Endometriosis in Adolescents

Diana Hristova, Ibryam Ibryam, Stanislava Hitrova‐Nikolova, Radko Tocev, I Kostov
In: Acta Medica Bulgarica · 2025 · vol. 52(4) , pp. 84–89 · doi:10.2478/amb-2025-0081 · W4417156218
article OA: diamond CC0
📄 Open PDF Full text JSON View on OpenAlex View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-08 ⓘ

Endometriosis affects 4-17% of adolescents, particularly those with severe dysmenorrhea, with pathogenesis involving multiple theories, and diagnosis confirmed by imaging and laparoscopy, while treatment aims for pain relief and fertility preservation.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-06, 2026-06-12 · read from full text ⓘ

This 2025 review paper examines endometriosis in adolescents, summarizing epidemiology, proposed pathogenesis theories, risk factors, clinical features, diagnostic evaluation, imaging options, and diagnostic/therapeutic approaches using European Society of Human Reproduction and Embryology (ESHRE) guideline points. It reports that early-onset symptoms are common, estimates prevalence ranges among adolescents and higher figures in those with recurrent/chronic pelvic pain, and highlights common symptom patterns such as dysmenorrhea with cyclic or acyclic pelvic pain plus possible gastrointestinal and urinary manifestations, while noting that laparoscopy is the “gold standard” for confirming peritoneal disease and staging. The paper explicitly acknowledges limitations of diagnostic tools, stating that ultrasound can be inferior for superficial disease and that MRI cannot serve as a screening method due to cost, and that the overall pathogenesis is still not fully understood. This paper is centrally about endometriosis in adolescents — it focuses on disease mechanisms, diagnosis, and management in this age group, and also references adenomyosis as part of the differential diagnosis.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

Abstract Endometriosis is an estrogen-dependent chronic inflammatory disease characterized by the proliferation of endometrial glandular tissue and stroma outside the uterine cavity. It is estimated that 4 to 17% of adolescent girls have the same form of endometriosis, and it is particularly common among those with dysmenorrhea who respond poorly to analgesics or estroprogestins. For those suffering from recurrent and chronic pelvic pain, the percentage rises to 25-38%. Possible explanations for the pathogenesis of endometriosis are: coelomic metaplasia, embryonic Müllerian rests, iatrogenic implantation, vascular and lymphatic metastasis, the genetic theory, and endometrial stem/progenitor cells that represent different hypotheses besides Sampson’s theory, the classic retrograde menstruation, which is the most widely accepted theory to explain the ectopic implantation of endometrium. According to the ESHRE guidelines, suggestive manifestations for endometriosis include early menarche, severe dysmenorrhea, dyspareunia, abnormal uterine bleeding, midcycle or acyclic pain, resistance to empiric medical treatment, and gastrointestinal and genitourinary symptoms. Known risk factors for developing endometriosis include: genetic predisposition; epigenetic variables – prematurity, bottle feeding, exposure to some pollutants with estrogenic activity; dysregulation of the immune and inflammatory response, as well as obstructive anomalies of the reproductive tract. Diagnosis is made by accurate anamnesis – personal and family history, gynecological examination and ultrasonographic evaluation (transabdominal and transvaginal ultrasound). Magnetic resonance can be useful to detect obstructive reproductive tract anomalies and to identify and characterize endometriotic lesions that are difficult to locate by ultrasound. A multidisciplinary diagnostic approach should be considered for a complete evaluation of these patients. Laparoscopic evidence serves as the gold standard for verifying peritoneal endometriosis and determining its stage, spread, and severity. A differential diagnosis of gastrointestinal pathologies, Müllerian anomalies, recurrent infections, and adenomyosis must be made. The treatment of this disease includes medical and surgical interventions, and a combination of both. ESRHE guidelines advise clinicians treating women with endometriosis to prescribe hormonal contraceptives or progestins to reduce endometriosis-associated pain. The use of gonadotropin hormone-releasing hormone agonists is acceptable in adolescents only if the patient with known endometriosis is refractory to other medical therapies or surgical treatments. The goals of medical therapy in the adolescent patient include symptomatic relief, suppression of disease progression, and protection of future fertility.
Full text 28,030 characters · extracted from oa-pdf · 3 sections · click to expand

