Ultrasonographic and color Doppler analysis in the treatment of polycystic ovary syndrome

Transcription

1 Ultrsound Ostet Gynecol 1998;12: Ultrsonogrphic nd color Doppler nlysis in the tretment of polycystic ovry syndrome C. Bttgli A. D. Genzzni P. G. Artini M. Slvtori S. Giulini nd A. Volpe Deprtment of Ostetrics nd Gynecology University of Moden nd Pis Itly Key words: DOPPLER PCOS THERAPY ULTRASONOGRAPHY HIRSUTISM GnRH-A ABSTRACT Ojective To compre the effect of gondotropin relesing hormone (GnRH) nlog plus dd-ck orl contrceptive (OC) therpy with OC therpy lone on the clinicl nd hormonl prmeters tht re chrcteristic of polycystic ovry syndrome (PCOS). Design Prospective rndomized study. Sujects Thirty PCOS ptients were rndomly ssigned to tretment with leuprolide cette for depot suspension plus comined monophsic OC (Group I) or to OC lone (Group II). Methods Hormonl (luteinizing hormone (LH) follicle stimulting hormone (FSH) LH : FSH concentrtion rtio estrdiol ndrostenedione testosterone) clinicl (Ferrimn Gllwey score) ultrsonogrphic (ovrin volume numer of sucpsulr follicles stroml score) nd Doppler (uterine rtery nd ovrin intrprenchyml vessels pulstility index ovrin stroml vsculriztion) prmeters were evluted during 6 months therpy nd 6 months follow-up. Results Significnt chnges in ll the prmeters nlyzed occurred s result of therpy nd the chnges were more mrked in the group undergoing tretment with GnRH nlog plus OC. Conclusions GnRH nlog plus OC use hs more rpid nd mrked effect on the hormonl milieu s well s the ovrin rchitecture nd vsculriztion in ptients with PCOS thn OC used lone. The former tretment my e more efficient therpy for PCOS. INTRODUCTION Since the originl description y Stein nd Leventhl of the syndrome chrcterized y menorrhe infertility nd hirsutism ssocited with sclerocystic ovries the polycystic ovry syndrome (PCOS) hs een extensively investigted. However its pthogenesis is still oscure. The heterogeneity of the clinicl nd endocrine symptoms mkes the definition of PCOS difficult. A high pituitry output of luteinizing hormone (LH) ssocited with the secretion of excessive mounts of ndrogens constitutes the sis for hirsutism nd chronic novultion in PCOS 12. Vrious therpeutic pproches hve een ttempted in PCOS including dieting nd the use of phrmcologicl gents such s orl contrceptives (OCs) nti-ndrogens nd glucocorticoids 34. These molecules either y inhiition of the hypothlmo pituitry ovrin xis nd consequent reduction in ovrin ndrogen production or y competitive inhiition of ndrogen trget orgn receptors hve succeeded in chieving clinicl improvements. However the tretment is fr from optiml. The trditionl therpy with OCs hs often een disppointing ecuse of the incomplete ovriostsis (lmost suppressed ovrin steroid production) nd lso ecuse the progestin component of most OC pills hs some ndrogenic ctivity 5.In recent yers gondotropin relesing hormone gonists (GnRH-A) hve een introduced in the tretment of PCOS nd n effective ovrin hormonl suppression hs een reported 6 8. However long-term GnRH-A therpy ws found to e ssocited with side-effects secondry to the hypoestrogenic stte. More recently conventionl ddck therpy hs een introduced to eliminte hypoestrogenic effects nd conceivly to ct synergisticlly with GnRH-A to reduce the hyperndrogenic stte Assessment of ovrin morphologicl nd functionl chnges during tretments with the ove regimen re generlly lcking or contrdictory results hve een reported 3.No dt on the ultrsonogrphic nd Doppler chnges in the follow-up period hve een reported. We recently showed tht significnt chnges in introvrin vsculriztion nd n incresed lood flow resistnce t the level of the uterine rteries occur in PCOS ptients Correspondence: Dr C. Bttgli Deprtment of Ostetrics nd Gynecology University of Moden Vi del Pozzo Moden Itly ORIGINAL PAPER 18 Received Revised /53 Accepted

