madman
Super Moderator
Abstract
Background: Androgenetic alopecia (AGA) is the most common form of hair loss consisting of a characteristic receding frontal hairline in men and diffuse hair thinning in women, with frontal hairline retention, and can impact an individual's quality of life. The condition is primarily mediated by 5-alpha-reductase and dihydrotestosterone (DHT) which causes hair follicles to undergo miniaturization and shortening of successive anagen cycles. Although a variety of medical, surgical, light-based, and nutraceutical treatment options are available to slow or reverse the progression of AGA, it can be challenging to select appropriate therapies for this chronic condition.
Aims: To highlight treatment options for androgenetic alopecia taking into consideration the efficacy, side effect profiles, practicality of treatment (compliance), and costs to help clinicians offer ethically appropriate treatment regimens to their patients.
Materials and Methods: A literature search was conducted using electronic databases (Medline, PubMed, Embase, CINAHL, EBSCO) and textbooks, in addition to the authors' and other practitioners' clinical experiences in treating androgenetic alopecia, and the findings are presented here.
Results: Although topical minoxidil, oral finasteride, and low-level light therapy are the only FDA-approved therapies to treat AGA, they are just a fraction of the treatment options available, including other oral and topical modalities, hormonal therapies, nutraceuticals, PRP and exosome treatments, and hair transplantation.
Discussion: Androgenetic alopecia therapy remains challenging as treatment selection involves ethical, evidence-based decision-making and consideration of each individual patient's needs, compliance, budget, the extent of hair loss, and aesthetic goals, independent of potential financial benefits to the practitioners.
1 INTRODUCTION
Androgenetic alopecia, also known as male or female pattern baldness, is the most common type of hair loss and affects at least 80% of men and half of women by age 70, with the incidence increasing with age.1–3 Although commonly encountered by practicing dermatologists and hair specialists, it can be one of the most challenging conditions to address as treatment selection often involves a complex consideration of multiple factors and ethical decision-making. Effectiveness, side effect profiles, practicality leading to compliance, and cost of treatment are among the most important factors to be considered especially given the chronic nature of AGA. Physician knowledge base, familiarity with specific treatment modalities, and financial compensation can also limit and obscure, respectively, a clinician's ability to select the most appropriate treatment option for each patient.4
The large variety of treatment options available and lack of standardization among existing studies complicates treatment selection even further. This makes it difficult to determine which treatment options are best in part because standardized grading techniques have not been consistently implemented. In meta-studies of current data available, change in anagen hair count appears to be the most consistent endpoint in determining treatment success.5–7 This review is intended to help guide practitioners in their decision-making processes with regard to treating AGA by deconstructing the medical literature, presenting the breadth of treatment options available, and identifying the ethical consequences involved in selecting each treatment. Before deciding on the most optimal treatment for AGA, practitioners must have an understanding of its etiology and molecular mechanisms.
Androgenetic alopecia is an autosomal dominant condition composed of the gradual conversion of terminal hairs into intermediate and vellus hairs. Alterations in the hair cycle include reduced duration of the anagen phase and increased duration of the telogen phase, resulting in shorter hairs and eventual balding.8 Early-onset AGA has a strong association with severe coronary artery disease and metabolic syndrome and individuals with a high body mass index have been found to have increased incidences of severe AGA.9 Recent evidence has also demonstrated that AGA, occurring in both genders, has been linked to a number of severe cases of COVID-19 which has been termed the “Gabrin sign.”10–13
In men, AGA begins as a bitemporal thinning of the frontal scalp which spreads to the vertex. In women, AGA presents as diffuse hair thinning between the frontal scalp and vertex, typically sparing the frontal hairline, which creates a more visible scalp. The condition is particularly more common among those undergoing menopause.14 The diagnosis is usually clinical, but follicular miniaturization is the histological footprint of AGA.15 Hair loss negatively impacts self-esteem and overall quality of life. Multiple studies have shown that men who experience premature loss of hair often exhibit emotional distress and express significant concern to their peers and family.16,17 Studies have also shown that the psychological impact in women is more devastating than in male counterparts.18
Current FDA-approved therapies include topical minoxidil, oral finasteride, and low-level light therapy. However, there is a multitude of other primary and complementary treatment options commonly utilized among practitioners. The efficacy and mechanisms of existing, alternative, and upcoming therapeutics for AGA, as well as ethical and financial factors to consider when selecting a treatment option, will be covered in the following sections.
