Hair follicle: 5 million hair follicles on the human skin
100,000 on the scalp(plus eyelashes & eyebrows) Three types:
lanugos, vellus, terminal Anagen: 90-95% of normal scalp hairs (3
yrs=1000 days) Catagen: 1-2% (3 weeks) Telogen: 5-10% (3 months=100
days)
Non CA CA Androgenetic alopecia Alopecia areata Traction
alopecia
Slide 7
Synonyms Male pattern hair loss (MPHL) Male pattern baldness
(MPB) Androgenetic alopecia (AGA) Common baldness
Slide 8
Androgenetic alopecia -At least 80% of Caucasian men show some
signs of AGA by age 70. Although testosterone is the major
circulating androgen in men, the testosterone metabolite, DHT,
plays a dominant role in AGA. In scalp biopsy: in men with MPHL:
5aR activity & DHT levels are increased
Slide 9
AGA The conversion of T to DHT is catalyzed by 5aR DHT:
temporal scalp hair recession, acne, growth of prostate,
development of terminal hairs in the beard region, external ears,
nostril & on the limbs. Type 1 5aR is widely expressed but its
physiological function is uncertain (in sebaceous glands &
liver) Type 2 5aR is expressed in androgen-dependent tissues such
as the prostate & hair follicle (scalp, beard& chest)
Slide 10
Slide 11
AGA MPHL is absent in men with genetic deficiency of type 2
5aR. Treatment with finasteride, a selective inhibitor of type 2
5aR, slows the progression of MPHL and produces some regrowth of
hair in about 2/3 of men. The primary target of androgen action in
the hair follicle: in dermal papilla & dermal sheath.
Slide 12
AGA Genetic factors predispose to AGA, but their nature and the
mode of inheritance is uncertain. Inheritance is most likely
polygenic. There is increased frequency of AGA in sons of men with
AGA. The maternal influence on AGA is less well defined. Women with
FPHL are less likely than men to have a strong family history of
the disorder
Slide 13
Female pattern hair loss (FPHL) FPHL undoubtedly, but not
necessarily, occurs in women with hyperandrogenism (MPHL, hirsutism
and/or menstrual disturbance) FPHL with hyperandrogenism may
respond to treatment with finasteride, or cyproteron acetate Most
of women with FPHL show no other clinical or biochemical evidence
of androgen excess. There was no response in postmenopausal women
to treatment with finasteride or in women without signs of androgen
excess to cyproteroterone acetate.
Slide 14
Clinical finding In men Onset: may begin anytime post-puberty,
usually by age 40. 14% in 15-17 yrs. Pattern: most common:
bitemporal, frontal, mid scalp, vertex Uncommon: diffuse scalp hair
loss or female pattern with diffuse central scalp hair thinning
Hair pulling: may be positive in active early hair loss in the
central scalp but generally negative in long-standing hair
loss
Slide 15
MPHL Affected hair: miniaturization (finer, shorter) and
decreased hair density Scalp: generally normal, concomitant
seborrheic is common. If perifollicular erythema or hyperkeratoses
= biopsy for R/O cicatricial alopecia Associated finding: high
incidence coronary artery dis. (CAD), Hypertension,
hypercholesterolemia. Family history: commonly positive but in 20%,
not have a FH of MPHL.
Slide 16
Clinical finding (women) Onset: may begin any time post
menarche In central scalp +/-sides of scalp Pattern: A- diffuse
central thinning of the crown with preservation of the frontal hair
line B- frontal accentuation (Christmas tree) C- Fronto-temporal
recession/vertex loss (male pattern) is uncommon. Bitemporal
thinning is commonly associated with, but not necessarily
indicative of FPHL. Pulling test : may be positive in active early
loss in the central scalp, but generally negative in long-standing
hair- loss
Slide 17
FPHL Affected hair: miniaturization of hair Scalp: generally
normal, seborrhea, R/O Cicatricial alopecia Associated finding:
sign or symptoms of hyprndrogenism (hirsutism,severe acne,
galactorrhea, infertility, irregular mense, A.Nigricance) Family
history: FPHL are less likely than men with MPHL to have a history
of first-degree relatives with MPHL.
