mesodermal interaction system (16). The hair follicles go through regenerative cycles that are said to be repetitive. Each of these regenerative cycles has three stages; anagen, catagen, and telogen. The anagen stage is the rapidly growing stage and the most active among the three stages. The catagen stage is also known as the physiological involution stage is an apoptosis-driven regression stage. The telogen stage is the resting stage and which is accompanied by little cell growth (8). The region of the outer root sheath which is located beneath the sebaceous glands is mainly made up of bulge stem cells which then concede with the point of support with the arrestor pili muscle (16). As the cell growth develops from telogen stage to anagen stage, the activation of these bulge epithelial is tightly controlled and also at the same time transient amplifying progeny cells are given rise from the secondary hair germ cells (10). A robust proliferation of the TA cells takes place throughout the anagen phase in the epithelial matrix of the hair follicle. The proliferating trichocysts then terminate in a differential manner giving rise to the formation of bulk hair filaments which becomes the final product of the hair cycle (16). The most common hair loss in men is the Androgenetic Alopecia (AGA) contributing to around 50% hair loss to male population (4). This type of hair loss refers to the hair loss that occurs in those individuals who are genetically susceptible. The hair loss is caused by the effects of androgens which includes testosterone as well as its derivative dihydrotestosterone (DHT). Testosterone can be defined as a lipophilic compound with the ability to diffuse across the cell membrane. This hormone is then converted to DHT by a cytoplasmic enzyme which is more active than before. These types of reductase are of two types namely type 1 which is found in the keratinocytes, sweat glands, sebocytes as well as in the fibroblasts (10). Type 2 is then found in the skin as well as in the inner root sheath of the hair follicle. The DHT then causes binding of the nuclear androgen receptor which regulates the rate of gene expression (4). Disruption of the epithelial progenitor as well as TA cell proliferation due to abnormal levels of androgens signaling forms the important pathophysiological component of the above condition. This component then leads to the continuous miniaturization of sensitive terminal hair follicles as well as their conversions to vellus hair follicles (4). The other forms of hair loss include Alopecia Areata (AA), chemo-therapy-induced alopecia as well as telogen effluvium (TE).

2. LLLT for Prevention and reversal of Hair Loss

Research on the carcinogenic potential of the lasers was started back in the 1960s. A low power ruby laser of measurement 694 nm on the mice was used. The mice were shaved in such a way that they were the part of the experimental protocol. The research showed that the laser did not cause cancer but instead it caused an improvement of the hair growth around the region on the back of the animal (10). This was the first demonstration to be done and it opened a pathway in the photo-biostimulation pathway of medicine field (4). The increase in the hair density, the color of the hair as well as the combination of these variables has been confirmed at those sites that have been treated for the removal of hair. This occurrence is known as Paradoxical hypertrichosis (16). The incidence of occurrence of this phenomenon varies from 0.6% to about 10% for a given group of people. Terminalization is a term given to a situation whereby small vellus hairs are transformed into larger terminal hairs together with low fluency diode laser treatment (10). Although the temperature that is released by the laser is lower than that necessary to cause thermolysis of hair follicles, it is enough to induce follicular stem cell proliferation. This temperature may also cause an increase of the level of the heat shock proteins which is very important in regulating the level of the heat shock proteins. The laser also causes sub-therapeutic injury which can lead to the cycling of the cells (10).

3. LLLT for hair regrowth

FDA approved LLLT as an appropriate safe treatment to both male and female patients who has pattern loss (4). Laser photography stimulates anagen phase re-entry in the telogen hair follicles, increase the duration of the anagen phase, activate the anagen hair follicles and also prevent premature development of catagen (8). Although the mechanism that is used in the LLLT is not well known, what is well know is that LLLT acts on the mitochondria and in one way or another it may change the functioning of the cell metabolism through a process known as photo dissociation of the nitric oxide. This process acts as an inhibitory and it arises from cytochrome c oxidase (CCO) (8).  LLLT may also cause an increase in production of ATP and allow induction of the transcription factors to take place. These transcription factors include factors such as hypoxia-inducible factor-1, nuclear factor cover as well as oxygen modulation of reactive species (16). These effects are of major concern especially for the health of the patients. As such, they need to be addressed keenly in order to solve these problems. The transcription factors cause protein synthesis that triggers other effects down the stream. These effects include alteration of the cytokines levels, increase of the oxygenation of the tissues, increase of cell proliferation as well as inflammatory mediators (9). The working mechanism of these transcription factors has some similarities with that of minoxidil. Minoxidil contains an N-oxide group that can release NO. NO is considered to be an important cellular signaling molecule that takes place in many pathological as well as physiological processes (8). The product is also a vasodilator. Minoxidil is also sensitive to ATP especially the ATP K which acts as a channel opener. Minoxidil responses to ATP K by causing an increase in the hyperpolarization of the cell membranes (16). As such, these issues need to be seriously addressed which calls for further study to be carried out in order to increase the efficiency of how they are evaluated.

