1

ivane javaxiSvilis saxelobis Tbilisis saxelmwifo

universiteti medicinis fakulteti

meanoba – ginekologiis da reproduqtologiis departamenti

xelnaweris uflebiT

diana WanuyvaZe

korelaciebi hiperandrogenizmis klinikur

da hormonalur maxasiaTeblebs Soris

disertacia

warmodgenili medicinis doqtoris akademiuri xarisxis

mosapoveblad

samecniero xelmZRvaneli:

med. mec. doqtori. asoc. prof. jenara qristesaSvili

Tbilisi 2012

avtoris stili daculia

2

Sinaarsi

Sesavali ---------------------------------------------------------------------------------------- 5

aqtualoba ---------------------------------------------------------------------------------- 5

amocanebi ----------------------------------------------------------------------------------------------------- 8

mecnieruli siaxle ----------------------------------------------------------------------------------------- 8

praqtikuli Rirebuleba ----------------------------------------------------------------- 10

gamoqveynebuli Sromebis sia ------------------------------------------------------ 11

Tavi 1. literaturis mimoxilva ----------------------------------------- 12

1.1 androgenebis biosinTezi ----------------------------------------------------------------------- 13

1.2 hirsutizmi ------------------------------------------------------------------------------------------------ 18

1.3 seborea da akne ---------------------------------------------------------------------------------------- 20

1.4 hiperandrogenizmis meqanizmebi -------------------------------------------------------------- 21

1.5 androgenebis transportireba ---------------------------------------------------------------- 22

1.6 policistozuri sakvercxeebis sindromi ---------------------------------------------- 24

1.7 adrenogenitaluri sindromi ------------------------------------------------------------------ 30

1.8 hiperandrogenizmis sxva mizezebi -------------------------------------------------------- 32

1.9 idiopaTiuri hirsutizmi ------------------------------------------------------------------------- 33

1.10 hiperandrogenizmis eqstraovariuli faqtorebi -------------------------------- 33

1.11 hirsutizmis Sefaseba da diagnostika ----------------------------------------------- 36

112 hirsutizmis mkurnaloba ---------------------------------------------------------------------- 39

3

Tavi 2. kvlevis obieqti da meTodebi ------------------------------------------ 42

2.1 kvlevis obieqti ----------------------------------------------------------------------------------------- 42

2.2 kvlevis meTodebi ----------------------------------------------------------------------------------- 43

2.2.1 hormonebis raodenobrivi gansazRvra ------------------------------------------------- 43

2.2.2 hirsutuli ricxvis gansazRvra ----------------------------------------------------------- 44

2.2.3 Tavisufali androgenebis indeqsis gansazRvra ----------------------------- 44

2.2.4 Tavisufali da bioSeRwevadi testosteronis

gaangariSebis maTematikuri modelebi ------------------------------------------------------ 44

2.2.5 insulinrezistentobis indeqsis Homa-2 gansazRvra ------------------------- 44

2.2.6 policistozuri sakvercxeebis sindromis dadgenis

kriteriumebi ------------------------------------------------------------------------------------------------ 45

2.2.7 kvlevis ultrabgeriTi meTodi --------------------------------------------------------- 45

2.2.8 monacemebis statistikuri damuSaveba ----------------------------------------------- 45

Tavi 3. საკუთარი კvlevis Sedegebi -------------------------------------- 47

3.1. pacientebis klinikuri da hormonaluri maxasiaTeblebi ------------------ 47

3.2. pacientebSi hiperandrogenizmis klinikuri simptomebis

da androgenuli parametrebis korelaciebiD ------------------------------------------ 52

3.3. korelaciebi hiperandrogenizmis klinikur da

hormonul markerebs Soris qalebSi

policistozuri sakvercxeebis sindromiT,

adrenogenitaluri sindromis araklasikuri formiT

da hiperprolaqtinemiis sindromiT --------------------------------------------------------- 65

4

3.4.hiperandrogenizmis Sefasebis diagnostikuri meTodebis

SedarebiTi analizi axalgazrda qalebSi hirsutizmiT ------------------------ 70

თავი 4. miRebuli Sedegebis ganxilva -------------------------------------- 73

Tavi 5. daskvnebi ----------------------------------------------------------------------- 86

Tavi 6. praqtikuli rekomendaciebi ---------------------------------------- 88

Tavi 7. gamoyenebuli literatura ---------------------------------------- 94

danarTi ------------------------------------------------------------------------------------ 107

5

Semoklebebi

ags – adreno-genitaluri sindromi

kok- kombinirebuli oraluri kontraceptivi

smi – sxeulis masis indeqsi

w.g/T.g. - welis garSemowerilobis da TeZos

garSemowerilobis Tanafardoba

17α-OHP - 17α - hidroqsiprogesteroni

cBio-T - gaangariSebuli bioSeRwevadi testosteroni

cFT - gaangariSebuli Tavisufali testosteroni

DHEA-S - dehidroepiandrosteron- sulfati

E2 – estradioli

FAI - Tavisufali androgenebis indeqsi

FSH - folikulmastimulirebeli hormoni

FT - Tavisufali testosteroni

Homa-IR - insulinrezistentobis indeqsi

LH - maluTeinizirebeli hormoni

Prl – prolaqtini

SHBG - seqssteroidSemboWveli globulini

TSH – Tireomastimulirebeli hormoni

TT – saerTo testosteroni

6

Sesavali

Temis aqtualoba:

hiperandrogenizmi Tanamedrove endokrinologiuri ginekologiis

mniSvnelovan problemas warmoadgens. hiperandrogenizmi warmoadgens

qalebSi iseTi garegani paTologiuri simptomebis arsebobas, rogoric aris

hirsutizmi, akne, seborea, alopecia da virilizacia. hiperandrogenizmis

uxSires mizezs (40-80%) hiperandrogenia warmoadgens [22,85,129].

literaturuli monacemebiT hiperandrogenia aReniSneba reproduqciuli

asakis qalTa 7-10% [19,54,92].Ahiperandrogenizmis mizezTa Soris ganixileba

aseve sisxlSi sasqeso steroidebis SemboWveli globulinis koncentraciis

daqveiTeba, ris Sedegadac matulobs Tavisufali androgenebis done [15,22].

sakmaod xSiria hiperandrogenizmis is forma, romelic viTardeba kanSi

ferment 5α-reduqtazas aqtivobis momatebis fonze, sisxlSi androgenebis

normaluri Semcvelobisas. Ahiperandrogenizmis am ukanasknel variants

idiopaTiur an konstituciur formad ganixilaven [21,29,35].

mizezebisMdamoukideblad, pacientebis mier TviT hiperandrogenizmi sakmaod

mwvaved aRiqmeba, Ffsiqologiuri stresis mizezi xdeba da xels uSlis

sazogadoebaSi integrirebas. amdenad, hiperandrogenizmi warmoadgens metad

mniSvnelovan, aqtualur ara mxolod samedicino, aramed socialur

problemasac.

hiperandrogenizmis mizezebia: policistozuri sakvercxeebis sindromi,

hiperandrogenuli insulin-rezistentuli acanthosis nigricans sindromi,

Tirkmelzeda jirkvlebis Tandayolili hiperplazia (klasikuri da

araklasikuri forma), kuSingis sindromi, androgenmaproducirebeli

simsivneebi (sakvercxis, Tirkmelzeda jirkvlis), hiperprolaqtinemiis

sindromi [25,31]. hiperandrogenizmis klinikuri gamovlinebebis SemTxvevaTa

5-15% aris idiopaTiuri [21]. am dros aRiniSneba mocirkulire androgenebis

normaluri donis mimarT Tmis folikulebis momatebuli mgrZnobeloba,

romlis mizezi aris 5-α reduqtazas aqtivobis mateba. aRniSnuli

paTologiebi sakmaod farTod aris Seswavlili, Tumca jer kidev rCeba

7

rigi sakiTxebisa, romelTa kvleva mniSvnelovania hiperandrogenizmis

sxvadasxva formebis paTogenezuri meqanizmebis dasazusteblad.

bolo periodSi gansakuTrebul yuradRebas imsaxurebs iseTi tipis

hiperandrogenia, romelic ukavSirdeba simsuqnes da insulinrezistentobas.

kerZod dadgenilia, rom arsebobs urTierTkavSiri hiperinsulinemias da

hiperandrogenias Soris da am ori tipis darRvevis Tanaarseboba qmnis

mankier wres. naklebad aris Seswavlili kavSirebi RviZlis funqciis

gaTvaliswinebiT, zusti korelaciebi sisxlSi seqssteroidSemboWveli

globulinis, saerTo da Tavisufali testosteronis koncentraciebs Soris

daAmsgavsi kavSirebi pacientebSi policistozuri sakvercxeebis sindromiT

an mis gareSe.E aseve xazgasasmelia is faqti, rom simsuqne da

insulinrezistentoba xSirad pacientebis mier ar aRiqmeba saTanadod,

rogorc mZime metaboluri darRveva, maT Soris, Saqriani diabetis tipi II-is

ganviTarebis risk-faqtori. amdenad, es pacientebi jamrTelobis dazianebis

seriozuli riskis qveS imyofebian. aseve, sayuradReboa is faqtic, rom

insulinrezistentoba SeiZleba aRiniSnebodes pacientebSi gamoxatuli

Warbi wonis gareSe cximis Warbi gadanawilebiT, rac miTumetes yuradRebis

gareSe rCeba. cnobilia, rom sisxlSi mocirkulire testosteronis

ZiriTadi nawili 80% SeboWilia seqssteroidSemboWvel globulinTan, 19%

- albuminTan da mxolod 1% cirkulirebs Tavisufal mdgomareobaSi.

seqssteroidSemboWveli globuliniT SeboWili steroidebi Znelad

misaRwevia samizne qsovilebSi SesakavSireblad da samoqmedod. samizne

ujredebSi biologiur efeqts axdens sasqeso hormonebis Tavisufali da

albuminTan SekavSirebuli fraqciebi. amdenad, androgenuli efeqti

korelirebs seqssteroidSemboWveli globulinis donesTan. mozrdil

qalebSi seqssteroidSemboWveli globulinis koncentracia 2-jer maRalia,

vidre mamakacebSi. es sqesobrivi gansxvaveba imiT aixsneba, rom estrogenebi

astimulireben, xolo androgenebi Trgunaven seqssteroidSemboWveli

globulinis produqcias [15,49,78]. am nivTierebis done sisxlSi iTvleba

androgenebsa da estrogenebs Soris biologiur makontrolirebel

faqtorad. seqssteroidSemboWveli globulini aris Sratismieri

glikoproteini, romelic warmoiqmneba RviZlSi. misi sinTezi da gamoyofa

8

regulirdeba garda sasqeso steroidebisa rigi sxva faqtorebiTac,

romelTagan zogierTi (Tireoiduli hormonebi, stresi, naxSirwylebis

maRali koncentracia) zrdis, xolo zogierTi (gacximovneba, insulini,

prolaqtini, zrdis hormoni, progesteroni, glukokortikoidebi) amcirebs

mis dones [6].

ginekologebis da reproduqtologebis mier xSir SemTxvevaSi ar eqceva

saTanado yuradReba hiperandrogenizmis mizezebis dazustebas da aseT

pacientebs Tavazoben ara eTiopaTigenezur, aramed simptomur mkurnalobas

antiandrogenebiT, rac dinamikaSi iwvevs arsebuli metaboluri darRvevebis

gaRrmavebas.

Tavisufali testosteroni yvelaze gavrcelebuli diagnostikuri markeria

qalebSi hiperandrogenemiiT, magram misi gansazRvra rutinulad yvela

laboratoriaSi ver xorcieldeba. Tavisufali testosteronis gansazRvris

“oqros standartia” wonasworobis dializis meTodi da amoniumiT

precipitacia. Tumca es meTodebi aris Zalian Sromatevadi,

ZviradRirebuli da moiTxovs maRal teqnikur kvalifikacias. axlaxans

Seqmnilia Tavisufali testosteronis gaangariSebis modelebi saerTo

testosteronis, seqssteroidSemboWveli globulinis da albuminis

maCveneblebis meSveobiT [151,153]. miuxedeavad SezRuduli korelaciebisa

yvela endokrinul parametrs da Tmianobis xarisxs Soris (aRwerili

feriman-galveis sqemis mixedviT) gaangariSebuli Tavisufali

testosteroni, biologiurad aqtiuri testosteroni da Tavisufali

androgenizaciis indeqsi SesaZloa iyos ufro adekvaturi markerebi

hiperandrogeniis Sesafaseblad qalebSi hirsutizmiT, vidre mxolod

androgenebis donis gansazRvra [106,109]. garda amisa, Tavisufali

testosteronis maCveneblis gansazRvra ar iZleva saSualebas dadgindes,

riT aris ganpirobebuli am maCveneblis mateba testosteronis sekreciis

matebiT Tu Tavisufali biologiurad aqtiuri fraqciis zrdiT

seqssteroidSemboWveli globulinis daqveiTebis fonze. amgvarad, mxolod

Tavisufali testosteronis maCveneblis gansazRvra ar iZleva

hiperandrogenizmis ganviTarebis meqanizmebis dadgenis saSualebas.

dReisaTvis metad aqtualuria hiperandrogenizmis klinikuri

9

gamovlinebebis Sesafaseblad ufro maRal informatiuli, uaxlesi

markerebis gamoyeneba adeqvaturi samkurnalo taqtikis SesamuSaveblad.

zemoT Tqmulidan gamomdinare kvlevis mizans warmoadgenda:

korelaciebis dadgena hiperandrogenizmis klinikur da hormonalur

maCveneblebs Soris axalgazrda qalebSi hiperandrogenizmiT gamovlenili

sxvadasxva endokrinul–ginekologiuri sindromebiT.

kvlevis amocanebi:

1. gaangariSebuli androgenuli parametrebis – Tavisufali

androgenebis indeqsis, gaangariSebuli Tavisufali da bioSeRwevadi

testosteronis da seqssteroidSemboWveli globulinis maCveneblebis

gansazRvris mniSvnelobis dadgena hiperandrogenizmis klinikuri

maxasiaTeblebis ganviTarebis meqanizmebis Sesafaseblad pacientebSi

sxvadasxva ginekologiur–endokrinuli sindromebiT (policistozuri

sakvercxeebis sindromi, adreno-genitaluri sindromis araklasikuri

forma, hiperprolaqtinemiis sindromi).

2. korelaciebis gamovlena hiperandrogenizmis klinikur gamovlinebebsa

da hormonul–androgenul maCveneblebs Soris axalgazrda qalebSi

etiopaTogenezurad gansxvavebuli sindromebiT.

3. visceraluri simsuqnis kavSiris dadgena hiperandrogenizmis

hormonul maCveneblebTan.

4. gaangariSebuli androgenuli parametrebis da imunofermentuli

meTodiT gansazRvruli Tavisufali testosteronis maCveneblebis

SesaZleblobis dadgena hiperandrogenizmis klinikuri simptomebis

SefasebaSi da hiperandrogenizmis meqanizmebis ganviTarebaSi.

10

naSromis mecnieruli siaxle:

pirvelad dadgenil iqna, rom gaangariSebuli androgenuli parametrebi –

Tavisufali androgenebis indeqsi, gaangariSebuli Tavisufali da

bioSeRwevadi testosteroni warmoadgens ufro adekvatur alternatiul

markerebs imunofermentuli meTodiT gansazRvrul Tavisufal

testosteronTan SedarebiT hiperandrogenizmis klinikuri maxasiaTeblebis

ganviTarebis meqanizmebis Sesafaseblad pacientebSi sxvadasxva

ginekologiur–endokrinuli sindromebiT (policistozuri sakvercxeebis

sindromi, adrenogenitaluri sindromis araklasikuri forma,

hiperprolaqtinemiis sindromi).

dadgenil iqna, rom gaangariSebuli androgenuli parameterebis

maCveneblebi da seqssteroidSemboWveli globulinis koncentracia ar

korelirebs hirsutizmis xarisxTan, rac SeiZleba ganpirobebuli iyos imiT,

rom hirsutizmis xarisxi damokidebulia ara mxolod androgenebis

koncentraciaze sisxlis SratSi, aramed Tmis folikulebis

mgrZnobelobaze androgenebis mimarT.

visceraluri simsuqnis mqone pacientebSi hirsutizmiT gamovlinda

gaangariSebuli androgenuli parameterebis statistikurad sarwmunod

maRali da seqssteroidSemboWveli globulinis koncentraciis

statistikurad sarwmunod dabali maCveneblebi im pacientebTan SedarebiT,

romelTac aReniSnebodaT ginoiduri simsuqne msgavsi xarisxis hirsutizmiT.

es albaT ukavSirdeba Homa-IR indeqsis ufro maRal maCvenebels

pacientebSi visceraluri simsuqniT da am fonze testosteronis

biologiurad aqtiuri fraqciis matebas.

gansxvavebiT sxva formebisagan, hirsutizmis mZime xarisxis SemTxvevebSi

gamovlinda gaangariSebuli Tavisufali testosteronis ufro mZlavri

diagnostikuri mniSvneloba imunofermentuli ELISA-meTodiT gansazRvruli

Tavisufali testosteronis maCvenebelTan SedarebiT.

dadginda, rom gaangariSebuli androgenuli parameterebis maCveneblebi da

11

naSromis praqtikuli Rirebuleba:

praqtikuli TvalsazrisiT metad mniSvnelovania kvleviT miRebuli

Sedegebi imis Sesaxeb, rom hiperandrogenizmis ganviTarebis meqanizmebis

dadgenisTvis mizanSewonilia gaangariSebuli androgenuli parameterebis,

rogoric aris gaangariSebuli Tavisufali testosteroni, bioSeRwevadi

testosteroni, seqssteroidSemboWveli globulinis maCveneblebis da

Tavisufali androgenebis indeqsis gansazRvra.

aseve metad mniSvnelovania praqtikuli TvalsazrisiT im faqtis dadgena,

rom axalgazrda qalebSi hirsutizmiT gaangariSebuli Tavisufali

testosteroni, bioSeRwevadi testosteroni, seqssteroidSemboWveli

globulini da Tavisufali androgenebis indeqsi ufro adekvaturi

alternatiuli markerebia hiperandrogenizmis Sesafaseblad, vidre mxolod

imunofermentuli ELISA-meTodiT gansazRvruli Tavisufali testosteronis

maCvenebeli.

12

gamoqveynebuli Sromebis sia

1. Correlation of biochemical markers and clinical signs of hyperandrogenism in

women with Polycistic Ovary Syndrome (PCOS) and women with Non-classic

Congenital Adrenal Hyperplasia (NCAH). Iranian Journal of Reproductive

Medicine Vol. 10. N 4. July 2012.

2. Influence of abdominal obesity on the calculated androgen parameters in the

young women with different syndromes in Georgia // Proceedings Book of the

XV World Congress of Gynecological Endocrinology ―Gynecological

Endocrinology 2012‖. Firenze, March7-10; 2012.p.129-130.

3. hirsutizmi (literaturis mimoxilva). reproduqtologia 1

(40), 2011, gv. 30-34.

4. Effectivness of different diagnostic methods for assessment of

hyperandrogenism in young women with hirsutism. Georgian Medical News, N

12, 2011. P. 25-30.

5. Корреляции между клиническими и гормональными показателями у

девушек с гирсутизмом. Georgian Medical News, N 12, 2011, с. 30-35.

naSromis aprobacia

naSromis fragmentebis aprobacia ganxorcielda Tsu medicinis

fakultetis koloqviumebze (2011wl) da saerTaSoriso

samedicino konferenciaze “reproduqciuli medicinis

aqtualuri problemebi” 26.11.2011 wl. Tbilisi.

13

თავი 1

ლიტერატურის მიმოხილვა

hiperandrogenizmi – qalebSi androgenebiT ganpirobebuli garegani

paTologiuri simptomebia: hirsutizmi, akne, seborea, alopecia da

virilizacia. hiperandrogenizmi ZiriTadad viTardeba sakvercxismieri an

Tirkmelzeda jirkvlebis androgenebis Warbi sekreciis Sedegad, rac

hiperandrogeniis terminiT aris cnobili. hiperandrogenizmis ganviTarebis

mTavar mizezs hiperandrogenia warmoadgens, Tumca SesaZloa androgenebis

done iyos normis farglebSi. hiperandrogenia Tanamedrove endokrinuli

ginekologiis mniSvnelovani problemaa. is reproduqciuli asakis qalebSi

reproduqciuli da menstruaciuli funqciis darRvevis (oligomenorea,

anovulacia, uSviloba) erT-erTi yvelaze xSiri mizezia. literaturis

monacemebiT hiperandrogenia vlindeba reproduqciuli asakis qalTa

daaxloebiT 7%-Si [19,54,92]. hiperandrogenemiis klinikur gamovlinebebs

pirvelad hipokratem miaqcia yuradReba. man aRwera ori qali kunZul

kosidan, romlebsac, gaezardaT wverebi. Sua saukuneebSi viliam keisma

(1520-1550 wl.) daxata qali wver-ulvaSiT. hiperandrogenizmis fenomenis

mecnieruli Seswavla me-XΙX saukuneSi daiwyo. 1866 w. moxsenebuli iyo

„mamrobiTi“ sqesis gvamis gakveTis angariSi, sinamdvileSi is aRmoCnda qali

mZime virilizaciiT da Tirkmelzeda jirkvlebis hiperplaziiT. 1935 w.

Steinma da leventalma aRweres sakvercxeebis policistozis sindromi.

Sroma exeboda sakvercxeebis policistozis kliniko-morfologiur

Taviseburebebs. maT mier gamoiTqva mosazreba, rom sakvercxeebis

policistozi aris hormonuli zemoqmedebis Sedegi [140]. hiperandrogeniis

mizezebia: policistozuri sakvercxeebis sindromi, hiperandrogenuli

insulin-rezistentuli acanthosis nigricans sindromi, adrenogenitaluri

sindromi (klasikuri da araklasikuri forma), kuSingis sindromi,

androgenmaproducirebeli simsivneebi (sakvercxis, Tirkmelzeda jirkvlis),

14

hiperprolaqtinemiis sindromi [25,31]. hiperandrogenizmis klinikuri

gamovlinebebis SemTxvevaTa 5-15 % aris idiopaTiuri. am dros aRiniSneba

mocirkulire androgenebis normaluri donis mimarT Tmis folikulebis

momatebuli mgrZnobeloba da romlis mizezi aris 5-α reduqtazas

aqtivobis mateba [21,35,42,161].

1.1 androgenebis biosinTezi

androgenebi - mamakacis sasqeso hormonebia, romlebic qimiuri

struqturis mixedviT C19 - steroidebs miekuTvnebian. qalis organizmSi

ZiriTadad sinTezirdeba Semdegi androgenebi: dehidroepiandrosteroni,

dehidroepiandrosteron-sulfati, androstendioni, androstendioli,

testosteroni da dihidrotestosteroni. cnobilia, rom qalis organizmSi

androgenebi ZiriTadad gamomuSavdeba sakvercxeebSi, Tirkmelzeda

jirkvlebis badisebur SreSi da periferiul qsovilebSi.

testosteronis 25%-i gamomuSavdeba sakvercxeebSi, 25%-i Tirkmelzeda

jirkvlebis mier da daaxloebiT 50%-i warmoiqmneba periferiul

qsovilebSi androstendionis konversiis Sedegad. androstendionis

sekreciis naxevari xdeba sakvercxeebSi, xolo meore naxevri Tirkmelzeda

jirkvlebSi [138]. qalis organizmis fiziologiaSi androstendioni

TamaSobs mniSvnelovan rols, rogorc testosteronis an estronis

prehormoni periferiul qsovilebSi.

