PREVALENZA DELL’ENDOMETRIOSI Massimo Luerti U.O. di Ostetricia Ginecologia 1 A.O. della Provincia di Lodi massimo.luerti@ao.lodi.it Unità Operativa di OSTETRICIA E GINECOLOGIA 1

PREVALENCE AND INCIDENCE OF ENDOMETRIOSIS the number of people who currently have the condition Incidence the annual number of people who have a case of the condition

GENERAL PROBLEMS WITH DATA Unclear sources Data ranges Different definitions of prevalence Different sources Different study methodologies Different disease categories Different years Different locations Different age groups Different racial factors Inherent reporting bias Country-specific information

PROBLEMS WITH PREVALENCE DATA Diagnosed versus undiagnosed prevalence Different methods of gathering prevalence data Prevalence and "cured" or "remission" conditions

PROBLEMS WITH ENDOMETRIOSIS PREVALENCE Need for a surgical diagnosis Atypical endometriosis Pelvic and extrapelvic localizations Histologic confirmation Racial factors Infertility Pain

ENDOMETRIOSIS Need for a surgical diagnosis The only reliable way of determining its presence is through surgery or at autopsy. Surgical incidence is biased by the selection process bringing the patient to the operating room. No large cadaver study examining autopsy specimens for endometriosis has reported data that has been widely accepted. Eric Daiter, M.D

Atypical endometriosis lesione tipica: Nodulo nero Lesione a chiazza giallo-bruno Lesione cicatriziale bianca lesione atipica: Lesioni rosse a fiamma Escrescenze ghiandolari Opacizzazioni bianche peritoneali Petecchie peritoneali Aree di ipervascolarizzazione Aderenze sotto ovariche Aree giallo brunastre Chiazze peritoneali giallastre Difetti peritoneali

Atypical endometriosis

PELVIC AND EXTRAPELVIC LOCALIZATIONS ovaie legamenti utero-sacrali cul-de-sac peritoneo della pelvi setto retto-vaginale intestino, retto e appendice cicatrici laparotomiche vescica vagina polmone, linfonodi, pleura, cuore, osso

PELVIC AND EXTRAPELVIC LOCALIZATIONS Typical age range at diagnosis 20-40 years About 10% of the cases in women under the age of 20 2-4% of postmenopausal women In 60% of the cases, ectopic implants in the cul-de-sac and/or the uterosacral ligaments In 50% of the cases the ovaries are involved In 15% of the cases the bladder is involved In 10% of the cases fallopian tubes are involved Extrapelvic endometriosis without genital tract implants is rare and occurs in less than 8% of cases Up to 20% of patients may experience endometriosis that affects the bowel, rectum, appendix, or ureter if they have pelvic endometriosis Extra-abdominal endometriosis is rare K.W. Schweppe, 1988

ENDOMETRIOSIS Histologic confirmation La conferma istologica varia dal 3% al 100% Peritoneo macroscopicamente normale può risultare sede di microfocolai di endometriosi nel 15-25% dei casi

Unique ultra-orthodox Jewish population Racial factors Unique ultra-orthodox Jewish population over the past 20 years 1,434 hysterectomy specimens reviewed incidence of adenomyosis among the hysterectomy specimens decreased from 15.14% in the first 10 years to 9.24% in the second decade (p < 0.05) the incidence of endometriosis remained unchanged, and was very low (1.12%) compared to published data. Effects of heredity, religious and social behavior on the prevalence of endometriosis Bocker J, Tadmor OP, Gal M, Diamant YZ, Asia Oceania J Obstet Gynaecol. 1994 Jun;20(2):125-9.

Racial factors Extrapolation of Prevalence Rate of Endometriosis to Countries and Regions The following table attempts to extrapolate the above prevalence rate for Endometriosis to the populations of various countries and regions. As discussed above, these prevalence extrapolations for Endometriosis are only estimates and may have limited relevance to the actual prevalence of Endometriosis in any region

INFERTILITY LAPAROSCOPIA DIAGNOSTICA ed INFERTILITA’

INFERTILITY L’incidenza dell’endometriosi è più elevata nelle donne con sterilità rispetto alle donne fertili. Incidenza della endometriosi nella sterilita’ ed infertilita’: risultati del Centro di Sterilita’ di Reggio Emilia in 1011 donne sottoposte a laparoscopia di bilancio per sterilità o infertilità * Stadio endometriosi Donne N° %** %*** I 158 15,6 41,9 II 103 10,2 27,4 III 60 5,9 15,9 IV 56 5,5 14,8 * Donne infertili con sospetto di utero setto o bicorne ** Riferita alle 1011 donne sterili o infertili sottoposte a laparoscopia *** Riferita al totale delle 377 donne con endometriosi

