Vol.3, No.9, 571-576 (2
opyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
011) Health
Pelvic pain in endometriosis: is s uccess of therapy gone
in cigarette smoke?
Agnes Koppan1*, Judit Hamori2, Ildiko Vranics1, Janos Garai3, Ildiko Kriszbacher1,
Jozsef Bodis2, Frank Oehmke4, Hans-Rudolph Tinneberg4, Miklos Koppan2,4
1Institute of Nursing and Clinical Sciences, Faculty of Health Sciences, University of Pécs, Pécs, Hungary;
*Corresponding Aut hor: akoppan@gmail.com
2Department of Obst e t r i c s and Gynecology, Faculty of Medicine, University of Pécs, Pécs, Hungary;
3Department of Pathophysiology and Gerontology, Faculty of Medicine, University of Pécs, Pécs, Hungary;
4Department of O b stetrics and Gynecology, Faculty of Medicine, University of Giessen, Giessen, Germany.
Received 17 January 2011; revised 1 June 2011; accepted 10 August 2011.
The objective of the study was to assess poten-
tial individual factors influencing the efficac y of
combined surgical and medical therapy in en-
dometriosis patients with pelvic pain. For this
purpose we performed a prospective study us-
ing a specifically design ed questionnaire among
patients suffering from persistent pelvic pain
and undergoing laparoscopy and further GnRH
analogue therapy in a university-based gyne-
cologic department. Eighty-one women of re-
productive age with histologically confirmed
endometriosis were enrolled. A questionnaire
gathered information from women on the fol-
lowing groups of variables: age, marital status,
education, reproductive and medical history
including previous pregnancies and parity,
knowledge of accompaniing pelvic disorders,
concurrent cigarette smoking, as well as gen-
eral quality of life estimates including self-im-
age. Pelvic pain was scored using a visual ana-
logue scale. Patients filled out the question-
naires before surgery and upon completing
medical therapy. Data were statistically evalu-
ated. After cessation of therapy, 53% of patients
reported absence of pain. Only 12% of pain-free
patients were smokers. This corresponded to
slightly more than one third (35%) of all smok-
ers in the study. However, 56% of non-smoker
participants reported a positive outcome that
proved to be significantly larger than the ra tio of
pain-free smoker participants (p = 0.02). Im-
provement in q uali ty of l ife was repo rt ed by 74%
of all patients, and only 9% of them were smok-
ers. However, 47% were smokers among pa-
tients reporting no change or worsening in
quality of life (p < 0.01). Based on our results,
we can conclude, that regular smoking might
have a disadvantageous impact on the success
rate of combined surgical and medical therapy
for endometriosis related pelv ic pain.
Keywords: Pelvic Pain; Endometriosis; Cigarette
Endometriosis affects millions of women world wide.
It can severely alter quality of life and leads to exten sive
problems with fertility and loss of work time [1]. Endo-
metriosis might remain asymptomatic and discovered
accidentally. However, it may cause symptoms, which
include chronic pelvic pain, bleeding, infertility, and
increases susceptibility to development of adenocarci-
noma [2]. Signs and symptoms arise from cyclic bleed-
ing into the surrounding tissues, resulting in inflamma-
tion and formation of scarring and adhesions. It is pecu-
liar, that symptom severity does not correlate well with
the extent or progression of the lesions [3]. Minor
laparoscopic findings might come with severe com-
plaints, while extensive lesions might remain undetected
and revealed only accidentally. The exact roles of dif-
ferent factors contributing to the establishment and per-
sistence of the endometriotic lesion are still not fully
understood. Despite the high associated morbidity and
health care costs, the incidence, prevalence, and risk
factors of endometriosis remain uncertain.
Symptomatic endometriosis can be managed surgi-
cally and/or medically. The aim is pain relief and/or
amelioration of infertility. Medical treatment is usually
long term, and recurrence is frequent after its cessation.
Classic endometriosis pharmacotherapy is represented
A. Koppan et al. / Health 3 (2011) 571-576
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by GnRH agonists, oral contraceptives and Type II pro-
gesterone receptor ligands [4]. All medical treatments
seem to be equally effective in managing endometriosis.
Although about 80% - 85% of patients have improve-
ment in their symptoms [5], many women experience
unsatisfactory results. However, little is known about
factors on patient’s side influencing the efficacy of gen-
erally accepted therapeutic approaches used to alleviate
symptoms caused by endometriosis.
In our study, we investigated the effectiveness of
combined surgical and medical therapy of patients with
histologically confirmed endometriosis with regard to
pain relief and overall quality of life issues. To deter-
mine these parameters we used a questionnaire before
laparoscopic surgery and upon cessation of post-surgery
medical therapy. With that, we determined efficacy of
therapy from the patient’s point of view, with relation to
several non-medical variables such as marital status,
level of education and smoking.
