Female pattern hair loss.

Abstract

Female pattern hair loss is a common condition characterized by a diffuse reduction in hair density over the crown and frontal scalp with retention of the frontal hairline. The prevalence increases with advancing age. It has been widely thought to be the female counterpart of male balding and is often referred to as female androgenetic alopecia. However, the role of androgens is not fully established. Scalp hair loss is undoubtedly a feature of hyperandrogenism in women but many women with female pattern hair loss have no other clinical or biochemical evidence of androgen excess. Female pattern hair loss is probably a multifactorial genetically determined trait and it is possible that both androgen-dependent and androgen-independent mechanisms contribute to the phenotype. In managing patients with female pattern hair loss the physician should be aware that the adverse effects on quality of life can be quite severe and do not necessarily correlate with the objective degree of hair loss. The treatment options are currently limited but modest improvements in hair density are achievable in some women.

Full text

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Female pattern hair loss
M. P. Birch, S. C. Lalla and A. G. Messenger
Department of Dermatology, Royal Hallamshire Hospital, Sheffield, UK
Summary
Female pattern hair loss is a common condition characterized by a diffuse reduction in
hair density over the crown and frontal scalp with retention of the frontal hairline. The
prevalence increases with advancing age. It has been widely thought to be the female
counterpart of male balding and is often referred to as female androgenetic alopecia.
However, the role of androgens is not fully established. Scalp hair loss is undoubtedly a
feature of hyperandrogenism in women but many women with female pattern hair loss
have no other clinical or biochemical evidence of androgen excess. Female pattern hair
loss is probably a multifactorial genetically determined trait and it is possible that both
androgen-dependent and androgen-independent mechanisms contribute to the
phenotype. In managing patients with female pattern hair loss the physician should
be aware that the adverse effects on quality of life can be quite severe and do not
necessarily correlate with the objective degree of hair loss. The treatment options are
currently limited but modest improvements in hair density are achievable in some
women.
Introduction
In a short but influential paper, published as recently as
1977, Ludwig described the distinctive features of
female pattern hair loss and classified it into three
grades of severity, often referred to as Ludwig I, II and
III.1Although Ludwig is rightly credited with delinea-
ting the clinical presentation of female pattern hair loss,
it was well known to previous generations that women
commonly develop an age-dependent form of scalp hair
loss. In 1935 Snyder and Yingling2examined 1883
women over 35 years of age and found that 8% were
balding, and Hamilton reported that 15–30% of women
aged over 30 showed temporal recession. Ludwig used
the term ?androgenetic alopecia? to describe female hair
loss in the belief that it is the same entity as male
balding. However, the role of androgens in women with
hair loss is far from clear-cut and in this article we use
the less committal term ?female pattern hair loss?.
Clinical features
Most women present with a history of gradual
thinning of scalp hair, often over a period of several
years. The hair loss can start at any time between
early teens and late middle age. There is frequently a
history of excessive hair shedding, but unlike telogen
effluvium, hair thinning is usually noticed from the
outset. Examination of the scalp shows a widening of
the central parting with a diffuse reduction in hair
density affecting mainly the frontal scalp and crown.
In some women the hair loss may affect a quite small
area of the frontal scalp whereas in others the entire
scalp is involved, including the parietal and occipital
regions. The frontal hairline is typically retained
although many women develop a minor degree of
postpubertal recession at the temples (equivalent to a
Norwood–Hamilton II frontal hairline), whether or not
they have diffuse hair loss. Some women have more
pronouncedtemporalrecession
experience this usually manifests as thinning rather
than the complete loss of temporal hair seen in men.
Venning and Dawber reported that 13% of premeno-
pausal women had fronto-temporal recession increasing
although in our
Correspondence: A. Messenger, Department of Dermatology, Royal Hal-
lamshire Hospital, Sheffield S10 2JF, UK.
Tel.: +44 114 2712188. Fax: +44 114 2713763.
