Hirsutism

Article Last Updated: May 12, 2006

AUTHOR AND EDITOR INFORMATION
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Author: George T Griffing, MD, )rofessor of Medicine, irector of *eneral Internal Medicine,
St Louis Uni+ersity
*eor,e # *riffin, is a $e$-er of the follo&in, $edical societies: A$erican Association for the
Ad+ance$ent of Science, A$erican Colle,e of Medical )ractice E.ecuti+es, A$erican Colle,e
of )hysician E.ecuti+es, A$erican Colle,e of )hysicians, A$erican ia-etes Association,
A$erican %ederation for Medical (esearch, A$erican /eart Association, Central Society for
Clinical (esearch, and Endocrine Society
Editors: Stanley Walla!, MD, E.ecuti+e irector, A$erican Colle,e of 0utrition, epart$ent
of Medicine, Clinical )rofessor, 0e& 1or" Uni+ersity School of Medicine2 Franiso Tala"era,
#!armD, #!D, Senior )har$acy Editor, eMedicine2 Don S S!al!, MD, epart$ent of
Internal Medicine, i+ision of Endocrinolo,y, )rofessor E$eritus, Uni+ersity of !isconsin
/ospitals and Clinics2 Mar$ %oo&er, MD, /ead, 3ascular i+ision, 4a"er Medical (esearch
Institute2 )rofessor of Medicine, Monash Uni+ersity2 Mi!ael E 'e"it(, MD, Assistant )rofessor
of Medicine, #he Chica,o Medical School2 Consultin, Staff, %inch Uni+ersity of the /ealth
Sciences, )ri+ate )ractice
Aut!or an) E)itor Dislosure
Synonyms an) relate) $ey*or)s+ hirsutis$, andro,en e.cess, +irili5ation, $asculini5ation,
e.cessi+e hairiness, e.cess -ody hair, endocrine disorders, con,enital adrenal hyperplasia, CA/,
polycystic o+ary syndro$e, )C6S, andro,en'secretin, tu$or, hyperandro,enis$, Cushin,
syndro$e, Cushin,7s syndro$e, %erri$an and *all&ay scale, idiopathic hirsutis$
INTRODU%TION
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,a$groun)
Althou,h hirsutis$ is -roadly defined as e.cessi+e hairiness, the co$$on clinical use of the
ter$ refers to &o$en &ith e.cess ,ro&th of ter$inal hair in a $ale pattern8 In this sense,
hirsutis$ is one of the $ost co$$on endocrine disorders, affectin, appro.i$ately 109 of
&o$en in the United States8 In these &o$en, the hairiness i$plies the presence of a-nor$al
andro,en action, &hich $ay represent a serious or, $ore li"ely, a nonserious $edical pro-le$8
(e,ardless of the etiolo,y, hirsutis$ can produce $ental trau$a and e$otional an,uish8 E+en
$ild cases of hirsutis$ $ay -e +ie&ed -y the patient and others as a presu$pti+e loss of
fe$ininity8 In $ore se+ere cases, hirsutis$ can -e a cos$etic catastrophe8 #he $a:or o-:ecti+es
in the $ana,e$ent of hirsutis$ are to rule out a serious underlyin, $edical condition and to
de+ise a plan of treat$ent8
#at!o&!ysiology
4oth hor$ones and the intrinsic characteristics of the hair follicle deter$ine the ;uality of hair
,ro&th8 3ellus hairs are fine, unpi,$ented hairs that co+er $ost of the -ody -efore pu-erty8
)u-ertal andro,ens pro$ote the con+ersion of these +ellus hairs to coarser, pi,$ented ter$inal
hairs8 #he le+el and duration of e.posure to andro,ens, the local <'alpha'reductase acti+ity, and
the intrinsic sensiti+ity of the hair follicle to andro,en action deter$ine the e.tent of con+ersion
fro$ +ellus to ter$inal hair8 /o&e+er, so$e ter$inal hair ,ro&th is andro,en'independent =e,,
scalp, eye-ro&s, lashes>8
#he de+elop$ent of ter$inal hair or re+ersion -ac" to a +ellus pattern $ay not -e i$$ediately
e+ident -ecause of the characteristics of the hair cycle8 #his cycle has 2 phases that include
acti+e hair ,ro&th =ana,en phase> and a restin, period =telo,en phase>, &hich follo&s the ana,en
phase8 urin, the restin, period, the hair shaft separates fro$ the der$al papillae at the follicle
-ase, and no further ,ro&th ta"es place8 E+entually, ,ro&th restarts and the ne& hair shaft
for$ed -y the reacti+ated papillae pushes the old hair out8 #he cycle $ay ta"e $onths to
co$plete, and this causes a delay in hair ,ro&th response to chan,es in the andro,en $ilieu8
ihydrotestosterone is the andro,en that acts on the hair follicle to produce ter$inal hair8 #his
hor$one is deri+ed fro$ -oth the -loodstrea$ and local con+ersion of a precursor, testosterone8
#he local production of dihydrotestosterone is deter$ined -y <'alpha'reductase acti+ity in the
s"in8 ifferences in the acti+ity of this en5y$e $ay e.plain &hy &o$en &ith the sa$e plas$a
le+els of testosterone can ha+e different de,rees of hirsutis$8
Fre-ueny
Unite) States
/irsutis$ affects appro.i$ately 109 of &o$en in the United States8
International
#he pre+alence rates of hirsutis$ in northern Europe are si$ilar to those in the United States2 in
other places, rates are not "no&n &ith certainty8
Mortality.Mor/i)ity
#he $ortality and $or-idity of hirsutis$ are deter$ined -y the underlyin, cause8
Most &o$en &ith idiopathic hirsutis$ ha+e no associated $ortality or $or-idity8
6n the other e.tre$e, a s$all nu$-er of &o$en $ay ha+e $ali,nant disease &ith a
,ra+e pro,nosis8
Rae
Ethnic ori,in si,nificantly affects ter$inal hair ,ro&th in healthy &o$en8
0orthern, fair's"inned Europeans ha+e the least a$ount of ter$inal hair, &hereas
southern European, dar"'s"inned Mediterranean &o$en ha+e the ,reatest a$ount of
ter$inal hair8
#he difference in the racial patterns of nor$al ter$inal hair ,ro&th $ay -e related to
,enetic differences of <'alpha'reductase acti+ity in the s"in8
!ith the e.ception of con,enital adrenal hyperplasia =CA/>, the pre+alence of diseases
that cause hyperandro,enis$ and hirsutis$ has not -een sho&n to differ a$on, persons
of different races8
Se0
As a $edical pro-le$, hirsutis$ predo$inates in &o$en8
Althou,h hirsutis$ can occur in $en, it is $ore difficult to reco,ni5e -ecause of the &ide
+aria-ility of healthy $ale ter$inal hair ,ro&th8
/irsutis$ in prepu-ertal children occurs e;ually -et&een se.es, is usually a si,n of
precocious pu-erty, and $ay si,nify a serious underlyin, disease8
#his discussion focuses on adult &o$en8
Age
#he a,e of onset of hirsutis$ depends on the etiolo,y8
Most for$s of nonneoplastic hirsutis$ -eco$e e+ident around pu-erty8 #his includes
polycystic o+ary syndro$e =)C6S>, CA/, and idiopathic hirsutis$8
/irsutis$ $ay also de+elop after &ei,ht ,ain and cessation of the use of oral
contracepti+es =6Cs> in youn, &o$en8
0or$ally, ter$inal hair ,ro&th -eco$es apparent after adrenarche and accelerates after
pu-erty8 #er$inal hair continues to de+elop ,radually in healthy &o$en until after
$enopause, &hen loss of o+arian andro,en leads to a loss of hair8
(apidly &orsenin, hirsutis$, especially in older &o$en, should raise the suspicion of an
andro,en'secretin, tu$or8
%1INI%A1
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History
An accurate history of the patient@s onset of hirsutis$ and de+elop$ental $ilestones can -e
helpful in the etiolo,ic dia,nosis8
A,e of onset

