Management of androgenic alopecia:

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ABSTRACT

We aimed to determine the efficacy of the various available oral, topical, and procedural treatment options for hair loss in individuals with androgenic alopecia. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of the National Library of Medicine was performed. Overall, 141 unique studies met our inclusion criteria. We demonstrate that many over the counter (e.g. topical minoxidil, supplements, low-level light treatment), prescription (e.g. oral minoxidil, finasteride, dutasteride), and procedural (e.g. platelet-rich plasma, fractionated lasers, hair transplantation) treatments successfully promote hair growth, highlighting the superiority of a multifaceted and individualized approach to management.




Introduction

Hair plays a vital role in self-identity, and hair loss can profoundly impact self-perception and life satisfaction. Patterned hair loss, or androgenic alopecia (AGA), is the most common form of hair loss, affecting more than half the adult population(1). Despite advancements in understanding the hair follicle and its natural cycle, hair loss remains a complex condition influenced by various biological, genetic, hormonal, chemical,and environmental factors (Figure 1).




Normal hair cycling

In disease states such as AGA, there is reduction in progenitor cells but HFSCs remain viable (5). Consequently, many believe that the reactivation of HFSCs could regenerate hair in balding scalps. This is an area of active research and has inspired several existing hair growth treatments.


Genetic influence

Population studies have reported a polygenic inheritance pattern of hair loss, with both maternal and paternal genetic influences. Of the genes identified to date, the androgen receptor(AR) gene on chromosome X represents a major determinant of hair loss (i.e. AGA) in both men and women (6). Specifically, the CAG repeat length within the AR gene influences the sensitivity of the androgen receptor to dihydrotestosterone (DHT),a hormonal derivative of testosterone. Individuals with shorter CAG repeat sequences have an increased risk of developing AGA. In contrast, men with > 40 repeats appear to be protected and have androgen insensitivity. Other implicated genes include Ectodysplasin A2 Receptor, as well as genes located on chromosomes 20p11 and 3q26; however, how these variants affect hair loss merits further investigation (4).


Hormonal influence

The role of testosterone in the pathogenesis of both male and female balding is well known and underscores the prevalent use of 5-alpha reductase inhibitors. The history of this class of medications is unique and emerged from a remote village in the Dominican Republic called Las Salinas. In this village, a small group of children born with ambiguous genitalia were initially raised as female, but then developed male characteristics during puberty. Following these young men into adulthood revealed that they had no enlargement of their prostate, acne, or patterned hair loss. Endocrinologists identified a deficiency of 5-alpha reductase, an enzyme responsible for converting testosterone to DHT, within this population, ultimately resulting in the development of Proscar (i.e. finasteride)by Merck Pharmaceuticals (7).

Additional research into the role of testosterone on hair loss has shown that type I and II isoforms of 5-alpha reductase reside at the level of the hair follicle, resulting in the accumulation of DHT. DHT then binds to the androgen receptors and activates the production of proteins harmful to the follicle, leading to disruption of the normal hair growth cycle.
Specifically, anagen phase is shortened, resulting in premature regression duringc atagen and telogen phases. With each hair cycle, the anagen phase further shortens, leading to progressive miniaturization of hair and, eventually, hair loss. Many over the counter (OTC) and prescription treatments, both oral and topical, inhibit these hormonal processes, with the intent of preventing hair loss.



Chemical factors


Environmental factors




*Topical minoxidil


*Oral minoxidil

*Finasteride/dutasteride

*Other hormonal therapies

*Ketoconazole

*Supplements

*Platelet-rich plasma

*Stem cells/growth factors

*Thread-embedding therapy

*Botulinum toxin A

*Low-level light treatment

*Fractionated laser therapy

*Drug delivery devices

*Hair transplantation surgery

*Other topical agents

*Other interventions





Discussion

Hair loss is a complex, multifactorial condition that holds the potential to significantly impact quality of life. While topical minoxidil (for men and women) and finasteride(for men) remain the only FDA-approved therapeutics, several other oral, topical, and procedural options exist. This literature review summarizes the key findings of 141 studies, demonstrating the greatest efficacy for those agents investigated using randomized study designs with objective hair growth parameters including hair count,density, and diameter.