E-mail: A.G.Messenger@Sheffield.ac.uk
Clinical dermatology • Review article
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to 37% in postmenopausal women.3In advanced
female pattern hair loss (Ludwig III) the hair becomes
very sparse over the top of the scalp but a rim of hair
is retained along the frontal margin. The vertex
balding seen in men is rare in women. On the other
hand a ?female? pattern of balding is not uncommon in
men. We found that 20 out of 331 balding men (6%)
showed a female pattern of hair loss (unpublished
observations) and in Asian men the frequency is much
higher.4
The diagnosis is usually straightforward but other
causes of diffuse hair loss may need to be excluded,
particularly when the hair loss progresses rapidly. In the
presence of overt hair loss a positive tug test should raise
the possibility of diffuse alopecia areata. Occasionally,
systemic lupus erythematosus can also present in this
way. In alopecia areata there may be hair loss in other
sites, and other symptoms, such as joint pain, may be
present in those suffering from lupus. In difficult cases a
biopsy should clarify the diagnosis. The hair loss seen in
thyroid deficiency closely resembles female pattern hair
loss and may indeed be identical.5,6Thyroid deficiency
also causes a reversible increase in hair shedding.7
Rapidly progressive hair loss with oligo- or amenor-
rhoea and other signs of virilization should prompt
measurement of serum testosterone to rule out the rare
cases of androgen-secreting tumour. The most difficult
differential diagnosis is from telogen effluvium, partic-
ularly the chronic form.8In some women with female
pattern hair loss excessive shedding may be present for
months or even years before there is an obvious
reduction in hair density and occasionally it develops
following typical acute telogen effluvium, suggesting
that the shedding episode has revealed a pre-existing
trait. A biopsy can be helpful in doubtful cases but needs
a pathologist experienced in the interpretation of hair
pathology.
Prevalence
Three recent studies from the USA,9Korea4and the
UK10have reported on the prevalence of female pattern
hair loss. All show an age-related increase in the
prevalence (Fig. 1). In the UK study, but not in the other
two, this increase became more pronounced in women
aged over 50 years. The UK and USA studies show
similar frequencies, increasing from 3% to 6% in women
aged under 30 years to 29–42% in women aged 70 and
over. The frequencies in the Korean study were lower;
this study also found a lower frequency of balding in
Korean men compared to reported frequencies in
European racial groups.
Hair density in female pattern hair loss
Using a macrophotographic method in an unselected
population sample of 377 women we found that mean
hair density on the frontal scalp became progressively
lower with increasing age after the age of about
40 years (Fig. 2).10Within each age group hair density
was normally distributed in the sample and there was
substantial overlap in hair densities between those
women classified clinically as having hair loss and those
without hair loss, an observation that can also be
Figure 1 Age related prevalence of female pattern hair loss (FPHL)
in the USA, UK and Korea.
Figure 2 The distribution of hair density by age in an unselected
sample of 377 women. Individual hair densities are shown as open
circles. The moving average is shown as a solid line. From Birch
et al.10
Female pattern hair loss • M. P. Birch et al.
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gleaned from other studies.11Low hair density was the
major factor in determining whether hair loss was
evident but it is apparent that other factors relating to
?hair quality? contribute to the subjective assessment of
hair status. This effect is well illustrated by the
observation that average hair density is lower in Korean
women than in European women,12yet the frequency
of clinical hair loss in this racial group is apparently
much lower.4This discrepancy is presumably due to
racial differences in other characteristics of the hair
which affect its overall appearance. The high frequency
of female hair loss reported by Venning and Dawber
(87% in premenopausal women) may have been due to
their method of wetting and combing the hair, thus
minimizing hair ?body?, before classifying hair status.3
Hair diameter is one factor which contributes to the
clinical assessment,10but there may be others such as
curl and hair fibre stiffness.
Genetics
Genetic factors are assumed to predispose to balding in
men although their nature and the mode of inheritance
are uncertain. Osborn proposed that balding in men and
in women is due to a single gene with two alleles, B
(balding) and b (nonbalding).13She suggested that
balding occurs in homozygous (BB) and heterozygous
(Bb) men but only in homozygous women. Smith and
Wells found that first-degree male relatives of women
with hair loss showed an increased frequency of balding
compared with the male relatives of nonbalding women
but they concluded that balding is unlikely to be due to
a single gene.14This idea was supported by Kuster and
Happle in a critique of the published data.15They
argued that the predisposition to balding is a polygenic
trait in which clinical expression represents a threshold
effect. As the less frequently affected sex women should
require more or stronger balding genes than men.
Balding in the male relatives of women with hair loss
should therefore be more common than in male
relatives of balding men. This idea, which assumes that
male and female patterns of balding are the same
condition, has yet to be tested, although the normal
distribution of hair density in the female population
strongly supports the idea that hair density is deter-
mined as a multifactorial trait.
