Androgenetic alopecia (AGA), also known as male and female pattern hair loss (FPHL), is a highly prevalent disorder that affects members of every society. There is evidence to suggest that AGA has been a health concern dating back to ancient times. According to Herodotus, one of the oldest medical specialties was the Egyptian ‘physician of the head’ who specialized in diseases of the scalp 1. In fact, Egyptian papyruses dating as early as 4000 BC list many remedies to treat hair loss; for example, a mixture of fats from hippopotamus, crocodile, tomcat, snake, ibex, and porcupine hair was boiled in water and applied to the scalp for 4 days 1. Every year, millions of dollars are spent on hair restoration products; yet, a true cure remains elusive. In this paper, we review the epidemiology, pathophysiology, and treatment of AGA.
Although the precise prevalence of AGA is unknown and difficult to establish, it has been estimated to affect around 50% of White men by the age of 50 and as many as 90% in their lifetime. It is considered to affect about 50% of White women in their lifetime 2–4. Although prevalence increases with age in all populations, thinning can begin as early as puberty 5.
The prevalence of AGA appears to vary between different races and ethnicities, although the methodology differs in the available studies, making it difficult to compare. Khumalo et al. 6 found that in South African adults, the prevalence of AGA was 14.6% in men and 3.5% in women, although it was a younger population than in other studies. In Asian populations, several studies have been carried out showing generally lower rates than Whites with an all-age prevalence around 20% in men and 5–6% in women 7–9. However, in a community study in Singapore with a high response rate, the overall prevalence was 63%, with 100% of those over 80 reporting some form of AGA 10. Despite the variation, AGA is highly prevalent and some consider it a normal physiologic variant 2.
In AGA, thick terminal hairs are gradually replaced with miniaturized, vellus hairs in well-recognized patterns. In men, classic pattern hair loss begins above the temples and the vertex of the scalp. As it progresses, a rim of hair at the sides and the rear of the head remains, an appearance referred to as a ‘Hippocratic wreath’; male AGA very rarely progresses to complete baldness. The most commonly used classification is the Norwood–Hamilton scale, which grades male AGA from type I (prepubertal scalp with terminal hair growth on the forehead and all over the scalp) to type VIII (confluence of the balding areas with hair remaining only around the back and sides of the head) 11,12. Types IIIa, IVa, and Va are characterized by prominent gradual receding of the middle portion of the frontal hairline; type IIIv is marked by hair loss mainly on the scalp vertex, with frontotemporal recession that never exceeds that of type III.
Women generally present with a different pattern than men, although overlapping characteristics do exist. There is typically diffuse thinning without hairline recession, rarely leading to complete hair loss 13. In the Ludwig 14 pattern, women have diffuse reduction in hair density that is most prominent in the frontal scalp and crown, which leads to the appearance of a widened frontal part. The Ludwig scale is used to grade the severity of FPHL and ranges from I (mild thinning over the crown and frontal scalp, sparing the frontal hairline) to III (severe thinning and hair loss over the crown and frontal scalp with a rim of frontal hair remaining). There is also the Sinclair scale, which is a modified version of the Ludwig scale, using a five-point visual analogue scale for hair loss, as well as the Savin scale 15,16.
There are several other patterns that have been described in women. The Hamilton pattern is similar to that seen in male AGA with frontal hairline recession and crown alopecia; this pattern has been seen in 13% of premenopausal women with FPHL and 37% postmenopausal women 17. The ‘Christmas tree’ pattern described by Olsen 18 shows increased hair loss at the scalp midline with frontal accentuation.
In AGA, there is shortening of the anagen phase, which shifts the anagen : telogen ratio from about 12 : 1 in a nonbalding scalp to less than 5 : 1 in AGA 19. The shortened anagen phase combined with a reduction in cell number and the overall size of the dermal papilla leads to follicular miniaturization or the production of shorter, thinner hair shafts 20. As additional follicles undergo miniaturization, hair coverage of the scalp progressively decreases. A combination of hormonal and genetic factors is likely responsible for these changes.
