Baldness treatments

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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.

Contents 1 General concerns 2 Minoxidil 3 Antiandrogens 3.1 Finasteride 3.2 Dutasteride 3.3 Ketoconazole 3.4 Saw palmetto 4 Caffeine 5 Copper peptides 6 Spin labels 7 Diet and lifestyle 8 Hair transplantation 9 Hair multiplication (under development) 9.1 wnt protein introduction 10 Scalp massage 11 Low-level laser therapy 12 Unsaturated fatty acids 13 Hedgehog agonists 14 General preventive warnings 15 FDA-approved treatments 16 Other treatments 17 Latest Research 18 See also 19 Footnotes 20 External links

[edit] General concerns

It is easier to prevent the apparent 'aging' and falling out of healthy hairs than to regrow hair in follicles that are already dormant. There are products that have good success rates with regrowth, including the scientifically proven 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.

The prospective treatment of hair multiplication/hair cloning, which extracts self-replenishing follicle stem cells, multiplies them many times over in the lab, and microinjects them into the scalp, has been shown to work in mice, and is currently under development, expected by some scientists to be available to the public in 2009-2015. Subsequent versions of the treatment are expected by some scientists to be able to cause these follicle stem cells to simply signal the surrounding hair follicles to rejuvenate.

The below treatments are some of the most prominent. Generic brands, often with identical chemical structure or the same active ingredients, may be equally effective and are cheaper.

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.^[2]

While treating hair loss most successfully is a multi-faceted, ongoing experiment for the individual, 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. New hairs only grow in a 2 or 3 year cycle, which is why it can take a year or more to be able to detect the success of a treatment.

This difficulty can be increased because it is speculated that many (scientifically proven) treatments often cause initial periods of shedding, as some resting hair follicles are ejected and a new cycle of growth begins, hopefully with a thicker follicle. Discontinuing all treatment will cause a period of shedding, likely to one's non-treatment baseline, but probably not worse.^{[citation needed]}

[edit] Minoxidil

Main article: 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.

Minoxidil is applied topically to the scalp, and has been shown to promote hair growth in about 25% of men and women^{[citation needed]}, though it may take several months to work. New hair is usually thinner and lighter, like baby hair, and grows mostly on the top of the head, not at the hairline. Skin irritation is the most commonly reported side effect. Dizziness and increased heart rate are listed side-effects on the UK patient information leaflet.

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. [1]

FDA clinical trials showed that 65% of men with androgenetic alopecia maintained or increased their hair count from the use of minoxidil 5% in liquid form. 54% of these men experienced moderate to dense regrowth and 46% experienced hair loss stabilisation and mild regrowth.^{[citation needed]}

In controlled clinical studies of women aged 18-45, two out of three women with moderate degrees of hereditary hair loss reported re-growth after using 2% minoxidil. Initial results occur at four months with maximum results occurring at eight months.^{[citation needed]}

The method of action for Minoxidil is not known. It is clearly not just the vasodialating effects which cause hair regrowth, as no other vasodilator has been shown to be effective in treating hair loss.

[edit] Antiandrogens

Main article: Antiandrogen

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. Ketoconazole, (often sold as Nizoral Shampoo) and is prescribed by medical professionals or available over the counter depending on the product, concentration and country.

[edit] Finasteride

Main article: 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 (5mg of finasteride daily) blocks 70%.[2] 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 (1mg daily) experienced visible results (42% of men taking Propecia experienced no further hair loss while 48% experienced no further hair loss and hair regrowth).[3] In clinical studies, finasteride, like Minoxidil, was shown to work on both the Crown (anatomy) area and the hairline area, but is most successful in the crown area.^[2]

On another study, a pharmaceutical company reportedly 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 mild to moderate 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. ^[3]

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.[4] 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. Other studies have shown that finasteride is effective for many women with follicular sensitivity to androgens.^{[citation needed]} Some doctors are now willing to prescribe finasteride to women on the condition that either the women is taking careful birth control measures or that the woman cannot become pregnant.