Tirkmelzeda jirkvlebSi sinTezirdeba dehidroepiandrosteroni

(90%) da dehidroepiandrosteron – sulfati (100%) [99]. (ix.sur.1)

15

sur. 1

androgenebis dReRamuri sekrecia sakvercxeebis da Tirkmelzeda

jirkvlebis mier (Speroff L., Glass R.H., Kase N.G. Clinical Gynecologic Endocrinology and

Infertility. 5th ed., Williams & Wilkins, 1994; 487)

16

androgenebis steroidogenezi sakvercxeebSi da Tirkmelzeda jirkvlebSi

msgavsi biosinTezuri gzebiT mimdinareobs. androgenebis sawyisi

substrati - qolesterinia. misi androgenad gardaqmna xdeba ujredis

sxvadasxva warmonaqmnSi: mitoqondriebSi, mikrosomebSi, endoplazmur

badeSi da citozolSi rigi fermentebis zemoqmedebiT. pirvel etapze

Tanmimdevruli reaqciebis Sedegad xdeba pregnenolonis warmoqmna,

romelsac ar axasiaTebs biologiuri aqtivoba. pregnenolonidan

androgenebis warmoqmna xdeba ori gziT - Δ 5 da Δ 4. Δ 5 gziT pregnenoloni

17α-hidroqsilazis zemoqmedebiT gardaiqmneba 17α-pregnenolonad da

Semdgom 17,20-liazebis aqtivobiT transformirdeba

dehidroepiandrosteronad, romlisgan Tavis mxriv warmoiqmneba

epiandrostendioni da testosteroni. Δ 4-gziT androgenebis sinTezisas

pregnenoloni 3β-oldehidrogenazas zemoqmedebiT gardaiqmneba

progesteronad. progesteroni - pirveli bioaqtiuri hormonia

steroidogenezis jaWvSi. is 17αα–hidroqsilazis meSveobiT gardaiqmneba

17α-oqsiprogesteronad, romelic Semdgom aseve testosteronad da

androstendionad gardaiqmneba. androgenebis biosinTezis erTi gzidan

meore gzaze gadasvla SesaZlebelia nebismieri Sualeduri produqtis

doneze anu xdeba e.w. Δ5 da Δ4 gzebis Suntireba. androgenebis

biosinTezis orive gza warmoebs, rogorc sakvercxeebSi, ise Tirkmelzeda

jirkvlebSi, magram Δ5 gza upiratesad Tirkmelzeda jirkvlebSi, xolo

Δ4 gza - sakvercxeebSi mimdinareobs [138].

17

androgenebis biosinTezis sqema (cvlilebebiT ) Speroff L., Glass R.H., Kase N.G. Clinical

Gynecologic Endocrinology and Infertility. 5th ed., Williams & Wilkins, 1994; 333)

aRsaniSnavia, rom qalebSi androgenebis warmoqmnis ZiriTadi gzaa -

testosteronis periferiuli sinTezi. swored periferiaze - kanSi,

cximovan qsovilSi, RviZlSi da kunTebSi xdeba androstendionis

gardaqmna testosteronad. amas amtkicebs is faqti, rom saerTo

testosteronis ≈50% warmoiqmneba kanSi, gansakuTrebiT cximovan

jirkvlebSi da Tmis folikulebSi [121].

18

Semdgom etapze testosteroni SesaZlebelia „gaaqtiurdes“ da

5α-reduqtazas meSveobiT gardaiqmnas 5α–dihidrotestosteronad

(5α –DHT) an „inaqtivirdes“ anu aromatazas zemoqmedebiT gardaiqmnas

estrogenad [65].

5 α - reduqtaza - enzimia, romelic awarmoebs testosteronis konversias

5α-DHT -ad. testosteronis konversia 5α–DHT-ad zrdis androgenul efeqts

2 meqanizmiT: 1) 5α–DHT – testosteronisgan gansxvavebiT, ver aromatizirdeba

estrogenad da amgvarad misi efeqti absoluturad androgenulia da

2) in vitro 5α–DHT ukavSirdeba androgenul receptorebs ufro Zlierad vidre

testosteroni da 5α–DHT/androgenis receptoris kompleqsi ufro

stabiluria [14]. bolo oci wlis ganmovlobaSi molekuluri kvlevebiT

gamoiyo 5α- reduqtazas ori izoenzimi: tipi 1 da tipi 2 lokalizebuli

sxvadasxva qromosomebze. maT axasiTebT sxvadasxvagvari bioqimiuri

Tvisebebi da qsovilebSi gadanawileba [17]. 5α-reduqtazas orive izoenzimis

aqtiuroba farTod gavrcelebulia mTel sxeulze, Tumca Tanamedrove

kvlevebiT dadginda, rom tipi 2 izoenzimi dominirebs saTesleebSi,

winamdebare jirkvalSi, wver-ulvaSis da genitaluri Tmebis folikulebSi

[144]. zogierTi mklevari aRniSnavs, rom Tavis Tmis folikulebSi

mxolod tipi 2 5α-reduqtazaa, xolo tipi 1 da tipi 2 warmodgenilia

adamianis cximovan jirkvlebSi [29]. 5α –DHT - metabolizdeba naklebad

potentur androgenebad: 3-α da 3β-androstendionad,

3-α და 3-β-glukuronidebad. es reaqcia katalizdeba kanSi enzim

3α-hidroqsisteroid dehidrogenazas (3α–HSD) aqedan gamomdinare, es enzimi

SesaZloa iyos DHT-is donis mniSvnelovani regulatori [115]. zogierTi

kvleviT hirsutizmis dros 3α-androstendiol glukuronidis done

mniSvnelovanad momatebulia da warmoadgens testosteronis periferiuli

metabolizmis Sesafasebel kriteriums [65].

19

1.2 hirsutizmi

hiperandrogenizmis erT-erTi xSiri klinikuri gamovlinebaa - hirsutizmi

anu paTologiuri Tmianoba. R.Azziz da Tanaavtorebis mier Catarebul

kvlevaSi, romelSic monawileobda 800 qali hiperandrogeniiT, hirsutizmi

gamouvlinda 75%-s, romelTa Soris 4%-s aReniSneboda Tmis cvena, xolo

4,8%-s akne [22].

qalebSi arsebobs paTologiuri Tmianobis ori forma - hirsutizmi da

hipertriqozi.

hipertriqozi - androgendamoukidebeli memkvidruli faqtorebiT

ganpirobebuli Warbi gaTmianebaa qalebisTvis damaxasiaTebel adgilebSi.

aseT SemTxvevaSi Tmis sigrZe da sisqe matulobs. izolirebuli

hipertriqozi ar warmoadgens hiperandrogeniis simptoms Tumca, SesaZloa

misi arseboba hirsutizmTan erTad hiperandrogeniis dros [129].

hirsutizmi - paTologiuri Tmianobaa (terminaluri Tma) mamakacisaTvis

damaxasiaTebel adgilebSi (zeda tuCze, nikapze, mkerdze, mucelze, welze)

da aReniSneba qalebis 5 – 10 %-s [22,85]. hirsutizmi ar aris daavadeba.

is endokrinologiur ginekologiaSi yvelaze xSiri simptomia, radganac

xSirad Tan axlavs iseT paTologiebs rogoricaa: policistozuri

sakvercxeebis sindromi, insulinrezistentuli metaboluri sindromi,

adrenogenitaluri sindromi, hiperprolaqtinemiis sindromi,

androgenmaproducirebeli simsivneebi da a.S [3].

Baron-is mier 15-19 wlis hirsutizmis mqone gogonebSi Catarebuli kvleviT

gamovlinda,rom hirsutizmis mizezi SemTxvevaTa 72,4%–Si aris sakvercxeebis

policistozi, 24,1%–Si – adrenogenitaluri sindromis araklasikuri

(gvian gamovlenili) forma da 3,4%-Si aris adrenogenitaluri sindromis

klasikuri forma [27].

Moran da Tanaavtorebis kvlevis Tanaxmad, 13-38 wlamde asakobriv jgufSi

hirsutizmis mizezi SemTxvevaTa 53%-Si sakvercxeebis policistozi, 18%-Si -

simsuqne, 2%-Si – adrenogenitaluri sindromis postpubertatuli forma,

20

0,8%-Si - sakvercxeebis simsivne da 0,4%-Si - kuSingis sindromi an

specifiuri medikamentebis miReba iyo [104].

qalebSi, garda samedicino problemisa, hirsutizmi iwvevs stress,

aqveiTebs cxovrebis xarisxs da fsiqoemociur ganviTarebas [125].

sxvadasxva avtorebi aRniSnaven, rom hirsutizmi azielebSi SedarebiT

iSviaTia, Tundac saxeze iyos metaboluri da endokrinuli darRvevebi

[18,38,63]. magaliTad, iaponel qalebs dadasturebuli hiperandrogeniiT

naklebad aReniSnebaT androgenizaciis movlenebi, vidre CrdiloeT amerikis

an italiel qalebs hiperandrogeniis igive xarisxiT [38,51]. nebismieri

Savgremani, SavTmiani qalebi ufro midrekili aris hirsutizmisken, vidre

TeTrkaniani qera qalebi [28].

50 milionamde Tmis folikuli faravs mTel sxeuls. maTgan 100,000- dan

150,000-de Tavzea, xolo danarCeni folikulebi saxeze da sxeulis sxva

nawilebzea. Tmis folikulebi ar aris mxolod fexis, xelis gulebze da

tuCebze. Tmis folikulebis umravlesoba viTardeba mucladyofnisas

gestaciis me-9-12 kvireebs Soris, xolo Tmis zrda iwyeba me-16-20 kviraze.

dabadebis Semdeg viTardeba SedarebiT mcire axali Tmis folikulebi da

maTi raodenoba qveiTdeba 40 wlis Semdeg. Tmis zrda moicavs

ganviTarebis 3 fazas. pirveli fazis (anageni) ganmavlobaSi Tmis Rero

aqtiurad izrdeba. anagenis fazis xangrZlivoba ZiriTadad damokidebulia

individualuri Tmis srul sigrZeze. meore fazaSi (katageni) Tmis zrda

wydeba, Tmis folikuli gadadis e.w. „mZinare mdgomareobaSi“. Tmis bolqvi

TandaTanobiT wydeba dvrils. katagenis faza Zalian xanmoklea daaxloebiT

3-4 kvira. mesame (telogeni) fazaSi Zveli Tma cviva da axali iwyebs

zrdas. am drois ganmavlobaSi Tmis folikulSi ujredebis ganaxleba

Sewyvetilia (daaxloebiT 3 Tve). axalad sinTezirebuli Tmis folikuli

uerTdeba Tmis dvrils da axali Tma Sedis anagenis fazaSi. TiToeul Tmas

aqvs cxovrebis „individualuri gegma“. amitomac sxvadasxva Tma erTsa da

imave dros aris ganviTarebis ciklis sxvadasxva stadiaSi, kerZod: 85% -

aqtiuri zrdis fazaSi (anagenSi), 1% - mosvenebis fazaSi (katagenSi), 14%-

cvenis fazaSi (telogenSi) [21]. struqturulad gamoyofilia Tmis 3 saxeoba:

21

Canasaxovani RinRli, RinRli da terminaluri Tma. Canasaxovani RinRli

rbili, arapingmentirebuli Tmaa, romelic faravs nayofis da axalSobilis

kans. RinRlic, aseve rbili da arapigmentirebuli Tmaa, xolo terminaluri

Tma - uxeSi, grZeli da pigmentirebulia. misgan Sedgeba Tavis Tma, warbebi,

wamwamebi, boqvenis da iRliis fosos Tmebi orive sqesis warmomadgenlebSi,

xolo mamakacebSi is ganviTarebulia aseve sxeulze da saxeze.

1.3 seborea da akne

mTel rig avtorTa monacemebiT [56,66] seborea da acne vulgaris

ganpirobebulia Tirkmelzeda jirkvlismieri hiperandrogeniiT -

dehidroepiandrosteron da dehidroepiandrosteron-sulfatis sekreciis

momatebiT. am hormonebs gaaCniaT tropizmi kanis cximovani jirkvlebis

mimarT da amdenad, maTi hipersekrecia ganapirobebs kanis cximovan

jirkvlebSi cximis Warb warmoebas [113,145]. seboreazea dafuZvnebuli aknes

ganviTareba, romelic multifaqtoruli hormondamokidebuli paTologiaa,

romelic warmoadgens cximovani jirkvlebis gamomtani sadinrebis

hiperkeratozis da cximis Segubebis Sedegad formirebul komedons. aknes

korinobaqteriis zemoqmedebiT viTardeba perifokaluri aseptiuri anTeba.

gamomdinare iqidan, rom DHEA-S da DHEA umTvresad gamomuSavdeba

Tirkmelzeda jirkvalSi akne da seborea Tirkmelzeda jirkvlismieri

hiperandrogeniis klinikur markerad iTvleba. Tumca, zogierTi avtoris

mier aRniSnulia, rom am simptomebis gamovlinebaze pasuxismgebelia

testosteronic.

avtorTa sxva jgufi aRniSnavs, rom aknes verifikacia hiperandrogenizmis

dros ar aris specifiuri simptomi, radganac is mozardebis 50%-s

aReniSneba da xSirad mxolod kosmetikuri problemaa. amavdroulad,

policistozuri sakvercxeebis sindromis diagnoziT pacientTaA 45%-s

aReniSneboda akne. Ees faqti miuTiTebs, rom hiperandrogenizmis dasadgenad

akne mniSvnelovani simptomia, magram gasaTvaliswinebelia aknes

ganviTarebis asaki da ganviTarebis paTogenezi [11].

22

1.4 hiperandrogenezmis meqanizmebi

Tmis tipis da sxeulze ganawilebis gansazRvraSi androgenebi mTavar

rols TamaSobs. androgenebis zemoqmedebiT: Zlierdeba epidermisis

ujredebis mitozuri aqtivoba da diferencireba, matulobs ujredSorisi

lipidebis sinTezi, izrdeba epidermaluri Sris sisqe, xdeba Tmis zrdis da

pigmentaciis stimulacia, matulobs kanis cximianoba da qveiTdeba

seqssteroidSemboWveli globulinis (ssSg) sinTezi RviZlSi. avtorebi

Tvlian, rom testosteronis gansazRvra adekvaturad asaxavs qalis

organizmSi sasqeso da Tirkmelzeda jirkvlebis androgenul funqcias,

androgenizaciis xarisxs, magram ar gvaZlevs saSualebas vimsjeloT

androgenebis wyaroze da mis mimarT samizne ujredebis mgrZnobelobaze

[53,115]. Tavisufali testosteroni yvelaze gavrcelebuli diagnostikuri

markeria qalebSi hiperandrogeniiT, magram misi gansazRvra rutinulad

yvela laboratoriaSi ara ganxorcielebadia. Tavisufali testosteronis

gansazRvris “oqros standartia” wonasworobis dializis meTodi da

amoniumiT precipitacia. Tumca es meTodebi aris Zalian Sromatevadi,

ZviradRirebuli da moiTxovs maRal teqnikur kvalifikacias. axlaxans

Seqmnilia Tavisufali testosteronis gaangariSebis modelebi saerTo

testosteronis, seqssteroidSemboWveli globulinis da albuminis

maCveneblebis meSveobiT [109]. Tavisufali testosteronis gamoTvla

SesaZlebelia veb–saitze http://www.issam.ch/freetesto.htm A.Vermeulen at al.

monacemebiT am programiT miRebuli Tavisufali da bioSeRwevadi

testosteronis monacemebi dadebiTad korelirebda wonasworobis dializis

da mas–speqtrometriiT miRebul monacemebTan [153]. miuxedeavad SezRuduli

korelaciebisa yvela endokrinul parametrsa da Tmianobis xarisxs Soris

(aRwerili feriman-galveis sqemis mixedviT) gaangariSebuli Tavisufali

testosteroni, bioSeRwevadi testosteroni da Tavisufali

androgenizaciis indeqsi SesaZloa iyvnen ufro adekvaturi markerebi

hiperandrogeniis Sesafaseblad qalebSi hirsutizmiT, vidre mxolod

androgenebis gansazRvra [108]. Tirkmelzeda jirkvlebis da sakvercxeebis

saerTo embriologiuri warmoSoba, steroidogenezSi analogiuri

fermentebis monawileoba da Tirkmelzeda jirkvlis paTologiis dros

23

sakvercxeebis paTologiur procesSi meoradad CarTvis SesaZlebloba,

arTulebs androgenebis hipersekreciis wyaros dadgenas. dReisaTvis

dadasturebulia genetikuri kavSiri Tirkmelzeda jirkvalsa da sakvercxes

Soris. dadgenilia orive jirkvalSi androgenebis biosinTezis

garkveulwilad identuri mimdinareoba zogierTi analogiuri fermentis

monawileobiT. aqedan gamomdinare, Tirkmelzeda jirkvlis qerqis

funqciuri mdgomareobis cvlileba SeiZleba aisaxos sakvercxis funqciaze

da piriqiT [9,10].

aRwerilia oTxi saxis meqanizmi, romelic marTavs Sereuli, adreno-

ovariuli hiperandrogeniis ganviTarebas [8,10,128].

1) ferment - 3β-hidroqsisteroiddehidrogenazas aqtivobis daqveiTeba,

romelic gvxvdeba rogorc sakvercxeebSi, aseve Tirkmelzeda jirkvalSi;

2) Tirkmelzeda jirkvlis steroidogenezSi monawile fermentebis

aqtivobis daqveiTeba sakvercxismieri androgenebiT;

3) Tirkmelzeda jirkvlis androgenebis zemoqmedebiT sakvercxeebis

policistozis ganviTareba;

4) sakvercxeSi Tirkmelzeda jirkvlis hormonebis eqtopiuri sekrecia

maTSi Tirkmelzeda jirkvlis narCeni qsovilebis arsebobis gamo.

1.5 androgenebis transportireba

mocirkulire androgenebis didi nawili aris SeboWili plazmis

specifiuri proteinebiT, rogorebicaa: seqssteroidSemboWveli globulini,

kortizolSemboWveli globulini da albumini. testosteronis 80%

SeboWilia seqssteroidSemboWveli globuliniT (ssSg), 19% - albuminiT

da mxolod 1% cirkulirebs Tavisufal mdgomareobaSi [131]. hirsutizmis

dros Tavisufali testosteronis done xSirad momatebulia, maSin rodesac

saerTo testosteronis done SesaZlebelia iyos normis farglebSi [129].

hirsutizmian qalebSi es ganpirobebulia ssSg-is SedarebiT dabali doniT.

seqssteroidSemboWveli globulini (ssSg) warmoiqmneba RviZlSi [91,72] da

gamoiyofa sisxlSi. is warmodgens sasqeso steroidebis moqmedebis

modulators. ssSg-is koncentracia sisxlSi sasqeso hormonebis

24

fiziologiuri moqmedebis da samizne qsovilebSi maTi SeRwevis ZiriTadi

gadamwyveti faqtoria [134]. ssSg-s geni lokalizebulia me-17 qromosomis,

mokle mxris p12-p13 lokusze. ssSg-i pirvelad identificirebuli iyo,

rogorc β-globulini, romelic boWavs 17β-estradiols da testosterons

adamianis sisxlis plazmaSi [89,94,126,132,153]. janmrTel qalTa populaciaSi

ssSg-is dones axasiaTebs didi cvalebadoba, rac nawilobriv axsnilia

genetikuri foniT an TviT hormonis garemos da kvebis SecvliT [77,131].

aRsaniSnavia, rom qalebSi ssSg-s donis cvalebadoba aseve nawilobriv

asocirebulia adamianis Shbg genSi lokalizebul kodificirebul da

arakodificirebul Tanmimdevrobebis polimorfizmTan da mutaciebTan

[78,79].

orive sqesis adamianebSi ssSg-is done dabadebisas Zalian dabalia.

sicocxlis pirveli kvireebis ganmavlobaSi misi done iwyebs matebas

da daaxloebiT 2-3 TvisTvis aRwevs mudmiv dones. pubertatis

periodisTvis, rodesac mdedrobiTi da mamrobiTi sqesis mozardebSi

iwyeba sasqeso steroidebis mateba, ssSg-s koncentracia SesamCnevlad

ecema mamakacebSi da SedarebiT mcired qalebSi. es sqesobrivi dimorfizmi

narCundeba mamakacebSi 60 wlamde, xolo qalebSi - postmenopauzamde.

Semdgom ssSg-s done mamakacebSi umniSvnelod matulobs da qalebSi

klebulobs [15,36]. orsulobis dros ssSg-s koncentracia sisxlSi 7-jer

matulobs. tradiciulad miCneuli iyo, rom androgenebi Trgunaven, xolo

estrogenebi astimulireben ssSg-is gamomuSavebas RviZlSi. estrogenebis

oraluri an transdermaluri daniSvna mniSvnelovnad zrdis ssSg-is dones,

magram mkurnalobis Sewyvetis Semdeg is ubrundeba bazalur dones [146].

iTvleba, rom hiperandrogenia ar warmoadgens ssSg-is koncentraciis

daqveiTebis mizezs. gonadotropin-rilizing hormonis agonistebiT

androgenebis sinTezis daTrgunvisas ssSg-is koncentracia ar icvleboda.

diazoqsidiT insulinis donis daqveiTebis Semdeg aRiniSneboda ssSg-is

koncentraciis mateba. am faqts adastureben sxva mklevarebic [62,112,118].

aRsaniSnavia, rom msuqan mozard gogonebSi ssSg-s dabali koncentracia

miuTiTebs uaryofiT kavSirze sxeulis masis indeqsis matebas da insulinis

sekrecias Soris [50,119]. aseve naadrevi pubarxes dros dasabuTebulia

25

momatebuli androgenizaciis da insulin rezistentobis ganviTarebis riski

[84]. Pierre-Henri Ducluzeau da Tanaavtorebis monacemebiT pacientebSi

normaluri sxeulis masiT da policistozuri sakvercxeebis sindromiT

insulinrezistentoba da glukuzo/insulinis Tanafardoba aris myar

kavSirSi ssSg-s donesTan. insulinrezistentobis xarisxzea damokidebuli

ssSg-is done [57].

