Hirsutism

Hirsutism
www.freelivedoctor.com

Outline
• Introduction
• Definition
• Causes
• Clinical evaluation
• Investigations
• Treatment
• Conclusion

Introduction

Gynecological,
Endocrinological,
Cosmetic &
Psychogenic: {great anxiety, nature of the disease,
social acceptance}

Incidence
Not known
Mediterranean> Asian
American females: 10%
European: 5%

Cycle growth of hair
Several months 2 weeks 3 months

Types of hair
Lanugo
Fetal hair
Vellus
Short,
fine,
Unpigmented
Before puberty
Terminal
Long,
coarse,
pigmented
arises from
vellus hair

Non sexual Ambi-sexual Male sexual
Sites Lower parts of
the scalp, eye
brow, lashes,
fore-arms, lower
legs
Temporal &
vertical parts of the
scalp,
axilla,
lower pubic hair.
Ears,
nasal tip,
chin,
sternum,
upper pubic triangle,
back.
Depend on Growth hormone
from pituitary
Androgen in low
concentration from
the adrenals &
ovaries in females &
adrenals in male
Androgen in
high
concentration
Sites of hair

Androgen production
Androstenedione
Testosterone
Adrenal DHEA Ovary
DHEAS
50% 50%
50%
25% 25%
90% 10%
100%

Androgen in the blood
Male Normal female Hirsute female
Free 3% 1% 2%
Albumin 19% 19% 19%
SHBG 78% 80% 79%

Androgen at target cell (hair follicle)
Testosterone (T)
5œ-reductase.
Dihydrtestosterone (DHT)
Androstanediol
Glucuronide
3 alpha androstanediol glucuronide(3 alpha AG)

Definitions

Virilization:
Defiminization:
Atrophy of the breast & vagina
Musculinization:
Hirsutism, deepening of voice, temporal balding.
Increase size of the clitoris, muscular mass & libido

Hirsutism: Latin hirsutus = shaggy, hairy
Excessive growth of
terminal hair in
male sexual sites.
Excessive: Socially unacceptable to the patient
F& G score >8

Hypertrichosis
Excessive growth of
Lanugo, vellus or terminal hair in
non-sexual sites (James et al, 2005)
•Cong
Acquired
•Localized
Generalized
Congenital hypertrichosis lanuginosaDrug-induced hypertrichosis

Hirsutism:
•Not an increase in the number of hair
follicles but an alteration in their character.
•An increase in the transformation of the
vellus to terminal hair.
{Androgens will convert lanugo & vellus hair
to terminal hair}.

Hirsutism is a consequence of several
factors. An increase in:
1. Androgen production
2. The sensitivity of the androgen
receptors at the level of the hair
follicle.
3. The activity of 5œ-reductase.

A. Ovarian:
.PCOS: 90%
{hyperandrogenism, oligo-ovulation, PCO}
.Virilizing ovarian tumors
{arrhenoblastoma, hilus cell tumor, lipod cell tumor, granulosa cell tumor}
.Luteoma of pregnancy
{ Not true tumor but an exaggerated reaction of ovarian stroma to chorionic gonadotropins. It is solid, usually unilateral & regress after
labour}
.Ovarian dysgenesis
Turner’s syndromewww.freelivedoctor.com

B. Adrenal:
•Cong adrenal hyperplasia
•Tumors
•Cushing syndrome
Congenital adrenal hyperplasia

C. PERIPHERAL
•Idiopathic: Regular ovulation & normal androgen levels
•Insulin resistance
– HAIRAN syndrome: HyperAndrogenic
Insulin-Resistant Acanthosis Nigricans
– 5H syndrome
acanthosis nigricans.

•Aromatase deficiency
•Glucocorticoid resistance
•Hyperprolactinema can cause an increase in
DHEAS. TT with bromocriptin: dec PRL
& DHEAS

Hirsutism
Anabolic steroids
Danazol
Metoclopramide
Methyldopa
Phenothiazines
Progestins
Reserpine
Testosterone
Hypertrichosis
Cyclosporine
Diazoxide
Hydrocortisone
Minoxidil
Penicillamine
Phenytoin
Psoralens
StreptomycinHunter, 2003
D. Drugs

Clinical evaluation

Primary objective:
Confirm diagnosis
Determine degree
Exclude life threatening diseases

History
.Virilization, psychological
.Onset & duration:
Rapidly progressive virilization: androgen secreting tumors
.Menstrual history:
PCOS, Pregnancy
.Family history:
Hair patterns are similar in families
.Drug intake

Examination
.General:
Thyroid disease,
Cushing syndrome,
Signs of virilization,
Signs of insulin resistance e.g. acanthosis nigricans.

