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Original Article

Gynecol Obstet Invest 2008;66:169177


DOI: 10.1159/000140513

Received: October 29, 2007


Accepted after revision: March 31, 2008
Published online: June 19, 2008

Risk Factors for Dysmenorrhea and


Its Severity in Women with Ovarian
Endometriomas
Xishi Liu a Lei Yuan a Yuedong Wang b Fanghua Shen a Sun-Wei Guo c
a

Department of Gynecology, Shanghai OB/GYN Hospital, and Department of Gynecology and Obstetrics,
Shanghai Medical School, Fudan University, Shanghai, PR China; b Department of Statistics and Applied Probability,
University of California, Santa Barbara, Calif., USA; c Renji Hospital, and the Institute of Obstetric and Gynecologic
Research, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China

Key Words
Dysmenorrhea Ovarian endometrioma Risk factors
Severity

Abstract
Objective: To identify factors associated with the risk of developing dysmenorrhea or the severity of dysmenorrhea in
women with surgically confirmed ovarian endometriomas.
Study Design: 710 patients with surgically diagnosed ovarian endometriomas were interviewed and their charts read.
Fourteen factors were considered. Among the 710 patients,
376 patients had major complaint of dysmenorrhea and
were evaluated to identify factors associated with the severity of dysmenorrhea. Results: The logistic regression model
identified younger age at surgery, previous medication use,
presence of adhesion, and presence of adenomyosis as risk
factors for dysmenorrhea. For the severity of dysmenorrhea,
the presence of adenomyosis was consistently and robustly
identified by several statistical models with rather different
assumptions as the factor associated with severity. The rAFS
stage was also associated with the severity, but the association may be explained by the presence of adenomyosis.
Conclusion: The presence of adenomyosis has been consistently identified as a risk factor for both dysmenorrhea and
its severity. Younger age at surgery, presence of adhesion,

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and previous use of endometriosis-related medication are


additional risk factors for dysmenorrhea. For the severity of
dysmenorrhea, there are other factors than the presence of
adenomyosis that may influence the severity of dysmenorrhea.
Copyright 2008 S. Karger AG, Basel

Introduction

Although it is generally accepted that endometriosis is


responsible for dysmenorrhea as well as other symptoms
such as infertility [1], the precise relationship between the
severity of dysmenorrhea and various characteristics of
disease, such as stage, type or site of endometriotic lesions, has been elusive and often a matter of heated debate, due largely to conflicting reports [2, 3]. For example,
while several studies found an association between rAFS
stage and frequency and severity of pain symptoms [46],
others found no such association [713]. Vercellini et al.
[14] recently summarized some of the published findings.
They found that the association between endometriosis
stage and severity of pelvic symptoms is marginal and
inconsistent and concluded that the association could
be demonstrated only with a major increase in study
power.
Sun-Wei Guo, PhD
Renji Hospital, and the Institute of Obstetric and Gynecologic Research
Shanghai Jiao Tong University School of Medicine
145 Shandong Zhong Road, Shanghai 200001 (PR China)
Tel./Fax +86 21 5388 2377, E-Mail hoxa10@gmail.com

Controversies and conflicting reports are certainly


not exclusively limited to studies on the relationship between dysmenorrhea and various characteristics of endometriosis. Many factors could potentially contribute to
the heterogeneous findings. These include, but are not
limited to, type of study (prospective vs. retrospective),
indication for surgery (infertility, pain, or pelvic mass),
type of endometriosis, definition of chronic pain, how
the pain is evaluated, and genuine heterogeneity among
different patient populations which could be amplified in
retrospective studies. Even sample size and the year of
publication may also be responsible [15].
This heterogeneity could, conceivably, be reduced or
minimized in several ways. For example, standardization
of pain evaluation, increasing the sample size, and the
proper use of multivariate statistical methodology can, in
principle, help find common grounds. In addition, focusing on a specific type of endometriosis, say, ovarian endometrioma, may also help.
In this study, we sought to identify risk factors for dysmenorrhea among 710 women with surgically confirmed
ovarian endometriomas using multivariate analysis. In
addition, we sought to identify the association between
the severity of dysmenorrhea and age, presence of adhesion, stage and other host characteristics in a cohort of
376 patients nested in the 710 women, who also complained of dysmenorrhea.