G.Cross da Tanaavtorebis azriT ssSg-is done SesaZloa monawileobdes

hirsutizmis ganviTarebaSi mozardobis asakSi da ara prepubertatul da

zrdasrul asakSi. maTi kvlevis Tanaxmad 13-14 wlis gogonebSi

mocirkulire androgenebis da ssSg-is koncentracia msgavsi iyo, rogorc

hirsutizmis mqone jgufSi, aseve sakontrolo jgufSi. 15-16 wlis gogonebSi

ssSg-is done hirsutizmis mqone gogonebis jgufSi mniSvnelovnad dabali

iyo sakontrolo jgufTan SedarebiT, amave dros androgenebis

koncentracia orive jgufSi msgavsi iyo. mozrdil qalebSi ki ssSg-is

koncentracia hirsutizmis mqone jgufSi umniSvnelod iyo daqveiTebuli

[46].

pacientebSi izolirebuli hirsutizmiT an akneTi nanaxia sarwmunod

daqveiTebuli ssSg-is done. Tavisufali testosteronis da testosteron

/ssSg-is Sefardeba ufro maRalia vidre sakontrolo jgufSi, Tumca

sarwmuno statistikuri sxvaoba jgufebs Soris nanaxi ar iyo [145].

1.6 policistozuri sakvercxeebis sindromi

hiperandrogenia da hirsutizmi yvelaze xSirad viTardeba policistozuri

sakvercxeebis sindromis dros. Azziz R. da Tanaavtorebis kvlevis Tanaxmad

hiperandrogeniis klinikuri gamovlinebebis mqone 878 qalTa 82%-s

aReniSneboda sakvercxeebis policistozi [22].

policistozuri sakvercxeebis sindromis dros hirsutizmi aRiniSneba

SemTxvevaTa 75%-Si, xolo araregularuli menstruaciuli ciklis dros

hirsutizmi gamovlinda SemTxvevaTa 75%-90%-Si [22,45]. hirsutizmi sxvadasxva

26

xarisxiT manifestirdeba. zogierT pacients paTologiuri Tmianoba ar

aReniSneba, rac SeiZleba aixsnas periferiuli qsovilebis mgrZnobelobis

daqveiTebiT androgenebis mimarT [4,98].

sakvercxeebis policistozi - xSiri endokrinuli sindromia, romelic

vlindeba reproduqciuli asakis qalTa 5-10%-Si [54,58]. roterdamis

konferenciis (2003) Tanaxmad sakvercxeebis policistozis

diagnostirebisTvis SeTavazebulia Semdegi kriteriumebi, romlebidanac

2 mainc unda iyos dadebiTi: 1. oligomenorea da/an anovulacia 2. sisxlSi

androgenebiss donis mateba da/an hiperandrogeniis klinikuri

gamovlinebebi da 3. policistozuri sakvercxeebi dadgenili ultrabgeriTi

kvleviT. amave dros unda iyos gamoricxuli yvela sxva SesaZlo mizezi,

romelsac axasiaTebs araregularuli menstruaciuli cikli da

hiperandrogenia (adrenogenitaluri sindromi, kuSingis sindromi,

androgenmaproducirebeli simsivne) [142]. amJamad cnobilia, rom qalebs

regularuli cikliT, hiperandrogeniiT da/an policistozuri

sakvercxeebis ultrabgeriTi suraTiT sakvercxeebis policistozis

sindromis diagnozi udgindebaT. aseve aRsaniSnavia, rom zogierT qals

sakvercxeebis policistozis sindromiT aReniSnebaT policistozuri

sakvercxeebi, sakvercxeebis disfunqcia da ar aRniSnebaT hiperandrogeniis

klinikuri gamovlinebebi [39]. qalebSi sakvercxeebis policistoziT

daaxloebiT 35%-Si aRiniSneba saerTo testosteronis, 70%-Si Tavisufali

testosteronis da 25%-Si dehidroepiandrosteron-sulfatis donis mateba

[20]. Tavisufali testosteroni yvelaze mgrZnobiarea bioqimiurad

hiperandrogeniis gamosavlenad qalebSi [136]. aRsaniSnavia, rom androgenebis

gansazRvra, Tavisufali testosteronis CaTvliT aris sakvercxeebis

policistozis diagnostirebis nawili da ara erTaderTi kriteriumi.

androgenebis gansazRvra mniSvnelovania hiperandrogeniis

diagnostirebisTvis pacientebSi hiperandrogeniis klinikuri

gamovlinebebis gareSe, rogorebicaa mag: mozardebi, azielebi da sxva

qalebi msubuqi hirsutizmiT [35].

literaturaSi arsebuli monacemebiT hiperandrogenia sakvercxeebis

policistozis dros warmoiSveba sakvercxis Teka ujredebSi CP17α-s

27

Tandayolili defeqtis Sedegad. CP17α (citoqrom P450C17α) - enzimia,

romelic akatalizebs 2 sxvadasxva SenaerTs: 17α- hidroqsilazas da 17, 20-

liazebs, romlebic sakvercxismieri androgenebis sekreciis mTavari

„gasaRebebia“. 17α-hidroqsilaza progesterons gardaqmnis

17α-hidroqsiprogesteronad, romelic 17,20-liazebis zemoqmedebiT

gardaiqmneba androstendionad, xolo androstendioni 17β-reduqtazas

zemoqmedebiT gardaiqmneba testosteronad [128,141]. In vitro, policistozuri

sakvercxeebis Teka ujredebSi, normalur sakvercxeebTan SedarebiT,

vlindeba 17α-hidroqsilazis, 17,20-liazebis da

3β-hidroqsisteroiddehidrogenazas momatebuli aqtivoba, rac umeteswilad

xsnis hiperandrogenias policistozuri sakvercxeebis sindromis dros

[111,157].

cnobilia rom, sakvercxismieri androgenebis gamoyofas aseve astimulirebs

maluTinizirebeli hormonis (mlh) Warbi sekrecia, romelic Tavis mxriv

aaqtivebs CP17α-s. mlh hipersekrecia sakvercxeebis policistozis

erT-erTi paTognomuri niSania da vlindeba SemTxvevaTa 40-80%-Si. mlh-is

hipersekreciis ganviTarebis mravali Teoria arsebobs, Tumca arcerTi ar

aris srulad dasabuTebuli [13,159]. mlh-is koncentraciis momatebis fonze

folikulmastimulirebeli hormonis (flh-is) koncentracia normaSi an

daqveiTebulia. Barnes-i da Tanaavtorebi [26] TavianT naSromSi miuTiTeben

gonadotropinebis centralur rolze androgenebis sinTezSi sakvercxeebis

policistozis dros. aseve gamovlinda, rom mlh-is stimulaciis sapasuxod,

matulobs 17α-hidroqsiprogesteronis da androstendionis sinTezi.

Minnanni-მ da Tanaavtorebma TavianT naSromSi gamoavlines dadebiTi

korelacia mlh-s da saerTo testosterons Soris sakvercxeebis

policistozis dros miuxedavad wonisa, rac miuTiTebs mlh-is wamyvan

rolze sakvercxeebis policistozis dros [101]. es kvlevebi Seesabameba

klinikur dakvirvebebs qalebze sakvercxeebis policistoziT, sadac mlh-is

done dadebiTad korelirebs mocirkulire testosteronis

koncentraciasTan [98]. sakvercxeebis policistozis GnRH-agonistebiT

mkurnalobis Semdeg mlh-s done klebulobs da Sesabamisad klebulobs

28

androgenebis done da hirsutizmis xarisxic [43]. amgvarad, mlh-s maRal

dones SeiZleba hqondes wamyvani roli hiperandrogeniis ganviTarebaSi.

Tumca aqve aRsaniSnavia, rom Teka ujredebis funqciis Seswavlis

safuZcelze Gilling-Smith da Tanaavtorebi [73] mividnen sawinaarmdego

daskvnamde, rom gonadotropuli funqciis daTrgunva ar aqveiTebs

androgenebis sinTezs Teka ujredebSi sakvercxeebis policistozis dros.

avtorebma gamoTqves mosazreba androgenebis avtonomiuri sekreciis

Sesaxeb.

wlebis manZilze policistozuri sakvercxeebis sindromis diagnozis

mTavar kriteriumad iTvleboda mlh/flh-is Tanafardobis gazrda ( >3-2,5 ).

magram, Dunaif da Tanaavtorebi [58] miiCneven, rom mlh/fmh Tanafardobis

gansazRvra ar unda iyos Setanili policistozuri sakvercxeebis

sindromis diagnozis kriteriumebSi. Mmlh da flh sekrecia xasiaTdeba

pulsaciuri riTmiT da hormonebis erTjeradi gansazRvra ar asaxavs mlh-is

donis da mlh/flh Tanafardobis realur suraTs.

policistozuri sakvercxeebis sindromiis dros xSirad mlh-s done normis

farglebSia, rac metyvelebs imaze, rom sxva faqtorebsac Seaqvs wvlili

hiperandrogeniis ganviTarebaSi. am faqtorebs Soris yvelaze

mniSvnelovania - insulini. jer kidev 1921 wels Archard-ma da Thiers-ma

SeniSnes kavSiri hiperandrogeniasa da naxSirwylebis cvlis darRvevas

Soris. am paTologias ewoda „wveriani qalebis diabeti“. 1980 w. Burghen,

Givens da Tanaavtorebma aRweres kavSiri hiperinsulinemiasa da hirsutizms

Soris qalebSi sakvercxeebis policistoziT. receptorebi insulinis

mimarT lokalizebulia sakvercxis Teka ujredebze, rogorc janmrTl,

aseve policistozuri sakvercxeebis sindromis mqone qalebSi. insulini

moqmedebs sakvercxeebze Tavisi receptorebis meSveobiT [60,158]. janmrTeli

sakvercxis Teka qsovilis in vitro SeswavliT daadgines, rom insulins

SeuZlia androgenebis sekreciis gazrda rogorc mlh-iT stimulaciis

sapasuxod, aseve damoukidebli moqmedebiT [30]. aRwerilia ramodenime

sindromi, romlis drosac aRiniSneba insulinrezistentobis da

hiperandrogeniis Tanxvedra. maTgan yvelaze xSirad gvxvdeba sakvercxeebis

policistozi. Tumca hiperandrogeniis da hiperinsulinemiis

29

urTierTmoqmedebis meqanizmebi bolomde Seswavlili ar aris. Teoriulad

SesaZloa maTi urTierTkavSiris ramodenime varianti: hiperandrogenia

ganapirobebs hiperinsulinemias, hiperinsulinemia ganapirobebs androgenebis

donis zrda da arsebobs sxva, mesame faqtori, romelic pasuxismgebelia

orive fenomenze [14]. sayuradReboa, is faqtic, rom literaturaSi arsebuli

monacemebiT insulinrezistentoba ganpirobebulia insulinis receptoris

autofosforilirebis darRveviT [13]. In vitro da in vivo kvlevebiT

sakvercxeebis policistozis mqone pacientTa naxevarSi adgili aqvs

serinofosfolirebis process insulinis receptorSi, rac signalis

Semdgom gadacemas aferxebs. mTeli rigi avtorebi amtkiceben, rom

serinofosfolireba warmoadgens erT-erT mTavar meqanizms ferment

citoqrom P450C 17α-hidroqsilazas gaaqtiurebaSi, romelic, rogorc

aRvniSneT, mniSvnelovani fermentia androgenebis sinTezis zrdaSi, rogorc

sakvercxeebSi, aseve Tirkmelzeda jirkvalSi [30,60]. rogorc cnobilia,

insulini sakvercxeze moqmedebs ara mxolod insulinis receptorebis

meSveobiT, aramed insulinismagvari zrdis faqtoris (i.m.z.f.)

receptorebiTac. insulinisgan gansxvavebiT, romelic sinTezirdeba

pankreasis da tvinis zogierTi midamos mier, imzf-1 gamomuSavdeba TiTqmis

yvela qsovilebSi ganviTarebis sxvadasxva periodSi. kerZod, sakvercxeebSi

imzf-1-is ZiriTadi sinTezi mimdinareobs granulozas ujredebSi.

granulozas ujredebSi insulini da imzf-1 zrdis bazalur da aseve

gonadotripinebiT da cikliuri adenozinmonofosfatis (camf) mier

stimulirebuli progesteronis da estrogenebis dones, aZlierebs

citoqromis enzimuri sistemis aqtivobas, zrdis mlh-is receptorebis

raodenobas da simWidroves. cnobilia, rom insulini da imzf-1 mlh-is

meSveobiT zrdian androgenebis sekrecias sakvercxeebis stromis da Teka

ujredebis mier, rac iwvevs hiperandrogenias da folikulebis kistozur

atrezias. Tirkmelzeda jirkvlebSi imzf-1 zemoqmedebiT izrdeba

badiseburi zonis ujredebis mgrZnobeloba adrenokortikotropuli

hormonis mimarT. aseve, aRsaniSnavia, rom insulinis Seyvana Tirkmelzeda

jirkvlebis ujredebSi ganapirobebs maT mier steroidebis sinTezis zrdas

androgenebis dagrovebis upiratesobiT, 17α-hidroqsilazis da

17,20-desmolazis aqtiurobis matebis xarjze [6]. albaT, amiT SeiZleba iyos

30

axsnili sakvercxismieri da Tirkmelzeda jirkvlismieri hiperandrogeniis

xSiri Tanxvedra. amave dros, policistozuri sakvercxeebis struqtura

damtkicebuli insulinrezistentobis da hiperinsulinemiis dros aReniSneba

mxolod pacientTa 13,1%-s. Sesabamisad sakvercxeebis policistozis

ganviTarebisTvis garda arsebuli insulinrezistentobisa unda arsebobdes

genetikuri ganwyoba am daavadebis mimarT [2]. insulins SeuZlia pirdapir

RviZlSi daTrgunos seqssteroidSemboWveli globulinis sekrecia, ris

Sedegadac sisxlSi matulobs Tavisufali testosteronis done da

vlindeba hiperandrogeniis simptomebi. sakvercxeebis policistozis mqone

pacientebSi miuxedavad wonisa ssSg-is koncentracia gacilebiT dabalia

sakontrolo jgufTan SedarebiT. es kanonzomiereba ufro gamokveTilia -

cximovani qsovilis matebasTan erTad. rac ufro metia sxeulis masis

indeqsi miT ufro dabalia ssSg-is koncentracia sisxlSi [106]. Tumca, sxva

kvlevis monacemebiT, romelSic monawileobas iRebda qalTa 2 jgufi - 21

qali sakvercxeebis policistoziT da sakontrolo jgufis 17 qali - ssSg-

is koncentraciis mixedviT sarwmuno sxvaoba ar gamovlinda [49].

Kajaia da Tanaavtorebis kvlevis SedegebiT ssSg-is done SeiZleba

gamoyenebuli iyos insulinrezistentobis sadiagnostiko markerad yvela

qalSi hiperandrogeniiT, ukeTesi korelaciiT Warbi wonis dros [88]. am

monacemnebs eTanxmeba sxva avtorebis monacemebic, Tumca es kvlevebi

moicavs pacientebis mcire jgufebs [32,86].

ssSg-is koncentracia gansxvavdeba qalebSi da mamakacebSi, amitom Saqriani

diabetis tipi 2 ganviTarebis riski SesaZloa gansxvavdebodes sqesis

mixedviT. korelaciuri kavSiri ssSg-is dabal donesa da Saqriani diabetis

tipi 2 ganviTarebis risks Soris, rogorc ukve cnobilia, ufro Zlieria

qalebSi, vidre mamakacebSi [55,76]. F.Bonnet da Tanaavtorebis [34] Catarebuli

kvlevis Tanaxmad, romelic grZeldeboda 9 weli, dakvirvebis qveS

imyofebodnen mamakacebi da qalebi 30-dan - 64-wlamde. 3482 pacients pirvel

vizitze aReniSneboda normoglikemia. maT Soris 227-s me-3 vizitze

(9 wlis Semdeg) aRmoaCnda hiperglikemia. isini Sedarebuli iyvnen sqesis,

asakis da sxeulis masis indeqsis mixedviT Sesabamis sxva 227 adamianTan,

romlebsac am droisTvis jer kidev normoglikemia aReniSneboda. kvlevis

31

Sedegad avtorebi Tvlian, rom ssSg-s dabali done, damoukideblad

insulinisa da adiponektinis donesa, aris Zlieri damoukidebeli markeri

Saqriani diabeti tipi 2 ganviTarebis momatebuli riskis dasadgenad

qalebSi, da ara mamakacebSi.

1.7 adreno-genitaluri sindromi

hirsutizmis sxva mizezebidan aRsaniSnavia - adrenogenitaluri sindromi

(ags), romelic moicavs hirsutizmis mqone pacientebis 2,7-4,5% [41,74].

ags ganpirobebulia im fermentul sistemaTa ukmarisobiT, romlebic

Tirkmelzeda jirkvalis qerqovan nivTierebaSi warmarTavs steroidebis

biosinTezis process. amis gamo ferxdeba glukokortikoidebis,

mineralkortikoidebis da androgenebis warmoqmna, anu viTardeba

steroidogenezis saboloo produqtebis naklovaneba da xdeba im

Sualeduri SenaerTebis Warbi dagroveba, rac ar gamoiyofa fiziologiur

pirobebSi an gamomuSavdeba umniSvnelo raodenobiT [7].

ags-i autosomur - recesiulad paTologiaa, romlis drosac aRiniSneba

21α-hidroqsilazas, 3β-hidroqsisteroiddehidrogenazis an

11β-hidroqsilazis deficiti [100]. 21α-hidroqsilazas deficiti aRiniSneba

pacientTa 95%-Si da vlindeba kortizolis deficitiT, aldosteronis

deficitiT an mis gareSe da hiperandrogeniiT. 21α-hidroqsilazas

deficitis markeria 17αα-hidroqsiprogesteronis mateba.

3-β-hidroqsisteroiddehidrogenazis deficitis Sedegad matulobs

pregnanolonis, 17α -hidroqsipregnenolonis da dehidroepiandrosteronis

done. 11 β-hidroqsilazis deficiti xasiaTdeba 11 -deoqsikortizolis,

deoqsikortikosteronis da mineralkortikoidebis momatebuli doniT.

adrenogenitaluri sindromis klinikuri gamovlineba mrafelferovania da

moicavs rogorc mZime formebs anu klasikur ags-s, aseve msubuq formebs

e.w. ags-s araklasikur anu postpubertatul formas. ags-is klasikuri

formis sixSire 1:15000 axalSobilze [143]. xolo ags-is araklasikuri forma

32

sakmaod xSiri paTologia da misi siSire TeTrkanian populaciaSi Seadgens

1:500-ze [148].

ags-iT klasikuri formiT mdedrobiTi sqesis axalSobilebi mucladyofnis

periodSi imyofebian androgenebis maRali koncentraciis zemoqmedebis qveS

da ibadebian gaurkveveli sasqeso organoebiT, rac moicavs gadidebul

klitors, Serwymul sasircxo bageebs da urogenitalur sinuss. SigniTa

sasqeso organoebi saSvilosno, kvercxsavali milebi da sakvercxeebi

normis farglebSia. am paTologiis diagnostireba Cveulebriv xdeba

adreul bavSvobis asakSi da amJamad SesaZlebelia misi prenataluri

diagnostika.

pacientebSi ags-iT araklasikuri formiT kortizolis deficitis da

hiperandrogeniis simptomebis gamovlineba iwyeba prepubartatul an

adreuli pubertatis periodSi [113]. aseT pacientebs axasiaTebs adreuli

pubarxe an hirsutizmi (60%), oligomenorea an amenorea (54%) sakvercxeebis

policistoziT da akne (33%) [103]. avtorebi miuTiTeben, rom Tirkmelzeda

jirkvlis paTologiis dros hirsutizmi aRiniSneba TiTqmis yvela

SemTxvevaSi. zogierTi avtoris monacemiT, paTologiuri gaTmianeba iwyeba

menarxemde, romelic Semdgom progresirebs [4]. hirsutizmis ganviTareba

adreno-genitaluri sindromis dros, iseve rogorc sxva paTologiis

SemTxvevaSi, dakaSirebulia yvelaze aqtiuri androgenis,

dihidrotestosteronis donis momatebasTan, romlis sinTezSic

monawileobs rogorc Tirkmelzeda jirkvali, aseve sakvercxe [56]. ags-is

paTofiziologiis SeswavliT naCvenebia endokrinopaTiebi damaxasiaTebeli

anomaliebiT Tirkmelzeda jirkvlebis qerqis, rac moicavs

adrenomedularul disfunqcias da insulinrezistentobas. qalebSi

hiperandrogenia damoukidebeli risk faqtoria hiperinsulinemiis

ganviTarebis da SesaZloa monawileobdes insulinrezistentobis an

sakvercxeebis policistozis ganviTarebaSi ags-is mqone pacientebSi [75,82].

33

1.8 hiperandrogenizmis sxva mizezebi

bolo wlebSi didi yuradReba eqceva prolaqtins, rogorc Tirkmelzeda

jirkvlebis qerqSi androgenebis sekreciis regulators. amis safuZvels

warmoadgens is faqti, rom hiperprolaqtinemiis da hipofizis adenomis

mqone pacientebSi aRmoCenili iqna dehidroepiandrosteronis koncentraciis

mateba zomieri testosteronemiis dros [107], Tumca sruli korelacia

prolaqtins da androgenebs Soris nanaxi ar iqna. R. Azziz da Tanaavtorebis

monacemebiT kvlevaSi monawile 1000 pacientidan hiperandrogeniiT

hiperprolaqtinemia aReniSneboda mxolod erT pacients (0,3%). maTi

monacemebi aseve emTxveva sxva avtorebis monacemebs [22,25,52,105,162].

hiperandrogeniis ganviTarebas fariseburi jirkvlis funqciis darRvevis

dros safuZvlad udevs seqssteroidSemboWveli globulinis donis

mniSvnelovani daqveiTeba, ris Sedegadac izrdeba androstendionis

testosteronad gardaqmnis siCqare da Tavisufali testosteronis fraqciis

gazrda. cnobilia, rom hipoTireozis dros rigi fermentebis da

hormonebis metabolizmi icvleba, maT Soris estrogenebisac. estrogenebis

sinTezi ZiriTadad ixreba estriolis da ara estradiolis mxares.

estradioli ar grovdeba da Sesabamisad pacientebs uviTardebaT

testosteronis biologiuri efeqtis klinikuri suraTi. С. Йена da Р. Джаффе

monacemebiT pacientebSi hipoTireoziT SesaZlebelia sakvercxeebis

meoradi policistozis ganviTareba [6]. Tumca, arsebobs kvlevebi, romelTa

Tanaxmadac hiperandrogeniis dros fariseburi jirkvlis disfunqcia,

kerZod hipoTireozi, aReniSneboda erTeul pacientebs [22,33,68].

wamlismieri hirsutizmi gamowveulia rigi samedicino preparatebiT.

esenia: ciklosporini, diazoqsidi, danazoli, glukokortikoidebi,

penicilamini, minoqsidili da androgenSemcveli hormonaluri preparatebi.

Tumca antiepilefsiuri preparatebic, rogoricaa fenitoini (difenini) da

fenobarbitali SesaZloa iwvevdnen hirsutizms [124].