2 Doppler nd PCOS therpy Bttgli et l. The im of the present study ws to determine whether GnRH-A plus dd-ck orl contrceptive therpy is more effective thn OCs lone in the tretment of PCOS ptients nd to evlute whether the hormonl vritions my induce ultrsonogrphic nd Doppler vritions during nd 6 months fter the end of the tretment. METHODS Ptients nd protocols The study protocol ws pproved y the locl Ethics Review Committee. Ptients with PCOS (n = 3) ttending the gynecologicl endocrinologicl clinic prticipted in the study fter giving written informed consent. Polycystic ovry syndrome ws dignosed on the sis of the following criteri: hirsutism menstrul disturnces incresed plsm circulting ndrogens rtio of LH/follicle stimulting hormone (FSH) of > 2.5 nd typicl echogrphic ovrin ptterns (high numer of smll sucpsulr follicles ugmented ovrin volume nd incresed ovrin strom echogenicity) 14. All the ptients hd cne nd/or seorrhe nd hirsutism (Ferrimn Gllwey score > 12) nd none hd hypertension (systolic lood pressure > 14 mmhg nd/or distolic pressure > 9 mmhg) or ws hevy smoker or took regulr intense exercise. Furthermore the ptients hd not received hormonl tretments for t lest 4 months efore the study. Ptients with ultrsound evidence of multifolliculr ovries were excluded from the study. Twenty-two (73%) ptients were oligomenorrheic (cycle length > 35 dys) nd eight (27%) were menorrheic (no vginl leeding for 6 months). The men ge ws 24.3 ± 4.1 yers (rnge yers). The ody mss index (weight (kg)/height 2 (m 2 )) ws 25.1 ± 2.8 (rnge 21 29). Ptients with ody mss index of > 3 were not included in the study. Hirsutism ws evluted ccording to the Ferrimn Gllwey method 15. Ptients rndomly received the following therpy: (1) Group I (n = 15): intrmusculr injection of leuprolide cette for depot suspension (3.75 mg Enntone Depot ; Tked Itly) t 28 dys intervl plus comined monophsic OC Mercilon (2 µg ethinylestrdiol + 15 µg desogestrel/dy for 21 dys; Orgnon Itli Itly) for 6 months; (2) Group II (n = 15): Mercilon for 6 months. Rndomiztion ws performed y rndom numer tle for tretment lloction lind to the investigtors. Nine ptients (five in Group I nd four in Group II) were lso prt of prllel study 16. Oligomenorrheic ptients received the therpy on the first dy of the menstrul cycle. Amenorrheic ptients were sumitted to the therpy fter ultrsound evlution showed thin (< 4 mm) endometrium nd the sence of dominnt follicles. Ptients were studied efore (seline) nd 3 nd 6 months fter the initition of therpy. Follow-up evlutions were crried out fter 1 3 nd 6 months from the suspension of the therpy. The durtion of the study lsted 1 yer. No ptients withdrew from the study. Ptients were studied for seline evlution in the erly folliculr phse (dy 3 5) if they were oligomenorrheic or t rndom if menorrheic. During the tretment nd follow-up periods the women were nlyzed within the first 5 dys fter the eginning of menstrul leeding. Ultrsonogrphic nd color Doppler nlysis hormonl ssy nd iochemicl evlution were performed in ll the ptients. Ultrsound nd Doppler exmintions Ultrsonogrphic exmintion of the ovries ws performed with the use of 6.5-MHz trnsvginl trnsducer (Esote AU 59 Asynchronous Esote Geno Itly): ovrin volume nd follicle distriution numer nd dimeter were recorded. The volume (V) ws clculted y using the formul: V = π/6 D1 D2 D3 where D1 is the longitudinl dimeter D2 the nteroposterior dimeter nd D3 the trnsverse dimeter of the ovry. Ovrin strom echogenicity ws scored s (norml) 1 (modertely incresed) or 2 (mrkedly incresed) 17. No significnt differences etween left nd right ovries were oserved nd therefore the verge vlue of oth ovries ws used. Endometril