o Idiopathic hirsutis$ and the other less'serious causes of hirsutis$ usually -e,in at
pu-erty8
o Con+ersely, hirsutis$ that occurs in $iddle'a,ed or older &o$en should su,,est
an adrenal or o+arian tu$or8

%a$ily history: A patient &ith a fa$ily history of hirsutis$ is consistent &ith con,enital
adrenal hyperplasia =CA/>2 ho&e+er, idiopathic hirsutis$ and polycystic o+ary
syndro$e =)C6S> can also -e fa$ilial8
/irsutis$ se+erity and rate of pro,ression
o #he history of a -eni,n for$ of hirsutis$ is usually characteri5ed -y pu-ertal
onset &ith slo& pro,ression o+er $any years8 #his is often true of hirsutis$ &ith
)C6S8
o !hen a history of rapid se+ere hirsutis$ or other si,ns of +irili5ation are
o-tained, an andro,en'secretin, tu$or is a possi-ility8

Adrenarche and pu-erty
o 4ecause the de+elop$ent of pu-ic hair depends on adrenal andro,ens, early
de+elop$ent points to&ard CA/8
o In contrast, o+arian hyperandro,enis$ is associated &ith nor$al adrenarche and
delayed $enarche or irre,ular $enses8
#!ysial
#he $ost i$portant ,oal in the clinical e+aluation of a patient &ith hirsutis$ is to rule out
si,nificant underlyin, disease8 #o do this, see" to understand the cause of hyperandro,enis$, if
this is present8
E.cess andro,ens can -e fro$ either an e.o,enous or an endo,enous source8
o An e.o,enous source of andro,ens can usually -e elicited -y history findin,s2
ho&e+er, surreptitious andro,en use has -een reported in fe$ale athletes,
especially those at a hi,h le+el of co$petition8
o Endo,enous andro,ens ori,inate fro$ either the adrenal corte. or the o+ary8
#herefore, the e+aluation of andro,en e.cess can focus on disorders of these 2
,lands8 #he principal possi-ilities are tu$ors of the o+ary or the adrenal corte.,
Cushin, syndro$e, CA/, and )C6S8 Idiopathic hirsutis$ is the $ost co$$on
etiolo,y, -ut it is a dia,nosis of e.clusion8 #herefore, see" other causes first8

#he initial tas" in the e+aluation of hirsutis$ +ia the physical e.a$ination is to ;uantitate
the disorder8 #his tas" re;uires that ter$inal hair, &hich depends on andro,en, -e
differentiated fro$ +ellus hair, &hich is andro,en'independent8
o 3ellus hair is fine, soft, and nonpi,$ented8 An e.cess of +ellus hair
=hypertrichosis> is associated &ith $eta-olic disorders =e,, hyperthyroidis$,
anore.ia ner+osa, porphyria> and &ith so$e $edications =e,, phenytoin,
dia5o.ide, $ino.idil, ,lucocorticoids, cyclosporine, he.achloro-en5ene>8
o 4y contrast, ter$inal hair is coarse, curly, and pi,$ented8 4ecause s$all a$ounts
of ter$inal hair are nor$al in &o$en, ;uantitation is i$portant8

#he $ost &idely accepted $ethod of ;uantitation uses the %erri$an and *all&ey scale8
/o&e+er, use care -ecause this $ethod has si,nificant intero-ser+er +aria-ility8 In this
approach, hair ,ro&th is :ud,ed in each of 11 andro,en'sensiti+e area8
o #he ,rade for each area ran,es fro$ 0 =no ter$inal hair> to A =fran"ly +irile>8
o #he -ody areas used to ,rade hirsutis$ are =1> the upper lip, =2> chin, =?> chest,
=A> le,, =<> thi,h, =6> upper ar$, =B> forear$, =C> upper -ac", =D> lo&er -ac", =10>,
upper a-do$en, and =11> lo&er a-do$en8
o Areas such as the a.illa and pu-is are not included -ecause ter$inal hair ,ro&s in
these places at nor$al andro,en le+els in &o$en8
o #he total score correlates rou,hly &ith the ele+ation of andro,en le+els8 A &o$an
&ith a score of C or hi,her is considered to ha+e hirsutis$8 Most &o$en &ho see"
$edical attention for the disorder ha+e scores of 1< or hi,her8 0or$al scores ha+e
also -een esta-lished for #ur"ey =up to 11> and #hailand =up to ? on the $odified
%erri$an and *all&ey scale>8