Introduction

( QGRPHWULRVLVLVDQHVWURJHQGHSHQGHQWFKURQLF LQÀDPPDWRU\GLVHDVHFKDUDFWHUL]HGE\WKHSUR OLIHUDWLRQ RI HQGRPHWULDO JODQGXODU WLVVXH DQG VWURPDRXWVLGH WKH XWHULQH FDYLW\ $FFRUGLQJ WR WKH $PHULFDQ(QGRPHWULRVLV$VVRFLDWLRQRIZRPHQ GLDJQRVHGZLWKSHOYLFHQGRPHWULRVLVUHSRUWRQVHWRI V\PSWRPVEHIRUHWKHDJHRI\HDUV>@ 7KH¿UVWHYLGHQFHRIWKLVGLVHDVHGDWHVEDFNWRWKH WKFHQWXU\ZKHQ5RNLWDQVN\H[SUHVVHGDQRSLQLRQ WKDW HQGRPHWULDO JODQGV DQG VWURPD FRXOG EH IRXQG LQ RYDULDQ DQG XWHULQH WXPRUV +H ZDV WKH ¿UVW WR GHVFULEH DGHQRP\RVLV FDOOLQJ LW DQ ³DGHQRPDWRXV SRO\S´&XOOHQZDVWKH¿UVWWRGHVFULEHSHULWRQHDOHQ GRPHWULRVLVFDOOLQJLW³DGHQRP\RPD´,Q5XV VHOO SXEOLVKHG HYLGHQFH RI XWHULQH PXFRVD FRYHULQJ WKHRYDU\EXW6DPSVRQZDVWKH¿UVWWRGHPRQVWUDWH HQGRPHWULDOF\FOHVSHFL¿FFKDQJHVLQHFWRSLFHQGR PHWULRWLFIRFL>@ $FFRUGLQJWRWKH:RUOG+HDOWK2UJDQL]DWLRQ :+2  HQGRPHWULRVLV LV GLDJQRVHG LQ  RI DOO ZRPHQ RI UHSURGXFWLYH DJH  PLOOLRQ ZRPHQ ZRUOGZLGH  ,W LV HVWLPDWHG WKDW  WR  RI DGROHVFHQW JLUOV KDYH VRPHIRUPRIHQGRPHWULRVLVDQGLWLVKLJKHUDPRQJ WKRVH ZLWK G\VPHQRUUKHD ZKR UHVSRQG SRRUO\ WR RU DUH XQDႇHFWHG E\ DQDOJHVLF RU HVWURSURJHVWLQ WKHU DS\ )RU WKRVH VXႇHULQJ IURP UHFXUUHQW DQG FKURQLF SHOYLFSDLQWKHSHUFHQWDJHUHDFKHV>@ 7KHUHDUHDQXPEHURIWKHRULHVDWWHPSWLQJWRH[SODLQ WKHSDWKRJHQHVLVRIWKLVGLVHDVHWKHPRVWFRPPRQ EHLQJ 6DPSVRQ¶V WKHRU\ DFFRUGLQJ WR ZKLFK HQGR PHWULRVLVLVWKHUHVXOWRIUHWURJUDGHPHQVWUXDWLRQDQG LPSODQWDWLRQ RI YLDEOH HQGRPHWULDO FHOOV LQ WKH SHUL WRQHDO FDYLW\ +RZHYHU WKLV WKHRU\ FDQQRW H[SODLQ WKHRFFXUUHQFHRIHQGRPHWULRVLVLQJLUOVEHIRUHPHQ DUFKH,WLVQHFHVVDU\WRWDNHLQWRFRQVLGHUDWLRQFRH ORPLFPHWDSODVLDRUWKHDSSHDUDQFHRIHQGRPHWULRWLF IRFL IURP 0OOHULDQ UHVWV ZKLFK DUH WUDQVIRUPHG E\ HQGRJHQRXV VWHURLG KRUPRQHV $FFRUGLQJ WR RWKHU SXEOLFDWLRQV WKH HDUO\ PDQLIHVWDWLRQ RI WKH GLVHDVH PD\ EH DVVRFLDWHG ZLWK QHRQDWDO XWHULQH EOHHGLQJ ZKLFKRFFXUVLQRIQHZERUQVEHWZHHQGD\V RIELUWK7KHOHQJWKRIWKHFHUYL[DQGWKHGHQVHFHU YLFDOPXFXVOHDGWRIXQFWLRQDOREVWUXFWLRQZLWKVXE VHTXHQW UHWURJUDGH EOHHGLQJ GXULQJ ZKLFK YLDEOH SURJHQLWRU FHOOV DUH VKHG LQWR WKH SHULWRQHDO FDYLW\ +DOEDQ¶VWKHRU\H[SODLQVWKHSUHVHQFHRIGLVWDQWOR FDOL]DWLRQVRIHQGRPHWULRWLFIRFLE\PHWDVWDWLFVSUHDG RIHQGRPHWULDOFHOOVYLDWKHEORRGDQGO\PSKDWLFYHV VHOV7KHUHDUHDOVRLDWURJHQLFJHQHWLFWKHRULHVDV ZHOODVLPSDLUHGLPPXQHDQGLQÀDPPDWRU\UHVSRQV HVLQSDWLHQWVDႇHFWHGE\WKLVGLVHDVHDQGGHVSLWHWKH QXPHURXVWKHRULHVWKHSDWKRJHQHVLVLVVWLOOQRWIXOO\ XQGHUVWRRG>@ RISK FACTORS *HQHWLF SUHGLVSRVLWLRQ LV SUHVHQW LQ  RI FDVHV ZLWKFRPPRQYDULDQWVIRXQGLQ,WLVNQRZQWKDW LQDQDႇHFWHG¿UVWGHJUHHUHODWLYHWKHULVNRIGHYHO