.Breast:
Galactorrhea {Hyperprolactinaemia can be
accompanied by increase in adrenal androgen}
.Pelvic:
mass

Degree of hirsutism
Photography or scoring systems
a. Ferriman & Gallwey(1961): 9 areas
upper lip,
chin,
chest
upper abdomen,
lower abdomen,
upper arm,
thighs,
upper back,
lower back/buttocks
minimal=1, mild=2, moderate=3, severe=4
>8 = hirsutismwww.freelivedoctor.com

Degree of hair growth
(Ferriman & Gallwey,1961)

b. Macnight (1964):
divided the body into 7 areas:
Face
Neck
Shoulders
Chest
Abdomen
back

Investigations

Initial laboratory investigation
(Speroph,2005)
1.Total testosterone:
measures the ovarian & adrenal activity.
2.17 OHP:
an intermediate metabolite in steroidogensis in
the adrenals.
DHEAS:
Good marker of Adrenal A production
Not essential

•DHES is not essential (Speroff,2005)
1. If 17 OHP is normal: adrenal enzyme defect can be excluded .
2. Moderate elevations of DHES can be suppressed by suppression
of ovulation.
3. DHES > 700 ug/dl is rare & is associated with high levels of T
4. Imaging of the adrenals is more cost-effective than measuring
DHES.

Testosterone (ng/dl)
>200 <200
U/S of the ovary Anovulation
(PRL, endom biopsy)
Adenxal mass Nothing
Laparotomy CT of the adrenala & ovaries
Laparotomy

Free testosterone
•Good correlation with total production rate
(= secretion rate + peripheral conversion rate)
Good correlation with degree of virilization
•Free androgen index(FAI)=
TX 100 / SHBG if > 4.5: PCOS
•Not done routinely in presence of hirsutism

3 alpha androstanediol glucuronide
•Metabolite of DHT
•Good marker of peripheral androgen action
•Inc {increased activity of 5 alpha reductase} {end
organ hypersensitivity}
•Not done routinely:
1. No change in diagnosis & treatment,
2. Values overlap in 20%

Ovarian tumors should be suspected
1. Rapid onset of virilization
2. Unilateral adenxal mass
3. Testosterone >200 ng/dl.
•TVS, CT or MRI.

Screening for late onset adrenal hyperplasia
•Incidence: 1-5%
•Clinical indication of ACTH stimulation test:
Strong family history
Severe hirsutism from puberty
Flatness of the breast
Hypertension
Short stature

17 oh P(ng/dl) morning
< 200 > 200
Rules out adrenal hyperplasia ACTH stimulation test (0.25
21-hydroxylase deficiency mg ACTH I.V.& 17 oh P at time
zero & after 1 hour)
Normal Abnormal
Rules out adrenal hyperplasia Adrenal hyperplasiawww.freelivedoctor.com

Screening for Cushing syndrome
•Rare
•Indications:
Centripetal obesity, buffalo hump
Moon face, Virilization
Pigmented stria, Hypertension

Dexamethazone suppression test
( 1 mg orally at bed time)
Free cortisol (ug/dl
> 6 < 6
long term dexamethazone test Normal

PCOS T
LH/FSH
usually inc
2/1
Late-onset CAH 17-OH-P >200 ng/dL
Androgen-secreting ov tumor Total T >200 ng/dL
Androgen-secreting ad tumor DHEAS >700 g/dL
Cushing syndrome Cortisol Increased
Exogenous androgen use Toxicology
screen
Increased

Treatment

I. General
II. Specific
III. Local
IV. Surgery

I. General
•Reassurance:
•explain the condition, treatment regimen & the time required
•Stop smoking
•Weight reduction:
{Inc SHBG: Dec FT}
Keep BMI around 21 kg / m2
Dec the risk of DM & CVD