34

1.9 idiopaTiuri hirsutizmi

iTvleba, rom hirsutizmi pacientebis 5-15%-Si aris idiopaTiuri [21].

idiopaTiuri hirsutizmis zusti gavrcelebis Sefaseba rTulia, vinaidan

bolo sami aTwleulis ganmavlobaSi idiopaTiuri hirsutizmis ganmartebaSi

Setanilia cvlilebebi. amJamad idiopaTiur hirsutizmad ganixileba,

hirsutizmis arseboba qalebSi normaluri ovulatoruli cikliT, sisxlSi

mocirkulire androgenebis normaluri doniT da sakvercxeebis

ultrasonografiuli kvleviT policistozuri sakvercxeebis ararsebobiT.

avtorebi Tvlian, rom idiopaTiuri hirsutizmi mocirkulire androgenebis

normaluri donis mimarT Tmis folikulebis momatebuli mgrZnobelobis

Sedegia, romlis mizezi savaraudod aris 5-α reduqtazas aqtivobis mateba

[29,65]. zogierTi kvlevis Tanaxmad idiopaTiuri hirsutizmis ganviTarebis

mizezad miCneulia androgenis receptoris genis polimorfizmi. androgenis

receptori lokalizebulia X-qromosomaze. Lyon-is hipoTezis Tanaxmad,

Cveulebriv mxolod erTi alelia samizne qsovilebSi gamoxatuli da

damokidebuli X-qromosomis inaqtivaciis SemTxveviT nimuSebze.

dauzustebelia, romeli X-damokidebuli alelia gamoxatuli hirsutizmis

mqone qalTa qsovilebSi, radganac bevr qals androgenis receptoris

genSi ganmeorebadi CAG regionis zomis mimarT aReniSneba

heterozigoturoba. aqedan gamomdinare, saWiroa Semdgomi kvlevebi, rom

ganisazRvros androgenuli receptoris genis polimorfizmis roli

idiopaTiuri hirsutizmis ganviTarebaSi [21].

1.10 hiperandrogenizmis eqstraovariuli faqtorebi

hiperandrogenizmis ganviTarebis eqstraovariuli faqtorebidan

mniSvnelovan rols TamaSobs cximovani qsovili, sadac warmoebs sasqeso

steroidebis - androgenebis da estrogenebis (ZiriTadad estronis)

aragonaduri sinTezi. am process aqvs avtonomiuri xasiaTi da ar aris

damokidebuli gonadotropul stimulaciaze. cximovani qsovili aris erT-

erTi mTavari adgili, sadac xdeba androgenebis efeqtis realizacia. bolo

wlebSi damtkicebulia, rom cximovani qsovili warmoadgens ara mxolod

35

energiis depos da steroiduli hormonebis metabolozmis adgils, aramed

is damoukidebeli endokrinuli organoa [12]. mniSvnelovania ara sxeulis

absoluturi wona, aramed cximovani qsovilis gadanawileba sxeulze.

ganasxvaveben mamakacuri (visceraluri, androiduli) tipis da qaluri

(ginoiduri) tipis simsuqnes. visceraluri tipis simsuqnis dros cximovani

qsovili upiratesad gadanawilebulia beWebis areSi, kisris ukana

zedapirze da muclis wina kedelze [13,50]. cximovani qsovili warmoadgens

cximovani ujredebis – adipocitebis erTobliobas. Ganasxvaveben TeTr da

rux cximovan qsovils. adamianis organizmSi farTod gavrcelebulia

TeTri cximovani qsovili, romelic ganlagebulia kanqveS ZiriTadad

muclis faris qvemo nawilSi, TeZoebze, dunduloebze da

intraabdominalurad (jorjalSi, retroperitonealur midamoSi) [5]. ruxi

cximovani qsovili ZiriTadad gvxvdeba bavSvebSi, Tumca SesaZloa

umniSvnelo raodenobiT zrdasrul adamianebSic aRiniSnebodes.

Termogenezi ZiriTadad ruxi cximovani qsovilis meSveobiT mimdinareobs,

romlis ujredebi efeqturad axdenen glukozis da cximovani mJaveebis

daJangvas [44]. gacximovnebis mqone adamianebs ruxi cximovani qsovili

SesaZloa saerTod ar hqondeT, rac aqveiTebs Termogenezs.

morfologiurad visceraluri cxomovani qsovilisaTvis damaxasiaTebelia

cximovani ujredebis hipertrofia, xolo ginoidurisaTvis cximovani

ujredebis zrda, amitom sxvanairad visceralur cximovan qsovils

hipertrofirebuls eZaxian, xolo ginoidurs hiperplaziurs [1]. simsuqnis

tipis gansazRvrisaTvis gamoiyeneba welisa da barZayis garSemowerilobis

Tanafardobis gansazRvra. Tu Tanafardobis indeqsi 0,8-ze metia, adgili

aqvs visceraluri tipis simsuqnes.

qalebSi visceraluri simsuqniT Cveulebriv ssSg-is done SedarebiT ufro

dabalia, vidre amave asakis da wonis qalebSi cximovani qsovilis Tanabari

gadanawilebiT [154]. amave azris arian sxva avtorebic [145]. rigi avtorebis

azriT, testosteronis koncentracia prepubertatSi myofi, rogorc msuqani,

aseve normaluri wonis gogonebSi ar gansxvavdeba [71,117]. Tumca sxva

avtorebis monacemebiT Warbi wonis mqone gogonebSi vlindeba

testosteronis da dehidroepiandrosteron-sulfatis sarwmunod

momatebuli done, normaluri wonis gogonebTan SedarebiT [147,155],

36

romelTa maCveneblebic wonis daqveiTebis SemTxvevaSi iklebs [145].

gacximovnebis visceraluri tipis formireba warmoadgens ufro

mniSvnelovan klinikur niSans metaboluri darRvevebis ganviTarebis

midrekilebis TvalsazrisiT, vidre sxeulis absoluturi masa. cximovani

qsovilis topografiis da metaboluri darRvevebis urTierTkavSiris

Seswavlis Sedegebi gvafiqrebinebs, rom visceraluri simsuqne genetikurad

ganpirobebuli insulinrezistentobis asaxvaa. insulinrezistentobas

safuZvled udevs insulinis signalis gadacemis meqanizmebis darRveva,

rogorc receptoruli, aseve postreceptorul doneze [60].

insulinrezistentoba simsuqnis dros viTardeba TandaTanobiT, pirvel

rigSi kunTebSi da RviZlSi. mxolod adipocitebSi lipidebis didi

raodenobiT dagrovebis, maTi zomaSi matebis Semdeg insulinrezistentoba

viTardeba cximovan qsovilSi, rac xels uwyobs insulinrezistentobis

Semdgom gaRrmavebas [117,158]. S.Cupisti da Tanaavtorebis azriT pacientebSi

hirsutizmiT da sakvercxeebis policistoziT simsuqne asocirebulia

saerTo testosteronis koncentraciis matebasTan da ssSg-is koncentraciis

daqveiTebasTan, ris Sedegadac matulobs gaangariSebuli Tavisufali da

bioSeRwevadi testosteroni [47]. simsuqne policistozuri sakvercxeebis

sindromis erT-erTi mTavari klinikuri simptomia. am sindromis mqone

pacientTa daaxloebiT 50%-Si simsuqne vlindeba sxvadasxva xarisxiT da

xSirad win uswrebs hiperandrogeniis da oligomenoreis ganviTarebas, rac

miuTiTebs simsuqnis paTogenezur mniSvnelobaze policistozuri

sakvercxeebis sindromis ganviTarebaSi [69]. simsuqnis mqone pacientebSi

sakvercxeebis funqciis darRvevis genezSi wamyvani faqtoria

hiperinsulinemia, ris Sedegadac viTardeba hiperandrogenemia da

policistozuri sakvercxeebi. amave dros policistozuri sakvercxeebis

struqtura damtkicebuli insulinrezistentobis da hiperinsulinemiis

dros aReniSneba mxolod pacientTa 13,1%-s. Sesabamisad sakvercxeebis

policistozis ganviTarebisTvis garda arsebuli insulinrezistentobis

unda arsebobdes genetikuri midrekileba am daavadebis mimarT [2].

sakvercxeebis policistozis mqone pacientebSi miuxedavad wonisa ssSg-is

koncentracia gacilebiT dabalia sakontrolo jgufTan SedarebiT. es

kanonzomiereba ufro gamokveTilia - cximovani qsovilis matebasTan erTad,

37

rac ufro metia sxeulis masis indeqsi miT ufro dabalia ssSg-is

koncentracia sisxlSi [116]. Tumca, sxva kvlevis monacemebiT, romelSic

monawileobas iRebda qalTa 2 jgufi - 21 qali sakvercxeebis

policistoziT da 17 qali sakontrolo jgufidan - ssSg-s koncentraciis

sarwmuno sxvaoba ar gamovlinda [49].

1.11 hirsutizmis Sefaseba da diagnostika

hirsutizmis gamoxatulobis xarisxi damokidebulia androgenebis donesa

da periferiaze androgenebis mimarT receptorebis mgrZnobelobis

urTierTkavSirze. androgenebis donis 2-jer da ufro metad matebis

SemTxvevaSi aRiniSneba hirsutizmis sxvadasxva xarisxi. miuxedavad amisa,

rig SemTxvevebSi hirsutizmis xarisxi dadebiTad ar korelirebs

androgenebis donesTan, radganac androgendamokidebuli Tmis

folikulebis pasuxi androgenebis matebaze individualuria sxvadasxva

adamianSi. rig SemTxvevebSi hirsutizmi viTardeba androgenebis normaluri

donis pirobebSi (idiopaTiuri hirsutizmi) [130], romelic msubuqi

hirsutizmis (feriman-galveis cxrilis mixedviT 8-16 qula) mqone

pacientebis 50%-Si xvdeba. xolo danarCen 50%-Si da mkveTrad gamoxatuli

hirsutizmis dros sisxlSi aRiniSneba androgenebis maRali done [122].

hirsutizmis xarisxis Sefaseba xdeba Ferriman, Galwey (1961w) mier

mowodebuli sqemis safuZvelze (sur.1), rac iTvaliswinebs, sxeulze

gamoyofil 11 zonaze 4 quliani sistemiT Tmianobis intensivobis Sefasebas

[67]. Ferriman da Galwey mier modificirebuli sqemis mixedviT, sadac

hirsutizmi fasdeba sxeulis 9 zonaze (fexis wvivebis da xelebis

gamoklebiT) 161 qalidan 9,9%-s hirsutizmi Seufasda 5 qulaze zemoT,

4,3 %s - 7 qulaze zemoT da 12%-s - 10 qulaze zemoT [67]. am monacemebiT

paTologiuri Tmianoba 8 qulaze zemoT ganixileba, rogorc hirsutizmi,

Tumca zogierTi eqspertis azriT hirsutizmi aRiniSneba 6 qulaze da

ufro zemoT [129]. gamoxatulobis xarisxis mixedviT hirsutizms yofen 3

formad: msubuqi ( 8-16 qulamde), saSualo simZimis (17-24 qulamde) da mZime

(25 qula da meti).

38

suraTi 1. hirsutizmis xarisxis Sefasebis feriman–galveis sqema

39

klinikur praktikaSi metad mosaxerxebelia hirsutizmis xarisxis

dasadgenad Baron -is sqema, sadac gamoyofilia hirsutizmis msubuqi,

saSualo da mZime xarisxi Tmianobis lokalizaciis gaTvaliswinebiT.

1

33

2

5

9

55

6

8

7

8

99

I xarisxi-msubuqi1 muclis TeTri xazi

(2) zeda tuCi

(3)Mdvrilebis irgvliv zona

II xarisxi-saSualo1,2,3+

4 nikapi

5 TeZoebis Sida zedapiri

III xarisxi-mZime1,2,3,4,5+

6 mkerdi

7 zurgi xerxemlis gaswvriv

8 dundulebi

9 beWebi

hirsutizmis Sefaseba BBaron-is mixedviT, 1974

40

1.12 hirsutizmis mkurnaloba

hirsutizmis mkurnaloba iwyeba misi ganviTarebis yvela SesaZlo mizezebis

dadgenis, androgenmaproducirebeli simsivnis da kuSingis daavadebis

gamoricxvis Semdeg. hirsutizmis efeqturi mkurnaloba moicavs Semdeg

kombinacias: cxovrebis wesis Secvlas, Tmis meqanikur moSorebas da

medikamentur Terapias. medikamenturi Terapia Sedgeba androgenebis

supresoruli preparatebisgan, antiandrogenebisgan da androgenuli

receptorebis blokatorebisgan.

cxovrebis wesis Secvla, rac moicavs jansaR kvebas, varjiSs da wonis

daklebas aris mkurnalobis safuZveli msuqani hirsutizmis mqone

pacientebisTvis. wonis dakleba awesrigebs naxSirwylebis da cximebis

cvlas, aqveiTebs insulinis dones, sakvercxismieri androgenebis sekrecias

da androstendionis konversias testosteronSi [93]. wonis dakleba da

insulinis donis daqveiTeba iwvevs seqssteroidSemboWveli globulinis

sekreciis matebas, rac ganapirobebs Tavisufali androgenebis donis

Semdgom daqveiTebas [70].

terminaluri Tmebis sicocxliunarianobis mixedviT efeqtis misaRwevad

saWiroa aranakleb eqvsi Tve, rom Tma gaxdes SedarebiT nazi da Txeli.

mkurnalobis Sedegad axali Tmebis amosvla wydeba, xolo Zveli Tmebi

cviva. Tmis meqanikurma moSorebam SesaZloa daaCqaros es procesi.

aRsaniSnavia, rom Tmis folikulebis destruqcia SesaZloa miRweuli iyos

deniT an lazero epilaciiT, Tumca is midrekilia xelaxla daiwyos zrda

medikamentebiT mkurnalobis Sewyvetis Semdeg. Tmis meqanikuri mocileba

SesaZlebelia ramodenime meTodiT. gauferuleba, gaparsva da depilaciis

kremebi umtkivneulo da iafi meTodebia, magram am dros ar xdeba Tmis

folikulze zemoqmedeba da efeqti xanmoklea. cviliT depilacia, nemsiT

eleqtro epilacia da lazeroepilacia SedarebiT Zviri da arakomfortuli

proceduraa, magram saboloo jamSi medikamentur TerapiasTan erTad

amcirebs Tmis zrdas da aCqarebs mkurnalobis efeqts [123].

androgenebis supresiuli Terapia mizanSewonilia androgenebis sekreciis

dasaqveiTeblad, gansakuTrebiT sakvercxismieri hiperandrogeniis dros. is

41

Zalian xelsayrelia hiperandrogeniiT gamowveuli hirsutizmis

samkurnalod, Tumca SesaZloa idiopaTiuri hirsutizmis mkurnalobaSic

TamaSobdes garkveul rols. androgenebis supresiuli Terapia pirvel

rigSi moicavs kombinirebul oralur kontraceptivebs (kok-ebs). kok-ebi

moqmedeben Semdegnairad: Trgunaven gonadotropinebis da ovariuli

androgenebis sekrecias, zrdian ssSg-is sekracias RviZlis mier, rac

amcirebs Tavisufali testosteronis dones [149]. SesaZloa

antiandrogenebis damateba, Tu mxolod kok-ze klinikuri pasuxi

aradamakmayofilebelia. alternatiulia, kok-i, romelic Seicavs

progestinis saxiT antiandrogens - ciproteron acetats. aseTi preparati

moqmedebs, rogorc sakvercxismieri androgenebis supresori da aseve

androgenebis receptorebis blokatori [90].

miuxedavad imisa, rom glukokortikoidebi Trgunaven Tirkmelzeda

jirkvlismier androgenebs, androgenebis receptorebis blokatorebi zrdis

efeqturobas, maSinac ki rodesac hirsutizmi ganpirobebulia

adrenogenitaluri sindromiT. erT-erT placebo kontrolirebad

randomizirebul kvlevaSi mkurnaloba tardeboda ciproteron acetatiT

an hidrokortizoniT [139]. 1 wlis Sedegad ciproteron acetatiT

namkurnaleb pacientebs aReniSnebodaT hirsutizmis xarisxis Semcireba

54%-iT, xolo hidrokortizoniT namkurnaleb pacientebs 26%-iT.

gonadotropin rilizing hormonis agonistebi SesaZloa gamoyenebuli iqnes

sakvercxismieri hiperandrogeniis da refraqteruli hirsutizmis

samkurnalod. isini iwveven medikamentozur ooforeqtomias [37]. Tumca, am

preparatebis xSiri hipoestrogenuli efeqti da osteoporozis

ganviTareba aucilebels xdis kombinirebuli gestagenebis damatebas.

insulinrezistentuli metaboluri sindromisas sakvercxeebis meoradi

policistoziT gamoiyeneba biguanidebis jgufis preparatebi (siofori,

metformini). am jgufis preparatebi pirvelad 1974 wels iyo warmodgenili.

biguanidebi iwvevs insulinrezistentobis donis daqveiTebas, zrdis

receptorebis mgrZnobelobas insulinisadmi da Sesabamisad umjobesdeba

glukozis utilizacia RviZlSi [97]. insulinis sekreciis daqveiTebas Tan

mohyveba Tavisufali testosteronis donis Semcireba da ssSg-is

42

koncentraciis mateba. Tumca, hirsutizmis mkurnalobaSi isini ar

xasiaTdeba swrafi efeqturubiT, rogorc antiandrogenebi [124].

antiandrogenuli moqmedebiT xasiaTdeba veroSpironi (spirolaqtoni). misi

xangrZlivi moqmedebisas aReniSneba hipertriqozis Semcireba. veroSpironi

Trgunavs ferment 5α-reduqtazas aqtivobas, romelsac testosteroni

gadayavs yvelaze aqtiur androgenSi dihidrotestosteronSi [110]. misi

gamoyeneba SesaZloa damoukideblad 100-dan -200-s mg dReSi an kombonaciaSi

kok-Tan [61].

flutamidi pirveli arasteroiduli antiandrogenia. mxolod flutamidi an

misi kombinacia kok-Tan ufro efeqturia vidre finasteridi an

spironolaqton - kok-is kombinacia [150]. misi hepatotoqsiuroba iSviaTia,

magram rekomendirebulia periodulad RviZlis funqciebis kontroli.

gverdiTi efeqtebi da hepatotoqsiuroba naklebad vlindeba 250 mg dozis

SemTxvevaSi.

finasteridi - ablokirebs 5α-reduqtazas da ZiriTadad gamoiyeneba

idiopaTiuri hirsutizmis mkurnalobaSi [102]. avtorTa monacemebiT

finasteridis zemoqmedebiT hirsutizmis xarisxi mcirdeba 30-60%-iT, aseve

mcirdeba Tmis sisqe. finasteridis efeqti msgavsia sxva antiandrogenebis

moqmedebis.

problemis aqtualobidan gamomdinare miznad davisaxeT korelaciebis

dadgena hiperandrogenizmis klinikur da hormonalur maCveneblebs Soris

axalgazrda qalebSi hiperandrogenizmiT gamovlenili sxvadasxva

endokrinul–ginekologiuri sindromebiT ( policistozuri sakvercxeebis

sindromi, adrenogenitaluri sindromis araklasikuri forma,

hiperprolaqtinemiis sindromi).

43

Tavi 2

Kkvlevis obieqti da meTodebi

2.1 kvlevis obieqti

kvleva Catarda i. Jordanias saxelobis adamianis reproduqciis s/k

institutis bazaze. kvlevaSi monawileobda 13-dan 30 wlamde asakis 111

pacienti, romelTa saSualo asaki Seadgenda 17,7 (±3,3). kvlevaSi monawile

pacientTa ZiriTadi Civilebi iyo: menstruaciuli ciklis darRveva,

WarbTmianoba, akne. kvlevaSi pacientTa CarTvis kriteriumebi iyo:

menarxedan gasuli unda yofiliyo 2 weli da pacienti ar unda yofliyo

namkurnalevi, maT Soris kontraceptivebiT.

pacientebs diagnozebis mixedviT Semdegnairad iyvnen gadanawilebuli:

policistozuri sakvercxeebis sindromi – 43 pacienti, adrenogenitaluri

sindromis araklasikuri forma –38 pacienti da hiperprolaqtinemiis

sindromi 30 pacienti. policistozuri sakvercxeebis sindromis dadgena

xdeboda roterdamis konsesusis (2003 w.) Tanaxmad. adrenogenitaluri

sindromis dadgena xdeboda Tirkmelzeda jirkvlis hormonis 17α–

hidroqsiprogesteronis maCveneblis mixedviT, xolo hiperprolaqtinemiis

sindromi dadgena xdeboda prolaqtinis maCveneblis mixedviT.

sakontrolo jgufi Sedgeboda 15–30 wlis askobrivi jgufis 20

praqtikulad janmrTeli qalisagan, romelTac ar aReniSnebodaT

hiperandrogenizmis klinikuri gamovlinebebi da menstruaciuli ciklis

darRvevebi.

44

2.2 kvlevis meTodebi

pacientebis obieqturi statusis Seswavlisas dgindeboda sxeulis

aRnagobis tipi. G. Brey-is (1978 w) mier mowodebuli formuliT isazRvreboda

sxeulis masis indeqi: sxeulis wona kg–Si gayofili sxeulis simaRlis

kvadratze (kg/m2). normaSi sxeulis masis indeqsi (smi) 20–dan – 25–is

farglebSia. I xarisxis simsuqnis dros smi 25–dan – 30–mdea; II xarisxis

simsuqnis dros smi – 30–dan – 35–mde; III xarisxis simsuqnis dros smi –

35–dan – 40–mde; IV xarisxis simsuqnis dros smi – 40–ze metia. cximovani

qsovilis gadanawilebis Taviseburebebis dadgenis mizniT xdeboda welisa

da barZayis garSemowerilobis Tanafardobis gansazRvra. zemo tipis,

visceraluri, anu mamakacuri tipis simsuqnis dros, welisa da barZayis

garSemowerilobis Tanafardobis indeqsad miCneulia 0,8–ze meti, xolo

qvemo, qaluri, ginoiduri tipis simsuqnis dros – 0,8–ze naklebi.

yuradReba eqceoda sxeulis safarvelis Taviseburebebs: kanis

hiperpigmentaciur ubnebs – acantosis nigricans, seboreas, aknes, alopecias da

klimaqteruli kuzis arsebobas.

2.2.1 hormonebis raodenobrivi gansazRvra

sisxlSi hormonebis raodenorivi gansazRvra xorcieldeboda

imunofermentuli meTodiT (ELISA) menstruaciuli ciklis me – 3–5 dReebSi

diliT uzmoze. isazRvreboda Semdegi maCveneblebis koncentracia: saerTo

testosteroni, Tavisufali testosteroni, seqssteroidSemboWveli

globulini, dehidroepiandrosteron–sulfati, 17 α –hidroqsiprogesteroni,

estradioli, prolaqtini, folikulmastimulirebeli da maluTinizirebeli

hormonis, C-peptidi, Tireomastimulirebeli hormoni. bioqimiuri meTodiT

sisxlSi uzmoze isazRvreboda glukozis koncentracia.

