Keywords endometriosis - endometrioma - pelvic pain - dysmenorrhea - quality of life
Palavras-chave endometriose - endometrioma - dismenorreia - dor pélvica - qualidade de vida
Introduction
Endometriosis is a chronic disease that is defined as the presence of endometrium-like
tissue (glands and/or stroma) outside the uterine cavity that affects young, sexually
active women of childbearing age.[1 ]
The most commonly reported complaint by patients is pain that can be expressed in
a variety of symptoms, including dysmenorrhea, dyspareunia, chronic pelvic pain, and
infertility. These symptoms affect social, emotional and physical well-being. The
quality of life and relationships of the patients are significantly affected by the
presence of dyspareunia.[2 ]
[3 ]
[4 ]
[5 ]
According to the main international guidelines, endometriosis should be seen as a
disease that requires an individualized planning for life, and repetitive surgical
procedures should be avoided.[6 ] Its definitive diagnosis is surgical, and the gold standard is laparoscopy with
confirmation through the anatomic-pathological study of the lesion. However, suspicion
and clinical diagnosis are starting points to reduce the delay between the onset of
symptoms and the recognition of the disease,[7 ]
[8 ]
[9 ] since a delay of up to 9 years is reported prior to the definitive diagnosis.[10 ]
[11 ]
Knowing that one of the most common locations of endometriosis is ovarian, transvaginal
ultrasonography (TVUSG) emerges as the most accessible imaging method to diagnose
pelvic endometriosis, and is still the preferred method to differentiate endometriomas
from other ovarian cysts.[12 ]
It is estimated that the current prevalence of endometriosis is ∼ between 6 and 10%
in the general population, but this number is still uncertain. About 17 to 44% of
these patients also present endometriomas that are defined as ovarian pseudocysts
due to the growth of ectopic endometrial tissue, which progressively invaginates the
ovarian cortex.[13 ]
[14 ]
[15 ]
[16 ]
Assessments of the real impact of pelvic pain on the mental health and on the health-related
quality of life of women have not yet yielded conclusive results.[17 ] Several questionnaires aim to evaluate the quality of life of patients with endometriosis,
but until recently, the most used are generic instruments that do not accurately reflect
the reality of this specific type of patient, because they do not collect information
on all of the areas of well-being that may be relevant to women with endometriosis.
Two endometriosis-specific questionnaires have been developed and used in previous
researches, but the validity of these instruments is questionable, given that most
of the items were derived by clinicians and/or were scales taken from generic health-status
questionnaires.[18 ]
[19 ]
In 2001, Jones et al[20 ] developed an endometriosis-specific questionnaire entitled Endometriosis Health
Profile - 30 (EHP-30). This questionnaire differs from others because it is a patient-generated
instrument, in which all of the participants included had surgically-confirmed endometriosis
and were symptomatic at the time of diagnosis. They performed psychometric tests using
the 87 items of the questionnaire to identify the most salient dimensions of endometriosis
that affect the quality of life of each patient. The EHP-30 has been extensively tested
and validated in different cultural environments in the American, Australian, Dutch,
Italian, Chinese, Iranian, Portugal and Brazilian Portuguese versions.[20 ]
[21 ]
[22 ]
[23 ]
[24 ]
[25 ]
[26 ] The use of these questionnaires allows for more complete assessments, and they are
also important in evaluating the perception of women of disease impact and treatment
effectiveness in clinical scenarios.
Studies that used both specific or generic questionnaires showed a lower quality of
life in patients with endometriosis. However, they did not distinguish peculiar (e.g.,
clinical, epidemiological) characteristics that could be associated with worse scores.
These prior works have also not approached the specific subgroup with ovarian endometriosis
who we hypothesized may have a different perception of pain due to the anatomical
distortion of the pelvis caused by the endometrioma. With this in mind, the present
study aimed to evaluate the existence of an association between ultrasound findings
and epidemiological and clinical factors using results obtained from the EHP-30 questionnaire
in women with ovarian endometriosis.
