Professional Documents
Culture Documents
2 Effects
2.1 Psychological
3 Diagnosis
4 Management
4.1 Conventional medicine
4.2 Alternative and future therapies
5 See also
6 References
7 External links
Causes
Androgenic alopecia in general
Hormonal etiology
Androgens can interact with the Wnt signalling pathway to cause to hair loss.
Research indicates that the initial programming of pilosebaceous units begins in utero.[9] The
physiology is primarily androgenic, with dihydrotestosterone (DHT) the major contributor at the
dermal papillae. Below normal values of Sex hormone-binding globulin (SHBG), Follicle-stimulating
hormone (FSH), testosterone and epitestosterone are present in men with premature androgenic
alopecia compared to normal controls.[10] Although follicles were previously thought permanently
gone in areas of complete hair loss, they are more likely dormant, as recent studies have shown the
scalp contains the stem cell progenitors from which the follicles arose.[11]
Transgenic studies have shown that growth and dormancy of hair follicles are related to the activity
of Insulin-like growth factor (IGF) at the dermal papillae, which is affected by DHT.[12]Androgens
are important in male sexual development around birth and at puberty. They
http://www.nlm.nih.gov/medlineplus/ency/article/003246.htm regulate sebaceous glands, apocrine
hair growth and libido. With increasing age,[13] androgens stimulate hair growth on the face, but
suppress it at the temples and scalp vertex, a condition that has been referred to as the 'androgen
paradox'.[14]
These observations have led to study at the level of the mesenchymal dermal papillae.[15][16]Type 1
and 2 5? reductase enzymes are present at pilosebaceous units in papillae of individual hair
follicles.[17] They catalyze formation of the androgens testosterone and DHT, which in turn regulate
hair growth.[14] Androgens have different effects at different follicles: they stimulate IGF-1 at facial
hair, leading to growth, but stimulate TGF ?1, TGF ?2, dickkopf1 and IL-6 at the scalp, leading to
catagenic miniaturization.[14] Hair follicles in anaphase express four different caspases. Tumor
necrosis factor inhibits elongation of hair follicles in vitro with abnormal morphology and cell death
in the bulb matrix.[18]
Studies look at serum levels of IGF-1 show it to be increased with vertex balding.[19][20] Earlier
work looking at in vitro administration of IGF had no effect on hair follicles when insulin was
present, but when absent, caused follicle growth. The effects on hair of IGF-I were found greater
than IGF-II.[21] Later work also showed IGF-1 signalling controls the hair growth cycle and
differentiation of hair shafts,[12] possibly having an anti-apoptotic effect during the catagen
phase.[22]In situ hybridization in adult human skin has shown morphogenic and mitogenic actions of
IGF-1.[23] Mutations of the gene encoding IGF-1 result in shortened and morphologically bizarre
hair growth and alopecia.[24] IGF-1 is modulated by IGF binding protein, which is produced in the
dermal papilla.[25]
DHT inhibits IGF-1 at the dermal papillae.[26] Extracellular histones inhibit hair shaft elongation
and promote regression of hair follicles by decreasing IGF and alkaline phosphatase in transgenic
mice.[27] Silencing P-cadherin, a hair follicle protein at adherens junctions, decreases IGF-1, and
increases TGF beta 2, although neutralizing TGF decreased catagenesis caused by loss of cadherin,
suggesting additional molecular targets for therapy. P-cadherin mutants have short, sparse hair.[28]
At the occipital scalp, androgens enhance inducible nitric oxide synthase (iNOS), which catalyzes
production of nitric oxide from L-arginine.[14] The induction of nitric oxide synthase usually occurs
in an oxidative environment, where high levels of nitric oxide produced interact with superoxide,
leading to peroxynitrite formation and cell toxicity. iNOS has been suggested to play a role in host
immunity by participating in anti-microbial and anti-tumor activities as part of the oxidative
burst[29] of macrophages.[30] The gene coding for nitric oxide synthase is on human chromosome
17.[31]
Men with androgenic alopecia typically have higher 5-alpha-reductase, lower total testosterone,
higher unbound/free testosterone and higher free androgens, including DHT.[10][33]5-alph-reductase converts free testosterone into DHT, and is highest in the scalp and prostate. DHT is most
commonly coatimundi sudden hair loss causes formed at the tissue level by 5?-reduction of
testosterone.[34] The genetic corollary that codes for this enzyme has been discovered.[35]
Prolactin has also been suggested to have different effects on the hair follicle across gender.[36] It
seasonally modulates[37] and can delay[38] hair growth in animal models. In vitro models show it
inhibits hair follicle growth.[39]In vivo it can inhibit facial hair growth in humans.[40] Researchers
have suggested it works through paracrine action.[41]
Genetics
researchers.[44] 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 that another gene on the X chromosome that lies close to the
androgen receptor gene is important 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. This finding has been replicated in at least three
following independent studies.