1.1 COMPARING AGA THERAPEUTIC OPTIONS
In order to appropriately compare various therapeutic options for AGA and attempt to create a choice matrix for each therapeutic class, we will evaluate the efficacy, side effect profiles, ease of use (compliance factors), and cost. It is also important to recognize that AGA is a chronic, lifelong condition, which makes comparing ease of use and cost more challenging. We therefore will look at the ease of use and cost monthly and over a 5 year period*. Additionally, we separate the medical options into topical and oral formulations.
2 TOPICAL THERAPIES
For patients that have early or mild-to-moderate hair loss, and want to avoid oral medications due to the potential systemic side effects, topical therapies may serve as a viable first-line option or adjuvant for the treatment of AGA.
2.1 Topical minoxidil
2.1.1 Background and efficacy
2.1.2 Side effects
2.1.3 Ease of use
2.1.4 Patient cost
2.2 Topical finasteride
2.2.1 Background and efficacy
2.2.2 Side effects
2.2.3 Ease of use
2.2.4 Patient cost
3 ORAL THERAPIES
Oral therapies are often the easiest treatment options for patients with progressing and moderate AGA, but certainly have more potential side effects than topical agents. Since oral medications are convenient options it is common for many medically-based physicians to default to this treatment option while dismissing other complementary, invasive, or alternative therapies that may very well be more effective and better-suited to particular subsets of patients.
3.1 Oral finasteride
3.1.1 Background and efficacy
3.1.2 Side effects
3.1.3 Ease of use
3.1.4 Patient cost
3.2 Oral dutasteride
3.2.1 Background and efficacy
3.2.2 Side effects
3.2.3 Ease of use
3.2.4 Patient cost
4 HORMONAL THERAPIES
4.1 Spironolactone
4.1.1 Background and efficacy
4.1.2 Side effects
4.1.3 Ease of use
4.1.4 Patient cost
4.2 Flutamide and bicalutamide
4.2.1 Background and efficacy
4.2.2 Side effects
4.2.3 Ease of use
4.2.4 Patient cost
4.3 Cyproterone acetate
4.3.1 Background and efficacy
4.3.2 Side effects
4.3.3 Ease of use
4.3.4 Patient cost
5 LIGHT THERAPIES
5.1 Low-level laser therapy
5.1.1 Background and efficacy
5.1.2 Side effects
5.1.3 Ease of use
5.1.4 Patient cost
5.2 Light-emitting diode devices
5.2.1 Background and efficacy
5.2.2 Side effects
5.2.3 Ease of use
5.2.4 Patient cost
6 INJECTABLES
6.1 Platelet-rich plasma
6.1.1 Background and efficacy
6.1.2 Side effects
6.1.3 Ease of use
6.1.4 Patient cost
6.2 Exosomes
6.2.1 Background and efficacy
6.2.2 Side effects
6.2.3 Ease of use
6.2.4 Patient cost
7 ADJUVANT THERAPY
7.1 Microneedling
7.1.1 Background and efficacy
7.1.2 Side effects
7.1.3 Ease of use
7.1.4 Patient cost
8 SUPPLEMENTS & OTC TREATMENTS
Phytomedicine was previously introduced as monotherapy or adjuvant therapy for several dermatologic conditions, such as photoprotection, vitiligo, and melasma.126–128 A variety of nutraceuticals have appeared in the market over the past few years.129 The oral regimens are convenient for many patients, but clinical evidence supporting its efficacy is still minimal. Nutraceuticals are tolerated in clinical trials and can be used as monotherapy or adjuvant therapy.