Histopathology
Male balding involves a change in the hair cycle and a
change in the size of hair follicles. The mean duration of
anagen falls so that hairs become shorter. In some men
there is also a prolongation of the latent period of the
hair cycle (the period between shedding of the club hair
and onset of the next anagen) giving rise to an increase
in the number ?empty? follicles.16The fall in anagen
duration predominates so that the overall effect is a
shortening of the hair cycle. Terminal hair follicles on
the scalp also become miniaturized, a change generally
thought to occur gradually over the course of several
hair cycles. These changes are reflected histologically by
an increase in the proportion of follicles in telogen and
an increase in the vellus : terminal ratio. The more
limited information available on female pattern hair loss
indicates that the histological features are similar, if not
identical, to those of male balding.17Mean hair diam-
eters are lower in women with hair loss than in those
with normal hair density.6,11This observation is gen-
erally taken to indicate a progressive reduction in the
diameter of individual hairs with falling hair density.
However, this interpretation may be incorrect. Low hair
density in women is associated with a smaller number of
terminal hairs of all diameters but with a proportion-
ately greater reduction in the number of large diameter
hairs.10We suggested that the fall in mean hair
diameter with increasing hair loss may be due to
preferential loss of large diameter hairs rather than a
reduction in the size of hairs produced by individual
follicles. The number of ?vellus? hairs is the same or only
slightly increased in women with low hair density.
Thus, if miniaturization does occur in female pattern
hair loss it may be a relatively rapid process, possibly
occurring within the space of a single hair cycle.
Is female pattern hair loss
androgen-dependent?
Hamilton showed that testosterone is necessary for the
development of male balding.18His inspired ideas arose
at least partly from case reports of balding in women
with virilizing ovarian tumours.19,20Although there are
no systematic studies, clinical experience suggests that
balding is common in women with hyperandrogenism,
where it is often associated with other features of
androgen excess such as hirsutes and oligo- or amen-
orrhoea. Balding can occur rapidly if the cause is an
androgen-secreting tumour. The anecdotal view is that
hyperandrogenism is more commonly associated with a
male pattern of balding, i.e. frontal recession and vertex
balding. However, many hyperandrogenic women show
a female pattern of hair loss and those with a male
pattern do not always have androgen excess.
Several groups have examined circulating androgen
levels in women with scalp hair loss. A reduced level of
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sex hormone-binding globulin (SHBG) compared to
control values, leading to elevated levels of free andro-
gens has been the most consistent finding.11,21–23
Vexiau and colleagues found that SHBG levels correla-
ted inversely with the severity of the alopecia.23Two
studies found significant elevations of the androgen
metabolites5a-androstane-3a,17b-diol
(3a-AdiolG), 5-androstene-3b,17b-diol sulphate and
5a-androstane-3a,17b-diol
levels correlated with the severity of alopecia. Not all
women with hair loss show biochemical evidence of
hyperandrogenism. In Vexiau’s study 23% of women
with alopecia alone and 16% of women with both
alopecia and hirsutism had normal hormonal profiles.23
In the earlier study by Futterweit and colleagues 67 out
of 109 women with hair loss (61%) had normal
androgen levels.22Elevated androgen levels were seen
in 79% of women with hirsutism or menstrual distur-
bance as well as hair loss but in only 16% of those with
hair loss alone. Schmidt and colleagues found no
significant elevation of circulating androgens in 46
women with hair loss although they did detect elevated
levels of thyroid stimulating hormone in this group.25
Other observations have further questioned the role of
androgens in female pattern hair loss. Norwood des-
cribed families where female pattern hair loss appeared
to be inherited independently of male balding,26and in
a single case report female pattern hair loss occurred in
a young woman who lacked circulating androgens or
other signs of postpubertal androgenization.27The
5a-reductase inhibitor finasteride is effective in the
treatment of male balding but, in a randomized
controlled trial, failed to prevent the progression of hair
loss in postmenopausal women with female pattern hair
loss and normal androgen levels.28Taken together
these observations suggest that androgens play a role in
female pattern hair loss but that androgen-independent
mechanisms are also involved in some women.
glucuronide
sulphate.23,24
3a-AdiolG
Management
Female pattern hair loss may be considered a biologic-
ally normal ageing process. In contrast with the
prevailing attitude to male balding, however, society
generally regards it as abnormal for women to lose their
hair. Consequently the adverse effect of balding on
quality of life tends be more severe in women than in
men. As a group, women seeking medical advice for
their hair loss experience more negative body-image
feelings, more social anxiety, poorer self-esteem and
psychosocial well-being than control subjects with
nonvisible skin disease, as well as dissatisfaction with
their hair. In quality of life studies, individual responses
were more related to self-perception of hair loss than to
objective or clinical ratings and those women most
distressed by hair loss were more poorly adjusted and
had a greater investment in their appearance.29,30The
physician managing patients with female pattern hair
loss needs to be alert and sensitive to these issues and
needs counselling and psychotherapeutic skills which
go beyond merely prescribing treatment.