Androgens are the primary hormones involved in the pathogenesis of male AGA, but have not consistently been associated with FPHL. In men, the marked increase in androgen production during puberty correlates with growth of facial hair, but suppression at the temples and scalp vertex, which has been referred to as the ‘androgen paradox’ 21. Early observations showed that males castrated before puberty did not develop AGA; later studies showed that those who had a family history developed pattern hair loss after being treated with testosterone 22. Although the hair loss stopped after withdrawal of testosterone, it did not reverse. Total plasma testosterone concentrations are similar in balding men compared with nonbalding men, but elevated levels of the active unbound fraction of testosterone have been detected in balding men 23.
In women, the role of androgens has been unclear; therefore, in 2002, the Dermatological Consortium on Women’s Health proposed that the term ‘female pattern hair loss’ should be used instead of AGA 24. Still, women with features of hyperandrogenism, such as acne and hirsutism, may show thinning hair, sometimes in a male pattern, leading some to use the term ‘androgenic alopecia’ for these cases. Several studies have shown lower circulating sex hormone-binding globulin (SHBG) as well as a lower estradiol to testosterone ratio in women with FPHL 25–27. However, a young woman who lacked circulating androgens as well as patients with androgen insensitivity syndrome have been reported to develop hair loss in a female pattern 28. Estradiol also plays an unclear role as it has been implicated in promoting both hair growth and hair loss 29,30. However, recent genetic studies, which will be reviewed below, have found associations of FPHL with androgen-related genes, similar to those found in men, perhaps allowing these to be considered as the same disease once more 31,32.
There is abundant evidence that dihydrotestosterone (DHT) plays a central role in the induction and promotion of male AGA. DHT is a potent metabolite of testosterone and comparatively has a five-fold greater affinity for the androgen receptor (AR) 33. The conversion of testosterone into DHT is mediated by the enzyme 5α-reductase, which exists in two isoforms in scalp hair follicles. The type II isoform plays a more predominant role in DHT production in the scalp relative to the type I isoform. Men with AGA have increased expression of type II 5α-reductase in dermal papilla cells and a higher concentration of DHT 34. Furthermore, AGA is absent in patients with 5α-reductase type II deficiency. Young men with AGA have higher levels of cellular 5α-reductase and a higher quantity of both DHT and ARs in the balding scalp relative to nonbalding controls.
There are a number of factors involved in mediating these changes in androgens and ARs in male AGA. The AR coactivator Hic-5/ARA55 is highly expressed in dermal papilla cells from androgen-sensitive sites, and loss of Hic-5/ARA55 expression can reduce AR transactivation by over 64% 35. In-vitro studies have also shown that androgen-inducible transforming growth factor-β1 is involved in epithelial cell growth suppression 36. Other androgen-induced mediators, which include transforming growth factor-β2, dickkopf1 (DKK-1), and interleukin 6, have also been reported to suppress follicular epithelial cell growth 21. Androgens may also inhibit the Wnt-signaling pathway, thereby inhibiting normal hair follicle differentiation 37.
The heritability of AGA has been well documented. In one study of ∼500 monozygotic male twins and 400 dizygotic male twins between the ages of 25 and 36 years, 80% of the variance in total hair loss was attributed to genetic effects 3. Although it was once believed that hair loss had autosomal dominant inheritance in men and autosomal recessive in women, more recent evidence suggests complex polygenic inheritance with variable penetrance.
Overall, candidate gene and genome-wide association studies have identified at least eight chromosomal loci where a strong association exists between AGA and single-nucleotide polymorphisms 38–42. Seven genome-wide association studies have been carried out to date in male White populations in Australia, Iceland, Great Britain, Germany, and Switzerland 43,44. A recent meta-analysis was carried out of these studies, evaluating a total of 12 806 individuals of European ancestry 42. The strongest loci are at 20p11 and Xq11–12, the latter of which represents the AR. Table 1 summarizes some of the genetic susceptibility loci that have been identified thus far.
