ORIGINAL ARTICLE

Relation between severity of dysmenorrhea and endometrioma

NICOLAS CHOPIN, MARCOS BALLESTER, BRUNO BORGHESE, ARNAUD

FAUCONNIER, HERVE FOULOT, CECILE MALARTIC & CHARLES CHAPRON

Universite Rene Descartes (Paris V); Assistance Publique Hopitaux de Paris (AP-HP); Groupe Hospitalier UniversitaireOuest; Service de Gynecologie Obstetrique et Medecine de la Reproduction (Pr Chapron), Unite de Chirurgie Gynecologique,

CHU Cochin, Paris, France

AbstractBackground . To evaluate the relationship between the severity of dysmenorrhea and endometrioma. Methods. Descriptivestudy with prospective design. Two hundred and thirty-nine women with histologically proved endometriomas. The severityof dysmenorrhea was assessed prospectively with a 10-cm visual analog scale. Various indicators concerning theendometrioma and the extent of deep infiltrating endometriosis were recorded during surgery in 239 patients. Correlationswere sought with a multiple regression logistic model. Results. According to univariate analysis, the following variables wererelated to more severe dysmenorrhea: subperitoneal infiltration (uterosacral ligament and rectal infiltration) and R-AFSscore of implants. None of the specific characteristics of endometriomas were associated with severe dysmenorrhea. Aftermultiple regression analysis, rectal infiltration and R-AFS score of implants were the only factors that remained related todysmenorrhea severity. Conclusions. When there is an endometrioma, severe dysmenorrhea is not directly related with thecharacteristics specific to these ovarian cysts. The associated deep infiltrating endometriotic lesions and in particular rectalinfiltration could explain these symptoms.

Key words: Endometrioma, deep infiltrating endometriosis, pelvic pain, dysmenorrhea

Deeply infiltrating endometriosis (DIE) is a specific

affliction responsible for painful functional symp-

toms, sometimes associated with infertility (1,2).

The types of pelvic pain (dysmenorrhea (DM), deep

dyspareunia, non-cyclic chronic pelvic pain, lower

urinary and gastrointestinal symptoms) are related to

the anatomic location of DIE (3). DM is very

common in the general population (4) and is

especially frequent in women with endometriosis

(5). Endometriosis is frequently located on the ovary

and tends to be associated with other sites affected

by the disease (6). In the case of DIE, the intensity of

the pain is recognized as being proportional to the

depth to which the lesions penetrate (1,7,8). The

factors described as being responsible for pelvic pain

in case of endometriomas are not clearly defined

(1,712). Most studies address all types of endome-triotic lesions without drawing any distinction be-

tween DIE and other types of endometriosis. Their

inclusion criteria are generally the existence of

painful symptoms or infertility, resulting in a hetero-

geneous population of patients who do not necessa-

rily present any endometriotic cyst.

Our aim is to clarify which factors and which

characteristics of endometriotic cysts are responsible

for severe DM, working on a prospective basis with a

homogeneous population of patients with endome-

triomas.

Materials and methods

Population study

This descriptive study with a prospective design

includes all the women presenting an endometrioma

who underwent surgery for pelvic pain symptoms

between January 2000 and December 2003. This

Correspondence: Charles Chapron, Service de Gynecologie Obstetrique II, Clinique Universitaire Baudelocque, 123 Bld Port-Royal, 75014 Paris, France.

E-mail: charles.chapron@cch.ap-hop-paris.fr

Acta Obstetricia et Gynecologica. 2006; 85: 13751380

(Received 21 February 2006; accepted 22 July 2006)

ISSN 0001-6349 print/ISSN 1600-0412 online # 2006 Taylor & FrancisDOI: 10.1080/00016340600935490

selection was made during the diagnostic phase and

was based on preoperative ultrasound examination

revealing an endometrioma of over 2 cm. Only

histologically proved endometriomas were included.

Endometriotic lesions were considered histologically

confirmed when endometrial glands and stroma

were present at microscopic examination.

Variables

DM intensity was assessed prospectively with a 10-

cm visual analog scale reading recorded during the

month before surgery by means of a self-assessment

questionnaire. Severe DM was defined as a pain

score of 7 or above on the linear scale (13). The

patients characteristics (age, height, weight, body

mass index (BMI) (kg/m2), parity, history of medical

or laparoscopic treatment for endometriosis) were

recorded. Concerning the endometriomas, the fol-

lowing characteristics were recorded: number of

endometriomas, mean size of each in case of multi-

ple locations, laterality, and CA-125 level.

