cleveland clinic journal of medicine 2010 harrison 388 98

7/28/2019 Cleveland Clinic Journal of Medicine 2010 HARRISON 388 98

1/11

Update on the managementof hirsutism

AbstrAct

Hirsutism is a source o signicant anxiety in women.

While polycystic ovary syndrome or other endocrineconditions are responsible or excess androgen in manypatients, other patients have normal menses and normalandrogen levels (idiopathic hirsutism). The goal othe evaluation is to rule out any underlying pathology.The goals o therapy are to treat any underlying condi-tion and to remove the excess hair. Current options orhair removal are discussed. Educating patients so theyhave reasonable treatment expectations is essential, assignicant improvement may take weeks or months, andtreatment may need to be repeated on an ongoing basis.

Key Points

The nding o polycystic ovaries is not required or thediagnosis o polycystic ovary syndrome, nor does theirpresence prove the diagnosis. Gonadotropin-dependentunctional ovarian hyperandrogenism is believed tocause this syndrome; however, mild adrenocorticotropic-dependent unctional adrenal hyperandrogenism also isa eature in many cases.

Even women with mild hirsutism with subtle symptomsand signs o hyperandrogenism can have elevated andro-gen levels, and thus, they deserve a laboratory evaluation.

Laser treatment does not result in complete, permanenthair reduction, but it is more eective than shaving, wax-ing, and electrolysis,producing partial hair reduction orup to 6 months.

Hirsutism causes signiicant xyd lk o l- wo. Al-

hoh l b odo, o

h o dly d pobly odo odo.A w wll d, h do b

wh dld hoy d phyl x-o, wh lbooy d dd o o o l o dly. M b wh p d-o d ppo d ld h ovld d o y dly -bol d.

prevalence and impact

H oo dod o xowh o l h do-dp-d l dbo wo, ldh h, pp lp, b, pp bk, dbdo.1 I 5% o 10% o wo opodv .1,2

H hold b dd ohypho, whh b hdy oqd, d whh dd dl h owh do-dpd

.

1

Ex h olly o owo d ly l--.3 Nol o pbl h owh d-pd o wo hy d h pp-o o ll, ll, d ol oo h qy d dbo o h. Md- wo lly hv do o body d l h, wh Awo hv l o.1,4,5

H b llly dd odo h F-Gllwy l2,6 d dd

F-Gllwy o o 8 o hh.1

*Dr. Harrison received unding in 2008 rom the F.C. Florance Bequest, administered through theAustralasian College o Dermatologists.

doi:10.3949/ccjm.77a.08079

Shannon harriSon, MBBS, MMd, FaCD*Dermatologist in private practice, Hobart, Tasmania, Australia

reVieW

najwa SoMani, MDAssistant Proessor o Dermatology andPathology and Laboratory Medicine, AssociateDirector o Dermatopathology, Departmento Dermatology, Indiana University School oMedicine, Indianapolis

wilMa F. BergFelD, MDHead, Section o Clinical Research, Dermatol-ogy and Plastic Surgery Institute, and Head,Section o Dermatopathology, Department oAnatomic Pathology, Cleveland Clinic

EDUCATIONAL OBJECTIVE: Readers will recognize signs o androgen excess and will consider currenttreatment options or hirsutismCREDIT

CME

388 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 77 NUMBER 6 JUNE 2010


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CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 77 NUMBER 6 JUNE 2010 389

HArrison And colleAgues

How circulating androgensaect Hair ollicles

I do-dpd , l -

do f h olll h.Ado h z d d oh h b do-dpd, pby wh h o-o o vll h (ll, opdh) o l h (l, pdh) h pb d xlly o wo, wll h bd .2,7Ily, h l do zo o h pbl holll o h l lp.7 Th pbl-y o h h olll o h o h -

do y b lly dd.7,8H o hypdo

d d o o do o holll. I wo, bo hl o loo o h ov d d-l ld; h o o pph-l ovo o wk do (h dodo podd by h dld ov) o oo.9 Dhydop-doo l (DHEAS) oly h dl ld.9,10 Too ovd o h o po dhydo-oo (DHT) by yp II 5-lph d h k, whh h o pblh olll.7,11 Tho, h b oq o doo do ov-podo o h ov o h dlld (o boh), o xpo o xooo o do h d, o o hh-d h olll vy d bolo ol l do lvl (d-o dyo).1