There has been considerable focus on the gene encoding the AR with the theory that elevated AR expression underlies the pathogenesis of AGA 47. AR gene polymorphisms have correlated most consistently with AGA susceptibility in men 41,48–52, with some also implicated in FPHL 31,51. These polymorphisms, however, are of uncertain relevance. For example, although the StuI polymorphism found in exon 1 of AR is present in 98% of young men and 92% of old men with AGA, 77% of men without AGA also have this polymorphism, suggesting that this variance is necessary, but not sufficient to produce AGA 49. The StuI polymorphism has also not been shown to produce any change in the function or the product of the AR gene. Nonetheless, there is strong evidence that DNA variation responsible for AGA may be located near the AR locus in regions that may exert a regulatory effect on the AR, such as EDA2R, which is expressed in the hair bulb and in differentiating hair matrix cells during embryonic life, the first weeks of life, and then again after the 17th year of life 52. It has been estimated that variation of the AR gene accounts for about 40% of the heritability of AGA in men 41.
In women, the CAG repeat length in exon 1 of the AR gene has been associated with AGA, acne, and hirsutism in those with hyperandrogenism, and has been associated with better response to antiandrogenic therapies 51. More recently, a single-nucleotide polymorphism of EDA2R was associated with FPHL in women from the UK, especially those with early-onset hair loss, but not in those from Germany 31.
Looking beyond the AR gene, there have been some surprising results. For example, mutations in the 5α-reductase genes have not been found to be associated with either male or female AGA 47,53,54. Recently, polymorphisms of the aromatase gene (CYP19A1) and estrogen receptor β (ESR2) were found to be associated with FPHL and suggest a role for estrogens in this condition 30,55. There have been associations between AGA and other comorbidities, such as cardiovascular disease, hypertension, dyslipidemia, obesity, metabolic syndrome, and polycystic ovary syndrome, which may help identify other candidate genes 56–60. Interestingly, the recent meta-analysis of genome-wide association studies identified risk alleles with susceptibility loci common to early AGA, Parkinson’s disease, and decreased fertility 42.
Despite the progress made in better understanding the genetics of AGA, there is still much that is unknown about the heritable risk. Variation in different populations, phenotypic diversity, and variable expression of the X chromosome in women are all limiting factors in understanding the role of genetics in AGA. The identification of additional gene candidates may provide new insights into the pathophysiology of AGA and allow for more targeted therapies to be developed.
Other possible factors
A recent study analyzed suggestive loci from the meta-analysis carried out by Li et al. 42, and identified a strongly associated locus at 2q35 related to Wnt signaling, suggesting that this could be a critical biochemical pathway involved in AGA 45. This pathway is involved in regulating the telogen-to-anagen transition and maintaining anagen-phase characteristics in dermal papilla cells through the β-catenin pathway 61–64. These findings show that impaired Wnt signaling may lead to deregulation of the normal hair cycle, resulting in delay of the telogen-to-anagen transition and shortening of the anagen phase.
Garza et al. 65 used global gene expression to define differentially expressed genes in balding versus nonbalding scalp in men undergoing hair transplantation and found elevated levels of prostaglandin D2 synthase at mRNA and protein levels and low levels of prostaglandin E2 (PGE2) in bald scalp. They also showed that both prostaglandin D2 and its nonenzymatic metabolite, 15-deoxy-D12,14-prostaglandin J2, inhibit hair growth in both mouse and human hair follicles. Prostaglandins have a multitude of functions in the human body, often opposing each other, and play a large role in mediating inflammation and possibly immunity. In mice, prostaglandin D2 synthase is highly testosterone responsive and prostaglandin D2 is highly expressed in male genitalia. Furthermore, minoxidil has been shown to increase the production of PGE2, which has been shown to enhance hair growth in mice, and prostaglandin analogues, specifically PGF2α, have been found to increase hair growth in eyelashes and on scalp 66,67. More recently, however, Heilmann et al.46 found no evidence of a genetic basis for prostaglandin involvement in the etiology of AGA. More research is needed to elucidate the role of prostaglandins in AGA.
