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===Minoxidil===
===Minoxidil===
[[Minoxidil]], applied topically, is widely used for the treatment of hair loss. It is effective in helping promote hair growth in both males and females with [[androgenic alopecia]].<ref name=Var2014/> About 40% of men experience hair regrowth after 3–6 months.<ref>{{cite journal | pmid = 25112173 | doi=10.1111/dth.12164 | volume=28 | issue=1 | title=Clinical utility and validity of minoxidil response testing in androgenetic alopecia. | journal=Dermatol Ther | pages=13–6}}</ref> It is the only topical product that is FDA approved for androgenic hair loss.<ref name=Var2014>{{cite journal|last1=Varothai|first1=S|last2=Bergfeld|first2=WF|title=Androgenetic alopecia: an evidence-based treatment update.|journal=American journal of clinical dermatology|date=July 2014|volume=15|issue=3|pages=217–30|pmid=24848508}}</ref>
[[Minoxidil]] (''Rogaine'') has] received FDA approval.

It is effective at both the front and scalp vertex. Minoxidil can also be combined with other active ingredients such as tretinoin.<ref name="pmid22735503">{{cite pmid|22735503}}</ref>


=== Ketoconazole ===
=== Ketoconazole ===

Revision as of 18:54, 3 June 2015

Management of hair loss

The management of hair loss is a multidisciplinary effort that spans the medical, pharmaceutical, food supplement, exercise and fashion industries. Androgenic alopecia, alopecia areata, and telogen effluvium are the primary nonscarring alopecias.[1] The most common cause of hair loss in men is androgenic alopecia, the early stages of which can be slowed or reversed with medication, while more advanced cases may be amenable to hair transplantation. Alopecia areata presents as focal discoid patches of hair loss, and affects up to 2% of the U.S. population, occurring more often in children. Telogen effluvium can occur after stressful events, including severe illness, childbirth, or high fever, and can be seen with certain medications or deficiency of iron, particularly in females.[1] Thyroid dysfunction, both when increased and decreased, can lead to specific patterns of hair loss.

Medication

The two first line medications in treatment of male pattern baldness are minoxidil (Rogaine)[2] and finasteride (Propecia).[3] Both are recommended as first-line treatment for male pattern baldness. They may also be used simultaneously when hair loss is progressive or further regrowth is desired after 12 months.[2] A number of other medications used commonly off-label are dutasteride and ketoconazole, and in female androgenic alopecia spironolactone and flutamide.[4] Combinations of finasteride, minoxidil and ketoconazole are more effective than individual use, suggesting synergistic effects of the medications.[5]

Finasteride

Propecia (finasteride) 1 mg tablets.

Both topical and systemic finasteride are effective in androgenic hair loss.[6]

It may also leads to gynecomastia, erectile dysfunction and depression.[7]

In clinical studies, finasteride, like minoxidil, is effective at the crown and frontal hairline area, but more so at the crown.[8] A study over 2 years with 1,553 men between ages 18 and 41 with mild to moderate hair thinning taking 1 mg/day showed 83% maintained or increased hair growth.[9] In 1997, the drug was FDA-approved for male pattern baldness.

Topical formulations show some effect in reversal of androgenic effects on hair follicles,[10] as well as in hirsutism.[11] Small studies of topical finasteride formulations in combination with other drugs have also been found effective.[12]

Dutasteride

Avodart (dutasteride) 500 µg capsules.

Dutasteride (trademark name Avodart, manufactured by GlaxoSmithKline) is approved for the treatment of benign prostatic hyperplasia (BPH), and used off label for androgenic alopecia.[13] It is a dual 5-a reductase inhibitor that inhibits conversion of testosterone to dihydrotestosterone (DHT). The drug inhibits all 2 isoforms of 5-alpha reductase, whereas finasteride only inhibits type II.

Phase I and II clinical trials for dutasteride as a hair loss drug were started, but discontinued in late 2002 for unknown reasons. Phase II studies showed that dutasteride, at both 0.5 mg and 2.5 mg per day, showed a superior hair count as compared to finasteride 5 mg at 3 and 6 months.[14]

Phase II results at 24 weeks showed placebo to decrease by 32 hairs, dutasteride 0.5 mg to increase an average of 95 hairs, while the dutasteride 2.5 mg group increasing by 110 hairs. GlaxoSmithKline ran a phase III, six-month study in Korea to test the safety, tolerability and effectiveness of a once-daily dutasteride at 0.5 mg. They looked at male pattern baldness (MPB) at the vertex of the scalp, types III, IV and V on the Hamilton-Norwood scale. The study was completed in January 2009.[15][16] Future intentions by GlaxoSmithKline for FDA approval of dutasteride in androgenic alopecia are unknown.