RSLQJ WKH GLVHDVH LQFUHDVHV E\ VHYHQ WR WHQ WLPHV UHODWLYHWRWKHJHQHUDOSRSXODWLRQZKLFKLVOLNHO\GXH WRSRO\JHQLFDQGPXOWLIDFWRULDOLQKHULWDQFH>@ 2EVWUXFWLYH0OOHULDQDQRPDOLHVDUHDQRWKHUULVNIDF WRU ,Q WKHVH FDVHV WKH DPRXQW RI UHWURJUDGH PHQ VWUXDWLRQ LQFUHDVHV DQG WKH OLNHOLKRRG RI LPSODQWD WLRQ RI YLDEOH HQGRPHWULDO FHOOV LQFUHDVHV >@ (DUO\ DJHRIPHQDUFKH±EHIRUH\HDUVRIDJHDQGVKRUW PHQVWUXDOF\FOHVDUHDQRWKHUULVNIDFWRU>@7KHLQ ÀXHQFH RI FHUWDLQ SROOXWDQWV DQG IRRGV ZLWK HVWUR JHQLF LQÀXHQFH SUHPDWXULW\ DQG ORZ ELUWK ZHLJKW DQGSDVVLYHVPRNLQJLVGLVFXVVHG,PSDLUHGLPPXQH DQG LQÀDPPDWRU\ UHVSRQVHV LQ WXUQ WU\ WR H[SODLQ Key words: eQGRPHWULRVLVDGROHVFHQWVWKHUDSHXWLFPDQDJHPHQW &orresSoQdLQJ DXWKor: 'LDQD+ULVWRYD'HSDUWPHQWRI2EVWHWULFVDQG*\QHFRORJ\0HGLFDO8QLYHU- VLW\±6R¿D8QLYHUVLW\2EVWHWULFVDQG*\QHFRORJ\+RVSLWDO³0DLFKLQGRP´6R¿D%XOJDULD=GUDYH VWUWHOHPDLOGLGQD#DEYEJ ORCID: ±'LDQD+ULVWRYD ORCID: ±,EU\DP,EU\DP ORCID: ±6WDQLVODYD+LWURYD1LNRORYD ORCID: ±5DGNR7RFHY ORCID: ±,YDQ.RVWRY ReFeLYed: -DQXDU\$FFeSWed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ႇHUVLJQL¿FDQWO\IURPWKDW RI SDWLHQWV RI UHSURGXFWLYH DJH$Q DFFXUDWH DQDP QHVLV LV RI XWPRVW LPSRUWDQFH 7KH TXHVWLRQV IRFXV RQWKHFKDUDFWHULVWLFVRIWKHSDLQDQGLWVUHODWLRQVKLS WRWKHPHQVWUXDOF\FOH7KH9$6 )LJ ZKHUHSD WLHQWVUHSRUWSDLQJUHDWHUWKDQSRLQWVDQGVFUHHQ LQJTXHVWLRQQDLUHVWKDWSDWLHQWVFRPSOHWHDUHKDQG\ $WWHQWLRQLVSDLGWRWKHDJHRIPHQDUFKHGXUDWLRQRI PHQVWUXDOF\FOHVDQGIDPLO\KLVWRU\,WLVLPSRUWDQWWR DVVHVVKRZWKHSDLQV\QGURPHDႇHFWVGDLO\DFWLYLWLHV VXFKDVGD\VRႇVFKRROSK\VLFDODFWLYLW\VOHHSTXDO LW\DQGVH[XDODFWLYLW\>@ Fig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ႇHUHQWLDOGLDJQRVWLFSURFHVV7 HVWWRDYRLG±&D LVPRVWFRPPRQO\XVHGDVDELRPDUNHUIRURYDU LDQFDQFHUEXWFDQEHHOHYDWHGLQDQXPEHURIRWKHU FRQGLWLRQVDVZHOODVHQGRPHWULRVLV&$LVQRWD XVHIXOWHVWIRUVFUHHQLQJDQGGLDJQRVLVGXHWRLWVORZ VHQVLWLYLW\DQGVSHFL¿FLW\>@ IMAGING METHOD 7UDQVDEGRPLQDO XOWUDVRQRJUDSK\ YLVXDOL]HV RYDULDQ endometriosis but is an inferior method for diagnos  LQJVXSHU¿FLDOSHOYLFHQGRPHWULRVLVZKLFKLVWKHPRVW FRPPRQIRUPLQDGROHVFHQWSDWLHQWV7KHWUDQVYDJL QDO DSSURDFK DOORZV HYDOXDWLRQ RI WKH XWHULQH ERG\ YLVXDOL]DWLRQRIKHWHURHFKRJHQLFLVODQGVLQWKHP\R PHWULXPRUDYDVFXODUF\VWLFDUHDVZKHQDGHQRP\R VLVLVVXVSHFWHG 2YDULDQ HQGRPHWULRVLV DFFRUGLQJ WR WKH ,27$ FODV VL¿FDWLRQ LV PRVW RIWHQ UHSUHVHQWHG E\ XQLODWHUDO K\SRHFKRJHQLF³IURVWHGJODVV´W\SHF\VWVZLWKZHDN YDVFXODUL]DWLRQ,QRIFDVHVWKH\PD\KDYHDQ DW\SLFDO DSSHDUDQFH ± PXOWLORFXODU IRUPDWLRQV ZLWK DYDVFXODUSDSLOODU\JURZWKVK\SHUHFKRJHQLFIRFLGXH