What is Hair Loss & What Causes It

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From Wikipedia:

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.[1] 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.[2]

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 are not 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.[3] 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.[4] 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 an allele on chromosome 3. The allele is located at 3q26.[5] This allele is recessive.

There are also genes that are involved in hair loss, although not male pattern baldenss. In particular, three genes have been shown to both affect hair texture and also cause baldness in some people. One of these is P2RY5. Mutations in this gene affects hair structure "wooly hair".[6] Certain variants can lead to baldness.[7]

In May 2009, researchers in Japan identified a gene, Sox21, that appears to be responsible for hair loss in humans.[8]

Hormone levels correlated with androgenic alopecia: Men with androgenic alopecia typically have higher levels of 5-alpha-reductase, lower levels of total testosterone, higher levels of unbound/free testosterone, and higher levels of total free androgens including DHT.[9][10]

5-alpha-reductase is responsible for converting free testosterone into DHT. The genes for 5-alpha-reductase are known.[11] 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.[12]

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.[13]

Hair loss and lifestyle: While genetic factors seem to play the principal role in the development and progression of androgenic alopecia, lifestyle also plays a minor role as demonstrated by the vast increase in male and female pattern baldness in Japan after World War II. Pattern baldness (androgenic alopecia) was either rare or non-existent among hunter-gatherer and other, less westernized societies eating in their traditional manner. [14]

One study did show that free testosterone is lower 24 hours after intense aerobic exercise in men who already have high endurance[15] but it was not investigated whether that level remains lowered beyond that point, or whether that lowering affects male pattern baldness in any way. It has been suggested that weight training may have a detrimental effect on hair by increasing testosterone levels; however, there is at least one study that indicates a decline in free testosterone as result of weight training.[16]

Evolutionary theories of Male Pattern Baldness: This section does not cite any references or sources.
Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (November 2009)

One theory, advanced by Muscarella and Cunningham, suggests baldness evolved in males through sexual selection as an enhanced signal of aging and social maturity, whereby aggression and risk-taking decrease and nurturing behaviours increase. This may have conveyed a male with enhanced social status but reduced physical threat, which could enhance ability to secure reproductive partners and raise offspring to adulthood.

In a study by Muscarella and Cunnhingham, males and females viewed 6 male models with different levels of facial hair (beard and mustache or none) and cranial hair (full head of hair, receding and bald). Participants rated each combination on 32 adjectives related to social perceptions. Males with facial hair and those with bald or receding hair were rated as being older than those who were clean shaven or had a full head of hair. Beards and a full head of hair were seen as being more aggressive and less socially mature, and baldness was associated with more social maturity. A review of social perceptions of male pattern baldness has been provided by Henss (2001).

The assertion that male pattern baldness is intended to convey a social message is supported by the fact that pattern baldness is also common in other primates, and is often used to convey increased status and maturity. Gorillas evolved anatomically enlarged foreheads for this reason. This suggests that baldness could have evolved to enhance the apparent size of the forehead, and increase the area of the face to be displayed. It should also be noted that most ancestry primates had a shorter life-span, and as baldness usually occurs at a later stage in life, baldness could have been a sign of survival and longevity. Premature baldness could also have evolved in younger males to convey this message, which correlates with studies suggesting men with bald or receding hairlines were rated as older than those with a full head of hair.

Other evolutionary hypotheses include genetic linkage to beneficial traits unrelated to hair loss and genetic drift.

Diagnosis: Differential diagnosis involves eliminating other causes of hair loss (such as poisoning) and comparing the pattern of hair loss to a typical male pattern baldness progression.[17]