In &o$en &ith $oderate'to'se+ere hirsutis$ =score E1<>, see" additional si,ns of
hyperandro,enis$, includin, =1> te$poral hair recession, =2> oily s"in, =?> $asculine
+oice, =A> &ell'de+eloped $usculature, =<> enlar,e$ent of the clitoris =E?< $$
2
in
surface area>, =6> irre,ular $enses, and =B> psycholo,ical chan,es =e,, hei,htened li-ido,
a,,ressi+eness>8
#he de,ree to &hich these clinical factors are present su,,ests the le+el of andro,en
o+erproduction and, thus, helps to deter$ine the de,ree of concern for the presence of an
underlyin, disease8
#he e.tent of the e+aluation for the cause of hirsutis$ is ,reater in &o$en &ho ha+e
$ore se+ere clinical e+idence of $asculini5ation8
A thorou,h a-do$inal and pel+ic e.a$ination is i$portant in patients &ith hirsutis$
-ecause $ore than half of andro,en'secretin, adrenal and o+arian tu$ors are palpa-le8
E.a$ine the s"in for acanthosis ni,ricans, a $anifestation of insulin resistance8
!o$en &ith hirsutis$ are usually o-ese, &ith increased &aist'hip ratios, and are thou,ht
to -e at an increased ris" for atherosclerosis and coronary heart disease8 #hey also ha+e
increased -one $ineral density scores at the hip and spine8 #hese increases correlate &ith
hi,her le+els of seru$ free testosterone and estro,en8
%auses
Multiple diseases can cause hyperandro,enis$ and hirsutis$8 #he etiolo,ic for$s of hirsutis$
include endocrine'related, idiopathic, $edication'related, and $iscellaneous8
Endocrine'related causes include adrenocortical disorders and o+arian disorders8
o #u$ors, Cushin, syndro$e, and CA/ are the adrenocortical causes8
Adrenal tu$ors: Adrenocortical tu$ors are al$ost al&ays $ali,nant in
patients &ho present &ith hirsutis$8 #hese tu$ors are usually lar,e and
are associated &ith a +ery poor pro,nosis8
Cushin, syndro$e: In $ost instances, Cushin, syndro$e is caused -y
,lucocorticoid therapy8 4ecause pure ,lucocorticoids ha+e no andro,enic
acti+ity, the treat$ent rarely produces hirsutis$8 Instead, ,lucocorticoid
therapy is one of the causes of hypertrichosis =see )hysical>, resultin, in
+ellus hair ,ro&th, especially on the face8 #hus, e.cess ,ro&th of ter$inal
hair in a patient &ith the clinical sti,$ata of Cushin, syndro$e su,,ests
that the syndro$e has an endo,enous ori,in, ie, a pituitary tu$or that
secretes adrenocorticotropin hor$one =AC#/>, an adrenal tu$or that
secretes -oth cortisol and andro,ens, or an ectopic tu$or that secretes
AC#/8 #he pituitary tu$or is the $ost li"ely possi-ility8 Cushin,
syndro$e, as a cause of hirsutis$, is dia,nosed -ased on the presence of
de.a$ethasone that fails to suppress -oth andro,ens and cortisol8
CA/: CA/ is actually a fa$ily of defects in 1 of < en5y$es that are
responsi-le for the -iosynthesis of cortisol8 #he resultin, cortisol
deficiency hei,htens the secretion of AC#/ and there-y leads to adrenal
cell proliferation8 /o&e+er, only ? of these defects can produce hirsutis$
F21'hydro.ylase =$ost fre;uent>, ?'hydro.ysteroid dehydro,enase =less
fre;uent>, and 11''hydro.ylase deficiency =least fre;uent>8 If CA/ is
considered, an AC#/'sti$ulation test is indicated, &hich is a search for
e.a,,erated ;uantities of the precursors of cortisol8 #he sti$ulation test is
re;uired -ecause -aseline ele+ation of these steroids $ay -e in the
reference ran,e8 /yperandro,enis$ in CA/ can cause infertility, -ut
de.a$ethasone therapy in this settin, $ay induce o+ulation8 #&o
i$portant reasons for the dia,nosis of CA/ are that specific therapy is
a+aila-le and ,enetic counselin, $ay -e necessary
!o$en &ith -oth CA/ =21'hydro.ylase deficiency> and Cushin,
syndro$e ha+e -een descri-ed &ith particularly se+ere hirsutis$8