WRFDOFL¿FDWLRQVDQGVROLGDUHDV7KH\PD\EHUHS UHVHQWHGE\VROLGDQGOLTXLGFRPSRQHQWV>@%H FDXVHIRFLLQVXSHU¿FLDOSHOYLFHQGRPHWULRVLVDUHGLI ¿FXOWWRYLVXDOL]HE\XOWUDVRQRJUDSK\VRFDOOHG³VRIW PDUNHUV´DUHXVHGLHUHGXFHGPRELOLW\RIWKHRYDU\ DQGRUXWHULQHERG\DVZHOODVRIWKHUHFWXPUHODWLYH WRWKHXWHULQHERG\>@ 0DJQHWLF UHVRQDQFH LPDJLQJ 05,  FDQ EH XVHIXO IRU GLDJQRVLQJ REVWUXFWLYH DQRPDOLHV RI WKH UHSUR GXFWLYH WUDFW DQG IRU LGHQWLI\LQJ HQGRPHWULRWLF OH VLRQV WKDW DUH GLႈFXOW WR ORFDO L]HE\XOWUDVRXQGEXWGXHWRLWV KLJKFRVWLWFDQQRWEHXVHGDVD VFUHHQLQJPHWKRG>@ 7KHGLDJQRVLVLVRIWHQPDGHGXU LQJ ODSDURVFRSLF VXUJHU\ ZKLFK UHPDLQVWKHÄJROGVWDQGDUG³7KH XVH RI GLDJQRVWLF ODSDURVFRS\ LV LQGLFDWHG LQ FDVHV RI SHUVLVWHQW SDLQV\QGURPHIRUPRUHWKDQWKUHHPRQWKVRULQFDVHV RISRRURUQRUHVSRQVHWRQRQVWHURLGDODQWLLQÀDPPD WRU\GUXJVDQGRUKRUPRQDOWKHUDS\7KHODSDURVFRSLF ¿QGLQJV LQ DGROHVFHQW HQGRPHWULRVLV DUH PDLQO\ UHS UHVHQWHGE\DW\SLFDOFKDQJHVLHFOHDUUHGRUZKLWH OHVLRQVRUVPDOOSHULWRQHDOGHIHFWVZKLFKDUHVXEMHFW WRSDWKRKLVWRORJLFDOYHUL¿FDWLRQ>@ $ZLGHSDOHWWHRIGLVHDVHVDႇHFWLQJWKHJDVWURLQWHVWL QDOWUDFWXULQDU\V\VWHPVNHOHWDOPXVFXODUGLVHDVHV DQGQHXURORJLFDOGLVHDVHVFRPHVLQWRFRQVLGHUDWLRQ 87Endometriosis in adolescents LQWKHGLႇHUHQWLDOGLDJQRVWLFSODQ2QWKHVLGHRIWKH UHSURGXFWLYHV\VWHPWKHIROORZLQJVKRXOGEHH[FOXG HGDGHQRP\RVLVSRVWRSHUDWLYHDGKHVLYHV\QGURPH SHOYLFLQÀ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ÀDP PDWLRQPHGLDWHG HVWURJHQGHSHQGHQW GLVHDVH >@ 1RQVWHURLGDO DQWLLQÀDPPDWRU\ GUXJV 16$,'V  DUH LQGLFDWHG DV ¿UVWOLQH WUHDWPHQW IRU SDLQ V\QGURPH ZLWKGRVDJHEDVHGRQERG\ZHLJKWDQGLQWDNHVWDUW LQJ GHSHQGLQJ RQ WKH WLPLQJ RI V\PSWRPV )OXLG LQ WDNH LV LQFUHDVHG GXULQJ 16$,' DGPLQLVWUDWLRQ IRU QHSKURSURWHFWLRQ ,EXSURIHQ LV D ZLGHO\ DYDLODEOH DQGDႇRUGDEOH16$,'ZLWKJRRGWROHUDELOLW\,WUHDFK HV SHDN SODVPD FRQFHQWUDWLRQ LQ  PLQ DQG KDV D SODVPD KDOIOLIH RI  KRXUV$ FKDUDFWHULVWLF RI WKH GUXJLVWKDWLWGRHVQRWLQFUHDVHPHQVWUXDOEORRGORVV ZKLFK LV WKH HႇHFW RI .HWRSURIHQ DQG 1DSUR[HQ >@ &2;LQKLELWRUV &2;DUHHQ]\PHVNH\WRWKHSURGXF WLRQRILQÀDPPDWRU\PHGLDWRUV PD\FRPHLQWRFRQ VLGHUDWLRQ LQ SDLQ FRQWURO DQG DOWKRXJK ERWK &2; DQG&2;UHFHSWRUVDUHSUHVHQWLQHFWRSLFHQGRPH WULRWLFIRFLVWXGLHVKDYHVKRZQWKDW&2;UHFHSWRUV DUHSUHVHQWDWKLJKHUFRQFHQWUDWLRQV$ORQJZLWKSDLQ FRQWUROQHZVWXGLHVVXJJHVWWKDWVHOHFWLYH&2;LQ KLELWRUVPD\DOVRLQKLELWHQGRPHWULDOWLVVXHSUROLIHUD WLRQ LQGXFH DSRSWRVLV DQG VXSSUHVV QHRDQJLRJHQ HVLV>@ THERAPY &RPELQHGRUDOFRQWUDFHSWLYHV &2&V RUJHVWDJHQV DORQHDUHWKH¿UVWOLQHKRUPRQDOPHGLFDWLRQVXVHGLQ WKH WKHUDSHXWLF SODQ RI SDWLHQWV ZLWK HQGRPHWULRVLV 