Androgenetic Alopecia: Therapy Update (2024)

Table 1

Summary of treatments for androgenetic alopecia

QD daily, BID twice daily, FUT follicular unit transplantation, FUE follicular unit extraction, M male, F female, B both

Topical Minoxidil

First introduced as an antihypertensive medication in the 1970s, minoxidil is now used worldwide for various hair loss conditions. It is the first FDA-approved drug for AGA and is used off-label for many other hair loss conditions, such as central centrifugal cicatricial alopecia, alopecia areata (AA), and TE, among others. Minoxidil is converted to its active metabolite, minoxidil sulfate, and functions as a potent arteriolar vasodilator that activates potassium channels on the smooth muscles of the peripheral artery, inducing cell proliferation. Furthermore, minoxidil was found to increase vascular endothelial growth factor (VEGF) in dermal papilla cells in a dose-dependent fashion, as well as stimulate prostaglandin E2 production, leading to an increase in the duration of the anagen phase [11].

Minoxidil is typically dosed at 2% and 5% minoxidil solution, with 1mL applied twice daily for patients over the age of 18years. The 5% solution is preferred in men. Patients should be assessed after 6months. Studies have found that both the 2% and 5% formulations have shown a significant difference in hair growth versus placebo at 6months and 1 and 5years, described below. In men, the 5% formulation is significantly more effective than the 2% solution, whereas in women, both 2% and 5% showed promising improvements in FPHL [12, 13]. Concentrations higher than 5% have shown improvement in efficacy but have also been found to increase propensity for local irritation [14]. Side effects include contact dermatitis, headaches, and hypertrichosis. Local cutaneous side effects are more common with higher percent formulations of minoxidil solution, likely due to higher propylene glycol content. Short-term telogen shedding can be seen in the first 8weeks of therapy [15]. Overall, topical minoxidil is relatively inexpensive in the USA, costing patients around $12USD for a 60mL bottle [16].

Topical Finasteride

Finasteride is a member of a class of drugs known as 5-alpha-reductase inhibitors. These drugs block the enzyme 5-alpha-reductase, thus blocking the conversion of testosterone to its active form dihydrotestosterone (DHT). Finasteride is a type II 5-alpha-reductase inhibitor and dutasteride blocks both type I and type II. Given that higher levels of DHT are associated with AGA, it follows that blocking DHT would improve the condition. The promising effects of topical finasteride as treatment for hair regrowth were first published by Mazzarella etal. in 1997 in a placebo-controlled trial [17].

Topical finasteride is typically given as 0.25% finasteride spray, or 1% topical finasteride gel applied twice daily to the scalp. A recent phase III, randomized, controlled clinical trial of 458 patients found that topical 0.25% finasteride significantly improves hair count compared with placebo in patients with MPHL despite maintaining relatively stable serum DHT concentrations. Furthermore, it was found to be well tolerated, particularly in comparison with its oral formulation [18]. Although the use of topical 0.5% finasteride combined with 2% minoxidil solution was found to be effective in FPHL, the use of topical finasteride alone is not very effective and thus is not used [19]. Scalp pruritus, burning, irritation, contact dermatitis, and erythema may occur. These side effects are rare and localized to the application site. Overall, topical finasteride costs slightly more than minoxidil, costing patients <$30USD per month [16].

Latanoprost

The use of prostaglandin analogs for alopecia came about when eyebrow and eyelash hair growth were observed in glaucoma patients. Prostaglandin F2 (PGF2) and PGE2 cause hair growth and prolong the anagen phase, whereas PGD2 inhibits hair growth [20, 21]. Blume-Peytaavi etal. conducted a randomized control trial using 0.1% latanoprost, a PGF2 analog, in 16 patients with MPHL [22]. After 24weeks, there was significantly increased hair density compared with baseline and placebo-treated areas. A limitation of this study was that only young men with AGA were included in this study; therefore, the results may not be applicable to patients with differing demographics. Further studies would be helpful to evaluate the efficacy of latanoprost in treating AGA.

Oral Finasteride

Finasteride has been FDA-approved for MPHL since 1997. The drug works similarly to topical finasteride by inhibiting 5-alpha-reductase type 2, which blocks the conversion of testosterone to DHT and reduces androgen-mediated follicular miniaturization [23]. Finasteride is available in 1 and 5mg tablets. In patients with MPHL, it is usually prescribed as 1mg once daily. This drug is contraindicated in premenopausal women and is classified as pregnancy category X due to the feminization of male fetuses in several animal studies. It is used off-label to treat FPHL in postmenopausal women at doses of 2.5–5mg once daily [24].

