Relationship between stage, site and morphological characteristics of pelvic endometriosis and pain

Gruppo Italiano per lo Studio dell'Endometriosi*,1


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Acknowledgements
 References
 
BACKGROUND: The relationship between frequency and severity of pain symptoms and site, stage and morphological characteristics of endometriotic lesions was analysed in a multicentre cross-sectional observational study. METHODS: A total of 469 women (median age 31 years, range 18–45) who met the following criteria were consecutively observed in the participating centres during the study period: age 18–45 years, first laparoscopic or laparotomic diagnosis of endometriosis, pain symptoms lasting 6 months, pain as the main or only complaint of the condition, absence of pelvic anomalies and no previous pelvic surgery. Dysmenorrhoea and non-menstrual pain were evaluated using a multidimensional verbal rating scale. The women were requested to grade the severity of dysmenorrhoea, non-menstrual pelvic pain and deep dyspareunia using a 10-point linear analogue scale. RESULTS: Dysmenorrhoea was present in 77% of subjects with ovarian endometriosis, 88% of those with endometriosis of the peritoneum, 92% of subjects with endometriosis of both ovary and peritoneum and in all the subjects with endometriosis of rectovaginal septum. These differences were not statistically significant after Bonferroni's correction. No marked difference emerged between the severity of dysmenorrhoea and site of endometriosis, but women with ovarian endometriosis tended to have lower scores (not significant). No clear association emerged between frequency and severity of non-menstrual pain, dyspareunia and site of endometriosis and the presence and severity of dysmenorrhoea, non-menstrual pain and dyspareunia. Dyspareunia was more frequently reported in women with only atypical endometriosis (56.8%) versus 47.7% in women with typical endometriosis, but with borderline significance (P = 0.05). Dyspareunia occurred in 68.2% of patients with both typical and atypical lesions. CONCLUSIONS: The results of this study find no clear-cut association between stage, site or morphological characteristics of pelvic endometriosis and pain.

Key words: endometriosis/pain/site/stage


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Acknowledgements
 References
 
Clinical observations have linked the site of endometriosis with the type and intensity of pelvic pain. For example, the presence of dyspareunia has been related to endometriotic implants in the rectum, vaginal septum and intersacral ligaments (Cornillie et al., 1990Go; Koninckx et al., 1991Go; Ripps and Martin, 1991Go, 1992Go; Koninckx and Martin, 1992Go; Candiani et al., 1992Go; Perper et al., 1995Go). However, epidemiological evidence on the relationship between pain and the stage and site of endometriosis is not consistent (Fedele et al., 1990Go, 1992Go; Stout et al., 1991Go; Vercellini et al., 1996Go). Interest has recently been focused on the relationship between the type (typical/atypical) of endometriotic lesion and pain intensity (Vercellini et al., 1991Go).

To further analyse this topic, we have conducted a multicentre cross-sectional observational study, under the framework of the Gruppo Italiano Studi Endometriosi (Tinelli et al., 2000Go), to assess whether the prevalence and severity of pain are related to the disease stage, site and morphological characteristics.


    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Acknowledgements
 References
 
All consecutive women observed in the participating centres during the study period who met the following criteria were eligible: age 18–45 years, laparoscopic or laparotomic first diagnosis of endometriosis, pain symptoms lasting >=6 months, pain as the main or only complaint, no pelvic anomalies and no previous pelvic surgery.

Each patient completed a questionnaire on the presence and severity of dysmenorrhoea, deep dyspareunia and non-menstrual pelvic pain. Dysmenorrhoea and non-menstrual pain were evaluated using a modified version of Andersch and Milsom's multidimensional verbal rating scale (Andersch and Milsom, 1982Go), which defines pain according to the limitation of ability to work (unaffected = 0; rarely affected = 1; moderately affected = 2; clearly inhibited = 3), co-existence of systemic symptoms (absent = 0; present = 1) and need for analgesics (no = 0; rarely = 1; regularly = 2; inefficacious = 3), and ranks their simple sum in three groups (1–3 = mild; 4 and 5 = moderate; 6 and 7 = severe). The modifications included the definition of systemic symptoms only as present/absent, instead of `absent/few/apparent' as in the original questionnaire (Andersch and Milsom, 1982Go), based on our previous experience indicating that the answer `few' was reported only by a very low proportion (<5%) of subjects (L.Fedele, personal communication). The women were also asked to rate the severity of dysmenorrhoea, non-menstrual pelvic pain and deep dyspareunia using a 10-point linear analogue scale in which 0 indicates no pain and 10 unbearable pain. The pain questionnaire was administered before diagnostic surgery during the hospital stay.