Methods
A cross-sectional observational study was performed and was approved by the Brazilian
research ethics committee. It included the patients of the Endometriosis and Chronic
Pelvic Pain Outpatient Clinic of the Hospital do Servidor Público Estadual Francisco
Morato de Oliveira, São Paulo, state of São Paulo, Brazil, between July 2012 and May
2015. The sample size was calculated using the Open Source Epidemiologic Statistics
for Public Health (OpenEpi) software. Since the prevalence of ovarian endometriosis
varies between 17 and 44% of patients with endometriosis, up to 65 cases would be
necessary to obtain a 95% confidence level.[27 ]
The participants were recruited until we reached the sample size calculation. A total
of 65 sexually active Brazilian women of reproductive age with pelvic pain presenting
transvaginal ultrasound imaging suggestive of ovarian endometriotic cysts, which were
later confirmed by laparoscopy, were included. The patients had no other chronic pathology
justifying the pain symptoms, had not started any treatment, and also agreed to participate
in the research and signed the informed consent form after being briefed on the details
of the study by a physician. The participants were assured that their data would remain
confidential and that they could withdraw their consent at any time. Three patients
were excluded because they had no histological diagnosis of the disease. In the first
evaluation, we collected data regarding age, race, schooling, number of pregnancies,
and symptoms such as dysmenorrhea and dyspareunia. Afterwards, the patients self-completed
the standard EHP-30 questionnaire in its validated Brazilian Portuguese version in
a private office to access the baseline quality of life scores, in order to better
understand the real impact of the disease without any interference of previous therapeutic
approaches.
The EHP-30 is a self-reporting tool developed from interviews to assess health-related
quality of life that is specifically designed for patients with endometriosis. It
consists of a central questionnaire composed of 30 items that assess 5 dimensions
(i.e., pain, control and impotence, emotional well-being, social support, and self-image),
and a modular questionnaire composed of 23 items distributed into 6 sections. The
modular questionnaire sought to assess the impact of the disease in the following
six domains: work (Section A), relationship with children (Section B), sexual relations
(Section C), relationship with physician (Section D), treatment (Section E), and infertility
(Section F). These scales are transformed into a score from 0 to 100, in which 0 indicates
a better health status, while 100 indicates a worse quality of life.
The data collected was plotted using Microsoft Excel for Windows (Microsoft Corp.,
Redmond, WA, USA). The Statistical analysis was performed through IBM SPSS Statistics
for Windows, Version 22.0 (IBM Corp., Armonk, NY, USA) to provide a descriptive analysis
and a comparison of the data through linear multiple regression analysis to highlight
potential correlations between the epidemiological factors and symptoms and the questionnaire
scores. Linear multiple regression modeling was performed using the stepwise forward
technique to fit the best model. Statistical significance was attributed when p < 0.05, with a confidence interval (CI) of 95%.
Results
The data collection process of the study is shown in [Fig. 1 ]. The epidemiological characteristics of the sample studied were as follows: the
mean age of the 62 patients was 39.7 ± 7.1 years old (with a minimum age of 20 and
a maximum of 54 years old). The majority was Caucasian (64.5%), had a high level of
schooling with complete higher education (56.5%), and was nulligravida (40.3%). Of
these, 48.4% of the patients studied were infertile.
Fig. 1 Flowchart of the recruitment process of the patients.
Regarding the symptoms, the patients reported acyclic pain (80.6%), dysmenorrhea (79%),
and dyspareunia (61.3%); 21% had bilateral ovarian cysts (i.e., endometriomas), with
a mean cyst size of 37 mm (10–95 mm). For the evaluation of the averages, of the standard
deviations (SDs), and of the minimum and maximum scores in the central and modular
questionnaires of the EHP-30, the scales were transformed into a scoring system that
ranged from 0 to 100 ([Table 1 ]).
Table 1
Trend measures and descriptive statistics of the central and modular EHP-30 questionnaires
Variables of EHP-30
Average
Standard deviation
Minimum grade
Maximum grade
Central questionnaire (n = 62)
Modular questionnaire
61.61
18.37
20
95.33
Section A
Work
(n = 54)
54.49
22.72
20
92
Section B
Relationship with children
(n = 35)
50.28
25.26
20
100
Section C
Sexual Relations
(n = 55)
66.98
22.77
20
100
Section D
Relationship with physician
(n = 60)
37.58
20.65
20
90
Section E
Treatment
(n = 42)
50
21.75
20
93.33
Section F
Infertility
(n = 39)
51.07
24.21
16
100
Total score
55.52
15.85
19.53
83.59
The completion rate of all items in the central questionnaire was 100% (62/62). Regarding
the modular questionnaire, considering that not all dimensions are applicable to all
patients, the filling rate ranged from 56.45% (35/62) in Section B to 96.77% (60/62)
in Section D. For the multiple statistical analyses, the distribution of the outcome
variable (i.e., the dependent variable) was confirmed as a normal distribution. A
univariate analysis was performed between the outcome variable and the clinical and
epidemiological factors, and a linear multiple regression was conducted ([Table 2 ]).