References
^ "The latest on baldness cures" ([dead link] – Scholar search). Duke Health News. December 1994. findarticles.com/p/articles/mi_m0857/is_n6_v12/ai_16395133. Retrieved 2009-01-09.
^ www.webmd.com/skin-problems-and-treatments/hair-loss/hair-loss-causes
^ Hillmer AM, Hanneken S, Genetic variation in the human androgen receptor gene is the major determinant of common early-onset Androgenic Alopecia (AGA). Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
^ Levy-Nissenbaum E, Bar-Natan M, Confirmation of the association between male pattern baldness and the androgen receptor genr Danek Gartner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel
^ Hillmer AM, Flaquer A, Genome-wide scan and fine-mapping linkage study of AGA reveals a locus on chromosome 3q26. Department of Genomics, Life and Brain Center, University of Bonn, D-53127 Bonn, Germany.
^ Shimomura Y, Wajid M, Ishii Y, Shapiro L, Petukhova L, Gordon D, Christiano AM. (Mar 2008). "Disruption of P2RY5, an orphan G protein-coupled receptor, underlies autosomal recessive woolly hair.". Nat Genet. 40 (3): 335–9. doi:10.1038/ng.100. PMID 18297072.
^ Petukhova L, Sousa EC Jr, Martinez-Mir A, Vitebsky A, Dos Santos LG, Shapiro L, Haynes C, Gordon D, Shimomura Y, Christiano AM. (Nov 2008). "Genome-wide linkage analysis of an autosomal recessive hypotrichosis identifies a novel P2RY5 mutation". Genomics 92 (5): 273–8. doi:10.1016/j.ygeno.2008.06.009. PMID 18692127.
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^ Stárka L, Cermáková I, Dusková M, Hill M, Dolezal M, Polácek V (2004). "Hormonal profile of men with premature balding". Exp. Clin. Endocrinol. Diabetes 112 (1): 24–8. doi:10.1055/s-2004-815723. PMID 14758568.
^ Demark-Wahnefried W, Lesko SM, Conaway MR, et al. (1997). "Serum androgens: associations with prostate cancer risk and hair patterning". J. Androl. 18 (5): 495–500. PMID 9349747. www.andrologyjournal.org/cgi/pmidlookup?view=long&pmid=9349747.
^ Ellis JA, Panagiotopoulos S, Akdeniz A, Jerums G, Harrap SB (2005). "Androgenic correlates of genetic variation in the gene encoding 5alpha-reductase type 1". J. Hum. Genet. 50 (10): 534–7. doi:10.1007/s10038-005-0289-x. PMID 16155734.
^ Signorello LB, Wuu J, Hsieh C, Tzonou A, Trichopoulos D, Mantzoros CS (1999). "Hormones and hair patterning in men: a role for insulin-like growth factor 1?". J. Am. Acad. Dermatol. 40 (2 Pt 1): 200–3. doi:10.1016/S0190-9622(99)70188-X. PMID 10025745.
^ McElduff A, Hitchman R, McElduff P (2006). "Is sex hormone-binding globulin associated with glucose tolerance?". Diabet. Med. 23 (3): 306–12. doi:10.1111/j.1464-5491.2005.01780.x. PMID 16492215.
^ Cordain L, Eades MR, Eades MD (2003). "Hyperinsulinemic diseases of civilization: more than just Syndrome X". Comp. Biochem. Physiol., Part a Mol. Integr. Physiol. 136 (1): 95–112. doi:10.1016/S1095-6433(03)00011-4. PMID 14527633. linkinghub.elsevier.com/retrieve/pii/S1095643303000114.
^ Daly W, Seegers CA, Rubin DA, Dobridge JD, Hackney AC (2005). "Relationship between stress hormones and testosterone with prolonged endurance exercise". Eur. J. Appl. Physiol. 93 (4): 375–80. doi:10.1007/s00421-004-1223-1. PMID 15618989.
^ Ara, I.; Perez-Gomez, J.; Vicente-Rodriguez, G.; Chavarren, J.; Dorado, C.; Calbet, J. A. L. (2006). "Serum free testosterone, leptin and soluble leptin receptor changes in a 6-week strength-training programme." ([dead link] – Scholar search). British Journal of Nutrition 96 (6): 1053–9. doi:10.1017/BJN20061956. PMID 17181880. www.ingentaconnect.com/content/cabi/bjn/2006/00000096/00000006/art00009.
^ www.webmd.com/a-to-z-guides/hair-loss-diagnosis
^ www.webmd.com/a-to-z-guides/hair-loss-treatments
^ Fischer TW, Hipler UC, Elsner P (2007). "Effect of caffeine and testosterone on the proliferation of human hair follicles in vitro". Int. J. Dermatol. 46 (1): 27–35. doi:10.1111/j.1365-4632.2007.03119.x. PMID 17214716. www.blackwell-synergy.com/doi/abs/10.1111/j.1365-4632.2007.03119.x.