45

2.2.2 hirsutuli ricxvis gansazRvra

hirsutuli ricxvi isazRvreboda Ferriman-Gallway (1961 w.) modificirebuli

sqemis mixedviT, rac iTvaliswinebs sxeulze gamoyofil 9 zonaze 4

quliani sistemiT Tmianobis intensivobis Sefasebas. hirsutuli ricxvis

mixedviT pacientebi dayofil iqna 3 jgufad: I – hirsutizmi ar aris (0–7

qula), msubuqi hirsutizmi (8–16 qula) da saSualo simZimis da mZime

hirsutizmi (17 qula da meti).

2.2.3 Tavisufali androgenebis indeqsis gansazRvra

Tavisufali androgenebis indeqsis gamoTvla xdeba Semdegi formuliT

FAI = TT *100 / SHBG (nmol/l), sadac TT – saerTo testosteroni nmol/l da

SHBG -steroidSemboWveli globulini nmol/l.

2.2.4 Tavisufali da bioSeRwevadi testosteronis gaangariSebis

maTematikuri modelebi

Tavisufali da bioSeRwevadi testosteronis gaangariSeba SesaZlebelia

veb–saitze: http://www.issam.ch/freetesto.htm. am maTematikuri modelebis

gamoTvlisTvis aucilebelia saerTo testosteronis,

seqssteroidSemboWveli globulinis da albuminis koncentraciis

gansazRvra sisxlSi.

2.2.5 insulinrezistentobis indeqsis Homa-2 gansazRvra

insulinrezistentobis indeqsis Homa-2 kalkulatoris naxva

SesaZlebelia veb–saitze www.dtu.ox.ac.uk/homa. Homa-IR (the homeostasis model

assessment for insulin resistance) gamoTvlisTvis saWiroa bazaluri glukozis,

C-peptidis an insulinis koncentraciis gansazRvra.

46

2.2.6 policistozuri sakvercxeebis sindromis dadgenis

kriteriumebi

roterdamis konsesusis (2003 w.) Tanaxmad policistozuri sakvercxeebis

sindromis diagnostirebisTvis gamoyofilia 3 kriteriumi, saidanac 2 mainc

unda iyos dadebiTi: 1. oligomenorea da/an anovulacia 2. sisxlSi

hiperandrogenia da/an klinikuri hiperandrogenia 3. policistozuri

sakvercxeebi dadgenili ultrabgeriTi kvleviT. amave dros gamoricxuli

unda iyos yvela sxva SesaZlo mizezi, romelsac axasiaTebs

araregularuli menstruaciuli cikli da hiperandrogenia

(adrenogenitaluri sindromi, kuSingis sindromi, hiperprolaqtinemia,

androgenmaproducirebeli simsivne).

2.2.7 ultrabgeriTi kvlevis meTodi

yvela pacients utardeboda mcire menjis Rrus organoebis abdominaluri

an endovaginaluri ultrabgeriTi gamokvleva Siemens firmis Sonoline G 50

aparatiT. policistozuri sakvercxeebis dadgenis kriteriumad iTvleboda

Semdegi, Tu erT sakvercxeSi mainc aRiniSneboda 2–9 mm. zomis 12–ze meti

siTxuri CanarTi da/an sakvercxeebis moculoba iyo 10 sm3 meti (roterdamis

konsesusis (2003 w).

2.2.8 monacemebis statistikuri damuSaveba

monacemebi muSavdeboda statistikuri programiT SPSS software (statistical

Package for the Social Sciences, version 17.0 for windows XP; SPSS, Inc, Chicago, I17).

statistikurad sarwmunod ganixileboda sarwmunoebis maCvenebeli P–s

mniSvneloba naklebi 0,05–ze (P<0,05). ori jgufis saSualoebi Sedarebuli

iyo erTmaneTTan Independent-Samples T-test gamoyenebiT, xolo araparametruli

monacemebis SemTxvevaSi Mann-Whitney U test gamoyenebiT. or jgufze meti

jgufebis saSualoebi Sedarebuli iyo ANOVA with post hoc gamoyenebiT.

47

korelaciebi monacemebs Soris dgindeboda Pearson’s correlation–is

saSualebiT. meTodebis sadiagnostiko mniSvnelobis da erTmaneTis mimarT

damokidebulebis mrudis ageba xorcieldeboda ROC curve meTodiT.

48

Tavi III

sakuTari kvlevis Sedegebi

3.1 pacientebis klinikuri da hormonaluri maxasiaTeblebi

kvlevaSi monawileobas Rebulobda 13–28 wlamde 111 pacienti, romelTa

saSualo asaki Seadgenda 17,7 (±3,3) wels. pacientTa mTel jgufSi

hirsutizmi aReniSneboda 86 (77,5%) pacients , akne – 76 (68,5%), kanis

hiperpigmentacia acantosis nigricans – 30 (27%), sxeulis Warbi wona – 37 (33,3%),

visceraluri, mamakacuri tipis gacximovneba – 39 (35,1%). araregularuli

menstruaciuli cikli hqonda 85 (76,6%) pacients. diagnozebis mixedviT

pacientebi gadanawilda Semdegnairad: policistozuri sakvercxeebis

sindromi daudginda 43 pacients (38,7%), araklasikuri forma

adrenogenitaluri sindromis 38 pacients (34,2%) da hiperprolaqtinemiis

sindromi 30 pacients (27%).

mcire menjis Rrus organoebis ultrabgeriTi gamokvleviT savercxeebSi

mravlobiTi CanarTebi gamovlinda 42 pacientSi (37,8%), maT Soris 30

pacients (71,4%) sakvercxeebi gazrdili hqonda moculobaSi. xolo normis

farglebSi sakvercxeebis struqtura hqonda 69 pacients (62,2%), aqedan 18

pacients (43,2%) gazrdili hqonda sakvercxeebis moculoba (ix. diagrama 1).

diagrama 1. pacientebis ganawileba normaluri da policistozuri

sakvercxeebis struqturis mixedviT %

49

ojaxuri anamnezis SekrebiT pacientebis axlo naTesavebSi Warbi wona

gamovlinda 7 SemTxvevaSi (6,3%), WarbTmianoba - 20 SemTxvevaSi (18%),

Saqriani diabeti tipi 2 – 21 SemTxvevaSi (18,9%), Saqriani diabetis da

WarbTmianobas Tanaarseboba - 3 SemTxvevaSi (2,7%), pacientis dedas

anamnezSi sakvercxeebis policistozi aReniSneboda 10 SemTxvevaSi (9%),

janmrTeli memkvidreoba - 50 SemTxvevaSi (45%) (ix. diagrama 2).

diagrama 2. pacientTa ganawileba damZimebuli memkvidreobis da ojaxuri

anmnezis mixedviT %

50

gadatanili daavadebebis SeswavliT wiTela, wiTura, Cutyvavila

gadatanili hqonda - 63 pacients (56,8%), tonzileqtomia -25 (22,5%),

virusuli hepatiti „a“– 3 pacients (2,7%), raime gadatanil daavadebas ar

aRniSnavda -20 pacienti (18%) (ix. diagrama 3).

diagrama 3. pacientebis ganawileba gadatanili daavadebebis mixedviT (%)

sakontrolo jgufi Seadgina sakvlevi jgufis Sesabamisi asakis (15–30 w.

saSualo asakis) praqtikulad janmrTelma qalma, romlebsac ar

aReniSnebodaT androgenizaciis gamovlinebebi da menstruaciuli ciklis

darRvevebi.

51

pacientTa saerTo jgufSi Catarda hormonaluri maCveneblebis saSualoebis

SedarebiTi analizi sakontrolo jgufSTan. jgufebs Soris parametruli

monacemebi Sedarebuli iyo erTmaneTTan Independent-Samples T-test gamoyenebiT,

xolo araparametruli monacemebis SemTxvevaSi Mann-Whitney U test-is

gamoyenebiT. pacientTa saerTo jgufSi saerTo testosteronis (TT) saSualo

maCvenebeli (2,4±1,1 ng/ml) iseve rogorc Tavisufali testosteronis (FT)

saSualo maCvenebeli (3,7±1,7 pgr/ml) statistikurad sarwmunod maRali iyo

sakontrolo jgufis monacemebTan SedarebiT, (1,7±0,4 ng/ml, p=0,001; 1,7±0,7

pgr/ml, p=0,037). Tavisufali androgenebis indeqsi (FAI) 15±4,8 statistikurad

sarwmunod maRali aRmoCnda sakontrolo jgufis Sesabamis maCvenebelTan

SedarebiT 4,8±2,2 (p=0,001). sapirispirod seqsteroidSemboWveli globulinis

(SHBG) saSualo maCvenebeli 28,7±23,1 nmol/l sakvlev pacientTa jgufSi

iyo statistikurad sarwmunod dabali sakontrolo jgufis maCvenebelTan

SedarebiT (40,5±23 nmol/l, p=0,044), gaangariSebuli Tavisuali

testosteronis (cFT) saSualo maCvenebeli pacientTa jgufSi iyo 2,3±0,8

statistikurad sarwmunod maRali sakontrolo jgufTan SedarebiT 1,7±0,4

(p=0,001), aseve gaangariSebuli bioSeRwevadi testosteroni

(cBio-T) statistikurad maRali iyo sakontrolo jgufTan SedarebiT 53,3±18,3

(p=0,001). dehidroepiandrosteron-sulfatis (DHEA-S) da

17α -oqsihidroqsiprogesteronis (17α–OHP) saSualo maCvenebeli pacientTa

jgufSi iyo statistikurad maRali sakontrolo jgufTan SedarebiT

(p=0,001; p=0,021). pacientTa saerTo jgufSi C–peptidi (C-peptide) saSualo

maCvenebeli iyo 2,2 ±1,1 ng/ml, statistikurad sarwmunod maRali aRmoCnda

sakontrolo jgufis Sesabamis maCvenebelTan SedarebiT

(1,3±0,2 ng/ml, p=0,001). insulinrezistentobis indeqsi (Homa-IR) 1,6±0,8; aseve

sarwmunod maRali aRmoCnda pacientTa jgufSi (p=0,041). prolaqtinis (Prl)

saSualo maCvenebeli pacientTa jgufSi 21,3 ±15,9 ng/ml, rac statistikurad

sarwmunod maRali iyo sakontrolo jgufis maCvenebelTan SedarebiT

13,8±8,5 ng/ml (p=0,005). statistikurad sarwmuno sxvaoba ar aRiniSna

jgufebs Soris folikulmastimulirebeli hormoni (FSH),

maluTeinizirebeli hormoni (LH), estradioli (E2) da

52

Tireomastimulirebeli hormoni (TSH) saSualo maCveneblebis mixedviT

(p=0,909; p=0,130; p=0,223; p=0,452).

cxrili 1

pacientTa sakvlev saerTo jgufSi da sakontrolo jgufSi hormonaluri

maCveneblebis saSualoebis SedarebiTi analizi

maCveneblebi sakvlevi saerTo

jgufi

sakontrolo

jgufi

P -value

TT 2,4 (±1,1)* 1,7 (±0,4) 0,001

FT 3,7 (±1,7)* 1,7 (±0,7) 0,037

SHBG 28,7 (±23,1)* 40,5 (±23) 0,044

FAI 15 (±4,8)* 4,8 (±2,2) 0,001

cFT 2,3 (±0,8)* 1,7 (±0,4) 0,001

cBio-T 53,3 (±18,3)* 39,8 (±9,2) 0,001

DHEA-S 2,8 (±1,7)* 1,5 (±0,4) 0,001

17α - OHP 1,3 (±0,6)* 0,9 (±0,2) 0,021

C-peptide 2,2 (±1,1)* 1,5 (±0,3) 0,001

Homa-IR 1,6 (±0,8)* 1,3 (±0,2) 0,041

FSH 8,8 (±3,0) 8,9 (±1,9) 0,909

LH 8,7 (±7,4) 5,1 (±1,6) 0,130

E2 38,2,6 (±30,6) 27,1 (±15,2) 0,223

Prl 21,3 (±15,9)* 13,8 (±8,5) 0,005

TSH 2,1 (±1,2)* 1,9 (±1,2 ) 0,452

SeniSvna: P<0,05 miCneuli iyo statistikurad sarwmuno maCveneblad.

* – sarwmuno sxvaoba jgufebs Soris

53

3.2 pacientebSi hiperandrogenizmiT klinikuri simptomebis da androgenuli

parametrebis korelaciebi

sakvlevi pacientebi dayofil iqna 2 ZiriTad jgufad : I jgufi Sedgeboda

hirsutizmis mqone 86 pacientisgan (77,5%) da II jgufi – 25 pacientisgan

hirsutizmis gareSe (22,5%). hirsutizmis mqone pacientebis jgufSi akne

aReniSneboda 61 pacients (70,9%), acantosis nigricans – 25 pacients (29,1%),

Warbi wona hqonda 28 pacients (32,6%), visceraluri simsuqne –

30 pacients (34,9%), araregularuli menstruaciuli cikli – 62 (72,1%)–s.

hirsutizmis ar mqone jgufSi akne aReniSneboda 15 pacients (60%), acantosis

nigricans – 5 pacients (20%), Warbi wona hqonda 9 (36%) pacients, visceraluri

simsuqne – 9 (36%), araregularuli menstruaciuli cikli hqonda 23 (92%).

(ix. diagrama 4).

diagrama 4. klinikuri simptomebis sixSire sakvlev I da II jgufebSi

(%).

54

I jgufSi sakvercxeebis policistozi daudginda 38 pacients (44,2%),

araklasikuri forma adrenogenitaluri sindromis 27 pacients (31,4%) da

hiperprolaqtinemiis sindromi daudginda 21 pacients (24,4%). II jgufSi

policistozuri sakvercxeebis sindromi daudginda 5 pacients (20%),

adrenogenitaluri sindromis araklasikuri forma 11 (44%) pacients da

hiperprolaqtinemiis sindromi daudginda 9 pacients (36%) (ix. diagrama 5).

hirsutizmis mqone pacientTa jgufSi akne gamovlinda ufro xSirad

hiperprolaqtinemiis sindromis dros 76%-Si, vidre policistozuri

sakvercxeebis sindromis (63%) da adrenogenitaluri sindromis

araklasikuri formis (59%) dros. xolo hirsutizmis ar mqone jgufSi akne

gamovlinda ufro xSirad adrenogenitaluri sindromis araklasikuri

formis mqone pacientebSi 81%-Si, vidre policistozuri sakvercxeebis

sindromis (40%) da hiperprolaqtinemiis dros (44,4%).

diagrama 5. I da II jgufis pacientebis ganawileba diagnozebis mixedviT (%)

55

I, II da sakontrolo jgufebSi sisxlis SratSi isazRvreboda hormonebis

da gaangariSebuli androgenuli parametrebis saSualo maCveneblebi da

Semdeg Catarebul iqna SedarebiTi analizi.

rogorc cxrili 2-dan Cans I jgufSi saerTo testosteronis (TT) saSualo

maCvenebeli (2,7±1,1 ng/ml), aseve Tavisufali testosteronis (FT) saSualo

maCvenebeli (4,0±3,2 pgr/ml) statistikurad sarwmunod maRali iyo

sakontrolo jgufTan SedarebiT (1,7±0,4 ng/ml, p=0,009; 1,7±0,7 pgr/ml,

p=0,005). Tavisufali androgenebis indeqsis (FAI) (14,0±10,9) saSualo

maCvenebeli statistikurad sarwmunod maRali aRmoCnda sakontrolo

jgufTan SedarebiT (4,8±2,2 p=0,001), sapirispirod seqssteroidSemboWveli

globulinis (SHBG) saSualo maCvenebeli sakvlev pacientTa jgufSi

(28,9±22,4 nmol/l) statistikurad sarwmunod dabali iyo sakontrolo

jgufis maCvenebelTan SedarebiT (40,5±23 nmol/l, p=0,006). gaangariSebuli

Tavisufali testosteronis (cFT) saSualo maCvenebeli (2,2±0,8) da

bioSeRwevdi testosteronis (cBio-T) saSualo maCvenebeli (52,7±17,8)

statistikurad sarwmunod maRali iyo sakontrolo jgufTan SedarebiT

(1,7±0,4;p=0,001;39,8±9,2;p=0,001).

17α-hidroqsiprogesteronis (17α-OHP) saSualo maCvenebeli (1,2±0,8 ng/ml) da

dehidroepiandrosteron-sulfatis (DHEA-S) saSualo maCvenebeli iyo

(2,9±1,8 µg/dl) aRmoCnda statistikurad sarwmunod maRali sakontrolo

jgufTan SedarebiT (0,5±0,2 ng/ml, p=0,015; 1,8±0,4 µg/dl, p=0,001). jgufebs

Soris statistikurad sarwmuno sxvaoba ar gamovlinda C–peptidis

(C-peptide), insulinrezistentobis indeqsi (Homa-IR),

folikulmastimulirebeli hormoni (FSH), maluTeinizirebeli hormoni (LH),

estradioli (E2), prolaqtini (Prl) da Tireomastimulirebeli hormonis

(TSH) saSualo maCveneblebis mixedviT (p >0,05) (ix. cxrili 2).

56

cxrili 2

hirsutizmis mqone da sakontrolo jgufebSi hormonaluri maCveneblebis

saSualoebis SedarebiTi analizi

maCveneblebi I jgufi

hirsutizmiT

sakontrolo

jgufi

p -value

TT 2,7 (±1,1)* 1,7 (±0,4) 0,009

FT 4,0 (±3,2)* 1,7 (±0,7) 0,005

SHBG 28,9 (±22,4)* 40,5 (±23) 0,006

FAI 14,0 (±10,9)* 4,8 (±2,2) 0,001

cFT 2,2 (±0,8)* 1,7 (±0,4) 0,001

cBio-T 52,7 (±17,8)* 39,8 (±9,2) 0,001

DHEA-S 2,9 (±1,8)* 1,8 (±0,4 ) 0,001

17α - OHP 1,2 (±0,8)* 0,5 (±0,2) 0,015

C-peptide 2,0 (±1,5) 1,5 (±0,3) 0,140

Homa-IR 1,5 (±1,3) 0,8 (±0,2) 0,303

FSH 8,6 (±3,1) 8,9 (±1,9) 0,783

LH 8,8 (±8,0) 5,1 (±1,6) 0,409

E2 42,7 (±34) 27,1 (±15,2) 0,205

Prl 20,5 (±16,6) 14,2 (±8,5) 0,067

TSH 2,2 (±1,9) 1,2 (±1,1) 0,426

SeniSvna: P<0,05 miCneuli iyo statistikurad sarwmuno maCveneblad.

* – sarwmuno sxvaoba jgufebs Soris

57

hirsutizmis ar mqone II jgufSi (ix. cxrili 3) saerTo testosteronis (TT)

saSualo maCvenebeli (2,1±0,7 ng/ml) ar iyo statistikurad sarwmunod

maRali sakontrolo jgufis maCvenebelTan SedarebiT (1,7±0,4 ng/ml; p=0,155).

Tavisufali testosteronis (FT) saSualo maCvenebeli (3,1±1,7 pgr/ml)

statistikurad sarwmunod maRali iyo sakontrolo jgufis Sesabamis

maCvenebelTan SedarebiT (1,6±0,7 pgr/ml; p=0,027). seqssteroidSemboWveli

globulinis (SHBG) saSualo maCvenebeli (29,9±25,6 nmol/l) statistikurad

sarwmunod dabali iyo sakontrolo jgufis maCvenebelTn SedarebiT

(40,5±23 nmol/l; p=0,027). Tavisufali androgenebis indeqsis (FAI) saSualo

maCvenebeli (11,6±7,9), gaangariSebuli Tavisufali testosteronis (cFT)

saSualo maCvenebeli (2,2±0,8), gaangariSebuli bioSeRwevadi testosteronis

(cBio-T) saSualo maCvenebeli (52,2±17,6) statistikurad sarwmunod maRali

iyo sakontrolo jgufis maCvenebelTan SedarebiT (4,8±2,2; p=0,004; 1,7±0,4

p=0,008; 39,8±9,2 p=0,004). aseve 17α-hidroqsiprogesteronis (17-OHP) saSualo

maCvenebeli (1,6±0,8 ng/ml) da dehidroepiandrosteron-sulfatis (DHEA-S)

saSualo maCvenebeli (2,6±1,2 µg/dl) statistikurad sarwmunod maRali iyo

sakontrolo jgufis maCvenebelTan SedarebiT (0,9±0,2 ng/ml, p=0,001;

1,5±0,4 g/dl, p=0,034). C-peptidis (C-peptide) saSualo maCvenebeli (2,7±1,0 ng/ml)

da insulinrezistentobis indeqsi (Homa-IR) (1,9±0,7) aRmoCnda statistikurad

sarwmunod maRali sakontrolo jgufis maCvenebelTan SedarebiT

(1,5±0,3 ng/ml, p=0,001; 1,9±0,7ng/ml; p=0,005). prolaqtinis (Prl) saSualo

maCvenebeli iyo (24,5±13,8 ng/ml) statistikurad sarwmunod maRali

sakontrolo jgufis maCvenebelTn SedarebiT (13,8±8,5 ng/ml; p=0,004).

jgufebs Soris statistikurad sarwmuno sxvaoba ar gamovlinda

folikulmastimulirebeli hormonis (FSH), maluTeinizirebeli hormonis

(LH), estradiolis (E2) da Tireomastimulirebeli hormonis (TSH) saSualo

maCveneblebis mixedviT (p >0,05).

58

cxrili 3

hirsutizmis ar mqone da sakontrolo jgufebSi hormonaluri

maCveneblebis saSualoebis SedarebiTi analizi

maCveneblebi II jgufi

hirsutizmis gareSe

sakontrolo

jgufi

P -value

TT 2,1 (±0,7) 1,7 (±0,4) 0,155

FT 3,1 (±1,7)* 1,6 (±0,7) 0,027

SHBG 29,9 (±25,6)* 40,5 (±23) 0,027

FAI 11,6 (±7,9)* 4,8 (±2,2) 0,004

cFT 2,2 (±0,8)* 1,7 (±0,4) 0,008

cBio-T 52,2 (±17,6)* 39,8 (±9,2) 0,004

DHEA-S 2,6 (±1,2)* 1,5 (±0,4) 0,034

17α - OHP 1,6 (±0,8)* 0,9 (±0,2) 0,001

C-peptide 2,7 (±1,0)* 1,5 (±0,3) 0,001

Homa-IR 1,9 (±0,7)* 1,3 (±0,2) 0,005

FSH 9,5 (±2,6) 8,9 (±1,9) 0,568

LH 7,9 (±5,6) 5,1 (±1,6) 0,273

E2 26,6 (±13,8) 27,1 (±15,2) 0,938

Prl 24,5 (±13,8)* 13,8 (±8,5) 0,004

TSH 1,9 (±1,1) 1,9 (±1,2 ) 0,913

SeniSvna: P<0,05 miCneuli iyo statistikurad sarwmuno maCveneblad.

