Alopecia or hair loss is the medical description of the loss of hair from the head or body, sometimes to the extent of baldness. Unlike the common aesthetic depilation of body hair, alopecia tends to be involuntary and unwelcome, e.g., androgenic alopecia. However, it may also be caused by a psychological compulsion to pull out one's own hair (trichotillomania) or the unforeseen consequences of voluntary hairstyling routines (mechanical "traction alopecia" from excessively tight ponytails or braids, or burns to the scalp from caustic hair relaxer solutions or hot hair irons).
In some cases, alopecia is an indication of an underlying medical concern, such as iron deficiency.
When hair loss occurs in only one section, it is known as alopecia areata. Alopecia universalis is when complete hair loss on the body occurs, similar to how hair loss associated with chemotherapy sometimes affects the entire body.
The pattern of hair loss in women differs from male pattern baldness. In women, the hair becomes thinner all over the head, and the hairline does not recede. Androgenic alopecia in women rarely leads to total baldness.
Male pattern baldness is caused by a genetic sensitivity of hair follicles to DHT, which causes them to shrink when exposed to it. This shortens their lifespan and prevents them from producing hair normally.
Large studies in 2005 and 2007 stress the importance of the maternal line in the inheritance of male pattern baldness. German researchers name the androgen receptor gene as the cardinal prerequisite for balding. They conclude that a certain variant of the androgen receptor is needed for AGA to develop. In the same year the results of this study were confirmed by other researchers. This gene is recessive and a female would need two X chromosomes with the defect to show typical male pattern alopecia. Seeing that androgens and their interaction with the androgen receptor are the cause of AGA it seems logical that the androgen receptor gene plays an important part in its development.
Other research in 2007 suggests another gene on the X chromosome, that lies close to the androgen receptor gene, is an important gene in male pattern baldness. They found the region Xq11-q12 on the X-chromosome to be strongly associated with AGA in males. They point at the EDA2R gene as the gene that is mostly associated with AGA.
Other genes involved with hair loss have been found. One of them being a gene on chromosome 3. The gene is located at 3q26. This gene is recessive.
Another gene that might be involved in hair loss is the P2RY5. This gene is linked to hair structure. Certain variants can lead to baldness at birth, while another variant causes "wooly hair."
In May 2009, researchers in Japan identified a gene, Sox21, that appears to be responsible for hair loss in people.
5-alpha-reductase is responsible for converting free testosterone into DHT. The genes for 5-alpha-reductase are known. The enzymes are present predominantly in the scalp and prostate. Levels of 5alpha-reductase are one factor in determining levels of DHT in the scalp and drugs which interfere with 5alpha-reductase (such as finasteride, which inhibits the predominant type 2 isoform) have been approved by the FDA as treatments for hair loss.
Sex hormone binding globulin (SHBG), which is responsible for binding testosterone and preventing its bioavailability and conversion to DHT, is typically lower in individuals with high DHT. SHBG is downregulated by insulin.
Increased levels of Insulin Growth Factor-1 (IGF-1) have been correlated to vertex balding.
High insulin levels seem the likely link between metabolic syndrome and baldness. Low levels of SHBG in men and non-pregnant women are also correlated with glucose intolerance and diabetes risk, though this correlation disappears during pregnancy.
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 both the frontal areas of the scalp and the vertex area in treating 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.
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.
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 US FDA for the treatment of benign prostatic hyperplasia (BPH). The drug works by binding to 5-alpha-reductase, the enzyme responsible for the conversion of free testosterone to DHT.
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.
In 1997, Finasteride was approved by the US 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). 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.
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.
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). GlaxoSmithKline has published the results of the study.
The future impact that this study will have on the US FDA's approval or disapproval of Avodart for the treatment of male pattern baldness in the United States is yet to be determined.
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, 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. Ketoconazole has not been FDA-approved for hair loss, though it is used for other scalp conditions.
In some cases, alopecia is an indication of an underlying medical concern, such as iron deficiency.
When hair loss occurs in only one section, it is known as alopecia areata. Alopecia universalis is when complete hair loss on the body occurs, similar to how hair loss associated with chemotherapy sometimes affects the entire body.
Causes
- Androgenetic alopecia (Male pattern baldness)
- Fungal infection such as "black dot" tinea or tinea capitis
- Chemical breakage such as over processing, or frequent use of chemical relaxer
- Heat damage as from repeated hot comb use
- Chronic exposure to traction on hair shaft such as Traction alopecia
- Compulsive hair pulling such as trichotillomania
- Hypothyroidism
- Iron deficiency
- Alopecia areata
- Telogen effluvium resulting from physical or psychological stress
- Hereditary disorder of the hair shaft or genodermatoses
- Secondary syphillis can cause "moth eaten hairloss"
- Discoid lupus erythematosus or chronic cutanous lupus erythematosus
- Lichenplanopilaris
- Pseudopelade of Brocq
- Tufted folliculitis
- Dissecting cellulitis
- Alopecia mucinosa
- Keratosis follicularis spinulosa decalvans
- Adverse effect from certain drugs such as chemotherapy
- Testosterone booster tablets.
Androgenic alopecia
Androgenic alopecia (also known as androgenetic alopecia or alopecia androgenetica) is a common form of hair loss in both female and male humans, chimpanzees, and orangutans. In male humans in particular, this condition is also commonly known as male pattern baldness. Hair is lost in a well-defined pattern, beginning above both temples. Hair also thins at the crown of the head. Often a rim of hair around the sides and rear of the head is left, or the condition may progress to complete baldness.The pattern of hair loss in women differs from male pattern baldness. In women, the hair becomes thinner all over the head, and the hairline does not recede. Androgenic alopecia in women rarely leads to total baldness.