idiopatHic Hirsutism:a misleading diagnosis

My wo wh h od ohv polyy ovy ydo h d-ly , b h lo oolylbld doph wh o who obvo , , wo wh l d ol do lvl d wh-o po o oh o h-.1,2,12,13 B whl h oolyd,1,12 y b ld, plly h

do o doph h bd o

dd lbooy , whh do o lwyd do x.2,13 Mo ov odl ol hypdo,14 -d pphl vy o 5-lph d-

h h olll, o bol h do po hv b pld h pho o o-lld doph h-.2,15

Hirsutism andpolycystic ovary syndrome

Polyy ovy ydo, bol y-do, p llly wh ll h olooh ooh, ly, d o hyp-

do h h, , o do- lop.16,17 Mbol dbld l , pd lool, hyplpd, d oby (body dx > 30 k/2) lo o, h dovl k.1618

Th d o polyy ov oqd o k h do o polyyovy ydo, d h p do opov h do.16,19 Godoop-dp-d ol ov hypdo blvd o h ydo; howv,ld doooop-dpd -ol dl hypdo lo y . I , polyyovy ydo p wh oldlvo o DHEAS.16,20

otHer conditions o excess androgen

Th ydo o hypdo, l, d ho , bbv-d HAIR-AN, p o polyy-

ovy ydo; hz opo hd ydo od wh vbol bol o l d lobol d wh kd ll ohypdo.12

Th ydo o boh, , h-, d ho , bbvd SAHA, whl o l do, llp o dolo d ypolo od wh hypdo. Th h y p wh h HAIR-ANydo o wh oh o x -

do, h doph, ov, dl,

normal

or apabl

hair growh

dpd o

hiiy ad

amilial,

ulural,

ad oial

orm


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Hirsutism

o hyppol hypdo.21

Thyod d, hyppol, o-ly, Ch ydo, xoo oh do d, d ollol dl hyppl lo po-d h.12 I oll oldl hyppl, whh yplly dby dy o 21-hydoxyl, pp wh p pbh, h h ppbl y, d l -l ld py oh.22,23

Ipo o h ldb d l do- -o o dl o ov o. I h -, h hv o o pdpoo d y b od wh -

o vlzo, h dpd vo,

d l , do lop,looly, d d lbdo.12

a tHorougH History is critical

to diagnosisA hooh dl hoy povd -po do l wo wh h-. Th l hold l dlbo h o d poo o h howh,12,15 pvo , d y -o o hypdo, h , boh, ho , o p-d h lo.

Alo po h l hoyd hoy o ly. Py o-

h dd l o by 16

Figure 1. A modication o the Ferriman-Gallwey scoring system. A score o 8 or more indicates hirsutism.


4/11



y o ody xl hhv dvlopd, o by 14 y o o -ody xl h hv dvlopd,d d oll ol d-

l hyppl.Th l hold lo y o d-

h p h hoy o lo-h o ypo o vlzo (, dpdvo, looly, d l ); ly hoy o h, polyy ovyydo, HAIR-AN ydo, bolodo h yp 2 db ll,o dovl d12,15; o hoy oypo o y odo kow o podh, h Ch d, o-ly, o hyod dod. Alo po

d hoy o d h p hk d h do, bol -od, o vlpo d (Dpko).20

tHe pHysical examination

Th phyl xo volv o hF-Gllwy h o y o odd F-Gllwy o y(Figure 1), whh hlp oz h vyd dbo o x h owh. A F--Gllwy o o 8 o 15 (o o po-bl 36) d od h, wh o bov 15 d v h.2,15

Aoh popod pdo o h h l h o h h o h low b-do (F-Gllwy o 2) ly100% v d 27% p pdol-body h.24

A p o h phyl xo, hl hold lo look o oh -o o hypdo, h ,do lop, d boh. A-ho o l .Hh d wh hold b d dh body dx lld. Blood p- hold b odd, hh blood p- y b Ch ydo d po dovl k o. So vlzo hold b dd. Idoo Ch d h , oo , dbo, l k, d poxlyophy hold b od wll ohyod d, h xl k h,o, d h lo. Expbl o po-

o loh hyppol.

