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More than half of men are affected by male pattern baldness by age 50, and baldness treatments are estimated to be a US $1 billion per year industry.^[1] Since the 1980s, drug therapy has increasingly become a realistic management option for baldness for men and women. Increased understanding of the role of dihydrotestosterone (DHT) in male and female pattern baldness has led to targeted intervention to prevent this hormone from acting on receptors in the scalp. Coupled with chance discoveries and the ever-present lure of a breakthrough involving stem cells and hair multiplication, scientifically proven baldness treatments continue to be an area of research that receives a large amount of funding.

There are only two FDA-approved treatments for male baldness: Minoxidil^[2] and Finasteride ^[3]. Finasteride is recommended first for male pattern baldness.^[2] Experts warn that many treatments marketed as hair loss cures are ineffective aside from the placebo effect.^[2]

Contents 1 General concerns 2 Minoxidil 3 Antiandrogens 3.1 Finasteride 3.2 Dutasteride 3.3 Ketoconazole 4 Copper peptides 5 Spin labels 6 Diet and lifestyle 7 Hair transplantation 8 Hair multiplication 8.1 WNT Protein Introduction 9 Scalp massage 10 Low-level laser therapy 11 Unsaturated fatty acids 12 Hedgehog agonists 13 Plant remedies 13.1 Caffeine 13.2 Black Cohosh 13.3 Lignans 14 Genetic research 15 See also 16 Footnotes 17 External links

[edit] General concerns

It is easier to prevent the apparent "aging" and falling out of healthy hair than to regrow hair in follicles that are already dormant. There are products that have good success rates with regrowth, including finasteride (marketed in the U.S. as Propecia) and minoxidil (marketed in the U.S. as Rogaine, and outside the U.S. as Regaine). Without preventive treatment, in three double-blind, placebo-controlled, randomized studies, 72% of the balding men on placebo had lost hair compared to baseline by 24 months. This is compared to 17% of participants on Propecia.

Subsequent hair multiplication/hair cloning treatments are expected by some scientists to be able to cause these follicle stem cells to simply signal the surrounding hair follicles to rejuvenate.

Interestingly, placebo treatments in studies often have reasonable success rates, though not as high as the products being tested, and even similar side-effects as the products. For example, in finasteride (Propecia) studies, the percent of patients with any drug-related sexual adverse experience was 3.8% compared with 2.0% in the placebo group.^[4]

There are three principles, sometimes called "The Three P's" that are considered important to help produce success and avoid the somewhat common mistakes that can sabotage treatments. The Three P's are: proven treatments first, take pictures, and be patient. The average hair loss treatment takes a minimum of 6 months to begin working, and sometimes up to 24 months to truly see optimal results. Treating hair loss takes time because of hair cycles. The process of hair loss is the process of "miniaturization," which takes many years. Hairs grow in, cycle into dormancy, and then grow in again several months later. Each time they re-emerge, they do so thinner, shorter, and less pigmented. In time, they become so small that they are no longer noticeable. This can take many years.

[edit] Minoxidil

Minoxidil is a vasodilator and originally was exclusively used as an oral drug (Loniten) to treat high blood pressure. It was discovered, however, to have the side effect of hair growth and reversing baldness, and in the 1980s, Upjohn Corporation received FDA approval to market a topical solution that contained 2% minoxidil to be used to treat baldness and hair loss as Rogaine.

Objective evidence shows that minoxidil is effective in frontal areas of the scalp, and not just in the vertex area in male-pattern hair loss. At the conclusion of a 48 week study, improvements were seen in the frontal scalp regions of 51% of men using 5% minoxidil, 42% using 2% minoxidil, and 13% of placebo users. Among these men, 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 users. [11]

The method of action for Minoxidil is not known.

[edit] Antiandrogens

Antiandrogens block DHT already produced and present in the blood stream from binding with hair follicles. Their specificity varies greatly from specific antiandrogens such as finasteride which inhibit the conversion of testosterone to DHT by interfering with 5-alpha-reductase to more broad spectrum antiandrogens (fluconazole, spironolactone, etc.) Although unusual in clinical doses, antiandrogens can have serious side effects including gynecomastia.