Other genes involved with hair loss have been found, including a gene located at 3q26.[46] This
gene is also involved in a type of baldness associated with mental retardation. It 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".[50]
Recent research confirmed the X-linked androgen receptor as the most important gene, with a gene
on chromosome 20 being the second most important determinant gene (snpedia). This research
suggests that heredity of AGA is X-linked; however, research has also shown that a person with a
balding father has a significantly greater chance of experiencing hair loss. Men whose fathers had
experienced hair loss were 2.5 times more likely to experience hair loss themselves, regardless of
the mother's side of the family, which may suggest Y-linked heredity plays a role.[51][52]
Age
Two men practicing Tahtib, one of them with androgenic alopecia, on an Ostraca from Ancient
Egypt, Louvre
Androgen stimulate growth of facial hair, but can suppress scalp hair, a condition that has been
called the 'androgen paradox'.[14] The American Academy of Dermatology reports that in adult men,
the incidence of androgenic alopecia is roughly equivalent to chronological age, with half of men
experiencing hair loss by age 50.[53]
Metabolic syndrome
A number of studies have found a link between androgenic alopecia and metabolic syndrome,
suggesting the combination as a male homologue to PCOS.
Multiple cross sectional studies have found association between early androgenic alopecia, insulin
resistance and metabolic syndrome,[59][60] with low HDL being the component of metabolic
syndrome with highest association.[61] Linolenic and linoleic acids, two major dietary sources of
HDL, are 5 alpha reductase inhibitors.[62] It has been suggested that premature androgenic
alopecia and insulin resistance are a clinical constellation that represents the male homologue, or
phenotype, of polycystic ovary syndrome.[63] Others have found a higher rate of hyperinsulinemia in
family members of women with polycystic ovarian syndrome.[64]
In support of the association, finasteride improves glucose metabolism and decreases glycosylated
hemoglobin HbA1c, a surrogate marker for diabetes mellitus.[65] The low SHBG seen with
premature androgenic alopecia is also associated with, and likely contributory to, insulin
resistance,[66] and for which it still is used as an assay for pediatric diabetes mellitus.[67]
Obesity leads to upregulation of insulin production and decrease in SHBG. Further reinforcing the
relationship, SHBG is downregulated by insulin in vitro, although SHBG levels do not appear to
affect insulin production.[68]In vivo, insulin stimulates both testosterone production and SHBG
inhibition in normal and obese men.[69] The relationship between SHBG and insulin resistance has
been known for some time; decades prior, ratios of SHBG and adiponectin were used before glucose
to predict insulin resistance.[70] Patients with Laron syndrome, with resultant deficient IGF,
demonstrate varying degrees of alopecia and structural defects in hair follicles when examined
microscopically.[24]
Because of its association with metabolic syndrome and altered glucose metabolism, both men and
women with early androgenic hair loss should be screened for impaired glucose tolerance and
diabetes mellitus II.[71] A low fat and high fiber diet combined with regular aerobic exercise
increases SHBG and insulin sensitivity.[72] Regarding androgenic impact of diet with exercise, a
study found increased protein intake led to higher concentrations of free and total testosterone
immediately post exercise.[73]
Measurement of subcutaneous and visceral adipose stores by MRI, demonstrated inverse association
between visceral adipose and testosterone/DHT, while subcutaneous adipose correlated negatively
with SHBG and positively with estrogen. Subcutaneous fat did not correlate with androgens once the
SHBG relationship was taken into account.[74] SHBG association with fasting blood glucose is most
dependent on intrahepatic fat, which can be measured by MRI in and out of phase imaging
sequences. Serum indices of hepatic function and surrogate markers for diabetes, previously used,
itself is also associated with higher levels of DHT.[82][83] Other hypotheses include genetic linkage
to beneficial traits unrelated to hair loss and genetic drift.
