Hirsutism
Hirsutism is defined as the excessive growth of thick dark hair in
an androgen-dependent pattern where hair growth in women is usually
minimal or absent e.g. the face, chest, and areolae. It occurs as a result
of increased androgen production, increased skin sensitivity to
androgens, or both.
Idiopathic hirsutism and polycystic ovary syndrome (PCOS) are
the most common causes. When hirsutism in women is accompanied by
other signs of virilism, it may be a manifestation of a more serious
underlying disorder causing hyperandrogenism, such as an ovarian
tumor or adrenal neoplasm.
Normal hair growth
Human hair grows in three phases:
1. Anagen: the growing phase, it lasts for several months and up to
2-5 years on the scalp.
2. Catagen: follows anagen and lasts for about 2 weeks; during this
period the hair stops growing and the lower portion of the hair
follicles involutes.
3. Telogen: resting phase that lasts about 3 months .
Epidemiology
Hirsutism is a common disorder affecting between 5% and 15% of
women of reproductive age. It is less common in Asian people.
The Ferriman-Gallwey score is used in evaluation of hirsutism, and
reflects the amount of terminal hair over different body areas. This may
require adjustment for racial variation.
Obesity is associated with increased hirsutism
Pathogenesis
The dermal papillae androgen receptors interact with
dihydrotestosterone, the active metabolite of testosterone, this
interaction results in an increase in the size of the hair follicle and affects
the type of hair produced by the follicle.
Causes
1) Idiopathic hirsutism:
o
Common and often familial.
o
Is a diagnosis of exclusion and thought to be related to
disorders in peripheral androgen activity.
o
Onset occurs shortly after puberty with slow progression.
o
There are no other signs of virilism, and menstrual function
and investigations are normal.
2) Drug-induced hirsutism
For example, anabolic steroids, danazol, minoxidil,
metoclopramide, methyldopa, phenothiazines and progestogens.
3) Ovarian causes
o
PCOS: virilization is minimal, and hirsutism is often
prominent. This is the most common cause and is present in
approximately 70% of cases.
o
Menopause.
o
Androgen-producing ovarian tumours - eg, luteoma of
pregnancy, arrhenoblastomas, Leydig cell tumours, hilar cell
tumours, thecal cell tumours.
4) Adrenal causes
o
Androgen-producing adrenal tumor.
o
Congenital adrenal hyperplasia (CAH).
o
Cushing's syndrome.
5) Other causes
: Severe insulin resistance, anorexia nervosa,
prolactinoma, acromegaly, hypothyroidism and porphyria.
Presentation
Excess terminal hair in a masculine pattern: face (particularly the
moustache, beard and temple areas), chest, areolae, linea alba, upper
and lower back, buttocks, inner thighs, external genitalia.
Virilism
Signs of associated virilism (hyperandrogenism) may be present,
and include:
Acne
Alopecia, temporal hair recession
Male-pattern (truncal) obesity
Clitoromegaly
Deepening of voice
Increased libido
Increased muscle mass (primarily shoulder girdle)
Loss of breast tissue or normal female body contour
Malodorous perspiration
Infertility
Menstrual dysfunction
Differential diagnosis
Hypertrichosis
: this is androgen-independent and causes
uniform growth of vellus hair over the body, especially in non-sexual
areas. The aetiology of hypertrichosis includes:
1. Familial.
2. Related to drugs - eg, phenytoin, ciclosporin or topical steroids.
3. Non-endocrine causes such as anorexia nervosa.
Management
It is important to investigate in order to establish the cause of
hirsutism, even when mild, as the degree of hirsutism does not correlate
well with the magnitude of androgen excess. However, the first stage is
careful history and examination, and if there is no suggestion of
hyperandrogenism, full endocrine evaluation may not be required.
History
Age of onset, rate of progression.
Menstrual history, age of menarche.
Medication including over-the-counter preparations and anabolic
steroids.
Family history of hirsutism.
Level of distress caused by hirsutism
Examination
Signs of hyperandrogenism.
Signs of Cushing's syndrome (moon face, stretch marks, easy
bruising, proximal muscle weakness).
To exclude pelvic masses.
Blood pressure.
BMI.
Initial investigations
These include:
1) Testosterone:
A high total testosterone concentration indicates that
hyperandrogenaemia may be caused by an ovarian or
adrenal tumour.
If the total testosterone is normal or only slightly raised, an
androgen-secreting tumour can be excluded.
Free testosterone is more sensitive and may be raised in
PCOS.
Testosterone concentrations more than 1.5 - 2 times the
upper limit of normal or a history of rapid virilization are
likely
to
be
caused
by
tumour
-
associated
hyperandrogenism.
Dehydroepiandrosterone sulfate and androstenedione
should then be measured to identify an adrenal or ovarian
source of the hyperandrogenaemia.
2) Free Androgen Index:
Total testosterone is often normal in PCOS but the free
androgen index is raised because sex hormone-binding
globulin is suppressed.
The free androgen index is calculated by also measuring sex
hormone-binding globulin (free androgen index is total
testosterone concentration divided by sex hormone-binding
globulin concentration multiplied by 100).
3) Follicle stimulating hormone (FSH) and luteinising hormone (LH):
Women with PCOS may have an increased LH/FSH ratio (>2 is
common).
4) 17-hydroxyprogesterone:
Blood should be taken at about 9 a.m. in the first half of the
menstrual cycle.