o #u$ors =$ali,nant or -eni,n> and )C6S are the o+arian causes of hirsutis$8
6+arian tu$ors: 6+arian tu$ors $ay -e $ali,nant, and the threat can -e
serious8 Andro,en'secretin, o+arian tu$ors are a less'serious threat8 #he
$ost co$$on a$on, the$ is arrheno-lasto$a, &hich accounts for less
than 19 of all o+arian tu$ors8 In patients &ith this neoplas$, the seru$
testosterone le+el is al&ays ele+ated, and $ost patients ha+e a$enorrhea
and a palpa-le o+arian $ass8
*onado-lasto$as usually de+elop in youn,er persons =a,ed 10'?0 y> &ho
are ,enetic $ales &ith fe$ale e.ternal ,enitalia8 0early half of these
tu$ors are $ali,nant, and $any are -ilateral8 )el+ic e.a$ination findin,s
are a-nor$al -ecause internal fe$ale ,enitalia are a-sent8
o Lipoid cell tu$ors are of 2 histolo,ic types: adrenalli"e cells =in youn,er
patients> and hilar or Leydi,li"e cells =in older patients>8 #hese tu$ors are
usually palpa-le -ut are seldo$ $ali,nant8 6+arian tu$ors, &hich are
e+en less fre;uently encountered, include dys,er$ino$as, 4renner
tu$ors, and cystic ,ranulosa'theca cell tu$ors8
)C6S: )C6S is the $ost co$$on o+arian disorder associated &ith
hirsutis$8 Althou,h the cause of )C6S is not "no&n, the etiolo,y is
speculated to -e $ultifactorial8 4y definition, polycystic o+aries ha+e 20
or $ore su-capsular follicles, &hich ran,e fro$ appro.i$ately 1'1< $$
in dia$eter8 #he follicles are at +arious states of atresia, and hyperplasia of
the theca interna, the anato$ic source of o+arian andro,ens, is present8
/o&e+er, the -asic a-nor$alities in )C6S are functional, rather than
anato$ic, in nature8 In particular, le+els of luteini5in, hor$one =L/> are
tonically ele+ated =&ith L/ le+els hi,her than those of follicle'sti$ulatin,
hor$one G%S/H>8
Many &o$en &ith )C6S ha+e insulin resistance, $anifested -y acanthosis ni,ricans and
ele+ated plas$a insulin le+els8 Increased insulin le+els ha+e -een speculated to sti$ulate
andro,en production fro$ the o+arian theca interna cells8 An e.peri$ent in nature supports this
hypothesis2 &o$en &ith )C6S &ho ha+e a specific ,enetic $utation that lo&ers insulin
resistance ha+e lo&er hirsutis$ scores8 In addition, the i$portance of insulin resistance is
e$phasi5ed -y the therapeutic effect of insulin'sensiti5in, $edications =e,, $etfor$in,
thia5olidinediones>, &hich restore nor$al o+arian andro,en production and o+ulation8
)C6S usually -e,ins at pu-erty8 #he incidence has -een esti$ated to -e appro.i$ately <9
a$on, adolescent ,irls and adult &o$en in the United States8 As noted, the characteristic
endocrine a-nor$ality is an ele+ation in le+els of plas$a free testosterone that is not suppressed
-y de.a$ethasone2 ho&e+er, as $any as <09 of patients also sho& a-nor$al adrenal andro,en
secretion8
Idiopathic hirsutis$ is a dia,nosis of e.clusion8
o #he patient@s hirsutis$ is not caused -y &ell'defined a-nor$alities such as an
andro,en'secretin, tu$or or CA/8
o #he spectru$ of clinical presentations ran,es fro$ nor$al $enses and $ild
hirsutis$ to a$enorrhea and si,ns of +irili5ation, and testosterone le+els ran,e
fro$ nor$al to fran"ly ele+ated8
o #he hirsutis$ usually -e,ins at pu-erty8
o #he disorder is often fa$ilial and $ay -e associated &ith o-esity and insulin
resistance8
o So$e classification sche$es distin,uish patients &ith ele+ated adrenal andro,en
le+els =dehydroepiandrosterone sulfate G/EASH>2 in these cases, the disorder is
called idiopathic adrenal hyperandro,enis$8
o So$e patients &ith idiopathic hirsutis$ ha+e nor$al plas$a andro,en le+els8 As
noted a-o+e, the underlyin, $echanis$ in these patients $ay -e an increase in
andro,en sensiti+ity or in <'alpha'reductase acti+ity in the s"in8 Increased acti+ity
of the en5y$e has -een de$onstrated -ased on s"in -iopsy findin,s and -y a
findin, of ele+ated urinary le+els of dihydrotestosterone $eta-olites2 ho&e+er,
presently, tests for <'alpha'reductase acti+ity ha+e -een used only in research8