Aoly od wh o d ld hd d . My o h -dooph b d by pydo, whh vl ld

d, o vl ld hold b xd.25Th xo hold lo xld y pl-pbl ov o dl .12

wHen is additional testing needed?

Lbooy d dolo pwh h y b dd o o hdo o pd dly odoo o xld o dly pholoy(table 1).1,12,1518,20,22,23,2528

Th Edo Soy d-

l20 od ob ly-o- oo blood lvl h ollowp: Wo wh od o v h Wo wh h o y d wh

dd o o pd poo, o -opd by o ypo ly o polyy ovy ydo:, l ly, ly, -l oby, looly, o ho.15,20

T do lvl ld, old h- h o b pov o b l o ol .20

A ly-o ol o oolvl h l h lbooy vl-o o h.12,15 Addol plzdlbooy y b dd o dh oo lvl,15 h o-o o vlbl ll lboo.A ol ol oo lvl do o x-ld hypdo b hdo o doph h.15

Fh dd h ol -oo lvl ol o oly lhly l-vd, o h o ll poo dly odo h do-ophy o o. I lo l pwho h pod pooly o dl15 ( do blow).

I h ol oo lvl lvd, h h od o v, h od ypo, o h o

pov, h doolo wokp

Polyyi

ovary

ydrom,

high prolai,

aromgaly,

cuhig

ydrom,

ad rai

drug a

produ hypr-adrogim


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Hirsutism

table 1

t h wkp f h

condition clinical presentation tests

ih h HirsutismRegular menstrual cycle

Total and ree testosterone levels

p

HirsutismIrregular menstrual cycle, inertilityWeight gainAcanthosis nigricansMetabolic syndrome (obesity, insulin resistance,type 2 diabetes, lipid abnormalities, cardiovascular disease)

Total and ree testosterone levelsSex hormone-binding globulinDehydroepiandrosterone sulateAndrostenedioneTransvaginal ovarian ultrasonographyMetabolic screen

Hair-an (h, ,h )

HirsutismIrregular menstrual cycle, inertilityWeight gainAcanthosis nigricansMetabolic syndrome (obesity, insulin resistance,type 2 diabetes, lipid abnormalities, cardiovascular disease)

Total and ree testosterone levelsSex hormone-binding globulinDehydroepiandrosterone sulateAndrostenedioneTransvaginal ovarian ultrasonographyMetabolic screen

n h

Hirsutism onset beore pubertyMenstrual irregularities or primary amenorrheaPremature pubarche

Total and ree testosterone levelsSex hormone-binding globulinDehydroepiandrosterone sulateAndrostenedione17-hydroxyprogesterone level

H HirsutismHistory o galactorrhea (spontaneous, expressible)Visual eld deects i pituitary in origin

Serum prolactin

a HirsutismVisual eld deect, coarse acies, large hands and eet

Somatomedin C (insulin-like growthactor 1) level

a

Hirsutism (acute onset, severe, or progressive)Virilization (increased libido, deepened voice,clitoromegaly, increased muscle mass)

Total and ree testosterone levelSex hormone-binding globulinDehydroepiandrosterone sulateAndrostenedioneComputed tomography or magneticresonance imaging (abdomen or pelvis)

th HirsutismHot or cold intolerance

Diuse scalp hair lossWeight changeTextural skin changes

Total and ree testosterone levelSex hormone-binding globulin

Dehydroepiandrosterone sulateAndrostenedioneThyroid-stimulating hormone, ree T4Thyroid autoantibodies

ch HirsutismMood or sleep disturbanceStriae, bruising, ragile skinWeight gainFat redistibution, moon acies, supraclavicular at padProximal weakness, atigueHypertensionInsulin resistance

24-hour urinary ree cortisolDexamethasone suppression test


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tig

adrog

lvl i mild,

iolad

hiruim

ha o b

how o alr

maagm

dd,15 pobly ld o oo, x hoo-bd lob-l, DHEAS, d dodo.15 F -oo, bod o x hoo-bd

lobl, h bololly v o, whh lvl o bd lobl d by dh ol opv15 d dd byhh l lvl l .25

t h h?Alhoh h dl h o d-dol wokp y o wo whld h, w vl ll p whh d ho wh h SAHA l-l p by d ol -oo d DHEAS. I o xp,

v wo wh ld h wh blypo d o hypdod ld h o hv lvd -do lvl.