The efficacy of finasteride for AGA has been investigated in several studies. The drug improves hair growth within 1year of treatment, and further improvement up to 10years of treatment [25]. It is more effective at regrowing hair at the vertex scalp compared with the frontal/centroparietal scalp, and its efficacy does not reduce over time. Several studies have shown that patients older than 30years seem to have better hair growth than patients younger than 30years [26, 27]. A randomized control trial (RCT) showed better results with 1mg finasteride than 5% minoxidil foam in 65 male patients with mild to severe AGA [28].

Finasteride 1mg once daily is generally well tolerated and side effects resolve with cessation of the drug [29]. Reported side effects include sexual dysfunction, altered libido, erectile dysfunction, ejacul*tory dysfunction, and gynecomastia. Some patients may have persistent sexual side effects for at least 3months despite cessation of the drug, which may lead to increased rates of depression and suicidal thoughts [30]. In regards to concerns about prostate cancer as a side effect of 5-alpha-reductase inhibitors, a recent meta-analysis showed that finasteride does not increase the risk of developing high-grade prostate cancer [31]. For a 30day supply of finasteride 1mg tablets, the average retail price is $78USD [16].

Oral Dutasteride

Dutasteride is a dual inhibitor of type 1 and type 2 5-alpha-reductase and is a potential alternative to finasteride with reported improved efficacy in treating AGA. It is 100 times more potent at inhibiting type 1 5-alpha-reductase compared with finasteride and three times more potent at inhibiting type 2 [32]. Dutasteride is available in 0.5mg tablets as treatment for AGA.

In two large, randomized control trials, dutasteride was found to improve hair growth within 12–24weeks and 6months, respectively, compared with finasteride [33, 34]. In addition, a recent meta-analysis showed that 0.5mg dutasteride once daily was significantly more efficacious at increasing hair count at 24weeks compared with 1mg finasteride once daily and 0.25/5mg minoxidil once daily [35]. Despite studies showing that dutasteride is more efficacious, finasteride is still the first-line treatment for AGA due to its FDA approval and therefore greater likelihood of being covered by insurance.

Like finasteride, side effects of dutasteride include sexual dysfunction, altered libido, erectile dysfunction, ejacul*tory dysfunction, and gynecomastia [36]. For a 30day supply of dutasteride 0.5mg tablets, the average retail price is $150USD [16].

Oral Minoxidil

Although not FDA approved, low-dose oral minoxidil has recently received more attention for the treatment of AGA. Oral minoxidil is available as a 2.5mg tablet that can be split in half or quarters to achieve the ideal dose based on patient and provider preferences.

A combination of 0.25mg oral minoxidil and 25mg spironolactone has been shown to decrease hair shedding and improve hair density in patients with FPHL [37]. An open-label prospective clinical trial showed that 5mg oral minoxidil once daily significantly improved hair growth in 30 men aged 24–59years [38]. In a retrospective study of 12 women with AGA, hair density improved by 38% and 23% in the frontal and vertex scalp, respectively, after 24weeks of treatment with 0.50mg minoxidil that was increased to 2mg daily at 3months [39]. Ramos etal. compared the efficacy of 1mg oral minoxidil daily with 5% topical minoxidil solution daily and found that oral minoxidil was as effective as the topical form. In addition, oral minoxidil showed better improvement of hair shedding scores [40].

The most common reported adverse effect of oral minoxidil is hypertrichosis. It is more common among patients on higher doses of minoxidil (5mg daily) whereas those on 2.5mg daily had a lower incidence of hypertrichosis [41]. Cardiovascular effects such as hypotension, tachycardia, pericardial effusion, lower limb edema, and electrocardiogram (ECG) changes (tachycardia, preventricular contractions, t-wave changes) are feared complications that make topical minoxidil more favorable. In general, the side effects of oral minoxidil are typically dose dependent and reversible with cessation of the drug [39]. For a 30day supply of minoxidil 2.5mg tablets, the average retail price is $17USD [14].

