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HIRSUTISM |
Hirsutism
is androgen-stimulated excessive hair growth. It generally occurs
in the midline.
The term vin'lization
includes hirsutism accompanied by recession of the temporal hairline,
deepening of the voice, loss of female
body contour, development of a male-type pubic hair
pattern, enlargement of the clitoris, or some or all of the above.
True hirsutism must be distinguished from hypertrichosis,
which is the presence of
increased terminal
hairs on the extremities in the absence of excess androgen.
Physiology
There
are two kinds of hair on the body: vellus hairs, which are short,
fine, nonpigmented
hairs that have not
responded to hormones, and terminal hairs, which are long, coarse,
pigmented, and in certain areas of the body, responsive
to hormonal influence.
The terminal hairs undergo a defined growth cycle
that includes a growing phase (anagen), an involutional
phase (catagen), and a resting phase (telogen).
The
number of hairs per unit area of skin is fixed by heredity, and follicle
units are
developed during early embryogenesis.
Because the number and distribution of
pilosebaceous
units are largely controlled by genetic factors, hirsutism in women
occurs
more often in some ethnic or racial
groups than in others.
The endocrinologic
factors that influence the pilosebaceous unit (sebaceous gland and
the hair follicle) include:
Rate and amount
of androgen secretion
Concentration of
sex hormone-binding globulin (SHBG)
Peripheral
conversion of weak androgens to potent androgens (ie: metabolism)
Sensitivity of the pilosebaceous unit to androgens
In general, the sebaceous gland is more sensitive
to androgens than is the hair follicle.
Hyperstimulation of the sebaceous gland accompanied
by bacterial infection results in acne and, rarely,
hidrandenitis suppurativa.
Androgenic stimulation of the hair follicle can transform
some vellus hairs into terminal
hairs.
A certain amount of androgenic stimulation is expected
in the normal woman. However,
pronounced
androgenization results in virilization.
The
ovary secretes the androgens androstenedione (0.8 - 1.6 mg/d) and
dehydroepiandrosterone (0.3 - 3.0 mg/d), whereas
the adrenal gland secretes primarily
dehydroepiandrosterone
and its sulfate DHEAS) (6-8 mg/d) and androstenedione (0.8 -
1.6 mg/d). Testosterone is secreted in approximately
equal quantities by the ovary and
adrenal
gland and is also converted from androgen precursors in the periphery.
Determinations of testosterone, androstenedione,
and DHEAS concentrations in senun may provide
some clue to the source of excessive androgen. Many clinicians do
not measure androstenedione because concentrations
fluctuate widely even in normal women.
Etiologies
1. Altered androgen metabolism
2.
Increased androgen production
3. Decreased
androgen binding in the circulation
4.
Exogenous androgen ingestion
Altered
Androgen Metabolism
Idiopathic
hirsutism appears to be caused by an increased conversion of testosterone
to
dihydrotestosterone locally in the
skin and not by an increase in the number of androgen
receptors.
Increased Androgen Production
The adrenal glands and the ovaries are the only sex
steroid-secreting glands in adult
women.
There are two mechanisms by which these glands produce excess androgen:
1) hypersecretion of precursors that are converted
to testosterone at other sites and
2)
direct secretion of testosterone or conversion to DHT by 5-alpha-reductase.
Adrenal Glands
Adrenal
abnormalities that result in excessive androgen production are relatively
uncommon. Disorders include virilizing congenital
adrenal hyperplasia, Gushing
syndrome,
and androgen-secreting neoplasms.
Virilizing
CAH is most commonly caused by a deficiency of steroid 21-hydroxylase
or,
much less commonly, 1 l-hydroxylase
or 3B-hydroxy-deltaS-ster~id dehydrogenase.
In
addition, the adrenal gland is enriched with prolactin receptors;
patients with
hyperprolactinemia might
experience excessive stimulation of adrenal androgen
biosynthesis.
Although up to 40% of patients with hyperprolactinemia and a
macroadenoma may have increased secretion of androgens
from the adrenal gland,
peripheral action
of androgens is limited by the blocking action of prolactin on the
conversion of testosterone to DHT and its metabolites.
As a result, hirsutism is relatively
uncommon
and , if present, mild in hyperprolactinemic patients.
Ovaries
The
most common cause of excessive androgen production is PCO, which is
often
characterized by menstrual aberration
and variable degrees of excessive androgen.
Hyperthecosis
may represent the most severe form of PCO and may result in hirsutism
and virilization.
Insulin resistance
also may be associated with excessive androgen effect
Hyperandrogenism, insulin resistance, and aconthosis
nigricans (a velvet, pigmented skin lesion located
in intertriginous regions) are common in hyperandrogenic patients.