t h h h?I wo wh doph h, oo o ol ov d dl hy-pdo blvd o ply ol d hoh o b dbl wh ov-ol .25 Th odoop-lhoo (GRH) lo lo y ov ol hypdo h, b d h ool ddo o ly hv pplo oll p.14

I po o b h owo wh pp doph hd hoy o l l yl lly olo-ovloy o ovloy. Ih , oh do hold bodd,13 d l o doolo- o h vlo o ovloy -o odd.13

current use o diagnostic imaging

wh A oo lvl bov 200 /dL ov o, d DHEAS lvl bov700 /dL dl o.26 How-v, o ll o p wh h hhdo lvl, d dd o o h-, pd poo o h, o ovlzo o.15 I h ,

vl loophy, opd o-

ophy, o o (MRI) o h bdo xld ov- o dl o.

wh Th do o polyy ovy ydo od by wo o o h : Olo-ovlo o ovlo Cll o lbooy o hyp-

do Ulooph vd o polyy

ov, wh xlo o oh ohypdo.

additional laboratory testing

t A o polyy ovy ydo -volv vl loophy, b l-ooph vd o polyy ovy o y o h do.16 A lpd pol d lo -odd, d h lo ol, ol lo ol -odd.17

So hv pod h oo lz hoo o olll-l- hoo h wokp o polyyovy ydo, d o h2 h b odd dv b odo.16,25 Th dvdl lvl o l-z hoo, olll-l ho-o, d dol o po h vlo o ly d ovloydyo. I p wh lvo oh hoo o wh h ypo,l o ly wh doolo o yolo o-dd.25

a ch , h Ch ydo b d o wh 24-ho ool, ovh low-do dx-ho ppo , d l-hlvy ool.27,28 Rl o do-olo o h dbw ooop-dpd o o-oop-dpd Ch ydo.25Ch ydo o od whhypdo, plly ho

d by dl o.29


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Hirsutism

Th pol lvl d h lvl o o-od C (l-lk owh o 1) b d o l o hyppold oly, pvly.12 I Ch y-

do, hyppol, o oly dod by doolo , pyMRI hold b pod.12,25

Rl o pl wh x-p wh h odo l.

Noll ol dl hyppl b d o by 17-hydoxy-poo lvl d h olllph.12 M o hyod-lhoo, hyox, d hyod pox-d bod o hyod d.12H h b pod wh h o-

o L-hyox hpy.30

tHe principles o treatment

P do d h o h- d obl xpod ool ppo po h o h. Alo po l ollow-p o d doh po o ; h ldp F-Gllwy o, kphooph o d , d do lvl 3 o 6 oh.12

T b od o oo- , d o pholo k p o 3 o 6 oh o pod - pov.1

Wh dly odo d-od, o h odo l.Ado- o q l.12 Ch d, hyppol-, d oly hold b lllypp o xo d , dppop l d dd hold b d. Exoo o o -do h do po o -bol od hold b dod. Lyl po, d wh lo ob p wh polyy ovy ydo pov h wll -dovl k o.31

I l ol dl hyppl,loood hpy boh ovl-o do d h.20 Howv, oll ol dl hyppl,

loood hpy ppo ovlo -

do, b h lly q bohy do d h ovl.20

current options or Hair removal

Th y o o h ov h x h. Opo (table 2)ld xpv, ho-bd, l-hod h plk, hv, wx, dploy , d blh, do xpv l-bd h l-bd wx, loly, d lh ovl. Th hod lo b o-bd wh d hpy.1

Th ho o hod dpd o pp, dv , h d o h-

, h lvl o d, pvo -, d o.1,15,32

s- hSl- hod o oly poy d-o o x h. Plucking ov h h, ld- h oo, b pl d -o-, d oly pl o whw h x, h o h .1

Shaving y, xpv, d p-l ho o h ovl. Alhoh o-o bl h hv ohk h owh, hv hh d o h o owh o hh.32 Gv l oo, hv- o pbl o o wo xpphp o o h l d xll.1,32Shv o, olll, p-doolll, d o.1