Materials and Methods


We included 850 consecutive patients with ovarian endometrioma undergoing conservative or semi-radical (defined as surgical removal of cysts plus hysterectomy with preservation of bilateral or unilateral ovary) surgery via either laparotomy or laparoscopy at the Shanghai OB/GYN Hospital affiliated with Fudan
University Shanghai Medical College from 2003 to 2004 [16]. All
diagnoses were confirmed histologically to have endometrial
glandular and stroma in the ovaries. The diagnosis of adenomyosis was based on histology if hysterectomy was performed or clinically on a combination of symptomology, pelvic examination
and transvaginal ultrasonographic evaluation by experienced
physicians, as reported previously [17]. Among the 850 patients,
710 of them were followed up for an average of 22.4 months, with
a duration of follow-up ranging from 11.8 to 38.8 months, and
were included in this study. Of 710 recruited patients, 553 (78%)
received conservative surgery, as reported previously [18].
For each patient, information was collected through reading
medical charts and interview on demographics, age at surgery,
age at menarche, body mass index at surgery (BMI), pelvic examinations and results, type of surgery, mode of surgery (conservative or semi-radical), complaint of dysmenorrhea or not, duration and severity of dysmenorrhea, if any, number of induced
abortions prior to surgery, presence of adenomyosis or not, previ-

170

Gynecol Obstet Invest 2008;66:169177

ous use of endometriosis-related medication or not prior to surgery, previous endometriosis-related surgeries, laterality of endometrioma, size of the largest endometrioma, presence of adhesion
or not, rAFS scores and stage, postoperative use of medication or
not, and improvement of symptomatology. Following the custom
in China, the severity of dysmenorrhea was classified as mild
(pain but no interference with routine daily life or work and no
need for analgesics; the pain score = 0), moderate (pain interfering
with routine daily life or work to some extent and relief of pain
after taking analgesics; the pain score = 1), and severe (pain seriously interfering routine daily life or work, and no relief of pain
after taking analgesics; the pain score = 2).
Of the 710 patients with follow-up, 376 of them (53%) complained of dysmenorrhea, with 245 (65.2%), 107 (28.5%) and 24
(6.4%) being mild, moderate, and severe, respectively. For the
purpose of identifying risk factors for dysmenorrhea, a data set of
710 patients was used. For identification of risk factors for the severity of dysmenorrhea, a data set of 376 patients, nested in that
of the 710 patients, was used in this study. There were only 11 patients whose length of dysmenorrhea was not recorded. Observations on all other variables were complete.
All data were entered into a Microsoft Excel database, and
their quality and integrity were checked rigorously. This study
was approved by the Ethics Committee of the Shanghai OB/GYN
Hospital.
Data Analysis
The comparison of distributions of continuous variables between or among two or more groups was made using the Wilcoxon and Kruskal-Wallis tests, respectively. Spearmans rank
correlation coefficient was used when evaluating correlations between two variables. The relationship between various clinical
and pathological parameters was compared with 2 tests and
evaluated by logistic regressions starting with a full model that
includes all covariates. To investigate the effect of laterality and
bilaterality of ovarian cysts, the laterality was coded by a dummy
variable b taking the value of 1 if the patient has bilateral cysts or
0 otherwise, or by two dummy variables, l and r, with l = 1 (r = 1)
if the patient has left-sided (right-sided) cysts and 0 otherwise.
To identify the risk factors for dysmenorrhea among patients
with ovarian endometriomas, a logistic regression analysis was
performed. To identify the association between the severity of
dysmenorrhea and size, laterality, stage and other host characteristics, two statistical models were employed. We first used a binary logistic regression model based on a coding system that
codes mild dysmenorrhea as 0 and moderate and severe dysmenorrhea as 1. Since only about 6% of patients with dysmenorrhea
had severe dysmenorrhea, we did not use another coding
scheme.
The second model was a cumulative logit model for ordinal
data, also known as the proportional odds model [19]. The proportional odds model would be appropriate if the slope parameters in the logit model are independent of cut-off points [19, 21].
The proportional odds assumption was evaluated using the score
test with the alternative hypothesis that the logit model has different slope parameters for each different cut-off point. We also
fit partial proportional odds models [20] to the same data set.
Since the rAFS stage is merely a staging system and the staging
numeric (I, II, III, or IV) does not necessarily imply that the difference in severity between two consecutive stages is the same