* – sarwmuno sxvaoba jgufebs Soris

59

I da II jgufebs Soris Catarebuli saSualoebis SedarebiTi analiziT ar

gamovlinda statistikurad sarwmunod sxvaoba arcerT parametrs Soris

(p >0,05) (ix. cxrili 4). amgvarad, hirsutizmis mqone da ar mqone pacientTa

jgufebSi gamovlinda hormonaluri maCveneblebis da androgenuli

parametrebis saSualo maCveneblebis matebis tendencia, Tumca jgufebs

Soris statistikurad sarwmuno sxvaoba ar gamovlinda.

cxrili 4

hirsutizmis da hirsutizmis ar mqone jgufebSi hormonaluri maCveneblebis

saSualoebis SedarebiTi analizi

მაჩვენებლები I ჯგუფი II ჯგუფი P -value

TT 2,4 (±1,1) 2,1 (±0,7) 0,230

FT 4,0 (±3,2) 3,1 (±1,6) 0,733

SHBG 28,9 (± 22,4) 29,9 (±25,6) 0,951

FAI 14,0 (±10,9) 11,6 (±7,9) 0,505

cFT 2,2 (±0,8) 2,2 (±0,8) 0,894

cBio-T 52,7 (±17,8) 52,2 (±17,6) 0,895

DHEA-S 2,9 (±1,8) 2,6 (±1,2) 0,704

17α - OHP 1,2 (±0,5) 1,6 (±0,9) 0,060

C-peptide 2,0 (±1,1) 2,7 (±1,0) 0,043

Homa-IR 1,5 (±0,8) 1,9 (±0,7) 0,044

FSH 8,6 (±3,1) 9,5 (±2,6) 0,431

LH 8,8 (±8,0) 7,9 (±5,6) 0,782

E2 42,7 (±34) 26,6 (±13,8) 0,151

Prl 20,5 (±16,6) 24,5 (±13,8) 0,078

TSH 2,2 (±1,2) 1,9 (±1,1) 0,463

SeniSvna: P<0,05 miCneuli iyo statistikurad sarwmuno maCveneblad.

60

hirsutizmis xarisxis Sefaseba moxda Ferriman, Galwey (1961w) mier

modificirebuli sqemis mixedviT, sadac hirsutizmi fasdeba sxeulis 9

zonaze (fexis wvivebis da xelebis gamoklebiT) da gamoxatulobis

xarisxis mixedviT gamoyofilia hirsutizmis 3 forma: msubuqi (8-16 qula),

saSualo simZimis (17-24 qula) da mZime (25 qula da meti). Sesabamisad

pacientebi dayofili iyvnen 3 jgufad: msubuqi hirsutizmi aReniSneboda

25 pacients (22,5%), saSualo simZimis hirsutizmi - 50 pacients (45%) da mZime

hirsutizmi - 36 pacients (32,4%). jgufebs Soris Catarebuli androgenuli

markerebis saSualoebis parametruli monacemebi Sedarebuli iyo

erTmaneTTan Independent-Samples T-test gamoyenebiT, xolo araparametruli

monacemebis SemTxvevaSi Mann-Whitney U test-is gamoyenebiT. sarwmunod maRali

msubuqi hirsutizmis mqone pacientTa jgufis saSualo maCvenebelTan

SedarebiT (P1=0,008, P2=0,029), xolo mZime da saSualo simZimis hirsutizmis

mqone pacientTa jgufebs Soris saerTo testosteronis (TT) saSualo

maCvenebeli statistikurad sarwmunod ar gansxvavdeboda (P3=0,815).

aRsaniSnavia, rom Tavisufali testosteronis (FT) saSualo maCvenebeli

msubuqi, saSualo da mZime hirsutizmis mqone pacientTa jgufebs Soris

statistikurad sarwmunod ar gansxvavdeboda (P1=0,097, P2=0,082, P3=0,796).

seqssteroidSemboWveli globulinis (SHBG) saSualo maCvenebeli msubuqi,

saSualo da mZime hirsutizmis mqone pacientTa jgufebs Soris aseve

statistikurad sarwmunod ar gansxvavdeboda (P1=0,210, P2=0,340, P3=0,854).

Tavisufali androgenebis indeqsis (FAI) saSualo maCvenebeli mZime da

saSualo simZimis hirsutizmis mqone pacientebSi iyo statistikurad

sarwmunod maRali msubuqi hirsutizmis mqone pacientebis maCvenebelTan

SedarebiT (P1=0,007, P2=0,019). sainteresoa rom, mZime da saSualo simZimis

hirsutizmis mqone pacientTa jgufebes Soris Tavisufali androgenebis

indeqsis (FAI) saSualo maCvenebeli statistikurad sarwmunod ar

gansxvavdeboda (P3=0,922). aRmoCnda, rom gaangariSebuli Tavisufali

testosteronis (cFT) saSualo maCvenebeli. msubuqi, saSualo da mZime

hirsutizmis mqone pacientTa jgufebs Soris statistikurad sarwmunod ar

gansxvavdeboda (P1=0,094, P2=0,182, P3=0,852). aseve gaangariSebuli

bioSeRwevadi testosteronis (cBio-T) saSualo maCvenebeli msubuqi, saSualo

61

da mZime hirsutizmis mqone pacientTa jgufebs Soris sarwmunod ar

gansxvavdeboda (P1=0,075, P2=0,153, P3=0,852). dehidroepiandrosteron–sulfatis

(DHEA-S) saSualo maCvenebeli msubuq hirsutizmis da saSualo simZimis

hirsutizmis mqone pacientTa jgufebs Soris statistikurad sarwmunod ar

gansxvavdeboda (P1=0,545). Tumca aRsaniSnavia, rom mZime xarisxis

hirsutizmis pacientTa jgufSi dehidroepiandrosteron–sulfatis (DHEA-S)

saSualo maCvenebeli iyo statistikurad sarwmunod maRali (P2=0,002,

P3=0,004) vidre msubuqi hirsutizmis da saSualo simZimis hirsutizmis mqone

pacientTa jgufebSi. 17α – OHP saSualo maCvenebeli msubuqi, saSualo da

mZime hirsutizmis mqone pacientTa jgufebs Soris statistikurad

sarwmunod ar gansxvavdeboda (P1=0,546, P2=0,831, P3=0,714) (ix. cxrili 5).

hirsutizmis armqone jgufis pacientebSi androgenuli parametrebis mateba

aRniSneboda 15 SemTxvevaSi (60%). saerTo testosteronis mateba -

15 pacientSi (60%), Tavisufali androgenebis indeqsis 8-ze zemoT –

15 pacientSi (60%), gaangariSebuli Tavisufali testosteronis da

bioSeRwevadi testosteronis maRali maCvenebeli - 14 pacientSi (56%), xolo

seqssteroidSemboWveli globulinis normaze dabali maCvenebeli –

12 SemTxvevaSi (48%). sainteresoa, rom 8 SemTxvevaSi (32%) gamovlinda

saerToO testosteronis maCvenebeli normis farglebSi da

seqssteroidSemboWveli globulinis dabali maCvenebeli.

62

cxrili 5

sakvlevi jgufis pacientebSi hirsutizmis xarisxis da androgenuli

parametrebis SedarebiTi analizi

maCveneblebi 0 – 7 qula 8 -16 qula 17 > qula

TT 1,9 (±0,6)

2,5 (± 1,2)

P1=0,008

2,4 (± 1,2)

P2=0,029

P3=0,815

FT 2,5 (± 1,4)

3,9 (±2,5)

P1=0,097

4,1 (±4,0)

P2=0,082

P3=0,796

SHBG 34,6 (±24,8) 28,5 (±21,7)

P1=0,210

29,5 (±23,7)

P2=0,340

P3=0,854

FAI 8,6 (±6,9) 14,1 (±11,1)

P1=0,007

13,9 (±10,9)

P2=0,019

P3=0,922

cFT 2,0 (±0,7) 2,3 (±0,8)

P1=0,094

2,2 (±0,7)

P2=0,182

P3=0,852

cBio-T 46,7 (±15,7) 53 (±18,2 )

P1=0,075

52,3 (±17,5)

P2=0,153

P3=0,852

DHEA-S 2,1 (±1,1) 2,4 (±1,4)

P1=0,545

3,6 (±2,0)

P2=0,002

P3=0,004

17α - OHP 1,2 (±0,8) 1,1 (±0,6)

P2=0,546

1,2 (±0,4)

P2=0,831

P3=0,714

SeniSvna: P<0,05 miCneuli iyo statistikurad sarwmuno maCveneblad.

* – sarwmuno sxvaoba jgufebs Soris

63

pacientTa sakvlev jgufSi pirsonis meTodiT Catarebuli korelaciuri

analiziT sxeulis masis indeqsa da androgenul parametrebs Soris

gamovlinda statistikurad sarwmuno dadebiTi korelaciebi sxeulis masis

indeqssa da Tavisufali androgenuli indeqsis (FAI) (r=0,234; p=0,008),

gaangariSebuli Tavisufali testosteronis (cFT) (r=0,216; p=0,014),

gaangariSebuli bioSeRwevadi testosteronis (cBio-T) (r=0,218; p=0,013)

maCveneblebs Sorisn da statistikurad sarwmuno uaryofiTi korelacia

seqsteroidSembowvel globulinTan (SHBG) (r=-0,248; p=0,005). aseve, sxeulis

masis indeqsa da insulinrezistentobis indeqsis (Homa-IR) maCveneblebs

Soris gamovlinda statistikurad sarwmunod dadebiTi korelacia

(r=0,454; p=0,001). aRsaniSnavia, rom korelacia ar gamovlinda sxeulis masis

indeqsa da saerTo testosterons (TT) (r=0,119; p=0,179), Tavisufali

testosteronis (FT) (r=-0,009; p=0,948) maCveneblebs Soris (ix. cxrili 6).

cxrili 6

sakvlev pacientTa jgufSi korelaciuri analizi pirsonis meTodiT

sxeulis masis indeqsa da androgenul parametrebs Soris

maCveneblebi r - koeficienti p-value

TT 0,119 0,179

FT -0,009 0,948

SHBG -0,248 0,005

FAI 0,234 0,008

cFT 0,216 0,014

cBio-T 0,218 0,013

Homa-IR 0,454 0,001

SeniSvna: P<0,05 miCneuli iyo statistikurad sarwmuno maCveneblad.

64

I jgufis pacientebi davyaviT 2 qvejgufad cximovani qsovilis ganawilebis

mixedviT. Ia - qvejgufi Seadgina 30 pacientma, romelTa welis da TeZos

garSemowerilobis Sefardeba (w.g/T.g.) iyo ≥0,8 da Ib - qvejgufi –

56 pacientma, romelTa w.g/T.g. iyo ≤0,79. sainteresoa, rom Ib - qvejgufSi

Tavisufali androgenebis indeqsis (FAI) (23,2 ±19,6; p=0,022), gaangariSebuli

Tavisufali testosteronis (2,6±0,7; p=0,005) da gaangariSebuli bioSeRwevadi

testosteronis (61,1±16,6; p=0,005) saSualo maCvenebeli statistikurad

sarwmunod maRali iyo Ia - qvejgufis Sesabamis saSualo maCvenebelTan

SedarebiT. sapirispirod, Ib-qvejgufis pacientebSi seqssteroidSemboWveli

globulinis (SHBG) (p=0,001) saSualo maCvenebeli statistikurad sarwmunod

dabali iyo Ia -qvejgufis saSualo maCvenebelTan SedarebiT. arcerT

qvejgufSi ar gamovlinda statistikurad sarwmuno sxvaoba saerTo

testosteronis (TT), Tavisufali testosteronis

(FT),dehidroepiandrosteron–sulfatis(DHEA-S),

17α-hidroqsiprogesteronis (17α-OHP), C–peptidis (C-peptide) da

insulinrezistentobis indeqsis (Homa-IR) maCveneblebs Soris (p>0,05)

(ix. cxrili 7).

65

cxrili 7

I jgufis ginoiduri da visceraluri simsuqnis mqone pacientebis

hormonaluri maCveneblebis saSualoebis SedarebiTi analizi

maCveneblebi

Ia qvejgufi –

pacientebi

ginoiduri

simsuqniT

I b qvejgufi –

pacientebi

visceraluri

simsuqniT

P -value

TT 2,4 (±1,2) 2,5 (±1,0) 0,647

FT 4,0 (±2,9) 3,9 (±3,7) 0,971

SHBG 33,4 (±25,0)* 18,9 (±12,4) 0,016

FAI 12,1 (±10,0)* 23,2 (±19,6) 0,032

cFT 2,1 (±0,8)* 2,6 (±0,7) 0,018

cBio-T 49,5 (±18,6)* 61,1 (±16,6) 0,019

DHEA-S 2,8 (±1,8) 3,0 (±1,9) 0,729

17α- OHP 1,1 (±0,5) 1,4 (±0,9) 0,206

C-peptide 1,8 (±1,1) 2,2 (±1,0) 0,106

Homa-IR 1,3 (±0,8) 1,6 (±0,7) 0,090

SeniSvna: P<0,05 miCneuli iyo statistikurad sarwmuno maCveneblad.

*– sarwmuno sxvaoba jgufebs Soris

66

3.3 korelaciebi hiperandrogenizmis klinikur da hormonul markerebs

Soris qalebSi policistozuri sakvercxeebis sindromiT,

adrenogenitaluri sindromis araklasikuri formiT da

hiperprolaqtinemiis sindromiT.

diagnozebis mixedviT pacientebi ganawilda 3 jgufSi. I jgufi

policistozuri sakvercxeebis sindromiT Seadgina – 43 pacientma, II jgufi

adrenogenitaluri sindromis araklasikuri formiT - 38 pacientma da III

jgufi hiperprolaqtinemiis sindromiT - 30 pacientma.

policistozuri sakvercxeebis sindromis mqone pacientT jgufSi sxeulis

Warbi wona aReniSneboda 24 pacients (55,8%), visceraluri simsuqne –

22 (51,2%), hirsutizmi – 38 (88,4%), akne – 29 (67,4%) da acantosis nigricans –

15 (34,9%). araregularuli menstruaciuli cikli aReniSneboda 35 pacients

(81,4%) da ultrabgeriTi gamokvleviT policistozuri sakvercxeebi

13 pacients (30,2%).

araklasikuri adrenogenitaluri sindromis mqone pacientTa jgufSi

sxeulis Warbi wona aReniSneboda 7 pacients (18,4%), visceraluri simsuqne-

7 (18,4%), hirsutizmi – 27 (71,1%), akne – 27 (71,1%) da acantosis nigricans –

5 (13,2%). araregularuli menstruaciuli cikli gamouvlinda 25 pacients

(65,8%) da ultrabgeriTi gamokvleviT policistozuri sakvercxeebi

16 pacients (42,1%).

hiperprolaqtinemiis sindromis mqone pacientTa jgufSi Warbi wona

aReniSneboda 11 pacients (36,7%), visceraluri simsuqne – 10 (33,3%),

hirsurtizmi – 21 (70%), akne – 20 (66,7%) da acantosis nigricans 10 (33,3%).

araregularuli menstruaciuli cikli aReniSneboda 25 pacients (83,3%) da

ultrabgeriTi gamokvleviT policistozuri sakvercxeebi 13 pacients

(43,3%). (ix.diagrama 6.)

67

diagrama 6. sxvadasxva klinikuri simptomis sixSire pacientebSi

policistozuri sakvercxeebis sindromiT, adrenogenitaluri sindromis

araklasikuri formiT da hiperprolaqtinemiis sindromiT (%).

68

policistozuri sakvercxeebis sindromis mqone pacientT jgufSi (43)

androgenuli markerebis saSualo maCveneblebi Seadgenda: saerTo

testosteroni (TT) 2,4±1,1 ng/ml; Tavisufali testosteroni (FT) 3,4 ±1,9

pgr/ml; seqssteroidSemboWveli globulini (SHBG) 28,3±21 nmol/l;

Tavisufali androgenebis indeqsi (FAI) 14,9±12,2; gaangariSebuli Tavisufali

testosteroni (cFT) 2,3 (±0,8); gaangariSebuli bioSeRwevadi testosteroni

(cBio-T) 53,3±20; dehidroepiandrosteron–sulfaTi (DHEA-S) 3,0 ±2,3 g/dl;

estradioli (E2) 40,3±31,2 ng/ml; insulinrezistentobis maCveneblebi

C–peptidi (C-peptide) 2,0 ±1,1 ng/ml; insulinrezistentobis indeqsi (Homa-IR)

1,5 ±0,9.

araklasikuri adrenogenitaluri sindromis mqone pacientTa jgufSi (38)

androgenuli markerebis saSualo maCveneblebi Seadgenda: saerTo

testosteroni (TT) 2,4±1,0 ng/ml; Tavisufali testosteroni (FT)

4,2 ±2,8 pgr/ml; seqssteroidSemboWveli globulini (SHBG) 32,2 ±26,4 nmol/l;

Tavisufali androgenebis indeqsi (FAI)12,4±9,4; gaangariSebuli androgenuli

testosteroni (cFT) 2,1±0,7; gaangariSebuli bioSeRwevadi testosteroni

(cBio-T) 50,2 ±17,3; dehidroepiandrosteron–sulfaTi (DHEA-S) 2,9 ±1,5g/dl;

estradioli (E2) 30,1±22,6 ng/ml; insulinrezistentobis maCveneblebi

C–peptidi (C-peptide) 2,1 ±0,7 ng/ml; insulinrezistentobis indeqsi (Homa-IR)

1,4 ±0,6.

hiperprolaqtinemiis sindromis mqone pacientTa jgufSi (30) androgenuli

markerebis saSualo maCveneblebi Seadgenda: saerTo testosteroni (TT)

2,2±1,0 ng/ml; Tavisufali testosteroni (FT) 3,9±3,4 pgr/ml;

seqssteroidSemboWveli globulini (SHBG) 26,4 ±21,8 nmol/l; Tavisufali

androgenebis indeqsi (FAI) 12,9±8,6; gaangariSebuli Tavisufali

testosteroni (cFT) 2,3±0,7; gaangariSebuli bioSeRwevadi testosteroni

(cBio-T) 54,5 (±16,9); dehidroepiandrosteron–sulfaTi (DHEA-S) 2,6±1,2 µg/dl;

estradioli (E2) 42,5 ±34,5 ng/ml; insulinrezistentobis maCveneblebi

C–peptidi (C-peptide) 2,5 ±1,2 ng/ml; insulinrezistentobis indeqsi (Homa-IR)

1,9 (±0,8).

69

jgufebs Soris Catarebuli androgenuli da insulinrezistentobis

markerebis saSualoebis parametruli monacemebi Sedarebuli iyo

erTmaneTTan Independent-Samples T-test gamoyenebiT, xolo araparametruli

monacemebis SemTxvevaSi Mann-Whitney U test-is gamoyenebiT. Catarebuli

analiziT jgufebs Soris arcerTi maCveneblis mixedviT statistikurad

sarwmunod sxvaoba ar gamovlinda (p >0,05) (ix. cxrili 8).

amgvarad, policistozuri sakvercxeebis sindromis, araklasikuri

adrenogenitaluri sindromis da hiperprolaqtinemiis sindromis mqone

pacientebSi gamovlinda yvela androgenuli parametris maRali

maCveneblebi. Tumca, aRsaniSnavia, rom jgufebs Soris am parametrebs Soris

statistikurad sarwmuno sxvaoba ar gamovlinda.

70

cxrili 8

sxvadasxva sindromebis mqone pacientTa androgenuli da

insulinrezistentobis markerebis saSualoebis SedarebiTi analizi

maCvenebeli sakvercxeebis

policistozi

(n=43)

adrenogenitaluri

sindromis

araklasikuri

forma (n=38)

hiperprolaqtinemis

sibdromi (n=30)

p-value

TT 2,4 (±1,1) 2,4 (±1,0) 2,2 (±1,0) p >0,05

FT 3,4 (±1,9) 4,2 (±2,8) 3,9 (±3,4) p >0,05

SHBG 28,3 (±21) 32,2 (±26,4) 26,4 (±21,8) p >0,05

FAI 14,9 (±12,2) 12,4 (±9,4) 12,9 (±8,6) p >0,05

cFT 2,3 (±0,8) 2,1 (±0,7) 2,3 (±0,7) p >0,05

cBio-T 53,3 (±20) 50,2 (±17,3) 54,5 (±16,9) p >0,05

DHEA-S 3,0 (±2,3) 2,9 (±1,5) 2,6 (±1,2 ) p >0,05

E2 40,3 (±31,2) 30,1 (±22,6) 42,5 (±34,5) p >0,05

C-peptide 2,0 (±1,1) 2,1 (±0,7) 2,5 (±1,2) p >0,05

Homa-IR 1,5 (±0,9) 1,4 (±0,6) 1,9 (±0,8) p >0,05

SeniSvna: P<0,05 miCneuli iyo statistikurad sarwmuno maCveneblad

71

3.4 hiperandrogenizmis Sefasebis sxvadasxva diagnostikuri meTodebis

SedarebiTi analizi axalgazrda qalebSi hirsutizmiT

35 pacients hirsutizmiT da sxvadasxva diagnoziT Cautarda Tavisufali

androgenebis indeqsis, Tavisufali da bioSeRwevadi testosteronis

gaangariSeba da Tavisufali testosteronis gansazRvra sisxlSi -

imunofermentuli (ELISA) meTodiT. Catarda korelaciuri analizi

gamokvlevis mocemuli meTodebiT miRebul Sedegebs Soris. gamovlinda

sarwmunod dadebiTi korelaciebi ELISA–meTodiT gansazRvrul Tavisufal

testosteronsa, saerTo testosteronsa (r=0,592; p=0,001) da Tavisufali

androgenebis indeqss (r=0,461; p=0,005) Soris. Tavisufal testosterons da

seqsteroidSemboWveli globulinisa (SHBG), gaangariSebuli Tavisufali

testosteronisa (cFT), gaangariSebuli bioSeRwevadi testosteronisa

(cBio-T), hirsutul ricxvTan korelaciebi ar gamovlinda (ix. cxrili 9).

cxrili 9

pirsonis korelaciebi imunofermentuli (ELISA) meTodiT gansazRvruli

Tavisufal testosteronis maCvenebels da hiperandrogenemiis hormonalur

parametrebs, gaangariSebul androgenul parametrebs, hirsutul ricxvTan

maCveneblebi r- koeficienti p-value

TT 0,461 0,005

SHBG -0,251 0,146

FAI 0,592 0,001

cFT 0,298 0,082

cBio-T 0,229 0,081

hirsutuli ricxvi

(feriman-galvei-iT)

0,083 0,637

SeniSvna: P<0,05 miCneuli iyo statistikurad sarwmuno maCveneblad

72

gaangariSebuli androgenuli markerebis diagnostikuri mniSvnelobis

dasadgenad hirsutizmis sxvadasxva xarisxis dros agebul iqna ROC

(Receiver operating characteristics) mrudeebi. hirsutizmis saSualo xarisxis mqone

pacientTa jgufSi FT da FAI diagnostikuri mniSvneloba iyo Tanabari

(saSualo simZimis hirsutizmisTis (n=21) auROC (FT)=0,554; auROC (cFT) = 0,493;

auROC (FAI) = 0,539). saSualo simZimis hirsutizmis mqone pacientebSi

gamovlinda Tavisufali testosteronis da Tavisufali androgenebis

indeqsis TiTqmis Tanabari diagnostikuri mniSvneloba. hirsutizmis mZime

xarisxis mqone pacientTa jgufSi gamovlinda gaangariSebuli Tavisufali

testosteronis ufro mZlavri diagnostikuri mniSvneloba, vidre

Tavisufali testosteronisa da Tavisufali androgenebis indeqsisa (mZime

hirsutizmisTis (n=14) auROC (FT)=0,446; auROC (cFT) = 0,507; auROC (FAI) = 0,461).

diagrama 7.

