Androgenetic alopecia (AGA) is by nature progressive. Medical treatment should ideally help in arresting progression as well as inducing new hair growth. Cosmetic improvement should cover the increase in hair density and diameter. At present, the evidence-based medical management of AGA mainly revolves around a few limited options– topical minoxidil, oral 5-alfa-reductase inhibitors, low level laser therapy (LLLT), and platelet-rich plasma (PRP).
The exact mechanism of action of minoxidil in AGA is not clear, but it is considered to promote hair growth by dermal vessel vasodilation and inducing early anagen switch.
Minoxidil scores are high in terms of the available evidence, efficacy, safety, and ease of use. Minoxidil is available as preparation of 2%, 5%, and also 10%. It is available as spray, solutions, and foam. The recommended dose is 1 ml once or twice daily. Minoxidil has shown good efficacy in both males and females. In male patients, 5% applied twice daily is more effective than 2% applied twice daily and in females, 5% applied once daily was found to be comparable to 2% applied twice daily.
The response to topical minoxidil is to be reassessed at the end of 6 months and needs continued maintenance to maintain the benefit. If no response/persisting shedding even at 6 months, can consider combining with oral finasteride. Patients should be counseled regarding increased loss initially due to transient telogen hair shedding. Other possible side effects seen are hypertrichosis and contact dermatitis (both irritant and allergic).
There are insufficient data regarding the use of minoxidil during pregnancy and lactation, hence the general recommendation is to stop the use of minoxidil during pregnancy.
Oral minoxidil has been used effectively in both male and female patients with AGA. However, standardization of dosage and protocols require more evidence. At present, oral minoxidil is used in doses ranging from 0.25 mg to 5 mg per day. Low dose minoxidil (0.25 mg/day) has also been found to be effective in a limited number of studies and in general lower doses are more effective in female patients as compared to males. Side effects reported include hypertrichosis, lower limb edema, electrocardiogram abnormalities, and telogen effluvium. However, in general, oral minoxidil is considered to be safe. Absolute contraindications include– pheochromocytoma and relative contraindications include– hypotension and pregnancy.
5 Alpha Reductase Inhibitors
Dihydrotestosterone (DHT), the main pathogenic androgen in AGA, is produced by the conversion of testosterone, which is catalyzed by the 5-alfa-reductase (5-AR) isoenzyme family. Finasteride and dutasteride are inhibitors of these enzymes. Finasteride, which is a single receptor 5-AR inhibitor (5-ARI), acts by blocking DHT. Dutasteride, a dual receptor DHT blocker, has a higher potency than its predecessor, finasteride. The androgenic component leading to miniaturization in AGA is mediated by DHT. Conversion of testosterone to DHT is blocked by 5-ARIs, like finasteride and dutasteride, thereby leading to clinical improvement in AGA. There are 3 iso-enzyme forms of 5 alfa-reductase. Finasteride is a single receptor inhibitor (Type 2), while dutasteride is a dual receptor inhibitor (Type 1 and 2) and is more potent than finasteride. 5 alfa-reductase inhibitors are mainly used in male AGA. There is limited evidence in female pattern hair loss (FPHL) and is not licensed for use in women. It is contraindicated in women of childbearing age and pregnancy, because of the risk of feminization of male fetus. In postmenopausal women, 1 mg is not very effective. The higher dose of 5 mg is considered to be effective, but there are limited studies.
The recommended dose of finasteride is 1 mg/day and that of dutasteride is 0.5 mg/day for male AGA. The usual practice is to start finasteride initially for 6–12 months, and in case of lack of response shift to 0.5 mg dutasteride.
The main side effects of finasteride are– gynecomastia, reduced libido. Erectile/ejaculation dysfunction and testicular pain. Mood alterations have also been reported. The persistence of symptoms for months, after stopping finasteride, is referred to as the postfinasteride syndrome. Postfinasteride syndrome is more common in patients with a history of previous psychological issues/sexual dysfunction and hence, finasteride is contraindicated in patients with existing sexual dysfunction and depression.
The use of intralesional dutasteride has been suggested as a possible treatment option for AGA, with the advantage of having less systemic effects.
The use of other antiandrogens/oral estrogens (both topical and systemic) has limited evidence in the treatment of AGA. The use of oral spironolactone also does not have much evidence for use in AGA, however recently a combination of topical spironolactone with minoxidil has been suggested to have a role in the treatment of AGA.