Associations and comorbidities
AGA is often considered solely a cosmetic problem, but both recent and older evidence show potential comorbid conditions. Gatherwright et al.68 compared 98 monozygotic female twins to identify possible environmental factors that may contribute toward AGA. Overall, increased stress, smoking, multiparity, and a history of hypertension or cancer were associated with increased hair thinning.
The association of FPHL in women with polycystic ovary syndrome provides a potential link with insulin resistance, obesity, and metabolic syndrome 69. In men, an association has similarly been identified in those with early AGA 70. Insulin can increase testosterone and reduce the level of SHBG, both of which have been associated with early AGA in men and women. A study of 12 men on finasteride for 1 year found significantly lower HgA1C levels and markers of insulin resistance after treatment 71. Individuals with metabolic syndrome and hyperglycemia also have lower levels of insulin-like growth factor 1, which is mitogenic in dermal papilla cells and promotes elongation of hair follicles 72,73.
Multiple studies have suggested an association between cardiovascular disease and cardiovascular risk factors and early AGA in both men and women 74,75. The independent association of coronary artery disease and male AGA is particularly strong in early-onset hair loss (men <30 years of age) and Norwood–Hamilton grade III or higher or vertex type 76–77. Various cardiovascular risk factors have been evaluated including metabolic syndrome, carotid atheromatosis, family history of cardiovascular disease, and dyslipidemia, but there have been mixed results 74,78.
A case–control study by Arias-Santiago et al.78 examined 300 patients with early AGA for specific cardiovascular risk factors. Compared with nonalopecic controls, men and women with AGA had significantly higher triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels; women with FPHL also had lower high-density lipoprotein cholesterol (HDL-C) values. Sadighha et al.79 also found that men with AGA have significantly higher levels of triglyceride and total cholesterol/HDL-C ratio and lower HDL-C values than controls. One population study examining men found that the odds ratio for coronary vascularization was 3.57 (95% CI 1.19–10.72) in men with early AGA versus men with normal hair or late AGA 80.
Benign prostatic hyperplasia and prostate cancer
Given the critical role of DHT in the pathophysiology of benign prostatic hyperplasia and prostate cancer, it is not surprising that there has been a correlation between these medical conditions and AGA. Arias-Santiago et al.81 found that early-onset AGA was associated with early signs of benign prostatic hyperplasia in asymptomatic patients. There have been mixed results on the association of AGA with prostate cancer, with most showing no association 82. Two studies showed a decreased relative risk for prostate cancer in patients with early-onset AGA, whereas five studies have shown an increased risk 83–85. In some of these studies, treatment of AGA was not considered, although that could affect the rate of prostate cancer 83.
A large number of treatment modalities currently exist in the market, including topical products, supplements, low-level laser therapy, and hair transplantation, but the results are mixed and, for the most part, have not been studied rigorously. Currently, the only Food and Drug Administration (FDA)-approved medications are oral finasteride and topical minoxidil.
Minoxidil is a vasodilator that was initially used as an oral antihypertensive agent that was found to cause hypertrichosis. Although systemic minoxidil has been largely replaced with other antihypertensives, topical minoxidil has become a first-line treatment for AGA. Its mechanism for increasing hair growth has not been fully elucidated; however, it may lead to vasodilation, increase angiogenesis, enhance cell proliferation and DNA synthesis, open potassium channels, or mediate immunity 86–88. Studies show that minoxidil shortens telogen, extends anagen, and increases the size of shrinking follicles 89. In men, a study by Olsen et al.90 found that 5% minoxidil increased both absolute hair count and hair weight in men compared with placebo and less concentrated formulations.