Waxing ov h h. Whl o xpv h plk, owh low-, o ov wk. I pl d hl b, o, olll, -, d pofoy dypo.1

Chemical depilatories, lly holyol-l d ppo, xpv, p-l, d y o . Howv, h lh do o ho do b hh h oly ovd h lvl o hk .1 Thy lo d-.1

Bleaching wh hydo poxd x-pv d of dk l h,b lo k doloo d -

o.1

shavig

i o

a prrrd

opio or mo

wom, xp

or h lg

ad axilla


8/11



c- h Electrolysis o l pdo h owh.1,32 A dl pld o h h olll d ll ppld. Eh olll d -dvdlly.1,32 B l o dkh p wh lh k, b b d o ll k yp d h olo.1,32

Eloly opo-dpd, dh US Food d D Ado(FDA) lo d loly h-q. I q lpl , d pl d yh, olll-, pdoolll, o, , dpofoy dypo.1,32 Sopo h po wx d plko h d h h by w h hh, k loly o dl.32

Laser treatment lh o wv-lh o d h h olll. Whl l- h ovl do o l oplo p h ovl, o -v h hv, wx, d loly,pod pl h do o p o 6oh; h hd wh lpl

.33,34

Th b o -

qd dpd o h l yp d o h o h p h olll.35

L y o h ovl o v-o wvlh d lo ld pld lh y. Th ho o y d-pd o h p k yp d h olo.Wo wh k d dk h dldd; lo-wvlh l p-d o dk o d k yp.

Adv o l h ovl -ld p, yh, b, dyp-o, d . L ool dv pv o z o o h . L-

h lo b kow o pdoxl h owh.1,33,34

drug tHerapies or Hirsutism

Aoh opo o h ovl p- wh h d hpy(table 3).1,12,15,20,31,32,3642 Svl -lyhv dd d o hd dl hv b pb-lhd.20,3638 Howv, h d ldby h hoy o p wh h-

, ll pl z, ld hodoloy,

table 2

Ha va h a h pa ff

metHod skin irritation,

dermatitis

olliculitis,

pseudoolliculitis

dyspigmentation scarring pain

bh +++ None None None None

d +++ + None None None

sh + +++ + a + a None

p + + + a + a +

w ++ +++ ++ a + a +++

e + +++ ++ ++ +++

l, h

None Rare b Rare b Rare b + c

aTypically ollows olliculitis.bRare i perormed by a trained practitioner; dyspigmentation and scarring are more likely in skin photoypes III-VI.cPain is usually only mild i perormed by a trained practitioner using a topical anesthetic and laser cooling device.

thE INFORMAtION IN thIs tABLE Is BAsED ON thE pERsONAL ExpERIENCE OF wILMA F. BERgFELD, MD.


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Hirsutism

d l o dh bw h yp oh.

Th d o ooly d o h- ol opv (o-lbl ) d

do d (o-lbl ). Topl -loh (Vq) FDA-ppovd oh b l ooly d. Il -z, GRH lo, d oh d oolly d (o-lbl) o h.

t fh Topl foh l h- by low h o h owh; do h by vbly hb ohdboxyl, zy l o howh.39,40 Sd howd h w-dly

pplo dd wd l h wo 24 wk o .39,40 T- b oo, h owhpdly o h p by 8wk do foh.39,40Wh wo hv b how o podb h blk wo.39 Adv ld ld b o, , p-doolll bb, o, d llo d.39,40 Ipovd oohv b d wh foh obd wh l h ovl.41

o Ol opv ooly d o-lbl o h o h.20 Olopv pp h o o l-z hoo d, h, h yho ov do, hby lv-l o x hoo-bd lobl d d- pl oo.1,20 Adldo podo lo lhly dd.20

Ol opv lly ob yh o d po. Cpo o do d hold bvodd.1

Fo h, ol opvhold b d h o low-dopo h ypoo (ovlbl h Ud S), dopo(, Y), o (, OhoT-Cyl), o dol (, M).1,20

Sd o ol opv ldb d, ol p, hd-h, lo o lbdo, hypo, d h po-

l k o vo hobobol.1,15,32,36

table 3

P ff f a f h

t fh (vq)Mild burning sensationAcne, pseudoolliculitis barbaeIrritant and allergic contact dermatitisEect reverses 8 weeks ater discontinuation

o (- )Breast tendernessIrregular periods and vaginal bleedingMood change, atigue, headacheHypertensionWeight gain

