Androgenetic
alopecia
Salient
features
·
Androgenetic
alopecia (AGA) is a non scarring progressive miniaturization of the hair
follicle in genetically predisposed men and women, usually in a specific
pattern distribution.
·
AGA
onset may be at any age following puberty, showing an increasing frequency with
age.
·
The
etiology of AGA is multifactorial and polygenic with, as of this writing, 12
genetic regions recognized to associate with AGA in men. In men, AGA is an
androgen-dependent trait. Even though the role of androgens in female AGA is
less certain than in men, there is a subset of women with AGA and associated
hormonal dysregulation.
·
Generally,
diagnosis of AGA is based on history and clinical examination. Depending on
patient history and clinical evaluation, however, additional diagnostics may
become necessary to exclude differential diagnoses; for example, ferritin level
or thyroid-stimulating hormone in diffuse effluvium or endocrinologic workup in
women with signs of hyperandrogenism.
·
Biopsy
is very rarely indicated in AGA. Biopsy is indicated only if, for example, the
differential diagnoses cicatricial alopecia or diffuse alopecia areata are
suspected.
·
AGA
has a naturally progressive course, meaning that the main therapeutic aim is
the prevention of disease progression or enhancement of hair growth during the
early, mild to moderate stages of the disease.
·
The
best clinical evidence according to current study data exists for topical
application of minoxidil in both genders and for the oral intake of finasteride
in men. Alternatively, cosmetically satisfactory results can be achieved using
hair transplantation in nonprogressive stable AGA with sufficient available
donor area.
Introduction
Androgenetic
alopecia (AGA) is the most common type of hair loss in men and women that result
from a progressive
shortening in
the duration of
successive anagen phase leading to miniaturization of the hair follicle
with a
conversion of scalp terminal hairs follicles into miniaturized vellus-like hair
follicles,
an increase in the duration of telogen in genetically predisposed men and
women, usually in a specific pattern distribution.
Frequency and
prevalence
The onset may be at any age following puberty
leading to a progressive hair loss in a pattern distribution.
Men
The frequency and severity of male AGA
increase with age in all ethnic groups. Initial signs of AGA, including some
recession of the frontal hair line and at the temples, usually develop during
teenage years. Progression to deep frontal recession and ⁄or vertex balding may
also start shortly after puberty, although in most men the onset is later. By
the age of 70 years, up to 80% of men are bald (Hamilton–Norwood VI–VII).
Women
As in men, the population frequency and
severity of AGA increase with age in women, more prevalent following menopause.
Age of onset for FPHL is later than that seen in men. Most common form of
alopecia in women aged 20-40 years. Affect 50% women during their lifetime.
Hair
Growth Cycle
Hair
follicles normally exist in three phases of growth:
1. A growth period called
the Anagen phase, typically lasting three or four years,
followed by
2. A brief shriveling up period
called the Catagen phase, usually lasting 3 weeks, followed by
3. A dormant or resting period
called the Telogen phase, usually lasting three or four
months.
A telogen hair does not grow and is shed from the follicle after about 3 months.
So, a normal
hair follicle will typically grow for about three years and then rest for about
three months, before regrowing a brand new hair strand. As the new hair grows
and lengthens, it ejects the old hair strand resulting in the normal shedding
of hair that we experience every day (we normally shed up to 50 or more hairs
per day). This cycling will typically allow the hair shaft to grow about 18 to
24 inches (e.g. shoulder length hair) before it sheds. Some exceptional
individuals have a naturally longer growth cycle and can, therefore, achieve
much greater hair length (e.g. waist length hair).
Most of the
follicles, approximately 90% to 95% (most people start out with about 100,000
hair follicles), are in the growth phase, growing approximately one half inch
per month.
If the
growth cycle is unusually short, the hair shaft won’t achieve much length. As
mentioned, that’s one of the things that happen when the “Androgen sensitive”
follicles within the pattern are continually exposed to normally present DHT.
Every hair
follicle has a genetic code determined at conception. This genetic code
controls “if” and “when” each follicle will become vulnerable to the hair
killing effects of a normally present male hormone called dihydrotestosterone
or DHT. When this happens, DHT begins to slowly diminish the now vulnerable
follicles by:
1. Causing Miniaturization, and
2. Shortening the Anagen Phase
As a result,
hair within the thinning or balding pattern becomes progressively finer,
shorter, loses pigment, and sheds/cycles more frequently.
In both males and females there is
transition from large, thick, pigmented terminal hairs to thinner, shorter,
indeterminate hairs and finally to short, wispy, non pigmented vellus hairs.
This
transformation follows a progressive course with each hair cycle in the
following manner. MPHL and FPHL exhibit a progressive decrease in anagen
duration with each cycle. In each
cycle, the duration of anagen phase becomes shorter with the telogen phase remaining constant. As a result, more
hairs are in the telogen phase, and patient may notice an increase in hair
shedding. The following anagen phase is even shorter and the
new hair is shorter, thinner and less pigmented. Eventually, the pale vellus like
hairs are the results. Ultimately, anagen duration becomes so short that the
growing hair fails to reach the surface of the skin, leaving an empty
follicular pore.