II. Specific
I. Ovarian suppression:
1. OCPs 2. Progestagen 3. GnRha
II. Adrenal suppression: Corticosteroids
III. Antiandrogens:
1. Spironolactone 2. Cyproterone acetate
3. Flutamide 4. Ketoconazole
IV. 5 alpha reductase inhibitors: Finasteride
V. Insulin sensitizer: Metforminwww.freelivedoctor.com

I. Ovarian suppression:
1. Oral contraceptive pills
The first line of therapy
Mechanism:
P: suppress ov steroidogenesis
E: inc SHBG: dec FT

Best type:
Avoid OCs containing norethisterone or levonorgestrel
less androgenic,
high estrogen
Diane (cyproterone acetate),
Gynera (gestodene),
Marvelon (desogestrel),
Cilest (norgestimate).
Effect:
1. Dec T after 1-3 mo.
2. Additional benefits

2. Progestins
Indication: If pills is contraindicated or unwanted
Mechanism:
inhibit ov steroidogenesis,
inc clearance of androgen,
inhibit 5 alpha reductase
dec SHBG:inc FT
Dose: DMPA: 150 mg IM / 3 mo.
MPA: 30 mg PO / d
Effect: comparable to OCPs

3. Gn Rh analogue
Indications:
Failure of usual management
Overweight with severe hirsutism
Dose:
leuprolide acetate depot: IM / mo.
The initial stimulatory effect can be avoided by starting
therapy in the luteal phase when Gnt are already
suppressed by elevated progesterone levels.
Once maximal response has been obtained OCP or
antiandrogen for long term suppression of hair growth.
Treatment should be limited to 6 mo.

Mechanism of action:
Side effects:
of estrogen deficiency
Use with OCPs:
{avoid problems associated with E deficiency &
add benefits}
Effects:
highly effective & better than OCP alone

II. Adrenal suppression: Glucocorticoids
Indication:
1.High not moderate elevation of
DHEAS (Sperof,2005)
2. CAH
Mechanism:
inhibit ACTH dependant androgen

Dose:
Nocturnal {maximal suppression of the CNS
adrenal axis that peaks during sleep}
Dexamethazone: 0.3 mg or 0.25 mg/ other evening
Prednisone: 3 mg
Adrenal hyperplasia: higher doses
Effects:
1. No cortisol suppression
2. No Cushingoid side effects

III. Antiandrogens:
1. Spironolactone (Aldactone)
Dose:
100-200 mg/d
remission: dec dose to 25-50 mg
100-200 mg/d from D1-D21
Mechanism :
on receptor
ovary & adrenals
Liver
kidney www.freelivedoctor.com

Side effects: minimal.
Mens irregularities, mastalgia, feminization of
male fetus, transient diuresis, hyperkalemia, ?
carcinogenic
Use with OCP:
1. Dramatic effect, but not impressively better
2. Prevent feminization of male fetus
3. Regular menstruation
Effects: maximal by 6mo
Cessation : relapse

2. Cyproterone acetate (androcure)
Dose:
50-100 mg from D5 to D15 &
EE2: 30-50 ug from D5 to D25.
Dec dose after remission
Mechanism:
on receptors
Progestational effect
Weak corticosteroid effectwww.freelivedoctor.com

Side effects:
mens irregularities, mastalgia, feminization of
male fetus, loss of libido, fatigue, edema, weight
gain, decrease HDLP & cholesterol, glucose
intolerance.
Use with EE2 or OCPs
Effects:
maximal by 3mo
improvement in 60-90%
Cessation: relapse

3. Flutamide (Eulexin)
Indication: under tertiary center supervision
Severe cases
Failure of spironolactone & OCPs
Dose:
250 - 500 mg/d
Mechanism:
antiandrogen.

Side effects:
dryness of the skin, increase appetite
hepatotoxicity, expensive.
It is unsuitable for treatment of hirsuitism (Speroff, 2005)
Use with OCPs:
1. Add benefit 2. Avoid block androgen receptors in male fetus.
Effects:
Similar or better than Spironolactone

IV. 5 alpha reductase inhibitors
Finasteride (Proscar)
Indication: under tertiary center supervision.
Severe cases
Mode of action:
Inhibit 5 alpha reductase activity: blocking conversion of T to
DHT.
Dose:
2.5 - 5 mg /d

Side effects:
very minimal. Teratogenic
Use with OCPs:
To avoid risk on male fetus & added benefits.
Effects:
Flutamide or Spironolactone is more effective

V. Insulin sensitizer:
Metformin
•PCOS
IH: {insulin resistance} (Unluhizarci et al, 2004).
•1500 mg/d
•Dec serum insulin & T.
Dec F&G score (Kazerooni et al, 2003 ; Kelly & Gordon, 2003)

• Metformin Vs Dianette (EE2: 35 ug + cyproterone acetate: 2 mg)
Dianette was more effective (Harborne et al, 2003).