In women, minoxidil has also been shown to be an effective treatment. Treatment with either 2% minoxidil or 5% minoxidil for 48 weeks showed a statistically significant improvement in scalp coverage on the basis of physician assessment of hair growth; however, the patient assessment in the 2% minoxidil group did not show treatment superiority over placebo, whereas those in the 5% group did 91. A randomized, single-blind trial comparing twice-daily application of a 2% minoxidil solution versus daily 5% minoxidil foam found nonsignificant better efficacy with the foam, but significantly preferred texture and lower rates of side effects, such as pruritus and dandruff 92. At the time of this writing, only 2% topical minoxidil is FDA approved for FPHL.
Minoxidil has few adverse effects, the most common of which is pruritus at the site of application or, less commonly, contact dermatitis 93. Topical minoxidil has not been shown to have any cardiovascular effects, such as hypotension 94. Women may also experience facial hypertrichosis with the use of minoxidil, and the medication is classified as pregnancy category C 95.
The two medications in this class, finasteride and dutasteride, work by blocking the conversion of testosterone into DHT through competitive inhibition of 5α-reductase 96. This mechanism of action also helps increase the hair shaft thickness for better scalp coverage 97. The use of finasteride can decrease DHT levels by 60% in both the serum and the scalp 98. One randomized trial comparing finasteride with minoxidil found that 52% of minoxidil patients showed hair growth compared with 80% of finasteride users 99. A meta-analysis of 12 randomized placebo-controlled trials examining male AGA determined that there was moderate-quality evidence to support the use of finasteride 100. Across 3927 patients, there was an average increase in hair count of 9.4% after 6 months of therapy (95% CI 7.95–10.90). The difference between the placebo and the finasteride groups further increased after 12 months of therapy, both because of increased hair count in the finasteride group and hair loss in the placebo group 98.
There are several factors that may influence response to finasteride treatment. Patient response varies on the basis of age; younger patients, particularly those younger than 26 years of age, show a relatively greater response to treatment 101. In addition, high serum levels of DHT have been associated with a favorable response, but there are no current recommendations to check the levels before starting treatment 99. It may take up to a year to establish benefit from finasteride and, once medication is withdrawn, hair loss resumes and previous benefits are lost in 6–9 months 102. Topical finasteride has been used outside of the USA, with good results 103,104.
It is documented that finasteride can exert adverse effects on sexual function despite little evidence to show any direct effect on testosterone or ARs 94. Finasteride can cause erectile dysfunction with a number needed to harm of 82, with other studies showing similar or higher frequencies of sexual dysfunction, including decreased libido, difficulty reaching orgasm, and reduced sexual arousal 98. One set of interviews of 71 men found that sexual dysfunction associated with finasteride in some cases persisted for at least 3 months after the cessation of treatment 105. The mean duration of sexual dysfunction was 40 months and follow-up studies found that 20% still had sexual dysfunction after 6 years 106. Baseline sexual function was not determined in these cases, and in the placebo-controlled trials, the treatment groups showed a slightly increased rate of sexual dysfunction that mostly resolved without discontinuing the medication 107.
The results of finasteride in FPHL have been mixed. A placebo-controlled randomized trial by Price et al.108 examining postmenopausal women younger than 59 years of age found no difference between placebo and 1 mg daily use of finasteride. However, an uncontrolled study by Yeon et al.109 showed a moderate improvement in hair growth with a higher dose of 5 mg daily in women between 21 and 69 years of age. In women taking oral contraceptives, 62% reported that the concurrent use of finasteride 2.5 mg on a daily basis resulted in improved scalp hair coverage 110. Nonetheless, it is classified as pregnancy category X and women of childbearing age must use reliable contraception while on treatment.
Another potential risk is that of breast cancer. In men, the incidence is one in 100 000 person-years 111. At least 50 cases of male breast cancer in patients on finasteride have been reported in the literature since 2009, but review of the UK adverse drug reaction profile found 75 cases. These patients were on 5 mg finasteride daily. Fewer than 10 cases have been reported at 1 mg daily. Four cases have been reported in women, but it is unclear how many women have actually been treated with finasteride. Overall, it is estimated that there may be a 100–200-fold increased risk of male breast cancer, and although this still comprises a very low absolute risk, appropriate counseling may be indicated, especially in those patients with a strong family history of breast cancer 109.