7KHWKHUDSHXWLFHႇHFWRI&2&VLVPHGLDWHGE\VXS SUHVVLRQ RI WKH K\SRWKDODPLFSLWXLWDU\RYDULDQ D[LV +32  DFWLYLW\ UHGXFLQJ PHQVWUXDO EORRG ORVV DQG LQSDUWLFXODUUHWURJUDGHPHQVWUXDWLRQDVZHOODVWKH SHULWRQHDO LQÀDPPDWRU\ UHVSRQVH7KHLU DGPLQLVWUD WLRQ LQGXFHV HQGRPHWULDO K\SRWURSK\ VXSSUHVVHV &2; DQG SURVWDJODQGLQ V\QWKHVLV DQG UHGXFHV DF\FOLF DQG RYXODWRU\ SDLQ $V D SRVLWLYH Hႇ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ႇHFWHGE\ HPSLULFWKHUDS\>@ 7KH DGPLQLVWUDWLRQ RI JHVWDJHQV DV D VWDQGDORQH WKHUDS\ KDV DQ DQWLJRQDGRWURSLF HႇHFW OHDGLQJ WR DQRYXODWLRQ DQG VXSSUHVVLRQ RI RYDULDQ VWHURLGRJHQ HVLVDVZHOODVWRGHFLGXDOL]DWLRQDQGDWURSK\RIHF WRSLF IRFL 7KH\ PRGXODWH WKH LPPXQH UHVSRQVH E\ VXSSUHVVLQJWKHV\QWKHVLVRILQÀDPPDWRU\PHGLDWRUV 3*V ,/V  DQG JURZWK IDFWRUV 1*)V 9*)V  1RUH WKLVWHURQHDFHWDWH 1(7$ DWDGRVHRIPJGD\ LVUHFRPPHQGHGIRUXVHLQDGROHVFHQFH,WKDVDORQJ KDOIOLIH  KRXUV  DQG LV SDUWLDOO\ PHWDEROL]HG WR HWKLQ\OHVWUDGLRO$WDGRVHRIPJGD\LWVXSSUHVVHV WKHSUHRYXODWRU\/+SHDN,WVSURORQJHGXVHUHVXOWVLQ VHFRQGDU\ DPHQRUUKHD ZLWK WKH SRVVLELOLW\ RI EUHDN WKURXJKEOHHGLQJ1HZRQVHWDFQHKDVEHHQUHSRUWHG DV D VLGH HႇHFW ,WV LQÀXHQFH RQ SODVPD OLSLGV DQG ERQH PLQHUDO GHQVLW\ LV QHJOLJLEOH$QRWKHU JHVWDJHQ ZLWK ZLGHVSUHDG XVH LV 'LHQRJHVW '1*  DW D GRVH RIPJGD\,WVSURORQJHGDGPLQLVWUDWLRQOHDGVWRHQ GRPHWULDOK\SRWURSK\WKURXJKGLUHFWUHFHSWRULQWHUIHU HQFHDQGWKHVXSSUHVVLRQRIQHRDQJLRJHQHVLVDQGWKH V\QWKHVLV RI LQÀDPPDWRU\ PHGLDWRUV '1* SURPRWHV DSRSWRVLVLQHFWRSLFIRFL,WVKDOIOLIHLVKRXUVDQG LWLVZHOOWROHUDWHG$VVLGHHႇHFWVKDYHEHHQUHSRUWHG ± VSRWWLQJ VHFRQGDU\ DPHQRUUKHD FKHVW WLJKWQHVV KHDGDFKH /HVV IUHTXHQWO\ FKDQJHV LQ ERG\ ZHLJKW DQG LQ PRRG PD\ EH REVHUYHG ,W DOVR DႇHFWV OLSLG SUR¿OH DQG ERQH PLQHUDO GHQVLW\ 7KHVH VLGH HႇHFWV WHQGWRGLPLQLVKDIWHUWKH¿UVWVL[PRQWKVRIXVH1RU PDO PHQVWUXDO F\FOHV DUH XVXDOO\ UHVWRUHG ZLWKLQ WZR PRQWKVDIWHUGLVFRQWLQXDWLRQRI'1*WKHUDS\ /HYRQRUJHVWUHOUHOHDVLQJLQWUDXWHULQHGHYLFHV /1* ,86  FRQWDLQ  PJ RI OHYRQRUJHVWUHO ZLWK  PL FURJUDPVRIWKHKRUPRQHUHOHDVHGLQKRXUVRYHU  \HDUV %HWWHU FRPSOLDQFH KDV EHHQ UHSRUWHG E\ DYRLGLQJRUDODGPLQLVWUDWLRQDQGGDLO\FRPPLWPHQW (ႇHFWVRI/1*,8'VDUHHQGRPHWULDODWURSK\K\SR PHQRUUKHD ZLWK UHGXFWLRQ LQ UHWURJUDGH PHQVWUXD WLRQ DQG KLJKHU SURJHVWHURQH FRQFHQWUDWLRQ LQ WKH 88 '+ULVWRYD,,EU\DP6+LWURYD1LNRORYDHWDO SHULWRQHDO FDYLW\ VXSSUHVVLQJ HFWRSLF IRFL DFWLYLW\ 7KHHႇHFWLQWHUPVRISDLQV\QGURPHLVFRPPHQVX UDWHZLWKWKDWRIWKHXVHRI*Q5+DJRQLVWV$ORZHU UHFXUUHQFHUDWHDIWHUGLVFRQWLQXDWLRQRIWKHUDS\KDV DOVREHHQUHSRUWHG/1*,8'VDUHQRWDSSURSULDWH