INFERTILITY LAPAROSCOPIA DIAGNOSTICA ed INFERTILITA’ Rilievo Laparoscopico

INFERTILITY LAPAROSCOPIA DIAGNOSTICA ed INFERTILITA’ Riscontro Laparoscopico nella sterilità inspiegata Alterazioni tubariche (34%) Occl. tubarica monolat. (20%) Occl. bil. (12%)

DOLORE PELVICO CRONICO (CPP) PAIN DOLORE PELVICO CRONICO (CPP) 1300 donne sottoposte a LPS per CPP nessuna lesione 40% endometriosi 28% aderenze 25% Howard, 1993

Differences in the indications for laparoscopy and laparotomy Differences in the prevalence of the disease vary by as much as 30–40 times. Differences in the indications for laparoscopy and laparotomy Differing degrees of attention paid by surgeons to the accurate identification of endometriotic lesions and by selective mechanisms drawing patients with suspected endometriosis towards specialized centres. There are no published studies on representative samples of the general population. It is difficult to compare estimates of prevalence because the published studies include women with different conditions, and are conducted in centres that apply different diagnostic criteria and exhibit different levels of clinical interest in endometriosis. Best Practice & Research Clinical Obstetrics and Gynaecology Vol. 18, No. 2, pp. 177–200, 2004

ENDOMETRIOSIS: INCIDENCE RATES The "Public testimony to the US Senate Committee on Labor and Human Resources, Subcommittee on Aging“ report in 1993: about 5 million women in the USA are affected by endometriosis. Widely used numbers for the incidence of endometriosis include 3-10% of all reproductive age women and 25-40% of all women with an infertility problem. Eric Daiter, M.D

Animal Studies in Endometriosis: A Review Lisa Story and Stephen Kennedy ILAR Journal, Volume 45, Number 2 2004 The exact prevalence of endometriosis in the population cannot be ascertained because of the need to perform an invasive procedure to determine who is affected. Nevertheless, estimates range from 2 to 22% in asymptomatic women, 40 to 60% in women with dysmenorrhea, and 20 to 30% in women being investigated for subfertility (Farquhar 2000).

Human Reproduction, Vol. 17, No Human Reproduction, Vol. 17, No. 6, 1415-1423, June 2002 What makes a good case–control study? Design issues for complex traits such as endometriosis Krina T. Zondervan1,3, Lon R. Cardon1 and Stephen H. Kennedy Because of the need for a surgical diagnosis, the prevalence of endometriosis in the general population is unknown. Estimates from asymptomatic fertile subpopulations undergoing tubal ligation have varied greatly, from 0.7 to 43% around a mean of 4% (Eskenazi and Warner, 1997 ). However, up to 90% of these women were diagnosed with minimal or mild endometriosis.

Prevalence and Incidence of Endometriosis The National Women’s Health Information Center, NICH, NIH: 10 to 20 percent of American women of childbearing age have endometriosis; up to 2 million women in the UK. The National Women’s Health Information Center, Bioscience: approx 1 in 20 or 5.00% or 13.6 million people in USA ()

PREVALENCE OF PELVIC PAIN (selected studies) Authors, Country Number of subjects Class age Prevalence Jamieson Steege, 1996 701 18-45 39 Mathias, 1996, USA 5263 (phone interview) 18-50 15 Zondervan 1998, UK Review Fertile age 10-50 Zondervan 2001, UK 3916 (postal quest) 18-49 24

PREVALENZA DI ENDOMETRIOSI SECONDO INTERVENTO E DIAGNOSI U.O. Ostetricia Ginecologia 1 – A.O. della Provincia di Lodi, 2005

PREVALENCE OF ENDOMETRIOSIS Female population unknown In gynecological laparotomies 1-50% In gynecological laparoscopies 5-53% In infertile women 15-24% In unexplained infertility 70-80% In female population (estimated) 2% In laparoscopic sterilization 2-4% K.W. Schweppe, 1988

ENDOMETRIOSI NELLE ADOLESCENTI L’incidenza di endometriosi nelle adolescenti è tuttora sconosciuta. Vercellini (1989) 38% Reese (1996) 73%