THE MECHANISM ACTION OF LLLT

The use of low-level laser technology has been recently suggested to be an alternative treatment for preventing hair loss and also in the stimulation of growth of hair in both the cases of Female Pattern Hair Loss (FPHL) and Male Pattern Hair Loss) MPHL. The use of this type of technology has been argued to produce better outcomes and also cause minimal risk to patients (14).The use of low laser therapy is known to stimulate; the re-entry of anagen into the hair follicles, the prolongation of the anagen period, the increase in the frequency of proliferation that occurs in the case of the active anagen hair follicles and lastly prevent the early and premature development of catagen (Hopkins et al., 2004, 102). The use of LLLT acts on the mitochondria alters the rate of cell metabolism that occurs through the photo-dissociation of the inhibitory nitric oxide from CCO such as cytochrome oxidase (12) This acts increases production of the ATP which affect the modulation of the number of the oxygen species present (14) and the induction of the transcription factors, for example, kappa B and hypoxia-inducible factor-one (1). These transcription factors help activate the synthesis of proteins thus triggering further the factor-down-effects such as the increased cell proliferation and migration, the alteration in terms of the levels of cytokines, the increase in the number of growth factors and the inflammatory mediators and an increased rate of tissue oxygenation(15). NO is known to be a potent vasodilator via its effects on cyclic guanine monophosphate production (14) Moreover, the use of LLLT  has been argued to cause the photo-dissociation of the nitric oxide not only from the CCO (12)  but also the intracellular stores such as the two goblin forms of the nitrosylated i.e. The hemoglobin and myoglobin thus leading to vasodilatations (15) and the increased blood flow. The result of this is stimulation of hair follicles (2) in patients suffering from AGA. It by this reason that this systematic and meta-analysis research paper aims to evaluate the already available literature on the Androgenetic Alopecia and low-level laser technology specifically in determining whether the use of low-level laser technology is indeed an effective therapy and treatment mechanism for AGA. STEP BY STEP GUIDE ON HOW THE SYSTEMATIC AND META ANALYSIS REVIEWS WERE CONDUCTED Step 1: Clear framing of the questions and the topic of the research review The research problem was specified in a clear and a structured way before the beginning of the research process. Modifications and alterations were only allowed when the outcomes, interventions and the study designs become apparent to the problem under study (Hopkins et al., 2004, 80). Step 2: Identification of the relevant work After the definition of the research problem, the next step involved the identification of the relevant sources, articles and other research papers that talked about the problem. A number of sources both in the digital and printed formats were searched with no language restrictions in mind. Step 3: Assessing the quality of the studies After identification of the relevant resources talking about the problem of the study, general critical appraisal guides, and design –based quality checklists were used to subject the resources to a more refined quality assessment with the help of the use of the (Hopkins et al., 2004, 80). This point by point quality evaluation was utilized for investigating heterogeneity and illuminating choices with respect to the appropriateness of meta-examination. Furthermore, they help in surveying the quality of deductions and making proposals for future research Step 4: Summary of the evidence This step involved the synthesis of the data obtained from the resources. This involved cross tabulations, analysis of the characteristics, the quality, and the effects, and the use of statistical methods in exploring the differences among the studies  (15). In cases where an overall meta-analysis was not possible, subgroup meta-analysis was used. Step 5: Interpretation of the research findings After all the above steps were followed to the latter, there was need to interpret the findings so as to answer the problem of the study. Investigation for heterogeneity helped to decide if the general synopsis can be trusted, and, if not, the impacts seen in superb examinations ought to be utilized for creating derivations. Any suggestions ought to be reviewed by reference to the qualities and shortcomings of the confirmation were stated in this step.

