ANDROGENETIC ALOPECIA IN WOMEN (HAIR LOSS)
Androgenetic alopecia (AGA), also known in
women as female pattern hair loss, is caused by androgens in genetically
susceptible women and men. The thinning begins between ages 12 and 40 years, the
inheritance pattern is polygenic, and the incidence is the same as in men. In
Susceptible hair follicles, dihydrotestosterone binds to the androgen receptor,
and the hormone-receptor complex activates the genes responsible for the gradual
transformation of large terminal follicles to miniaturized follicles. Both young
women and young men with AGA have higher levels of 5x reductase and androgen
receptor in frontal hair follicles compared to occipital follicles. At the same
time, young women have much higher levels of cytochrome p-450 aromatase in
frontal follicles than men who have minimal aromatase, and women have even
higher aromatase levels in occipital follicles. The diagnosis of AGA in women is
supported by early age of onset, the pattern of increased thinning over the
occipital scalp, retention of the frontal hairline, and the presence of
miniaturized hairs. Most women with AGA have normal menses and pregnancies.
Extensive hormonal testing is usually not needed unless symptoms and signs of
androgen excess are present such as hirsutism, sever unresponsive cystic acne,
virilization, or galactorrhea. Topical minoxidil solution is the only drug
available for promoting hair growth in women with AGA. Efficacy has been shown
in double-blind studies using hair counts and hair weight.
Androgenetic
alopecia (AGA), also known in women as female pattern hair loss, is common and
distressing cause of hair loss in women and men. In spite of its prevalence,
many clinicians and clinical investigators have difficulty making the diagnosis
in women. The hair thinning begins between the ages of 12 and 40 in both sexes
(Hamilton, 1951; Trancik et al, 2001) and approximately half the population
expresses this trait to some degree before the age of 50 years (Venning and
Dawber, 1988; Olsen, 1994). Inheritance pattern of AGA is polygenic (complex
inheritance) and is inherited from either or both sides of the family (Kuster
and Happle, 1984; Sreekumer et al, 1999). |
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AGA is induced by androgens in genetically susceptible women
and men. Hair follicles of women and men with AGA have increased 5x-reductase
activity and increased levels of dihydrotestosterone (DHT) (Schweikert and
Wilson, 1974; Dallob et al, 1994; Kaufman, 1996; Sawaya and Price, 1997). DHT,
which is formed by the peripheral conversion of testosterone by 5x-reductase, is
thought to be responsible for the characteristic miniaturization of scalp hair
follicles in AGA. In genetically susceptible hair follicles, DHT binds to the
androgen receptor, and the hormone-receptor complex then activates the genes
responsible for the gradual transformation of large, terminal follicles to
small, miniaturized follicles (Price, 1975; Uno et al, 1985; Messenger, 1993;
Kaufman, 1996). Over successive hair cycles in AGA, the duration of anagen
shortens and matrix size decreases, resulting in smaller follicles that produce
shorter, finer, miniaturized hairs that cover the scalp less and less well.
These miniaturized hairs of various lengths and diameters are the hallmark of
AGA (Frieden and Price, 1986; Whiting, 1993; Olsen, 1994). The number of
follicles per unit area, however, remains the same (Whiting, 1993).
In
women with AGA, the extent of hair loss is generally less than in men. It has
been assumed that the hormonal basis for AGA is similar in women as in men
although earlier studies did not include female subjects (Price, 1975; Frieden
and Price, 1986). In order to compare and clarify the underlying hormonal basis,
a study was conducted in 12 young women (ages 14-33) and 12 young men (ages
18-30) with AGA (Sawaya and Price, 1997). Androgen receptor, type I and type II
5x-reductase, and cytochrome p-450 aromatase, were measured in hair follicles
from scalp biopsies of these young subjects. Both young women and young men had
higher levels of type I and type II 5x-reductase and androgen receptors in
frontal hair follicles compared to occipital hair follicles; however, the levels
in women were approximately half the levels in men (Sawaya and Price, 1997). At
the same time, young women had much higher levels of cytochrome p-450 aromatase
in frontal follicles than men who had minimal aromatase, and women had even
higher aromatase levels in occipital follicles. The differences in aromatase,
which is capable of converting testosterone to estradiol, are particularly
notable. The findings of this study suggest that the milder expression of AGA in
women may in part be the result of lower levels of 5x-reductase and androgen
receptors in frontal follicles of women compared to levels in men; additionally,
higher levels of aromatase in women may result in increased local formation of
estradiol from testosterone, and less formation of 5x-reductase products such as
DHT.