Slide 18
Slide 19
Slide 20
Slide 21
Evaluation R/O other cause of hair loss (iron def., acute &
chronic telogen effluvium, Sisaipho,) In men: anabolic steroids or
supplemental androgens may worsen MPHL Consider check TSH if the
hair loss is diffuse & not localized exclusively to typical
MPHL Consider iron (in vegetarian or otherwise deficient
diet,..)
Slide 22
Evaluation In hyperandrogenism, blood test should be include: 1
-free and/or total T +/- DHEAS at a minimum=done off of OCP
(inhibit both ovarian & adrenal source of androgens). If these
tests are normal on OCPs, but the suspicion is high for hyper A,
they should be repeated at least one month after cessation of OCPs.
2 if T is greater than 2.5x normal or >200ng/dl, or DHEAS is
greater than 2x normal or >700 micro g/dl in pre or >400 in
postmenopausal women, a work up for tumor with radiographic
test.
Slide 23
Evaluation If galactohhhea or increased T or free T = check
prolactin If T or DHEAS is elevate = screen for CAH. An early
morning serum 17-OH progesterone during the follicular phase of the
cycle (day 1-14) would be a reasonable screening test for the most
common form of CAH, ie, 21- hydroxylase def. If prolactin or 17-OH
progesterone is increased = refer to endocrinologist.
Slide 24
Evaluation In women: screening blood work is generally
recommended in all of women In otherwise healthy women, check TSH
& serum ferritin R/O Iron def.:by serum ferritin or serum iron
and TIBC. Low serum ferritin is diagnostic of iron def. depleted
iron stores in patients with chronic disease may not be detected by
serum ferritin (ferritin is acute phase reactant and inflammatory
disorders, malignancy, infections increase its synthesis) If check
iron & TIBC: pts. Should not be taking iron preparations
(multivitamin with iron or OCP with iron) for at least 24h
Slide 25
Evaluation Iron supplements taken for > 3 wk can falsely
elevated ferritin levels in the face of iron def. Iron defficiency
is associated with low serum iron & relatively high TIBC &
low percent saturation. Other screening test may be indicated by
history = CBC and/or T4 The majority of FPHL have no clinical or
biochemical evidence of androgen excess.
Slide 26
Specific investigations: Often non required Scalp biopsy Iron
studies, serum electrolytes, Urea, Cr Thyroid function tests
Androgen profile (if suspicious of virilization) Testosterone, DHT
SHBG LH, FSH ANA Scalp photography
Slide 27
Histopathology A- indication for biopsy: Diagnosis: Males:
usually not necessary unless a FPHL, diffuse HL or scalp changes
suggestive of scarring alopecia or prepubertal boy with a Ludwig
PHL. -Females: sometimes necessary to exclude chronic T.E, diffuse
AA or cicatricial hair loss Site of biopsy: central scalp (should
not be from the bitemporal =miniaturized hair independent of MPHL
or FPHL) A punch biopsy (not less than 4 mm), into the subcutaneous
fat. Many dermatopathologists favor horizontal sectioning of
biopsy.
Slide 28
histology The ratio of terminal to vellus or vellus-like hair
normally is 7:1. in PHL, decrease to 2:1 The total number of hairs
per unit area is usually normal in PHL (30-50 / 4mm punch), but
reduced in severe baldness A perifollicular infiltrate,
lymphohistiocytic Perifollicular fibrosis
Slide 29
First line therapies: Topical minoxidil A Finasteride A
Dutasteride C Spironolactone B Cyproteron acetate B Camouflage D
Second line therapies: Scalp surgery or transplantation C
Slide 30
Treatment Prevent further hair loss & if possible stimulate
hair growth General: pts should avoid hair care products likely to
damage scalp/hair. Pts should maintain an adequate diet (especially
protein) Topical medications work only where the medication is
applied If possible, any drugs that could negatively affect hair
growth should be stopped. Treat any underlying scalp disorder
(seborrhea, pso,..)