The topical formulation of finasteride is being increasingly studied recently, with the aim of reducing the systemic side effects. Topical finasteride has been tried both as monotherapy and in combination with topical minoxidil. Different strengths have been tried from 0.1% to 0.5% solutions. There are limited studies, but available evidence indicates that systemic absorption is low with these strengths and hence safety profile is good. However, more studies are needed to evaluate the efficacy, either as monotherapy or in combination with other options.
PRP has emerged as a safe and effective option for the treatment of various types of nonscarring alopecia. Dosage, frequency, and preparation methods, however, need to be standardized more effectively for optimum use.
The evidence for the benefit of PRP in AGA has been encouraging over the last few years– and has shown to increase both hair density and thickness, however, there still are some conflicting results due to inconsistent reporting and poorly designed studies. There is a need for better designed randomized control trials, especially low risk-of-bias randomized controlled trials (RCTs) to optimize protocols and to really substantiate the effectiveness of PRP in AGA. Combining PRP, especially using microneedling, with medical treatment, has shown to lead to improved and faster treatment outcomes. PRP has been found to be effective in both male and FPHL. Some studies have suggested that the efficacy of PRP is more in male AGA as compared to females.
Photobiomodulation, also known as low-level laser or light therapy (LLLT), is an emerging modality in the treatment of AGA. The basic premise of photobiomodulation is that the absorption of red or near-infrared light energy can enhance mitochondrial Adenosine Triphosphate (ATP) production, cell signaling, and synthesis of growth factors and can also reduce oxidative stress. In general, these devices are safe and can be effective by themselves or in combination with other medical options. There are two primary types– one using light-emitting diodes (LED) and the other using lasers. The devices are safe for home use. The main concerns are lack of standardization and also limitations of cost. Like in the case of PRP, more well-designed RCTs are required to substantiate the efficacy of LLLTs in AGA. The large number of devices available in the market is a concern as it can lead to a lack of clarity and confusion among the consumers. The recommendation is to not use LLLT for a period beyond 6 months. Important parameters which can affect the improvement are fluence, duration of the sessions, and the light pulsing. TRICHOBIOLIGHT a combination of mesotherapy with a subsequent photo biostimulation session with LED light (630 nm) has shown to give good cosmetic results.
The other laser which has been used in the treatment of AGA includes the fractional Erbium-Yag laser which has been shown to increase both hair density and thickness in both males and females. It has been shown to increase follicular units, anagen hair count, and also the anagen: Telogen ratio.
There are isolated reports of nonablative/fractional radiofrequency devices being used effectively to improve hair counts in AGA.
Combinations, in general, are more effective as compared to monotherapy. Although there are limited studies, combing finasteride with 5% minoxidil in male AGA has shown to lead to better outcomes as compared to monotherapy.
Prosthesis, Wigs, Camouflage
Camouflage options for patients with alopecia, in general, include– partial or full wigs, hair extensions, concealing powders/sprays, and medical tattooing.
Topical hair fibers are basically colored fibers of rayon, cotton, wool, or rice keratin that adheres to the negatively charged terminal and vellus hair fibers on the scalp. It needs existing hairs to bind, so does not work well on a completely bald scalp. Common brands used include Toppik®, Caboki® and Boldify®. The fibers are available in different colors.
Wigs can be either natural or synthetic. Natural wigs use natural human hair and therefore have the advantage of a natural appearance, and can be styled as such (including coloring and perming). The main disadvantages are that they are more expensive.
Synthetic hair wigs are less expensive and easier to maintain but tend to have a more unnatural appearance and need to be frequently replaced. The foundation of the wig can be of various types– wefted (base of synthetic hairs), net (mesh-like base made of natural hairs), or custom-made vacuum bases (using a mold made of materials like silicone or polyurethane). Integration wigs use the concept of pulling existing hairs through perforations in the foundation of the wig to combine the effect of the original and the wig hair.
Hair extensions are made of either natural or synthetic fibers, attached to existing hairs. They are usually used for partial or patch alopecia for improving cosmesis. Hair extensions have been known to be associated with traction alopecia.