Liu /Yuan /Wang /Shen /Guo

Table 1. Characteristics of 710 patients and p value from univariate analysis of the risk factor for dysmenorrhea
Covariates

Findings

p value from univariate


analysis of risk of dysmenorrhea

Covariates

Findings

p value from univariate


analysis of risk of dysmenorrhea

31.2820.5
28
2144

0.051

33 (4.7)
84 (11.8)
407 (57.3)
186 (26.2)

0.26

Age at surgery, years


Mean
35.787.7
1.1 ! 105
Median
35
Range
1655
Age at menarche, years
Mean
0.065
14.381.5
Median
14
Range
1025
Reproductive age at surgery, years
Mean
21.487.3
3.5 ! 105
Median
21
Range
439
Previous use of endometriosis-related medication
None
637 (89.7)
1.9 ! 105
GnRH agonists
20 (2.8)
Progestins or
other medication
53 (7.5)
Previous endometriosis-related surgery
No
648 (91.3)
0.18
Yes
62 (8.7)
Number of previous induced abortions
0
354 (49.9)
0.24
1
226 (31.8)
2
130 (18.3)
Parity
0
128 (18.0)
0.068
1
567 (79.9)
2
15 (2.1)
BMI
<19
110 (15.5)
0.011
1924
468 (65.9)
>24
132 (18.6)
Combination with adenomyosis
No
431 (60.7)
0.44
Yes
279 (39.3)
Complaint of dysmenorrhea
No
335 (47.0)
not applicable
Yes
376 (53.0)
Infertility (primary and secondary)
No
600 (84.5)
0.048
Yes
110 (15.5)
Laterality
Left only
249 (35.1)
0.57
Right only
201 (28.3)
Bilateral
260 (36.6)
Size
5 cm
330 (46.5)
0.76
510 cm
345 (48.6)
>10 cm
35 (4.9)
Adhesion
No
303 (42.7)
0.048
Yes
407 (57.3)

rAFS score
Mean
Median
Range
rAFS staging
I
II
III
IV

Risk Factors for Dysmenorrhea

Gynecol Obstet Invest 2008;66:169177

Findings are means with SD, medians, ranges or numbers,


with percentages in parentheses. Percentages in some variables
may not add up to precisely 100% due to rounding errors.

across all four stages, we used three dummy variables to code


stages II, III, and IV separately. This coding system does not assume an equal difference between two consecutive stages and is
more general.
To measure the effect size of each variable, we computed the
odds ratio (OR). For a categorical variable such as previous medication use, the OR is the ratio of the odds of dysmenorrhea occurring in one group (e.g. previous medication use = yes) to the
odds of dysmenorrheal occurring in another group (e.g. previous
medication use = no). For a continuous variable such as age at
surgery, the OR is computed as the ratio of odds when the variable
is increased by one unit.
The OR computed from the proportional odds model can be
interpreted as the odds of begin low pain score or high pain
score regardless of how the pain scores are divided into these two
categories. For example, the pain scores may be divided as 0 as low
and 1, 2 as high, or 0, 1 as low and 2 as high.
p ! 0.05 was considered statistically significant, yet no adjustment was made for multiple testing. With the exception of fitting
of the proportional odds and partial proportional odds models
which were made with SAS procedures logistic and genmod, all
computations were made using the software R 2.5.1 [21] (see also:
http://www.r-project.org). To ensure numerical stability in the
computation, non-dichotomous covariates were rescaled into the
interval 0, 1, and was transformed back when the results were interpreted. The preoperative use of medication, if ever, was lumped
into one category.

Results

Characteristics of Patients and Interrelationship


among Various Factors
The characteristics of the 710 patients with surgically
confirmed ovarian endometrioma are summarized in table 1, and the characteristics of the 376 patients with a
171

Table 2. Characteristics of 376 patients with dysmenorrhea and p-value from univariate analysis of dysmenorrhea severity