METHODS

(a)    Literature review, search and the research procedure Studies published up to the year December 31, 2016, were obtained. These reseach were obtained from the medical and health journals websites which include the medicine and health website, Medline, Embase, American Journal of Medicine, the tropical medicine and Health website and the Google scholar homepage. The research focused on reports or journals that talked about Low-level laser technology as a treatment for the Androgenetic Alopecia (Hopkins et al., 2004, 82). Furthermore, the reference lists of the original articles and journals and the review articles were also jotted down for reference and also for quality assurance purposes of this research paper. (b)    The inclusion and the exclusion criteria. To determine which article and journals were to be included in the study process, all the research hits were viewed and screened. After examination of these articles for the relevance and the possibility of them being included in the study was done, those articles which were potentially relevant were then read thoroughly and fully analyzed to determine the possibility and the eligibility for them being included in the final inclusion. Those articles that seemed not to provide enough relevant studies on the use of LLLT for treatment of AGA were excluded from the list. Articles and journals were marked as eligible for inclusion if they at least satisfied two of the following criteria proposed by (13)

• In the article, there were adults included in the study of the Androgenetic Alopecia (AGA)
• The article in its study investigated at least one type of the low level laser technology (LLLT)
• The article must have been written in English for us to critically review it.
• The article must have been written on or before 31st December 2016.

(c)    The study quality assessment To ensure the achievement of quality results, the study was divided accordingly using a criterion referred to us as the Cochrane Based Medicine pyramid. This division criterion allows the study designs with the greater or strong evidence to be ranked at the top. To prevent the risk of bias from happening when assessing the quality of the study, the evaluation of the following study design characteristics was taken into consideration.

• Blinding of outcome assessment for example through the use of a computer software for the outcome assignment
• Randomization of the group assignment to reduce bias
• The investigator and subject blinding of the group given assignment and
• The standardization of the outcome assessments such as through the provision of the same lighting to all the sample subjects, the use of the same head hair position, use of the same hair style when assessing hair count among many others

(d)    Data extraction To minimize the chances of bias, the data regarding the study design, the type of the intervention and the outcome were independently extracted by the reviewers. The study design characteristics were extracted using the outlines stipulated in the Agency for healthcare and research Quality’s manuscript (13). These agency outlines down the essential and necessary study elements that are both critical and also important when incorporating and designing the study assessment tool. The assessment is suitable for use in the randomized controlled trials abbreviated as RCTs and also that are suitable for use in the observational studies (Hopkins et al., 2004, 90). In this research, the following study characteristics were recorded;

• Study designs which include case reports, case series, randomized control trials, prospective cohort study, and retrospective cohort study
• Blinding and
• The number of participants to be used as the sample size.

RESULTS

1. Study selection procedure

From the literature review study, a total of one hundred and sixty-two studies were reviewed. From that number, fifteen of the studies were strongly relevant based on their title and also the data from the abstracts. Among these fifteen related and relevant titles and abstracts, two out of the fifteen titles investigated animals (2).  Other two studies out of the fifteen did not study the Androgenetic Alopecia (AGA).This left us with only eleven possible studies. After a further evaluation, one was found to be a case report. Another study was a case series and four others were found to be cohort studies. The remaining five were randomized controlled trials (RCTs)