8.1 Oral nutraceutical supplement containing Synergen Complex®
8.1.1 Background and efficacy
8.1.2 Side effects
8.1.3 Ease of use
8.1.4 Patient cost
8.2 Marine complex supplement
8.2.1 Background and efficacy
8.2.2 Side effects
8.2.3 Ease of use
8.2.4 Patient cost
8.3 Serenoa repens
8.3.1 Background and efficacy
8.3.2 Side effects
8.3.3 Ease of use
8.3.4 Patient cost
8.4 Plant-based oils: rosemary oil, tea tree oil, pumpkin seed oil, coconut oil, castor oil, amla oil
8.4.1 Background and efficacy
8.4.2 Side effects
8.4.3 Ease of use
8.4.4 Patient cost
8.5 Ketoconazole
8.5.1 Background and efficacy
8.5.2 Side effects
8.5.3 Ease of use
8.5.4 Patient cost
9 COMBINATION THERAPY
10 HAIR TRANSPLANTATION
10.1 Background and efficacy
10.2 Side effects
10.3 Ease of use
10.4 Patient cost
11 NEW AND UPCOMING TREATMENT OPTIONS
11.1 Clascoterone
11.2 Oral JAK inhibitors
11.3 Prostaglandin analog
12 A DISCUSSION OF THE ETHICAL CONSIDERATIONS IN TREATING AGA
12.1 Consideration of efficacy
12.2 Consideration of side effect profiles
12.3 Consideration of ease of use (Compliance)
12.4 Consideration of cost
12.5 Patient and physician choice of treatment options
13 CONCLUSION
There are a variety of options in a practitioner's armamentarium for treating AGA which include oral and topical medications, hormonal therapies, nutraceuticals, PRP, exosomes, micro-needling, and more invasive techniques such as hair transplantation. The treatment of AGA can be particularly challenging due to non-uniformity in patient response to conventional therapies and even the incomplete understanding of the exact pathogenesis of the condition itself. Patients must adhere to lifelong therapy as AGA continues to progress if treatment is stopped. Oral finasteride, topical minoxidil, and LLLT are currently the only FDA-approved treatments for this condition, all of which may be effective in treating particular patients with AGA. However, selecting appropriate therapy for a patient should take into consideration the individual's age and aesthetic concerns, lifestyle and preferences, access to treatment, compliance, the extent of hair loss, and financial budget.
As clinicians, we have an ethical obligation to do what is best for our patients: to provide treatments with the greatest efficacy and fewest side effects and to exclude personal financial compensation as a factor in treatment selection. Practitioners should advise patients of all possible AGA treatment options, so both parties may make informed decisions. Moreover, if providers are inexperienced or unable to provide a particular modality of treatment that may be more suited to a patient's needs, he or she should be willing to refer to an expert colleague that may offer that particular modality.
Although many therapies are reported to be helpful and well-tolerated, most studies are yet limited by small sample sizes and varying study methodologies. Direct comparisons among the various therapeutic options are not commonly reported. As a result, treatment efficacy is often derived from cross-study comparisons of published results. Future high-quality randomized controlled trials and head-to-head trials should be conducted to better characterize the net change in hair counts vs. placebo/control groups, particularly ones that utilize the change in anagen hair counts as an endpoint as this may provide a more accurate measure of treatment efficacy. Further research in these avenues will help to clarify efficacies of different treatments among diverse groups of patients and varying degrees of AGA so that practitioners and patients can make more informed decisions when selecting the optimal treatment.
Background: Androgenetic alopecia (AGA) is the most common form of hair loss consisting of a characteristic receding frontal hairline in men and diffuse hair thinning in women, with frontal hairline retention, and can impact an individual's quality of life. The condition is primarily mediated by 5-alpha-reductase and dihydrotestosterone (DHT) which causes hair follicles to undergo miniaturization and shortening of successive anagen cycles. Although a variety of medical, surgical, light-based, and nutraceutical treatment options are available to slow or reverse the progression of AGA, it can be challenging to select appropriate therapies for this chronic condition.
Aims: To highlight treatment options for androgenetic alopecia taking into consideration the efficacy, side effect profiles, practicality of treatment (compliance), and costs to help clinicians offer ethically appropriate treatment regimens to their patients.
Materials and Methods: A literature search was conducted using electronic databases (Medline, PubMed, Embase, CINAHL, EBSCO) and textbooks, in addition to the authors' and other practitioners' clinical experiences in treating androgenetic alopecia, and the findings are presented here.
Results: Although topical minoxidil, oral finasteride, and low-level light therapy are the only FDA-approved therapies to treat AGA, they are just a fraction of the treatment options available, including other oral and topical modalities, hormonal therapies, nutraceuticals, PRP and exosome treatments, and hair transplantation.
Discussion: Androgenetic alopecia therapy remains challenging as treatment selection involves ethical, evidence-based decision-making and consideration of each individual patient's needs, compliance, budget, the extent of hair loss, and aesthetic goals, independent of potential financial benefits to the practitioners.
1 INTRODUCTION
Androgenetic alopecia, also known as male or female pattern baldness, is the most common type of hair loss and affects at least 80% of men and half of women by age 70, with the incidence increasing with age.1–3 Although commonly encountered by practicing dermatologists and hair specialists, it can be one of the most challenging conditions to address as treatment selection often involves a complex consideration of multiple factors and ethical decision-making. Effectiveness, side effect profiles, practicality leading to compliance, and cost of treatment are among the most important factors to be considered especially given the chronic nature of AGA. Physician knowledge base, familiarity with specific treatment modalities, and financial compensation can also limit and obscure, respectively, a clinician's ability to select the most appropriate treatment option for each patient.4
The large variety of treatment options available and lack of standardization among existing studies complicates treatment selection even further. This makes it difficult to determine which treatment options are best in part because standardized grading techniques have not been consistently implemented. In meta-studies of current data available, change in anagen hair count appears to be the most consistent endpoint in determining treatment success.5–7 This review is intended to help guide practitioners in their decision-making processes with regard to treating AGA by deconstructing the medical literature, presenting the breadth of treatment options available, and identifying the ethical consequences involved in selecting each treatment. Before deciding on the most optimal treatment for AGA, practitioners must have an understanding of its etiology and molecular mechanisms.