Covariates

Findings

p value from univariate


analysis of severity of
dysmenorrhea

Age at surgery, years


Mean
0.51
34.587.6
Median
34
Range
1851
Age at menarche, years
Mean
0.69
14.281.5
Median
14
Range
1021
Reproductive age at surgery, years
Mean
0.45
20.387.1
Median
19
Range
436
Previous use of endometriosis-related medication
None
320 (85.1)
0.029
GnRH agonists
16 (4.3)
Progestins or
other medication
40 (10.6)
Previous endometriosis-related surgery
No
338 (89.9)
0.028
Yes
38 (10.1)
Number of previous induced abortions
0
197 (49.9)
0.55
1
112 (31.8)
2
67 (18.3)
Number of live births
0
77 (20.5)
0.16
1
292 (77.7)
2
7 (1.9)
BMI
<19
71 (18.9)
0.17
1924
243 (64.6)
>24
62 (16.5)
Combination with adenomyosisa
No
223 (59.3)
0.003
Yes
153 (40.7)
Type of dysmenorrhea
Primary
125 (33.2)
0.055
Secondary
251 (66.8)
Duration of dysmenorrhea (in months)
Mean
0.34
100.98107.5
Median
60
Range
0.5420
n with missing value
11
Infertility (primary and secondary)
No
308 (81.9)
0.84
Yes
68 (18.1)
Laterality
Left only
126 (33.5)
0.36
Right only
106 (28.2)
Bilateral
144 (38.3)

172

Gynecol Obstet Invest 2008;66:169177

Covariates

Size
5 cm
510 cm
>10 cm
Adhesion
No
Yes
rAFS score
Mean
Median
Range
rAFS staging
I
II
III
IV

Findings

p value from univariate


analysis of severity of
dysmenorrhea

179 (47.6)
180 (47.9)
17 (4.5)

0.021

147 (39.1)
229 (60.9)

0.32

31.9819.5
28
2136

0.052

17 (4.5)
44 (11.7)
205 (54.5)
110 (29.3)

0.027

Findings are means with SD, medians, ranges or numbers,


with percentages in parentheses. Percentages in some variables
may not add up to precisely 100% due to rounding errors.
a All 279 patients had adenomyosis, and 37 of them additionally had myoma.

major complaint of dysmenorrheal are summarized in


table 2. As a subgroup, the women with dysmenorrhea
were similar to the entire cohort in all the characteristics
considered (tables 1, 2).
For the 710 patients, the previous use of endometriosis-related medication and previous endometriosis-related surgery were found to be highly correlated (p = 4.9 !
10 5), reflecting, possibly, the common need for medical
attention. As expected, the rAFS score and the size of the
ovarian cyst is correlated (r = 0.27, p = 9.5 ! 10 14). Age
at surgery and the rAFS stage were negatively correlated
(r = 0.13, p = 0.0005), with median (range) age at surgery
in the groups of patients with stages I, II, III and IV being
44 (2750), 37 (1851), 34 (1655), and 34 (1853) years,
respectively. The difference was statistically significant
(23 = 23.8, p = 2.9 ! 105, Kruskal-Wallis test). This negative correlation was also present in the 376 patients with
dysmenorrhea (23 = 17.6, p = 5.3 ! 10 4, Kruskal-Wallis
test).
Women who complained about dysmenorrhea were
about 3 years younger than those who did not, with the
median age in the two groups being 37 and 34 years old,
respectively. This difference was statistically significant
(p = 3.5 ! 10 5, Wilcoxons test). The number of previous
Liu /Yuan /Wang /Shen /Guo

Table 3. Parameter estimates of the logistic regression model on risk factors for dysmenorrhea

Covariate
Adhesion
Age at surgery
Previous use of medication
Presence of adenomyosis

Estimates
0.0885
0.0152
0.2516
0.1358

SE

Odds ratio (95% CI)

p value

0.0367
0.0027
0.0601
0.0428

1.092 (1.017, 1.174)


0.985 (0.980, 0.990)
1.286 (1.143, 1.446)
1.145 (1.053, 1.245)

0.0162
3.6 ! 108
0.0003
0.0016

Table 4. Parameter estimates of the dichotomous logistic regression model on risk factors for severity of dysmenorrhea lumping moderate and severe into one group

Covariate
Presence of adenomyosis
Duration (in 12 months)

