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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,
Introduction
170
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
Table 1. Characteristics of 710 patients and p value from univariate analysis of the risk factor for dysmenorrhea
Covariates
Findings
Covariates
Findings
31.2820.5
28
2144
0.051
33 (4.7)
84 (11.8)
407 (57.3)
186 (26.2)
0.26
rAFS score
Mean
Median
Range
rAFS staging
I
II
III
IV
Results
Table 2. Characteristics of 376 patients with dysmenorrhea and p-value from univariate analysis of dysmenorrhea severity
Covariates
Findings
172
Covariates
Size
5 cm
510 cm
>10 cm
Adhesion
No
Yes
rAFS score
Mean
Median
Range
rAFS staging
I
II
III
IV
Findings
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
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
p value
0.0367
0.0027
0.0601
0.0428
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
SE
p value
0.0502
2.75 ! 103
0.0002
0.0414
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
SE
p value
0.2285
0.7141
0.6721
0.6821
0.2914
0.1256
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
175
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