Janus-Kinase (JAK) inhibitors

JAK inhibitors have shown promise as an effective treatment for AA, especially with the FDA approval of baricitinib in June 2022. The pathogenesis of AA is mediated by interleukin-15 production by hair follicles in response to interferon-gamma secretion. JAK 1/2 and JAK 1/3 signaling in T-cells release more interferon-gamma in response to interleukin-15, creating a positive feedback loop [42]. JAK inhibitors halt this positive feedback loop, leading to hair regrowth. Unfortunately, JAK inhibitors may not be an effective treatment for AGA. Yale etal. reported a case series of four men diagnosed with AA and treated with an oral JAK 1/2 inhibitor for 24–40weeks [43]. They found that these patients experienced notable hair regrowth, except regrowth occurred in an AGA pattern (bitemporal recession). Further studies need to be done to characterize the role of JAK inhibitors in treating AGA.

Oral Spironolactone

Spironolactone is a potassium-sparing diuretic and antiandrogen. It decreases testosterone production by inhibiting 17-alpha hydroxylase and 17, 20 lyase [44]. Its antiandrogen properties make it a great treatment for FPHL but contraindicated in male AGA. The standard dose for FPHL is 12.5–200mg daily.

Sinclair etal. performed a single center before–after open interventional study including 80 women with FPHL between the ages of 12 and 79years receiving 200mg of spironolactone daily for 12months. They found that 44% of these subjects showed improvement in hair regrowth [45]. Furthermore, significant hair regrowth was noted after 6months in a 9-year-old patient with FPHL receiving 100mg of spironolactone daily [46]. In a retrospective study of 79 patients receiving an average dose of 100mg of spironolactone daily, all patients noted stable or improved hair growth [47]. However, patients with a Sinclair Score of 2.5 or higher noted greater improvement. Side effects include postural hypotension, electrolyte imbalances, breast tenderness, and irregular menses [48]. For a 30day supply of spironolactone 25mg tablets, the average retail price is $16USD [16].

Oral Flutamide and Bicalutamide

Flutamide is a potent antiandrogen that inhibits androgen receptors. It is shown to be effective in hyperandrogenic women with FPHL at a dose of 250mg daily [49]. A case report showed that flutamide reversed hair loss in a patient with FPHL who was nonresponsive to spironolactone and topical minoxidil [50]. In a large prospective study including 101 women with FPHL receiving varying doses of flutamide for 4years, there was a significant reduction in alopecia scores compared with baseline. The maximum drug effect occurred after 2years and was maintained for 2years thereafter [51]. Flutamide has a well-known risk of causing elevated liver enzymes, especially at high doses [51], something not seen commonly with another drug in its class, bicalutamide.

Bicalutamide is a novel nonsteroidal, pure antiandrogen medication that has a better safety and tolerability profile than flutamide [52, 53]. In a retrospective study including 17 FPHL patients treated with 50mg bicalutamide daily or every other day for 24weeks, 57% of patients had significant regrowth and 12.5% of patients had a mild elevation of liver enzymes [54].

A retrospective review of 316 women on oral bicalutamide showed that the drug is well tolerated [55]. The most common side effect was a mild elevation in liver enzymes in nine patients that resolved without a dose change in four out of nine of these patients. Two patients previously discontinued flutamide due to the development of colitis but tolerated bicalutamide without issue [55].

For a 30day supply of bicalutamide 50mg tablets, the average retail price is $126USD [16]. For a 30day supply of flutamide 125mg tablets, the average retail price is $31USD [16].

Oral Cyproterone Acetate

Cyproterone is an antiandrogen that blocks gonadotropin-releasing hormones and androgen receptors. It is commonly used for FPHL in Europe, but it is not available in the USA. An RCT of 20 patients receiving 50mcg ethinyl-estradiol and 2mg cyproterone acetate on days 1–14 and an additional 20mg cyproterone acetate on days 5–20 of their menstrual cycle found a significant increase in the number of anagen hairs on the frontal scalp [56]. A 12month randomized control trial comparing 2% topical minoxidil and cyproterone for treatment of FPHL found that cyproterone was more effective in treating women with additional signs of hyperandrogenism, while topical minoxidil was more effective in women without hyperandrogenism [57]. Cyproterone is associated with weight gain, breast tenderness, and decreased libido [58].

Topical Clascoterone

Clascoterone is a novel topical androgen receptor inhibitor. It has shown promising results for use in patients with acne vulgaris [59]. It is thought that the antiandrogenic properties of clascoterone may be helpful in treating AGA.