Androgenetic alopecia is an autosomal dominant condition composed of the gradual conversion of terminal hairs into intermediate and vellus hairs. Alterations in the hair cycle include reduced duration of the anagen phase and increased duration of the telogen phase, resulting in shorter hairs and eventual balding.8 Early-onset AGA has a strong association with severe coronary artery disease and metabolic syndrome and individuals with a high body mass index have been found to have increased incidences of severe AGA.9 Recent evidence has also demonstrated that AGA, occurring in both genders, has been linked to a number of severe cases of COVID-19 which has been termed the “Gabrin sign.”10–13
In men, AGA begins as a bitemporal thinning of the frontal scalp which spreads to the vertex. In women, AGA presents as diffuse hair thinning between the frontal scalp and vertex, typically sparing the frontal hairline, which creates a more visible scalp. The condition is particularly more common among those undergoing menopause.14 The diagnosis is usually clinical, but follicular miniaturization is the histological footprint of AGA.15 Hair loss negatively impacts self-esteem and overall quality of life. Multiple studies have shown that men who experience premature loss of hair often exhibit emotional distress and express significant concern to their peers and family.16,17 Studies have also shown that the psychological impact in women is more devastating than in male counterparts.18
Current FDA-approved therapies include topical minoxidil, oral finasteride, and low-level light therapy. However, there is a multitude of other primary and complementary treatment options commonly utilized among practitioners. The efficacy and mechanisms of existing, alternative, and upcoming therapeutics for AGA, as well as ethical and financial factors to consider when selecting a treatment option, will be covered in the following sections.
1.1 COMPARING AGA THERAPEUTIC OPTIONS
In order to appropriately compare various therapeutic options for AGA and attempt to create a choice matrix for each therapeutic class, we will evaluate the efficacy, side effect profiles, ease of use (compliance factors), and cost. It is also important to recognize that AGA is a chronic, lifelong condition, which makes comparing ease of use and cost more challenging. We therefore will look at the ease of use and cost monthly and over a 5 year period*. Additionally, we separate the medical options into topical and oral formulations.
2 TOPICAL THERAPIES
For patients that have early or mild-to-moderate hair loss, and want to avoid oral medications due to the potential systemic side effects, topical therapies may serve as a viable first-line option or adjuvant for the treatment of AGA.
2.1 Topical minoxidil
2.1.1 Background and efficacy
2.1.2 Side effects
2.1.3 Ease of use
2.1.4 Patient cost
2.2 Topical finasteride
2.2.1 Background and efficacy
2.2.2 Side effects
2.2.3 Ease of use
2.2.4 Patient cost
3 ORAL THERAPIES
Oral therapies are often the easiest treatment options for patients with progressing and moderate AGA, but certainly have more potential side effects than topical agents. Since oral medications are convenient options it is common for many medically-based physicians to default to this treatment option while dismissing other complementary, invasive, or alternative therapies that may very well be more effective and better-suited to particular subsets of patients.