Endometriosis was staged according to the revised American Fertility Society (rAFS) classification (The American Fertility Society, 1985Go). Typical and atypical lesions were as defined in Vercellini et al. (Vercellini et al., 1991Go).

The study started September 1998 and ended October 1999. A total of 469 women identified in 42 centres were enrolled (mean number per centre 11.2, range 5–34) (median age 31 years, range 18–45). Tests of statistical significance for the differences in the frequency of symptoms in relation to disease stage, site and morphological characteristics were based on Pearson's {chi}2 test. Differences in median pain scores were compared by nonparametric Kruskal–Wallis analysis of variance by ranks. Bonferroni's test was used to investigate the differences between means.


    Results
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Acknowledgements
 References
 
Out of a total of 469 women studied, 139 (29.6%) identified endometriosis in the ovary only, 82 (17.5%) in the peritoneum only, and in 233 endometriosis was found in both the ovary and peritoneum (49.7%). Endometriosis of the rectovaginal septum was found in 15 cases (3.2%). With regard to stage distribution, 53 were stage 1 (11.3%), 57 stage 2 (12.2%), 239 stage 3 (51.0%) and 102 stage 4 (21.7%); in 18 cases the information was missing.

Table IGo shows the distribution by site, frequency and severity of symptoms. Dysmenorrhoea was present in 77% of women with ovarian endometriosis, 88% of those with endometriosis of the peritoneum, 92% of those with endometriosis of ovary and peritoneum, and in all 15 with endometriosis of the rectovaginal septum. No marked difference emerged between the severity of dysmenorrhoea and site of endometriosis, but women with ovarian endometriosis tended to have lower scores; however, this finding was not significant. No association emerged between frequency and severity of non-menstrual pain, dyspareunia and site of endometriosis. Dyspareunia was reported by 80% of women with rectovaginal endometriosis, a higher proportion than reported by women with endometriosis of ovary and peritoneum, but the difference was not significant.


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Table I. Presence and severity of pain symptoms according to site of endometriosis in 469 women
 
When the presence and severity of dysmenorrhoea, non-menstrual pain and dyspareunia were analysed according to disease stage in 451 women, no significant association was observed. In particular, the frequency of dysmenorrhoea was 83.0, 89.5, 86.2 and 88.2% in stage I, II, III and IV respectively. The corresponding figures for non-menstrual pain and dyspareunia were 66.0, 59.6, 61.14 and 74.5%, and 53.8, 49.1, 47.9 and 50.5% respectively. None of these differences were statistically significant. The main values of linear analogue scales for dysmenorrhoea were 7.7, 7.5, 7.4 and 7.6 for stage I, II, III and IV respectively, and for non-menstrual pain 6.5, 6.2, 6.2 and 6.3 respectively (these differences were not statistically significant).

Information regarding the type of endometriosis (typical/atypical) was available only for women in 24 centres, for a total of 217 cases. The relationship between type of endometriosis and pain symptoms in shown in Table IIGo. Dyspareunia was more frequent in women with atypical than with typical mixed endometriosis, but this finding was of borderline statistical significance ({chi}2 heterogeneity P = 0.05).


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Table II. Presence and severity of pain symptoms according to type of endometriosis in 217 women
 

    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Acknowledgements
 References
 
These results suggest that the stage of endometriosis, according to the r-AFS classification, is not related to the presence and severity of pain. Ovarian endometriosis was associated with a lower frequency, but not less severity, of pain symptoms. Rectovaginal endometriosis was associated with more frequent dyspareunia; however, this finding was not significant. The type of endometriosis was not related to the frequency and severity of dysmenorrhoea and non-menstrual pain, but dyspareunia was more frequent, with borderline significance, in patients with atypical lesions.