•Cyprotrone acetate was compared
to (spironolactone, flutamide,
finastride, GnRHa, Ketconazole):
No differences in clinical outcomes
(Cochrane library, 2003)

•Spironolactone 100 mg/d is superior to
finastride 5 mg/d & low dose cypr
acetate 12.5 mg/d (first 10 days of the cycle) up to 12
months after the end of the treatment(Cochrane library, 2003)

III. Local
Suppress hair growth: Eflornithine Hydochloride (Vaniqa)
Remove hair pigment: Bleaching
Temporary depilation: shaving, chemical depilators
Temporary epilation: plucking, waxing
Permanent removal: Electrolysis, Laser & intense
pulsed light

1. Suppress hair growth: Eflornithine 13.9% (Vaniqa)
cream
•inhibits ornithine decarboxylase (an enzyme in hair
dermal papilla that is essential for hair growth).
•Face, neck
•Minimal s effects, can be used with other tt e.g. lasers,
intense pulsed light, regrowth can take 2 ms
•Must be continued indefinitely to prevent regrowth
S effects: stinging, burning, tingling

2. Bleaching (remove hair pigment)
•Hydrogen peroxide, often combined with
amonia.
•Face, arms
•Hair lightens & softens, inexpensive
•Hair discoloration, skin irritation, Lack of
effectiveness

3. Temporary depilation (remove part of hair)
a. Shaving:
•All areas
•Inexpensive, effective & does not cause
change in hair quality, quantity or texture.
•Daily need, skin irritation, quick regrowth
folliculitis, time consuming, beard stubble

b. Chemical depilators:
•Break down & dissolve hair by hydrolysing
disulhide bonds.
•Extremities, groin, face
•Quick, inexpensive, effective
•Regrowth in days, skin irritation

4. Temporary epilation (remove the entire hair)
a. Plucking:
•Face, eyebrows, nipples, bikini area
•Effective for small amount, inexpensive, regrowth
can take weeks
• Pain, skin irritation, postinflam pigmentation,
folliculitis, slow, ingrown hairs, scarring

b. Waxing: group plucking
•Face, eyebrows, groin, trunk, extremities
•Regrowth can take 6 weeks
•Pain, postinflam pigmentation, scarring, slow,
expense, irritation, folliculitis

5. Permanent removal (destruction of the dermal papilla)
a. Electrolysis:
•Needle is inserted into the hair follicle & a current is used to
destroy the dermal papilla.
•All areas, usually the face
•May give permanent removal
•Pain, scarring, painful, repeat treatments needed, time
consuming, expensive, pigmentation

b. Laser & intense pulsed light
•Selective phototricholysis. A light source sufficient to penetrate to
the follicular bulge & the papillae is directed at the hair by probe.
•All areas
•May give permanent hair reduction, efficient, painless
•Dark hair required, expensive, scarring, skin pigmentation, repeated
treatments usually necessary

IV. Surgery
•Tumor
•LOD
Discrepant & variable response.
A modest & sustained improvement in 25%
(Amer et al, 2002).

Guidelines for management
1. The most desirable & effective tt is
combination of OCP & antiandrogen.
2. Response is relatively slow, & at least
6 mo are required to demonstrate an
improvement.
3. TT should be continued for at least 1-
2 yr.

4 There is no evidence that one agent is
better than another & choices should be
governed by cost & side effects.
5. The addition of GnRHa should be
reserved for patients resistant to initial
therapy.
7. Local methods should be used but
reserved until hormonal therapy has reduced
the rate of hair growth i.e. after 6 mo.

Conclusion
2
Tests: T & 17 Oh P
Drugs: COCs & Spironolactone
Years Treatment

Hirsutism

Recomendados

Recomendados

Más contenido relacionado

La actualidad más candente

La actualidad más candente (20)

Destacado

Destacado (20)

Similar a Hirsutism

Similar a Hirsutism (20)

Más de raj kumar

Más de raj kumar (20)

Hirsutism