Among OTC treatments, topical minoxidil is the mainstay of therapy due to its proven effectiveness, low cost,ease of accessibility, and tolerable side effect profile. Many OTC supplements have similarly proven to be beneficial as complementary treatments. These supplements are not FDA-approved; and, therefore, patients should be cautious when purchasing oral formulations as the efficacy and safety of these products may be variable. Additionally, LLLT has shown promise as a potential adjunctive treatment. These devices can be purchased online; however, they tend to be costly and regular compliance may pose a challenge for some individuals. With respect to prescription medications, oral minoxidil, finasteride, and dutasteride appear to have the highest efficacy in treating hair loss across studies. Interestingly, dutasteride may be more effective than finasteride in regrowing hair and reducing hair loss. Further, the longer half-life of dutasteride also allows for every other day or every third day dosing, thereby minimizing the side effect profile without compromising clinical efficacy. Ketoconazole shampoo is well-tolerated and inexpensive, making it an easy adjunctive therapy for patients desiring a combination treatment approach Finally, PRP, both with and without hair restoration surgery, appears to be the most promising procedural treatment, stimulating long-lasting hair growth and enhancing overall scalp health. Use of fractionated lasers, other drug-delivery devices, and hair restoration surgery have also shown benefit. These procedural treatments, however, are not covered by insurance, can be very costly, and are oftent imes associated with pain and discomfort. In clinical practice, the ideal treatment approach should be both multifaceted and individualized, considering the degree of hair loss, patient preferences, associated costs, and comorbid conditions. Future clinical trials with sufficient sample sizes, adequate follow-up time, and standardized outcomes are necessary to better delineate the efficacy and safety of various therapeutics, alone and in combination. Finally, because AGA is a chronic condition, follow-up studies evaluating the sustainability of hair regrowth following treatment discontinuation are warranted.
 

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Figure 1. Factors involved in regulating the hair cycle.
1719190385485.png
 
Figure 3. Female Patient with AGA: Before and 6 Months After 1 Session of PRP (from the author’s clinical practice).
Screenshot (37232).png

Screenshot (37233).png
 
Figure 4. Male Patient with AGA: Before and 4 Months After 2 Sessions of PRP Spaced 6 Months Apart (from the author’s clinical practice).
1719191316727.png
 
*Specifically, the CAG repeat length within the AR gene influences the sensitivity of the androgen receptor to dihydrotestosterone (DHT),a hormonal derivative of testosterone. Individuals with shorter CAG repeat sequences have an increased risk of developing AGA. In contrast, men with > 40 repeats appear to be protected and have androgen insensitivity. Other implicated genes include Ectodysplasin A2 Receptor, as well as genes located on chromosomes 20p11 and 3q26; however, how these variants affect hair loss merits further investigation (4).

*The role of testosterone in the pathogenesis of both male and female balding is well known and underscores the prevalent use of 5-alpha reductase inhibitors. The history of this class of medications is unique and emerged from a remote village in the Dominican Republic called Las Salinas. In this village, a small group of children born with ambiguous genitalia were initially raised as female, but then developed male characteristics during puberty. Following these young men into adulthood revealed that they had no enlargement of their prostate, acne, or patterned hair loss. Endocrinologists identified a deficiency of 5-alpha reductase, an enzyme responsible for converting testosterone to DHT, within this population, ultimately resulting in the development of Proscar (i.e. finasteride) by Merck Pharmaceuticals (7).

*Additional research into the role of testosterone on hair loss has shown that type I and II isoforms of 5-alpha reductase reside at the level of the hair follicle, resulting in the accumulation of DHT. DHT then binds to the androgen receptors and activates the production of proteins harmful to the follicle, leading to disruption of the normal hair growth cycle.
 
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