ETIOLOGY
AND PATHOGENESIS
Andro refers to Androgens or male
hormones. Male hormones are normally present to a greater degree in men and to
a much lesser degree in women. The term genetic refers to the
genetic or inherited nature of pattern balding. Every hair follicle has a
genetic program inherited from both parents at conception (not the mother only)
that controls this type of hair loss. At some point in time, because of this
genetic program, certain follicles within the balding pattern become sensitive
or vulnerable to the follicle killing effects of a very specific male hormone
called dihydrotestosterone (DHT). Other follicles outside the pattern with a
different genetic program remain insensitive or invulnerable to DHT.
So it’s not
an excess of male hormones or the location of the follicle, but the follicle
itself, and more specifically the genetic program affecting each follicle.
These DHT sensitive follicles then begin to change, becoming progressively
smaller, called miniaturization. The miniaturized follicles
also have a shortened growth phase, so the hair strands become
progressively shorter. If this process continues, uninterrupted, the hairs
become extremely petite and lose pigment; the once large and long growing
pigmented hairs are thus transformed into hair of similar quality to the tiny
virtually invisible blonde hairs that grow on our face (vellus hair).
Risk factors: the etiology of AGA is
multifactorial and polygenic.
MEN
AGA is an androgen-dependent trait, which
leads to progressive miniaturization of the hair follicle in predisposed men.
It is thought that enhanced androgen effects at the genetically predisposed
hair follicles are mediated by raised androgen receptor density and ⁄or
increased activity of 5-alpha-reductase type II. DHT is
the androgen chiefly responsible for follicular pathology. DHT probably act
primarily on dermal papilla, the predominant site of androgen receptor and type
II 5 alfa reductase enzyme expression within the hair follicle. Nearly
all men afflicted with AGA have normal circulating androgen levels. The
predisposition to AGA is predominately due to genetic factors. Family analyses
show a significantly increased risk for the development of AGA in men with a
father suffering from AGA. Conversely, the risk of AGA is significantly
decreased in those men with a non-balding father.
Utilizing
gene expression arrays of scalp biopsies from men with AGA, enhanced expression
of the gene that encodes prostaglandin D2 synthetase is observed in bald scalp
as compared to haired scalp; prostaglandin D2 synthetase converts prostaglandin
H2 (PGH2) to PGD2. Increased levels of PGD2 are also found in balding scalp,
PGD2 is shown to inhibit hair growth. This inhibition of hair growth by PGD2
requires interactions with one of its receptors, raising the possibility of a
potential therapeutic target.
WOMEN
Less is known about the etiology of AGA in women. In women, a similar androgen-related pathophysiology is
postulated. Women who develop balding shortly after puberty often have a
positive family history for pattern hair loss in both male and female family
members. In women who develop pattern alopecia during the perimenopausal period
and menopause, it may be due to a genetic predisposition as well as alterations
in androgen metabolism at the level of the hair follicle and systemic hormonal
changes.
The European Consensus Group agreed not to
differentiate between androgenic alopecia and AGA, but to define a subset of
women with AGA and associated hormonal dysregulation.
 Rarely, AGA develops in prepubertal children (ages
6–10 years). Affected boys and girls demonstrate a FPHL pattern without
bitemporal recession, and they have a strong family history of AGA (present
in at least one parent). No evidence has been found for abnormal circulating
testosterone levels or precocious puberty.   Testosterone
is converted to the more potent dihydrotestosterone by 5α-reductase. Skin
cells contain 5α-reductase (types I and II). The
type I enzyme is found in sebaceous glands, and the type II enzyme is found
in hair follicles and the prostate gland. Testosterone and
dihydrotestosterone act on androgen receptors in the dermal papilla. The
impact of androgen on hair follicles is site specific. For example, hair
located on the chest, pubic area, and beard area reacts positively to the
presence of androgens by producing terminal--or thick, pigmented--hair. In
contrast, hair follicles located on the scalp are reduced in size and produce
non pigmented vellus hairs in response to androgens. As the duration of
anagen shortens with successive hair cycles, so the follicles become progressively smaller (reduced in size), in what is called “miniaturization,”
and this causes them to produce shorter and shorter fine hair
shafts. Eventually, they stop producing hairs completely,
leaving a bald area. Androgenetic
alopecia does not develop in men with a congenital absence of 5α-reductase type II.