thickness ws mesured on the frozen ultrsound imge. The mximum thickness of oth sides of the midline ws mesured in the plne through the centrl longitudinl xis of the uterus. Doppler flow mesurements of the uterine nd introvrin vessels were performed trnsvginlly with 6.5-MHz color Doppler system (Esote AU 59 Asynchronous color Doppler Esote Geno Itly). All the ptients were studied etween 8. nd 11. to exclude effects of circdin rhythmicity on the uterine lood flow 18. Furthermore they rested in witing room for t lest 15 min efore eing scnned nd completely voided the ldder in order to minimize externl effects on lood flow 19.A 5-Hz filter ws used to eliminte low-frequency signls originting from vessel wll movements. Color signls were sought in the ovrin strom t the mximum distnce from the surfce of the ovry. The ovrin strom ws considered vsculr if no lood flow ws demonstrted y color Doppler. Wheres severl lood vessels were detected inside the ovrin strom only the one with the lowest downstrem impednce ws selected for Doppler mesurements 11. Color flow imges identified the scending rnches of the uterine rteries which were smpled lterl to the cervix in sgittl plne. The ngle of insontion ws lwys djusted to otin mximum color intensity. When good color signls were otined lood flow velocity wveforms were recorded with the smple volume plced cross the vessel nd the pulsed Doppler mode entered. The pulstility index (PI) defined s the difference etween pek systolic nd end-distolic flow divided y the men mximum flow velocity ws clculted for oth the uterine rteries nd stroml rteries of the ovries. For ech exmintion the men vlue of three consecutive wveforms ws otined. No significnt differences etween the PIs of the left nd right uterine nd ovrin stroml rteries were oserved nd therefore the verge vlue of oth Ultrsound in Ostetrics nd Gynecology /53

3 Doppler nd PCOS therpy Bttgli et l. rteries ws used. The correltion etween PI nd hert rte ws tested y liner regression nlysis. A wek nd sttisticlly non-significnt inverse correltion ws found. Therefore in the results the PI nd resistnce index (RI) were not corrected for hert rte. Ultrsound nd color Doppler nlyses were performed y single exminer (C.B.) who ws unwre of the ptient s tretment group. Hormonl ssy nd iochemicl evlution Peripherl lood ws otined from ll ptients etween 8. nd 11. fter n overnight fst on the sme dy tht Doppler exmintion took plce nd different hormonl prmeters were nlyzed. Three plsm smples collected t 1-min intervls were pooled nd LH nd FSH were ssyed (Rdim Pomezi Itly). The LH : FSH concentrtion rtio ws then clculted. Estrdiol testosterone nd 4 -ndrostenedione were determined y rdioimmunossy (Rdim Pomezi Itly). In ll ptients totl cholesterol high density lipoprotein (HDL) nd triglyceride plsm levels were evluted. Totl serum cholesterol nd triglycerides were mesured y stndrd enzymtic methods (Sclvo Dignostici Sien Itly). HDLcholesterol levels in the superntnt were determined y using enzymtic regents (Bio Meriux Lille Frnce). Sttisticl nlysis Dt re presented s men ± stndrd devition unless otherwise indicted. Differences etween groups were ssessed with Student s t test one-wy nlysis of vrince nd χ 2 test where indicted. The reltionship etween the nlyzed prmeters ws ssessed y liner regression. A proility of.5 ws considered s sttisticlly significnt. RESULTS The seline levels for the two groups were similr for ultrsonogrphic hormonl iochemicl nd clinicl prmeters. Furthermore hormonl findings (incresed LH : FSH rtio nd elevted ndrostenedione levels) ultrsonogrphic findings (high numer of smll sucpsulr follicles ugmented ovrin volume nd incresed echogenicity of the ovrin strom) nd color Doppler findings (elevted uterine rtery PI nd decresed stroml vessel