[edit] Finasteride

Finasteride, marketed as the brand-name drug Propecia and Proscar by Merck, belongs to a class of drugs called aza-steroids. Finasteride is a "DHT inhibitor" and was originally approved by the FDA for the treatment of benign prostatic hyperplasia (BPH). It accomplishes this by blocking the production of 5-alpha-reductase, the enzyme responsible for the conversion of free testosterone to DHT.

Propecia (1 mg of finasteride daily) blocks approximately 55% of DHT activity and Proscar (5 mg of finasteride daily) blocks 70%.[12] In 1997, Finasteride was approved by the FDA for the treatment of male pattern baldness. A 5 year study revealed that 9 of 10 men taking finasteride (1 mg daily) experienced visible results (42% of men taking Propecia experienced no further hair loss while 48% experienced no further hair loss and hair regrowth).[13] In clinical studies, finasteride, like Minoxidil, was shown to work on both the crown area and the hairline area, but is most successful in the crown area.^[4]

In another study, Merck sought to find the smallest effective quantity of finasteride and test its long-term effects on 1,553 men between ages 18 and 41 with mildly to moderately thinning hair. Based on their research, 1 mg. daily was selected, and after two years of daily treatment, over 83% of the 1,553 men experiencing male hair loss had actually maintained or increased their hair count from baseline. Visual assessments concluded that over 80% had improved appearances. ^[5]

Finasteride is usually only prescribed for men and should not be used by pregnant or potentially pregnant women, as it has been speculated that it could cause severe birth defects in male fetuses.[14] Studies have shown that finasteride is ineffective for treating hair loss in women. However, finasteride's supporters respond that the study was on post-menopausal women whose hairloss was more likely related to the loss of estrogen versus a sensitivity to testosterone. Some doctors are now willing to prescribe finasteride to women on the condition that either they are taking careful birth control measures or that they cannot become pregnant.

[edit] Dutasteride

In 2001, GlaxoSmithKline released another aza-steroid called dutasteride. Dutasteride is marketed as Avodart. Like finasteride, dutasteride was originally developed for the treatment of benign prostatic hyperplasia (BPH). While hair count studies showed that 2.5 mg of dutasteride was about 1.5 times as effective as finasteride for hair regrowth (adding on average 108 versus 72 hair per 1" diameter area), Glaxo stopped FDA hair loss studies after phase II. Although the exact reason was never made public, it was speculated that the product was too similar to finasteride, which itself had not lived up to expectations commercially. As such, the 2.5 mg dosage was not released. The FDA trials for BPH continued, and Avodart became the first drug shown to shrink an enlarged prostate in a clinical study. The .5 mg version of the drug (shown in the same study to add on average 92 hairs to the same area) is increasingly available to hair loss sufferers via the grey-market of online prescription medication, and physicians increasingly willing to prescribe drugs "off-label."

In December 2006, GlaxoSmithKline embarked on a new Phase III, six month study in Korea to test the safety, tolerability and effectiveness of a once-daily dose of dutasteride (0.5 mg) for the treatment of male pattern baldness in the vertex region of the scalp (types IIIv, IV and V on the Hamilton-Norwood scale). [15] The future impact that this study will have on the FDA's approval or disapproval of Avodart for the treatment of male pattern baldness in the United States is yet to be determined.

[edit] Ketoconazole

Ketoconazole is a synthetic antifungal drug used to prevent and treat skin and fungal infections, especially in immunocompromised patients such as those with AIDS. Because it is both an anti-fungal, a 5-alpha reductase inhibitor and a hair growth stimulant,^[6] it can help to slow the balding process.^[7][8] There has been some suggestion that ketoconazole could inhibit testosterone synthesis in utero, which could potentially inhibit genital development of a male fetus. However, this has not been documented in any controlled studies.^[9] Ketoconazole has not been FDA-approved for hair loss, though it is used for other scalp conditions.