ROC (Receiver operating characteristics) mrude hirsutizmis saSualo xarisxsa

da FT, FAI, cFT Soris

73

diagrama 8

ROC (Receiver operating characteristics) mrude hirsutizmis saSualo xarisxsa da

FT,FAI, cFT Soris

74

Tavi 4

miRebuli Sedegebis ganxilva

hiperandrogenizmi Tanamedrove endokrinologiuri ginekologiis

mniSvnelovan problemas warmoadgens. termini hiperandrogenizmi aRniSnavs

qalebSi iseTi garegani paTologiuri simptomebis arsebobas, rogoric aris

hirsutizmi, akne, seborea, alopecia da virilizacia uxSiresad

hiperandrogenemiis fonze. qalebSi, garda samedicino problemisa

hiperandrogenizmi socialur problemasac warmoadgens, vinaidan misTvis

damaxasiaTebeli klinikuri gamovlinebebi iwvevs stress, aqveiTebs

cxovrebis xarisxs da fsiqoemociur ganviTarebas. hiperandrogenizmi

ZiriTadad sakvrcxeebSi an Tirkmelzeda jirkvlebSi androgenebis Warbi

sekreciis Sedegad viTardeba. Tumca, paTologiuri Tmianoba SesaZloa

gamoxatuli iyos androgenebis normaluri sekreciis fonze idiopaTiuri

hirsutizmis dros.

yovelive zemoT aRniSnulidan gamomdinare, naSromis mizans warmoadgenda

korelaciebis dadgena hiperandrogenizmis klinikur da hormonalur

parametrebs Soris im axalgazrda qalebSi, romelTac aReniSnebodaT

hiperandrogenizmiT gamovlenili sxvadasxva endokrinul–ginekologiuri

sindromebi (policistozuri sakvercxeebis sindromi, adrenogenitaluri

sindromis araklasikuri forma, hiperprolaqtinemiis sindromi).

kvlevis farglebSi gamokvleul iqna 13-dan - 30 wlamde asakis 111 pacienti,

romelTa ZiriTadi Civilebi iyo: menstruaciuli ciklis darRveva da/an

WarbTmianoba, akne.

Cvens mier gamokvleuli 111 pacientidan 86-s aReniSneboda hirsutizmi

(77,5%), 76 pacients – akne (68,5%). hirsutizmis mqone pacientebSi akne

gamoxatuli hqonda 61 pacients (70,9%). literaturis monacemebiT

hirsutizmi hiperandrogenizmis erT-erTi yvelaze xSiri klinikuri

gamovlinebaa. R.Azziz da Tanaavtorebis (21) mier Catarebul kvlevaSi,

75

romelSic monawileobda 800 qali hiperandrogenemiiT, hirsutizmi

gamouvlinda 75%-s, maT Soris 4,8%-s - akne. sayuradReboa, rom Cveni kvlevis

farglebSi akne gamovlinda hirsutizmis mqone pacientTa ufro did nawils.

es albaTAdakavSirebulia imasTan, rom Cvens kvlevaSi monawile pacientTa

34,2% aReniSneboda adrenogenitaluri sindromis araklasikuri forma,

romlisTvis akne damaxasiTebeli simptomia.

Cven mier gamokvleul pacientebs menstruaciuli cikli upiratesad

darRveuli hqondaT oligoamenoreis tipiT (76,6%). literaturaSi arsebuli

monacemebiT policistozuri sakvercxeebis sindromis mqone pacientTaA

60-85%-Si aReniSnebaT menstruaciuli ciklis darRveva ZiriTadad

oligoamenoreis tipiT [21, 41]. gansakuTrebiT sainteresoa is faqti, rom

kvlevaSi monawile hirsutizmis da araregularuli menstruaciuli ciklis

mqone pacientebSi akne aReniSneboda - 64,5%-Si, xolo pacientebSi

hirsutizmis gareSe da araregularuli menstruaciuli cikliT - 56,5%-Si,

rac albaT aixsneba imiT, rom sakvlev jgufSi CarTul pacientebis

mniSvnelovan wils garda policistozuri sakvercxeebis sindromis

aReniSneboda sxva sindromebic.

literaturaSi arsebuli monacemebiT hirsutizmis mqone pacientTa

mdedrobiTi sqesis naTesavebSi paTologiuri Tmianoba ufro xSirad

aRiniSneba, rogorc idiopaTiuri hirsutizmis SemTxvevebSi, aseve sxvadasxva

endokrinuli paTologiebis dros [81]. am paTologiebis ojaxuri

ganviTarebis tendencias SesaZloa hqondes genetikuri safuZveli

mag: policistozuri sakvercxeebis sindroms axasiaTebs mZlavri

memkvidruli winaswarganwyoba. Cveni monacemebiT pacientTa ojaxuri

anmnezis Sekrebisas axlo naTesavebSi gamovlinda: WarbTmianoba (18%),

Saqriani diabeti tipi 2 (18,9%) da pacientis dedas policistozuri

sakvercxeebis sindromi (9%).

Cveni kvlevis farglebSi CavatareT pacientTa saerTo jgufis da

sakontrolo jgufis SedarebiTi analizi hormonaluri androgenuli

saSualo parametrebis mixedviT. pacientTa saerTo jgufSi yvela

androgenuli parametris saSualo maCvenebeli, rogoric aris

76

testosteroni, Tavisufali testosteroni, Tavisufali androgenebis

indeqsi, gaangariSebuli Tavisufali da bioSeRwevadi testosteroni,

dehidroepiandrosteron-sulfati da 17α-hidroqsiprogesteroni

statistikurad sarwmunod maRali aRmoCnda sakontrolo jgufTan

SedarebiT. xolo seqssteroidSemboWveli globulinis maCvenebeli ki

statistikurad sarwmunod dabali iyo sakontrolo jgufTan SedarebiT.

literaturaSi arsebuli monacemebic adastureben, rom hiperandrogenizmis

mqone pacientebSi uxSiresad aRiniSneba zemoT mocemuli androgenuli

parametrebis maRali maCveneblebi [46,53,85].

literaturis monacemebiT hiperandrogenizmi damaxasiaTebelia iseTi

paTologiebisaTvis, rogoric aris: policistozuri sakvercxeebis

sindromi, hiperandrogenuli insulin-rezistentuli acanthosis nigricans

sindromi, Tirkmelzeda jirkvlebis Tandayolili hiperplazia (klasikuri

da araklasikuri forma), kuSingis sindromi, androgenmaproducirebuli

simsivneebi (sakvercxis, Tirkmelzeda jirkvlis), hiperprolaqtinemiis

sindromi) [25,28,53]. roterdamis konsesusis (2003 w.) Tanaxmad

policistozuri sakvercxeebis sindromis diagnostirebisTvis gamoyofilia

3 kriteriumi, saidanac 2 mainc unda iyos dadebiTi: 1. oligomenorea da/an

anovulacia 2. sisxlSi hiperandrogenia da/an hiperandrogenizmis klinikuri

simptomebi 3. ultrabgeriTi kvleviT dadgenili policistozuri

sakvercxeebi. amave dros gamoricxuli unda iyos yvela sxva SesaZlo

mizezi, romelsac axasiTebs araregularuli menstruaciuli cikli da

hiperandrogenia (adrenogenitaluri sindromi, kuSingis sindromi,

hiperprolaqtinemia, adrogenmaproducirebeli simsivne) [142]. Cveni kvlevis

safuZvelze hiperandrogenizmis mqone pacientebSi policistozuri

sakvercxeebis sindromi gamovlinda SemTxvevaTa - 38,7%-Si,

adrenogenitaluri sindromis araklasikuri forma - 34,2%-Si,

hiperprolaqtinemiis sindromi - 27%-Si. avtorebi aRniSnaven, rom

hiperandrogenemia da hirsutizmi yvelaze xSirad viTardeba

policistozuri sakvercxeebis sindromis dros. Moran da Tanaavtorebis

[105] monacemebiT 13-38 wlamde asakobriv jgufSi hirsutizmis mizezi

SemTxvevaTa 53%-Si policistozuri sakvercxeebis sindromi, 18%-Si –

77

simsuqne, 2%-Si –adrenogenitaluri sindromis araklasikuri forma, 0,8%-Si

– sakvercxeebis simsivne da 0,4%-Si – kuSingis sindromi an specifiuri

medikamentebis miReba iyo. Tumca, gansxvavebiT literaturis monacemebisgan

Cveni kvlevis monacemebiT hiperandrogenizmis mqone pacientebSi pacientebSi

gacilebiT xSiri aRmoCnda adrenogenitaluri sindromis araklasikuri

forma da hiperprolaqtinemiis sindromi.

ultrabgeriTi kvleviT dadgenili policistozuri sakvercxeebi

roterdamis konsesusis Tanaxmad erT-erTi Semadgeneli kriteriumia

policistozuri sakvercxeebis sindromis. Tumca, amave dros SesaZlebelia

sakvercxeebis normaluri morfologiuri suraTis SemTxvevaSi, rodesac

saxezea hiperandrogenizmi da menstruaciuli ciklis darRveva, daisvas

policistozuri sakvercxeebis sindromis diagnozi [142,83]. am kriteriumis

Tanaxmad ultrabgeriTi kvleviT sakvercxeebi moculobaSi gazrdili unda

iyos da/an erT sakvercxeSi mainc aRiniSnebodes 12-ze meti wvrilcisturi

CanarTi. sayuradReboaE is faqtic, rom policistozuri sakvercxeebi

SesaZloa dadgenil iqnes im SemTxvevaSic ki, rodesac erT sakvercxeSi

mainc aReniSneba 12-ze meti wvrilcisturi CanarTi, diametriT 2-9mm [23].

uaxlesi monacemebiT policistozuri sakvercxeebis sindromis

gansazRvraSi ufro didi mniSvneloba eniWeba sakvercxeebis moculobas,

vidre wvrilcistur CanarTebis arsebobas [87]. ACvens kvlevaSi monawile

pacientTa 37,8%-sNsakvercxeebis ultrabgeriTi kvleviT daudginda

policistozuri sakvercxeebisTvis damaxasiaTebeli morfologiuri

struqtura (12-ze meti wvrilcisturi CanarTi) da maT Soris 71,4%-s

sakvercxeebi gazrdili iyo moculobaSi. sakvercxeebis normaluri

struqtura dadginda pacientTa 62,2%-Si, aqedan 43,2%-s gazrdili hqonda

sakvercxeebis moculoba. zemoaRniSnuli monacemebi miuTiTebs imaze, rom

ultrabgeriTi gamokvleviT calsaxad sakvercxeebis gansazRvra moiTxovs

seriozul araerTmniSvnelovan Sefasebas.

imisaTvis rom gagverkvia Tu rogor damokidebulebaSia hiperandrogenizmis

sxvadasxva sindromebi erTmaneTTan androgenuli parametrebis mixedviT

pacientebi dayofil iqna 3 jgufad nozologiebis mixedviT:

I - policistozuri sakvercxeebis sindromi (38,7%), II - adrenogenitaluri

78

sindromis araklasikuri forma (34,3%) da III - hiperprolaqtinemiis

sindromi (27%). Catarebuli analiziT jgufebs Soris arcerTi

androgenuli parametris saSualo maCvenebels Soris ar gamovlinda

statistikurad sarwmunod sxvaoba (P>0,05). literaturaSi arsebuli

monacemebiT pacientebSi policistozuri sakvercxeebis sindromiT da

adrenogenitaluri sindromis arklasikuri formiT androgenuli

parametrebis maCveneblebi ar gansxvavdebodnen erTmaneTisgan da

statistikurad sarwmunod maRali iyo, vidre idiopaTiuri hirsutizmis

dros [41]. amasTan, literaturaSi ar moipoveba sakmarisi informacia am

sindromebs da hiperprolaqtinemiis sindroms Soris androgenuli

parametrebis urTierTdamokidebulebis Sesaxeb, rac Cvens kvlevaSi iyo

asaxuli. kerZod, miuxedavad etiopaTogenezuri sxvaobisa,

hiperprolaqtinemiis sindromis mqone pacientebis androgenuli parametrebi

aseve ar gansxvavdeboda policistozuri sakvercxeebis sindromis da

adrenogenitaluri sindromis araklasikuri formis mqone pacientebis

jgufSi dadgenili Sesabamisi maCveneblebisgan.

Tumca zemoT mocemuli sindromebis SemTxvevebSi androgenuli

parametrebis maCveneblebis mixedviT ar gamovlinda statistikurad

sarwmuno sxvaoba, policistozuri sakvercxeebis sindromis mqone

pacientebSi ufro xSirad gamovlinda Warbi wona, cximovani qsovilis

visceralur tipad gadanawileba da menstruaciuli ciklis darRveva, vidre

adrenogenitaluri sindromis araklasikuri formis da hiperprolaqtinemiis

sindromis dros. Carmina E da Tanaavtorebi [39] Tavisi kvlevis safuZvelze

aRniSnaven, rom pacientebSi policistozuri sakvercxeebis sindromis dros

Warbi wona ufro xSiria, vidre sxva hiperandrogenuli sindromebis dros.

isini Tvlian, rom sxeulis masis gazrda SesaZloa iyos policistozuri

sakvercxeebis sindromis fenotipis da aseve anovulaciis ganmsazRvreli

mniSvnelovani komponenti.

hiperandrogenizmis erT-erTi yvelaze xSiri klinikuri simptomis mixedviT,

rogoric aris hirsutizmi, kvlevaSi monawile pacientebi dayofil iqna

2 ZiriTad jgufad. I jgufSi gaerTianda hirsutizmis mqone 86 pacienti

(77,5%), II jgufSi – 25 pacienti (29,1%) hirsutizmis gareSe. hirsutizmis

79

xarisxis Sefaseba xdeboda Ferriman, Galwey (1961w) [67] mier modificirebuli

sqemis mixedviT, sadac hirsutizmi fasdeboda sxeulis 9 zonaze (fexis

wvivebis da xelebis gamoklebiT). jgufebs Soris ar gamovlinda

statistikurad sarwmuno sxvaoba hiperandrogenizmis sxva klinikur

simptomebis mixedviT, rogoricaa akne, acantosis nigricans, Warbi wona,

visceraluri simsuqne da menstruaciuli ciklis darRveva. ris

safuZvelzec SeiZleba davaskvnaT, rom hiperandrogenizmis erT-erTi

klinikuri simptomi - hirsutizmi ar korelirebs hiperandrogenizmis sxva

klinikur simptomebTan. am TvalsazrisiT literaturaSi ar arsebobs raime

sarwmuno monacemebi.

pacientTa orive jgufis (hirsutizmiT da hirsutizmis gareSe) androgenuli

parametrebi SevadareT rogorc erTmaneTs, aseve sakontrolo jgufis

maCveneblebs. orive jgufSi yvela androgenuli parametri statistikurad

sarwmunod maRali iyo sakontrolo jgufis maCveneblebTan SedarebiT,

xolo jgufebs Soris statistikurad sarwmuno sxvaoba arcerT

androgenul parameters Soris ar gamovlinda. avtorebis erTi jgufi

miiCnevs, rom hirsutizmi azielebSi da mozardebSi [133] SedarebiT iSviaTia,

TviT metaboluri da endokrinuli darRvevebis drosac. Savgremani,

SavTmiani TeTrkaniani qalebi ufro midrekili aris hirsutizmisken, vidre

TeTrkaniani qera qalebi [21, 51]. avtorTa monacemebiT hirsutizmi

mozardebSi aRiniSneba ufro xSirad adrenogenitaluri sindromis

araklasikuri formis dros ufro xSirad, vidre sxva hiperandrogenizmiT

mimdinare sindromebis dros [41]. AimisaTvis, rom gagverkvia Tu romel

asakobriv jgufSi aRiniSneba paTologiuri Tmianoba ufro xSirad

hirsutizmis mqone pacientebi davyaviT 3 asakobriv jgufad: I jgufi - 13-14

wl, II jgufi- 15-18 wl. da III jgufi - 19-30wl. Cvens masalis analiziT

gamovlinda, rom 13-14 wlis mozardebSi hirsutizmi aReniSneboda pacientTa

A-15%-Si, 15-18 wlis asakobriv jgufSi - 52,3%-Si, xolo 19-30 wl -32,6%-Si.

imave asakobriv jgufebSi aseve davadgineT aknes sixSire. gamovlinda, rom

pacientTa 13-14 wl jgufSi akne aReniSneboda- 17,1%-Si, 15-18 wl – 51,3%-Si

da 19-30 wl -31,6%-Si. amgvarad, Cveni monacemebiT rogorc hirsutizmis, aseve

aknes sixSire ufro naklebi aRmoCnda 13-14 wlis mozardebSi da

80

mniSvnelovnad ufro maRali 15-18 wlis asakobriv jgufSi. es faqti

SesaZlebelia aixsnas paTologiuri procesis progresirebiT dinamikaSi,

magram am TvalsazrisiT Znelad asaxsnelia hiperandrogenizmis klinikuri

gamovlinebebis SedarebiT dabali sixSire 19-30 wlis asakis qalebSi. aseve

sainteresoa aRiniSnos, rom gamoyofil asakobriv jgufebSi hirsutizmis da

aknes sixSire korelirebs erTmaneTTan.

Cveni kvlevis Sedegebis analizis safuZvelze SeiZleba davaskvnaT, rom

hiperandrogenizmis SefasebaSi mniSvnelovani roli eniWeba androgenuli

parametrebis gansazRvras, miuxedavad imisa hirsutizmi gamoxatulia Tu

ara. Cvens masalaze 25 pacientidan hirsutizmis gareSe akne gamouvlinda

15 pacients (60%), menstruaciuli ciklis darRveva oligoamenoreis tipiT

23 pacients (92%). amave jgufis pacientebSi policistozuri sakvercxeebis

sindromi dadginda – 5 SemTxvevaSi (20%), adrenogenitaluri sindromis

araklasikuri forma – 11 SemTxvevaSi (44%), hiperprolaqtinemiis sindromi –

9 SemTxvevaSi (36%). pacientebSi policistozuri sakvercxeebis sindromiT

akne gamovlinda 2 SemTxvevaSi (40%), adrenogenitaluri sindromis

araklasikuri formis mqone pacientebSi – 9 SemTxvevaSi (81,8%),

hiperprolaqtinemiis sindromis mqone pacientebSi – 4 SemTxvevaSi (44,4%).

amgvarad, hirsutizmis armqone pacientTa Soris hiperandrogenizmiT akne

yvelaze xSirad aRmoCnda (81,8%-Si) adrenogenitaluri sindromis

araklasikuri formis mqone jgufSi.

metad sainteresoa, rom hirsutizmis mqone pacientTa jgufSi akne

gamovlinda yvelaze xSirad hiperprolaqtinemiis sindromis dros - 76%-Si,

policistozuri sakvercxeebis sindromsa (63%) da adrenogenitaluri

sindromis araklasikur formasTan (59%) SedarebiT. hirsutizmis ar mqone

pacientTa jgufSi akne gamovlinda yvelaze xSirad adrenogenitaluri

sindromis araklasikuri formis mqone pacientebSi 81%-Si, vidre

policistozuri sakvercxeebis sindromis (40%) da hiperprolaqtinemiis

dros (44,4%). literaturaSi ar moipoveba monacemebis hiperprolaqtinemiis

da aknes kavSirze. Tumca, SeiZleba axsnili iyos imiT, rom

hiperprolaqtinemiis mqone pacientebSi xSirad aRiniSneba

81

dehidroepiandrosteronis da dehidroepiandrosteron-sulfatis

koncentraciis mateba [6,107], testosteronis da androstendionis

koncentraciis normaluri maCveneblebis fonze. Cveni kvlevis farglebSi

hiperprolaqtinemiis sindromis mqone pacientebSi dehidroepiandrosteron-

sulfatis maRali maCvenebeli gamovlinda 35%-Si, xolo testosteronis

maRali maCvenebeli -50%-Si.

hirsutizmis armqone jgufis pacientebSi androgenuli parametrebis mateba

aRniSneboda 15 SemTxvevaSi (60%). saerTo testosteronis mateba - 15

pacientSi (60%), Tavisufali androgenebis indeqsis 8-ze zemoT – 15

pacientSi (60%), gaangariSebuli Tavisufali testosteronis da

bioSeRwevadi testosteronis maRali maCvenebeli - 14 pacientSi (56%), xolo

seqssteroidSemboWveli globulinis normaze dabali maCvenebeli –

12 SemTxvevaSi (48%). sainteresoa, rom 8 SemTxvevaSi (32%) gamovlinda

saerToO testosteronis maCvenebeli normis farglebSi da

seqssteroidSemboWveli globulinis dabali maCvenebeli. es faqti SeiZleba

aixsnas imiT, rom aknes da hirsutizmis ganviTarebaSi androgenebis

maCveneblebTan erTad mniSvnelovan rols TamaSobdes cximis da Tmis

folikulebis receptorebis gansxvavebuli mgrZnobeloba androgenebis

mimarT. aqedan gamomdinare gaangariSebuli androgenuli parametrebis –

Tavisufali androgenebis indeqsis, gaangariSebuli Tavisufali da

bioSeRwevadi testosteronis da seqssteroidSemboWveli globulinis

maCveneblebis gansazRvra mniSvnelovania hiperandrogenizmis klinikuri

maxasiaTeblebis ganviTarebis meqanizmebis dadgenaSi pacientebSi sxvadasxva

ginekologiur–endokrinuli sindromebiT (policistozuri sakvercxeebis

sindromi, adrenogenitaluri sindromis araklasikuri forma,

hiperprolaqtinemiis sindromi).

