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This is an old revision of this page, as edited by Lenny Kaufman (talk | contribs) at 09:21, 6 January 2013 (rewrote the article to discuss management of all types of alopecia, as it is mostly about androgenic alopecia currently. I spent a lot of time on it -- please let me know if feedback!). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

The management of baldness 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. 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. Thyroid dysfunction, both when increased and decreased, can lead to specific patterns of hair loss.

Androgenic alopecia

Androgenic hair loss is due to the activity of androgens, predominantly DHT, at the dermal papillae of the individual follicles. In adult men, its incidence is roughly equivalent to chronologic age, and it has a strong genetic component.

The physiology is primarily androgenic, with dihydrotestosterone (DHT) the major contributor. Androgens are important in male sexual development around birth and at puberty. They regulate sebaceous glands, apocrine hair growth and libido. With increasing age, androgens stimulate hair growth on the face, but suppress it at the temples and scalp vertex, a condition that has been referred to as the 'androgen paradox'.

Several lines of evidence support the dermal papilla of the hair follicle as the androgenic target for hair loss prevention and reversal. 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, leading to growth, but stimulate TGF β1, TGF β2, dickkopf1 and IL-6 at the scalp, leading to miniaturization.

Female androgenic alopecia more often causes diffuse thinning without hairline recession, and like its male counterpart rarely leads to total hair loss. 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. Specialized scalp tattoos can also mimic the appearance of a short buzzed haircut. 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.

Androgenic impact of exercise

Exercise can impact androgenic hair loss by affecting androgen and estrogen levels.

Quantification of androgen indices in response to exercise can be understood in four categories: short versus long term, and anaerobic versus aerobic. These are indirect assays of exercise impact on hair loss, although the ability of exogenous androgen to worsen or precipitate miniaturization in the genetically predisposed is well documented. Investigations have been either self-report, or cross-sectional and cohort studies with exercise and serum hormonal indices, but no phase III clinical trials. In some studies, conflicting results are thought related to differences in exercise mode, volume, or physical condition of subjects.

In cross-sectional analyses, aerobic exercisers have lower basal total and free testosterone compared to the sedentary. Anaerobic exercisers also have lower testosterone compared to the sedentary but a slight increase in basal testosterone with resistance training over time. Acutely, testosterone briefly increases when comparing aerobic, anaerobic and mixed forms of exercise. A study assessed men who were resistance trained, endurance trained, or sedentary in which they either rested, ran or did a resistance session. Androgens increased in response to exercise, particularly resistance, while cortisol only increased with resistance. After initial post-exercise increase, there was decline in free and total testosterone during resistance recovery, particularly in resistance-trained subjects. Endurance-trained subjects showed less change in hormone levels in response to exercise than resistance-trained subjects. Another study found relative short term effects of aerobic, anaerobic and combined anaerobic-aerobic exercise protocols on hormone levels to not be different. It showed increases in testosterone and cortisol immediately after exercise that returned to baseline in 2 hours.

In trained long term aerobic exercisers, basal levels are unchanged, or decreased. Acutely, endurance based aerobic efforts cause testosterone to rise. A year long, moderate-intensity aerobic exercise program increased DHT and SHBG in sedentary men age 40-75, but had no effect on other androgens. Both DHT and SHBG increased 14% in exercisers at 3 months, and at 12 months they remained 9% above baseline. SHBG is protective against DHT as it binds free androgen.

It is unknown if anaerobic training changes individual hormone profiles, or if conditioned athletes in studies self-selected because of physiologic predisposition to athletic conditioning. There is variation of response to anaerobic stress depending on exercise intensity, age, gender, length of time studied, and time at which serum indices were drawn. Most studies report that testosterone increases or is unchanged acutely, though some even report it to decrease. Anaerobic exercisers have testosterone levels below sedentary controls in cross sectional analysis. Over months to years, levels are stable to slightly increased.

The ratio of testosterone to cortisol can both increase and decrease during resistance training, depending on intensity of exercise. When comparing men and women in the 30, 50 and 70 year age groups, young and middle aged men showed increased testosterone after exercise, with the latter also having increased cortisol. Elderly men showed no change. There is a 27% greater testosterone response using protocols with simultaneous use of all four limbs. A number of studies have looked at effects of anaerobic exercise over months to years, showing it to be constant or slightly increased. A small case-control of anaerobic training in young untrained males over six weeks found decline in free testosterone of 17 percent. With men in their 60s, resistive training over 16 weeks did not affect baseline anabolic hormone levels, although GH increased acutely with exercise. A study over 21 weeks in male strength athletes showed basal hormone levels to be constant, despite strength increase. A follow up study looked at a larger group of weight trainers over 24 weeks, with 12 week decompensation. Training caused no change in total testosterone, but there were decreases in free testosterone, progesterone, androstendione, DHEA, cortisol, transcortin, and in the cortisol:CBG ratio, suggesting androgen turnover increased with training intensity, without change in total testosterone. A study looking at young men and resistance training over 48 weeks found increases in baseline serum testosterone from 20 ± 5 to 25 ± 5 nmol/l, and an increase in testosterone:SHBG ratio, LH and FSH.