Minoxidil

Minoxidil, applied topically, is widely used for the treatment of hair loss. It is effective in helping promote hair growth in both males and females with androgenic alopecia.[17] About 40% of men experience hair regrowth after 3–6 months.[18] It is the only topical product that is FDA approved for androgenic hair loss.[17]

Ketoconazole

Ketoconazole is a mild topical anti-androgen available over the counter and in prescription strength in the United States. It is established as treatment for tinea capitis, but also has anti-androgenic and microfloral benefit in androgenic hair loss. Spironolactone and flutamide are potent topical and systemic anti-androgens, typically not used in men as they have a high incidence of feminizing side effects.[19] They can be prescribed off-label as part of a more aggressive medical regimens, and are effective in female androgenic hair loss.[20]

Ketoconazole is a topical anti-fungal agent. As an imidazole, ketoconazole is effective for the treatment of dermatitis and dandruff, and its action on scalp microflora may benefit those with AGA associated follicular inflammation.[4][21][22] It is also an anti-androgen, and may improve hair growth in AGA through androgen dependent pathways.[23]

Spironolactone

Spironolactone is a possible selective androgen receptor modulator,[24] and both reduces adrenal androgen production and exerts competitive blockade on androgen receptors in target tissues.[19] It can be administered topically or systemically. In addition to anti-androgenic activity, it increases estrogen production, which in turn increases production of SHBG. SHBG binds free DHT and decreases free androgen indices.[25] Due to its feminizing side effects and risk of infertility in men[26] It is used more often in female androgenic alopecia,[27] particularly PCOS.[28] As it is also a potassium sparing anti-hypertensive, it can also be associated with hypotension, hyperkalemia, and cardiac dysrhythmia. Also, women who are pregnant or trying to become pregnant generally cannot use the medication as it is a teratogen, and can cause ambiguous genitalia in newborns.[20]

Flutamide

Flutamide has more anti-androgenic activity than spironolactone, and is also referred to as chemical castration. It can cause marked reduction in libido and estrogenic side effects including gynecomastia, lipid profile changes, and emotional lability, although when used in women it can be associated with increased positive affect. There is a significant incidence of hepatic dysfunction with the medication in women.[29] Like spironolactone, it is more often used clinically in female androgenic alopecia.[30]

Hair transplantation

Main article: Hair transplantation

Hair transplantation is a surgical technique that moves individual hair follicles from a part of the body called the donor site to bald or balding part of the body known as the recipient site. It is primarily used to treat male pattern baldness. In this condition, grafts containing hair follicles that are genetically resistant to balding are transplanted to bald scalp. It is also used to restore eyelashes, eyebrows, beard hair, chest hair, and pubic hair and to fill in scars caused by accidents or surgery such as face-lifts and previous hair transplants. Hair transplantation differs from skin grafting in that grafts contain almost all of the epidermis and dermis surrounding the hair follicle, and many tiny grafts are transplanted rather than a single strip of skin.

Since hair naturally grows in follicles in groups of 1 to 4 hairs, transplantation takes advantage of these naturally occurring follicular units. This achieves a more natural appearance by matching hair for hair through Follicular Unit Transplantation (FUT).

Donor hair can be harvested in two different ways. Small grafts of naturally-occurring units of one to four hairs, called follicular units, can be moved to balding areas of the hair restoration. These follicular units are surgically implanted in the scalp in very close proximity to one another and in large numbers. The grafts are obtained in one or both of the two primary methods of surgical extraction, Follicular Unit Transplantation (FUT), colloquially referred to as "strip harvesting", or Follicular Unit Extraction (FUE), in which follicles are transplanted individually.

In FUT, a strip of skin containing many follicular units is extracted from the patient and dissected under stereoscopic microscope. Once divided into follicular unit grafts, the surgeon implants each individually into small recipient sites made by incision at the bald scalp. In newer technique, roots are extracted from the donor area and divided into strips for transplantation. The strip, two to three millimeters thick, is isolated and transplanted to bald scalp.[31] After surgery, bandaging is worn for two days for healing.[32]

More recently, bioengineered hair follicles have been successfully transplanted to create histologically normal hair follicles. Specifically, bioengineered hair follicle germ, which was reconstituted with embryonic skin-derived epithelial and mesenchymal cells were ectopically transplanted. On histology, the bioengineered hair follicles also autonomously connected with nerves and the arrector pili muscle at the permanent region and exhibited piloerection ability.[33]

Mechanism

Hair follicle with mesenchymal dermal papilla, labelled at top, location of hair follicle stem cells and thought to be site of action of DHT.