Although hair thinning in women with AGA may be diffuse,
nevertheless there is a pattern in women as there is in men, with the frontal
and parietal scalp generally showing the greatest hair density. From a clinical
perspective, hair follicles of the occipital scalp behave differently form
frontal and parietal scalp follicles: in AGA, occipital follicles are typically
spared by the hormonal influences; and in alopecia areata, occipital follicles
affected by the ophiasis pattern are typically more resistant to regrowth. These
different behaviors of occipital and frontal/parietal follicles may result from
the embryological derivation of the dermis in these two regions. It is known
from avian embryology that the dermis of the frontal/parietal scalp is of neural
crest origin (Ziller, 1996). Regulatory genes, growth factors, and cell-cell
interactions may influence hair follicles differently in the two regions based
on their dermal origin, and this may explain the patterning that is frequently
seen in scalp hair loss. |
» CLINICAL FEATURES OF AGA IN WOMEN
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Women first notice hair thinning over the frontal area, and
generally the scalp becomes more visible. Over time the thinning, although it is
often diffuse and may involve most of the scalp, nevertheless is usually
patterned with most marked thinning over the frontal and parietal scalp, and
with greater density over the occipital scalp. Women typically retain a rim of
hair along the frontal hairline, even when the scalp is visible behind the
hairline (Ludwig, 1977). Miniaturized hairs, the shorter finer hairs of various
lengths and diameters, are the hallmark of AGA (Frieden and Price, 1986;
Whiting, 1993) and result from the shortening of anagen phase and reduction in
matrix size. Increased spacing between hairs makes the central part appear wider
over the frontal scalp compared to the occipital scalp.
Less commonly,
hair density appears normal proximally, but the hair no longer grows to its
previous length, resulting in wispy distal ends; in this case, the shortening of
anagen progresses more rapidly than matrix reduction. The patient may note that
her ‘pony tail’ is smaller in girth and the hair is cut to shorter lengths in
order to give a fuller appearance. Rarely, advanced thinning occurs with loss of
the frontal hairline, but this is invariably associated with markedly elevated
circulating androgens (Ludwig, 1977).
Androgenetic alopecia in women is
not usually accompanied by increased shedding. However, in some instances, an
episode of telogen effluvium following childbirth, major illness or other causes
may uncover a latent predisposition to AGA. Sometimes the number of hairs shed
is misleading in women who seldom comb their hair after shampooing, leaving it
to dry naturally; and later when their hands ‘comb’ through the hair many loose
hairs appear on the fingers. |
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Extensive hormonal testing is usually not needed unless
symptoms
and signs of androgen excess are present. Most women with AGA have
normal menses and pregnancies. Women who require endocrine evaluation
are identified in the office with careful inquiry regarding menses,
history of fertility, and the presence of hirsutism, severe unresponsive
cystic acne, virilization, or galactorrhea. If any one of these
is
present, laboratory measurement of serum total or free testosterone,
dehydroepiandrosterone sulfate and prolactin are indicated. Other
common
causes of hair loss are ruled out by measurement of serum
thyrotropin, iron
studies including serum iron and ferritin, complete
blood count, and
RPR. |
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The diagnosis of AGA in women is supported by early age of
onset, the pattern of increased hair thinning over the frontal/parietal scalp
with greater hair density over the occipital scalp, retention of the frontal
hairline, and the presence of miniaturized hairs.