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Hair Loss Causes and Conditions
By John P. Cole, MD

There are many causes of hair loss in men and women, including disease, nutritional deficiency, hormone imbalance, and stress. However, by far the most common cause is what is called adrogenetic alopecia. Alopecia is simply the medical term for hair loss. Androgenetic refers to the fact that both a genetic predisposition to balding, and the influence of androgens, or male hormones, play a part in this type of hair loss.
In fact, there is a third factor, which is the passage of time, or aging. In other words, in order for androgenetic alopecia to occur, there must be:

* a genetic propensity for balding
* the presence of androgens, or male hormones
* enough aging time to allow the first two factors to exert their influence on the hair follicles

Genetics

Genetics is not always simple, and such is the case with balding. Just the presence or absence of balding in one’s parents or grandparents, on either the mother’s or father’s side, is not necessarily predictive of one’s likelihood of balding. Certainly, if a man’s father is completely bald, and this man begins to rapidly lose hair in his early twenties, it’s a safe bet that he will develop extensive balding at some point. In short, it’s very hard to accurately predict who will go bald and how rapidly.

This inherent uncertainly about the progression of balding is of utmost importance in planning surgical hair restoration, as we will see in later sections. We must always plan for a "worst case scenario" in order to give patients the best possible results in the long term, as well as in the short term. Anything less is irresponsible.

Androgenic Hormones

All normal men and women produce "male" hormones. The most common of these are testosterone, androsteinedione, and dihydrotestosterone (DHT). Androgens are produced by the testicles and adrenals in men, and by the ovaries and adrenal glands in women. These hormones are quite important in both sexes, but occur in different concentrations, being much more predominant in males than in females. This, in part, is responsible for the typical differences between the genders.

It is the exposure of the hair follicles to DHT, in a genetically susceptible person, over a period of time, which leads to androgenetic alopecia, or male and female pattern baldness. How does this exposure to DHT occur?

In certain cells of the hair follicle, and in the sebaceous glands, there are high levels of an enzyme called 5-alpha-reductase. What this enzyme does is to convert testosterone, which is delivered to these areas by the blood, into DHT. This is important not only in understanding the mechanisms of balding, but also one medical treatment now available: Propecia (finasteride). What Propecia does is inhibit, or limit the activity of, this 5-alpha-reductase enzyme. Therefore, there is less conversion of testosterone to DHT, and lower levels of DHT are found in the follicle. In later sections, we will discuss this and other medical treatments in much greater detail.

Aging

There is no set age at which balding occurs. It is a process, and this is a simple, but oft-ignored fact. Like any process, it can be rapid or slow, it can begin toward the end of life or in the late teens, and it can progress in a predictably inexorable fashion, or it can stop and start, seemingly stabilize, and then begin again. Once we understand and accept this as a dynamic process, then we can better plan for the present and for the future in terms of how we treat it. This quest for understanding, which you have begun just by opening this book, will do more than all the despairing thoughts, hand-wringing, and self-pity, toward allowing a clear-eyed, rational, long term approach to the problem of hair loss.

So we now have looked at these three interdependent factors that play into the common types of balding. Again, they are: hormones, genetics, and Father Time. So what exactly does happen to the hair? Let’s take a look.

Assuming we have a genetically predisposed person, then as the follicles are continuously exposed to DHT, an interesting phenomenon occurs. Remember the anagen phase, or active growth phase of the hair? This phase becomes gradually briefer and briefer, and eventually the hair becomes finer and shorter, and less deeply colored. We call this "miniaturization" of hairs. This is also the point at which hair loss tends to first be noticed. It’s not that there are fewer hairs on the head, but that their caliber (cross-sectional area), color and length are so diminished that they no longer provide "coverage" for the scalp beneath. Light penetrates through to the shiny scalp, and this is perceived by the observer as "thinning" or balding.

Also, the ratio between hairs in the anagen phase and those in the telogen, or resting phase, is increased. This simply means that, at any given time, an increased number of hairs are in the telogen phase. These extra numbers of telogen hairs will be found in the susceptible zone for common balding, which is the front, top, and crown of the head. The so-called "permanent" zone, the familiar horseshoe-shaped wreath of hair around the back and sides, is unaffected by these changes. The telogen hairs are easily dislodged during washing, drying, or combing, and this is the second sign of balding: in addition to the apparent thinning seen with miniaturization, we begin to see larger numbers of hairs on the comb, the towel, the pillowcase, or in the bathroom drain. This can be quite traumatic, especially for the younger man or for women. In the next section, we will discuss the natural history of balding, that is, the way it first presents or appears, the different ways it progresses, and how it affects the different regions of the head.