[edit] Dutasteride

Main article: 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 .5mg 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 (0.5mg) for the treatment of male pattern baldness in the vertex region of the scalp (types IIIv, IV and V on the Hamilton-Norwood scale). [5] 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

Main article: 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 and also a 5-alpha reductase inhibitor, it can help to slow the balding process.^[4][5] 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.^[6]

[edit] Saw palmetto

Main article: Saw Palmetto

Saw palmetto (Serenoa repens) is an herbal DHT inhibitor which is cheaper than most commercial drugs and is claimed to have fewer side effects than finasteride and dutasteride. Unlike other 5-alpha-reductase inhibitors, saw palmetto extract inhibits the conversion of testosterone to DHT without interfering with the cellular capacity to secrete PSA.^[7]

Saw palmetto extract has been demonstrated to inhibit both isoforms of alpha-5-reductase, unlike finasteride which only inhibits the (predominant) type 2 isoenzyme of alpha-5-reductase.^[8][9][10] In one of those studies it was noted improvement in six of ten subjects over a six month period. Dosages were not reported.^[8] The small size of the study and its relatively short duration must be noted. It was disputed on the 20/20 TV program in January 2003[6].

[edit] Caffeine

Main article: Caffeine

Caffeine has been identified as a stimulator of human hair growth in vitro, and reduced testosterone-induced follicle growth suppression.^[11] 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.^[12] 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. [7]

[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. Copper peptides generally have superoxide dismutation activity.^[13]

SOD's likely work by destroying superoxide, the antagonist to Nitric oxide (NO), the natural form of minoxidil. Superoxide has an "agonist-antagonist" relationship with Nitric oxide or "Endothelium-derived Relaxing Factor".^[14]

A product called Tricomin, released by Procyte, based on Copper Peptides was shown in FDA studies to produce results similar to 2% minoxidil. FDA studies were discontinued, according to Procyte, because of the expense. While by today's standards these results are quite sub-par, compounds based on this formula are licensed by Procyte to "cosmo-ceutical" makers, and have been shown in clinical studies to help hair grafts take after the transplant.^{[citation needed]}

[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".

[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. Some speculate the increase in baldness in the population of Japan after World War II^{[citation needed]} demonstrates that hair loss can be influenced by diet and lifestyle. Increased fat or caloric intake, decrease in aerobic exercise and general "westernization" was accompanied by a dramatic increase in incidence of male pattern baldness.^{[citation needed]}

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,^[15] which would significantly lower baseline DHT.

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. However, exercise has not been shown to prevent male-pattern baldness.^[16][17]

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^[18]) 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.^[19][20]

[edit] Hair transplantation

Main article: 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. This recent hair transplant procedure is called "follicular unit transplantation". Given the improved naturalness of hair transplantation surgery hair loss sufferers are increasingly selecting this hair loss treatment.^{[citation needed]}

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 (under development)

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. This treatment is expected to initially work through harvesting such cells from existing follicles, multiplying them many times over in the lab, and microinjecting or implanting groups of cells into the scalp.^{[citation needed]} Subsequent versions of the treatment are expected by some scientists to be able to cause these follicle stem cells to simply signal the surrounding hair follicles to rejuvenate.^{[citation needed]}

The first products are now expected to hit the market in 2010. However, it remains unclear how effective they are going to be. It has been suggested that only future generations of HM will allow patients to grow as much hair as they want.^{[citations needed]}

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).^[21][22]

On October 2006, Intercytex announced they have successfully tested a method of removing hair follicles from the back of the neck, multiplying them and then reimplanting the cells into the scalp. The initial testing resulted in 70% of male patients regrowing hair. This treatment method is expected to be available to the public by 2010 [8][9][10]. The company was awarded a £1.85 million ($3.63 million) grant by the UK Department of Trade and Industry (DTI) through the Technology Programme to develop an automated manufacturing process for ICX-TRC, Intercytex’s novel hair regeneration therapy^{[citation needed]}. The grant will be used primarily to develop a dedicated robotic system to support the commercial-scale production of dermal papilla (DP) cells, the main cells involved in hair regeneration and the key component of ICX-TRC.

In June 2008, Intercytex announced positive results of their Phase II trial for a form of cloning based Hair multiplication technique called follicular cell implantation.[11] The treatment is being hailed as a major advance in hair restoration and is backed by a £1.9 million government grant. The treatment is predicted to be availale to patients withn 5 years.

In January 2007, Italian stem-cell researchers say they've come up with a new technique for curing baldness. Pierluigi Santi of a Genoa clinic said stem cells could be used to "multiply" hair roots. He said the clinic would be ready to perform its first hair transplants on priority patients - those who have lost their hair in fires or other accidents - within a few months. After that, he said, "we'll open our doors to paying customers". Santi's approach works by splitting roots and growing new follicles.^{[citation needed]} m

[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. [12] [13] [14] [15] [16][17] [18] [19].