PI) confirmed PCOS in ll ptients. Hormonl chnges Plsm levels of LH FSH ndrostenedione testosterone estrdiol nd the LH : FSH rtio significntly decresed during tretment (Figure 1) nd the rte nd extent of the chnges were greter in the GnRH-A plus OC group (Figure 1). During the follow-up period plsm LH levels in Group I ptients were significntly lower thn efore the therpy (Figure 1) nd ll the women reported the resumption of norml menstrul leeding. Group II ptients showed significnt plsm LH reduction during the first 3 months fter the strt of the therpy nd y 1 yer from the eginning of the study they hd returned to seline levels (Figure 1). The plsm FSH levels were comprle in oth the tretment groups wheres the LH : FSH rtio ws significntly lower nd more stle in the GnRH-A plus OC group (Figure 1). During the follow-up period the plsm levels of oth ndrostenedione nd testosterone slowly ut constntly returned to pretretment vlues (Figure 1). No further significnt vritions in hormonl prmeters were oserved in either group. Clinicl nd metolic chnges During therpy no significnt vritions were found in ody mss index HDL totl plsm cholesterol nd triglyceride levels. Within the 6th month of therpy the Ferrimn Gllwey score showed significnt decrese in ll the ptients (Figure 2). This importnt clinicl prmeter showed greter nd more rpid decrese in Group I (fter 3 months) in comprison with Group II (Figure 2). All ptients of oth groups hd vginl leeding during the week s intervl etween tking the OC. No spotting or rekthrough leeding nd no significnt side-effects were experienced during the tretment. Only two ptients (6%) oth in Group I reported nuse during the first 2 months of therpy. After suspension of the tretments in oth groups the first spontneous vginl leeding occurred in 29 (97%) ptients fter 32 ± 2 dys (rnge dys). The remining ptient (Group II) ws menorrheic till the 6th month of the follow-up period. The ody mss index remined unchnged. The Ferrimn Gllwey score showed progressive increse to the pretretment vlues ut this increse ws slower in Group I thn in Group II ptients (Figure 2). Ultrsonogrphic nd color Doppler chnges Significnt differences were found in the results of ultrsonogrphic nd color Doppler nlysis following therpy nd the chnges were more mrked in the GnRH-A plus OC group (Figures 2 nd 3). No significnt vritions in endometril thickness were oserved during the study s ll evlutions were crried out in hypoestrogenic phse of the cycle. The percentge of ptients with n echodense ovrin strom (score = 2) decresed during tretment in oth groups (Figure 2). After 3 months therpy significnt reduction in uterine rtery PI ws oserved in oth groups. The stroml vsculriztion disppered in 11 women (73%) in Group I fter 3 months nd in further ptient (n = 12; 8%) fter 6 months of therpy. In Group II the introvrin vessels were not oserved in eight (53%) ptients fter oth 3 nd 6 months (p <.5). Where the ovrin intrprenchyml vsculriztion ws visulized the PI ws significntly higher in Group I thn in Group II (Figure 3). 182 Ultrsound in Ostetrics nd Gynecology 98/53

4 Doppler nd PCOS therpy Bttgli et l. LH (IU/l) Therpy (month) Androstenedione (nmol/l) 12 6 Therpy (month) FSH (IU/l) 6 3 Therpy (month) Testosterone (nmol/l) Therpy (month) LH : FSH rtio 4 2 Therpy (month) Estrdiol (pmol/l) Therpy (month) Figure 1 Hormonl vritions induced y the two different therpies in ptients with polycystic ovry syndrome. LH luteinizing hormone; FSH follicle stimulting hormone; htched rs tretment with gondotropin relesing hormone gonist plus orl contrceptive (OC) (Group I); open rs tretment with OC lone (Group II). Significnce: <.5; <.1 (Group I vs. Group II); <.5; <.1 (in comprison with sl vlues) During the post-therpy oservtionl period significntly