Abnormal liver unctionGastrointestinal upsetDecreased libidoVenous thromboembolism risk

s (a)Irregular periods and vaginal bleedingAbnormal liver unctionGastrointestinal upsetDecreased libidoBreast tenderness, irritability pre-periodPostural hypotensionHyperkalemiaFeminization o a male etus

c Irregular periods and vaginal bleedingWeight gainDecreased libidoFeminization o a male etusVenous thromboembolism risk

(p)HepatotoxicityGastrointestinal upsetDecreased libidoFeminization o a male etus

Pregnancy category X

HepatotoxictyFeminization o a male etusPregnancy category X

g- h Hot fushesOsteoporosisAtrophic vaginitisPregnancy category X

eforihi

ram ra

aial

hiruim by

lowig h

ra o hair

growh


10/11



a Svl do d d o-l-bl o h. Spironolactone (Aldo), op-

v hbo o h do po d5-lph d vy,20 b v h o h. Moohpywh poolo, who ol o-pv o oh lbl o o o-po, o odd b o ho pol o ll do oz dvlop l .20 Th, l-bl opo hold b d lo hldb wh do- hpy.

Th do o poolo o h

lly 100 o 200 dly.1,20 Hypk-l, poly, pol hypoo, -l , d lv bol oh pobl dv (table 3).Spoo-lo w od o b o ld, lhoh h h kow lv h.36

Cyproterone, do o vl-bl h Ud S,42 opvlyhb h do po d 5-lph-d vy.1,20,36 I b d o olyh 10 dy o h l yl (50-o 100- do) wh ol opvpll, o low do obd ol o-pv pll (D-35 Cd d hUd Kdo).1

Sd l o ho o ol o-pv d ld , ood h,k o vo hobobol, d d-d lbdo.1,15,36 Ipoly, wo ohldb , h h pol k ozo o l , o lbl o-po b d.15,36

Flutamide, vol do-, h how po h oh.20 Fld oodl o-pv hbo o do po bd-. I k o hpoox-y.1,15

Finasteride (Pop) 1 oly o-olly d h o h(o-lbl ). I hb yp II 5-lph-d o pp dhydooo lv-l.32 I k o ol d-b, dd lbdo, hpooxy, d

zo o l (py -

oy X), o lbl opo qd ll l o hldb , wh lldo1 (table 3). Dutasteride (Avod), yp I d II

5-lph-d hbo, h o bdd o h o h (p-y oy X).

i z Metformin (Gloph) d oh -l z l v h -do d h.20,38 Howv,o v d ovlo p wh polyy ovy ydo.38Gol p oo d -; l do o b dv

.1

g-h GRH lo opo oly olopv d do d l p wh v hyp-do.20 Thy pp o olz hoo d h yh oov do.1,20 Th d v ohly l jo, llywh o o o o-po pl-, GRH lo olvl o ll o opl lvl.1

Sd ld d ypoo op ld ho fh, ophv, d oopoo.1,15 Th doplly hb ovlo, d o do-olo d yolo do o h opo wo o hldb- y o h o. Howv, GRHlo o ppovd opvd py oy X.

oh Oh d wh do vy ldd d koozol.12 Cd(T) o v o h oh, d koozol (Nzol) o-d wh k o doolppo12 d hpooxy ddo olpl d o, v oh hp P450 zy y.

ACKNOWLEDGMENT: Many thanks to Rebecca Tung, MD, der-

matologic surgeon, Cleveland Clinic, for her advice on lasers.

svral drug

ar o

ud o-labl

o ra

hiruim


11/11


Hirsutism

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2. azzz r, Cmn e, Swy Me. Idiopathic hirsutism.

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4. Wmson K, gnn aJ, Johnson N, Msom Sr. The

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9. loncop C. Adrenal and gonadal androgen secretion in

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10. bnsn gD. Testis. In: Gardner DG, Shoback D, edi-

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ADDRESS: Wilma F. Bergfeld, MD, Dermatology and PlasticSurgery Institute, A61, Cleveland Clinic, 9500 Euclid Avenue,

Cleveland, OH 44195; e-mail [email protected].

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