3.1 Oral finasteride
3.1.1 Background and efficacy
3.1.2 Side effects
3.1.3 Ease of use
3.1.4 Patient cost
3.2 Oral dutasteride
3.2.1 Background and efficacy
3.2.2 Side effects
3.2.3 Ease of use
3.2.4 Patient cost
4 HORMONAL THERAPIES
4.1 Spironolactone
4.1.1 Background and efficacy
4.1.2 Side effects
4.1.3 Ease of use
4.1.4 Patient cost
4.2 Flutamide and bicalutamide
4.2.1 Background and efficacy
4.2.2 Side effects
4.2.3 Ease of use
4.2.4 Patient cost
4.3 Cyproterone acetate
4.3.1 Background and efficacy
4.3.2 Side effects
4.3.3 Ease of use
4.3.4 Patient cost
5 LIGHT THERAPIES
5.1 Low-level laser therapy
5.1.1 Background and efficacy
5.1.2 Side effects
5.1.3 Ease of use
5.1.4 Patient cost
5.2 Light-emitting diode devices
5.2.1 Background and efficacy
5.2.2 Side effects
5.2.3 Ease of use
5.2.4 Patient cost
6 INJECTABLES
6.1 Platelet-rich plasma
6.1.1 Background and efficacy
6.1.2 Side effects
6.1.3 Ease of use
6.1.4 Patient cost
6.2 Exosomes
6.2.1 Background and efficacy
6.2.2 Side effects
6.2.3 Ease of use
6.2.4 Patient cost
7 ADJUVANT THERAPY
7.1 Microneedling
7.1.1 Background and efficacy
7.1.2 Side effects
7.1.3 Ease of use
7.1.4 Patient cost
8 SUPPLEMENTS & OTC TREATMENTS
Phytomedicine was previously introduced as monotherapy or adjuvant therapy for several dermatologic conditions, such as photoprotection, vitiligo, and melasma.126–128 A variety of nutraceuticals have appeared in the market over the past few years.129 The oral regimens are convenient for many patients, but clinical evidence supporting its efficacy is still minimal. Nutraceuticals are tolerated in clinical trials and can be used as monotherapy or adjuvant therapy.
8.1 Oral nutraceutical supplement containing Synergen Complex®
8.1.1 Background and efficacy
8.1.2 Side effects
8.1.3 Ease of use
8.1.4 Patient cost
8.2 Marine complex supplement
8.2.1 Background and efficacy
8.2.2 Side effects
8.2.3 Ease of use
8.2.4 Patient cost
8.3 Serenoa repens
8.3.1 Background and efficacy
8.3.2 Side effects
8.3.3 Ease of use
8.3.4 Patient cost
8.4 Plant-based oils: rosemary oil, tea tree oil, pumpkin seed oil, coconut oil, castor oil, amla oil
8.4.1 Background and efficacy
8.4.2 Side effects
8.4.3 Ease of use
8.4.4 Patient cost
8.5 Ketoconazole
8.5.1 Background and efficacy
8.5.2 Side effects
8.5.3 Ease of use
8.5.4 Patient cost
9 COMBINATION THERAPY
10 HAIR TRANSPLANTATION
10.1 Background and efficacy
10.2 Side effects
10.3 Ease of use
10.4 Patient cost
11 NEW AND UPCOMING TREATMENT OPTIONS
11.1 Clascoterone
11.2 Oral JAK inhibitors
11.3 Prostaglandin analog
12 A DISCUSSION OF THE ETHICAL CONSIDERATIONS IN TREATING AGA
12.1 Consideration of efficacy
12.2 Consideration of side effect profiles
12.3 Consideration of ease of use (Compliance)
12.4 Consideration of cost
12.5 Patient and physician choice of treatment options
13 CONCLUSION
There are a variety of options in a practitioner's armamentarium for treating AGA which include oral and topical medications, hormonal therapies, nutraceuticals, PRP, exosomes, micro-needling, and more invasive techniques such as hair transplantation. The treatment of AGA can be particularly challenging due to non-uniformity in patient response to conventional therapies and even the incomplete understanding of the exact pathogenesis of the condition itself. Patients must adhere to lifelong therapy as AGA continues to progress if treatment is stopped. Oral finasteride, topical minoxidil, and LLLT are currently the only FDA-approved treatments for this condition, all of which may be effective in treating particular patients with AGA. However, selecting appropriate therapy for a patient should take into consideration the individual's age and aesthetic concerns, lifestyle and preferences, access to treatment, compliance, the extent of hair loss, and financial budget.
As clinicians, we have an ethical obligation to do what is best for our patients: to provide treatments with the greatest efficacy and fewest side effects and to exclude personal financial compensation as a factor in treatment selection. Practitioners should advise patients of all possible AGA treatment options, so both parties may make informed decisions. Moreover, if providers are inexperienced or unable to provide a particular modality of treatment that may be more suited to a patient's needs, he or she should be willing to refer to an expert colleague that may offer that particular modality.
Although many therapies are reported to be helpful and well-tolerated, most studies are yet limited by small sample sizes and varying study methodologies. Direct comparisons among the various therapeutic options are not commonly reported. As a result, treatment efficacy is often derived from cross-study comparisons of published results. Future high-quality randomized controlled trials and head-to-head trials should be conducted to better characterize the net change in hair counts vs. placebo/control groups, particularly ones that utilize the change in anagen hair counts as an endpoint as this may provide a more accurate measure of treatment efficacy. Further research in these avenues will help to clarify efficacies of different treatments among diverse groups of patients and varying degrees of AGA so that practitioners and patients can make more informed decisions when selecting the optimal treatment.
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