10% of women in the reproductive age group have endometriosis 30-50% of infertile women have endometriosis Occurs primarily in women in their 20's and 30's Once thought that middle-class, white patients who are high achievers and perfectionists were at higher risk Int J Gynaecol Obstet. 1997  

ESTIMATED PREVALENCE OF ENDOMETRIOSIS: REVIEW OF THE LITERATURE Diagnostic procedure Author and year % Sterilization Strathy (1982) 2 Kirshon (1989) 7 Drake (1980) 5 Kresch (1984) 15 Liu (1986) 43 Moen (1991) 19 Mahmood (1991) 19 Laparoscopy for infertility Drake (1980) 48 Mahmood (1991) 21 Hasson (1976) 23 Laparoscopy for pelvic pain Kresch (1984) 32 Mahmood (1991) 15 Hasson (1976) 12 Haleh Sangi-Haghpeykar, Alfred N. Poindexter III Obstet Gynecol 1995;85:983-92

Eric Daiter, M.D Endometriosis: incidence rates The literature on the prevalence of endometriosis in selected groups of women suggest a 2% rate for those undergoing elective tubal sterilization, an 8-12% rate for those undergoing hysterectomy, a 30% rate for those undergoing operative laparoscopy and a 55% rate for teenagers undergoing diagnostic laparoscopy for pelvic pain. In 1987, the "National Center for Health Statistics" report on hysterectomies performed in the USA between 1965 and 1984 described about 2 million US women with a diagnosis of endometriosis who had a hysterectomy. An interesting finding from this report was that the number of women with endometriosis having a hysterectomy increased steadily throughout the target time period, with less than 150,000 women in 1965-67 and greater than 350,000 women in 1982-84. This increase was not fully accounted for by an increase in hysterectomies in general and occurred during a time when increasingly conservative management for endometriosis became popular. Therefore, the increase may reflect an increase in the incidence or severity of endometriosis in the USA.

Trattamento chirurgico della sterilità associata a endometriosi I-II stadio

Trattamento chirurgico della sterilità associata a endometriosi III-IV stadio

endometriosi L’incidenza della endometriosi nella polazione femminile in età fertile, varia tra il 7 e 10%.

endometriosi infiltrante del cul-de-sac anteriore l’1% delle donne affette da endometriosi presentano lesioni del tratto urinario, l’84% delle quali coinvolgono la vescica

endometriosi infiltrante del cul-de-sac anteriore due forme distinte di endometriosi del detrusore: spontanea contemporanea presenza di patologia più generalizzata il nodulo ha origine nella cupola vescicale iatrogena disseminazione intraoperatoria in corso di taglio cesareo

endometriosi infiltrante ureterale rara (tra 0.01% e 0.6%) origina dall’estensione di un impianto pelvico peritoneale lungo la faccia laterale gonadica e la fossetta ovarica spesso coesiste una endometriosi ovarica lesioni ostruttive del terzo distale, pressoché esclusive sul lato sinistro (50% - fossetta ovarica, 50% legamento utero-sacrale) intrinseca: tessuto endometriosico nell’ambito di una muscularis iperplastica e fibrotica estrinseca: restringimento del lume da compressione e/o fibrosi

L’ENDOMETRIOSI PROFONDA Definizione : lesione profonda >= 5 mm. 11-16 % dei casi di endometriosi presenta localizzazioni profonde, di cui: 55 % Douglas 35 % leg. utero-sacrali 11% setto retto-vaginale 5 % retto-sigma 2-4 % vie urinarie ( 25-30 % rene escluso !)

INCIDENZA ENDOMETRIOSI MINIMA-LIEVE 7-10% nella popolazione generale 20-70 % nelle pazienti infertili 70-80% nelle pazienti con dolore pelvico cronico 40% donne asintomatiche

PREVALENZA DI ENDOMETRIOSI IN DONNE SOTTOPOSTE AD INTERVENTO (Parazzini, 1994) DIAGNOSI 95% confidence Sterilità 30 26-35 Dolore pelvico 45 39-52 Fibromi 12 10-14 Cisti ovarica 35 31-40

L’ ENDOMETRIOSI PROFONDA Chirurgia del setto retto-vaginale : quando intervenire - sintomi presenti ( dispareunia, dismenorrea) - massa pelvica da definire - infertilità Indagini diagnostiche : eco transrettale, RMN Tecnica : isolamento del nodulo a partire dal connettivo lasso extraperitoneale procedendo in senso centripeto verso la lesione - se lesione è molto laterale : tecnica di Hudson per il cancro infiltrante - eventuale resezione vaginale se coinvolta la mucosa vaginale