smller ovrin volumes nd smller numers of smll sucpsulr follicles nd lower percentge of stroml score of 2 were oserved in the Group I women (Figure 2). Furthermore t lest one follicle with the mximum dimeter of 1.2 cm ws oserved in four (27%) seven (47%) nd five (33%) ptients t 1 3 nd 6 months fter GnRH-A plus OC suspension respectively. Amongst these ptients three (6%) out of the five infertile ptients who were on witing list for ssisted reproductive techniques (ART) hd successful pregnncies. In Group II the ovrin volume nd numer of smll sucpsulr follicles progressively returned to pretretment vlues (Figure 2). The numer of ovries with stroml score of 2 returned to pretretment vlues more quickly in comprison with Group I ptients (Figure 2). The incidence of t lest one follicle of 1.2 cm in mximum dimeter ws oserved in none of the ptients t 1 (p <.1) nd 3 months (p <.1) fter suspension of therpy ut fter 6 months it ws present in 13% of the ptients (p <.5). However norml menstrul leeding occurred in 12 (8%) ptients. None of the four ptients witing for ART in Group II chieved pregnncy. The ovrin intrprenchyml vsculriztion in Group I ws sent in 53% 47% nd 47% of the cses t 1 3 nd 6 months fter therpy respectively. In Group II it ws not oservle in 27% (p <.1) 2% (p <.1) nd 14% (p <.1) t 1 3 nd 6 months fter therpy respectively (Figure 3). In the remining ptients in whom stroml vsculriztion ws present no significnt differences in PI vlues were oserved etween the groups (Figure 3). In the whole study group the introvrin stroml rtery PI vlues were negtively correlted (r =.3851; p <.1) with the LH : FSH rtio. Furthermore the Ultrsound in Ostetrics nd Gynecology /53

5 Doppler nd PCOS therpy Bttgli et l. Ferrimn Gllwey score Therpy (month) Uterine rtery PI 4 2 Therpy (month) Ovrin volume (ml) Therpy (month) Stroml rtery visuliztion (%) 1 5 Therpy (month) Sucpsulr follicles (n) Stroml score of 2 (%) Therpy (month) Therpy (month) LH : FSH rtio ws positively correlted with ovrin volume (r =.3887 p <.1) nd the numer of smll Figure 2 Ferrimn Gllwey score vritions induced y gondotropin relesing hormone gonists plus orl contrceptives (OC) (htched rs; Group I) nd OC lone (open rs; Group II) in ptients with polycystic ovry syndrome; nd ultrsonogrphic modifictions during nd fter the two therpies. Significnce: <.5; <.1 (Group I vs. Group II); <.5; <.1 (in comprison with sl vlues) Ovrin rtery PI sucpsulr follicles (r =.321 p <.5). In ddition plsm ndrostenedione levels were positively correlted with men uterine PI vlues (r =.31 p <.5). Finlly introvrin PI vlues were inversely correlted with the numer of smll sucpsulr follicles (r =.2988 p <.5). DISCUSSION Therpy (month) Figure 3 Doppler nlysis of uterine nd ovrin intrprenchyml rteries in ptients with polycystic ovry syndrome. Modifictions due to different therpeutic regimens (gondotropin relesing hormone gonists plus orl contrceptives (OC); htched rs; Group I; nd OC lone; open rs; Group II). Significnce: <.5; <.1 (group I vs. group II); <.5; <.1 (in comprison with sl vlues) In PCOS the incresed mplitude nd frequency of pulstile LH secretion ccount for the incresed ovrin ndrogen production 1. The min purpose of therpy is reduction of chroniclly elevted plsm ndrogen levels nd regultion of the ssocited sequele 2. Trditionlly the first-line therpy for PCOS ptients is represented y ovriostsis 184 Ultrsound in Ostetrics nd Gynecology 98/53