[edit] Scalp massage

Scalp massage stimulates blood flow, which in turn helps feed the hair follicles. Nourishment is sent to the capillary vessels in hair papillae to activate the hair cells. Often it helps to prevent and fight avoidable hair loss, and reestablish the natural development of healthy hair.^{[citations needed]}

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. [20][21]

[edit] Low-level laser therapy

A low level laser is shone directly on the scalp 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 no peer-reviewed evidence to support this claim. There is some debate over the FDA's acknowledgment of the Lasercomb, but it has been accepted by the FDA as effective in the submitted claims.^[23][24] The Lasercomb was cleared by the FDA as being "substantially equivalent" to predicate devices legally marketed before May 28, 1978. This clearance is not the same as approval because it only applies to the lasercomb and not to any other similar laser based hair devices. The devices that the lasercomb proved itself equivalent to were a variety of FDA approved laser based/non hair growth 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 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. The TGA advertising board is now investigating all advertising that relates to Leimo Lasers.^{[citations needed]}

[edit] Unsaturated fatty acids

Particular unsaturated fatty acids such as gamma linolenic acid are 5 alpha reductase inhibitors if taken internally. [22]

[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.^[25]

[edit] General preventive warnings

Main article: Hair care

This article or section contains instructions, advice, or how-to content. The purpose of Wikipedia is to present facts, not to teach subject matter. Please help improve this article by removing or rewriting the how-to content, which may qualify for a move to http://www.wikihow.com/ or http://howto.wikia.com/.

• When using blow dryers, always keep the heat a good distance from your scalp and hair. Avoid heating the scalp and hair excessively.

• Avoid getting hair creams, lotions, styling gels and sprays directly on the scalp as this can clog your hair follicles.

• After swimming in a pool, shampoo your hair as soon as possible to remove any chlorine residue. Chlorine is extremely damaging to the hair and scalp.

• Avoid over-exposing your hair and scalp to the wind and sun.

• Avoid tight hats and caps as they contribute to poor circulation, depriving the hair of proper nutrition. Sweat, dirt, and grime around the rim will inhibit follicle health and contribute to build-up.

• Brushing too much or too roughly can strip away your hair's cuticle, or even cause hairs to break.

[edit] FDA-approved treatments

There are only 2 FDA-approved treatments for male baldness: Minoxidil and Finasteride.^[26][27]

There is some debate over the FDA's acknowledgment of the Lasercomb, but it has been accepted by the FDA as effective in the submitted claims.^[28][29]

[edit] Other treatments

• Azelaic acid - A study found a 90% inhibition of 5-alpha-reductase activity in vitro with an azelaic acid and zinc combination. There was an additive effect between the two compounds.^[30]
• He Shou Wu
• Procapil manufactured by Croda International Plc
• Pumpkin seed - Used to aid in the breakdown of DHT by the liver.^{[citation needed]} An extract is often used, as unprocessed pumpkin seeds are high in fat which can exacerbate hair loss in susceptible patients.
• Regenix
• RU58841
• Spironolactone
• Stinging nettle
• Tretinoin (aka Retinoic acid and as tradename Retin-A); chemical peel stimulation of scalp)
• Zinc - While oral zinc supplementation may help prevent the conversion of testosterone to DHT, it also increases total testosterone levels^{[citation needed]}.
• Electrotrichogenesis

[edit] Latest 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.[23][24]

In May 2008, researchers at the University Pennsylvania unveiled a new scientific breakthrough that may cure baldness with stem cells. A product could be on the market within three years. [25][26].

[edit] See also

• baldness
• comb over
• toupee

[edit] Footnotes

[edit] External links

• Children's Alopecia Project
• International Society of Hair Restoration Surgery Resources for finding doctors, and more information about hair loss. This is one of the leading organizations in the world on hair loss.
• "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.
• How Hair Replacement Works Covers oral medications, hair transplant surgery, and topical treatments.
• The Trichological Society

v • d • e Other dermatological preparations (D11) Medicated shampoos Cetrimide - Cadmium compounds - Selenium compounds - Povidone-iodine - Sulfur compounds - Xenysalate Other dermatologicals seborrhoeic dermatitis/dandruff (Lithium succinate, Pyrithione zinc) skin whitening/depigmenting (Hydroquinone, Mequinol, Monobenzone) anti-inflammatory/Immunomodulators (Oxaceprol, Gamolenic acid), Pimecrolimus, Tacrolimus) baldness treatments (Finasteride, Minoxidil) hair growth inhibiting agent (Eflornithine) other (Calcium gluconate, Magnesium sulfate, Tiratricol)