Table 2
Linear multiple regression for the analysis of clinical and ultrasound factors correlated
with the weighted overall EHP-30 score (n = 62)
Analyzed variable
Unadjusted analysis
p-value (CI)
Final adjusted model
p-value (CI)
Dyspareunia
0.000 (9.18–23.56)
0.001 (5.72–19.84)
Acyclic pain
0.001 (7.09–25.82)
0.001 (6.37–22.78)
Dysmenorrhea
0.032 (0.93–20.13)
0.131 (- 1.95–14.70)
Bilateralism
0.159 (- 2.81–16.81)
0.229 (- 3.15–12.89)
Larger cyst diameter
0.177 (- 0.72–0.38)
0.725 (- 0.15–0.22)
Abbreviation: CI, confidence interval.
In the multiple analyses for the general questionnaire score, we observed that dyspareunia
and acyclic pain were independent correlation factors for a higher total EHP-30 score
adjusted for dysmenorrhea, cyst bilateralism, and larger cyst diameter. The suitability
of the linear regression model was confirmed by the residue distribution graph, which
confirmed the trend of linearity as well as the homogeneous dispersion of residues.
When we applied the statistical model to the modular questionnaire, in Section A,
no variable was significantly correlated with an increase in the score. When applied
to Section B, the variables age and Caucasian women were presented as independent
correlation factors with higher scores, and age was inversely correlated with score,
while Caucasian women had direct correlation and were adjusted by the variables dyspareunia
and acyclic pelvic pain ([Table 3 ]).
Table 3
Linear multiple regression for the analysis of clinical and ultrasound factors correlated
with weighted scores for EHP-30 Section B (children) (n = 35)
Analyzed variable
Unadjusted analysis
p-value (CI)
Final adjusted model
p-value (CI)
Age
0.002 (- 3.04–-0.72)
0.020 (- 2.71–- 0.24)
Caucasian
0.014 (5.02–40.57)
0.036 (1.35–37.64)
Dyspareunia
0.023 (2.90–36.14)
0.249 (- 6.75–25.04)
Acyclic pain
0.051 (- 0.09–47.43)
0.501 (- 15.13–30.26)
Abbreviation: CI, confidence interval.
When Section C was evaluated, the only variable that presented a positive correlation
with score in this section was dyspareunia (p = 0.015), adjusted for abortion, parity, acyclic pain, and greater cyst diameter.
In Sections D and E, all variables in the final statistical model, even after being
adjusted, did not present a significant correlation with the EHP-30 scores. Conversely,
in Section F, it was observed that dysmenorrhea and dyspareunia were associated with
higher scores in this section ([Table 4 ]).
Table 4
Linear multiple regression for the analysis of clinical and ultrasound factors correlated
with weighted scores for EHP-30 Section F (infertility) (n = 39)
Analyzed variable
Unadjusted analysis
p-value (CI)
Final adjusted model
p-value (CI)
Dysmenorrhea
0.022 (4.33–53.02)
0.007 (8.69–50.29)
Dyspareunia
0.046 (0.32–32.25)
0.022 (2.74–33.18)
Age
0.156 (- 1.61–0.27)
0.153 (- 1.58–0.26)
Abortion
0.717 (- 16.49–11.47)
0.686 (- 16.26–10.82)
Abbreviation: CI, confidence interval.
Discussion
Endometriosis can occur in any woman who menstruates, and a higher risk has been found
in women aged between 35 and 44 years old .[28 ] The mean age of the patients in our study was 39.7 ± 7.1 years old, corresponding
to the age range in which endometriosis is usually diagnosed. Complaints of acyclic
pain (80.6%), of dysmenorrhea (79%), of dyspareunia (61.3%), and of infertility (48.4%)
were slightly higher than those found by Bellelis et al (2010), showing a profile
of clinical-epidemiological characteristics among population samples.[29 ]
In the present study, the EHP-30 questionnaire was applied to evaluate the quality
of life of patients with endometriosis. It is important to mention that a cutoff point
for the scores obtained in this questionnaire has not yet been established in the
literature, and this makes it difficult to fully understand impairments in quality
of life. Therefore, comparisons were made to correlate linearity through the regression
analysis.