Associated endometriotic lesions were superficial

peritoneal endometriosis, DIE, adnexal adhesions,

and Douglas pouch adhesions (absent, partial ob-

literation, complete obliteration). The disease stage

was scored according to the revised American

Fertility Society classification (14) and subscores

for implants and adhesions were also recorded.

Anatomic locations of DIE-associated nodules were

coded according to a previously published classifica-

tion (15). According to this classification, patients

were classed in four groups according to the location

of the DIE lesions: uterosacral ligament (USL),

when lesions infiltrated the USL(s) only; vagina,

when lesions infiltrated the anterior rectovaginal

pouch, posterior vaginal fornix, and retroperitoneal

area between the anterior rectovaginal pouch and the

posterior vaginal fornix; bladder, when lesions

infiltrated the bladder muscularis propria; and in-

testine, when lesions involved the muscularis pro-

pria of the bowel. When there were several locations

in the same patient, she was classed in the group for

the lesion that was considered to be the most severe.

By definition, the increasing order of severity was the

following: USL, vagina, bladder, intestine.

Statistical analysis

Women with severe DM were compared with the

other patients. For univariate statistical analysis we

used the following tests: Pearsons chi-square test for

qualitative variables or Fishers exact test as appro-

priate; paired Students t-test for quantitative

variables or Wilcoxon signed-rank as appropriate.

We used the KruskalWallis test to compare multi-ple quantitative variables. Subsequently, the vari-

ables associated with severe DM at the threshold of

p/0.20 in univariate analysis were tested in amultiple logistic regression model. A final model

was constructed including only those variables

independently associated with severe DM at the

threshold of B/0.05. The parameter values of thefinal model were estimated by the maximum like-

lihood method, and adjusted odds ratios and their

confidence intervals calculated from the models

coefficients and their standard deviations.

Results

During the study period, 310 patients presenting a

histologically proven endometrioma measuring

over 20 mm and pelvic pain were operated. Se-

venty-one (22.9%) were excluded for the following

reasons: amenorrhea and menopausal status 11cases (3.6%); failure to respond to the questionnaire

60 cases (19.4%). The final study populationincluded 239 women (77.1%).

Out of the 239 patients eligible, the mean value of

the visual analog DM scale reading was 5.19/3.2.The symptoms were distributed as follows: 154

patients had DMB/7/10 and 85 women had DM]/7/10. Their mean values were 3.39/2.6 and 8.39/1.1respectively (Table I). Among these 239 women, 211

(88.3%) presented endometrioma(s) only versus 28

(11.7%) associated DIE lesions. Their DM scales

were 5.19/3.2 versus 5.59/3.3; p/0.37.Disease stage was scored according to the R-AFS

classification and details of the scores are reported in

Table II.

After univariate analysis the following variables

were related to more severe DM: subperitoneal

infiltration (USL and rectal infiltration) and R-AFS

score of implants (Table III). None of the specific

characteristics of endometriomas were associated

with severe DM.

After multiple regression analysis, rectal infiltra-

tion and R-AFS score of implants above 26 were the

only factors that remained related to DM severity

(Table III).

Discussion

While it is accepted that there is an association

between DM and endometriosis (16), the data in the

literature concerning the painful physiopathology of

endometriotic cysts are heterogeneous, few in num-

ber and contradictory (1,712).Our aim is to clarify which factors and which

characteristics of endometriotic cysts are responsible

1376 N. Chopin et al.

Table I. Patients characteristics according to the severity of their dysmenorrhea.

DMB/7/10 (n/154 patients) DM]/7/10 (n/85 patients)

Variables Mean9/SD (extremes) n (%) Mean9/SD (extremes) n (%) p

Intensity of dysmenorrhea 3.39/2.6 (0/6.9) 8.39/1.1 (7/10)Patients characteristics

Age (year) 35.19/7.8 (20.5/49.8) 34.89/7.4 (17.4/49.0) 0.72a

Weight (kg) 59.59/10.7 (42/103) 58.89/9.3 (42/89) 0.32a

Height (cm) 165.59/7.2 (148/186) 164.59/6.3 (151/182) 0.64a

No. pregnancies

0 126 (81.8) 66 (77.7)

1 14 (9.1) 11 (12.9)

]/2 14 (9.1) 8 (9.4) 0.48b

History of treatment for endometriosis

Laparoscopic treatment

0 101 (66.0) 48 (56.5)