Combined training

One study showed GH increase with anaerobic effort to be blunted in those who performed aerobic training for 60 minutes prior to strength training. Testosterone levels remained high only at the end of the training session with aerobic training followed by strength training, a phenomenon not seen with weight training done before aerobics. In an 11 week soccer training program focusing on combined vertical jumps, short sprints, and submaximal endurance running, total testosterone increased, but SHBG rose in parallel, maintaining a constant free androgen index.

Conventional medication

The two first line medications in treatment of male pattern baldness are minoxidil (Rogaine) and finasteride (Propecia). 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. A number of other medications used commonly off-label are dutasteride and ketoconazole, and in female androgenic alopecia spironolactone and flutamide. Combinations of finasteride, minoxidil and ketoconazole are more effective than individual use, suggesting synergistic effects of the medications.

5 alpha reductase inhibitors

Finasteride

Finasteride (marketed by Merck under the trade names Propecia and Proscar) is a type-2 isoenzyme 5 alpha-reductase inhibitor. It was originally FDA approved for treatment of benign prostatic hyperplasia (BPH), and binds 5-alpha-reductase, preventing conversion of testosterone to DHT. Its effects on androgenic alopecia were not unexpected due to observations of the pseudo-hemaphrodite population in Papua, New Guinea. Both systemic and topical formulations are effective in androgenic hair loss.

Inhibition of 5α-reductase results in decreased conversion of testosterone to dihydrotestosterone (DHT) by reducing the Δ4,5 double-bond. This, also leads to increased levels of testosterone and estradiol. Gynecomastia, erectile dysfunction and depression, are some possible side-effects. Other locally expressed enzymes can compensate to a degree, including DHT conversion through reductive 17b-hydroxysteroid dehydrogenase, oxidative 3a-hydroxysteroid dehydrogenase, and 3b-hydroxysteroid dehydrogenase enzymes.

In clinical studies, finasteride, like minoxidil, is effective at the crown and frontal hairline area, but more so at the former. 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. In 1997, the drug was FDA approved for male pattern baldness. A 5-year study revealed that 9 of 10 men taking finasteride at 1 mg/day experienced results. 42% had no further loss while 48% experienced regrowth.

The drug is lipophilic, and development of a liposomal system of finasteride for topical application has been a subject of recent study, with vehicles shown stable for up to two months in refrigerated preparation. Topical formulations show some effect in reversal of androgenic effects on hair follicles, as well as in hirsutism. Studies of transgenic mice have shown hair regrowth with topical administration. More recent studies have looked at microemulsions and liquid crystalline nanoparticles for topical finasteride delivery. In the latter, addition of glycerol, propylene glycol, and polyethylene glycol 400, increased finasteride permeation, while addition of oleic acid made it decrease. Topical 0.1% finasteride in combination with topical 3% minoxidil is more effective than topical minoxidil alone. Small studies of topical finasteride formulations in combination with other drugs have also been found effective. Surfactants have been shown to aid topical absorption. Topical finasteride gel has been shown an effective route of administration. Of note, the studies evaluating topical finasteride did not correlate with serum PSA in humans, or prostatic weight in animal studies to see if effects were related to systemic absorption. Other studies have shown lower doses of topical finasteride to be less effective. The medication is not entirely benign. Some patients experience neurologic or psychiatric sequellae after discontinuation of the drug, a condition described in medical literature as 'post-finasteride syndrome'.

Dutasteride

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

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.

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 completed in January 2009. Future intentions by GlaxoSmithKline for FDA approval of dutasteride in androgenic alopecia are unknown.

Alfatradiol

Alfatradiol is a topical 5α-reductase inhibitor that has been shown to slow progression of hair loss in women. It is marketed as Avixis, ELL Cranell Alpha and Pantostin.

Other topical treatments

Minoxidil and ketoconazole are two long standing topical treatments of androgenic alopecia, with only the former having FDA approval for androgenic alopecia in the United States. Ketoconazole is also used as an anti-fungal in the treatment of tinea capitis.