Compared with the data presented in the other studies that validated the EHP-30 in
several countries, in the modular questionnaire, we obtained the highest mean scores
related to impact on work, sexual intercourse, and relationship with children, and
the lowest mean scores regarding infertility.
After a multiple linear regression analysis, [Table 2 ] shows that dyspareunia and acyclic pain presented as independent factors of positive
correlation with the total score of the EHP-30 questionnaire, and that the high prevalence
of these symptoms significantly interferes with the personal and sexual lives of the
patients, which may reflect a greater negative impact on their quality of life. This
finding is corroborated by de Freitas Fonseca et al.[30 ]
Lukic et al[31 ] studied women with pelvic endometriosis and found that the symptom perceived as
being most responsible for the deterioration of quality of life for women with endometriosis
is dyspareunia. They also found that, after surgery, these women experienced a significant
decrease in this symptom. In the specific group of patients with ovarian endometriosis,
we believe that pain may also be due to the anatomical distortion that endometriomas
create in the pelvis, which does not respond completely to conservative treatment,
thus indicating that the localization of endometriotic foci are responsible for the
intensity of the pain symptoms.
In the present study, a higher score is observed in the modular questionnaire in Section
C, which evaluates the effects of endometriosis on sexual relations. The mean score
was 66.98 ± 22.77 (20–100), and this trend measure could also potentially interfere
with the prevalence of the dyspareunia symptom found in the studied population (61.3%).
Previous studies have also shown that women with endometriosis and dyspareunia experience
worse sexual function than women without endometriosis.[32 ]
[33 ]
[34 ] We know that endometriosis affects young and sexually active women; therefore, sexual
health should be a primary concern in the clinical management of this disease. This
negative impact between endometriosis, pain and sexual function have also been confirmed
by Vercellini et al.[35 ]
Another relevant finding of our study was the association of dysmenorrhea and dyspareunia
with high scores on the question of infertility. This association largely reiterates
the negative influence of pain on the general quality of life and sexual satisfaction
that, in turn, interferes with the reproduction of patients with endometriosis. It
is well-established in the literature that chronic pelvic pain and the experience
of pain during intercourse affects negatively the lives of the patients.[36 ] Authors have also shown that endometriosis affects negatively several aspects of
the quality of life of women – both physically and mentally.[10 ]
[37 ]
In addition, we found a correlation between a worse quality of life and the relationship
with children and Caucasian women, but this fact may be only associated with the higher
prevalence of Caucasians in our study. Soliman et al also found a higher prevalence
of white patients with endometriosis in their case studies.[38 ]
One of the most difficult moments in the management of ovarian endometriosis is deciding
when to opt for surgical treatment, because it is known that patients have had both
pain and endometrioma recurrence even after laparoscopy.[39 ] Because the treatment for endometriosis aims to improve the quality of life, we
believe that a perspective for further studies with this specific subgroup of endometriosis
patients could explore the prognostic value of the EHP-30 to define a cutoff point
in which the patient with endometrioma would benefit more from surgical or clinical
treatment. This could potentially guide gynecologists and surgeons in carefully tailoring
their strategies to each individual case. Currently, the EHP-30 has not been greatly
applied in the clinical practice of gynecologists, neither in studies evaluating quality
of life in patients with endometriosis.[20 ]
The strengths of the present study include the fact that we have only selected women
with ovarian endometriosis who also had not begun any treatment before answering the
questionnaire. This enabled us to understand the real impact of the disease without
any influences. To our knowledge, this is the first Brazilian study that has tried
to correlate clinical and epidemiological factors with quality of life scores using
a disease-specific questionnaire in women presenting with ovarian endometriosis.
The limitations of the present study were derived from the study design, from the
small sample size, and from the fact that we have only evaluated women at baseline.
Results after surgical intervention were not yet analyzed, which could limit the interpretation
and the external validity of the results of the present study. However, we have already
developed a research line to continue the longitudinal investigation with a larger
sample to compare quality of life before and after treatment. These results might
help to better understand the effects of therapeutic interventions on the quality
of life of these patients.
Conclusion
The results of the present study showed an association between dyspareunia and acyclic
pain, exerting a negative influence on the overall EHP-30 score at baseline prior
to any treatment. This reflects a worse quality of life among patients with ovarian
endometriosis who present those clinical factors. Also, it reinforces that endometriosis
affects several areas in the lives of women and that improved general well-being should
be the main goal of gynecologists.