Several lines of evidence support the dermal papilla of the hair follicle as the androgenic target for hair loss prevention and reversal.[34] Type 1 and 2 5α reductase enzymes are present at pilosebaceous units in papillae of individual hair follicles. They catalyze formation of the androgens testosterone and DHT, which in turn regulate hair growth. Androgens have different effects at different follicles: they stimulate IGF-1 at facial hair, causing hair regrowth, but stimulate TGF β1, TGF β2, dickkopf1 and IL-6 at the scalp, causing hair follicle miniaturization.[35]

Female androgenic alopecia is characterized by diffuse crown thinning without hairline recession, and like its male counterpart rarely leads to total hair loss.[36] Finasteride and minoxidil are usually first line therapy for its treatment. Other options include topical or systemic spironolactone or flutamide, although they have a high incidence of feminizing side effects and are better tolerated in female androgenic hair loss.

More advanced cases may be resistant or unresponsive to medical therapy, however, and require hair transplantation. Naturally-occurring units of one to four hairs, called follicular units, are excised and moved to areas of hair restoration. These follicular units are surgically implanted in the scalp in close proximity and in large numbers. The grafts are obtained from either Follicular Unit Transplantation (FUT) – colloquially referred to as "strip harvesting" – or Follicular Unit Extraction (FUE). In the former, a strip of skin with follicular units is extracted and dissected into individual follicular unit grafts. The surgeon then implants the grafts into small incisions, called recipient sites.[32][37] Specialized scalp tattoos can also mimic the appearance of a short buzzed haircut.[38][39] Androgenic alopecia also occurs in females, and more often presents as diffuse thinning without hairline recession. Like its male counterpart, the condition rarely leads to total hair loss. Treatment options are similar to those for men, although topical or systemic estrogen is used more often.[36][40]

Research

Main article: Experimental treatment of androgenic alopecia
Capsaicin is the active ingredient in chili pepper, with animal studies showing it to affect hair regrowth.

The field of research to prevent and treat androgenic hair loss is vast, with systemic and topical therapies with varying degrees of efficacy. In the United States alone, it is a multi-billion dollar industry. The entire field of research cannot be appropriately addressed in a single article, but the following section discusses those with the greatest degree of peer reviewed research and recognition. Prostaglandin F2α (PGF2a) analogues induces hair regrowth in animal models of androgenic alopecia with transgenic mice,[41] and stump-tailed macaques,[42] and initially generated 'great expectations' in pharmaceutical research for potential effectiveness in alopecia.[43] Latanoprost and bimatoprost are specific PGF2a analogues applied topically, and have been found to lengthen eyelashes,[44][45] darken hair pigmentation[46] and elongate hair.[4] Bimatoprost (Latisse®) is available as treatment for eyelash growth.[47] Latanoprost (Xalatan®) has shown ability to promote scalp hair density and pigmentation,[48] and is theorized to function at the dermal papilla.[49] A study found latanoprost ineffective on eyelashes in a patient with alopecia areata.[50] It has also been found ineffective in treatment of eyebrow hair loss.[51] A study in which a combination of subcutaneous capsaicin and isoflavone was administered to bald (CGRP knockout) mice resulted in rise of dermal IGF-1 at hair follicles and hair regrowth. The mechanism was thought to be through activation of vanilloid receptor-1 causing release of CGRP from neurons, in turn causing release of IGF-1.[52] Other studies on less painful medications found topical raspberry extract to work through a similar mechanism.[53] Caffeine stimulates human hair growth in vitro, and reduced testosterone-induced follicle growth suppression.[54] Estrogens are indirect anti-androgens, and can be used to treat androgenetic hair loss in females with oral contraceptives. Systemic estrogen increases SHBG, which binds androgens, including testosterone and DHT, in turn reducing their bioavailability. Topical formulations are available in Europe.[55] Hair follicles have estrogen receptors and it is theorized topical compounds act on them directly to promote hair growth and antagonize androgen action. Large clinical studies showing effectiveness are absent. Topical treatment is also usually unavailable in North America.[4] HIF-1 help prevents apoptosis, or cell death, in hypoxic conditions. In vitro, when supernatant from HIF-1 transfected fibroblast cells was administered to hair follicle cells, it induced VEGF, which had stimulatory effects on hair follicle cells. VEGF promotes growth of blood vessels, which would be an appropriate response to low oxygen conditions.[56] Other studies have suggested hypoxia initiates a potentially self-perpetuating cycle involving HIF, VEGF, and AKT activation. Ciclopirox, otherwise known as ciclopiroxolamine, is used as a topical shampoo, has anti-fungal properties, and may induce HIF-1.[57]