Estimates
0.1880
5.62 ! 103

induced abortions was moderately correlated with the


number of live births (r = 0.25, p = 2.2 ! 10 11). As expected, the presence of adhesion was associated with
higher rAFS stage (p = 3.2 ! 10 7, 2 test).
Characteristics of Women with Dysmenorrhea
Among women with dysmenorrhea, the severity of
dysmenorrhea was positively associated with rAFS stage
(p = 0.02, 2 test) by univariate analysis. As expected, the
duration of dysmenorrhea appeared to be negatively associated with the severity (median duration in the mild,
moderate and severe groups was 84, 48 and 36 months,
respectively), but that correlation was not statistically significant (p = 0.34, Kruskal-Wallis test). The patients who
also had adenomyosis had slightly more severe dysmenorrhea than those with ovarian endometrioma only
(mean severity level: 1.54 vs. 1.32, p = 0.003, 2 test), although the difference in duration of dysmenorrhea was
not significant (p = 0.53, Wilcoxons test).
It is interesting to note that the average size of cysts
was negatively associated with severity (p = 0.03, 2 test),
but the presence of adhesion was not associated with severity at all (p 1 0.05).

SE

Odds ratio (95% CI)

p value

0.0502
2.75 ! 103

1.207 (1.093, 1.332)


0.9944 (0.9891, 0.9998)

0.0002
0.0414

ysis identified 6 factors for dysmenorrhea: age at surgery,


reproductive age at surgery, previous use of endometriosis-related medication, BMI, infertility, and adhesion (table 1).
Based on a multiple logistic regression analysis, younger age at surgery (OR = 1.02 for each subtracted year,
95% CI = 1.011.02), previous medication use (OR = 1.29,
95% CI = 1.141.45), adhesion (OR = 1.09, 95% CI = 1.02
1.17), and the presence of adenomyosis (OR = 1.15, 95%
CI = 1.051.25) were identified to be risk factors for dysmenorrhea among patients with ovarian endometriomas
(table 3).

Risk Factors for Dysmenorrhea


We sought to identify risk factors for dysmenorrhea in
patients with ovarian endometrioma using a multiple logistic regression model. We examined age at surgery, age
at menarche, BMI, parity, rAFS score, rAFS stage and several other factors, as listed in table 1. The univariate anal-

Risk Factors for the Severity of Dysmenorrhea


The univariate analysis yielded that previous use of
medication, history of endometriosis-related surgery,
presence of adenomyosis, size of the largest cyst, and
rAFS stage were associated with severity of dysmenorrhea (table 2). We further used two different statistical
models for multivariate analysis. The first model was a
multiple logistic regression for dichotomous response by
lumping moderate and severe dysmenorrhea into one
group. This approach yielded two factors that are positively associated with the severity of dysmenorrhea: the
presence of adenomyosis (OR = 1.21, 95% CI = 1.091.33)
and shorter duration of dysmenorrhea (OR = 0.994 for
each additional year) (table 4).
The second approach was based on a proportional
odds model using the logistic link. With this model, we
identified the presence of adenomyosis (OR = 2.14, 95%

Risk Factors for Dysmenorrhea

Gynecol Obstet Invest 2008;66:169177

173

Table 5. Parameter estimates of the proportional odds regression model on factors associated with the severity

of dysmenorrhea
Covariate
Presence of adenomyosis
rAFS stage II
rAFS stage III
rAFS stage IV
Previous medical treatment
Previous abortions

Estimates
0.7602
1.4591
0.8848
1.5027
0.6356
0.2883

CI = 1.373.35), the rAFS stage, previous use of medication (OR = 1.89, 95% CI = 1.073.34) as risk factors and
having previous induced abortions as a protective factor
(OR = 0.75, 95% CI = 0.590.96) associated with the severity (table 5). Interestingly, the same class of the model
with different links, such as extreme value, probit, and
Cauchit, all identified the presence of adenomyosis as one
of the risk factors, but they also resulted in a slightly different set of risk factors (data not shown). The score test
indicated that the assumption of proportional odds is acceptable (p = 0.4431). The analysis based on partial proportional odds models also led to the same proportional
odds model.