Nevertheless, some women are content to be reas-
sured that their hair loss is not a manifestation of a
serious disease and that it is very unlikely that they will
go bald. For those who are keen to be treated there are
two medical options: anti-androgens and minoxidil
lotion. In both cases it should be stressed that treatment
will, at best, produce only a modest increase in hair
density and that it is not possible to fully reverse hair
loss. Furthermore, in those who respond, treatment
probably has to be continued indefinitely to maintain
the response.
Anti-androgens
The androgen receptor blocker cyproterone acetate has
been widely used in Europe to treat female pattern hair
loss, usually in a cyclical regimen in combination with
Dianette?, but its effectiveness has not been studied in a
randomized blinded trial. In a trial of cyclical treatment
with cyproterone acetate in women with serum ferritin
levels above and below 40 lg ⁄L (10 subjects in each
group) hair densities increased by about 15% in the
high ferritin group after 1 year of treatment whereas
the low ferritin group failed to respond.31Hair densities
in an untreated control group fell by about 7% after
1 year. In a trial of the anti-androgen, spironolactone,
women receiving spironolactone showed less hair loss
than an untreated control group after 1 year but did not
have more hair than at baseline.32Anti-androgen
treatment is not without problems. Dose-related side-
effects of cyproterone acetate, including weight gain,
fatigue, loss of libido, mastodynia, nausea, headaches
and depression, are common. Cyproterone acetate is
potentially hepatotoxic and liver function tests should
be performed periodically. The main side-effects of
spironolactone are breast soreness and menstrual
irregularities.
Minoxidil
Minoxidil was introduced in the early 1970s as a
systemic treatment for hypertension. A high proportion
of patients taking oral minoxidil develop hypertrichosis
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which is not confined to androgen-dependent sites. This
led to the use of a topical formulation, initially for the
treatment of male balding. A 2% formulation of
minoxidil lotion is now licensed for the treatment of
hair loss in women in most European countries. Trials
in female pattern hair loss using hair counts as a
primary endpoint have shown a mean increase in hair
growth of 15–33% in the minoxidil-treated groups com-
pared with 9–14% in the vehicle control groups.33–35
One small study using hair weight as the endpoint
found an increase of 42.5% in hair weights in the
minoxidil group compared to 1.9% in the controls.36In
the investigator and subject assessments minoxidil was
superior to the vehicle but about 40% of subjects
appeared not to respond to minoxidil.34,35None of the
trials has been extended beyond 32 weeks and the long-
term results of minoxidil treatment are uncertain. In
men the beneficial effects on hair growth are lost rapidly
on cessation of treatment and it is likely that the same is
true in women. The increase in hair counts following
treatment with minoxidil lotion is noticeable within
8 weeks and has peaked after 16 weeks. It is unlikely
that this rapid increase in terminal hair counts can be
explained by reversal of follicular miniaturization; a
more plausible explanation is that minoxidil triggers
follicles in a latent phase of the hair cycle into anagen.
Minoxidil is a safe treatment. Some patients complain
that it leaves unsightly deposits on the hair. Occasion-
ally it causes scalp irritation which may be severe
enough to cause a temporary increase in hair shedding
and patients should be warned about this. Hypertricho-
sis on the face and on more remote sites has been
reported, particularly when higher concentrations of
minoxidil are used.37This resolves if treatment is
stopped.
In the authors’ experience minoxidil lotion is more
reliably effective and better tolerated than anti-andro-
gen treatment. The gains are modest and it is helpful to
have an objective measure, such as serial standardized
clinical photographs, to convince the patient (and the
physician) of the response.
Hair surgery
Hair transplantation is a well-established treatment for
male balding. It is increasingly being used in female
hair loss although the expense and trauma mean that
only a small minority of women pursue this avenue of
treatment. Surgery is most suited to those women in
whom hair loss is limited in extent and who fail
medical treatment. A skilled surgeon is essential for
good results.
Finally, we should be aware that the distress caused
by female pattern hair loss means that some women are
prepared to go to great lengths in search of effective
treatment (the same is true of male balding), making
them vulnerable to exploitation by the unscrupulous.
The physician has an important role in explaining the
reality of what can be achieved by treatment and
dissuading the sufferer from indulging in illusory and
expensive ?cures?.
Acknowledgements
M.P.B. receives financial support from the Sheffield
Hospitals Charitable Trust.
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