Wednesday, December 15, 2004
Androgenetic alopecia (AGA) occurs in both sexes when there is
progressive miniaturization of hair follicles, shortening of the
anagen phase of the hair cycle, and prolongation of the telogen
phase. The scalp has a three-phase cycle of hair, with almost 90%
of hair in the anagen or growth phase (which may last up to 2-6
years), 1% in the catagen phase (which may last 3 weeks), and 10%
in the telogen or resting phase (which may last 3 months). This
ratio is usually uniformly distributed over the entire scalp. When
the hair in the telogen phase is expelled, another follicle pile in
the anagen VI phase emerges to replace it, although this does not
always occur. In fact, some follicles may remain empty after the
final moment of the telogen phase, and this new phase is known as
the kenogen or lag phase.1
Some men tolerate androgenetic alopecia (AGA) without concern,
while other men and many women find it to be unacceptable when hair
loss goes beyond culturally defined limits. Substantial hair loss
may cause anguish and low self-esteem, confirming the concept that
hair has significant psychological function. Thus, hair loss should
be approached as both a medical and an aesthetic
AGA is a common genetic condition in which hair loss occurs due
to the action of circulating androgens in genetically susceptible
men and women. Thinning of the hair begins between 12 and 40 years
of age in both sexes,3,4 and approximately 50% of the
population expresses this trait to some degree before 50 years of
age.5,6 Research has been directed toward understanding
the miniaturization of the hairs. It is unknown whether this is an
abrupt phenomenon or whether it occurs over several hair cycles.
It's also unknown how this phenomenon is
In order to understand the pathogenesis of AGA, it is important
to know the different embryological origins of dermal papilla cells
of the follicle piles in different areas of the scalp. The
frontal-parietal dermis is derived from the neural crest, while
that of the occipital-temporal is derived from the mesoderm. For
this reason, the different follicles may have different responses
to the same androgenic stimulus.9
Follicles in areas affected by AGA undergo a process of
miniaturization, while those in other areas remain unaffected (such
as those in the occipital region). In most cases of female AGA, as
in almost all cases of male AGA, there are no alterations in the
production of hormones. The problem lies in the target organ - that
is, how each hair follicle responds to circulating androgens. When
androgens reach the dermal papilla cells, they may be metabolized
by 5-alpha-reductase to dihydrotestosterone (DHT). DHT, which is
more potent than testosterone, causes miniaturization of follicles
in the area of the AGA. Androgens can also be metabolized by
aromatase-producing 17-beta-estradiol, an estrogen that does not
cause involution of the follicle. DHT links to a cytoplasmic
receptor and penetrates the cell nucleus, initiating its action at
the level of the DNA with transcription of messengers; it starts
miniaturization by DHT-induced acceleration of the mitotic rate of
the matrix, which shortens the time allowed for differentiation.
Miniaturization is also started by the increased telogen shedding
that occurs as a result of the shortening of the hair cycle, which
increases telogen number per unit of time. The duration of
miniaturization and the frequency with which miniaturization occurs
vary in accordance with age and the severity of the AGA; how this
mechanism is related to DHT remains uncertain.1,6,8
In most women, AGA appears at an early age. Thinning occurs with
reductions in both the physiological diameter and the number of
hairs. There is thinning of the hairs on the apex of the scalp,
with the retention of a strip of hair on the frontal region and the
presence of miniaturized hairs, the Ludwig pattern. In men, there
is a genetically determined deficiency, leading to loss and
progressive thinning of hair, with an easily recognized clinical
pattern marked by the anterior and medium bitemporal recession of
the follicle piles in the scalp, the Hamilton pattern. This pattern
may also be found in some women, where it is associated with
androgenetic endocrine pathologies.10
Women with AGA usually have normal menses and pregnancies, so
hormonal testing is not needed unless symptoms and signs of excess
androgens are present (hirsutism, unresponsive cystic acne,
virilization, or galactorrhoea).6 When any one of these
features is present, laboratory measurement of total serum or free
testosterone, dehydroepiandrosterone sulfate, and prolactin is
Scalp biopsies are taken from active sites of hair loss, and
horizontal sectioning is preferred because of the large number of
follicular structures that can be studied, where they show an
increased number of miniaturized hairs.11,12
Figure 1. 21-year-old female patient with AGA Ludwig I,
before topical 17 alpha-estradiol.