There is no consensus regarding the details of the evolution of male pattern baldness. The assertion
that MPB is intended to convey a social message is supported by the fact that the distribution of
androgen receptors in the scalp differs between men and women, and older men or women with high
androgen levels often exhibit diffuse thinning of hair as opposed to male pattern baldness.
Male pattern baldness is mostly the result of a genetic event that causes dihydrotestosterone (DHT),
a male hormone, to cause the hair follicles to atrophy. The hair produced is progressively smaller,
until it is practically invisible (or may disappear completely). Other evolutionary hypotheses include
genetic linkage to beneficial traits unrelated to hair loss, and genetic drift.
Other theories
An ancient phenomenon:
Greek philosophers with and without much hair (from left to right: Socrates, Antisthenes,
Chrysippus and Epicurus, 5th to 3rd century BC)
There are many myths regarding the possible causes of baldness and its relationship with one's
virility, intelligence, ethnicity, job, social class, wealth, etc. While skepticism may be warranted in
many cases due to a lack of scientific validation, some claims may have a degree of underlying truth
and are supported by research.
"
You inherit baldness from your mother's father.
"
Research suggests that the gene for the androgen receptor, which is significant in determining
probability for hair loss, is located on the X chromosome and so is always inherited from the
mother's side for men.[84] There is a 50% chance that a person shares the same X chromosome as
his maternal grandfather. Because women have two X chromosomes, they will have two copies of the
androgen receptor gene while men only have one. However, research has also shown that a person
with a balding father also has a significantly greater chance of experiencing hair loss. Men whose
fathers had experienced hair loss were 2.5 times more likely to experience hair loss themselves,
regardless of the mother's side of the family.[51][52]
"
Levels of free testosterone are strongly linked to libido and DHT levels, but unless free testosterone
is virtually nonexistent, levels have not been shown to affect virility. Men with androgenic alopecia
are more likely to have a higher baseline of free androgens. However, sexual activity is multifactoral,
and androgenic profile is not the only determining factor in baldness. Additionally, because hair loss
is progressive and free testosterone declines with age, a male's hairline may be more indicative of
his past than his present disposition.[90][91]
"
Frequent ejaculation causes baldness.
"
There are many misconceptions about what can help prevent hair loss, one of these being that lack
of sexual activity will automatically prevent hair loss. While a proven direct correlation exists
between increased frequency of ejaculation and increased levels of DHT, as shown in a recent study
by Harvard Medical School, the study suggests that ejaculation frequency may be a sign, rather than
necessarily a cause, of higher DHT levels.[92] Another study shows that although sexual arousal and
masturbation-induced orgasm increase testosterone concentration around orgasm, they reduce
testosterone concentration on average (especially before abstinence) and because about 5% of
testosterone is converted to DHT, ejaculation does not elevate DHT levels.[93]
The only published study to test correlation between ejaculation frequency and baldness was
probably large enough to detect an association (1390 subjects) and found no correlation, although
persons with only vertex androgenetic alopecia had had fewer female sexual partners than those of
other androgenetic alopecia categories (such as frontal or both frontal and vertex). One study may
not be enough especially in baldness, where there is a complex with age.[94] Marital status has been
shown in some but not all studies to influence hair loss in cross-sectional studies (NHANES1).