2. The study characteristics

The studies yielded a total of four hundred and forty-four males and a total of two hundred and forty-six females. From the eleven possible studies, nine of them exclusively used the wavelength ranging between 625nm and 655nm (5) where the most popular wavelength was being 650nm.One of the remaining studies utilized a wavelength of between 650nm and 780 nm (15). The remaining study did not specify the amount of wavelength of the laser device used in the survey. Moreover, an approximate of eighty-one percent of the eleven studies utilized a power setting of 5megawatts and lower while at the same time one study used a power setting of between 25 and 30MW. The remaining study did not specify the power rating it used during its study (13). Considering the irradiance setting of the laser device used, one out of the eleven studies reported an irradiance environment while the remaining ten did not record their irradiance setting of the laser device they were using. The one study that reported an irradiance environment, it valued it at 90mW/cm2 (5).Among the eleven studies, only one provided the energy value of the laser device used. That value was at 3.0J per session. Six of the eleven studies utilized a length of time of either twenty-two or twenty-five weeks however the treatment length varied between two months and two years (13). Considering the frequencies per week and the time duration per session, we can say that the differences were negligible. Considering the changes in the hair, a number of different methods were utilized which include the use of the area trichogram (UAT), phototrichogram, global photography, investigator global assessment and without forgetting the use of the direct scalp hair count (2). After this was done, the hair analysis was done by the experts and also with the help of an investigator. Computer software was also used for analysis. Using this different hair analysis and counting tools, a number of outcomes were achieved. However, the important aspect to this research paper is the total hair count, the hair thickness and the tensile strength. Furthermore the study included the secondary outcomes which were aimed at determining the level of the patient’s satisfaction and also the global assessment of the subject under study (14).

3. Study quality control

All the randomized controlled trials (RCTs) were done randomly as the name itself suggests. Many observational studies blinded their outcomes assessors. The assessors were blinded through either the side of the patient that received treatment or through the reviewers in chronological order of the way in which the photographs of the scalp were taken. Doing this ensured that the reviewers of the photographs were not aware of which photographs were either pre or post treatment (14). Among the observational groups, two of them did not blind their outcome assessors’. Out of the eleven studies that showed high positive correlation, one showed no signs of standardization in their measurements (13) The important of standardizing the measurements is to ensure that the measurements are comparable. The changes in the hairstyles, the hair color, the lighting and the head positioning during the follow-up studies can result in changes of total number of hair count and the hair strength. Furthermore, the lack of standardization may lead to differences in techniques among the multiple outcome assessors. These technique differences have the potential of causing a measurement bias when a misappropriate number of participants from only one group were evaluated by one of the outcome assessors (2). Although standardization is necessary, in most scenarios, there is no gold standard for the measuring the irradiation parameters. Moreover, there was no standard measurement for the dose used regarding the minutes taken per session, the frequency of the meetings and also the treatment lengths for Androgenetic Alopecia AGA (18). Furthermore, it was hard to assess the studies considering the regimen treatment. Also, there is no standard for the hair analysis criteria thus making it difficult to gauge how best the results were, basing only on the measurement tools that are implemented in each of the studies.

THE PRIMARY OUTCOMES

• Hair count i.e. the hair density

Out of the eleven studies which assessed hair count i.e. the hair density as the endpoint, nine of the studies recorded a statistically significant improvement in the way in which both the females and the males’ respondent to the low-level laser therapy treatment (14). Among these, three studies had a positive correlation concerning the results and showed an increase in the hair density on the vertex regions (Hopkins et al., 2004, 104). The three studies also showed an increase in the overall hair count by an estimated ninety percent in the temporal regions and also the vertex. Among the retrospective cohort study, one study found a significant increase regarding the subjects from the previous value of twenty-five to a new value of thirty subjects (18). Considering the randomized control trials (RCTs), five of them recorded an improvement in the hair density when treated using the low-level laser therapy as compared to the sham-treated individuals. A multi-centered randomized control trials which consisted of four trials, discovered that there was an increase in the terminal density of the hairs in both genders averaging to a 16 hairs/cm2 for those who were treated using the LLLT (14) as compared to the control individuals. Another study also revealed an increase in the terminal hair density where the low-level laser therapy group experienced an increase by an average of 20 hairs per cm squared (19) as compared to those subjects who were treated using sham. Similarly, two separate studies in males and females among the eleven studies carried out by the same group of researchers revealed that the subjects treated with LLLT recorded an increase of approximately forty percent in the case of males and an increase of forty-two percent in the case of females compared to the control subjects. Furthermore two out of the eleven studies did not record a statistically significant increase in the number of hair density in their subjects of study when treated with the low level laser therapy. Also one study recorded a no difference between the areas irradiated for a period of six months using the Hair Max Laser Comb device compared to the areas which were non-irradiated in the case of their investigation of two males with the Androgenetic Alopecia. A second study where the subjects were six females and one male showed an increase of 7.8 terminal hairs (11). However this value was statistically insignificant. Among the eleven studies, four of them examined hair thickness following treatment using the low-level laser therapy. Out of these four, two studies demonstrated a significant statistical improvement in the tensile strengths and also the level of the hair thickness. However, the remaining two studies did not find any difference (18).The table below summarizes the primary findings from these systematic and Meta-analysis reviews. From the table, it can be seen that the hair texture for the entire group grew by 0.84 and 1.08 in the case of women alone. For men, it was at 0.58. It is clear from the findings that hair texture growth rate was higher for the case of women than men. This signifies that women responded more positively than men in the use of LLLT. The same case applies for the case of hair loss and also the level of satisfaction. For the case of hair loss, the entire group reduced hair by 0.62. The hair loss for women reduced by 0.55 while that of men reduced by 0.69. The level of satisfaction in terms of the use of LLLT in the treatment of AGA was 0.28 on a four point scale for the whole group. On an individual scale, women were much satisfied at 0.46 compared to men whose satisfaction level was 0.10. In a prospective cohort study which consisted of twenty-eight male subjects and seven female subjects revealed a positive improvement in the tensile strength of approximately eighty percent (1). In the randomized controlled trials, the males who were treated using the low-level laser therapy were found to have a higher mean of the standard of the hair thickness (Hopkins et al., 2004, 45) as compared to those subjects who have been submitted to the treatment using the sham-treated males However, one among the eleven studies did not show any change in the case report of two male patients who were suffering from Androgenetic Alopecia (AGA) while also at the same time, a second study among the eleven studies revealed a no statistical significance when comparing the extent of the hair thickness in their study which involved a number of six females and also one male suffering from Androgenetic Alopecia AGA (1). The results obtained from this study may not be so accurate and thus they are much of approximation and averaging.

