Key words endometriosis - infertility - sterility - endocrine treatment - adenomyosis uteri
interna - compliance
Schlüsselwörter Endometriose - Infertilität - Sterilität - endokrine Therapie - Adenomyosis uteri
interna - Compliance
Introduction
On average, 8–15 % of women aged 15–50 years suffer from the typical symptoms and
sequelae of endometriosis such as dysmenorrhea, dyspareunia, abdominal and pelvic
pain, and infertility [1 ]. The pathophysiology of this disease and its multiple clinical presentations is
still not completely clear. Studies have shown increasing evidence for endometriosis
being caused by altered immune responses [2 ]. Despite the high incidence of endometriosis, its diagnosis is still delayed (on
average by 10.4 years) [3 ]. Diagnostic and therapeutic options for this disease have been recently standardized
in national [4 ] and international consensus statements [5 ].
Nevertheless, there are only a few studies on womenʼs own perception of the disease
and the long-term risks of endometriosis, such as infertility or chronic pain. These
aspects were investigated in an Australian study which used focus groups and recruited
61 women suffering from endometriosis. The study showed that patients were mainly
concerned with the lack of support and their own daily struggle; patients reported
being stressed by the personal losses caused by the disease which affected their family,
partnership and career [6 ]. Women found dealing with endometriosis difficult and time-consuming. After having
received sufficient information about the disease, they wanted to be able to decide
on the management of their disease and quality of life for themselves. Another analysis
by Cox et al. showed that women preferred to take decisions on treatment options such
as endoscopic surgery themselves [7 ].
Endometriosis is a chronic disease which is associated with frequent pain, repeated
surgeries, hormone treatment and long-term sequelae such as infertility; it can therefore
have an impact on all aspects of a womanʼs life. A retrospective analysis of health-related
distress and interference with life activities emphasized the strong impact of frequent
pain [8 ]. Dyspareunia affects the womenʼs partnership, sexual life and fertility, resulting
in a reduced quality of life [9 ]. In a qualitative study of 30 women in Great Britain it was shown that 86 % of women
experienced dyspareunia, leading the majority of them to avoid sexual intercourse.
Only the desire to become pregnant could motivate these women to endure the pain caused
by the disease and be sexually active [9 ].
The aim of this study was to evaluate patientsʼ perception of endometriosis with regard
to treatment strategies and changes in symptoms due to treatment.
Material and Methods
Patient recruitment
221 patients with endometriosis were recruited at the Department of Gynecology and
Obstetrics of the Technical University of Dresden, Germany. Women diagnosed with endometriosis
or adenomyosis between January 2000 and December 2005, irrespective of the actual
cause of hospitalization and surgery, were included in this study. Inclusion criteria
were macroscopically and histologically confirmed endometriosis or adenomyosis. Age
and pre- or postmenopausal status were not inclusion or exclusion parameters. The
women were contacted by mail and were asked to return a completed questionnaire. Written
consent was obtained from all patients.
Questionnaire
Questionnaires on symptoms and on pain resulting from endometriosis have recently
been developed and are increasingly being used in diagnosis and to control the efficacy
of treatment (e.g. endometriosis health profile [10 ]). Short versions are available as German translations (http://www.endometriose-liga.eu/files/anamnesebogen.pdf).
As the aim of this study was to evaluate the perception of treatment in four clinical
subgroups, a new questionnaire was developed. Due to the concept of the study, there
was no initial survey of the health status of participating women prior to treatment.
The quantitative questionnaire technique was believed to be appropriate to obtain
an insight into individual perspectives of the disease, including subjective assessment
of diagnosis, complaints, and therapeutic interventions as well as changes in lifestyle
due to endometriosis.
The authors developed a questionnaire and a symptom checklist to collect data. The
questionnaire was designed to evaluate the patientʼs medical history and included
diagnostic procedures and symptoms prior to diagnosis and at the time of answering
the questionnaire. In addition, initial and ongoing surgical and medical treatment
(including frequency, duration and type of treatment) as well as changes in symptoms
and fertility and patientʼs perception of disease and treatment were analyzed. Women
in the infertility subgroup were asked about their wish to become pregnant and about
what they knew about infertility, diagnostic procedures and infertility treatment.