Discussion

In this study, we found that previous use of endometriosis-related medication, presence of adhesion, younger
age at surgery and the presence of adenomyosis are risk
factors for dysmenorrhea. For the severity of dysmenorrhea, however, the risk factors are somewhat different and
the results vary slighthy depending on the statistical model employed to analyze the data. Regardless, all models
consistently yielded the presence of adenomyosis as one
of the risk factors. The presence of adenomyosis also happens to be a risk factor for dysmenorrhea, indicating that
adenomyosis is associated with or possibly responsible
for both dysmenorrhea and its severity.
Strengths and Limitations of Our Study
Our study has at least three strengths: First, the large
sample size of patients exclusively with ovarian endometrioma. The inclusion of patients with ovarian endometrioma alone ensures the homogeneity of disease subtype,
reducing the likelihood of heterogeneous findings due to
different subtypes of endometriosis. Second, we consid174

Gynecol Obstet Invest 2008;66:169177

SE

Odds ratio (95% CI)

p value

0.2285
0.7141
0.6721
0.6821
0.2914
0.1256

2.139 (1.367, 3.347)


4.302 (1.061, 17.439)
2.423 (0.649, 9.044)
4.494 (1.180, 17.109)
1.888 (1.067, 3.343)
0.750 (0.586, 0.959)

0.0004
0.021
0.094
0.014
0.015
0.011

ered over a dozen potential factors associated with dysmenorrhea or its severity, increasing the likelihood that
potential confounding factors can be properly controlled
for. Third, we fitted several different statistical models
some of them are not reported for ease of exposure and
all of them identified consistently the presence of adenomyosis as a risk factor. The proportional odds assumption was checked by the score test and the analysis based
on partial proportional odds models.
Our study is not without limitations. First, several potentially important prognostic factors, such as adhesion
score, were not measured. As a result, their prognostic
importance, relative to or in combination with other factors, cannot be evaluated in this study. Second, our hospital, being the largest OB/GYN hospital in Shanghai
with 19 million residents, is essentially a tertiary hospital, and hence the way the patients were admitted to our
hospital may bias our results in ways unknown to us. Finally, the identification of risk factors for dysmenorrhea
was conducted for patients with ovarian endometrioma,
not in a general population of women with endometriosis.
Risk Factors for Dysmenorrhea
Just over half of the patients in this cohort complained
of dysmenorrhea. That adenomyosis may be responsible
for both dysmenorrhea and its severity is not surprising.
Dysmenorrhea is one of the chief complaints among
women with adenomyosis [22], and in our data 40.7% of
the women with dysmenorrhea had adenomyosis.
Adenomyosis results from the infiltration of basal endometrium into the underlying myometrium. The lesions are composed of endometrial glands, stroma and
surrounding hyperplastic myometrium [23], and characterized by a dispersed distribution of tissues, which respond to fluctuation of sex hormones and cause repeated
bleeding and, consequently, strong contraction of the
Liu /Yuan /Wang /Shen /Guo

uterus. Hence, patients who also have adenomyosis may


thus have a higher propensity for dysmenorrhea than
those without it. This may be especially true for patients
with a history of prolonged dysmenorrhea [24]. It also has
been reported that for patients with concurrent endometriosis and adenomyosis, endometriotic lesions tend to be
more severe in the posterior wall of the uterus, which
would easily adhere to the rectum and infiltrate into the
sacral nerve plexus, resulting in exacerbated dysmenorrhea [25].
Younger age at surgery was identified as a risk factor
for dysmenorrhea, which is consistent with the findings
of Vercellini et al. [14] who found an inverse relationship
between age at surgery and moderate-to-severe dysmenorrhea. As women age, the estrogen production and the
circulating estrogen levels decrease. Hence age at surgery
may well be a surrogate marker for the circulating estrogen level in the body. Higher estrogen levels in younger
women may thus help perpetuate and amplify the positive feedback loop that ultimately causes inflammation
and pain in women with endometriosis [26]. Alternatively, younger age at surgery may correlate with younger age
at onset of ovarian endometrioma, and younger age at
onset may represent a disease form that may be different
from that with older age of onset and may be more prone
to dysmenorrhea. In addition, younger age at surgery
may simply be the result of the need to seek medical attention early because of the pain.
The presence of adhesion may alter the reaction to sex
hormones by the lesions. Repeated rupturing, bleeding
and fibrin effusion in the endometriotic tissues may
eventually lead to adhesion to the surrounding viscera.
Since this process takes time, the formation of adhesion
and its presence may correlate with longer disease history
with worse severity.
Ovarian endometriomas often adhere to the pelvic
peritoneum and sacral ligament, where pelvic plexus exists. The resultant stimuli from those sites may easily lead
to pelvic pain and abdomen discomfort. During menstruation, the lesions congest and bleed, which may exacerbate the symptoms and result in more severe dysmenorrhea.
Patients who had previous use of endometriosis-related medication may be indicative of a prior diagnosis and
the presence of persistent endometriosis may be the cause
for dysmenorrhea. In addition, the use of medication may
signal a more persistent form of the disease or possibly
the presence of more massive adhesion, and thus pose a
challenge for surgery. Since medication can only alleviate
pain temporarily in most cases, patients with previous