The TOPHAT results

Out of the five studies carried out, there were a total number of four hundred and four participants, out of which two hundred and fifty-four participants were male. The rest of the participants were female. All of the participants were using the Hair Max Laser Comb (18). Two RCTs trials and two cohort studies showed positive results. The results implied an increase in the number of hair counts, an increase in the tensile strength, increase in the terminal hair density and also a tremendous decrease in the rate at which hair loss occurred (16).  Furthermore, one study which involved two males as the subjects did not find the HairMax Laser Comb to be an effective treatment method for MPH (16).

SECONDARY OUTCOMES

To assess the secondary outcomes, five studies were used to determine the level of the patients’ satisfaction and also the subject assessment as a secondary endpoint. Out of these five studies, one study revealed that two patients found the use of the low-level laser treatment as helpful, at the same time two of the patients also were not sure if the use LLLT was necessary or not (2). Also, three patients reported that the use of low-level laser therapy treatment did not help them in one way or another. In another study which consisted of twenty-four male patients, the reviewers found out that approximately eighty-four percent of the subjects to have contended with the results that the use of LLLT provided (5). However, a randomized controlled trials study yielded varying results concerning the use of LLLT for the treatment of Androgenetic Alopecia in both the males and the females (6). One of the trials which used only females as its subject demonstrated that there was a statistically significant improvement in the subjects. For instance, the hair loss and thickness of the strands following the use of low-level laser therapy as compared to those subjects which were under the control experiment improved. The second trial which also contained females only produced results which were statistically insignificant in either of the two categories of subjects (6). The Bar graph below shows how the subjects under study availed themselves for the study during the study duration. Considering the third and the fourth tests which were conjoined showed statistically significant results in the subject perceived thickness and also fullness. However, the overall hair loss improvement did not reach a statistically significant level (12). Another randomized controlled trial found out that relationship between the subject global assessments and also the satisfaction level between the two groups did not reach a statistically significant level. This implies they were no significant differences despite their being positive findings in the primary outcomes earlier discussed above. Other secondary outcomes included patients reporting a slower rate of the hair loss, an overall increase in the hair growth, scalp health, the presence of some level of thickness and also the presence of shine and hair improvements (12). Despite all these findings, the study, however, did not find any statistical significance relating the to the patient’s perception. As such, it never showed if there was an increase in the length of hair growth or even the manageability of the condition in both the males and the females.