12 48 (31.3) 32 (37.7)]/3 4 (2.61) 5 (5.9) 0.14b

Hormonal treatment

Progestational hormones 55 (36.4) 24 (29.6)

LH-RH analogs 28 (18.5) 26 (32.1)

Other 2 (1.3) 1 (1.2) 0.13c

Anatomic location and number of deeply infiltrating endometriosis

Bladder

No 153 (99.4) 84 (98.8)

Yes 1 (0.7) 1 (1.2) 1b

USL

No 135 (87.7) 72 (84.7)

Yes 19 (12.3) 13 (15.3) 0.03b

Vagina

No 51 (98.1) 79 (92.9)

Yes 3 (2.0) 6 (7.1) 0.07b

Rectum

No 153 (99.4) 78 (91.8)

Yes 1 (0.7) 7 (8.2) 0.003b

Total number of lesions

0 143 (92.9) 68 (80.0)

1 5 (3.3) 7 (8.2)

2 5 (3.3) 4 (4.7)

3 1 (0.7) 1 (1.2)

4 1 (1.2)

5 1 (1.2)

6 2 (2.4)

7 1 (1.2) 0.003c

Endometrioma characteristics

No. of endometriomas 1.49/0.6 (1.0/4.0) 1.69/0.8 (1.0/5.0) 0.36d

Size of endometrioma no. 1 (mm) 43.89/26.6 (20.0/250.0) 40.29/17.8 (4.0/100.0) 0.68d

Size of endometrioma no. 2 (mm)* 27.49/13.5 (5.0/80.0) 29.59/14.9 (15.0/80.0) 0.65d

Laterality

Right 36 (23.38) 22 (25.88)

Left 80 (51.95) 34 (40.00)

Bilateral 38 (24.68) 29 (34.12) 0.17e

CA-125 assay (UI/ml) 61.79/78.6 (5.0/563.0) 629/54.8 (8.0/238.0) 0.39d

aStudents t -test.bKruskalWallis test.cFishers exact test.dWilcoxon test.ej2 test.

*Size of endometrioma no. 2 is size of second endometrioma when there are bilateral cysts (the smaller of the two cysts being taken by

convention as endometrioma no. 2).

Relation between severity of dysmenorrhea and endometrioma 1377

for severe DM working on a homogeneous painful

population of patients with endometriomas. To our

knowledge no study has addressed a homogeneous

population of patients with endometriomas on a

prospective basis.

Our study found two independent factors asso-

ciated with severe DM: rAFS score for implants

exceeding 26 and the presence of associated deeply

infiltrating rectal endometriosis.

The specific characteristics of the endometriomas

do not appear to be correlated with the severity of

the DM. The innervation characteristics of endome-

triomas could explain this finding. Nerve infiltration

by deeply infiltrating endometriotic lesions has been

shown to correlate with the severity of DM. This

association has been clearly demonstrated in case of

vaginal or GI tract lesions, and implants that

penetrate the wall of adjacent organs have closer

relationships with nerve fibers than those that do not

(13,17). Unlike the case for these lesions, there are

Table II. Severity of dysmenorrhea according to the revised American Fertility Society Classification (14).

DMB/7/10 (n/154 patients) DM]/7/10 (n/85 patients)

Variable Mean9/SD (extremes) n (%) Mean9/SD (extremes) n (%) p

AFS superficial peritoneum 0.68a

0 93 (61.2) 51 (60.0)

1 3 (2.0) 0 (0.0)

2 16 (10.5) 9 (10.6)

4 35 (23.0) 20 (23.5)

6 5 (3.3) 5 (5.9)

AFS deep peritoneum 0.19a

0 112 (73.7) 57 (67.1)

2 6 (4.0) 1 (1.2)

4 21 (13.8) 14 (16.5)

6 12 (7.9) 13 (15.3)

16 1 (0.7) 0 (0.0)

AFS total implants 25.29/8.0 (16/46) 28.09/9.4 (10.0/46.0) 0.01b

Right ovary adhesions 0.73a

0 54 (35.3) 28 (32.9)

1 19 (12.4) 5 (5.9)

2 8 (5.2) 6 (7.1)

4 14 (9.2) 17 (20.0)

8 39 (25.5) 18 (21.2)

16 19 (12.4) 11 (12.9)

Left ovary adhesions 0.22a

0 39 (25.5) 17 (20.0)

1 13 (8.5) 8 (9.4)

2 10 (6.5) 2 (2.4)

4 25 (16.3) 17 (20.0)

8 44 (28.8) 24 (28.2)

16 22 (14.4) 17 (20.0)

AFS Douglas 0.99a

0 90 (58.8) 48 (57.1)

4 27 (17.7) 19 (22.6)

40 36 (23.5) 17 (20.2)

AFS total adhesions 23.89/27.7 (0.0/104.0) 25.99/28.9 (0.0/104.0) 0.23b

AFS total (implants/adhesions) 49.09/31.5 (16.0/150.0) 53.99/33.7 (14.0/150.0) 0.13b

aKruskalWallis test.bWilcoxon test.