Women who became pregnant were asked about the time interval till becoming pregnant,
the birth, weeks of gestation at delivery, and their perception of the effects of
treatment. The questionnaire was filled out retrospectively at a mean of 2.7 years
after diagnosis. Medical data obtained from clinical records were included in the
analysis.
Statistical analysis
Clinical data of the study population were analyzed. The study population was divided
into 4 subgroups depending on the predominant clinical and diagnostic manifestations
(infertility, incidental findings, ovarian cysts and pain or symptoms related to menstruation
and sexual intercourse). This subgrouping was performed prior to analysis of the questionnaire
based on the coding of the diagnoses (endometriosis and adenomyosis uteri interna)
and confirmed by medical chart review. In cases with overlapping symptoms, the main
clinical presentation was chosen as the basis for categorization.
The statistical significance of differences between studied subgroups was assessed
using Pearsonʼs χ2 -Test and the standardized residual method. Differences in median values were compared
by nonparametric Mann-Whitney test. Significance was defined as p ≤ 0.05.
Results
Description of study population
The rate of return for the questionnaires was 51/157 (32.5 %) ([Fig. 1 ]). In spite of the relatively low response rate, the proportion of returned questionnaires
for the subgroups was comparable to the distribution of the subgroups in the whole
study population ([Table 1 ]). When we compared the subgroups, women in the subgroups ‘infertility’ and ‘incidental
findings/asymptomatic’ differed significantly with regard to age. The higher median
age was due to the studyʼs recruitment strategy of including women of all ages with
histological findings of endometriosis and adenomyosis. The oldest patient who answered
the questionnaire was 66 years old and was in the group of incidental findings. The
indication for vaginal hysterectomy was incontinence, and adenomyosis uteri was confirmed
histologically. The age of the oldest women with a histological diagnosis of endometriosis,
but not adenomyosis uteri interna, was 48.
Fig. 1 Recruitment of the study population (recruited and contacted women, drop-outs).
Table 1 Analysis of response rate and median age in different subgroups of patients with
endometriosis (* p-value < 0.05).
Main clinical presentation
All patients
Median age (years, STD, range)
Study population
Median age (years, STD, range)
p-value
Infertility
81 (36.7 %)
30.2 ± 5.26 (17–41)*
19 (37.3 %)
32.2 ± 5.0 (23–41)*
0.034
Incidental findings
38 (17.2 %)
44.6 ± 15.0 (16–77)*
9 (17.6 %)
47.4 ± 11.4 (31–66)*
0.013
Ovarian cysts
42 (19.0 %)
37.5 ± 13.2 (16–72)
9 (17.6 %)
31.7 ± 10.9 (16–49)
0.431
Dysmenorrhea/hypermenorrhea
60 (27.1 %)
36.1 ± 9.4 (17–53)
14 (27.4 %)
37.2 ± 5.7 (29–48)
0.644
Total
221
35.6 ± 11.3 (16–77)
51
36.2 ± 9.6 (16–66)
0.432
The completed questionnaires and the clinical data of 51 women were analyzed in this
study. The following clinical parameters were assessed using the clinical charts of
the study population: diagnosis, complaints, treatments received, medical history,
deliveries, abortions, ectopic gravidity, organ manifestations, stage of endometriosis
according to the revised classification for endometriosis of the American Society
for Reproductive Medicine (rASRM-score) [10 ], histology, surgical intervention, and further recommended treatment. The clinical
data of the study population based on medical records are shown in [Table 2 ].
Table 2 Characteristics of the study population.