For the sake of completeness, let’s briefly mention some of the other patterns of hair loss, if only to distinguish them from androgenetic alopecia (male and female pattern baldness). There is alopecia areata, where discrete patches of scalp go bald; triangular alopecia, which tend to occur in a triangular pattern in the temporal area; alopecia universalis, in which the entire body may be affected; and various "toxic" alopecias, including those following a severe illness, sometimes with high fever, or following pregnancy. Toxic alopecias may also occur with low thyroid and/or pituitary gland function, or following chemotherapy. The cicatricial (scarring) alopecias occur following tissue destruction and inflammation.

Also seen are the so-called diffuse alopecias (patterned and unpatterned), in which there is widespread thinning that may affect the "permanent" zone as well as the areas vulnerable to balding. In any or all of these less common types of balding above, it may be necessary to have a complete physical and laboratory workup, possibly including scalp biopsy.

So again, the common types of balding are directly related to the presence of male hormones in a genetically predisposed person over time. This can occur in both men and women. The process involves progressive miniaturization of the terminal hairs, and diminished length of the active hair growth cycle. Now, let’s take a look at how this microscopic, cellular process is manifested on the head; we can call this the natural history of balding.

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Hair Loss - Why?
By Bradley Wolf, MD

Hair Loss – Why?

Though humans no longer make use of hair for protection, heat retention, or camouflage, it still remains a very important means by which individuals display and are recognized. Appropriate appearance and grooming are still very important in social organization and the human relationships.
The human body contains approximately five million hair follicles while the scalp (prior to any kind of hair loss) contains 100,000 - 150,000 hair follicles. Blondes have the greatest number of scalp follicles, followed by brunettes. Humans with red hair have the fewest number of scalp follicles. The normal growth rate of scalp hair is one-fourth to one-half inch per month.

THE NORMAL HAIR GROWTH CYCLE

It is important to understand the normal hair growth cycle to understand why hair loss occurs. The hair follicle is an anatomical structure which evolved to produce and extrude (push out) a hair shaft. Hair is made up of proteins called keratins. Human hair grows in a continuous cyclic pattern of growth and rest known as the "hair growth cycle". Three phases of the cycle exist: Anagen= growth phase; Catagen=degradation phase; Telogen= resting phase. Periods of growth (anagen) between two and eight years are followed by a brief period, two to four weeks, in which the follicle is almost totally degraded (catagen). The resting phase (telogen) then begins and lasts two to four months. Shedding of the hair occurs only after the next growth cycle (anagen) begins and a new hair shaft begins to emerge. On average 50-100 telogen hairs are shed every day. This is normal hair loss and accounts for the hair loss seen every day in the shower and with hair combing. These hairs will regrow. Not more than 10 percent of the follicles are in the resting phase (telogen) at any time. A variety of factors can affect the hair growth cycle and cause temporary or permanent hair loss (alopecia) including medication, radiation, chemotherapy, exposure to chemicals, hormonal and nutritional factors, thyroid disease, generalized or local skin disease, and stress.
Androgens (testosterone, dihydrotestosterone) are the most important control factors of human hair growth. Androgens must be present for the growth of beard, axillary (underarm), and pubic hair. Growth of scalp hair is NOT androgen-dependent but androgens are necessary for the development of male and female pattern hair loss.

MALE PATTERN HAIR LOSS (Androgenetic Alopecia)