L’ ENDOMETRIOSI PROFONDA Chirurgia del retto-sigma : quando intervenire - se lesione sintomatica : dischezia, dispareunia, sindrome subocclusiva ( 30 % asintomatica) - se sintomo algico : escissione di losanga parietale a mucosa integra - se sintomo meccanico : resezione intestinale con anastomosi T- T Ausili diagnostici : clisma opaco, rettosigmoidoscopia, RMN NB: lasciare isolata una piccola area di endometriosi rettale (malattia residua) non comporta un maggiore rischio di recidiva del sintomo NB: in caso di soluzione di continuo sutura laparoscopica in duplice strato NB: ricordare che è lesione benigna: ampi interventi demolitivi sul tubo digerente sono giustificati solo su casi molto selezionati

L’ENDOMETRIOSI PROFONDA Chirurgia delle vie urinarie : quando intervenire vescica (1%): lesione sintomatica ( dolore, disuria, stranguria, ematuria) NB: la lesione coinvolge sempre la tonaca muscolare tecnica : escissione possibilmente extramucosa con sutura in unico o duplice strato (muscolare-mucosa e sierosa) uretere (1%): coinvolto quasi sempre ab estrinseco la lesione va sempre trattata ( valutare rene escluso) tecnica : ureterolisi ureteroureterostomia ureteroneocistostomia

Il trattamento dell’endometriosi lieve Familiarità Le donne con una parente di I grado affetta da endometriosi hanno un rischio aumentato da 6 a 10 volte di ammalarsi

Risk factors associated with endometriosis include the Animal Studies in Endometriosis: A Review Lisa Story and Stephen Kennedy ILAR Journal, Volume 45, Number 2 2004 Risk factors associated with endometriosis include the following: increasing age within the reproductive years, greater exposure to menstruation because of short cycle length, long duration of flow and reduced parity, and increased peripheral body fat associated with increased serum estrogen levels. Factors thought to decrease estrogen levels (e.g., exercise and smoking) show an inverse relation with the disease (Eskenazi and Warner 1997).

Apart from generally consistent associations with increasing age and prolonged menstruation, other findings such as for smoking, exercise, body mass index, parity and tampon use were either inconsistent or simply not tested in more than one study (Eskenazi and Warner, 1997

L’ENDOMETRIOSI DELL’ OVAIO Patogenesi : invaginazione della corticale adesa all’endometriosi peritoneale Sintomatologia : - per coinvolgimento peritoneale - per rapida crescita della cisti Tecnica : stripping della capsula dopo completa mobilizzazione dell’annesso Vantaggi della enucleazione : -minore rischio di recidiva ( circa 6-8 %) -comparsa di recidiva dopo intervallo più lungo -pregnancy rate significativamente più elevata ( 67 vs 23 %) ( Busacca : studio randomizzato stripping vs diatermocoagulazione) Fert-Steril 1998; 70 , 6 Escludere sempre localizzazioni profonde ed extraperitoneali

ENDOMETRIOSIS AND INFERTILITY There are two published RCTs comparing diagnostic laparoscopy alone to surgical ablation of minimal-mild endometriosis. In the study by Marcoux et al 50/172 women in the treatment group became pregnant and had pregnancies that continued beyond 20 weeks compared to 29/169 in the non-treatment group (cumulative probabilities 30.7% and 17.7% respectively). However, in a smaller study by Parazzini 10/51 women (19.6%) in the treatment group as opposed to 10/45 women (22.2%) in the control group became pregnant within one year following laparoscopy suggesting no difference. Thus the two studies disagree. Although the study by Marcoux et al was larger, neither study was blinded and there is remaining uncertainty.

Laparoscopia Operativa Laparoscopia Diagnostica Laparoscopia nelle donne infertili con endometriosi minima o lieve Laparoscopia Operativa Laparoscopia Diagnostica P N°Pazienti 54 47 N°Pazienti che hanno cercato gravidanza 51 45 N°gravidanze 12 (24%) 13 (29%) n.s. N°aborti spontanei 2 (3,9%) 3 (6,6%) Birth Rate 10 (19.6%) 10 (22.2%) F. Parazzini Hum Repr 1999 May; 14(5):1332-4

LAPAROSCOPIA DIAGNOSTICA ed INFERTILITA’ % età 32,7 +/- 3,6 (range 24-41) indicazioni