DV¿UVWOLQHKRUPRQDOWKHUDS\LQSDWLHQWVLQWKH¿UVW \HDUVDIWHUPHQDUFKHDQGLQWKRVHZKRGRQRWKDYH DVH[XDOOLIH$SSURSULDWH/1*,8'VPD\EHSODFHG LQ WKH FRXUVH RI ODSDURVFRSLF VXUJLFDO UHPRYDO RI HQGRPHWULRWLF IRFL ZLWK WKH JRDO RI FRQWLQXHG KRU PRQDO WKHUDS\ WR SUHYHQW VXEVHTXHQW UHFXUUHQFHV >@ 7KHVHFRQGOLQHRIKRUPRQHWKHUDS\LVWKHJURXSRI *Q5+DJRQLVWV7KHLUVXFFHVVIXOXVHLVEDVHGRQWKH IDFW WKDW WKH\ OHDG WR K\SRHVWURJHQLVP E\ EORFNLQJ RYDULDQ VWHURLGRJHQHVLV ZKLFK DFFHOHUDWHV WKH UH JUHVVLRQ RI HFWRSLF HQGRPHWULRWLF LPSODQWV 'XULQJ WKH ¿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ႇHFWV RI K\SRHVWURJHQLVP ± ERQH PDVVORVVYDJLQDODWURSK\DQGGU\QHVVKRWÀDVKHV DQG DEQRUPDOLWLHV LQ OLSLG SUR¿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±SOHXUDOLQWUDFUDQLDOSHUL FDUGLDOHWF>@ &RPSDUHGWR*Q5+DJRQLVWV*Q5+DQWDJRQLVWVGR QRW FDXVH DQ LQLWLDO ÀDUHXS RI V\PSWRPV DQG WKHLU DGPLQLVWUDWLRQ UHVXOWV LQ OHVV SURQRXQFHG K\SRHV WURJHQLVP 7KLV JURXS RI PHGLFDWLRQV KDV D EHWWHU VLGHHႇHFWSUR¿OH(ODJROL[LVDQRUDO*Q5+UHFHSWRU DQWDJRQLVW WKDW LQKLELWV HQGRJHQRXV *Q5+ VLJQDO LQJ E\ FRPSHWLWLYHO\ ELQGLQJ WR *Q5+ UHFHSWRUV LQ WKH SLWXLWDU\ JODQG ,W ZDV DSSURYHG IRU XVH E\ WKH )'$ LQ -XO\  IRU WKH WUHDWPHQW RI PRGHUDWH WR VHYHUH SDLQ DVVRFLDWHG ZLWK HQGRPHWULRVLV ,WV DG PLQLVWUDWLRQ UHVXOWV LQ GRVHGHSHQGHQW VXSSUHVVLRQ RI /+ DQG )6+ UHOHDVH UHVXOWLQJ LQ K\SRHVWURJHQ LVP(ODJROL[DQG/LQ]DJROL[DUHSDUWRIWKHWKHUDSHX WLFSODQLQSDWLHQWVRIUHSURGXFWLYHDJHEXWWKHUHDUH FXUUHQWO\LQVXႈFLHQWVWXGLHVDQGGDWDRQWKHLUXVHLQ DGROHVFHQWSDWLHQWV>@ $URPDWDVHLQKLELWRUVDUHXVHGWRWUHDWSDWLHQWVZLWK HQGRPHWULRVLVDWUHSURGXFWLYHDJH $URPDWDVH3 is the key enzyme for estrogen biosynthesis in the RYDU\,WFDWDO\]HVWKHFRQYHUVLRQRIDQGURVWHQHGL RQHDQGWHVWRVWHURQHV\QWKHVL]HGLQRYDULDQWKHFD FHOOV WR HVWURQH DQG HVWUDGLRO (  LQ JUDQXORVD FHOOV7KHUHLVDEXQGDQWHYLGHQFHVKRZLQJWKDWHQ GRPHWULRWLFOHVLRQVH[SUHVVDURPDWDVHDQGDUHDEOH WR V\QWKHVL]H WKHLU RZQ HVWURJHQV ,Q YLHZ RI WKLV REVHUYDWLRQ WKH XVH RI D WKLUGJHQHUDWLRQ DURPD WDVHLQKLELWRU/HWUR]ROH $, WRWUHDWHQGRPHWULRVLV LVDQDWWUDFWLYHFRQFHSW7KHUHDUHLQVXႈ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¶VQRUPDODQDWRP\,Q DGROHVFHQW SDWLHQWV VXUJLFDO LQWHUYHQWLRQV VKRXOG EHDVVSDULQJDVSRVVLEOH5DGLFDOH[FLVLRQRIVX SHU¿FLDOHQGRPHWULRVLVLVQRWSUDFWLFHGEHFDXVHRI WKHULVNRIH[WHQVLYHDGKHVLYHSRVWRSHUDWLYHFRP SOLFDWLRQV&RPSDUHGZLWKSDWLHQWVRIUHSURGXFWLYH DJHWKRVHLQDGROHVFHQFHKDYHEHHQUHSRUWHGWR KDYHDKLJKHUUHFXUUHQFHUDWHRYHUD\HDUSHULRG ZLWKDUHFXUUHQFHUDWHLQDGROHVFHQWVZLWK RXW VXEVHTXHQW VXUJLFDO WUHDWPHQW ZLWK KRUPRQH WKHUDS\>@