Table III. Determinants for severity of DM results from multiple

logistic regression analysis.

Independent variable Adj OR for severity of DM 95% CI

Rectal infiltration

Yes 1 No 0.082 0.0100.687

Score rAFS implants*

]/24 1 B/24 0.521 0.3000.905

CI, confidence interval.

*Score according to the revised American Fertility Society

Classification (14).

1378 N. Chopin et al.

no nerve fibers to be found in endometriomas (18),

which may be the reason why these cysts are not very

painful. Two studies only found a correlation be-

tween DM and the presence of endometriomas

(12,19). Fedele et al. found an association between

unilateral or bilateral endometriomas and the sever-

ity of DM. Muzii et al. described a correlation

between the presence of an endometriotic cyst and

the severity of DM. On the contrary, for Vercellini

et al. (10) DM was less frequent in patients with

ovarian endometriosis only, than in those with

associated lesions at other sites. Porpora et al. (8)

found an association between DM and endometrio-

mas by univariate analysis. This relationship would

seem to disappear after adjustment, and analysis

suggests that this pain is related to periovarian

adhesions rather than to the cyst itself. The physio-

pathological mechanism by which these periadnexal

adhesions might be associated with DM remains

unclear. Similar results have been reported by other

authors (10,20).

Our results, concerning rectal involvement as an

independent factor correlated with the severity of

DM in the case of endometrioma, appear to confirm

the results of earlier works (7). Although the initial

population in this study concerned patients with

DIE with or without specific ovarian endometriotic

lesions, the authors had already revealed an associa-

tion between the severity of DM and the depth of

posterior subperitoneal disease involvement. One of

the hypotheses evoked was the correlation between

compression or infiltration of the nerves by these

endometriotic lesions in the subperitoneal pelvic

space, in particular in the posterior area (20).

For Redwine (6), deep involvement of the bowel is

significantly greater in patients presenting an en-

dometrioma. Moreover, whether in the presence of

an endometrioma or not, many studies have found a

link between the intensity of DM and the extent of

the disease measured by the rAFS score (12,19,21),

the number of endometriotic implants, or the pre-

sence of associated deeply infiltrating lesions (11).

So, in agreement with those of other authors, our

results show that in cases of severe DM, the

existence of an endometrioma suggests more diffuse

and in particular subperitoneal presence of endome-

triotic disease involvement. But it is important to

underline that with respect to the rAFS score for

implants these results remain difficult to interpret.

This is because the weighting associated with an

endometriotic cyst in this classification system is

particularly high, with a score of at least 16 in case of

a cyst measuring over 2 cm and at least 20 in case of

a cyst measuring over 3 cm. To this score for the

cystic implants is then added the score for any

associated deeply infiltrating lesions. All our patients

had at least one endometrioma over 2 cm in size. So

in our study the implant score tends necessarily to

reach a high figure without it being possible,

unfortunately, to know whether this is due to the

presence of the cyst or the associated lesions. As

already mentioned, these results underline the limits

of the rAFS classification with respect to DIE

(10,22). The score was initially proposed for patients

presenting with infertility in a context of endome-

triosis without taking the problem of pelvic pain into

account when scoring deep endometriotic lesions.

Such lesions appear to be underestimated. In the

case of endometrioma the score is overestimated.

Our results show that endometriomas as such are

not much involved in the genesis of DM. The pain is

most probably secondary to the presence of asso-

ciated subperitoneal lesions, and rectal lesions in

particular. The existence of an endometriotic cyst

when there is severe DM would appear to form part

of a more diffuse endometriotic disease context. It

justifies a preoperative search for the exact location

of possible associated deeply infiltrating lesions by

precise questioning, perimenstrual clinical examina-

tion, and possibly an in-depth imaging work-up.

Acknowledgements

The authors thank Aventis-Synthelabo Laboratories

(France) for providing technical assistance in statis-

tical analysis.

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