6 Doppler nd PCOS therpy Bttgli et l. nd it is known tht OCs re effective in suppressing ovrin ndrogen production. Furthermore the comintion of estrogens nd progestins suppresses pituitry gondotropin secretion (prticulrly LH) nd stimultes the heptic production of steroid hormone inding gloulin. However in OC formultions the progestin is often n ndrogen derivtive nd the 7 dys intervl in cyclic OC dministrtion my fvor n escpe of pituitry suppression llowing sufficient increse in LH pulstile secretion Recently the use of long-term GnRH-A therpy hs llowed complete suppression of ovrin ndrogen production through the inhiition of LH relese 6 8. However the induced hypoestrogenic sequele limit its use suggesting the employment of dd-ck therpy 91. In the present study women treted with OC or GnRH-A plus OC showed n improvement of ll the studied PCOS clinicl signs. The use of GnRH-A plus OC produced more rpid intense nd long-lsting effect thn did OC lone. We hve shown tht LH levels were suppressed to greter degree with GnRH-A plus OC thn OC lone t oth 3 nd 6 months of therpy wheres less significnt vritions were found in FSH plsm concentrtions without significnt differences etween the groups. Therefore significnt decrese of the LH : FSH rtio during the therpy occurred. Similrly plsm ndrogens nd plsm estrdiol vlues decresed to mjor extent in the GnRH-A plus OC group. At the end of therpy the Ferrimn Gllwey score ws reduced to similr degree y oth tretments. The decline in hirsutism fter 3 months in the group with GnRH-A plus OC s evluted y the Ferrimn Gllwey score ws more rpid thn tht shown y Tiitinnen nd co-workers who found tht goserelin tretment decresed hirsutism only fter 6 months of therpy 24. Proly the low LH plsm levels induced y GnRH-A plus OC dministrtion deprive the thec interstitil cell components of gondotropin support for ndrogen iosynthesis. The chnges in hormonl findings were ssocited with ultrsonogrphic vritions. In ll PCOS ptients significnt fll in men ovrin volume ws oserved during the 6 months therpy. The reduction ws lredy cler t 3 months nd ecme highly significnt t 6 months in oth groups. These chnges in ovrin volume were more rpid in the GnRH-A plus OC group nd were ssocited with contemporneous nd similr decrese in stroml density. The ove results were not ssocited with complete cystic regression ut with significnt even though incomplete disppernce of smll sucpsulr follicles. These dt disgree with those shown y Couzinet nd ssocites 3 who oserved complete ovrin cystic regression. The difference my e explined y the different pproch used in the study of ovrin morphology. The use of high-resolution trnsvginl proe llowed us clerly to identify the numerous sucpsulr cysts tht might hve een missed y Couzinet nd collegues who used the trnsdominl pproch. The correltion etween the morphologicl ovrin dt nd the improved hormonl sttus is confirmed y the significnt correltion etween the LH : FSH rtio nd the numer of smll sucpsulr follicles. This finding supports the prominent role of LH in the morphologicl nd functionl ovrin trnsformtion in PCOS ptients. Furthermore the importnce of LH is confirmed y Doppler dt Elevted plsm LH levels my e responsile for incresed stroml vsculriztion y different mechnism e.g. neongiogenesis ctecholminergic stimultion or leukocyte nd cytokine ctivtion 11. The medicl cstrtion induced y therpy ws ssocited with rpid intense nd specific disppernce of stroml vsculriztion which ws more evident in the GnRH-A plus OC group. Furthermore the reduced ndrogen production tht correlted with the low LH levels ws ssocited with slow ut significnt improvement in PI vlues in the uterine rteries. The inverse correltion with plsm ndrostenedione levels suggests direct ndrogen vsoconstrictive effect on vsculr tissues proly medited through specific receptors on rteril wlls 11. The chnges in rteril tone were not ssocited with significnt vritions in lipid profile nd ody weight vlues. This suggests tht n dequte hormonl therpy in PCOS ptients ssocited with dietry restrictions nd weight loss my reduce the well-known predisposition of such ptients to