Miscellaneous causes of hirsutis$ include other causes of insulin resistance and andro,en
e.cess8
/ypertrichosis should not -e confused &ith hirsutis$ -ecause hirsutis$ usually i$plies
hyperandro,enis$8 /ypertrichosis, on the other hand, usually in+ol+es nonandro,enic
hair8 /ypertrichosis can -e caused -y porphyria, $edications =phenytoin, $ino.idil,
cyclosporine, dia5o.ide, corticosteroids, strepto$ycin, he.achloro-en5ene,
penicilla$ine, hea+y $etals, sodiu$ tetradecyl sulfate, aceta5ola$ide, interferon>, and
,enetic factors8
DIFFERENTIA1S
Section A of 11
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ifferentials
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Adrenal Adeno$a
Adrenal Carcino$a
C'11 /ydro.ylase eficiency
C'1B /ydro.ylase eficiency
Cushin, Syndro$e
Mali,nant Lesions of the 6+aries
6+arian Cancer
6+arian )olycystic isease
Ot!er #ro/lems to /e %onsi)ere)
Andro,en'secretin, adrenal tu$ors
Andro,en'secretin, o+arian tu$ors
E.o,enous andro,ens
Con,enital adrenal hyperplasia
Idiopathic hirsutis$
WOR2U#
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ifferentials
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#reat$ent
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(eferences
1a/ Stu)ies
Appro.i$ately <09 of &o$en &ith e+en $ini$al hirsutis$ ha+e e.cessi+e andro,en8
La-oratory studies in hirsutis$ ser+e -oth to confir$ the clinical i$pression of
hyperandro,enis$ and to identify the source of e.cess andro,ens, either adrenal or
o+arian8 #he &or"up descri-ed in I$a,e 1 reco$$ends 2 +isits, a -aseline e+aluation
follo&ed -y a 2'&ee" de.a$ethasone treat$ent period8 Specific discussion of the testin,
is -elo&8
o #estosterone: #he $ost i$portant assay is the le+el of seru$ testosterone, the
$a:or circulatin, andro,en8 If the total seru$ testosterone le+el is nor$al,
$easure the free seru$ le+el -ecause hyperandro,enis$ =and insulin resistance, if
present> decreases se. steroid'-indin, ,lo-ulin, such that the un-ound,
-iolo,ically acti+e testosterone $oiety $ay -e ele+ated e+en if the total le+el is
unre$ar"a-le8 E.tre$ely hi,h testosterone le+els are li"ely to -e associated &ith
adrenal or o+arian tu$ors, &hereas idiopathic and -eni,n etiolo,ies result in +ery
$ild ele+ations8 Indeed, in idiopathic hirsutis$, the results fro$ testin, andro,en
le+els are often nor$al8 In so$e of these &o$en, hirsutis$ is thou,ht to -e
caused -y increased s"in sensiti+ity to andro,en or -y increased s"in <'alpha'
reductase acti+ity8 #his en5y$e is located in the s"in near the hair follicle, and it
con+erts plas$a testosterone to the andro,en $eta-olite dihydrotestosterone8
o ehydroepiandrosterone sulfate =/EAS>: 4ecause testosterone can ori,inate in
either the adrenal corte. or the o+ary, an ele+ated testosterone le+el does not
indicate the ,land of ori,in8 Accordin,ly, $easure$ent of ele+ated plas$a le+els
of /EAS, an andro,en synthesi5ed al$ost e.clusi+ely -y the adrenal corte.,
can indicate e.cess adrenal function8 Ele+ations in -oth testosterone and /EAS
su,,est an adrenal ori,in, &hereas an isolated testosterone ele+ation indicates an
o+arian source8
o e.a$ethasone suppression =see I$a,e 1>: La-oratory testin, of testosterone
=free or total> and /EAS can -e perfor$ed on the initial +isit8 At the sa$e ti$e,
a dia,nostic trial of de.a$ethasone therapy for B'1A days can -e initiated to help
e.clude adrenocorticotropin hor$one =AC#/>Idependent hirsutis$8 !hen the
patient returns, free testosterone, /EAS, and plas$a cortisol le+els are
$easured8 e.a$ethasone'$ediated suppression of andro,ens is o-ser+ed in
healthy &o$en &ho do not ha+e hirsutis$ and in those &ith con,enital adrenal
hyperplasia =CA/> and idiopathic hirsutis$8
o Adrenocorticotropin sti$ulation: An AC#/'sti$ulation test =2<0 $c, for ?0 $in>
can help differentiate -et&een CA/ and idiopathic hirsutis$ -ecause CA/
produces a-nor$al findin,s =ele+ations in $eta-olic precursors of cortisol>8
/irsutis$ caused -y CA/ is due to 1 of ? cortisol -iosynthetic defects, ie,
21'hydro.ylase deficiency, ? ?'hydro.ysteroid dehydro,enase, or 11''
hydro.ylase deficiency8
4ecause 21'hydro.ylase deficiency accounts for the +ast $a:ority of cases
of CA/ =appro.i$ately D09>, the discussion is focused on this dia,nosis8
In+esti,ate possi-le 21'hydro.ylase deficiency -y $easurin, plas$a 1B'
hydro.ypro,esterone le+els o-tained -et&een 0B00 and 0D0 hours8 3alues
of less than B n$olJL e.clude the dia,nosis, and +alues of ,reater than A<
n$olJL =in &o$en &ho are non,estational> confir$ 21'hydro.ylase
deficiency8 !hen -asal +alues of 1B'hydro.ypro,esterone are -et&een B
and A< n$olJL, an AC#/'sti$ulated concentration of ,reater than A<
n$olJL is also dia,nostic8
Althou,h ele+ated -asal plas$a 1B'hydro.ypro,esterone le+els =as hi,h as
1B n$olJL> $ay -e present durin, the luteal phase of the $enstrual cycle
and in )C6S, AC#/'sti$ulated incre$ents are -lunted8

o Cortisol suppression: In+esti,ation of su-nor$al de.a$ethasone suppression of
andro,ens can -e ,uided -y the patient7s cortisol le+el, &ithout the need for an
AC#/'sti$ulation test8 )C6S and adrenal and o+arian tu$ors are associated &ith
nor$al suppression of cortisol -y de.a$ethasone, &hereas cortisol le+els in
patients &ith Cushin, syndro$e are not suppressed8

