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
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 1980's, 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, 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. Its effects may fade with time. 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 now 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 percent of men using 5 percent minoxidil, 42 percent using 2 percent minoxidil, and 13 percent of placebo users. Among these men, moderate to great increases in hair growth were seen in the frontal scalp regions of 19 percent of men using 5 percent minoxidil, 10 percent using 2 percent minoxidil, and 3 percent of placebo users. [1]
[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.) which can have serious side effects including gynecomastia. Ketoconazole, (often sold as Nizoral Shampoo) and Neutrogena T-Gel have been clinically shown to have antiandrogen properties[citation needed] and are prescribed by medical professionals or available over the counter depending on the product, concentration and country.
[edit] Finasteride
Finasteride, marketed as the brand-name drug Propecia, belongs to a class of drugs called aza-steroids. It is a "DHT inhibitor" that is FDA approved to inhibit production of DHT through the entire body. It accomplishes this by blocking the production of 5-alpha-reductase, the enzyme responsible for the conversion of free testosterone to DHT. Finasteride is taken orally and has a reported 29-68% success rate (vs. 17-45% in patients receiving a placebo). It is effective only for as long as it is taken; the hair gained or maintained is lost within 6-12 months of ceasing therapy (Rossi, 2004). In clinical studies, finasteride, like minoxodil, was shown to work on both the crown area and the hairline,[2] but is most successful in the crown area.
Finasteride has been shown to be ineffective for treating hair loss in women, and should not even be touched by pregnant or potentially pregnant women, as it has been speculated that it could cause severe birth defects in male fetuses.[citation needed] 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[citation needed] have shown that finasteride is effective for many women with follicular sensitivity to androgens. Many doctors do prescribe it, but not without either careful birth control measures or assurance that the woman cannot become pregnant.
Recently, Glaxo Wellcome released another aza-steroid called dutasteride and marketed as "Avodart", also for 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. While the exact reason was never made public, it was leaked 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 hair 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, GlaxoSmithKlein 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). [2] 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 and also a 5-alpha reductase inhibitor, it can help to slow the balding process. [3] [4] 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. [5]
[edit] 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.[6] 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.[7] [8] It must be noted that DHT inhibition in vitro does not necessarily imply inhibition in vivo. A preliminary study of saw palmetto extract for treating hair loss noted improvement in six of ten subjects over a six month period. Dosages were not reported. [7] The small size of the study and its relatively short duration limit must be noted.
There hasn't been a single reputable study done showing that Saw Palmetto has any effect on treating hair loss. One study can be found in PubMed, but it was run by the makers of a saw palmetto product, and was publicly labeled as "Bunk" on 20/20 in January 2003 on nationwide television because it only included 10 participants and lasted only 6 months. [8]
[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. The most popular of these low level laser therapies is the Hairmax Lasercomb. There is no peer-reviewed evidence to support this claim. The Lasercomb is FDA approved only with regard to safety.[9]
[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. See US patent 5,470,876, "Topical SOD for treating hair loss". There is a strong belief in the hair loss treatment community that SOD based treatments may reduce scalp irritation and dandruff often associated with hair loss, and other hair loss treatments.
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". See "Endothelium-Derived Relaxing Factor and Minoxidil: Active Mechanisms in Hair Growth", Archives in Dermatology, vol 125, August, 1989
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
While 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 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]
Skeptics of this analysis believe the westernization that led to increased hair loss in Japan may have occurred in the gene pool, noting the higher propensity of hair loss in American soldiers of European descent stationed in and around Japan after the war.
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[10], 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. [11] [12]
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 [13]) 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. [14] [15]
[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 mimicing 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.
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 (upcoming treatment)
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, also called hair cloning, within three or four years[citation needed]. This treatment is expected to initially work through harvesting such cells from existing follicles, multiplying them in cultures, and injecting or implanting groups of cells into the scalp. Later treatments may be able to simply signal follicle stem cells to transmit chemical signals to nearby follicle cells which have shrunk during the aging process, which respond to these signals by regenerating and once again making healthy hair.
Unfortunately, this new approach to treating baldness appears to be taking longer than expected. The first products are now expected to hit the market in 2009/2010. 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.
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).[16] [17]
On October 2006, UK biotechnology firm 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 2009 [3][4]. On October 6, 2006, 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. 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 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.
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.[5] [6] [7] [8] [9][10]
[edit] FDA-approved treatments
There are only 2 FDA-approved treatments for male baldness: Minoxidil and Finasteride. [18] [19] The Lasercomb is FDA approved only with regard to safety.[20]
[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.[21]
- Spironolactone
- Tretinoin (aka Retinoic acid and as tradename Retin-A); chemical peel stimulation of scalp)
- Regenix
- Avacor
- 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.
- Procapil manufactured by Croda International Plc
- Stinging nettle
- Zinc - While oral zinc supplementation may help prevent the conversion of testosterone to DHT, it also increases total testosterone levels[citation needed].
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