Minoxidil

Minoxidil (Rogaine) is a vasodilator. It was originally used as the oral drug Loniten to treat hypertension, and discovered to cause hair growth as a side effect. Upjohn received FDA approval to market a topical solution that contained 2% minoxidil as Rogaine, marketed outside the United States as Regaine.

It is effective at both the front and scalp vertex. In a 12 month study, vertex improvements were seen in 51% of men using 5% minoxidil, 42% using 2% minoxidil, and 13% of placebo users. Moderate to great increases in hair growth were seen in the frontal scalp regions of 19% of men using 5% minoxidil, 10% using 2% minoxidil, and 3% of placebo. Although a mitogen for dormant telogen follicles, minoxidil can cause hairs in later phases of the cell cycle to shed early. This is often followed by growth of new, thicker hairs. The mitogenic effect is temporary and does not appear to change follicular structure, leading to indefinite minoxidil application to maintain growth. Use of minoxidil without propylene glycol as a vehicle can reduce associated itching. The drug can also be combined with other active ingredients such as tretinoin.

Anti-androgens

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. They can be prescribed off-label as part of a more aggressive medical regimens, and are effective in female androgenic hair loss.

Ketoconazole

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. It is also an anti-androgen, and may improve hair growth in AGA through androgen dependent pathways.

Spironolactone

Spironolactone is a possible selective androgen receptor modulator, and both reduces adrenal androgen production and exerts competitive blockade on androgen receptors in target tissues. 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. Due to its feminizing side effects and risk of infertility in men It is used more often in female androgenic alopecia, particularly PCOS. As it is also an anti-hypertensive, patients need to be monitored for hyperkalemia and associated 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.

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. Like spironolactone, it is more often used clinically in female androgenic alopecia.

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 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. After surgery, bandaging is worn for two days for healing.

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.

Experimental medication

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, and stump-tailed macaques, and initially generated 'great expectations' in pharmaceutical research for potential effectiveness in alopecia. Latanoprost and bimatoprost are specific PGF2a analogues applied topically, and have been found to lengthen eyelashes, darken hair pigmentation and elongate hair. Bimatoprost (Latisse®) is available as treatment for eyelash growth. Latanoprost (Xalatan®) has shown ability to promote scalp hair density and pigmentation, and is theorized to function at the dermal papilla. A study found latanoprost ineffective on eyelashes in a patient with alopecia areata. It has also been found ineffective in treatment of eyebrow hair loss. 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. Other studies on less painful medications found topical raspberry extract to work through a similar mechanism. Caffeine stimulates of human hair growth in vitro, and reduced testosterone-induced follicle growth suppression. It has been demonstrated that the addition of caffeine to a shampoo-formulation is effective in administering caffeine to the hair follicles in the scalp. Further research must be done to evaluate the efficacy and adequate dosage of caffeine in the treatment of androgenetic alopecia. Cyproterone is a topical agent in a lipid suspension that has anti-androgenic activity at the pilosebaceous unit. It has shown similar efficacy to 2% minoxidil in treatment of female androgenic hair loss, with cyproterone being more effective when women had high body mass indices, and minoxidil more effective when they weighed less. It has also been shown effective in acne and hirsutism, but no longer marketed due to theoretical risks of venous thromboembolism. More recent studies have shown that this risk is no greater than that seen with oral contraceptives. 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. 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. 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. 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.

In December 2012, topical application of IGF-1 in a liposomal vehicle led to thicker and more rapid hair growth in transgenic mice with androgenic alopecia. The study did not show measurable systemic levels or hematopoietic side effects, suggesting potential for use in humans. Low energy radiofrequency irradiation induces IGF-1 in cultured human dermal papilla cells. Adenosine stimulates dermal papillae in vitro to induce IGF-1, along with fibroblast growth factors FGF7, FGF-2 and VEGF. β-catenin transcription increased, which promotes dermal papillae as well. Dietary isoflavones increase IGF production in scalp dermal papillae in transgenic mice. Topical capsaicin also stimulates IGF at hair follicles via release of vanilloid receptor-1, which in turn leads to more CGRP. Ascorbic acid has led to increased IGF expression in vitro.

Piroctone olamine is a topical agent that has similar efficacy to 1% ketoconazole in small controlled trials. In 2012, scientists found the lipid prostaglandin D2 (PGD2) in balding male scalps at levels higher than controls, and theorized it prevented hair follicles maturation. The lead investigator said treatment could be possible within two years. Ginger can affect PGD2 levels in serum. Mouse models have found valproic acid activates alkaline phosphatase in human dermal papilla cells and induces hair regeneration in transgenic mice. Systemic valproic acid can cause alopecia, although this may be related to deficiencies of biotin and zinc.