A 17-hydroxyprogesterone value of 5 nmol/L has a
sensitivity of 100% and specificity of 88.6% for diagnosing
non-classical Congenital Adrenal Hyperplasia.
5) 24-hour urine cortisol (to rule out Cushing's syndrome if
suspected):
Cushing's syndrome is a rare cause of hirsutism and exclusion is
not necessary unless the patient has Cushingoid features.
6) Pregnancy should be ruled out in women with irregular or absent
menstrual cycles.
7) Prolactin:
Prolactin
affects
the
menstrual
cycle
and
hyperprolactinaemia can be associated with hirsutism.
8) TFTs: thyroid dysfunction can affect menstruation and
hypothyroidism is associated with changes in hair.
9) Ultrasound: patients with either menstrual disturbances or clinical
or biochemical evidence of hyperandrogenism alone should have
transvaginal ultrasound imaging of the ovaries.
10) Further investigations as indicated:
Glucose tolerance test with serial growth hormone
measurements if acromegaly is suspected.
Lipid profile.
HbA1c.
Ultrasound, CT, MRI: if an adrenal or ovarian tumour is
suspected. MRI brain scan: if a pituitary tumour is suspected.
TREATMENT
Treatment for hirsutism is unnecessary if no abnormal aetiology
can be diagnosed and if the patient is not concerned about the cosmetic
appearance. Management is mainly directed at any underlying cause if
present.
Lifestyle modification:
Encourage weight loss if overweight:
Weight loss increases steroid hormone-binding globulin levels and
decreases insulin resistance and the levels of serum androgens
and luteinising hormones.
Obesity has an adverse effect on the outcome of all systemic
treatments.
Women
who
are
overweight,
hyperandrogenic
or
hyperinsulinaemic are at increased risk of diabetes mellitus and
cardiovascular disease.
Smoking cessation advice.
Because of the cyclical nature of hair growth, any systemic
treatment may take up to six months to be effective. Treatment of
hirsutism is not usually curative, unless a treatable underlying cause has
been found.
Topical cosmetic therapies
Shaving, threading, waxing, using depilatory creams, electrolysis
and laser epilation or photo-epilation do not exacerbate hair
growth and are effective, at least as short -term measures.
Bleaching.
Shaving: Removes all hairs superficially but regrowth produces a
rough stubble. Most women prefer not to shave facial hair.
Chemical depilation may be suited to treatment of large hairy
areas in patients unable to afford more expensive treatments such
as electrolysis and laser epilation.
Temporary epilation:
o Plucking: this may result in irritation, damage to the hair
follicle, folliculitis, hyperpigmentation, and scarring.
o Waxing: this can be painful and sometimes results in
folliculitis. With repeated treatments it may reduce the
number of hairs permanently.
o Home epilating devices that remove hair by rotation or
friction: these may produce traumatic folliculitis.
Permanent epilation:
o Thermolysis (diathermy) and Electrolysis
Both Electrolysis and Thermolysis can be used on all skin
and hair colors, but they require multiple treatments although
Thermolysis is much faster than the traditional electrolysis
method.
The Results depend on the skill of the operator. In addition,
Electrolysis and thermolysis can be uncomfortable and may
produce folliculitis and post-inflammatory pigmentary changes
in the skin
o Laser epilation:
It can treat larger areas faster than electrolysis and
thermolysis and Is most effective on dark hairs in fair-skinned
people.
Multiple sessions may be necessary for long-term hair
destruction. However folliculitis, discomfort and pigmentary
changes may occur.
Drug therapy
The following drugs are effective: finasteride, oral contraceptive
pills, thiazolidinediones, cyproterone acetate and ethinylestradiol in
combination, spironolactone, and flutamide. However, a systematic
review of trials of insulin sensitisers concluded that this group of drugs is
of limited use as a sole treatment for hirsutism.
Combined oral contraceptives: are recommended as first-line
treatment. Pills containing progestogens with anti-androgenic
properties (eg, Co-cyprindiol (Dianette®) or Yasmin®) are
effective but those containing levonorgestrel and norethisterone
are more androgenic and could potentially exacerbate hirsutism.
Third-generation progestogens (eg, desogestrel or gestodene)
have relatively neutral androgenic effects and oral contraceptives
containing these progestogens can be combined with an anti-
androgen such as spironolactone.
Anti-androgens:
such
as
flutamide,
finasteride
and
spironolactone have all been found to be effective in the
management of hirsutism and are sometimes combined with oral
contraceptives for the treatment of hirsutism. However they have
certain side effects and are contraindicated in pregnancy, and thus
should be prescribed with secure contraception.
Gonadotrophin-releasing hormone (Gn-RH) agonists: these are
prescribed in severe cases, and are occasionally used in secondary
care.
Gn-RH agonists such as leuprorelin should be reserved for
use in women who do not respond to combination hormonal
therapy or those who cannot tolerate oral contraceptives.
Long-term adverse effects include hot flushes, bone
demineralisation, atrophic vaginitis.
Metformin has been shown to improve insulin sensitivity and
decrease testosterone levels in patients with PCOS but the
evidence is currently against it being effective for hirsutism alone.
Eflornithine, a topical hair growth retardant, inhibits the enzyme
ornithine decarboxylase. It may reversibly slow facial hair growth
in up to 70% of patients and it must be used indefinitely to
prevent regrowth.
It is only licensed for facial hair. A continuous use for eight
weeks is required before benefit is seen and It should be
discontinued in the absence of improvement after treatment for
four months.