Finasteride, which inhibits 5α-reductase type II,
slows or reverses the progression of androgenetic alopecia.  Follicular miniaturization is the
histological hallmark of AGA. Diffuse hair thinning and sometimes increased
hair shedding precede the clinical appearance of baldness by a number of
years. This is because the process of
follicular miniaturization which occurs in AGA does not simultaneously affect
all follicles within a follicular unit (FU). Instead, there is a hierarchy of
follicular miniaturization within FUs, and secondary follicles are affected
initially and primary follicles are miniaturized last. Scalp hairs arise from
FUs that are best seen on horizontal scalp biopsy. FUs comprise a primary
follicle that gives rise to an arrectorpili muscle (APM), a sebaceous gland,
and multiple secondary follicles that arise distal to the APM. Hairs from
secondary follicles commonly emerge from a single infundibulum.  Horizontal
section of skin biopsy from a hairy scalp showing features of early
androgenetic alopecia. Follicles
exist within follicular units comprising arrector pili muscle, sebaceous
gland, and derived secondary hairs, some of which have miniaturized to become
secondary vellus hairs. The image in the upper right depicts the level of the
follicle where the horizontal sections have been cut. Scalp
follicles exist as compound follicular units. In androgenetic alopecia, a reduction in the number of
hairs per follicular unit precedes the development of baldness. Miniaturization
occurs initially in the secondary follicles. This leads to a reduction in
hair density that precedes visible baldness. Bald scalp becomes visible only
when all of the hairs within a follicular unit are miniaturized. With
miniaturization, the arrectorpili muscle (APM) initially loses attachment to the
secondary follicles. When primary follicles eventually miniaturize and lose APM attachment, the hair loss becomes
irreversible.  Hair follicle
miniaturization is the hallmark of male pattern hair loss (MPHL), female
pattern hair loss (FPHL), and alopecia areata (AA). AA has the potential for
complete hair regrowth and reversal of miniaturization. MPHL and FPHL are
either irreversible or show only partial regrowth and minimal reversal of
miniaturization. Hypothesis: The
arrector pili muscle (APM) attaches to the outer root sheath (ORS) of the
follicle at the level of the bulge. The bulge is the main repository of
epithelial stem cells and this attachment may be necessary for reversal of
hair follicle miniaturization. In AA, contact is
maintained between the APM and the bulge of miniaturized follicles while in
MPHL and FPHL contact is lost. Contact between the APM and the bulge in AA
may be required for reversal of hair follicle miniaturization. Maintenance of
contact between miniaturized follicles in AA could explain the complete hair
regrowth while loss of contact between the APM and the bulge in MPHL and FPHL
may explain why the hair loss is largely irreversible. The relationship between
hair cortex diameter, hair matrix size, and volume of the dermal papilla is
well described, and disruption of this relationship may result in follicle
miniaturization. Normally scalp hairs exist as clusters (follicular units)
composed of three to five terminalhair shaft-producing
follicles surrounded by a fibrous connective tissue sheath, served by
a single arrector pili muscle (APM). The hairs often emerge on the scalp
through a single pore. One by one, as
follicles miniaturize, the follicular units within thinning regions of the
scalp begin to produce only one or two terminal hairs. Once all the follicles
within a follicular unit miniaturize, baldness is observed. AA also results in
follicular miniaturization. However, in contrast to androgenetic alopecia
which is of gradual onset and at best only partially reversible, AA has an
abrupt onset, is unpredictable, has no specific pattern, and is completely
reversed with successful treatment. |
Clinical features
The essential clinical feature of balding in
both sexes is patterned hair loss over the crown.
MPHL
HAMILTON NORWOOD TYPE
This is the most frequent pattern in men with
AGA and occasionally observed in women. Recession of the frontal hairline
mainly in M-shaped pattern is the characteristic finding, later followed by
vertex thinning with progression until the top of the scalp is completely bald.
Occipital area and the sides of the scalp are spared even in long standing
MPHL. About 10% of men, however, develop diffuse thinning of the crown with
retention of the frontal hairline with a pattern that resembles the Ludwig type
observed in women.
FPHL
Women usually show a more diffuse
distribution of hair loss with accentuation in the frontal and mid scalp and
preservation of the frontal hairline, but the parietal and occipital scalp may
also be involved. In cases of diffuse thinning, also think of diffuse telogen
effluvium and diffuse alopecia areata as a differential diagnosis or
concomitant condition.
LUDWIG TYPE
The so called FPHL is characterised by
diffuse central thinning of the crown with maintenance of the frontal hairline.
It is the most common type of AGA in women; it is occasionally observed in men.
There are two scales describing this pattern, the 3 point Ludwig scale and the
5 point Sinclair scale.
|
Ludwig's scale for female AGA |
|
Examination of the central part width can be used
to classify severity of FPHL via the Sinclair scale.
Sinclair scale for female pattern AGA
CHRISTMAS TREE PATTERN
Frequently observed in women, the Christmas
tree pattern shows diffuse thinning of the crown similar to the Ludwig pattern
with an additional breaching of the frontal hairline in a triangular shaped.
In young women with AGA, look for signs of virilization
(clitoral hypertrophy, acne, facial hirsutism) and, if present, rule out
endocrine dysfunction. However, most women with pattern hair loss are
endocrinologically normal.