Characteristics
Study population (n = 51)
Average age in years (range)
36.2 (16–66)
Marital status
39 (76.5)
12 (23.5)
Mean parity (range)
1.3 (0–5)
5 (9.8)
2 (3.9)
Clinical grading of endometriosis [rASRM score] (%)
17 (33.3)
7 (13.7)
12 (23.5)
3 (5.9)
Adenomyosis
13 (25.5)
Documented proposed further treatment (%)
26 (50.1)
16 (31.4)
2 (3.9)
4 (7.8)
Differences in symptoms and diagnostic methods in different subgroups
The questionnaires were analyzed for the four clinical subgroups. Although the numbers
in some groups were small, significant differences were observed ([Table 3 ]). Allocation to clinical subgroups corresponded to self-reported symptoms. Dysmenorrhea,
the most typical symptom of endometriosis, was reported for almost 80 % of the patients
in the symptomatic group, for one in every three women with infertility, and for one
in every two women with ovarian endometriosis. 3/9 women without typical symptoms
reported pelvic pain but no dysmenorrhea.
Table 3 Self-reporting questionnaire (n = 51 women); statistical analysis using standardized
residuals (values in italics) (* significant difference, p < 0.05).
Infertility (n = 19)
Incidental findings (n = 9)
Ovarian cyst (n = 9)
Clinical symptoms (n = 14)
p-value
Complaints before treatment
10 (52.6)0.1
3 (33.3)−0.7
4 (44.4)−0.3
9 (64.3)0.7
0.515
7 (36.8)−0.5
0 (0.0)*−2
5 (55.6)0.5
11(78.8)1.9
0.002
9 (47.4)−0.1
0 (0.0)−2.1
3 (33.3)−0.7
13 (92.9)*2.3
0.0001
5 (26.3)−0.5
1 (11.1)−1.2
2 (22.2)−0.6
9 (64.3)*2
0.030
Median rASRM score (1–4)
2.1
2
2.1
1.5
0.403
Adenomyosis (n)
2
6
1
4
0.110
Diagnostic assessment
3 (15.8)−0.4
2 (22.2)0.2
0 (0.0)−1.3
5 (35.7)1.4
0.194
4 (21.1)0.4
1 (11.1)−0.5
1 (11.1)−0.5
3 (21.4)0.3
0.845
6 (31.6)−0.1
4 (44.4)0.6
4 (44.4)0.6
3 (21.4)−0.8
0.589
16 (84.2)1.4
1 (11.1)*−1.9
3 (33.3)−1
10 (71.4)0.6
0.001
Therapeutic interventions
18 (94.7)0.9
2 (22.2)−1.9
7 (77.8)0
12 (85.7)0.4
0.0001
5 (26.3)0.9
0 (0.0)−1.3
4 (44.4)1.9
0 (0.0)−1.6
0.016
0 (0.0)−1.1
1 (11.1)0.6
0 (0.0)−0.7
2 (14.3)1.3
0.419
5 (26.3)−0.2
3 (33.3)0.2
1 (11.1)−1
6 (42.9)0.9
0.158
5 (26.3)−0.1
0 (0.0)−1.6
4 (44.4)1
5 (35.7)0.6
0.108
15 (78.9)1.1
3 (33.3)−1
5 (55.6)−0.1
7 (50.0)−0.4
0.541
Complaints after initiation of treatment
6 (31.6)0.7
2 (22.2)−0.1
0 (0.0)−1.5
4 (28.6)0.4
0.301
1 (5.3)−0.6
1 (11.1)0.1
1 (11.1)0.1
2 (14.3)0.5
0.850
1 (5.3)−0.4
1 (11.1)0.4
0 (0.0)−0.8
4 (28.6)0.9
0.598
1 (5.3)−0.4
1 (11.1)0.4
0 (0.0)−0.8
2 (14.3)0.9
0.598
Subjective changes due to surgery
6 (31.6)0.2
3 (33.3)0.2
1 (11.1)−1
5 (35.7)0.4
0.131
13 (68.4)0.3
6 (66.7)0.1
6 (66.7)0.1
7 (50.0)−0.6
0 (0.0)−1.2
0 (0.0)−0.8
0 (0.0)1.5
2 (14.3)0.9
Subjective changes with medication
8 (42.1)−1
7 (77.8)0.7
4 (44.4)−0.6
11 (78.6)1
0.113
10 (52.6)1.7
1 (11.1)−1.1
3 (33.3)0.1
2 (14.3)−0.3
1 (5.3)−0.6
1 (11.1)0.1
2 (22.2)1.2
1 (7.1)−0.3
Perception of diagnosis/treatment
15 (78.9)
7 (77.8)
7 (77.8)
8 (57.1)
0.511
12 (63.2)
1 (11.1)*
5 (55.5)
8 (57.1)
9 (47.4)
0
0
2 (14.3)
Infertility-specific diagnosis/treatment
13 (68.4)
5 (26.3)
4 (21.1)
3 (15.8)
The patients were questioned about the reasons their gynecologist had suspected and
diagnosed endometriosis. There were no statistical differences between subgroups.