The use of wigs has been shown to improve psychosocial parameters in both male and female patients with AGA. Since the late 90s, biocompatible polyamide fibers have been used for implantation in patients with AGA Biofibre® is a sterile, inert polyamide fiber used for implantation. These fibers can be washed and dried like normal hair. However, other procedures like bleaching or permanent waves cannot be done. The procedure can be combined with hair transplantation procedures to improve cosmetic outcomes.
Other medical treatment options used for AGA as of now have limited evidence and at most can be recommended as adjuvants. However, even for use as an adjuvant, safety parameters need to be evaluated further for many of them. Common groups based on mechanism of action include:
- DHT inhibition– beta-sitosterol, saw palmetto, Biochanin A, polysorbate 60, serenoa repens, curcuma aeruginosa, pumpkin seed extract, clascoterone cream 1%
- Anti-inflammatory-ketoconazole, zinc pyrithione
- Enhanced perifollicular vascularization– Niacin derivatives, rosemary, prostaglandin analogs like latanoprost
- Anti-apoptotic action– green tea extract
- Improved nutrition of hair follicles– peptide/amino acids, vitamins, and minerals
- Unclear mechanism– Electromagnetic field, botulinum toxin, tretinoin, red ginseng, millet seed extracts, grapeseed extract, melatonin, hibiscus extracts, acupuncture, aromatherapy, psychotherapy, carboxytherapy, mesotherapy, caffeine, garlic gel, capsaicin.
Newer Options in the Pipeline
Newer insights into the pathogenesis of AGA could open up the development on new medical treatment options.
The role of prostaglandins in AGA has garnered more interest in the recent past. Studies have shown that PGD2 and PGI2 levels are increased in the bald scalp, while levels of PGE2 and PGF2 alpha are reduced. This could suggest a possible role for specific drugs acting at the level of different prostaglandin receptors. Cetirizine which is known to decrease PGD2 production has been explored recently in the treatment of AGA.
Zyxin (ZYX, actin-interacting protein involved in cell adhesion and migration, has been recently proposed to play a role in stem cell properties of the dermal papilla and AGA. Zyxin expression is increased in animal models of AGA and hence, hypothetically Zyxin could emerge as a potential therapeutic target in the treatment of AGA.
The use of stems cells – autologous hair follicle stem cells (self-renewing dermal stem cells) and adipose-derived stem cells in being increasingly explored in AGA. The adipose tissue surrounding hair follicles is considered to be an important role in prolonging anagen. Adipocytes progenitor cells, surrounding the hair follicles are shown to increase during the transition from the telogen to the anagen phase and adipose-derived stem cells can stimulate hair follicle cells through peroxisome proliferator-activated receptors. The autologous whole fat injection has been shown to stimulate hair growth in resistant AGA.
Cold atmospheric (physical) plasma (CAP) is a partly ionized gas which has been used in various skin conditions like chronic ulcers. CAP has recently been used in AGA, with some clinical improvement.
Among the miscellaneous products, three which are being increasingly used in the recent past, include Capixyl (a biomimetic peptide), Procapil (a combination of oleanolic acid, apigenin, and glycine-histidine-lysine peptides), and Redensyl (a combination of multiple ingredients including botanicals, like Dihydroquercetin Glucoside and Epigallocatechin Gallate glucoside). However, as of now, the available evidence for these products, is relatively poor, although there are isolated controlled trials for the same.
As of now approved medical treatment options for AGA/FPHL include topical minoxidil, oral finasteride, and LLLT. For male pattern hair loss, minoxidil 5% applied twice daily is the first-line treatment. Evaluation should be done after 6 months (ideally up to 12 months) and in case of lack of effect, oral finasteride 1 mg can be added. For finasteride too, evaluation should be done after 6–12 months. For cases not responding to finasteride, even after 12 months, it would be prudent to consider hair transplant surgery. For FPHL, 5% minoxidil applied once daily or 2% applied twice daily should be the first line. For females with underlying hormonal conditions like Polycystic ovarian syndrome, other options like spironolactone can be considered. Other options like LLLT, and PRP have a paucity of evidence, but considering that they are safe, they can be added as adjuvants to the primary treatment. Combination regimens, in general, tend to work better as compared to monotherapy. The use of prosthesis, wigs, or camouflage, in addition to medical treatment, can help in improving psychological factors related to AGA.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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