In a phase I single-center, open label clinical trial, 18 patients with AGA applied topical clascoterone solution 5% twice a day to the affected areas [60]. They found that clascoterone levels in the bloodstream cumulatively increased 4h after application. However, day 28 pre-dose clascoterone concentrations were similar to 12h post-dose concentrations, indicating a steady state. In a phase II exploratory study, clascoterone was more effective than cyproterone acetate or 17-alpha estradiol in increasing hair shaft diameter and hair follicle density [60]. Furthermore, hair growth was higher in patients using clascoterone compared with topical minoxidil.

Clascoterone is generally well tolerated. In a phase II and III acne clinical trial, adverse effects included mild dryness, erythema, and hypertrichosis at the application site [59]. For one tube (60g) of 1% clascoterone, the average retail price is $656USD [16].

Topical Pyrilutamide

Pyrilutamide is another novel topical androgen receptor inhibitor. In a phase II clinical trial by Kintor Pharma, the drug was effective and showed good safety profile in patients with MPHL [61]. Currently, there are phase II and phase III clinical trials in China for FPHL and MPHL patients, respectively. In the USA, there is a phase II trial for MPHL patients.

Intradermal Botulinum Toxin

The use of injectable botulinum A toxin has gained popularity as a treatment for AGA in recent years because of its ability to interfere with the suppressive effect of DHT on the hair follicle. A prospective 24week study of 18 male patients with AGA showed significant improvement at week 24 (p=0.031) [62]. Another RCT found combination therapy of botulinum toxin A injections and oral finasteride and minoxidil to be more effective than treatment with oral finasteride and minoxidil alone [63]. More research has yet to be performed to understand the role of botulinum as treatment for AGA. The average cost per treatment was $466USD per unit of injection in 2020 [16].

Dutasteride Mesotherapy

Injectable dutasteride has gained popularity over the last several years due to limited systemic absorption, and therefore, reduced side effects. A multicenter retrospective study assessed 541 patients that were treated with dutasteride mesotherapy every 3months with at least 6months of follow-up. Response to the therapy was assessed in 16% of patients after 1year, and most reported improvement, with pain being the most frequent side effect (45.5%). This side effect was considered mild by most patients and self-limited [64]. One session costs between $250 and $500USD.

Platelet-Rich Plasma (PRP)

Platelet-rich plasma (PRP) is a more recent treatment modality for AGA that has risen in popularity due to its effectiveness, autologous nature, minimal side effect profile, and nominal responsibility placed on the patient. PRP consists of a preparation of plasma with concentrated platelets, growth factors, and cytokines that aid the body’s inherent capacity to regrow and regenerate. To prepare PRP, 10–30mL of blood are drawn from the patient via venipuncture and centrifuged under a “soft” speed for approximately 10min to separate the blood into various components of red blood cells (RBCs), platelets, and white blood cells (WBCs). Through this process, the normal 94:6 ratio of RBCs to platelets is reversed to achieve a 94:6 ratio of platelets to RBCs [65]. After separation, 4–8mL of the platelet-rich plasma component of the sample are injected into the patient. In some cases, an activator such as calcium, thrombin, and collagen may be added to enhance growth factor secretion [66].

Given that intact hair follicles are needed for treatment success, PRP is more often used on early stage AGA patients. It is not curative and must be continued long term to sustain growth. In a 2018 review of the literature on patients with FPHL and MPHL, PRP demonstrated therapeutic efficacy in 10 out of 12 studies, most of which used a control group as a comparison [66]. A recent 2022 review article found a significant increase in hair density and hair diameter in numerous studies in FPHL and MPHL patients, respectively [67]. A randomized controlled trial in 2020 reported a noted increased hair density in participants treated with PRP, although this difference was not significant when compared with patients treated with saline across 3months [68].

The standardization of PRP preparation is still debated in the literature. While some studies have conducted sessions every 2weeks, others wait a month between sessions or gradually increase the interval between sessions as they progress [69]. Potential side effects include scalp pain, pinpoint bleeding, headache, and burning sensation that typically subside 10–15min after injections. Most patients do not need any topical or oral pain medications to combat these effects and can resume their normal activities. Strenuous activity should be avoided 24h after treatment. Some patients with a history of bleeding disorders, active infection, or autoimmune disease should refrain from using PRP due to increased risks [66]. PRP is relatively expensive, ranging from $500 to $2500USD per treatment, and is not covered by insurance for hair loss [16].