There are two populations of scalp follicles: androgen-sensitive
follicles on the top and androgen-independent follicles on the sides and back
of the scalp.
Why do androgens stimulate beard and body hair but at the same time cause
loss of hair on the scalp? Even on the scalp there is regional variation, as
hair on the occiput is never lost. Testosterone is converted to DHT by the enzyme
5α-reductase, of which there are two isoenzymes, type I and type II. Type I
5α-reductase is present predominantly in sebaceous glands and the liver,
whereas type II 5α-reductase dominates in scalp, beard and chest hair
follicles, as well as in the liver and the prostate gland. DHT is then transferred, in a receptor mediated process, to the nucleus,
where it influences gene expression. In any event, the metabolism of androgens
in some follicles stimulates hair growth, while in others hair growth is
inhibited.
Differential Diagnosis
CLINICAL EVALUATION
Clinical examination should involve the scalp
skin and hair, facial and body hair and skin as well as the nails.
Scalp examination
The scalp skin usually appears normal in AGA,
but consider that seborrhoeic dermatitis of the scalp can be an associated and
potentially aggravating factor. Look for signs of inflammation (erythema,
scaling and hyperkeratosis), seborrhoea and signs of scarring (atrophy, loss of
hair follicle ostia). Consider alopecia areata and scarring alopecias, which can
mimic AGA, especially frontal fibrosing alopecia in women.
Look for signs of sun damage in balding
areas, which may be an aggravating factor for AGA. In long-standing AGA,
discrete atrophy of scalp skin can be present.
Hair examination
Scalp hair
Part the hair to assess scalp hair density.
Compare part width in the frontal, occipital and temporal regions toexamine the
characteristic pattern distribution of alopecia and look for short and fine
miniaturized or broken hairs, variation of hair calibre, length and regrowth.
Dermoscopy may be helpful.
The most frequently used scales in practice
are the Hamilton–Norwood scale for male pattern distribution and the Ludwig
scale or Olsen scale (frontal accentuation ⁄Christmas tree pattern) for a
female pattern. The experts agreed to use these scales in practice. The 5-point
Sinclair scale is more complicated than the Ludwig scale but offers a broader
range of categories. This could become important as more and more women consult
their doctor in the early stages of hair loss.
Facial and body hair
Look for abnormal facial and body hair
density and ⁄or distribution. Absent or reduced eyebrows ⁄eyelashes and ⁄or
body hair may suggest alopecia areata. Think also of frontal fibrosing alopecia
if eyebrows or eyelashes are absent or reduced. The experts stated that some
women with AGA also complain of reduction of eyebrows or eyelashes.
If there is excessive terminal body hair
growth, examine the distribution. Think of ethnic hypertrichosis,
hypertrichosis dueto medications or hirsutism. Look for signs of acne,
seborrhoea and obesity, which are clues for hyperandrogenism.
Nail examination
Nail abnormalities are not typical for AGA,
but occur in alopecia areata, certain deficiencies and lichen planus.
Laboratory
investigations
Investigations in female pattern hair loss
·
Full blood count
·
Serum ferritin
·
Thyroid function test
·
Fasting lipids
·
Fasting glucose
If
there are signs of hyperandrogenism:
·
Serum testosterone(total and free testosterone)
·
DHEAS (morning sample on
days 1–5 of cycle; make sure the patient is not on the oral contraceptive pill)
·
17‐hydroxyprogesterone
·
Androstenedione
·
Ovarian ultrasound
·
Adrenal imaging
An interdisciplinary approach involving
gynaecologists, endocrinologists and dermatologists is recommended if the
history and clinical examination are indicative of androgen excess [e.g.
polycystic ovary syndrome (anovulatory cycle, elevated hormonal levels), cycle
disturbances, and androgen-secreting tumours]. The group agreed to perform a
free androgen index test [FAI = total testosterone (nmol L -1) x 100
⁄sex hormone-binding globulin (SHBG) (nmol L -1)] and prolactin as
screening parameters. Depending on the results, further endocrinological
investigations may be required. Free testosterone and FAI seem to be sensitive
for the detection of hyperandrogenaemia. In women, at least 80% of bound serum
testosterone is bound to SHBG. Consequently, free serum testosterone levels are
substantially influenced by SHBG levels, which limit the interpretation of free
serum testosterone. The FAI takes this SHBG dependence into account. FAI levels
of 5 and above are indicative for polycystic ovary syndrome. Other disorders
presenting with clinical and ⁄or biochemical signs of hyperandrogenism such as
congenital adrenal hyperplasia, androgen-secreting tumors or Cushing syndrome
should be excluded. For this purpose further laboratory testing, e.g.
17-OH-progesterone, follicle-stimulating hormone, estradiol, prolactin or
cortisol may be necessary.
Note: It makes sense to take any hormonal
level only on the condition that there is no hormonal intake. Estrogens lead to
elevated SHBG levels, whereas testosterone levels may be only slightly changed.