Factors Associated with the Severity of Dysmenorrhea


Regardless of which statistical method is used, the
presence of adenomyosis has been consistently and robustly identified to be a factor associated with the severity of dysmenorrhea. This is not unexpected, since dysmenorrhea is one of the chief complaints among women
with adenomyosis [22]. However, the different methods
also yielded notably different sets of factors associated
with the severity of dysmenorrhea.
Dichotomization of the severity of dysmenorrhea may
have problems since it often results in a loss of information due to the collapsing of some categories of the
response [27]. In addition, different methods of dichotomization may yield different results. When the model assumptions hold, the proportional odds model, as employed also by Chapron et al. [28], is parsimonious with
nice interpretations for parameters. Since the proportional odds assumption is acceptable as suggested by the
score test and analysis based on partial proportional odds
models, it is reasonable to put more weight on the latter
model. The prediction performances of these two models
were similar based on tenfold cross-validations (results
not shown).
Since previous use of endometriosis-related medication is a clear indication that the patient has received
medical attention before because of endometriosis-related symptoms, it is understandable that it was identified
to be a risk factor for the severity of dysmenorrhea. The
previous use of medication, followed by surgery, suggests
that the patient may have had symptoms that need immediate relief hence increased risk of more severe dysmenorrhea. That previous induced abortion is a protective factor for the severity of dysmenorrhea is not very
surprising. It was reported that women with endometriosis had a longer period of uninterrupted menstrual
cycles [2931], suggesting that uninterrupted and unopposed exposure to estrogen increases the risk of endometriosis, which, in turn, may increase the risk of dysmenorrhea. Since rAFS stage is a basically a rough grouping
of rAFS scores which reflect the extensiveness of endometriosis and depth of adhesion, it may thus be responsible for the severity of dysmenorrhea. This appears to be
consistent with the study by Chopin et al. [32] who found
that rAFS score, along with rectal infiltration, was one of
two factors associated with the severity of dysmenorrhea. One factor we found to be not associated with the
severity of dysmenorrhea is adhesion. This seems to be

Risk Factors for Dysmenorrhea

Gynecol Obstet Invest 2008;66:169177

use of medication may thus have a higher risk of dysmenorrhea.

175

consistent with the finding reported by Parazzini et al.


[33].
That two different statistical models yielded slightly
but conspicuously different risk factors for the severity of
dysmenorrhea even though they were all based on exactly the same data set is actually not surprising. For
many studies, especially the cross-sectional ones, there is
often no single best-fit model for the data. Rather, there
may be several competing models which would lead to
somewhat different interpretations and sets of risk factors. This happens for a variety of reasons: for example,
covariates are correlated. Also, different models entail
different assumptions and may give slightly different results. The goodness-of-fit test for the proportional odds
model indicated that it fitted the data very well, suggesting the credibility of the results. The logistic model also
appeared to fit the data well based on the cross-validation.
This apparent discrepancy and our inability to identify the best-fit model underscore several caveats when
interpreting results from cross-sectional or retrospective
studies. First, due to the difference in statistical method-

ology, different results from different studies are to be


expected. Second, aside from sample size difference or
apparent deficiencies in study design, execution, or data
analysis, it is often difficult to tell which study is more
trustworthy than others. Even with the same data set,
lack of power may preclude a definitive identification of
the best-fit model.
However, if, as in our case, a risk factor is consistently
and robustly identified regardless of study or difference
in statistical methodology, then the likelihood is high
that it is truly a risk factor. This, of course, should be further supported by biological plausibility and validated by
independent studies. Risk factors identified by some
studies but not others may be spurious due to the nature
of the study or idiosyncrasy of the collected data.
In summary, we found that previous use of endometriosis-related medication, presence of adhesion, younger
age at surgery and the presence of adenomyosis are risk
factors for dysmenorrhea. For the severity of dysmenorrhea, the presence of adenomyosis has been consistently
identified to be the risk factor.

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