Laser therapy

There is some evidence that laser light can stimulate hair growth at some wavelengths.[58] With one exception,[59] however, there is limited clinical evidence of their benefit.[60]

Dietary supplements

Saw palmetto in one small study demonstrated increased hair growth in 6/10 men with mild to moderate androgenetic alopecia,[61] and another study revealed that saw palmetto extract applied topically in a lotion and shampoo base led to a 35% increase in hair density, but these studies were small and a proper larger clinical trial on androgenetic alopecia is needed.[62]

Other herbs include black cohosh (Actaea racemosa), dong quai (Angelica sinensis), false unicorn (Chamaelirium luteum), chasteberry (Vitex agnus-castus), and red clover (Trifolium pratense). Each of them purport hair promoting effects by various mechanisms. Common nutritional supplements include biotin, caffeine and melatonin.[55][63]

Stem cell therapy

Although follicles were previously thought gone in areas of complete baldness, they are more likely dormant, as recent studies have shown the scalp contains the stem cells from which the follicles arose.[64] Research on these follicular stem cells may lead to successes in treating baldness through hair multiplication (HM), also known as hair cloning.

One of the groups developing hair multiplication is Aderans Research Institute (ARI), a Japanese owned company in the United States.[65][66] In 2008, Intercytex announced results of a Phase II trial to clone hair follicles from the back of the neck, multiply them and then reimplant the cells into the scalp. Initial testing showed at least two thirds of male patients regrew hair. The company estimated treatment would take "a number of years to complete" Phase III trials.[67] After failing to achieve success in their trials, the company discontinued its hair multiplication project in 2010, with intention to sell off its assets and research.[68] Aderans Research Institute Inc. (ARI) then acquired technology from Regenerative Medicine Assets Limited (formerly Intercytex Group plc)[69] and is conducting Phase II clinical trials.[70]

Scientists grew the first artificial hair follicles from stem cells in 2010. Researchers in the study predicted that by 2015 people could grow new hair from their own stem cells, and have it surgically implanted at areas of hair loss. The lead investigator said preparations for clinical trials were "already in motion".[71] In their first human clinical trial, Replicel Life Sciences was able to regenerate 20% percent of hair on stem cell treated areas. Replicel is using dermal sheath cup cells instead of dermal papillae cells for multiplication, in distinction to Aderans. They will be conducting Phase II trials at the end of 2012.[72] In early 2012 a research group demonstrated "functional hair regeneration from adult stem cells" in mouse animal models with the potential for "organ replacement regenerative therapies".[73]

A March 26, 2015 study showed treatment using adipose-derived stem cells, had increased number of the number of hairs, and may be a future treatment for hair loss. Adipose-derived stem cells secrete various growth factors that promote hair growth.[74]

Genetics

Curis and Procter & Gamble spent $1,000,000 on development of a topical hedgehog agonist for hair loss. The agent did not meet safety standards, and the program was stopped in 2007.[75] In 2008 researchers at the University of Bonn announced they have found the genetic basis of two distinct forms of inherited hair loss. They found the gene P2RY5 causes a rare, inherited form of hair loss called hypotrichosis simplex. It is the first receptor in humans known to play a role in hair growth.[76][77][78] Researchers found that disruption of the gene SOX21 in mice caused cyclical hair loss. Research has suggested SOX21 as a master regulator of hair shaft cuticle differentiation, with its disruption causing cyclical alopecia in mice models.[79] Deletion of SOX21 dramatically affects hair lipids.[80]

Radiation induced hair loss

Radiation induces hair loss through damage to hair follicle stem cell progenitors and alteration of keratin expression.[81][82] Radiation therapy has been associated with increased mucin production in hair follicles.[83]

Studies have suggested electromagnetic radiation as a therapeutic growth stimulant in alopecia.[84]

Cosmeses

There have been advances in the fashion industry in wig design.

Certain hair shampoos and ointments visually thicken existing hair, without affecting the growth cycle.[85] There have also been developments in the fashion industry with wig design. The fashion accessory has also been shown to be a source of psychological support for women undergoing chemotherapy, with cancer survivors in one study describing their wig as a "constant companion".[86] Other studies in women have demonstrated a more mixed psychosocial impact of hairpiece use.[87]

Specialized scalp tattoos can mimic the appearance of a short buzzed haircut.[38][39]

Recently, prototypes of "follicular unit wigs" have been trialed in rabbit models, with good histocompatibility, a low loss rate, and satisfactory appearance in a year after transplantation.[88]

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External links

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