Low-Level Light Therapy (LLLT)

LLLT was first reported in the 1960s when hair regrowth was observed in mice exposed to low-energy lasers (694nm) [68, 69]. Since then, LLLT has been used to treat several types of alopecia. The proposed mechanism is that photons emitted from the LLLT oxidize cytochrome C oxidase, thus activating the electron transport chain and increasing ATP production [70]. Endogenous growth factors and nitric oxide are upregulated, leading to cellular proliferation and vasodilation, respectively [71]. LLLT at 650–900nm at 5mW is generally used for the treatment of AGA [72].

The HairMax LaserComb is a hand-held low-level laser containing one laser module (655nm). Leavitt etal. conducted a RCT involving 110 male patients with AGA. Patients in the treatment group used the HairMax LaserComb three times a week for 15min for a total of 6months. They found that patients in the treatment group showed significant improvement in hair regrowth with no serious adverse effects [73]. In another RCT, 40 subjects with AGA received treatment with a helmet LLLT (630, 650, and 660nm) daily or a sham device for 18min daily. After 24weeks, patients using the LLLT device showed greater hair density and mean hair diameter compared with those on the sham device [74]. LLLT in combination with minoxidil and finasteride showed efficacy in hair regrowth as well [75, 76]. Moreover, a systematic review found that phototherapies containing red and infrared light may be more effective at treating AGA [77].

LLLT is generally well tolerated. Reported side effects include scalp tenderness, paresthesia, and mild urticaria [78]. HairMax LaserComb costs range from $200 to $1900USD [16].

Exosomes

Mesenchymal stem cells (MSCs) are stromal cells that can self-renew and differentiate into various types of specialized cells. The concept of MSC-derived exosomes, or extracellular vesicles (EV), is relatively new and has been increasing in practice as a means of combining the regenerative capacity of MSCs with the cell–cell communication mediated by exosomes. MSC–exosomes are currently being used to treat a variety of medical conditions including cardiac and neurologic deficits, along with types of malignancy [79]. MSC–exosomes have shown promise in hair regrowth, as they contain cytokines and growth factors that play a role in hair restoration. A laboratory study that tested the efficacy of MSC–EV treatment on hair growth in an animal model demonstrated increased dermal papilla cell proliferation and increased levels of various growth factors. Injection of MSC–EVs intradermally into C57BL/6-strain mice promoted hair follicle conversion from telogen to anagen [80].

Hair follicle-derived MSCs have also been shown to reduce inflammation and decrease hair loss in vitro in mice with AA, an autoimmune type of hair loss [81]. However, specific guidelines on their use have not been generated. Furthermore, the use of exosomes in AGA is not well supported, as data showing clear efficacy and safety of exosomes for alopecia is lacking [82]. Additional research is necessary to justify the routine use of MSC–exosomes in treatment of AGA. Currently, the US Food and Drug Administration does not allow use of exosomes for the treatment of FPHL or MPHL.

Microneedling

Microneedling is a minimally invasive procedure whereby small percutaneous wounds are induced with small needles, resulting in the release of platelet-derived growth factor and VEGF. These factors promote angiogenesis and wound healing and reverse fibrosis. It was first described in 1996 by Orentreich for the use of wrinkles and atrophic scars but was found to have a beneficial effect as an adjunct treatment for hair loss through its effect on dermal papilla stem cell proliferation. Furthermore, the induced wounds form channels to improve absorption of topical treatments, such as 2–5% minoxidil or finasteride [83].

A review article by English Jr etal. published in 2021 found that among 17 clinical studies featuring 911 subjects with AGA, microneedling improved hair parameters when used with growth factor solutions, 5% minoxidil and/or PRP [84]. Another study from 2015 showed the benefits of using microneedling treatment in men with AGA who failed to respond to conventional oral finasteride and 5% minoxidil solution therapy for 2–5years [85].

Microneedling with a depth of 0.6mm in combination with minoxidil was found to be more effective than a depth of 1.2mm. Sessions last about 20–25min. Microneedling is often an adjunct treatment; therefore, the frequency of dosage varies by individual [86]. Pain, bruising, and folliculitis have been seen with microneedling, as with other procedures involving injections. The procedure costs vary widely depending on the device used but is approximately $100–500USD per treatment [86].