Figure 2. Same patient from Figure 1, 3 months
Treatments may be either topical or systemic and are only
suppressive, implying that there will be a reappearance of balding
when treatment is stopped. On average, improvement takes 8-12 weeks
to begin to appear. Of the topical medicines, the first to show
results was a 2% concentration of minoxidil applied to the dry
scalp twice a day. Mechanisms include increasing the rate of
mitosis of the follicle cells and prolonging the duration of the
anagen phase. Hair growth in areas other than that to which it has
been applied is a well-known phenomenon, occurring more frequently
in women than in men; it is reversible after stopping the drug. The
Food and Drug Administration (FDA) has authorized a concentration
of 5% for use in males. Some studies in women were conducted that
showed strong trends favoring the 5% concentration, but they did
not show enough statistical significance to gain final FDA
Another topical drug that has shown results is 17
alpha-estradiol applied to the scalp once a day.16 In an
ex vivo study, it was suggested that its action occurs
from an aromatase stimulus, with diversion of testosterone
metabolism toward the production of 17 beta-estradiol, leading to
the reduction of dihydrotestosterone synthesis.17
Figure 3. 32-year-old male patient with AGA Hamilton 4,
Figure 4. Same patient from Figure 3, 4 months after 1
mg of finasteride once a day.
One milligram (1 mg) of finasteride, a competitive inhibitor of
5-alpha-reductase type 2, taken orally, improves predominantly
vertex male pattern hair loss, and it is generally well tolerated.
It is contraindicated for women who are or may become pregnant, as
it may cause abnormalities to the external genitalia of the male
fetus. In post-menopause AGA, it is not
Surgical hair restoration, consisting of the implant of mini-
and micro-grafts (transplanting of single hairs or groups of 3-6
hairs in the occipital area), provides satisfactory results, and is
indicated in the most extensive cases of AGA. 20,21
Genetic therapy will probably be available in the next 10-20
years as an efficient treatment for AGA.
- Rebora A. Pathogenesis of androgenetic alopecia. J Am Acad
- Rutowitsch MS, Antonio JR, Steiner D, Talarico S. Alopecia
androgenetica. An Bras Dermatol. 1999;74:561-574.
- Hamilton JB. Patterned loss of hair in man: types and
incidence. Ann N Y Acad Sci. 1951;53:708-728.
- Trancik RJ, Spindler JR, Cuddihy RV, et al. Clinician
survey evaluating monoxidil topical solution in the treatment of
androgenetic alopecia in patients under 18 years of age. Poster
presented at 3rd Intercontinental Meeting of the Hair Research
Societies, June 13-15, 2001, Tokyo, Japan; 129.
- Venning VA, Dawber RPD. Patterned androgenic alopecia in women.
J Am Acad Dermatol. 1988;18:1073-1077.
- Price VH. Androgenetic alopecia in women. J Investig
Dermatol Symp Proc. 2003;8:24-27.
- Jahoda CA. Cellular and developmental aspects of androgenetic
alopecia. Exp Dermatol. 1998;7:235-248.
- Whiting DA. Possible mechanism of miniaturization during
androgenetic alopecia of pattern hair loss. J Am Acad
- Ziller C. Pattern formation in neural crest derivatives. In:
Van Neste D, Randall VA, eds. Hair Research for the Next
Millennium. Amsterdam: Elsevier Science B; 1996:19-23.
- Ludwig E. Classification of the types of androgenetic alopecia
(common baldness) occurring in female sex. Br J Dermatol.
- Whiting DA. The value of horizontal sections of scalp biopsies.
J Cutan Aging Cosmetic Dermatol. 1990;1:165-173.
- Whiting DA. Male pattern hair loss: Current understanding.
Int J Dermatol. 1998;37:561-566.
- Olsen EA, Dunlap FE, Funicella T, et al. A randomized
clinical trial of 5% topical minoxidil versus 2% topical minoxidil
and placebo in the treatment of androgenetic alopecia in males.
J Am Acad Dermatol. 2002;47:377-385.
- Lucky AW, Piacquadio DJ, Ditre CM, et al. A randomized
placebo controlled trial of 5% and 2% topical minoxidil solution in
the treatment of androgenetic alopecia in females. J Am Acad
- Boeck C, Parker J, Shank J, Hordinsky M. Safety of long term
therapy with 3% and 5% topical minoxidil in female androgenetic
alopecia. In: van Nest D, Randall VA, eds. Hair Research for
the Next Millennium. Amsterdam: Elsevier Science B;
- Orfanos CE, Vogels L. Topical therapy of androgenetic alopecia
with 17-alfa-estradiol. Dermatologica.
- Hoffmann R, Niiyama S, Huth A, et al. 17
alfa-estradiol induces aromatase activity in intact human anagen
hair follicles ex vivo. Exp Dermatol.
- Price VH, Roberts JL, Hordinsky M, et al. Lack of
efficacy of finasteride in postmenopausal women with androgenetic
alopecia. J Am Acad Dermatol. 2000;43:768-776.
- Whiting D, Olsen EA, Savin R, et al. Efficacy and
tolerability of finasteride 1 mg in men aged 41 to 60 years with
male pattern hair loss. Eur J Dermatol.
- Brandy DA. The art of mixing follicular groupings in hair
restoration surgery. Dermatol Surg. 2004;30:846.
- Lam SM, Hempstead BR, Williams EF. A philosophy and strategy
for surgical hair restoration: a 10-year experience. Dermatol