[edit] Copper peptides

Copper peptides are applied topically to the scalp, and shorten the resting phase of hairs, resulting in more hair follicles on the scalp being in the growing phase (as opposed to the resting or falling out phase) at one time.^{[dubious – discuss]} Copper peptides generally have superoxide dismutation activity.^[10]

SOD work by dismuting the superoxide anion into hydrogen peroxide, thereby preventing the converson of the superoxide anion to peroxynitrite (a free-radical) by combining with nitric oxide (a naturally occurring chemical messenger). The double effect of SOD therefore is the reduction in free-radical and increase in nitric oxide. It is thought that a key mechanism of action for minoxidil is the production of Nitric oxide (NO). Superoxide has an "agonist-antagonist" relationship with Nitric oxide or "Endothelium-derived Relaxing Factor".^[11]

Various SOD generating products are now available however one problem with SOD is the production of Hydrogen Peroxide as a bi-product of singlet oxygen (superoxide anion) quenching. In the human body, the enzyme catalase converts the SOD hydrogen peroxide byproduct into water and oxygen. Nanogen, a UK based skin research company is undergoing Phase I trials to ascertain the hair regrowth potential on a new "broad-spectrum" molecule which has been shown in extensive independent laboratory in-vitro testing to have both SOD and Catalase mimetic activity. The company has not released details of the molecule as it is pending patent but it is copper II based.

[edit] Spin labels

In animal models, the nitroxide spin labels TEMPO and TEMPOL enhance hair regrowth following radiation. National Cancer Institute-sponsored clinical trials report TEMPOL is similarly effective in humans. Also see United States Patent 5,714,482 "Topical spin labels and method"[16].

[edit] Diet and lifestyle

There are a number of genetic factors which determine a person's susceptibility to androgenic alopecia including androgen receptor polymorphisms, 5-alpha-reductase levels in the scalp, androgen receptor density and distribution in the scalp, and other factors some of which may not have been discovered.

Daily, vigorous aerobic exercise (as opposed to short workout periods designed to raise androgen levels and build muscle, or more sporadic exercise) and a diet which is adequate yet more moderate in terms of fat and total calorie intake have been shown to reduce baseline insulin levels as well as baseline total and free testosterone,^[12].

Lower insulin levels and reduced stress both result in raised levels of Sex Hormone Binding Globulin (SHBG). SHBG binds to testosterone, and prevents it from circulating free in the blood. Only free testosterone is converted to DHT. It is the level of free androgens and not total androgens which is relevant to the levels of DHT in the scalp and the progression of MPB. In short, aerobic exercise is capable of significantly lowering DHT. ^{[13] [14]} Exercise has not been shown to prevent male-pattern baldness.

Androgenic alopecia has been shown to correlate with metabolic syndrome. Medically increasing androgen levels does not worsen this condition, demonstrating that androgens do not cause metabolic syndrome. Instead, high insulin levels (and possibly chronic inflammation^[15]) seem the likely link in the demonstrated correlation between baldness and metabolic syndrome. This reinforces the notion that behaviors which help to keep insulin levels low and reduce chronic inflammation might also help to preserve hair.^[16][17]

[edit] Hair transplantation

Hair transplantation involves relocating (transplanting) bald resistant hair follicles from the back and sides of the head (the donor areas) to a person’s bald or thinning areas. The transplanted hair follicles will typically grow hair for a lifetime because they are genetically resistant to going bald. In recent years hair transplantation techniques have evolved from using large plugs and mini grafts to exclusively using large numbers of small grafts that contain from between 1 to 4 hairs.

Since hair naturally grows in follicles that contain groupings of 1 to 4 hairs, today’s most advanced techniques transplant these naturally occurring 1 – 4 hair "follicular units" in their natural groupings. Thus modern hair transplantation can achieve a natural appearance by mimicking nature hair for hair.

Another method is scalp reduction, in which skin in the balding area of the scalp is surgically excised. The left over skin is then pulled together and sutured.

[edit] Hair multiplication

Stem cells and dermal papilla cells have been discovered in hair follicles and some researchers predict research on these follicular cells may lead to successes in treating baldness through hair multiplication (HM), also called hair cloning.