Slide 31
Treatment (men) Finasteride 1mg/d & minoxidil 2-5% =FDA
approved for men > 18 years old. 5% is a more rapid onset of
action. Treatment should be used for 12 mo before making a decision
about efficacy although benefit may be seen sooner. Finasteride :
2/3 decreased DHT in serum & scalp Efficacy: target area hair
counts (TAHC): are circular target areas 1cm to 1 inch in diameter
typically at the anterior leading edge of the vertex balding area
where the terminal, non-vellus, or visible hairs are counted pre
& post treatment.
Slide 32
Finasteride TAHC increase over the first year and peak by 12
mo. : in men age 18-41, hair counts increase 17/cm2 for those on 1
mg finasteride vs-4/cm2 for placebo. Hair growth continue to
improve for at least the first 24 mo of treatment.in 18-41 yr, 50%
of men showed an increase in hair growth by 1 yr, and 66% by 2 yr,
compared to 7% & 7% by placebo (1 yr=10% increase) In 41-60 yr,
39% on finasteride versus 3% on placebo in 2 yr. (90% stop hair
loss in men for at least 5 yrs, hair regrowth in 65%) Discontinue:
any positive effect will be lost in 12 mo.
Slide 33
Slide 34
Slide 35
Androgenetic alopecia (horizontal). Even in the superficial
subcutis, variability in the caliber of hair follicles, with an
increased number of miniaturized hairs, is apparent. Several
fibrous streamers are also seen.
Slide 36
Slide 37
...Finasteride Safety: no known drug interaction, no effect on
liver, BM, kidney,, no effect on spermatogenesis Reversible
sexually related side effects (decreased libido, erectile
dysfunction, decreased ejaculate volume): in 2% versus 1% with
placebo. In 41-60 yr : increased side effect in 8% vs 5% on
placebo. Painful gynaecomastia (0.001%) This side effects often
resolve during continued treatment or within days to wks after
discontinued. The level of drug in semen is very low, and semen no
risk to a pregnant women or her fetus.
Slide 38
Finasteride F. is teratogen. In male fetus : hypospadias with
cleft prepuce, decreased anogenital distance, reduced prostate
weight, altered nipple formation. F. has not effect on
spermatogenesis or semen production No effect on bone density
Slide 39
... Finasteride Reduction in PSA is based on the effect
decreased DHT on the prostate. Recommendation is that any PSA test
value should be doubled for any man taking finasteride to
compensate for the effect of the drug. (40% reduced PSA in 40-49
yrs & 50% in 50-59 yrs.) Finasteride may selectively inhibit
low grade prostate tumors (Gleason stage 2-6),25% reduce among men
aged 55 and over. - low DHT may induce histologic changes that
mimic high grade disease -low DHT may induce higher grade prostate
cancers (Gleason stage 7-10) (5mg/d: high grade prostatic carcinoma
in elderly men (or reduced?)
Slide 40
...Finasteride Finasteride & dutasteride are both
teratogens with very long biological half-lives (activity may
persist into second trimaster), but pharmacokinetic half-life is 8
h. Photography is useful for monitoring, but unlikely to detect
changes of less than 20% in hair density. Max increase occur after
1 yr Further improvement : increase in hair length, diameter &
pigmentation.
Slide 41
Dutasteride D. is a combined type 1 & 2 5aR inhibitor. 0.5
mg/d a 53% reduction is scalp DHT and at 2.5 mg/d the reduction is
83%. Sexual side effects are more common but reversible.
Slide 42
Minoxidil FDA approved for upper 18 yrs old (in adolescents)
Mode of action: increases duration of anagen & enlarges
miniaturized follicles(enlargement of shaft diameter) - K channel
opener & vasodilator 1 ml twice daily, require 1h for
absorption Best result in early case (