These results should not be markedly affected by bias. The pain questionnaire was filled in before laparoscopy/laparotomy, so the women and physicians were blind to the site and characteristics of endometriosis. The study population comprised of women self-referring to a network of teaching and university hospitals. Thus, they cannot be considered representative of the Italian population of women with endometriosis and pelvic pain. Nevertheless the centres were distributed in the three main areas of the country and there was no marked difference in their results (data not shown), strongly suggesting the consistency of the general results. Finally, participation during the study period was practically complete. Although we did not collect information in all centres on the ratio of women who refused the interview, an informal enquiry in a sample of six centres indicated that <5% of eligible women refused. A senior researcher in each centre supervised the staging of endometriotic lesions and the co-ordinating centre checked the staging of endometriosis and the consistency of the study forms and clinical records.

The main interest of this study is that it provides an opportunity for analysing the relationship between pain and endometriosis in a large series, in different clinical conditions, using standard methods of data collection and staging of the disease. Specific directions were given to the physicians to take care in collecting the information on endometriosis.

Our results confirm those of the majority of previous studies, which found no relationship between frequency and severity of pain symptoms and disease stage. For example, no association was reported between stage and pain symptoms in a study of 244 women with endometriosis conducted in Milan (Vercellini et al., 1996Go). A study of 70 women (Perper et al., 1995Go) did find an association between the total number of ectopic endometrial implants, but not their location, and intensity of menstrual pain.

Attention has focused on deep retroperitoneal endometriotic foci that may penetrate the rectovaginal septum and infiltrate the posterior vaginal wall. This type of lesion may be very active, causing more severe pain than other endometriotic implants (Fedele et al., 1992Go; Vercellini et al., 1996Go). In our study, no significant association emerged between endometriosis of the rectovaginal septum and the frequency of deep dyspareunia.

Finally, pain—particularly dyspareunia—was associated only with `typical' peritoneal lesions (black nodules, stellate scars) and not with `atypical' fresh, clear implants (clear vesicles, clear or red papules, red polypoid lesions) (Vercellini, 1991). Our analysis partially confirmed this: we found a higher frequency and severity of dyspareunia, but not of dysmenorrhoea and pelvic pain, in women with active lesions, although the difference was of borderline significance. Pain at intercourse is probably related to traction and stretching of scar and inelastic tissue and mechanical pressure on endometriotic lesions, which may frequently cause pain where active. Otherwise, our data do not support the suggestion that fresh papular lesions exposed to peritoneal fluid are mainly responsible for functional pain (dysmenorrhoea or pelvic acyclic pain) due to abnormal production of prostaglandins.

In conclusion, this study does not find any clear-cut association between stage, site and morphological characteristics of pelvic endometriosis and pain.


    Acknowledgements
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Acknowledgements
 References
 
Writing Committee and data analysis: F.Parazzini, S.Cipriani, S.Moroni, P.G.Crosignani.