metad saintereso iyo korelaciebis dadgena hirsutizmis xarisxsa da

androgenul parametrebs Soris. hirsutizmis gamoxatulobis xarisxis

mixedviT gamovyaviT hirsutizmis 3 forma: msubuqi (8-16 qula), saSualo

simZimis (17-24 qula) da mZime (25 qula da meti). imis gasarkvevad Tu ra

diagnostikuri mniSvneloba gaaCnia sxvadasxva androgenul parametrs

hirsutizmis Sesafaseblad pacientebi dayofili iyvnen 3 jgufad: I jgufi-

82

hirsutizmi ar aReniSneboda (0-7qula) - 25 pacients (22,5%), II jgufi -

msubuqi hirsutizmi - 50 pacients (45%), III jgufi - saSualo simZimis da

mZime hirsutizmi – 36 pacients (32,4%). Catarebuli analiziT gamovlinda,

rom saerTo testosteroni da Tavisufali androgenebis indeqsi

statistikurad sarwmunod maRali iyo hirsutizmis nebismieri xarisxis

dros, vidre pacientebSi hirsutizmis gareSe. aseve sayuradReboa, rom

dehidroepiandrosteron - sulfatis maCvenebeli statistikurad sarwmunod

ufro maRali aRmoCnda mZime hirsutizmis mqone pacientebSi, vidre

pacientebSi msubuqi hirsutizmiT da hirsutizmis gareSe. jgufebs Soris

sxva androgenuli parametrebis maCveneblebis mixedviT statistikurad

sarwmunod sxvaoba ar gamovlinda, Tumca hirsutizmis msubuqi da mZime

formebis dros gamovlinda androgenuli parametrebis maCveneblebis

matebis da seqssteroidSemboWveli globulinis maCveneblis daqveiTebis

tendencia. amgvarad, gaangariSebuli androgenuli parameterebis

maCveneblebi da seqssteroidSemboWveli globulinis koncentracia

sarwmunod ar korelirebs hirsutizmis xarisxTan, rac SeiZleba

ganpirobebuli iyos imiT, rom hirsutizmis xarisxi damokidebulia ara

mxolod androgenebis koncentraciaze sisxlis SratSi, aramed Tmis

folikulebis mgrZnobelobaze androgenebis mimarT. literaturaSi ar aris

sakmarisi monacemebi kavSirze hirsutizmis hiperandrogenemiis xarisxs

Soris.

literaturaSi arsebuli monacemebiT hiperandrogenizmis SemTxvevebSi

xSiri klinikuri gamovlinebaa sxeulis Warbi wona. Cven mier Seswavlili

pacientebis 33,3%-Si gamovlinda Warbi wona. imisTvis, rom dagvedgina

kavSiri wonis matebasa da androgenul parametrebs Soris CavatareT

korelaciuri analizi pirsonis meTodiT. Catarebuli analiziT sxeulis

masis indeqsa (smi) da androgenul parametrebs Soris gamovlinda

statistikurad sarwmunod dadebiTi korelaciebi smi-sa da gaangariSebul

Tavisufal testosterons, gaangariSebul bioSeRwevad testosterons da

Tavisufal androgenebis indeqss Soris. statistikurad sarwmunod

dadebiTi korelacia gamovlinda aseve sxeulis masis indeqssa da

insulinrezistentobis indeqs Soris da sapirispirod gamovlinda

83

statistikurad sarwmunod uaryofiTi korelacia smi-sa da

seqssteroidSemboWveli globulinis maCveneblebs Soris. S.Cupisti da

Tanaavtorebis monacemebiT pacientebSi hirsutizmiT da sakvercxeebis

policistoziT simsuqne asocirebulia saerTo testosteronis

koncentraciis matebasTan da ssSg-is koncentraciis daqveiTebasTan, ris

Sedegadac matulobs gaangariSebuli Tavisufali da bioSeRwevadi

testosteroni [47].

bolo monacemebiT mniSvnelovania ara marto sxeulis absoluturi masa,

aramed cximovani qsovilis gadanawilebis tipi – ginoiduri Tu

visceraluri gacximovneba. cximovani qsovilis gadanawilebis

Taviseburebebis dadgenis mizniT xdeboda welisa da barZayis

garSemowerilobis Tanafardobis gansazRvra. zemo tipis, visceraluri, anu

mamakacuri tipis simsuqnis dros, welisa da barZayis garSemowerilobis

Tanafardobis indeqsad miCneulia maCvenebeli 0,8–ze meti, xolo qvemo,

qaluri, ginoiduri tipis simsuqnis dros – 0,8–ze naklebi. imisaTvis, rom

gagverkvia, Tu ra kavSirSia cximovani qsovilis gadanawileba androgenul

parametrebTan I jgufis hirsutizmis mqone pacientebi cximovani qsovilis

gadanawilebis tipis mixedviT, davyaviT qvejgufebad (Ia qvejgufi –

ginoiduri simsuqniT da Ib qvejgufi – visceraluri simsuqniT) da

gamovikvlieT sxvadasxva androgenuli parametri cximovani qsovilis

visceralur tipad gadanawilebasTan mimarTebaSi.

kvlevis miRebuli Sedegebi gviCveneben, rom hirsutizmis mqone pacientebSi

visceraluri tipis simsuqnT gaangariSebuli Tavisufali testosteroni,

gaangariSebuli bioSeRwevadi testosteroni da Tavisufali androgenebis

indeqsis saSualo maCveneblebi statistikurad sarwmunod maRalia,

ginoiduri tipis simsuqnis mqone pacientebTan SedarebiT. sapirispiro

maCvenebeli miviReT seqssteroidSemboWveli globulinTan mimarTebaSi. misi

saSualo maCvenebeli statistikurad sarwmunod dabali iyo visceraluri

simsuqnis mqone pacientebSi ginoiduri tipis simsuqnis mqone pacientebTan

SedarebiT. statistikurad sarwmuno sxvaoba ar gamovlinda

insulinrezistentobis indeqsis, C-peptidis, saerTo da Tavisufali

testosteronis, dehidroepiandrosteron-sulfatis da 17α-

84

oqsiprogestoronis saSualo maCveneblebs Soris, Tumca aRiniSneboda maTi

matebis tendencia w.g/T.g Sefardebis maCveneblis gaTvaliswinebiT. Mmsgavsi

monacemebi gamovlinda mTel rig avtorTa kvlevebSic [47,145,154]. maTi azriT

visceraluri simsuqnis dros seqssteroidSemboWvveli globulinis

maCvenebeli dabalia da saerTo testosteronis koncentracia ufro maRali,

vidre qalebSi cximovani qsovilis Tanabari gadanawilebiT. Sesabamisad

matulobs gaangariSebuli Tavisufali da bioSeRwevadi testosteroni.

hirsutizmis mqone pacientebSi visceraluri simsuqniT aReniSneba

hiperandrogenizmis gaRrmaveba da hirsutizmis progresireba. es albaT

ukavSirdeba imas, rom visceraluri simsuqnis dros aRiniSneba

insulinrezistentoba, rac ganapirobebs seqssteroidSemboWveli

globulinis sekreciis daTrgunvas, ris fonzec matulobs testosteronis

biologiurad aqtiuri fraqcia da Sesabamisad hiperandrogenizmis

klinikuri gamovlinebebis intensivoba.

qalebSi hiperandrogenizmis Sesafaseblad Tavisufali testosteroni

yvelaze gavrcelebuli markeria. Tavisufali testosteronis gansazRvris

“oqros standartad” miCneulia wonasworobis dializis da mass-

speqtrometriis meTodebi. Tumca, am meTodebiT misi gansazRvra rutinulad

yvela laboratoriaSi ver xorcieldeba. axlaxans Seqmnilia Tavisufali

testosteronis gaangariSebis modelebi saerTo testosteronis,

seqssteroidSemboWveli globulinis da albuminis maCveneblebis meSveobiT.

A.Vermeulen at al. monacemebiT aseTi gamoTvlebiT miRebuli Tavisufali da

bioSeRwevadi testosteronis monacemebi dadebiTad korelirebda

wonasworobis dializis da mas–speqtrometriiT miRebul monacemebTan

[151,152,153]. xSirad Tavisufali testosteronis koncentracia SeiZleba

momatebuli iyos maSin, rodesac saerTo testosteronis maCvenebeli

normis farglebSia, rac ganpirobebulia imiT, rom seqssteroidSemboWveli

globulinis dabali koncentracia ganapirobebs testosteronis

Tavisufali fraqciis matebas sisxlis plazmaSi [11,20,53,88].

imisaTvis, rom dagvedgina Tu romeli meTodiT miRebuli androgenuli

parametrebis maCvenebeli korelirebs hirsutizmTan kvlevis farglebSi Cven

movaxdineT Tavisufali testosteronis gansazRvra imunofermentuli

85

meTodiT (ELISA) da androgenuli parametrebis gaangariSeba saerTo

testosteronis da seqssteroidSemboWveli globulinis meSveobiT,

rogoric aris gaangariSebuli Tavisufali testosteroni, gaangariSebuli

bioSeRwevadi testosteroni da Tavisufali androgenebis indeqsi. miRebuli

SedegebiT calsaxad gamovlinda statistikurad sarwmonod dadebiTi

korelaciebi imunofermentuli ELISA-meTodiT gansazRvrul Tavisufal

testosteronsa da Tavisufali androgenebis indeqs Soris hirsutizmian

pacientebSi. agebuli ROC (Receiver operating characteristics) mrudeebiT saSualo

simZimis hirsutizmis mqone pacientebSi gamovlinda Tavisufali

testosteronis da Tavisufali androgenebis indeqsis TiTqmis Tanabari

diagnostikuri mniSvneloba. xolo hirsutizmis mZime xarisxis mqone

pacientTa jgufSi gamovlinda gaangariSebuli Tavisufali testosteronis

ufro mZlavri diagnostikuri mniSvneloba, vidre Tavisufali

testosteronis da Tavisufali androgenebis indeqsis. avtorTa jgufi

Brannian at al.; Morrimoto at al. da Qiao at al. [103,120]. miiCneven, rom Tavisufali

androgenebis indeqsis gansazRvra aucilebeli da farTod gamoyenebadi

meTodia androgenuli statusis Sesafaseblad. es meTodi SesaZloa iyos

Tavisufali testosteronis gansazRvris alternativa qalebSi, romelTac

aReniSnebaT menstruaciuli ciklis darRveva oligomenoreis tipiT da

hirsutizmi. Vermeulen-is and Kaufmann-is [152] azriT Tavisufali androgenebis

indeqsis gamoyeneba ar aris adekvaturi yvela pacientSi

hiperandrogenizmiT da is Sesaferisi markeria mxolod pacientebSi

hirsutizmiT da policistozuri sakvercxeebis sindromiT. isini aseve

miiCneven, rom gaangariSebuli Tavisufali testosteroni aris

alternatiuli meTodi Tavisufali testosteronis gansazRvris

wonasworobis dializis da amoniumis sulfatiT precipitaciis meTodebisa.

amgvarad, Catarebuli kvlevis safuZvelze SeiZleba davaskvnaT, rom

gaangariSebuli androgenuli parametrebiT – Tavisufali testosteroni,

bioSeRwevadi testosteroni da Tavisufali androgenebis indeqsi –

SesaZlebelia hiperandrogenizmis ganviTarebis meqanizmebis dadgena

(testosteronis absoluturi maCveneblis mateba da/an

seqssteroidSemboWveli globulinis daqveiTeba) da Sesabamisad

86

hiperandrogenizmis mkurnalobis adekvaturi taqtikis SemuSaveba

etiopaTogenezuri faqtorebis gaTvaliswinebasTan erTad.

87

Tavi 5

daskvnebi

1. axalgazrda qalebSi sxvadasxva sindromebiT (policistozuri

sakvercxeebis sindromi, adrenogenitaluri sindromis araklasikuri

forma, hiperprolaqtinemiis sindromi) hiperandrogenizmis

damaxasiaTebeli klinikuri gamovlinebebiT sisxlis SratSi dadginda

yvela gaangariSebuli androgenuli parametris statistikurad

sarwmunod maRali da seqsteroidSemboWveli globulinis

statistikurad sarwmunod dabali saSualo maCvenebeli sakontrolo

jgufTan SedarebiT.

2. ar gamovlinda statistikurad sarwmuno sxvaoba gaangariSebuli

androgenuli parametrebis da seqssteroidSemboWveli globulinis

koncentraciis mixedviT sxvadasxva klinikuri sindromebis mqone

(policistozuri sakvercxeebis sindromi, adrenogenitaluri

sindromis araklasikuri forma, hiperprolaqtinemiis sindromi)

pacientebis saSualo maCveneblebs Soris.

3. gaangariSebuli androgenuli parameterebis maCveneblebi da

seqssteroidSemboWveli globulinis koncentracia ar korelirebs

hirsutizmis xarisxTan, rac SeiZleba ganpirobebuli iyos imiT, rom

hirsutizmis xarisxi damokidebulia ara mxolod androgenebis

koncentraciaze sisxlis SratSi, aramed Tmis folikulebis

mgrZnobelobaze androgenebis mimarT.

4. visceraluri simsuqnis mqone pacientebSi hirsutizmiT gamovlinda

gaangariSebuli androgenuli parameterebis statistikurad

sarwmunod maRali da seqssteroidSemboWveli globulinis

88

koncentraciis statistikurad sarwmunod dabali saSualo

maCveneblebi im pacientebTan SedarebiT, romelTac aReniSnebodaT

ginoiduri simsuqne msgavsi xarisxis hirsutizmiT. es albaT

ukavSirdeba Homa-IR indeqsis ufro maRal maCvenebels pacientebSi

visceraluri simsuqniT da am fonze testosteronis biologiurad

aqtiuri fraqciis matebas.

5. gansxvavebiT sxva formebisagan hirsutizmis mZime xarisxis dros

dadginda gaangariSebuli Tavisufali testosteronis ufro mZlavri

diagnostikuri mniSvneloba imunofermentuli ELISA-meTodiT

gansazRvruli Tavisufali testosteronis maCvenebelTan SedarebiT.

6. gaangariSebuli androgenuli parametrebiT – Tavisufali

testosteroni, bioSeRwevadi testosteroni da Tavisufali

androgenebis indeqsi – SesaZlebelia hiperandrogenizmis ganviTarebis

meqanizmebis dadgena (testosteronis absoluturi maCveneblis mateba

da/an seqssteroidSemboWveli globulinis daqveiTeba) da Sesabamisad

hiperandrogenizmis mkurnalobis adekvaturi taqtikis SemuSaveba

etiopaTogenezuri faqtorebis gaTvaliswinebasTan erTad.

89

Tavi 6.

praqtikuli rekomendaciebi

1. hiperandrogenizmis ganviTarebis meqanizmebis dadgenisTvis

mizanSewonilia gaangariSebuli androgenuli parameterebis, rogoric

aris gaangariSebuli Tavisufali testosteroni, gaangariSebuli

bioSeRwevadi testosteroni, seqssteroidSemboWveli globulinis

maCveneblebis da Tavisufali androgenebis indeqsis gansazRvra.

2. axalgazrda qalebSi hirsutizmiT gaangariSebuli Tavisufali

testosteroni, bioSeRwevadi testosteroni, seqssteroidSemboWveli

globulini da Tavisufali androgenebis indeqsi ufro adekvaturi

alternatiuli markerebia hiperandrogenizmis Sesafaseblad, vidre

mxolod imunofermentuli ELISA-meTodiT gansazRvruli Tavisufali

testosteronis maCvenebeli.

90

Ivane Javakhishvili Tbilisi State University, Faculty of Medicine,

Department of Obstetrics - Gynecology and Reproductology

With the right of manuscript

Diana Chanukvadze

The correlations between the clinical and hormonal characteristics of

hyperandrogenism

The Ph.D Thesis

Presented for the academic degree of Doctor of Medicine

Research Director: Doctor of Medical Sciences, Associated Professor Jenara Kristesashvili

Tbilisi, 2012

91

The theme importance:

Hyperandrogenism - the existence of androgen depending symptoms in women such as acne,

seborrhea, hirsutism and alopecia is a quite common condition. The main cause of

hyperandrogenism (40-80%) is hyperandrogenemia [22,85,129]. According to the references,

hyperandrogenism is marked in 7-10% of women of reproductive age [19,54,92]. Among the

reasons of hyperandrogenism decrease of sex steroid binding globulin concentration in the blood is

also considered, resulting in increased levels of free androgens [15,22]. Quite common is the form

of hyperandrogenism that develops on the basis of increase of the enzyme 5α-reductase activity in

the skin with the normal concentration of androgens in the blood. This form of hyperandrogenism is

considered idiopathic or constitutional form [21,29,35].

Irrespective the reasons, hyperandrogenism is perceived by patients rather severally, it becomes the

cause of psychological stress and affects their quality of life. Therefore, hyperandrogenism is a very

important and actual medical as well as social problem.

The causes of hyperandrogenism are: polycystic ovary syndrome, hyperandrogenic insulin -

resistant acanthosis nigricans syndrome, congenital adrenal hyperplasia (classical and non-

classical forms), Cushing's syndrome, androgen producing tumors (ovarian, adrenal gland),

hyperprolactinemia syndrome [25, 31]. 5-15% out of all cases of hyperandrogenism clinical

manifestations is idiopathic [21]. In such cases there is marked hypersensitivity of hair follicles to

normal levels of circulating androgens, the reason for which is increase of 5-α reductase activity.

These pathologies have been widely studied, but there still remain a number of issues that are

important for research to clarify the pathogenic mechanisms of hyperandrogenism of different

forms. In recent years special attention deserves the type hyperandrogenism, linked to obesity and

insulin resistance. In particular, it is stated that there is a relationship between hyperinsulinemia

and hyperandrogenism and coexistence of these two types of disorders creates a vicious circle. The

relations are less explored with consideration of liver function, the exact correlation between blood

sex hormone binding globulin, total and free testosterone concentrations, and similar relations in

patients with polycystic ovary syndrome or without it. The fact should be also highlighted that

obesity and insulin resistance is often not considered by patients appropriately as severe metabolic

disorders, including a risk – factor for diabetes mellitus type II development. Therefore, these

patients are at risk of serious health damage. Also noteworthy is the fact that insulin resistance can

be found in patients without excessive weight, with visceral obesity, which is so left without

attention. It is known that the main part of circulating in the blood testosterone - 80% is bound with

92

sex hormone binding globulin, 19% - with albumin, and only 1% circulates in free condition.

Steroids, bound with sex hormone binding globulin can not achieve in target tissues for activating.

Therefore, the androgenic effects are in correlation with sex hormone binding globulin levels. In

adult women sex hormone binding globulin concentration is twice as higher as in men. This gender

difference can be explained by the fact that estrogens stimulate and androgens inhibit sex hormone

binding globulin producing. This substance level in blood is considered a biological controlling

factor between androgens and estrogens [15,49,78].. The sex hormone binding globulin is a serum

of glycoprotein, produced in the liver. Its synthesis and expression in addition to the sex steroids, is

regulated by a number of other factors, some of which (thyroid hormones, stress, high carbohydrate

concentration) increase, while others (obesity, insulin, prolactine, growth hormone, progesterone,

glucocorticoids) decrease its level [6].

Gynecologists and reproductologists often do not pay adequate attention to specification of the

reasons of hyperandrogenism, and offer to such patient’s not ethio-pathogenetic, but symptomatic

treatment with androgens. This in dynamics leads to the enhancement of existing metabolic

disorders.

Free testosterone is the most common marker in women with hyperandrogenism, but its

determination cannot be carried out routinely in all laboratories. The "gold standard" of free

testosterone measuring is the method of the equilibrium dialysis and ammonium precipitation.

However, these methods are very time-consuming, expensive and require high technical

qualifications. Recently there have been developed the models for calculating free testosterone

through total testosterone, sex hormone binding globulin and albumin indices [151,153]. Despite

the limited correlations between all the endocrine parameters and the degree of hirsutism

(described by Feriman – Gallwey scheme), calculated free testosterone, biologically active

testosterone and free androgen index may be more appropriate markers to assess

hyperandrogenism in women with hirsutism than definition of only androgens [106,109]. In

addition, the level of free testosterone determination does not allow stating what causes this index

increase: the increase of testosterone secretion or increase of free biologically active fraction on

the background of sex hormone binding globulin decrease. Therefore, the determination of free

testosterone index only does not allow specifying the mechanisms of hyperandrogenism. Currently

it is important to use more informative latest markers to evaluate the clinical manifestations of

hyperandrogenism in order to develop adequate tactics of treatment.

93

Based on the above-mentioned, the objective of the research was:

To detection the correlation between clinical signs and hormonal parameters of hyperandrogenism

in young women with various endocrine - gynecological syndromes manifested with

hyperandrogenism (polycystic ovary syndrome, non-classical form of the congenital adrenogenital

syndrome, hyperprolcatinemia syndrome)

Study objectives:

1. Based on the calculated androgenic parameters - calculated free and bioavailable testosterone,

free androgen index and sex hormone binding globulin- detected the importance of determination

for evaluation of mechanisms of development of hyperandrogenism clinical characteristics in

patients with various gynecological - endocrine syndromes (polycystic ovary syndrome, non-

classical form of the congenital adrenogenital syndrome, hyperprolcatinemia syndrome).

2. Revealing the correlations between clinical manifestations of hyperandrogenism and hormonal -

androgenic parametres in young women with pathogenetically different syndromes.

3. Determination of the correlation between visceral obesity with hormonal parametres of

hyperandrogenism.

4. Determination of diagnostic power of the calculated androgenic parameters and free

testosterone level determined by immunoferment method for evaluation of the hyperandrogenism

clinical symptoms and the development of hyperandrogenism mechanisms.

Scientific novelty of the work:

Firstly it was stated that the calculated androgenic parameters - free androgen index, calculated

free and bioavailable testosterone - are more adequate alternative markers for evaluation of the

mechanisms of hyperandrogenism than free testosterone determined by the immunoferment

method for clinical characteristics development in patients with various gynecological - endocrine

syndromes (polycystic ovary syndrome, non-classical form of congenital adrenogenital syndrome,

hyperprolactinemia syndrome).

94

It was detected that the calculated androgenic parameters and the concentration of sex hormone

binding globulin is not correlated with the degree of hirsutism, which may be due to the fact that

the degree of hirsutism depends not only on androgen concentrations in serum, but on the

sensitivity of hair follicles to the androgens.

In the patients with visceral obesity with hirsutism there were detected statistically reliable higher

levels of calculated androgenic parameters, and statistically reliable lower levels of sex hormone

binding globulin compared to those in the patients with gynoid obesity with the similar degree of

hirsutism. This is probably related to the higher Homa-IR index in patients with visceral obesity

with increased on this background biologically active fraction of testosterone.

Unlike other forms, in case of severe degree hirsutism, it was detected that calculated free

testosterone has more diagnostic power than free testosterone level determined by ELISA

immunoferment method.

It was revealed that the levels of calculated androgenic parameters and the concentration of sex

hormone binding globulin is not correlated with the degree of hirsutism, which may be due to the

fact that the degree of hirsutism depends not only on androgen concentrations in serum, but also

on the sensitivity of hair follicles to the androgens.

The practical value of the work:

In practical terms the research results are very important, as they show that it is reasonable to

determine calculated androgenic parameters such as calculated free testosterone, bioavailable

testosterone, sex steroid binding globulin and free androgen index in order to determine

mechanisms of hyperandrogenism development.

In practical terms it is also most important to establish the fact that in young women with hirsutism

the calculated free testosterone, bioavailable testosterone, sex hormone binding globulin and free

androgen index are more adequate alternative markers for evaluation of hyperandrogenism than

free testosterone concentration only determined by ELISA immunoferment method.

95

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danarTi

suraTi 1. saSualo simZimis hirsutizmi pacientis mkerdze

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suraTi 2. mZime hirsutizmi pacientis mkerdze da kiserze

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suraTi 3. mZime hirsutizmi pacientis saxeze da kiserze

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suraTi 4. mZime hirsutizmi pacientis saxeze

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suraTi 5. mZime hirsutizmi pacientis dunduloebze

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suraTi 6. mZime hirsutizmi pacientis mucelze