Vitamins/minerals

For many years, micronutrient deficiencies have been linked to increased hair loss and shedding. In the late 1700s, James Lind linked scurvy to vitamin C deficiency, noting hair loss as a prominent feature. Children with kwashiorkor and marasmus, along with other protein–energy malnutrition disorders, also demonstrate hair loss and skin changes. In more recent years, vitamin D, iron, vitamin B12, folate, and selenium have been found to be involved in hair aging and loss [87]. As a result, the concept of nutrient supplementation as a means of treating hair loss has emerged in recent years.

A variety of studies have shown the use of vitamin D supplementation in those with deficiency and hair loss, and the role of vitamin C supplementation in iron deficiency. In 2007, a randomized control trial was conducted to examine the role of Pantogar, a complex of vitamins, amino acids, keratin, and yeast, in women with TE, a self-limiting form of hair loss due to excessive shedding of telogen hair that follows a period of stress or imbalance. Significant improvement and normalization of the mean anagen hair rate was found in the Pantogar group within 6months of treatment, compared with no significant change in the placebo group [88, 89]. Additional large double-blind, placebo-controlled trials are needed to determine the effect of micronutrient supplementation in hair growth, particularly in AGA. No true evidence has found a space for biotin supplementation in AGA. Moreover, given that over-supplementation of vitamin A, vitamin E, and selenium has been shown to increase hair loss, vitamin and mineral supplementation should not be blindly encouraged [90].

Nutraceuticals

With the rise of Instagram, TikTok, and various other forms of social media advertising, oral and topical nutraceuticals have emerged as methods to increase hair growth and density. These supplements often contain phytochemicals or naturally derived, biologically active compounds that are thought to improve health. Although these products are regulated by the FDA, they are not as rigorously tested as pharmaceuticals [91]. Given this lack of regulation and easy accessibility, the safety and efficacy of these treatments may be compromised.

Launched in 2016, Nutrafol is a hair growth supplement made of a Synergen Complex consisting of 21 phytocompounds and other ingredients that prides itself on supporting “hair wellness from within.” Some of the active ingredients include ashwagandha, saw palmetto, curcumin, palm extract, amino acids, biotin, and hydrolyzed marine collagen, among others [91]. Ashwagandha is a botanical that works to reduce cortisol levels and subjective feelings of stress. Saw palmetto extract naturally inhibits both subtypes of 5-alpha-reductase. In 2018, a 6month randomized, double-blind, placebo-controlled trial found a statistically significant increase in hair growth and thickness in women with self-perceived thinning [92]. In 2022, a prospective, single-blind study involving a diverse group of healthy men and premenopausal women with mild-to-moderate hair thinning found that Nutrafol improved hair growth, fullness, and coverage with less noticeable hair shedding for men and women of various ethnic backgrounds. These results and various self-assessment parameters continued to improve at week 24, suggesting a time-dependent response [93]. None of these trials found significant side effects. The compound is taken orally with four pills daily. Limitations of these studies are the lack of hair counts done by trichoscopy, which is the gold standard in alopecia clinical trials, and the possibility that patients with self-resolving hair conditions such as telogen effluvium were included.

Viviscal is an oral-based marine complex supplement that consists of extracellular matrix components of shark and mollusks, millet seed extract, calcium, iron, vitamin C, horsetail extract, and flax seed extract, among others. Since its debut in 1990, it has been formulated in tablets, shampoos, creams, and conditioners, and has been used in patients with AGA [92]. In the last 30years, various 3–6month clinical trials have been conducted in patients with AGA and AA to evaluate the safety and efficacy of this supplement. The results have been largely positive, with reduced shedding, increased hair thickness and diameter, and increased growth. In addition to encouraging hair growth, Viviscal has shown to improve growth and appearance of eyebrows, nails, skin, and eyelashes in both men and women [94, 95]. Notable side effects have not been found in clinical trials. It is worth noting, however, that it is unclear who the sponsors of these studies are. Oral tablets are prescribed twice daily, but the supplement exists in various forms.

Caffeine

Given its easy penetrability across the skin barrier and stimulant properties, topical caffeine has been considered as a potential treatment for AGA. It is a phosphodiesterase inhibitor, and functions to increase cyclic adenosine monophosphate (cAMP) levels and cell metabolism. As a result, it triggers cell proliferation that helps to reverse hair follicle miniaturization. In various in vitro studies, topical caffeine at various concentrations was able to halt hair follicle growth suppression and stimulate growth [96, 97]. A trial in 210 males with AGA demonstrated that caffeine-related growth was not any less than growth seen with 5% minoxidil solution [90]. There was no difference in side effects between groups. Similar efficacy was also seen with caffeine-based shampoo formulations. It is important to note that female hair follicles appeared to be less resistant to caffeine than male hair follicles [98]. Oral caffeine supplements have not yet been studied treatment of alopecia.