Consequently, the FAI can be markedly improved by hormonal contraception.
Therefore, the minimum pause in hormonal contraception has to be 2 months. The
measurements should be taken between 08.00 and 09.00 h, ideally between the
second and fifth days of the menstrual cycle.
Women may benefit from screening for
hypertension, hypercholesterolemia and late‐onset
diabetes.
Investigations in MPHL
In men, laboratory testing for the diagnosis
of AGA is unnecessary, except if the history or examination provide clues for
another underlying disorder or associated disease.
Note: Additional laboratory examinations may
become necessary before starting specific treatments. Therefore, the Consensus
Group agreed that for men above 45 years measuring the prostate-specific
antigen (PSA) value should be recommended before starting finasteride therapy,
albeit PSA is controversially discussed. Nevertheless, finasteride reduces PSA
values and can delay diagnosis or mask detection of prostate cancer. The
treating urologist should be informed on the patient’s finasteride intake.
Children and adolescents
In children and adolescents with premature
onset of AGA an interdisciplinary approach between the dermatologist and
paediatric endocrinologist should be taken.
Diagnostic techniques
and clinical documentation
Pull test
The pull test is an examination that is easy
to perform and to repeat, to roughly judge active hair shedding. Briefly, 50–
60 hairs are grasped by thumb, index and middle fingers. While the hairs are
tugged away, the fingers slide along the hair shaft. The pull test is positive
when more than 10% of the grasped hair can be pulled out. The pull test should be performed in the
right and left parietal, frontal and occipital regions and in the visibly
affected areas, as shortening of the cycle increases telogen rates and the pull
test becomes positive. The pull test in different scalp regions is useful in
excluding diffuse telogen effluvium.
In patients with AGA the pull test is
positive only in the active phase with increased telogen hairs in the affected
area. It may be frontally accentuated or diffusely positive. A diffuse positive
pull test requires further diagnostic tests to exclude diffuse telogen
effluvium.
The pull test is usually negative in AGA,
except in active periods when there can be a moderate telogen hair shedding in
a pattern distribution. However, even with a diffusely positive pull test such
as in telogen effluvium or diffuse alopecia areata, underlying AGA may be
present.
Trichoscopy
KEY FEATURES
1. Hair
shaft diameters diversity of more than 20%.
2. Peripilar
sign
3. Yellow
dots
4. Vellus
hairs
Hair diameters diversity (Anisotrichosis >20%)
A diversity of hair shaft diameters >20%
per field of Dermoscope in frontal area is diagnostic for AGA. It is
characterised by simultaneous presence of hairs of different diameters such as
thick, thin, intermediate and vellus hairs. It reflects follicular
miniaturisation.
Peripilar sign
It is seen as a brown halo of approximately 1
mm diameter at the emergence of hair shaft. It correlates with perifollicular
inflammation. Extensive peripilar sign is a poor prognostic factor for AGA.
Yellow dots
They are feature of severe miniaturization and
are more numerous in patients with severe AGA. They correspond to follicular
Ostia filled with keratosebaceous material.
Vellus hairs
They are the sign of severe miniaturization.
Presence of up to 10% vellus hairs in frontal scalp is considered normal.
Beyond that is diagnostic for AGA.
Scalp biopsy
The scalp biopsy is an essential instrument
in the diagnosis of cicatricial and selected forms of noncicatricial alopecia.
A biopsy, mostly performed as a 4-mm cylindrical punch, is indicated in AGA
only in cases where the diagnosis is uncertain, e.g. where scalp changes
suggestive of cicatricial alopecia or diffuse alopecia areata are present.
Scalp biopsies should be reported by dermatopathologists who are experienced in
hair pathology using both vertical and horizontal sectioning.
A scalp biopsy allows a definitive diagnosis,
since it provides information on histological features, the number of terminal
and vellus hair per area and the number of anagen and telogen hair.
Site
of biopsy
The preferred area for biopsy is the central
scalp in an area representative of the hair loss process. Biopsies should not
be taken from the bitemporal area as this region may have miniaturized hairs
independent of AGA.
Type
of biopsy
Two 4-mm punch biopsies following the
direction of the hair shafts are taken lateral to the midline deep into the
subcutaneous fat where anagen hair bulbs are located. One biopsy is processed
for conventional vertical sectioning; the other is sectioned horizontally with
respect to the skin surface.
Horizontal sectioning allows a rapid
assessment of hair follicle numbers, diameter, grouping and morphology. In AGA,
there is an increased number and proportion of miniaturized (vellus-like) hair
follicles. The ratio of terminal to vellus-like hair follicles is typically
< 3: 1 in AGA-affected areas compared with > 7: 1 in the normal scalp.
Other features include an increased telogen count and an increase in the number
of follicular stelae (tracts beneath miniaturized follicles). A mild
perifollicular lymphohistiocytic infiltration primarily around the upper
follicle as well as perifollicular fibrosis may also be seen. Uninvolved scalp
(e.g. occiput) appears normal.