• Costs, safety, and adverse effects

From the eleven studies selected, it was discovered that majority of the subjects that were under study did not report any severe or adverse injuries on them although there were a few cases of minor injuries that were reported in some studies (6). Some symptoms of these minor injuries involved headache, skin drying, scalp tenderness, acne, irritations and redness in the head, pruritus and warm sensation in the areas subjected to LLLT among the subjects. Concerning the costs, there are commercially available devices which include the Hair Max Laser Comb, TOPHAT 655 among many others of which their prices vary according to the brand name, quality of the instrument and also according to the model type (6).

DISCUSSION

The primary aims of this systematic and meta-analysis review research paper was to determine whether the use of low-level laser therapy is an effective therapy for the treatment of the Androgenetic Alopecia (11). The paper also aims to some degree review the expectations the patients should have when they are planning to use these devices. In summary, using the results of the eleven studies which were investigating the safety and also the effectiveness of LLLT showed LLLT was favorable and efficient in the treatment of AGA. At least more than half of the eleven studies showed an improvement in the hair regrowth and also the prevention of the causes of hair loss among the subjects on which the studies were carried out. Furthermore, there was an enough evidence to support this claim since most of the patients reported no severe or adverse effects encountered during their treatment of the Androgenetic Alopecia (7). The great success of this Meta-analysis and systematic research review paper is that to our knowledge the first to systematically review all the evidence which is regarding the use of low-level laser therapy for the treatment of the Androgenetic alopecia. When analyzing the previous reviews concerning the effectiveness of using LLLT for the treatment of the hair loss, all the studies that have investigated the condition of AGA were not included. However, that does not prevent us making the main conclusion that the use of Low-level laser therapy is safe and effective as it is depicted in our results. Out of the eleven studies, two of them did not provide beneficial results using the laser therapy technique. The first of the results found out that there was no significant difference in those areas treated with the help of Hair Max Laser Comb and those areas which were untreated (11). However considering the amount of hair count, both areas showed an increased level in the amount of hair count and also the level of the hair thickness from the baseline. The Following Bar Graph shows the overall results of the study. The second study yielded results which showed there is an increase in the amount of hair count and also the diameter of the hair shaft after the treatment with the use of the laser therapy technique, however, these increases were statistically insignificant (11). Comparing how the use of the LLLT is relating with the commonly prescribed pharmacological AGA treatments. The meta analysis and systematic review showed that approximately thirty-five of the hair improvements for the patients with a long term use of the finasteride was of the time significantly detected at after around six months however in the case of females, the use of finasteride failed to show improvements in the hair loss especially for those women who were in their postmenopausal. For the women in their premenopausal, it was found to be effective. Taking into considerations the comparisons and the contrasting of the subject assessment with the quantitative results were useful in defining the realistic expectations for the patients who were using the low-level laser therapy (19). A good number of the studies showed a positive assessment of the patients while a few of the studies recorded a negative response concerning the patient's satisfaction despite the positive findings realized from the use of LLLT (11).This is clearly shown using the Bar Graph below. From the graph below, it is clear that the number of patients who reported that the use of LLLT for the first time affected them severely and also moderately severely was 35.7% in total whereas those who reported a slight effect was at 31.8% and considering the value of those who did not report any effect on the bodies was 31.5% of the total number of patients treated using LLLT. After thirty days, the proportion of patients affected severely and moderately more severely by use of LLLT reduced to 18.0% and this value dropped to 5.4% after ninety days. The proportion of those who reported slight and no effects also increased from 45.4% after thirty days to 67.6% after ninety days. The two possible reasons for the existence of this discrepancy between the qualitative and the quantitative can be attributed to the presence of a placebo effect or the effect of the observed changes following the laser device failing to achieve the expectations of the patients thus the negative feedback from the patients concerning its use (12). These research paper has put much emphasis on the importance of setting up achievable goals and expectations for the patients and also when recommending the use of the low-level laser therapy as the possible treatment. In this research paper, the importance of integrating the use of personalized medicine was addressed fully when considering using laser therapy. One of the studies found that patients with an AGA responded best because the amount of the hair that was present in this individuals was much sufficient for the biomodulation while not exceeding the threshold level for which the absorption of the laser was impeded by the existing hairs (17). Another study found out that the older patients/subjects of the