It is estimated that 35 million men in the United States are affected by androgenetic alopecia. "Andro" refers to the androgens (testosterone, dihydrotestosterone) necessary to produce male-pattern hair loss (MPHL). "Genetic" refers to the inherited gene necessary for MPHL to occur. In men who develop MPHL the hair loss may begin any time after puberty when blood levels of androgens rise. The first change is usually recession in the temporal areas, which is seen in 96 percent of mature Caucasian males, including those men not destined to progress to further hair loss. Hamilton and later Norwood have classified the patterns of MPHL (See Norwood-Hamilton Scale). Although the density of hair in a given pattern of loss tends to diminish with age, there is no way to predict what pattern of hair loss a young man with early MPHL will eventually assume. In general, those who begin losing hair in the second decade are those in whom the hair loss will be the most severe. In some men, initial male-pattern hair loss may be delayed until the late third to fourth decade. It is generally recognized that men in their 20’s have a 20 percent incidence of MPHL, in their 30’s a 30 percent incidence of MPHL, in their 40’s a 40 percent incidence of MPLH, etc. Using these numbers one can see that a male in his 90’s has a 90 percent chance of having some degree of MPHL.
Hamilton first noted that androgens (testosterone, dihydrotestosterone) are necessary for the development of MPHL. The amount of androgens present does not need to be greater than normal for MPHL to occur. If androgens are present in normal amounts and the gene for hair loss is present, male pattern hair loss will occur. Axillary (under arm) and pubic hair are dependent on testosterone for growth. Beard growth and male pattern hair loss are dependent on dihydrotestosterone (DHT). Testosterone is converted to DHT by the enzyme, 5a -reductase. Finasteride (Propecia) acts by blocking this enzyme and decreasing the amount of DHT. Receptors exist on cells that bind androgens. These receptors have the greatest affinity for DHT followed by testosterone, estrogen, and progesterone. After binding to the receptor, DHT goes into the cell and interacts with the nucleus of the cell altering the production of protein by the DNA in the nucleus of the cell. Ultimately growth of the hair follicle ceases.
The hair growth cycle (see "The Normal Hair Growth Cycle") is affected in that the percentage of hairs in the growth phase (anagen) and the duration of the growth phase diminish resulting in shorter hairs. More hairs are in the resting state (telogen) and these hairs are much more subject to loss with the daily trauma of combing and washing. The hair shafts in MPHL become progressively miniaturized, smaller in diameter and length, with time. In men with MPHL all the hairs in an affected area may eventually (but not necessarily) become involved in the process and may with time cover the region with fine (vellus) hair. Pigment (color) production is also terminated with miniaturization so the fine hair becomes lighter in color. The lighter color, miniaturized hairs cause the area to first appear thin. Involved areas in men can completely lose all follicles over time. MPHL is an inherited condition and the gene can be inherited from either the mother or father’s side. There is a common myth that inheritance is only from the mother’s side. This is not true.

In summary, male pattern hair loss (Androgenetic Alopecia) is an inherited condition manifested when androgens are present in normal amounts. The gene can be inherited from the mother or father’s side. The onset, rate, and severity of hair loss are unpredictable. The severity increases with age and if the condition is present it will be progressive and relentless.

FEMALE PATTERN HAIR LOSS (Androgenetic Alopecia)

Female pattern hair loss (FPHL) differs from male pattern hair loss (MPHL) in the following ways. It is more likely to be noticed later than in men, in the late twenties through early forties. It is likely to be seen at times of hormonal change, i.e., use of birth control pills, after childbirth, around the time of menopause, and after menopause. Recession at the temples is less likely than in men and women tend to maintain the position of their hairlines. Like in men, the entire top of the scalp is the area of risk. In women there is generally a diffuse thinning throughout the area as opposed to thinning in the crown of men. Ludwig has classified hair loss in women into three classes. (See Ludwig Classification) The vast majority of women affected fall into the Ludwig I class.

In the United States it is estimated that 21 million women are affected by FPHL. The incidence in women has been reported to be as low as eight percent and as high as 87 percent. It does appear to be as common in women as in men. The hair loss in women becomes particularly notable in menopause.
Androgens are responsible for hair loss in women by the same mechanisms they cause hair loss in men. Women do produce small amounts of androgens by way of the ovaries and adrenal glands. Also prehormones are produced by the ovaries that are converted to androgens outside of the ovaries or adrenal glands. Women rarely experience total loss of hair in an area if the loss is due to FPHL. If they do they should be evaluated for an underlying pathological (disease) condition. In women, the process of miniaturization of the hair follicle is more random with some hair being unaffected. Normal thick hairs are mixed with finer, smaller diameter hairs. The end result is a visual decrease in density of hair rather than total loss of hair. The hair growth cycle is affected as in men. The growth phase (anagen) is shortened resulting in shorter hairs and the resting phase (telogen) is increased resulting in fewer hairs.

If the cause of hair loss is suspected to be abnormally elevated or decreased amounts of hormones the patient should undergo laboratory tests to measure hormone levels.