Diagnostic algorithm for androgenetic alopecia
Sinclair grading
MANAGEMENT
Medical treatment
AGA has a naturally progressive
course, meaning that the main therapeutic aim is the prevention of disease
progression and enhancement of hair growth during the early, mild to moderate
stages of the disease.
Established medical management for pattern
hair loss consists of antiandrogens, 5α‐reductase
inhibitors and topical minoxidil. They may be used alone or in combination.
Although improvement may be seen after as soon as 4 months, 1 year of treatment
may be required before a clinical response is apparent. Maintenance therapy is
required to sustain any benefit.
Medical therapy is appropriate first line management for both MPB and
FPHL.
Treatment of male
pattern hair loss
Topical formulations of minoxidil
and oral finasteride have been approved by the US Food and Drug Administration
(FDA) for the treatment of men with male AGA.
Oral Finasteride
Finasteride (1 mg PO daily) is
a synthetic aza‐steroid that is a
potent and selective antagonist of 5α‐reductase
type 2, the
enzyme which inhibits the conversion of testosterone
to its metabolite DHT; this results in lower serum and scalp
levels of DHT.It halts hair loss in 90% of
patients, and partial hair regrowth occurs in 65% of those receiving finasteride.
A scalp biopsy study of patients with AGA found that
after 12 months of finasteride treatment, terminal hair counts increase and
vellus hair counts decrease, demonstrating the ability of finasteride to
reverse the miniaturization process and to encourage the growth of terminal
hairs.
Finasteride has no affinity for androgen receptors and
therefore does not block the important actions of testosterone (growth of the
phallus and scrotum, spermatogenesis, libido). Most men may begin to see first
benefit in slowing hair loss as early as 3 months. After 6 months, there is a
re-growth of terminal hair on the vertex and anterior mid-scalp but poor
response on the frontal area.
Significant improvement is seen in first 2 years; after which a
steady state is reached. If the drug is stopped, however, the hair that had
grown will be lost within 12 months. 2% of men taking finasteride report loss of libido, impotence, or
ejaculation failure, and patients should be appropriately warned of this
potential side effect. These
effects are reversible when the drug is stopped and disappears in two-thirds of
those who continue taking finasteride.
Dutasteride
It is a combined type 1 and 2 5α‐reductase
inhibitor. It produces a dose‐dependent
reduction in serum and scalp DHT levels to a greater degree than that seen with
finasteride, and is more effective than finasteride in stimulating hair
regrowth in male pattern baldness. Dutasteride is currently marketed at a 0.5
mg dosage for benign prostatic hypertrophy, but is also widely used off‐label
for treatment of AGA. Sexual side effects are more common with dutasteride than
with finasteride, and are also dose related. Retrograte ejaculation is reported
but appears to be reversible on cessation. Because of the long biological half‐life,
side effects may take many months to reverse.
Topical Minoxidil
Topical minoxidil (2% solution, 5% solution, 5% foam) is used.
Typically, 2% solution is used for females and 5% for males, may be helpful in reducing rate of hair loss and in partially
restoring lost hair in both males and females. 1ml of Minoxidil should be applied bd directly to dry scalp and spread lightly
with a finger. If
the hair has been shampooed, the hair and scalp should be at least towel-dry.
The lotion or foam should stay on the scalp for at least 4 hours before the
next shampoo. The patient should be informed that this is a lifelong treatment.
Minoxidil-induced hair growth is commonly associated with shedding of telogen
hairs and a paradoxical worsening of hair loss approximately 4 to 6 weeks
following initiation of treatment. This resolves with continued treatment. It
takes 4–6 months before the medication starts working and that the maximum
effect can be expected after 1 year.
When applied topically, minoxidil increased
terminal hair density in up to 30% of individuals. Terminal hair appeared to
regrow at the margins, but complete covering of the bald areas was seen in less
than 10% of responders. De Villez suggested that men who responded best to
minoxidil were those in whom the balding process was at an early stage, with a
maximum diameter of the bald area of less than 10 cm, and in whom the pre‐treatment
hair density was in excess of 20 hairs/cm2. There is a slight
increase in benefit if the concentration is increased to 5%. The benefit is
most pronounced in the first 6 months of therapy and thereafter is marginal. The younger subjects experience better
efficacy of topical minoxidil than the older subjects. Males show an inverse
relationship between the effects of topical minoxidil and the duration of
balding: males with duration of balding <5 years show a significantly better
effect than those with duration of balding >21 years. The diameter of vertex
balding in men shows an inverse relationship with efficacy of topical
minoxidil: males with <5cm diameter vertex balding area show a better effect
of treatment than subjects with diameters >15 cm.
Minoxidil increases the anagen hair growth phase, enlarges
miniaturized follicles and has a vasodilatory effect [improves blood supply to dermal
hair papilla via the induction of vascular endothelial growth factor (VEGF)].