Cause
A variety of genetic and environmental factors likely play a role in causing androgenic alopecia. Although researchers are studying the factors that may contribute to this condition, most of these remain unknown. Researchers have determined that this form of hair loss is related to hormones called androgens, particularly an androgen called dihydrotestosterone (DHT). Androgens are important for normal male sexual development before birth and during puberty. Androgens also have other important functions in both males and females, such as regulating hair growth and sex drive.Male pattern baldness is caused by a genetic sensitivity of hair follicles to DHT, which causes them to shrink when exposed to it. This shortens their lifespan and prevents them from producing hair normally.
Hair loss and genetics
Much research has gone into the genetic component of male pattern baldness, or androgenic alopecia (AGA). Research indicates that susceptibility to premature male pattern baldness is largely X-linked. Other genes that aren’t sex linked are also involved.Large studies in 2005 and 2007 stress the importance of the maternal line in the inheritance of male pattern baldness. German researchers name the androgen receptor gene as the cardinal prerequisite for balding. They conclude that a certain variant of the androgen receptor is needed for AGA to develop. In the same year the results of this study were confirmed by other researchers. This gene is recessive and a female would need two X chromosomes with the defect to show typical male pattern alopecia. Seeing that androgens and their interaction with the androgen receptor are the cause of AGA it seems logical that the androgen receptor gene plays an important part in its development.
Other research in 2007 suggests another gene on the X chromosome, that lies close to the androgen receptor gene, is an important gene in male pattern baldness. They found the region Xq11-q12 on the X-chromosome to be strongly associated with AGA in males. They point at the EDA2R gene as the gene that is mostly associated with AGA.
Other genes involved with hair loss have been found. One of them being a gene on chromosome 3. The gene is located at 3q26. This gene is recessive.
Another gene that might be involved in hair loss is the P2RY5. This gene is linked to hair structure. Certain variants can lead to baldness at birth, while another variant causes "wooly hair."
In May 2009, researchers in Japan identified a gene, Sox21, that appears to be responsible for hair loss in people.
Hormone levels correlated with androgenic alopecia
Men with androgenic alopecia typically have lower levels of total testosterone, higher levels of unbound/free testosterone, and higher levels of total free androgens including DHT.5-alpha-reductase is responsible for converting free testosterone into DHT. The genes for 5-alpha-reductase are known. The enzymes are present predominantly in the scalp and prostate. Levels of 5alpha-reductase are one factor in determining levels of DHT in the scalp and drugs which interfere with 5alpha-reductase (such as finasteride, which inhibits the predominant type 2 isoform) have been approved by the FDA as treatments for hair loss.
Sex hormone binding globulin (SHBG), which is responsible for binding testosterone and preventing its bioavailability and conversion to DHT, is typically lower in individuals with high DHT. SHBG is downregulated by insulin.
Increased levels of Insulin Growth Factor-1 (IGF-1) have been correlated to vertex balding.
High insulin levels seem the likely link between metabolic syndrome and baldness. Low levels of SHBG in men and non-pregnant women are also correlated with glucose intolerance and diabetes risk, though this correlation disappears during pregnancy.
Treatment
MinoxidilMinoxidil 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 both the frontal areas of the scalp and the vertex area in treating 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.
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.
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 US FDA for the treatment of benign prostatic hyperplasia (BPH). The drug works by binding to 5-alpha-reductase, the enzyme responsible for the conversion of free testosterone to DHT.
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.
In 1997, Finasteride was approved by the US 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). 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.
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.
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). GlaxoSmithKline has published the results of the study.
The future impact that this study will have on the US FDA's approval or disapproval of Avodart for the treatment of male pattern baldness in the United States is yet to be determined.
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, 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. Ketoconazole has not been FDA-approved for hair loss, though it is used for other scalp conditions.
Herbal Treatment
- he shou wu is a chinese herb that can be boiled to form a brown colored tea which is believed by some to cause moderate hair regrowth. The tea has a taste similar to roasted barley tea.
- Saw palmetto extract has been suggested as a potential treatment for male pattern baldness. It has been shown to inhibit both isoforms of 5-alpha-reductase without eliminating the cellular capacity to secrete PSA.
- Gingko biloba has been suggested as a treatment for baldness because is believed to increase blood circulation to the brain and skin.
- Green tea contains compounds called catechins, which inhibits 5 alpha reductase enzymes used by the body to transform testosterone into DHT. Some claim that it relaxes the blood vessels and increases circulation to the scalp.
- Generic Propecia is used for treating certain types of male pattern hair loss (androgenic alopecia) in men. It is also used to treat symptoms of benign prostatic hyperplasia (BPH) in men with an enlarged prostate. The Appecia is generic for The Propecia. The active substance is finasteride. Each tablet contains 1 mg finasteride.
- Studies have shown that after five years of treatment with Appecia, 90% of men maintained their hair or increased hair growth. Except of, 48% of men treated with Appecia demonstrated an increase in hair growth, 42% were rated as having no change (no further visible progression of hair loss from baseline) and 10% were rated as having lost hair when compared to baseline. For example, in comparison, 6% of men treated with placebo demonstrated an increase in hair growth, 19% were rated as having no change and 75% were rated as having lost hair when compared to baseline. Appecia does not affect hair on other parts of the body.
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