The following clinicians collected the data: Ancona: A.Ciavattini, G.Garzetti (Clinica Ostetrica, Università di Ancona); Arzignano (VI): G.Dolcetta, M.Scollo (Ospedale Civile Arzignano); Bari: M.Vicino, G.Loverro (II Clinica Ostetrica Ginecologica, Università di Bari), S.Sabatelli (I Clinica Ostetrica e Ginecologica, Az. Osp. Consorziale Policlinico, Università di Bari); Brescia: L.Decca, L.Falsetti (Ginecologia Endocrinologica, Università di Brescia); Bologna: E.Giacomucci, C.Flamigni (Clinica Ginecologica Prima, Policlinico S. Orsola, Università di Bologna); Cagliari: V.Mais, S.Guerriero (Sezione di Clinica Ginecologica ed Ostetrica, Università di Cagliari); Carbonara: F.Boscia, G.Sangiorgio (Rep. Ginecologia Osp. Di Venere, Carbonara); Catania: P.Scollo, A.Muriana (Presidio Ospedaliero Cannizzaro, Catania), M.La Greca, C.Distefano (II U.O. Ost. Gin. Presidio S. Bambino, Azienda Vittorio Emanuele, Catania); Como: C.Belloni (Osp. Generale di Zona Valduce, Como); Feltre (BL): L.Spolaor (Unità Socio Sanitaria n. 2, Div.Ostetricia Ginecologia, Feltre); Ferrara: A.Bianchi (Clinica Ostetrica Ginecologica, Ospedale S.Anna, Università di Ferrara); Firenze: M.Aretini, M.Franchini (S. Maria Annunziata), G.L.Bracco, M.E.Coccia, G.F.Scarselli (II Clinica Gin., Ost. Università, Firenze); Foggia: F.Ciuffreda (Rep. Ginecologia Osp. Casa Sollievo della Sofferenza, San Giovanni Rotondo); Latisana: C.Fiscella (U.O. Ostetricia Ginecologia, A.S.S. n. 5, Friuli Venezia Giulia, Osp. Latisana (UD); Lecce: F.Tinelli, C.A.Demarzi (A.O. `V. Fazzi', U.O. Ostetricia Ginecologia, Lecce); Mercato San Severino (SA): B.Bianco, A.Iannelli (P.O. Curteri, Mercato San Severino (SA); Milano: U.Radaelli, N.Meroni (Istituto Clinico Humanitas, Milano), D.Federici (Div. Ost. Ginecologia, Ospedale Sacco, Milano), C.Calia, P.Vercellini (I Clinica Ostetrico Ginecologica, Università di Milano), C.Bertulessi, F.Hanozet (Clinica Ostetrico Ginecologica III, Clinica Macedonio Melloni, Università di Milano); Milano: M.Busacca (II Clinica Ostetrico Ginecologica); Montebelluna: G.Dal Pozzo, A.Pieroni (Divisione Ginecologia ed Ostetricia, Montebelluna); Padova: P.Lita, R.Bracciante (Clinica Ostetrico Ginecologica, Università di Padova); Perugia: G.Baiocchi (Az. Osp., Università, U.O. Ostetricia e Ginecologia, Policlinico Monteluce, Perugia); Roma: M.A.Congiu (Università Campus Bio-Medico, Roma), R.Fanfani (Ospedale Cristo Re, Roma), F.Sesti, S.Bonifacio (Clinica Ostetrica Ginecologica, Università Tor Vergata, Osp. S. Eugenio, Roma), M.G.Porpora (II Istituto di Clinica Ostetrica e Gineocologica, Policlinico Umberto I, Roma); San Daniele del Friuli (UD): M.Pittino, G.Del Frate (U.O. Ostetricia Ginecologia, S. Daniele del Friuli); Sassari: S.Dessole, G.Capobianco (Dipartimento di Farmacologia Ginecologica e Ostetricia, Università); Tivoli (RM): M.Montanino Oliva, M.Primilerio (Ospedale S. Giovanni Ev, Tivoli (Roma)); Torino: S.Micalef, E.Ansaldi (Divisione di Ostetricia e Ginecologia, Ospedale di Venaria Reale), M.Massobrio, D.Guidetti (Dipartimento Discipline Ginecologiche e Ostetriche, Università di Torino); Trento: M.Rosati, A.Di Dionisio (Ospedale S. Camillo, Trento); Treviso: G.Bracalente (Div. Ostetricia e Ginecologia, Ospedale Ca' Foncello, Treviso); Trieste: S.Guaschino, L.Troiano, F.De Seta (Università di Trieste); Udine: M.Santuz, F.Petraglia (Clinica Ostetrico Ginecologica, Università di Udine); Urbino: E.Canducci (Dipartimento Materno Infantile, Ospedale Civile Urbino); Varese: P.Beretta (Clinica Ostetrico Ginecologica, Università dell'Insubria Varese); Vittorio Veneto: D.De Santo (Università di Vittorio Veneto).


    Notes
 
1 Correspondence should be addressed to: Fabio Parazzini, Istituto di Ricerche Farmacologiche `Mario Negri' Via Eritrea,62–20157 Milano, Italy. E-mail: parazzini{at}marionegri.it Back

* See Acknowledgements for details of members of the Gruppo Italiano per lo Studio dell'Endometriosi. Back


    References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Acknowledgements
 References
 
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Submitted on May 4, 2001; accepted on August 29, 2001.