6ther la-oratory tests
o Seru$ prolactin or %S/: !o$en &ith hirsutis$ and a$enorrhea of un"no&n
cause should ha+e a seru$ prolactin or %S/ test to e+aluate for either a
prolactino$a or o+arian failure8
o ia-etes screenin,: !o$en &ith hirsutis$, )C6S, o-esity, or acanthosis
ni,ricans $ay ha+e insulin resistance, and screenin, for dia-etes and
hyperlipide$ia is &arranted8 Appro.i$ately <09 of these &o$en ha+e increased
insulin le+els and <9 ha+e undia,nosed dia-etes $ellitus8
o )rostate'specific anti,en =)SA>: Ultrasensiti+e assays can detect )SA in &o$en
and is a potential $ar"er for andro,en e.cess8 Studies thus far, ho&e+er, ha+e not
sho&n a ,ood correlation &ith the chan,e in andro,en le+els after treat$ent8
#herefore, further studies are needed8
Imaging Stu)ies
If indicated -ased on the findin,s fro$ the clinical e+aluation and la-oratory testin,,
perfor$ o+arian ultrasono,raphy and adrenal co$puted to$o,raphy scannin, or
$a,netic resonance i$a,in, to e+aluate for either o+arian or adrenal sources of andro,en
production8
TREATMENT
Section 6 of 11
Authors and Editors
Introduction
Clinical
ifferentials
!or"up
#reat$ent
Medication
%ollo&'up
Miscellaneous
Multi$edia
(eferences
Me)ial %are
#he treat$ent of hirsutis$ -e,ins &ith a careful e.planation a-out the cause of the pro-le$ and
reassurance that the patient is not losin, her fe$ininity8 #hen, direct inter+ention, if possi-le, is
instituted for the underlyin, disorder8 If hirsutis$ persists =or the patient has idiopathic
hirsutis$>, other cos$etic or syste$ic treat$ent $ay -e necessary8 In so$e cases, cos$etic
$easures $ay -e sufficient8 In others, the slo& pro,ress of syste$ic therapy $ay necessitate
$ore i$$ediate cos$etic treat$ent8 #he $ost effecti+e strate,y is to co$-ine syste$ic therapy,
&hich has a slo& onset of effecti+eness, &ith $echanical depilation =sha+in,, pluc"in,, &a.in,,
depilatory crea$s>8
/irsutis$ re;uires a careful and syste$atic clinical e+aluation coupled &ith a rational approach
to treat$ent8 #hrou,hout this process, the patient $ust understand that, althou,h dia,nostic
testin, can -e ti$e consu$in, =and e+en inconclusi+e>, it is so$eti$es essential for deter$inin,
an effecti+e inter+ention8 In other cases, counselin, and education $ay -e all that is needed8 %or
the patient &ho desires treat$ent, a &ide +ariety of phar$acolo,ic strate,ies are a+aila-le8
Infor$in, the patient that current syste$ic therapy is i$perfect is i$portant8 %urther$ore, none
of the dru,s used to treat hirsutis$ ha+e US %ood and ru, Ad$inistration =%A> appro+al for
such use8 Initiate therapy only in patients &ho ,i+e infor$ed consent after a co$plete
e.planation of the potential -enefits and ris"s of a particular treat$ent and alternati+e
approaches8
Syste$ic therapies directed at hirsutis$ can -e di+ided into those that decrease o+arian or
adrenal andro,en production and those that inhi-it andro,en action in the s"in8 #he
syste$ic therapies include ,lucocorticoids, oral contracepti+es =6Cs>, spironolactone,
fluta$ide, finasteride, cyproterone acetate =not a+aila-le in the United States>, and insulin
sensiti5ers =$etfor$in and rosi,lita5one>8
o *lucocorticoids: *lucocorticoids =de.a$ethasone or prednisone>, &hich suppress
adrenocorticotropin hor$one =AC#/>Idependent adrenal andro,en synthesis,
ha+e -een used &ith +aria-le success in &o$en &ith adrenal hirsutis$, as in
con,enital adrenal hyperplasia =CA/> or idiopathic adrenal hyperandro,enis$8
Usually, 08<'1 $, of de.a$ethasone at -edti$e is sufficient to suppress AC#/
and adrenal andro,en production8 Unfortunately, so$e patients ,ain &ei,ht and
de+elop cushin,oid features, e+en &ith this s$all of a dose8 %urther in+esti,ations
$ay esta-lish that lo&er doses =perhaps 082< $,> can -e effecti+e &ithout ad+erse
effects8
o 6Cs: #he dru,s $ost &idely used to suppress o+arian andro,en production are
6Cs8 #hey are pro-a-ly the first choice for youn, &o$en &ith hirsutis$ &ho do
not &ant to -eco$e pre,nant8
6Cs are ine.pensi+e and pro$ote re,ular uterine -leedin,8 In addition,
6Cs can -e used in co$-ination &ith one of the antiandro,ens or other
for$s of therapy8 6n the other hand, do not use 6Cs in &o$en &ith a
history of $i,raines, "no&n or possi-le thro$-otic disease, or -reast or
uterine cancer8
Moreo+er, for se+eral reasons, 6Cs ha+e a si,nificant failure rate in
patients &ith hirsutis$8 Lo&'dose 6Cs and pro,estin'only $inipills fail to
suppress o+ulation in as $any as <09 of &o$en8 6+arian function
continues at a +aria-le rate, and o+arian andro,ens continue to -e
produced8 Second, the pro,estins in 6Cs are attenuated deri+ati+es of
testosterone and ha+e +aria-le de,rees of andro,enic acti+ity in &o$en8
#he de,ree depends on the type of pro,estin and, $ore i$portantly, on
indi+idual suscepti-ility8

o Spironolactone: Spironolactone, in daily doses of <0'200 $,, -loc"s andro,en
receptors8 Spironolactone also decreases testosterone production, $a"in, it
additionally effecti+e for hirsutis$8 Spironolactone is especially useful in a patient
&ith hypertension or ede$a -ecause the dru, is a $ild diuretic8
Se.ually acti+e &o$en ta"in, spironolactone should ensure that
contracepti+e $easures are ade;uate8 In so$e cases, spironolactone can -e
co$-ined &ith an 6C for added effect on the hirsutis$8
!ith current syste$ic therapies for hirsutis$, 6 $onths to a year of
therapy is usually re;uired -efore results are noticea-le8 E+en then, only
appro.i$ately one half to three ;uarters of patients sho& i$pro+e$ent8
#he pro-le$ $ay lie partially in the nature of the hair follicle, &hich
persists for 6 $onths to a year e+en after andro,en le+els ha+e -een
nor$ali5ed8 Ineffecti+eness $ay also -e due to the ina-ility of treat$ent to
co$pletely nor$ali5e ele+ated tissue dihydrotestosterone le+els8 0e&er
therapies directed at inhi-ition of <'alpha'reductase or -loc"ade of the
andro,en receptor $ay i$pro+e the a-ility to treat patients8