experiment experienced a strong linear trend of hair growth as compared to the young subjects (11). Considering the effectiveness, the cost and the safety of these laser devices, it was found out that the majority of the subjects did not report any serious adverse effects (19). One of the studies reported that patients developed basal cell carcinomas on their scalp (11). However, the authors of that article did not equate this condition as relating to the use of laser therapy. Despite these, it was found out that the cost of purchasing these devices is friendly and also advantageous. The reports showed that there is a one-time cost as compared to the cases of medications where one is supposed to purchase the drugs now and then, turning out to be more expensive in the long run (17). Also, the initial cost of purchasing these devices was found to be somehow affordable to a larger population compared that of carrying out hair transplantation (7). The topic of the light sources and the wavelength is also an important part that one needs to understand the use of LLLT. Wavelength, the irradiance measured in watts per square centimeters, the time taken, pulses and the possible coherence and polarization influence the final results produced from the low-level laser treatment. The ideal range for using LLLT ranges between 650nm and 750 nm (12). This range has been proven and used to treat the superficial tissues. Cases of insufficient irradiation can result in there being no results from the LLLT therapy. In other cases, if the irradiation time is too long, then it can inhibit the response thus becoming unreliable (7). The limited and varying information that was available on the parameters and the treatment dose of each study made it difficult to identify the possible patterns that can help identify the possible dissymmetry in the use of LLLT for the treatment of Androgenetic Alopecia. In order to identify the most effective dissymmetry, a suggestion is made that future studies should incorporate all the irradiation parameters and the treatment done in order to perform a standardized comparison (12). Looking into subject appraisal/persistent fulfillment with quantitative outcomes is helpful for characterizing sensible desires for patients when utilizing LLLT treatment. A few reviews detailed positive subject appraisals, while a couple thinks about did not locate a similar patient fulfillment in spite of positive target discoveries (19). Two conceivable methods of reasoning for the inconsistency between the quantitative and subjective subject results are the nearness of a misleading impact as well as the watched changes taking after laser treatment neglected to meet the desires of the patients. These discoveries stress the significance of setting practical objectives and desires for patients while suggesting LLLT as a conceivable treatment (19). The Androgenetic Alopecia pathogenesis is characterized by a step by step miniaturization of the hair follicle which results in the transformation of the villus of the hair terminal (3). The exact mechanism in which the therapeutic effects on the use of LLLT have on the hair growth and the hair cycle is not clearly elaborated (17). For example, the laser light is thought to be activating of the re-entry of the anagen in the telogen hair follicles. Previous studies have found out those one hundred and eleven genes to be affected by the use of LLLT therapy that coincides with the increase in the rate of proliferation, migration and tissue oxygenation (3). In any research process, there are always limitations. In our meta-analysis and systematic reviews, these challenges included the limited number of studies that have been carried out on the effects of LLLT in the treatment of AGA. Another disadvantage was that there was the lack of research on this same topic using a larger sample size. Most of the articles reviewed were using a smaller sample which may not give the representation of the whole population which is under study that could lead to unreliable results and conclusions (12). Another limitation was the challenge of comparing and contrasting the different AGA treatment methods. It took the research a lot of time and some keenness to come up with conclusive conclusions. The use of various devices was also a limitation as it lacked the consistency thus making it hard to make standardizations (19). These devices include the length of treatment of the subjects, the irradiation parameters used, treatment doses and the treatment frequencies. Out of the eleven studies selected; six of them reported the existence of a conflict of interest. A suggestion to avoid this conflict of interest will be through the use of large samples (19).

CONCLUSION

In conclusion, the use of the low-level laser therapy (LLLT) is a promising area that needs to be embraced for use in the treatment of Androgenetic Alopecia (AGA).The use of LLLT if fully utilized can be a better alternative for those individuals who are unwilling to use the medical therapy currently available which is much expensive or the possibility of undergoing through the hair transplantations and the surgical options that are currently available. Many of the results covered in this review showed that there is an overall improvement in the hair regrowth, thickness, the level of the patient’s satisfaction following treatment using the low-level laser therapy technology. The use of LLLT devices is safe and is seen as an effective way of treating AGA. However, more is needed to be done to help identify which patients are suitable and those not suitable for treatment using LLLT (11).Lastly, more extensive research needs to be done in this field so as to help determine which patients are the ideal for this type of treatment and those which are ideal for the alternative treatment methods.

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