Vaginal ultrasound led to the diagnosis of endometriosis or adenomyosis in a higher
percentage of the group with ovarian endometriosis and in the asymptomatic group,
but the difference was not statistically significant. In the infertility subgroup,
the most common diagnostic method was laparoscopy.
Differences in endocrine treatment between different subgroups
The incidence of endocrine treatment for endometriosis was comparable for all groups
but was especially high in the infertility group. A tendency, which was not statistically
significant, was found for women in the infertility group to be treated with gonadotropin-releasing
hormone analogues (GnRH agonists). The use of GnRH agonists across all groups was
quite high at 58.8 %, because the study was conducted before progestin-only medication
for patients with endometriosis was introduced in Germany in 2010.
Women reported relief of symptoms after endocrine treatment in the infertility and
the typical symptom groups (52.6 and 33.3 % of women, respectively). Significantly
fewer women in the asymptomatic group with predominantly confirmed adenomyosis (6 of 9 women)
considered endocrine treatment to be beneficial ([Table 4 ]). The reported symptoms (dysmenorrhea, heavy vaginal bleeding and premenstrual symptoms)
particularly improved in the symptomatic group. No statistical differences were found
between the 4 subgroups after initiation of treatment, although clinical differences
were statistically significant prior to treatment. 11/14 patients with symptoms did
not recall changes due to medication.
Table 4 Effect of treatment: statements of women with self-reported symptoms of dysmenorrhea
prior to treatment (n = 19; 4 out of 23 patients did not respond).
Surgical treatment beneficial
Surgical treatment NOT beneficial
No comment
Endocrine treatment beneficial
12
2
1
Endocrine treatment NOT beneficial
1
No comment
3
Differences in surgical treatment between different subgroups
Unexpectedly, 5/19 women with infertility reported that hysterectomy had been proposed
to them to treat endometriosis in spite of their initial and documented wish to have
a child. Two women suffering from pain and hypermenorrhea received initial treatment
with hysterectomy after unsuccessful infertility treatment. Surgery was performed
in these women because of severe dysmenorrhea and their strong desire for a definitive
treatment of endometriosis. One 33-year-old woman underwent multiple unsuccessful
IVF treatments and finally adopted a child. Because of the severe impairment of her
quality of life she underwent hysterectomy and bilateral oophorectomy. Another 3 women
underwent hysterectomy within 2 years after diagnosis.
In all subgroups, more than 50 % of the patients stated that their symptoms improved
post surgery. Two women stated that symptoms worsened after surgery, one in the group
with ovarian cysts and one in the group with clinical symptoms; both women had no
additional hormone treatment.
Differences in perception of treatment options between different subgroups
The questionnaire included the subjective perception of possible treatment effects.
The women were asked to complete multiple choice questions. More than 75 % women reported
a perceived effect of surgery. Only in the symptomatic group did fewer women consider
surgery to be a beneficial treatment for endometriosis (8/14). Three women stated
that only endocrine treatment was beneficial and another 3 believed that no treatment
was beneficial. Of the 9 women who believed that endocrine treatment is not beneficial,
2 were facing infertility and 4 were in the subgroup with asymptomatic endometriosis.
Only one woman with dysmenorrhea stated that endocrine treatment was not beneficial;
she also suffered from infertility. 23 women had confirmed dysmenorrhea prior to treatment.
[Table 4 ] shows the perception of endocrine treatment and surgery for these 23 women.