o %luta$ide: %luta$ide, an e.a$ple of the ne&er therapies, is a potent nonsteroidal
selecti+e antiandro,en &ithout pro,estational, estro,enic, corticoid, or
anti,onadotropin acti+ity8 )reli$inary data indicate that it is effecti+e as therapy
for hirsutis$ =and also acne>2 ho&e+er, fluta$ide is e.pensi+e and has caused
fatal hepatitis8
o %inasteride: %inasteride is a <'alpha'reductase inhi-itor appro+ed for the treat$ent
of -eni,n prostatic hyperplasia8 0o ad+erse effects ha+e -een reported in &o$en,
and the efficacy is si$ilar to that of spironolactone8 In at least one study,
finasteride &as added to spironolactone, de$onstratin, an additi+e reduction in
hirsutis$ scores8 #he $ain concern &ith finasteride, ho&e+er, is the ris" of
a$-i,uous ,enitalia in $ale fetuses e.posed to the en5y$e inhi-itor durin, the
first tri$ester8 #herefore, use this dru, only in &o$en &ho are post$enopausal
&ith no chance of -eco$in, pre,nant8
o Cyproterone acetate has -een effecti+e in the treat$ent of hirsutis$8 !hen added
to ethinyl estradiol, it is as effecti+e as fluta$ide in the treat$ent of hirsutis$8
Cyproterone is not a+aila-le in the United States8
o Insulin sensiti5ers: 4oth $etfor$in and rosi,lita5one i$pro+e insulin resistance
and ha+e -een sho&n to -e effecti+e in lo&erin, andro,en le+els and in treatin,
hirsutis$8
o Si-utra$ine: !ei,ht loss &ith this anorectic a,ent i$pro+es hirsutis$ scores,
andro,en le+els, and cardio+ascular ris" factors in &o$en &ith polycystic o+ary
syndro$e =)C6S>8
Cos$etic $easures for hirsutis$ and their disad+anta,es are as follo&s:
o /ydro,en pero.ide -leachin, is not suita-le for se+ere hirsutis$8
o )luc"in, can cause s"in irritation, folliculitis, and scarrin,8
o !a.in, can cause s"in irritation, folliculitis, and scarrin,8 #he &a. used
has a lo& $eltin, point8
o Sha+in, $ay -e psycholo,ically unaccepta-le8
o Che$ical depilatories can cause s"in irritation8
o Electrolysis can -e painful, and short'&a+e diather$y can cause scarrin,8
o Laser therapy has -een sho&n not only to reduce un&anted hair -ut also to
i$pro+e depression and an.iety in &o$en &ith hirsutis$8
MEDI%ATION
Section B of 11
Authors and Editors
Introduction
Clinical
ifferentials
!or"up
#reat$ent
Medication
%ollo&'up
Miscellaneous
Multi$edia
(eferences
#he $ost effecti+e strate,y for treatin, hirsutis$ is to co$-ine syste$ic therapy, &hich has a
slo& onset of effecti+eness, &ith $echanical depilation =sha+in,, pluc"in,, &a.in,, depilatory
crea$s>8
Syste$ic therapies directed at hirsutis$ can -e di+ided into those that decrease o+arian or
adrenal andro,en production and those that inhi-it andro,en action in the s"in8
Drug %ategory+ Oral contraceptives
6Cs inhi-it o+arian andro,en production and are pro-a-ly the first choice for youn, &o$en &ith
hirsutis$ &ho do not &ant to -eco$e pre,nant8 6Cs are ine.pensi+e, and they pro$ote re,ular
uterine -leedin,8 6Cs can -e used in co$-ination &ith antiandro,ens or other a,ents8 #hey ha+e
a si,nificant failure rate in hirsutis$ for se+eral reasons8 Lo&'dose 6Cs and pro,estin'only
$inipills fail to suppress o+ulation in as $any as <09 of &o$en8 6+arian function continues at a
+aria-le rate, and o+arian andro,ens continue to -e produced8 Second, the pro,estins in 6Cs are
attenuated deri+ati+es of testosterone and ha+e +aria-le de,rees of andro,enic acti+ity in &o$en8
#he de,ree depends on the type of pro,estin and, $ore i$portantly, on indi+idual suscepti-ility8
Drug Name
Estro,en'pro,estin co$-inations =6rtho'0o+u$,
6rtho #ri'Cyclen, #riphasil>
Desri&tion
(educes secretion of L/ and %S/ fro$ the
pituitary ,land -y decreasin, a$ount of
,onadotropin'releasin, hor$ones8
A)ult Dose 1 ta- )6 ;d
#e)iatri Dose 0ot esta-lished
%ontrain)iations
ocu$ented hypersensiti+ity2 thro$-ophle-itis2
undia,nosed +a,inal -leedin,2 cere-ral apople.y
Interations
May reduce hypoprothro$-ine$ic effects of
anticoa,ulants2 estro,en le+els $ay -e reduced
&ith coad$inistration of -ar-iturates, rifa$pin,
and other a,ents that induce hepatic $icroso$al
en5y$es2 corticosteroid le+els $ay increase &hen
ad$inistered concurrently &ith ethinyl estradiol2
use of ethinyl estradiol &ith hydantoins $ay cause
spottin,, -rea"throu,h -leedin,, and decreased
contraception2 increase in fluid retention caused -y
estro,en inta"e $ay reduce sei5ure control
#regnany K ' Contraindicated in pre,nancy
#reautions
Caution in patients &ith hepatic i$pair$ent,
$i,raine, sei5ure disorders, cere-ro+ascular
disorders, -reast cancer, thro$-oe$-olic disease,
asth$a, depression, and renal or cardiac
dysfunction
Drug %ategory+ Glucocorticoids
*lucocorticoids are used to inhi-it adrenal andro,ens8 #hese a,ents ha+e antiinfla$$atory
properties and cause profound and +aried $eta-olic effects8 *lucocorticoids suppress AC#/'
dependent adrenal andro,en synthesis8 #hese a,ents are used &ith +aria-le success in &o$en
&ith adrenal hirsutis$, CA/, and idiopathic adrenal hyperandro,enis$8
Drug Name )rednisone =eltasone, 6rasone, Meticorten>