In May 2007, U.S. company Follica Inc licensed technology from the University of Pennsylvania to regenerate hair follicles by reawakening genes from embryonic development. Studies began with the study of hair regrowth in wound healing in mice when Wnt proteins were introduced. Time till development of pharmaceutical treatment is expected to take several years. In other methods, cells are cultured and the supernatant is processed to produce a compound rich in hair growth promoting factors, like Wnt proteins. This approach is still in Phase I or II trials. Platelet rich plasma (PRP) isolated from whole blood can be used for its growth factors and stimulatory mediators. Some hair transplant surgeons use this product to encourage transplanted graft growth. PRP is also available as a standalone treatment for AGA, though there is only one small study to date in its support.

Laser therapy

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

Copper complexes

Topical copper complexes such as Tricomin have been reported successful in preventing hair follicle death.

Dietary supplements

The dietary supplement industry is distinct from the pharmaceutical industry, and is more loosely regulated than FDA approved medications. The most commonly used and well researched plants are saw palmetto (Serenoa repens), stinging nettle (Pygeum africanum), turmeric (Curcubita pepo), and Urtica dioica. 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. Other supplements for hair loss include L-arginine, , Boswellia serrata,, biotin, , L-Carnitine, TRX2 is a dietary supplement that predominantly contains carnitine., curcumin, ginger, grape seed extract, Grateloupia elliptica, green tea, lycopene, pumpkin seed oil (Curcurbitae pepo),, and resveratrol.

Saw palmetto

Saw palmetto (Sabal serrulatum or Serenao repens) may inhibit 5 alpha reductase and is approved for treatment of prostate disorders in Germany as well. Studies of Italian men have found it effective at 320 mg/day.A meta-analysis looking at effects of Serenao in BPH and prostate adenocarcinoma was unable to make conclusions regarding its effects in BPH due to limitations of studies in the literature.

Nettle

Nettle (Urtica dioica) inhibits 5 alpha reductase in vitro when given in combination with Pygeum africanum. It ameliorates symptoms of BPH in rats, and has been found protective against reperfusion injury in organ ischemia. Nettle is approved for treatment of prostate disorders in Germany.

Pygeum africanum

Pygeum africanum inhibits 5 alpha reductase in vitro when given with Nettle (Urtica dioica). In vitro cultured prostate stromal cells from patients with BPH show the herb to induce apoptosis. N-butylbenzene-sulfonamide (NBBS), isolated from Pygeum africanum bark, acts as an androgen antagonistic, inhibits AR nuclear translocation and prostate cancer cell growth. Atraric acid, isolated from bark material of Pygeum africanum, has anti-androgenic activity, inhibiting transactivation mediated by ligand-activated human AR. A meta-analysis looking at effects of Pygeum africanum in BPH and prostate adenocarcinoma was unable to make conclusions regarding its effects in BPH due to limitations of studies in the literature.

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. 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. 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. 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. Aderans Research Institute Inc. (ARI) then acquired technology from Regenerative Medicine Assets Limited (formerly Intercytex Group plc) and is conducting Phase II clinical trials.

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". 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 Adernas. They will be conducting Phase II trials at the end of 2012. 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".

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. 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. 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. Deletion of SOX21 dramatically affects hair lipids.

Alopecia totalis

Chemotherapy induced hair loss occurs by a non-androgenic mechanism, and can manifests as alopecia totalis, telogen effluvium, or less often alopecia areata. It is usually associated with systemic treatment due to the high mitotic rate of hair follicles, and more reversible than androgenic hair loss, although permanent cases can occur. Histology is similar to telogen or anagen effluvium on biopsy. Unlike its androgenic counterparts, it often progresses to alopecia totalis, although it usually is reversible, with prophylactic measures including scalp cooling, and temporary interval cosmeses such as wigs and head garments. Telogen effluvium can present with similar appearance to alopecia totalis, with further distinction by clinical course, microscopic examination of plucked follicles, or scalp biopsy. Histology would show telogen hair follicles in the dermis with minimal inflammation in effluvium, and dense peribulbar lymphocytic infiltrate in alopecia totalis. Androgenic alopecia would show perifollicular fibrosis on biopsy. Chemotherapy induces hair loss in women more often than men.

Scalp cooling has specifically been used to prevent alopecia in docetaxel chemotherapy, although it has been found prophylactic in other regimens as well. Treatment effects may take time to resolve, with one study showing breast cancer survivors wearing wigs up to 2 years after chemotherapy.