therosclerosis with myocrdil infrction nd stroke. After suspension of therpy lmost ll the ptients experienced regulr spontneous vginl leed in < 35 dys. During the 6 months follow-up more thn 9% of the ptients hd menses. However the presence of dominnt follicle (> 1.2 cm in the mximum dimeter) ws significntly higher in the GnRH-A plus OC group. Furthermore pregnncy ws chieved only in Group I ptients. In this group of ptients plsm LH vlues remined constntly lower thn efore the therpy nd the LH : FSH rtio elow the upper norml limit. Conversely the group of ptients treted with OC lone showed reduced LH plsm levels only until the first 3 months fter the suspension of the therpy nd the LH : FSH rtio ws significntly higher thn in Group I t the 6-month post-therpy evlution. Androgens slowly ut constntly returned to pthologicl vlues even though t lower levels thn efore the therpy. Elevted serum LH vlues impir fertility y inducing premture resumption of meiosis in post-mture oocytes leding to ovultion 25. Such oocytes hve reduced possiility of eing fertilized or my led to the production of pre-emryos with poor implnttion potentil. The prtil or complete normliztion of introvrin vsculriztion during the follow-up period ws inversely correlted with the LH : FSH rtio thus supporting the hypothesis tht reduced LH negtive control is the clue for recovering ovultory processes. Furthermore reduced uterine perfusion my e fctor tht does not llow norml lstocyst implnttion In the present study the improved hemodynmic uterine condition my hve contriuted to the incresed chnce of pregnncy in the ptients who ovulted normlly fter therpy. The ultrsonogrphic follow-up in ptients treted with GnRH-A plus OC showed significnt nd persistent improvement in ll prmeters tht define the polycystic ovry (ovrin volume incresed stroml echogenicity Ultrsound in Ostetrics nd Gynecology /53

7 Doppler nd PCOS therpy Bttgli et l. numer of smll sucpsulr follicles). Furthermore n inverse reltionship etween stroml vsculriztion nd numer of smll sucpsulr follicles confirms the fct tht profound pituitry gondl xis suppression due to the nlogs results in regression of the mjority of the multiple cysts trnsformtion of the stroml cells into poorly developed cells with low steroidogenic cpcity nd poorly developed vsculr system. Similr results hve een otined y ovrin wedge resection or y ovrin cuteriztion (lser photocogultion or electrocutery) 28. The min concern with lproscopic or lprotomic ovrin wedge resection or ovrin cuteriztion is the high incidence of periovrin dhesions which my induce mechnicl infertility s result of ovrin cortex injury 29. Although medicl tretment nd surgicl procedures re oth effective in showing temporry improvements in PCOS ptients invsiveness compliction rte nd cost of the surgicl pproch my led to reduction of surgicl procedures in PCOS therpy. Recent studies hve underlined tht fter 12 months of therpy the use of nlogs plus OCs does not cuse ny side-effects or reduction in one density 3. This would further increse ptients complince nd enle longer durtion of GnRH-A tretment. Evidence from our study suggests tht the use of GnRH-A plus OCs is rpid nd effective in meliorting the hormonl milieu s well s the ovrin rchitecture in ptients treted for PCOS. However the high cost of the nlogs is the min ostcle to their widespred use in the tretment of PCOS. In conclusion oservtions from this study hve confirmed tht Doppler evlution of uterine nd introvrin rteries cn e dded to the trditionl endocrinologicl nd ultrsonogrphic prmeters cliniclly used in the dignosis nd mngement of PCOS. Furthermore it confirmed tht the 6-month tretment with GnRH nlogs plus orl contrceptives is effective nd presumly sfe 3. 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