Female androgenic alopecia
Female androgenic alopecia, clinically known as 'female pattern hair loss,' (FPHL) more often causes
diffuse thinning without hairline recession. Approximately 30% of Caucasian adult females
experience hair loss.[95] Like its male counterpart, the condition rarely leads to total hair loss,
although it is possible.[95] Treatment options to arrest progression and stimulate growth include
finasteride, the androgen-independent growth promoter minoxidil, and androgen receptor
antagonists spironolactone and cyproterone acetate. These work best initiated early, and hair
transplantation can be considered in more advanced cases.[95]
A recently published study comparing monozygotic female twins found a number of factors
associated with hair loss in women with varying degrees of statistical certainty, and stratified by
pattern. Factors associated with increased temporal hair loss that were statistically significant (p <
0.05) were as follows:
more children (p = 0.005)
polycystic ovary syndrome. Thyroid disorders, anemia, chronic illness and some medications can also
cause female hair loss.[103]
In animals
Baldness is not only a human trait. One interesting case study is the maneless male Tsavo lion. The
Tsavo lions prides are unique in that they frequently have only a single male lion with an average of
7 to 8 adult females, as opposed to 4 females in other lion species prides. It is theorized that Tsavo
males may have heightened levels of testosterone, which could explain both their reputation for
aggression and dominance, indicating that lack of mane may at one time have had an alpha
correlation.[104]
Effects
Psychological
Androgenic alopecia is typically experienced as a "moderately stressful condition that diminishes
body image satisfaction".[105] However, although most men regard baldness as an unwanted and
distressing experience, they usually are able to cope and retain integrity of personality.[106]
Diagnosis
The diagnosis of androgenic alopecia can be usually established based on clinical presentation in
men. In women, the diagnosis usually requires more complex diagnostic evaluation. Further
evaluation of the differential requires exclusion of other causes of hair loss, and assessing for the
typical progressive hair loss pattern of androgenic alopecia.[107]Trichoscopy can be used for further
evaluation.[108] Biopsy may be needed to exclude other causes of hair loss,[109] and histology
would demonstrate perifollicular fibrosis.[110][111]
Management
Main article: Management of androgenic alopecia
Conventional medicine
Early stages of hair loss can be slowed or reversed with medication. FDA-approved drugs include
minoxidil and finasteride.[112] Finasteride is an oral medication taken at a standard daily dose of
1 mg for hair loss, and it works by reducing the level of DHT produced by the 5-alpha reductase type
2 enzyme by 85-90%, thereby protecting the hair follicles from further DHT
damage.[113]Dutasteride, a similar drug, is used off-label as a hair loss treatment. Dutasteride
lowers DHT levels more potently than finasteride, and is therefore, in theory, more effective.
However, it is not FDA approved as a hair loss treatment, and its long-term side-effects (including
possible neurological damage) are unknown. Minoxidil is a growth stimulant that stimulates alreadydamaged hair follicles to artificially produce normal hair.[114] Minoxidil does not, however, provide
any protection to the follicles from further DHT damage, and when a follicle eventually becomes
completely destroyed by DHT, minoxidil will no longer be able to have any more regrowth effects on
that follicle. Topical formulations of finasteride have been argued to be of similar efficacy to
systemic, though prostate weight and serum PSA levels were not measured to exclude systemic
absorption of topical application as the cause of hair growth.[115] Other treatment options not
already mentioned include tretinoin combined with minoxidil, ketoconazole shampoo, and
spironolactone.[116]
More advanced cases may be resistant or unresponsive to medical therapy, and require hair
transplantation. Naturally occurring units of one to four hairs, called follicular units, are excised and
moved to areas of hair restoration. These follicular units are surgically implanted in the scalp in
close proximity and in large numbers. The grafts are obtained from either Follicular Unit
Transplantation (FUT) or Follicular Unit Extraction (FUE). In the former, a strip of skin with
follicular units is extracted and dissected into individual follicular unit grafts. The surgeon then
implants the grafts into small incisions, called recipient sites.[117][118] Specialized scalp tattoos
can also mimic the appearance of a short buzzed haircut.[119][120]
Alternative and future therapies
The field of research to prevent and treat androgenic hair loss is vast, with systemic and topical
therapies with varying degrees of efficacy. In the United States alone, it is a multi-billion dollar
industry. Low-level laser therapy (LLLT) claims to stimulate hair growth through "photobiostimulation" of hair follicles, but has limited evidence of benefit or safety.[121]Saw palmetto
(Serenoa repens) in one small study demonstrated increased hair growth in 6/10 men with mild to
moderate androgenetic alopecia,[122] and another study revealed that saw palmetto extract applied
topically in a lotion and shampoo base led to a 35% increase in hair density, but these studies were
very small and a proper larger clinical trial on androgenetic alopecia is needed.[123] The dietary
supplement L-carnitine induces hair growth in vitro,[124] but it is not approved by the U.S. Food and
Drug Administration (FDA).[125] Consumption of grateloupia elliptica, a red seaweed in Jeju Island,
South Korea, has the potential to treat androgenic alopecia and alopecia areata.[126][127] Topical
IGF in a liposomal vehicle thickens and elongates hair in transgenic mice with androgenic
alopecia.[128] The enzyme prostaglandin D2 (PGD2) was present in the scalp of balding men at
higher levels than those with hair, and prevented hair follicle maturation, with the possibility of
treatment based on this research by 2014.[129][130][131][132]
See also
Baldness
Dihydrotestosterone
Hamilton-Norwood scale
Ludwig scale
Management of baldness
Noncicatricial alopecia
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How Hair Replacement Works Covers oral medications, hair transplant surgery, and topical
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