Like finasteride, dutasteride inhibits the 5α-reductase enzyme, but has a three-fold greater affinity for the type 2 isoform and is 100 times more potent at inhibiting type 1 112. It reduces DHT by 94% compared with the 60–70% reduction seen with finasteride 113. Trials have shown improved hair growth in men on 0.5 mg/day 114. A single case report showed the efficacy of dutasteride in a 46-year-old woman after 6–9 months of treatment 115. A study evaluating mesotherapy with a dutasteride-containing preparation for FPHL found that 12 weeks of treatment resulted in greater scalp hair coverage on the basis of clinical and patient assessments 116.
Dutasteride is not without its side effects, including increased levels with CYP3A4 inhibitors and inhibition of spermatogenesis with a longer half-life than finasteride 117. It is currently not FDA approved for the treatment of AGA.
The antiandrogens are another class of therapies that may be beneficial for FPHL, particularly those with signs of hyperandrogenism. Whereas oral contraceptives tend to have minimal effect on hair loss, they can help by increasing SHBG and, thereby, reducing testosterone bioavailability. Spironolactone and cyproterone acetate competitively inhibit the AR and reduce androgen production 118. When spironolactone or cyproterone acetate was used for an average of 16 months of therapy, ∼44% of women in both groups had no hair loss progression and another 44% experienced some hair regrowth 119. Other studies show that cyproterone acetate reduces hair loss progression in women, but no significant hair regrowth has been documented 120,121. In a study comparing cyproterone acetate and 2% minoxidil, patient estimation of hair loss on a scale of 1–100 mm resulted in a statistically significant reduction of −29±33 mm for the cyproterone acetate group and of −9±17 mm for the minoxidil group 119. Cyproterone acetate treatment was particularly more effective than minoxidil among women who showed clinical signs of hyperandrogenism.
Other antiandrogens that have been tested include flutamide and topical ketoconazole. A prospective cohort study found that flutamide used at a low dose (62.5 mg/day) resulted in marked improvement in alopecia scores, with the maximum drug effect occurring at 2 years following the initiation of treatment 122. Ketoconazole, an antifungal medication with antiandrogenic properties, has been postulated to work by reducing microbial-induced inflammation that may affect hair follicle growth 123. Men treated with 2% ketoconazole shampoo had results comparable to those with the use of a 2% minoxidil solution 121. The addition of 2% ketoconazole shampoo to finasteride has also been shown to improve the efficacy of treatment 124.
Like finasteride, there is a question of the risk of breast cancer with antiandrogens. For spironolactone, the FDA has a black-box warning of increased occurrence of breast cancer and other solid organ tumors in mice, and case reports have reported occurrence of breast cancer in women treated with spironolactone. Nonetheless, a recent study in the UK evaluated 1.3 million women over the age of 55 years, finding that 28 000 women who had been given at least two prescriptions for spironolactone had no significant increase in incidence of breast cancer over a mean follow up of 4 years as compared with 55 000 matched controls 125.
The PGF2α analogues latanoprost and bimatoprost are more recent therapies that have potential in the treatment of AGA. These medications are used mostly for the treatment of glaucoma; however, there was a noted side effect of increased eyelash thickness and length. Smith et al.66 showed increased eyelash prominence on a global assessment scale in patients treated with bimatoprost 0.03% versus placebo. A randomized trial involving treatment of 16 men with mild AGA and latanoprost 0.1% resulted in increased hair density on the latanoprost-treated site versus placebo after 24 weeks of treatment 67. Bimatoprost is currently under investigation for the treatment of AGA.