Any ovarian neoplasm (primary or metastatic) can
stimulate the stroma and cause excessive androgen production.
About 5-6% of ovarian tumors have functional activity, and most of
the functioning neoplasms are of the sex-cord
stromal type (Sertoli-Leydig cell tumors, granulosa cell tumors, and
gynandroblastomas).
Decreased
Androgen Binding in the Circulation
Almost
all androgens in the circulation are bound to SHBG or albumin. Only
the free
androgen is biologically active.
In general, estrogens increase and androgens decrease
hepatic
synthesis of SHBG. Thus, a relative increase in free testosterone
may lead to
hirsutism, as may estrogen
deficiency( e.g., menopause).
Exogenous
Androgens
Adding androgens $ estrogen replacement therapy has
been associated with hirsutism and frank virilization.
Other exogenous sources include:
Androgen-containing creams used for br of vulvar
dystrophies
Danazol used for the tx of
endometriosis
OCPs containing norgestrel
The use of anabolic steroids
Evaluation
Thorough history and physical exam. Document
objectively the extent of the findings by a detailed description or
photographs.
Laboratory studies: The purpose of laboratory evaluation
is to rule out androgen-producing tumors. The
basic lab studies should include determinations of total testosterone
and DHEAS. Concentrations of total testosterone
in serum correlate poorly with the degree of hirsutism or
virilization. It's important because values greater than 200 ng/dl
are usually found in the presence of a tumor.
Measurement of DHEAS greater
than 700 ug/dl is usually present with an adrenal
androgen-secreting
tumor.
The exceptions to the algorithm should be considered:
Cushing syndrome,
hyperprolactinemia,
and adult-onset congenital adrenal hyperplasia.
Cushing
syndrome may be manifested by truncal obesity, purple striae over
the abdomen,
buffalo hump, hypertension,
easy bruisability, or some combination of these symptoms. In
patients with physical signs of cortisol excess,
an overnight suppression test with dexamethasone should
be performed.
Hyperprolactinemia is
a rare cause of hirsutism. When it is suggested by amenorrhea or
galactorrhea, serum level of prolactin should be
determined.
The third exception to
the algorithm is nonclassical adrenal 21-hydroxylase deficiency (2-
5% of hirsute women). Measurements of 17-alpha-hydroxyprogesterone
levels both in the basal state and following
cordcotropin stimulation may be warranted in hirsute women of certain
racial groups (Ashkenazi Jews and Eskimos).
Measurement of 3 alpha-androstanediol glucuronide
in serum has been suggested to
determine
whether there is increased metabolism of testosterone in hair follicles.
Clinical
usefulness of this test, however,
has not been established.
Treatment
Hirsutism is a sign and not a specific disease. Once
an androgen-producing tumor,
Cushing syndrome,
and GAH have been ruled out, treatment should focus on the patient's
wishes.
The patient should be told
at the outset that successful treatment will take several months.
Options for tx include medical therapy and cosmetic-based
temporary and permanent hair removal. Temporary
methods of hair removal do not alter the rate of hair growth.
Medical treatment is generally successful in limiting
new hair growth but does not affect
existing
hair, which should be controlled by mechanical depilatory methods.
The mainstay of medical therapy is low-dose combination
OCPs, which effectively
suppress ovarian function and reduce ovarian androgen
secretion. Moreover, the estrogen in OCP's stimulates
hepatic synthesis of SHBG and results in greater binding of testosterone,
thus limiting its bioavailability.
Other medications
include spironolactone. Spironolactone is used for the treatment of
hypertension, it also inhibits a number of enzymes
important in androgen synthesis and
action.
It appears to compete directly at the androgen-receptor level. A daily
dose of 100-
200mg is often effective
in causing a repression of hirsutism.
Low-dose
combination OCP and spironolactone are commonly prescribed together.
Because in most cases of hirsutism; the problem ovarian,
routine use of glucocorticoid to achieve adrenal
suppression is not warranted in the treatment of hirsutism.
For anovulatory women who have slightly elevated
levels of DHEAS, glucocorticoids
(dexamethasone
0.25-0.5mg orally at bedtime) may be effective in inducing ovulation
when added to clomiphene citrate. |
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Reference:
ACOG Technical Bulletin Number 203 -- March
1995
An Educational Aid to Obsteriician
Gynecologists
Clinical Gynecologic
Endocrinology and Infertility
Speroff,
Glass, and Kase
Fifth edition, Copyright
1994
William & Wilkins |
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| Copyright 2003, Tulane
Department of Obstetrics and Gynecology |
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