Conclusion

(QGRPHWULRVLVLVDQHVWURJHQGHSHQGHQWFKURQLFLQ ÀDPPDWRU\ GLVHDVH ZLWK D SURJUHVVLYH FRXUVH WKDW DႇHFWV DOO DVSHFWV RI D JLUO¶V OLIH 7KH WKHUDSHXWLF DSSURDFK WR SDWLHQWV ZLWK DGROHVFHQW HQGRPHWULRVLV VKRXOGEHLQGLYLGXDOL]HGDQGFDVHVVKRXOGEHHYDOX DWHGE\DPXOWLGLVFLSOLQDU\WHDP7KHDLPLVWRVKRUW en the time from symptom onset to diagnosis and WKHLQLWLDWLRQRIWLPHO\WUHDWPHQW7KHJRDOVRIPHGL FDO WKHUDS\ LQ DGROHVFHQW SDWLHQWV LQFOXGH V\PSWRP 89Endometriosis in adolescents UHOLHI VORZLQJ GLVHDVH SURJUHVVLRQ DQG SURWHFWLQJ IXWXUHIHUWLOLW\ CoQÀLFW o I I QWeresW 6WDWePeQW: The authors declare no FRQÀLFWVRILQWHUHVWUHODWHGWRWKLVZRUN Funding:7KHDXWKRUVGLGQRWUHFHLYHDQ\¿QDQFLDOVXSSRUW IURPDQ\RUJDQL]DWLRQIRUWKLVUHVHDUFKZRUN (WKiFDO sWDWePenW: This study has been performed in ac- cordance with the ethical standards as laid down in the 'HFODUDWLRQRI+HOVLQNL