Low-level laser therapy
Low-level laser therapy has been increasing in popularity as a treatment for AGA and many devices are available for use at home or in a clinical setting. The biologic mechanism by which specific light wavelengths increase hair growth is not known, but may work by upregulation of PGE2, local inflammatory mediator release leading to follicular vascularization, direct stimulation of dormant follicles, and suppression of inhibitory cells that prevent progression of follicular stem cells to progenitor cells 126–129. The recommended course of treatment is typically 6–12 months 130. In 2007, the HairMax Laser Comb (Lexington International, LLC, Boca Raton, Florida, USA) received a 510(k) clearance from the FDA, classifying it as a moderate-risk medical device. This device uses low-level light at a wavelength of 655 nm that may work by stimulating the proliferation of hair cells 131,132. One study found that men treated with the HairMax Laser Comb three times a day for 26 weeks had increased hair density compared with a control group using a sham device 129. The study also found increased patient satisfaction following treatment, but failed to show a significant difference in the investigator subjective global assessments 129. One study involving seven patients treated with a laser helmet over a period of 3–6 months failed to show statistical significance 133. Various other modalities of low-level laser therapy are being investigated 134. Clinical trials and research to explain the potential mechanism of action are still needed.
Hair transplantation involves the relocation of hair from androgen-resistant areas to affected areas over the vertex and frontal scalp. Typically, hair is harvested from the occipital scalp in follicular units, which consist of up to four follicles that can be harvested, separated, and replanted in a natural pattern 135. This method, known as follicular unit transplantation, is now the most common technique used in hair transplantation; however, more recent specialized techniques have been created using follicular unit extraction to minimize the risk of scarring during harvesting. Hair transplantation costs from $5000 to $20 000 per session and the success and esthetics of this method are highly dependent on the skill of the technician.
Autologous platelet-rich plasma (PRP) contains highly concentrated platelets, which release up to 20 various growth factors, proteins, and chemokines, and has been used in such areas as wound healing and plastic surgery 136–139. PRP is believed to work in part by upregulating pathways involved in the growth of dermal papilla cells that increase stimulating mediators, such as fibroblast growth factor 7 and β-catenin 140,141. The use of PRP has been shown to increase the yield of follicular units when used in hair transplantation 142.
Stem cell research is a promising area for the treatment of AGA, but is still in the early phases. Hair follicle stem cells are maintained in the scalp of men with AGA, but hair follicle progenitor cells were found to be markedly decreased 128. There is also evidence that as the hairs miniaturize in AGA, they lose contact with the arrector pili muscle, which may account for the low likelihood for regrowth of hair 143. This may or may not have any relationship with stem cells. In-vitro studies have shown that dermal papilla cells and dermal sheath ‘cup’ cells placed proximal to interfollicular keratinocytes were capable of hair follicle induction 144. Furthermore, culture-expanded mesenchymal stem cells have been used to produce dermal papilla-like tissues to induce hair follicle growth in athymic mice. The availability of stem cell treatments for humans will likely take many more years and require more elucidation of the basic pathophysiology of AGA.
Camouflage and other treatments
Camouflage techniques with various over-the-counter products are also very viable options for patients. These may include sprays or keratin fibers, which can be applied to the hair and scalp to create a fuller appearance. Realistic-appearing hairpieces and wigs are also available.
There are a large number of over-the-counter supplements, which are not well regulated and may or may not help hair growth. These include, but are not limited to, biotin, saw palmetto, horsetail extract, and marine extracts, as well as iron, vitamin A, and vitamin D. Although some of these may play an important role in hair growth, the amounts needed and the particular formulations have not been studied rigorously.
AGA remains an emotionally distressing disorder despite attempts at finding remedies dating back to ancient civilizations. Multiple studies have begun to elucidate the underlying pathogenesis and genetic susceptibility of AGA, and the association of serious medical diseases, such as increased risk of cardiovascular disease, emphasizes the importance of medical screening in these patients. Although there are a variety of treatments available for AGA, few have been FDA approved, given the small number of rigorous studies carried out and limitations of efficacy and cost. A better understanding of the genetic factors involved in AGA as well as continued research into newer therapies, including cell-based therapies, will hopefully lead to more efficacious treatment and improved outcomes in patients with AGA.
Conflicts of interest
There are no conflicts of interest.
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