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. 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.
- 1 General concerns
- 2 Minoxidil
- 3 Antiandrogens
- 4 Caffeine
- 5 Copper peptides
- 6 Spin labels
- 7 Diet and lifestyle
- 8 Hair transplantation
- 9 Hair multiplication (under development)
- 10 Scalp massage
- 11 Low-level laser therapy
- 12 Unsaturated fatty acids
- 13 Hedgehog agonists
- 14 General preventive warnings
- 15 FDA-approved treatments
- 16 Latest research
- 17 See also
- 18 Footnotes
- 19 External links
- 20 Discuss
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 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.
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.
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.
Main article: Minoxidil
Minoxidil is a vasodilator and originally was exclusively used as an oral drug (LonitenÂ®) 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. 
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.
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.
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%. 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). 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.
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. 
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. 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.
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).  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.
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, it can help to slow the balding process. 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.
Caffeine has been identified as a stimulator 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.
A spray made with coffee beans is claimed to prevent age-related hair loss in women. 
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.
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".
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".
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,.
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.
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) 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.
Hair transplantation involves relocating (transplanting) bald resistant hair follicles from the back and sides of the head (the donor areas) to a personâ€™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, todayâ€™s most advanced techniques transplant these naturally occurring 1 â€“ 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.
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.
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).
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 .
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.
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.       .
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.
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. The HairMax 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.
Unsaturated fatty acids
Particular unsaturated fatty acids such as gamma linolenic acid are 5 alpha reductase inhibitors if taken internally.
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.
General preventive warnings
Main article: Hair care
- 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.
- Brushing too much or too roughly can strip away your hair's cuticle, or even cause hairs to break.
There are only 2 FDA-approved treatments for male baldness: Minoxidil and Finasteride.
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.
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.
In May 2007, researchers at the University of Pennsylvania unveiled a new scientific breakthrough that may cure baldness with stem cells. A product could be on the market within three years.
- ↑ Whyche, Stephanie. The Bald Truth About Hair Loss In Young Men. Retrieved on 2006-07-26.
- ↑ 2.0 2.1 Leyden J, Dunlap F, Miller B, et al (June 1999). "Finasteride in the treatment of men with frontal male pattern hair loss". J. Am. Acad. Dermatol. 40 (6 Pt 1): 930â€“7. PMID 10365924.
- ↑ Medscape summary of the full article
- ↑ Jiang, J. Tsuboi, R., Kojima, Y. and Ogawa, H. Topical application of ketoconazole stimulates hair growth in C3H/HeN mice. J Dermatol. 2005 Apr;32(4):243-7.
- ↑ Hugo Perez BS (2004). "Ketocazole as an adjunct to finasteride in the treatment of androgenetic alopecia in men". Med Hypotheses 62 (1): 112â€“115. doi:10.1016/S0306-9877(03)00264-0. PMID 14729013.
- ↑ Pierard-Franchimont C; De Doncker P, Cauwenbergh G, Pierard GE (1998). "Ketoconazole shampoo: effect of long-term use in androgenic alopecia". Dermatology 196 (4): 474â€“477. doi:10.1159/000017954. PMID 9669136.
- ↑ Ketoconazole-(P). Illinois Teratogen Inforamation Service. Retrieved on 2006-08-09.
- ↑ Fischer TW et al (2007). "Effect of caffeine and testosterone on the proliferation of human hair follicles in vitro" (abstract). International Journal of Dermatology 46(1): 27â€“35. doi:10.1111/j.1365-4632.2007.03119.x.
- ↑ Otberg N, Teichmann A, Rasuljev U, Sinkgraven R, Sterry W, Lademann J (2007). "Follicular penetration of topically applied caffeine via a shampoo formulation". Skin Pharmacol Physiol 20 (4): 195â€“8. doi:10.1159/000101389. PMID 17396054.
- ↑ US patent 5,470,876, "Topical SOD for treating hair loss"
- ↑ "Endothelium-Derived Relaxing Factor and Minoxidil: Active Mechanisms in Hair Growth", Archives in Dermatology, vol 125, August, 1989
- ↑ Daly W, Seegers CA, Rubin DA, Dobridge JD, Hackney AC (Jan 2005). "Relationship between stress hormones and testosterone with prolonged endurance exercise". Eur. J. Appl. Physiol. 93 (4): 375â€“80. doi:10.1007/s00421-004-1223-1. PMID 15618989.
- ↑ Barnard RJ, Aronson WJ, Tymchuk CN, Ngo TH (Nov 2002). "Prostate cancer: another aspect of the insulin-resistance syndrome?". Obes Rev 3 (4): 303â€“8. doi:10.1046/j.1467-789X.2002.00081.x. PMID 12458975.
- ↑ Barnard RJ, Aronson WJ (2005). "Preclinical models relevant to diet, exercise, and cancer risk". Recent Results Cancer Res. 166: 47â€“61. doi:10.1007/3-540-26980-0_4. PMID 15648182.
- ↑ Joffe HV, Ridker PM, Manson JE, Cook NR, Buring JE, Rexrode KM (Feb 2006). "Sex hormone-binding globulin and serum testosterone are inversely associated with C-reactive protein levels in postmenopausal women at high risk for cardiovascular disease". Ann Epidemiol 16 (2): 105â€“12. doi:10.1016/j.annepidem.2005.07.055. PMID 16216530.
- ↑ Cikim AS, Ozbey N, Sencer E, Molvalilar S, Orhan Y (Oct 2004). "Associations among sex hormone binding globulin concentrations and characteristics of the metabolic syndrome in obese women". Diabetes Nutr. Metab. 17 (5): 290â€“5. PMID 16295051.
- ↑ Heald AH, Anderson SG, Ivison F, et al (Oct 2005). "Low sex hormone binding globulin is a potential marker for the metabolic syndrome in different ethnic groups". Exp. Clin. Endocrinol. Diabetes 113 (9): 522â€“8. doi:10.1055/s-2005-865807. PMID 16235154.
- ↑ Hair Cloning Nears Reality as Baldness Cure. Webmd.com (2004-11-04). Retrieved on 2006-08-10.
- ↑ Big Baldness Breakthrough?. Associated Press (2004-03-15). Retrieved on 2006-08-10.
- ↑ http://www.cancer.org/docroot/ETO/content/ETO_5_3X_Aromatherapy.asp
- ↑ Hay IC, Jamieson M, Ormerod AD (Nov 1998). "Randomized trial of aromatherapy. Successful treatment for alopecia areata". Arch Dermatol 134 (11): 1349â€“52. PMID 9828867.
- ↑ 22.0 22.1 LaserComb Controvery at Tressless: The Hairloss Encyclopedia
- ↑ NBC2 News Online - Low level lasers approved for treating hair loss
- ↑ Liang T, Liao S (Jul 1992). "Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids". Biochem. J. 285 ( Pt 2): 557â€“62. PMID 1637346.
- ↑ "Curis and Procter & Gamble Enter into R&D Agreement for Hair Growth Program". Retrieved on 2006-08-24.
- ↑ http://www.webmd.com/skin-beauty/guide/hair-loss-treatments.
- ↑ http://www.fda.gov/cdrh/pdf6/K060305.pdf
- ↑ NBC2 News Online - Low level lasers approved for treating hair loss
- 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)
- How Hair Replacement Works Covers oral medications, hair transplant surgery, and topical treatments.
- The Trichological Society
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