Alopecia areata

Alopecia areata manifests as focal bald spots on the scalp, and can also occur in children. It can be self-contained and resolve without therapy, although there are relapsing and remitting forms of the illness. In distinction to androgenic hair loss, pulsed corticosteroid therapy has been found effective over the long term in its treatment. Topical calcipotriol, a vitamin D derivative, has been used successfully in treatment of areata.

Telogen effluvium

Telogen effluvium is hair thinning or shedding from early entry of the follicle into telogen. Emotional or physical stress can alter the normal hair cycle, causing the disorder. It can be caused by eating disorders, fever, childbirth, chronic illness, major surgery, anemia, severe emotional disorders, crash diets, hypothyroidism, and drugs. Effluvium can present with similar appearance to alopecia totalis, with biopsy in the former showing telogen hair follicles in the dermis with minimal inflammation in effluvium. Most cases are self-limited and resolve on their own, although zinc has shown some effectiveness in treatment.

Radiation induced alopecia

Radiation induces alopecia through damage to hair follicle stem cell progenitors and alteration of keratin expression. Radiation therapy has been associated with increased mucin production in hair follicles.

Spin labels and Pyridine-N-oxides

In animal models, the nitroxide spin labels TEMPO and TEMPOL act as free radical scavengers with superoxide dismutase, and protect against radiation induced cellular damage, with the first paper published on TEMPOL in 1974. It is under patent by physician and redox researcher Peter Proctor for regrowth after radiation induced alopecia. It has a number of active and pending patents with Mitos Pharmaceuticals as well, who recently concluded stage II trials with TEMPOL for radiation induced hair loss. There is currently a National Cancer Institute sponsored clinical trial for TEMPOL in radiation induced alopecia. Related pyridine-N-Oxides, such as nicotinic acid-N-oxide or "NANO" are also patented and used for non-androgenic hair loss treatment.

Electromagnetic radiation

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

Tinea capitis

Tinea capitis is a superficial fungal infection (dermatophytosis) of the scalp, and can mimic alopecia areata. The disease is primarily caused by dermatophytes in the Trichophyton and Microsporum genera that invade the hair shaft. The clinical presentation is typically a single or multiple patches of hair loss, sometimes with a 'black dot' pattern (often with broken-off hairs), that may be accompanied by inflammation, scaling, pustules, and itching. Uncommon in adults, tinea capitis is predominantly seen in pre-pubertal children, more often in boys than girls.

At least eight species of dermatophytes are associated with tinea capitis. Cases of Trichophyton infection predominate from Central America to the United States and in parts of Western Europe. Infections from Microsporum species are mainly in South America, Southern and Central Europe, Africa and the Middle East. The disease is infectious and can be transmitted by humans, animals, or objects that harbor the fungus. The fungus can also exist in a carrier state on the scalp, without clinical symptomatology. Treatment of tinea capitis requires an oral antifungal agent; griseofulvin is the most commonly used drug, but other newer antimycotic drugs, such as terbinafine, itraconazole, and fluconazole have started to gain acceptance.

Traction alopecia

Traction alopecia is recession of the hairline due to chronic traction, or hair pulling, and is characterized by a fringe along the marginal hairline on physical exam.It is commonly seen with certain hair styles or braiding patterns that pull the hairline forcefully towards the vertex of the scalp, and has been reported more often in African American women, in whom it can cause scarring It has also been seen in female ballerinas, and in cultural traditions where the hair is voluntarily not cut in religious obeisance, the latter caused by progressively increasing weight of the hair itself. Traction alopecia is mechanical in etiology, rather than androgenic, and treatment is typically not pharmaceutical. Management includes cessation of the chronic traction, cosmeses, with surgical restoration reserved for more severe cases.

Cosmeses

Certain hair shampoos and ointments visually thicken existing hair, without affecting the growth cycle. 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". Other studies in women have demonstrated a more mixed psychosocial impact of hairpiece use.

Specialized scalp tattoos can mimic the appearance of a short buzzed haircut.

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.

See also

• Androgenic alopecia
• Baldness
• Dihydrotestosterone
• Hamilton-Norwood scale
• Ludwig scale
• Noncicatricial alopecia

References

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External links

• The Trichological Society
• How Hair Replacement Works
• International Society of Hair Restoration Surgery
• "Medical Treatments for Balding in Men", April 1999, American Family Physician (medical journal)
• Health Alternatives: zinc, silica, methylsulphonylmethane (MSM) and cod-liver oil, to slow down the process.

• Dermatologic procedures