About 5-10% develops scalp dryness and pruritus and rarely allergic CD and can be alleviated by application
of a topical corticosteroid, such as triamcinolone 0.1% lotion.
These side effects are more common with 5% solution, but seen
less frequently when the 5% is in the foam base. Systemic side effects have not
been reported. Avoid during pregnancy and lactation.
Hypertrichosis of the
temples may also occur but does not necessitate
discontinuing the medication. In men with early vertex hair loss, acceptable
cosmetic hair growth occurs in patients by 4-8 months. Frontal-bitemporal
recession often fails to respond. Therapy must be continued. If
treatment is stopped, clinical regression occurs within 6 months to the state
of baldness that would have existed if treatment had not been applied. Patients
should be warned that in order to maintain any beneficial effect, applications
must continue once or preferably twice daily indefinitely. When they are stopped, hair loss starts
again.
1mg of oral finasteride once daily is the first line treatment for male
AGA in men between 18 and 40 years of age with mild to moderate
AGA. Oral finasteride retains its efficacy in men over
40 years of age, though to a lesser degree and with a higher frequency of
sexual adverse effects compared to men between 18 and 40 years. Again response
to treatment for both topical minoxidil and oral finasteride should be assessed
at 6 months, although in some men response to finasteride may not become
evident until 12 months. If no effect is seen after 12 months, further
treatment is unlikely to be of benefit. For greater efficacy, the combination of topical minoxidil 5% solution
1ml twice daily and oral finasteride 1mg daily may be considered.
Treatment of female
pattern hair loss
As a general rule, topical minoxidil 2% solution twice daily or 5%
solution 1ml once daily represents the first-line treatment for female AGA,
irrespective of age. Increase of hair growth is evident within 8 weeks of
treatment and gradually peaks by 16 weeks. Response to treatment should be assessed
at 6 months. If successful, treatment needs to be continued to maintain
efficacy. In case of treatment failure, topical minoxidil 5% solution twice
daily may be tried, and in postmenopausal women without a family or personal
history of breast cancer, 5 mg of oral finasteride once daily may be
considered.
All patients, unless contraindicated, initiate therapy with
topical minoxidil 5% foam daily. This is the only therapy that is approved by
the FDA for FPHL and has been shown to be safe and effective.
Antiandrogens
In the
setting of hyperandrogenemia, women with
FPHL may benefit from oral contraceptives (to suppress ovarian androgen
production) or spironolactone
100-200mg/day. These must not be used in men.
Figure
Androstenedione, which is mostly produced in
the ovary and adrenal glands, is converted to testosterone by
17β-hydroxysteroid dehydrogenase. Testosterone then circulates throughout the
body to reach its target tissues. Androgen-metabolizing enzymes have been found
in many parts of the hair follicle. The presence of those enzymes makes the
pilosebaceous unit a site of androgen metabolism and synthesis. Circulating
free testosterone either binds to intracellular androgen receptors in the hair
bulb and dermal papilla, which facilitates miniaturization of the follicle, or
is metabolized into dihydrotestosterone (DHT) by the enzyme 5-alpha-reductase.
DHT then binds the same receptor but with much greater affinity. Of the
androgens depicted in Figure, only
DHT and testosterone bind to androgen receptors.
Androgen-metabolizing
enzymes in the pilosebaceous unit
|
Dermal Papilla |
Aromatase, 17β-HSD,
5α-reductase (type II) |
|
Outer Root Sheath |
Aromatase, 17β-HSD,
5α-reductase (types I & II) |
|
Inner Root Sheath |
Aromatase,
5α-reductase (types I & II) |
|
Sebaceous Gland |
Aromatase,
5α-reductase (type I) |
|
Sebaceous Duct |
5α-reductase (type
II) |
17β-HSD, 17β-hydroxysteroid dehydrogenase.
Surgical
Treatment
Hair transplantation
Ultimately, surgery, specifically follicular unit transplantation (FUT),
can be considered in male patients with unsatisfactory results of 1 year of
pharmacological treatment and sufficient occipital donor hair. Surgical
treatment of male balding involves the redistribution of terminal hair to cover
the balding scalp – the number of terminal hair follicles on the scalp remains
the same. In most cases this means transplanting hair follicles from the
occipital scalp to the balding areas. Grafts
are taken from androgen-insensitive hair sites such as peripheral occipital
hairy areas to bald androgen sensitive scalp areas. Hair transplantation is
possible because these androgen-insensitive areas are genetically resistance
against baldness causing androgens. This phenomenon is called donor dominance.
The advantage of HT is that the improvement is permanent; the disadvantages are
the high initial cost and the inconvenience of a surgical procedure. In most
cases, however the cosmetic result is not as good as that achieved by natural
regrowth of the local hair with minoxidil or finasteride. Although simultaneous minoxidil
therapy to prevent future hair loss is recommended by some, it is not of proven
benefit. In males, the combination of FUT with 1mg of oral
finasteride daily is recommended to achieve more sustained results.