References

1. 'HL0%UXQL93HGLDWULFDQGDGROHVFHQWJ\QDHFRORJ\2(2 2ႈFLQD(GLWRULDOH2OWUDUQR 2. %HQDJLDQR*%URVHQV,/LSSL'7KHKLVWRU\RIHQGRPHWULR VLV*\QHFRO2EVWHW,QYHVW    5RJHUV 3$ 'µ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¿OLSSR - (QGRPHWULRVLV LQ WKHDGROHVFHQWSDWLHQW6HPLQ5HSURG0HG 8. 6KDIULU$/ )DUODQG /9 6KDK '. HW DO 5LVN IRU DQG FRQVH TXHQFHV RI HQGRPHWULRVLV $ FULWLFDO HSLGHPLRORJLF UHYLHZ %HVW3UDFW5HV&OLQ2EVWHW*\QDHFRO  &KDSURQ&0DUFHOOLQ/0DLWURW0DQWHOHW/HWDO4XHVWLRQQDLUH EDVHG VFUHHQLQJ RI DGROHVFHQWV DQG \RXQJ DGXOW ZRPHQ FDQ LGHQWLI\ PDUNHUV DVVRFLDWHG ZLWK HQGRPHWULRVLV +XP 5HSURG     6DUÕGR÷DQ($GROHVFHQWHQGRPHWULRVLV(XU-2EVWHW*\QH FRO5HSURG%LRO 11. 6DVDPRWR1'H3DUL09LWRQLV$) HWDO(YDOXDWLRQRI&$ LQUHODWLRQWRSDLQV\PSWRPVDPRQJDGROHVFHQWVDQG\RXQJ DGXOWZRPHQZLWKDQGZLWKRXWVXUJLFDOO\FRQ¿UPHGHQGRPH WULRVLV3/R62QH  H 12. *HUJHV % /X & 5HLG 6 DW DO 6RQRJUDSKLF HYDOXDWLRQ RI LPPRELOLW\ RI QRUPDO DQG HQGRPHWULRWLF RYDU\ LQ WKH GHWHF WLRQ RI GHHS HQGRPHWULRVLV 8OWUDVRXQG 2EVWHW *\QHFRO   2OLYHLUD ,7  3LQWR 39 %HUQDUGHV -)  1RQLQYDVLYH GLDJQRVLV RIHQGRPHWULRVLVLQDGROHVFHQWVDQG\RXQJIHPDOHDGXOWVD V\VWHPDWLF UHYLHZ - 3HGLDWU$GROHVF *\QHFRO 6     7\VRQ 1LFKROH HW DO 6XUJLFDO &RQVLGHUDWLRQV LQ WKH 0DQDJH PHQW RI $GROHVFHQW (QGRPHWULRVLV ± $Q ([SHUW &RPPHQWDU\ -RXUQDORI0LQLPDOO\,QYDVLYH*\QHFRORJ\   15. +DUHO='\VPHQRUUKHDLQDGROHVFHQWVDQG\RXQJDGXOWV DQ XSGDWH RQ SKDUPDFRORJLFDO WUHDWPHQWV DQG PDQ DJHPHQW VWUDWHJLHV ([SHUW 2SLQ 3KDUPDFRWKHU   16. /DL==<DQJ+/+D6< HWDO&\FORR[\JHQDVHLQ(QGRPH WULRVLV,QW-%LRO6FL    0LWFKHOO -% &KHWW\ 6 .DWKUDGD )  3URJHVWLQV LQ WKH V\PS WRPDWLF PDQDJHPHQW RI HQGRPHWULRVLV D PHWDDQDO\VLV RQ WKHLU Hႇ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µV QHZ" &XUU 2SLQ 3HGLDWU   

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

⚙ Ask this paper AI returns verbatim quotes from the full text · source: oa-pdf ⓘ

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosisadenomyosischronic_pelvic_paindysmenorrheadyspareunia

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (19)

Source provenance

openalex
last seen: 2026-06-10T17:14:06.276822+00:00
License: CC0 · commercial use OK