Knowledge of patients about infertility and the success of intervention
12 of the 19 women with endometriosis and infertility recalled undergoing functional
testing of the tubes; 7 reported having attempted several methods of artificial reproductive
medicine. Interestingly, 9 of 19 women facing infertility responded to the question
about what they thought of the diagnosis and treatment of infertility with “I donʼt
know” (47.4 %).
11/19 women in the infertility group reported a pregnancy after receiving a diagnosis
of endometriosis. The time to pregnancy was less than 2 years in 9 of these women.
Four of the 11 women became pregnant with artificial reproduction methods. Three women
who underwent in-vitro fertilization or intracytoplasmatic sperm injection did not
achieve a pregnancy by the time this survey was completed.
Discussion
Endometriosis is a chronic disease with many clinical manifestations. The subjective
perception of the disease was assessed by a questionnaire-based survey which compared
three symptomatic subgroups with endometriosis and an asymptomatic group of women
who had an incidental diagnosis of endometriosis.
The women in the infertility group were significantly younger than women in the other
groups. The asymptomatic group had a higher age at the first diagnosis of endometriosis/adenomyosis
uteri interna. In spite of the pre-categorization into 4 subgroups there were no significant
differences in rASRM score, although the rASRM score tended to be lower in the asymptomatic
group. This finding corresponds to the literature where a reversed score has been
proposed by the American Society of Reproductive Medicine as a classification model
for the severity of endometriosis; however, it still correlates only poorly with pain
and sterility [11 ], [12 ]. There were no cases of severe, deep, infiltrating endometriosis involving the bladder
and colorectum in our study.
Infertility is correlated with endometriosis and vice versa, although the pathophysiological
mechanisms for this correlation are still not clear [13 ]. Clinical records revealed that endometriotic cysts were found in more than 50 %
of the patients in the infertility group, a significantly higher percentage than in
the asymptomatic group. It is still not clear whether endometriotic cysts have a direct
negative influence on fertility or whether they only lead to impaired ovarian reserve
due to surgery. The indication for cyst excision must therefore be evaluated carefully
for each patient [14 ].
The medical approach to treat endometriosis consists of different hormone treatment
options. The capacity of oral contraceptives, local or systemic progestins, or GnRH
agonists to reduce endometriosis-related pain is well proven. The high proportion
of women treated with GnRH agonists in this study can be explained by the absence
of an approved progestagen for endometriosis in the study period.
Even though clinical symptoms differed significantly in the preselected subgroups
prior to treatment, the evaluation of patientsʼ perception of the disease and treatment
only showed a few significant differences between groups after initiation of treatment.
Significant differences were only found for self-reported symptoms, especially dysmenorrhea
and other menstrual symptoms. Interestingly, after initiation of treatment with surgery
and additional proposed medical treatment, the groups no longer differed with regard
to symptoms. No other statistical differences were found overall with regard to the
effects of surgery and medical treatment, but a significantly lower belief in the
beneficial effect of endocrine treatment was reported for the asymptomatic group.
This can be easily attributed to a lack of any subjective benefit from medication.
In contrast, a high percentage (12/19) of women with prior dysmenorrhea reported that
combined endocrine and surgical treatment was beneficial.
10/19 of women with infertility reported an improvement of symptoms with endocrine
treatment. These women were in favor of hormone treatment, even though medication
prolonged the time to pregnancy. Nevertheless, 50 % of women with infertility reported
becoming pregnant within 2 years after medical treatment. The perceived positive effect
of hormone treatment and subsequent pregnancy led to the high retrospective assessment
of endocrine treatment as “beneficial”. This positive assessment of hormone treatment
(oral contraceptives, progestin only or GnRH agonists) in the infertility group may
be interpreted as a good understanding of the pathophysiological condition of endometriosis.
Women in this group may have been influenced by the reduction of pain and the reduced
risk of recurrence of endometriosis, which allowed women to postpone their wish to
become pregnant.