Surgical treatment can achieve very
satisfactory results but careful patient selection and surgical skill allied to
the aesthetics of scalp hair growth are essential. Key considerations include
the following:
There should be an adequate donor area, i.e.
good hair density in the occipital scalp.
Age – the predictive value for men aged
<25 years is very uncertain. Surgery in young men may result in misplaced
hairlines or an unnatural appearance 20–30 years later as balding progresses.
The correction of established frontal hair
loss is more effective than vertex balding, which tends to progress with time.
Thicker hair shafts give better coverage than
fine‐calibre hair.
Experienced surgical teams can give
significant improvement after 1–2 sessions. The final results take 5–6 months
to become apparent.
Complications of surgery include scalp
erythema and crusting, and facial oedema. Less common problems include infection,
postoperative bleeding, and scarring and arteriovenous fistula formation.
Hair transplantation is less widely used in
treating FPHL but can give good results in selected cases. It is most
appropriate in women with pronounced hair loss of limited extent who retain
good hair density in the donor site. Those with a mild degree of hair loss are
less suitable as are those with involvement of the occipital region.
Evidence-based (S3) guideline for the treatment of androgenetic
alopecia in women and in men –2017
Therapeutic recommendation for minoxidil
Male patients
1. Topical
Minoxidil 2–5% solution 1 mL or half a cap of 5% foam twice daily is
recommended to improve or to prevent progression of AGA in male patients above
18 years with mild to moderate AGA (Hamilton Norwood II-V).
2. It
is suggested that 5% solution or half a cap of 5% foam can be used for greater
efficacy.
3. The
response to treatment should be assessed at 6 months. If successful, treatment
needs to be continued to maintain efficacy.
4. For
greater efficacy the combination of oral finasteride 1 mg/day and topical
Minoxidil 2–5% solution, twice daily can be considered.
Female patients
1. Topical
Minoxidil 2% solution 1 mL twice daily or half a cap of 5% minoxidil topical
foam once daily is recommended to improve or to prevent progression of AGA in
female patients above 18 years with AGA.
2. The
response to treatment should be assessed at 6 months. If successful, treatment
needs to be continued to maintain efficacy.
Therapeutic recommendation for 5a-reductase inhibitors
Male patients
Finasteride
1. Oral
Finasteride 1 mg/day is recommended to improve or to prevent progression of AGA
in male patients above 18 years with mild to moderate AGA (Hamilton-Norwood
II-V).
2. The
response to treatment should be assessed at 6 months, although in some men it
may not become evident before 12 months. If successful, treatment needs to be
continued to maintain efficacy.
3. It
cannot be recommended for or against treatment with topical finasteride at the
present time
4. For
greater efficacy the combination of oral finasteride 1 mg/day and topical
Minoxidil 2–5% solution or 5% foam twice daily can be considered.
Dutasteride
1. Oral
Dutasteride 0.5 mg/day can be considered in case of ineffective previous
treatment with 1 mg finasteride over 12 months as a second line treatment to
improve or to prevent progression of AGA in male patients above 18 years with
mild to moderate AGA (Hamilton-Norwood III-V)
Therapeutic recommendation for hormonal treatment
Female patients
1. It
cannot be recommended for the use of oral anti-androgens (cyproterone acetate
(CPA), drospirenone, and spironolactone) to improve or prevent progression of
AGA in normoandrogenic female patients at the present time.
2. Oral
CPA can be considered to prevent progression of AGA in women with clinical or
biochemical evidence of hyperandrogenism.
Therapeutic recommendation for surgery
Male patients
1. Surgery,
especially follicular unit transplantation (FUT) can be considered in male
patients with sufficient donor hair.
2. It
is suggested that follicular unit transplantation (FUT) to be combined with
finasteride 1 mg daily to achieve a better clinical outcome.
Female patients
1. Surgery
especially follicular unit transplantation (FUT) can be considered in female
patients with sufficient donor hairand no overlying diffuse telogen effluvium
is present
2. In
women, hair transplantation can be considered in the male pattern and the
frontal accentuation subtypes and Ludwig stage II of stabilized AGA.
3. The
final result can be evaluated at 9–12 months. In many cases, more than one
surgical session is required.
Therapeutic recommendation for platelet-rich plasma (PRP) Male
and female patients
1. There
is no standardized technique for performing PRP to permit objective evaluation
of its effects on AGA.
2. A
recommendation cannot be made for or against treatment of AGA with
platelet-rich plasma at the present time
Therapeutic recommendation for Low-level Laser therapy (LLLT)
Male and female
patients
1. LLLT
can be recommended as ancillary therapy for AGA with devices that use energy
levels shown to be effective in randomized controlled clinical trials
2. A
recommendation cannot be made for or against treatment for more than 6 months
with LLLT for AGA at the present time