Desri&tion
May inhi-it AC#/'dependent andro,en synthesis
throu,h ne,ati+e feed-ac"8
A)ult Dose < $, )6 ;hs
#e)iatri Dose 0ot esta-lished
%ontrain)iations
ocu$ented hypersensiti+ity2 +iral infection2
peptic ulcer disease2 hepatic dysfunction2
connecti+e tissue infections2 fun,al or tu-ercular
s"in infections2 *I disease
Interations Coad$inistration &ith estro,ens $ay decrease
clearance2 concurrent use &ith di,o.in $ay cause
di,italis to.icity secondary to hypo"ale$ia2
pheno-ar-ital, phenytoin, and rifa$pin $ay
increase $eta-olis$ of ,lucocorticoids =consider
increasin, $aintenance dose>2 $onitor for
hypo"ale$ia &ith coad$inistration of diuretics
#regnany
4 ' Usually safe -ut -enefits $ust out&ei,h the
ris"s
#reautions
A-rupt discontinuation of ,lucocorticoids $ay
cause adrenal crisis2 hyper,lyce$ia, ede$a,
osteonecrosis, $yopathy, peptic ulcer disease,
hypo"ale$ia, osteoporosis, euphoria, psychosis,
$yasthenia ,ra+is, ,ro&th suppression, and
infections $ay de+elop &ith ,lucocorticoid use
Drug Name e.a$ethasone =ecadron, AL'e., Al-a'e.>
Desri&tion
May inhi-it AC#/'dependent andro,en synthesis
throu,h ne,ati+e feed-ac"8
Lo&er doses =e,, 082< $,> $ay pro+e to -e
effecti+e &ith fe&er ad+erse effects8
A)ult Dose 08<'1 $,Jd )6 ;hs
#e)iatri Dose 0ot esta-lished
%ontrain)iations
ocu$ented hypersensiti+ity2 acti+e -acterial or
fun,al infection
Interations
Effects decrease &ith coad$inistration of
-ar-iturates, phenytoin, and rifa$pin2 decreases
effect of salicylates and +accines used for
i$$uni5ation
#regnany
C ' Safety for use durin, pre,nancy has not -een
esta-lished
#reautions
Increases ris" of $ultiple co$plications, includin,
se+ere infections2 $onitor adrenal insufficiency
&hen taperin, dru,2 a-rupt discontinuation of
,lucocorticoids $ay cause adrenal crisis2
hyper,lyce$ia, ede$a, &ei,ht ,ain, osteonecrosis,
$yopathy, peptic ulcer disease, hypo"ale$ia,
osteoporosis, euphoria, psychosis, $yasthenia
,ra+is, and ,ro&th suppression $ay de+elop
Drug %ategory+ Antiandrogens
Antiandro,ens are used to -loc" andro,en action8
Drug Name Spironolactone =Aldactone>
Desri&tion
ecreases testosterone production8 Can -e
co$-ined &ith 6Cs for added effects8
A)ult Dose <0'200 $, )6 ;d
#e)iatri Dose 0ot esta-lished
%ontrain)iations
ocu$ented hypersensiti+ity2 anuria2 renal failure2
hyper"ale$ia
Interations
May decrease effect of anticoa,ulants2 potassiu$
and potassiu$'sparin, diuretics $ay increase
to.icity
#regnany ' Unsafe in pre,nancy
#reautions
Caution in renal and hepatic i$pair$ent2
contraception is i$perati+e in se.ually acti+e
&o$en
Drug %ategory+ 5 alpha-reductase inhibitors
#hese a,ents are indicated for treat$ent of -eni,n prostatic hyperplasia and $ale pattern
-aldness8 An unla-eled use is for the treat$ent of fe$ale hirsutis$8
Drug Name %inasteride =)roscar, )ropecia>
Desri&tion
Specific inhi-itor of the intracellular en5y$e that
con+erts testosterone into the andro,en <''
dihydrotestosterone8 Efficacy in hirsutis$ is
si$ilar to that of spironolactone8 #o -e used only
in post$enopausal &o$en &ith no chance of
-eco$in, pre,nant8
A)ult Dose < $, )6 ;d
#e)iatri Dose o not ad$inister
%ontrain)iations
ocu$ented hypersensiti+ity2 not to -e used in
children, pre,nancy, or &o$en &ho $ay -eco$e
pre,nant
Interations 0one reported
#regnany K ' Contraindicated in pre,nancy
#reautions
Caution in hepatic i$pair$ent2 $ay cause
a$-i,uous ,enitalia de+elop$ent in $ale fetus
durin, first tri$ester of pre,nancy
FO11OW3U#
Section C of 11
Authors and Editors
Introduction
Clinical
ifferentials
!or"up
#reat$ent
Medication
%ollo&'up
Miscellaneous
Multi$edia
(eferences
#rognosis
)ro,nosis depends on the etiolo,y of the hirsutis$, e,, -eni,n or $ali,nant8
#atient E)uation
/irsutis$ re;uires a careful and syste$atic clinical e+aluation coupled &ith a rational
approach to treat$ent8 #hrou,hout this process, the patient $ust understand that,
althou,h dia,nostic testin, can -e ti$e consu$in, =and e+en inconclusi+e>, it is
so$eti$es essential for the deter$ination of an effecti+e inter+ention8 In other cases,
counselin, and education $ay -e all that is needed8
%or the patient &ho desires treat$ent, a &ide +ariety of phar$acolo,ic strate,ies are
a+aila-le8 Infor$in, the patient that current syste$ic therapy is i$perfect is i$portant8
%urther$ore, none of the dru,s used to treat hirsutis$ has %A appro+al for such use8
Initiate therapy only in patients &ho ,i+e infor$ed consent after a co$plete e.planation
of the potential -enefits and ris"s of a particular treat$ent and alternati+e approaches8
MIS%E11ANEOUS
Section D of 11
Authors and Editors
Introduction
Clinical
ifferentials
!or"up
#reat$ent
Medication
%ollo&'up
Miscellaneous
Multi$edia
(eferences
Me)ial.1egal #itfalls
0one of the dru,s used to treat hirsutis$ has %A appro+al for such use8

#herapy should -e initiated only in patients &ho ,i+e infor$ed consent after a co$plete
e.planation of the potential -enefits and ris"s of a particular treat$ent and alternati+e
approaches8