When these features are
present, the diagnosis is not problematic. However, AGA is common and other
causes of hair loss may coexist and need to be recognized or excluded. Scalp
biopsy usually solves the differential diagnosis. Biopsies are taken from
active, representative sites, and horizontal sectioning is preferred because of
the larger number of follicular structures that can be studied (Headington,
1984; Whiting, 1990). In AGA, biopsy shows increased numbers of miniaturized
hairs, abundant and even enlarged sebaceous glands, and minimal inflammation
though the latter is controversial (Lattanand and Johnson, 1975; Whiting,
1998).
Chronic telogen effluvium (CTE) may present a difficult
differential diagnosis even though the features of CTE seem distinct. In CTE,
women in the fourth to sixth decade, with above average hair density, describe
sudden onset of marked shedding from the entire scalp. Hair pull test may
extract increased numbers of telogen hairs easily, yet scalp hair density
appears normal or minimally decreased even though the shedding may be prolonged.
Miniaturized hairs are not seen. Horizontal sections of a scalp biopsy
distinguish CTE from AGA: the ratio of terminal hairs to miniaturized hairs in
CTE is 9:1, in AGA is 2:1 and in a normal scalp is 7:1 (Whiting, 1996). Acute
telogen effluvium may occur in a woman with long-standing AGA or unmask latent
AGA. A careful history will usually identify the cause of profuse hair shedding
such as high fever, severe dietary protein deficiency, or chronic blood loss as
in women with prolonged heavy menses. Relevant laboratory tests are noted above.
Categories of drugs that may cause hair loss include anticancer drugs,
anticoagulants, anticonvulsants, antithyroid drugs, beta blockers, tricyclic
antidepressants, and progestins with androgenic effects (Mirmirani and Price,
2000). Both patchy and diffuse alopecia areata may coexist with AGA and
sometimes present a challenging differential which is resolved by a scalp biopsy
showing a peribulbar lymphocytic infiltrate around anagen hair bulbs. An adult
with loose anagen syndrome has a history of decreased hair density since early
childhood, and the pull test is strongly positive (Price and Gummer, 1989). Low
power microscopy of the easily extracted hairs shows misshapen anagen bulbs, a
“ruffled” cuticle just distal to the bulb, and absent inner root
sheath. |
» MEDICAL TREATMENT OF AGA IN WOMEN |
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Topical minoxidil solution is the only approved drug available
for promoting hair growth in women with AGA (Price, 1999). Efficacy has been
shown in double blind, placebo-controlled studies using hair counts and hair
weight as the primary end points (Price, 1999). Minoxidil-treated women had
significantly higher hair counts and an increase in hair weight compared to
women who received placebo. A double-blind study of women ages 22-41 years using
2% topical minoxidil solution showed a significant increase over placebo in mean
change in hair weight at 16 weeks (Price and Menefee, 1990). It should be noted
that clinical perception of improved scalp coverage may take longer, up to 6-12
months, until hair length and mass are increased sufficiently. Minoxidil
solution must be applied twice daily to a dry scalp.
Finasteride is a
competitive inhibitor of type II 5x-reductase, and is contraindicated in women
who are or may become pregnant, because 5x-reductase inhibitors may cause
abnormalities of the external genitalia of a male fetus. Finasteride was not
effective in postmenopausal women in a placebo-controlled study (Price et al,
2000).
Women are devastated by their thinning hair (Cash et al, 1993),
and need thoughtful evaluation and management, as well as reassurance that they
may safely use hair cosmetics to make their hair appear fuller. |
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Cash TF, Price VH, Savin RC, Psychological effects of
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NS, Unger W, et al: The effect of Finasteride, a 5x-reductase, inhibitor, on
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male pattern baldness. J Clin Endocrinol Metab 79:703-706, 1994
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