Plant-Based Oils

Rosemary oil (Rosmarinusofficinalis) contains caffeic acid, rosmarinic acid, camphor, and 12-methoxycarnosic acid that work together to reduce inflammation and infection. In a randomized, single-blind clinical trial of 100 male AGA patients, both the experimental group, treated with 1mL of 3.7mg/mL rosemary oil lotion, and the control group, treated with 2% minoxidil, experienced increased hair counts after 6months of continued treatment. Both groups experienced similar side effects of increased pruritis [99].

Pumpkin seed oil containing various saturated and unsaturated fatty acids has been hypothesized to inhibit 5-alpha-reductase and thus reduce levels of DHT. A double-blind clinical trial of 76 males with AGA demonstrated increased self-rated improvement and satisfaction along with increased mean hair count of 40% in the experimental group compared with 10% in the placebo group [100].

Seronoarepens (saw palmetto)

Saw palmetto, or Serenoarepens, is derived and extracted from the berries of the American dwarf palm tree and contains fatty acids, beta carotene, polysaccharides, and phytosterols. It is thought to competitively inhibit both types of 5-alpha-reductase at multiple sites, and thus reduce binding of DHT to the androgen receptor. It also reduces levels of DHT by converting it to a weaker metabolite. It is produced for topical use and has been incorporated in soft gels for oral use [101]. When administered to male AGA patients, saw palmetto led to significantly improved outcomes and increased hair compared with a placebo group [102]. However, when a group receiving 320mg saw palmetto and a group receiving 1mg oral finasteride for 24months were compared, the finasteride group experienced significantly greater outcomes, with growth in both the front and vertex versus only the vertex from saw palmetto [103]. Across various studies, minor side effects including cold feeling and burning sensation were seen with saw palmetto administration [102, 103].

Hair Transplant

Patients with AGA who do not have success with medical treatment may opt for a hair transplant. In fact, the most common indication for hair transplantation in both men and women is AGA [121]. There are two types of hair transplant techniques: follicular unit transplantation (FUT) and follicular unit extraction (FUE). In FUE, individual hair follicles are extracted and transplanted on the alopecic areas of the scalp. FUT involves a single-strip method of donor hair using an elliptical incision followed by suturing. FUE is more common due to its potential advantages compared with FUT such as an increased number of harvestable grafts, less postoperative pain and healing time, and the ability to target follicular groups of a specific size and hair shaft diameter [122]. However, FUE has a longer operative time compared with FUT [122]. In general, healthy patients with enough scalp hair loss, sufficient donor hair, and no evidence of cicatricial alopecia are great candidates for hair transplantation. Contraindications to this procedure include patients with diffuse unpatterned alopecia, cicatricial alopecia, AA, unstable hair loss, insufficient hair loss, sparse donor hair, and those with psychological issues such as body dysmorphic disorder and trichotillomania [122]. Anxiety and depression are not contraindications to hair transplantation.

A retrospective study of 52 patients with AGA found that patients less than 33years old and with Hamilton stage 4a or less showed significant improvement in hair density [123]. In another retrospective study of 1106 male AGA patients, hair transplantation significantly improved self-esteem and increased patient satisfaction regarding their appearance [124]. General complications of hair transplants are bleeding, tachycardia, pain, pruritis, scarring, and edema [125]. Hair transplant costs can range anywhere from $4000 to $20,000USD [125].

Funding

None.

Conflicts of Interest

Shivali Devjani, Ogechi Ezemma, Kristen J. Kelley, Emma Stratton and Maryanne Senna all declare that they have no conflicts of interest.

Ethics Approval

Not applicable.

Patient Consent to Participate

Not applicable.

Patient Consent to Publish

Not applicable.

Availability of Data and Material

Not applicable.

Code Availability

Not applicable.

Author contributions

Shivali Devjani and Ogechi Ezemma contributed equally to this work and should be co-first authors. Kristen J. Kelley and Emma Stratton edited the manuscript. Maryanne Senna contributed greatly and edited the final manuscript. All authors read and approved the final manuscript.

Shivali Devjani, Ogechi Ezemma have contributed equally to this work and should be co-first authors.

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