The high proportion of infertile women treated with GnRH analogues despite having
only mild endometriosis reflects the usual procedure at the time of the survey. Based
on strong evidence (recommendation grade A), current guidelines do not recommend the
prescription of GnRH agonists to infertile women with minimal or mild endometriosis
[5 ].
Women with a documented diagnosis of endometriosis and/or adenomyosis were included
in this analysis. Age was not defined as an inclusion or an exclusion criterion; a
small subgroup of women was therefore above 50 years of age and was postmenopausal
(n = 5). Four of these women were in the subgroup with incidental findings, and all
of them had adenomyosis. Although the number of older women is too small to draw any
conclusions, it is important to underline the fact that endometriosis/adenomyosis
may also be present in postmenopausal women, as noted recently in a retrospective
analysis [15 ].
It is worth mentioning hysterectomy as a treatment option for endometriosis, even
for infertility patients; hysterectomy was initially used in 2/19 of women and subsequently
in a further 3 women. These women were aged 33–43 years and had undergone many years
of infertility treatment. Hysterectomy was the final treatment option for endometriosis
in spite of the womenʼs infertility.
Traditionally, hysterectomy and oophorectomy have been considered an effective treatment
option, especially in women with endometriosis involving the uterus [16 ]. Hysterectomy without oophorectomy is sufficient for adenomyosis uteri interna,
but not for endometriosis in general [17 ], even if a woman, possibly due to a misunderstanding of the pathophysiology of endometriosis,
asks for this intervention. If the woman suffers from severe symptoms, other treatment
options are ineffective and fertility is no longer desired, the indication for hysterectomy
with or without oophorectomy in women with endometriosis should be made based on an
individual risk-benefit evaluation and a decision-making consensus [18 ], [19 ].
Seven out of 19 infertility patients used an artificial reproduction method, and 50 %
of all women with infertility became pregnant within 2 years after the first diagnosis
as a result. Half of the women with infertility reported that they could not decide
on the value of diagnostic and therapeutic infertility treatments (“I do not know”).
This finding shows the importance of adequate education about the special nature of
endometriosis. The importance of a biopsychosocial approach to pain was recently emphasized
by Siedentopf et al. [20 ]. Adapted counseling techniques are needed for doctors and patients to understand
the nature of endometriosis as a complex chameleonic disease and the effect of treatment.
Nevertheless, the experience with certified endometriosis centers in Germany shows
that complex treatment options for patients should be discussed individually in specialized
interdisciplinary boards [21 ].
A limitation of the study was the small number of participating women. The quantitative
questionnaire was sent by mail to 221 women; 64 of them could not be reached and the
envelope was returned, possibly because of a change of address. All women were only
contacted by mail and could opt not to answer by not returning the questionnaire to
the clinic or returning an uncompleted questionnaire. This led to an unexpectedly
low return rate of 32.5 %, although the usual return rate of about 40–50 % had been
expected. Fortunately, mean age and proportional subgrouping into the four clinical
groups were comparable with the initially intended study sample.
The self-reporting of symptoms, the treatment and the changes associated with treatment
(mean interval between the first treatment and completion of the questionnaire was
about 2–3 years) may have led to distorted and possibly false memories. This study
can therefore not serve as a study on compliance with proposed treatment. Nevertheless,
future studies on this aspect of endometriosis are needed.
The design of this study with a newly developed questionnaire was only appropriate
for quantitative research done in a small study sample. Qualitative research to clarify
the perception of endometriosis is needed, using structured interview techniques or
a focus group design.
Modern information technologies allow women to obtain medical information and exchange
medical information via the internet. This means of communication in patient communities
has been described in detail for endometriosis-support groups in Canada [22 ]. Modern media and social networks should be used for research and as a way to reach
a broad range of women with endometriosis.
Conclusion
It is difficult to understand what endometriosis means to women suffering from this
disease, as it can have many different clinical manifestations. This questionnaire-based
survey analyzed four clinical subgroups and showed that women with endometriosis demonstrate
different responses to symptoms and treatment, even if these differences were not
statistically significant. It is obvious that symptoms and perceptions of each woman
may vary, leading to the conclusion that personalized and intensive counseling is
extremely important.