HM is being developed by two independent companies: ARI (Aderans Research Institute, a Japanese owned company in the USA) and Intercytex, a company in Manchester (UK).^[18][19]

In 2008, Intercytex announced positive results of a Phase II trial for a form of cloning hair follicles from the back of the neck, multiplying them and then reimplanting the cells into the scalp. The initial testing resulted in at least two thirds of male patients regrowing hair. As of 2009, the company estimates this treatment will take "a number of years to complete" Phase III trials before it can go to market.^[20]

[edit] WNT Protein Introduction

In May 2007, U.S. company Follica Inc, announced they have licensed technology from the University of Pennsylvania which can regenerate hair follicles by reawakening genes which were once active only in the embryo stage of human development. Skin apparently can be brought back to this embryonic state when a wound is healing. Hair growth was discovered in the skin wounds of mice when wnt proteins were introduced to the site. Development of a human treatment is expected to take several years.^[21]

[edit] Scalp massage

A randomized clinical trial of patients with bald patches on their scalp or skin showed a daily scalp massage with essential oils to be a safe and effective treatment for hair loss resulting from alopecia areata, a condition in which damage to hair follicles is caused by the patient's own immune system.^[22][23]

[edit] Low-level laser therapy

Although there is no peer-reviewed evidence to support this claim, devices are sold that use a low level laser shone directly on the scalp with the intent to stimulate hair growth through "Photo-Biostimulation" of the hair follicles. One product of these low level laser therapies is the Hairmax Lasercomb. There is some debate over the FDA's acknowledgment of the Lasercomb.^[24] Under the looser standards applicable to medical devices, the HairMax LaserComb was cleared by the FDA as being "substantially equivalent" to predicate devices legally marketed before May 28, 1978. The devices that the lasercomb proved itself equivalent to were a variety of FDA approved non hair growth/laser based devices intended for hair removal and pain relief, and two non FDA approved non laser based/hair growth devices such as the Raydo & Wonder Brush and the Vacuum Cap. These last two devices were sold in the early 1900s and are well established as medical quackery, but they were legal to market at the time which does satisfy the FDA's minimal 510k SE criteria. The 510k number for the Lasercomb is K060305.

The Leimo laser was recently approved by the TGA (Therapeutic Goods Administration) of Australia as a Class IIa Medical Device. It was approved for safety but not for efficacy of results. The company is advertising that this unit is TGA approved to grow hair, which is false.

[edit] Unsaturated fatty acids

Particular unsaturated fatty acids such as gamma linolenic acid are 5 alpha reductase inhibitors if taken internally.^[25]

[edit] Hedgehog agonists

Through 2006, a drug development company spent $1,000,000 on a hair growth program focused on the potential development of a topical hedgehog agonist for hair growth disorders such as male pattern baldness and female hair loss. The hair loss research program was shut down in May 2007 because the process did not meet the proper safety standards.^[26]

[edit] Plant remedies

[edit] Caffeine

Caffeine has been identified as a stimulator of human hair growth in vitro, and reduced testosterone-induced follicle growth suppression.^[27] 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.^[28] Further research must be done to evaluate the efficacy and adequate dosage of caffeine in the treatment of androgenetic alopecia.

A spray made with coffee beans is claimed to prevent age-related hair loss in women. [17]

[edit] Black Cohosh

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Black Cohosh (the most popular non-synthetic treatment in women for menopause in the world) has also been patented by the Germans as a baldness treatment. Its mechanism of action is not fully understood but it is known to cause estrogen/progesterone receptors to bias in favour of estrogen, thus increasing the amounts present in the male user. Estrogen has a limited effect as an anti-androgen, but it is also responsible for the production of a soft layer of fat and thus a softening of the scalp.

[edit] Lignans

Lignans from flax seed, sesame seed, or Norwegian spruce have been proposed as baldness cures, but are scientifically unproven.^{[citations needed]}

[edit] Genetic research

In February 2008 researchers at the University of Bonn announced they have found the genetic basis of two distinct forms of inherited hair loss, opening a broad path to treatments for baldness. They found that a 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. The fact that any receptor plays a specific role in hair growth was previously unknown to scientists and with this new knowledge a focus on finding more of these genes may be able to lead to therapies for very different types of hair loss.^[29] Their patent-pending work on the various loci region of Chromosome 20 are the subject of two Nature articles. Researchers in Germany (University of Bonn) and the UK (Pangaea Laboratories Ltd.) are working on the feasibility of drug target treatments and predictive testing for alopecia with the emphasis on screening patients for their likelihood to first lose their hair and second to ensure determine which patients are likely to benefit from which drug treatment avoiding the need for unsuccessful courses and side effects.

[edit] See also

• Baldness
• Comb over
• Toupee

[edit] Footnotes

[edit] External links

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

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