2.1. Stud y Population and Sample
The prospective cohort study population consisted of
patients of reproductive age complaining about persis-
tent pelvic pain and undergoing laparoscopy in our de-
partments (Department of Obstetrics and Gynecology,
Faculty of Medicine, University of Pécs, Hungary and
Department of Obstetrics and Gynecology, Faculty of
Medicine, University of Giessen, Germany). Following
laparoscopy and histological examination, a random
sample of 150 patients with histologically proven endo-
metriosis were then recruited. This initial number of
recruited patients was arbitrarily set and reached in a 6
month period between June and December, 2008. Ran-
domization was based on the unpaired character of pa-
tients’ social security number. The refusal rate upon
reaching the desired number of 150 was less than 5%,
however, the drop-out rate during the entire study period
was 46%. Those who were lost for follow-up did not
differ in any characteristics based on the collected data
comparing to those who completed both questionnaires.
Final statistics were carried out using data from those 81
patients completing the study. Prior to the operation pa-
tients consented to participate in the study. A standard-
ized questionnaire elicited information from women on
the following groups of variables: age, marital status,
education, reproductive and medical history. The ques-
tionnaire was purposefully designed to ascertain infor-
mation on p otential co nfounders, wh ich includ ed gravid-
ity (number of pregnancies regardless of outcome) and
parity (number of live births), knowledge of accompani-
ing pelvic disorders, concurrent cigarette smoking and
caffein intake, since all have been reported as risk fac-
tors for endometriosis [6,7]. Further variables were con-
currently used medication including pain killers, as well
as daily habits of excersice, type of work and general
quality of life estimates including self-image. Pelvic pain
was scored using a visual analogue scale from 0 - 10.
Only patients with histologically confirmed endometrio-
sis and with no other pelvic/abdominal alteration or dis-
ease confirmed at laparoscop y were then eligible to con-
tinue the study. Patients then received a 6 month GnRH
analogue therapy and were asked to fill out the same
questionnaire upon completing medical therapy. The
number of eligible patients completing both question-
naires was 81.
2.2 Operative Procedures
Laparoscopies were performed by highly trained and
experienced surgeons. Following the operations they
completed a standardized operative report to ascertaine
information on postoperative diagnosis and other pa-
thology regardless of surgical indication. Severity of
endometriosis was staged according to the American
Fertility Society’s revised definition. In all patients en-
dometriosis lesions were laparoscopically removed and/
or electrocauterized and histological examination con-
firmed diagnosis. The affiliated University gave Institu-
tional Review Board approval for the conduct of this
2.3. Statistical Analysis
Analysis of data was performed using Microsoft Excel
and SPSS 15 programs. We applied chi-square test,
analysis of variance (ANOVA), and Pearson-Spearman’s
rank correlation test. Data are presented as percentage
Mean age of participating patients was 31.2 years
(21 - 43 years, SD = 5.24). Out of them, 17.2% were
regular smoke r s .
3.1. Outcomes in Pain Relief
At the end of the treatment period, 53% of patients
reported the total absence of pain that they had specifi-
cally complained about at the beginning of the study.
Only 12% of pain-free patients were smokers. This
means that slightly more than one third (36%) of all
smokers, while 57% of all non-smoker participants re-
ported a positive outcome in the study. This difference
proved to be significant, as calculated by Chi-Square test
(p = 0.02, Figure 1).
A. Koppan et al. / Health 3 (2011) 571-576
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3.2. Outcomes in Overall Quality of Life
(Self-Image) The correlation between smoker status and negativ qual-
ity of life outcome proved to be significant, as calculated
by the Pearson’s correlation test (2-tailed, p < 0.01, Fig-
ure 2).
Overall, 74% of patients reported improvement in
their general quality of life, while no improvement or
even deterioration was reported by 26% of all partici-
pants. Among those with improved quality of life only
9% were smokers, while 47% were smokers among pa-
tients reporting no change or even worsening in their
quality of life. That means, only 36% of all smokers in
the study reported improvement in their quality of life,
while 64% of them reported no change or worsening.
Detailed analyses revealed no significant differences
in pain relief and quality of life measures at the end of
therapy with relation to marital status, level of education,
number of previous pregnancies regardless of outcome
and parity (number of live births). Furthermore, analyz-
ing the data concerning th e extent of the disease (i.e. the
stage of endometriosis recorded at laparoscopy) and pain
scores and quality of life values at the beginning and the
Figure 1. Correlation between smoker status and absence of specific pain as a basis for com-
plaints after combined surgical and medical therapy of endometriosis patients. Data are pre-
sented as percentage values. *p = 0.02; pain, specific pain is present; no pain, specific pain is
Figure 2. Ratio of smokers among endometriosis patients with regard to positive or negative
outcome in self-image at the end of combined surgical and medical therapy. Data are pre-
sented as percentage values. **p < 0.01; pos, positive change in general quality of life; neg, no
or negative change in general quality of life.
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A. Koppan et al. / Health 3 (2011) 571-576
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end of the study revealed no sig nificant correlation s.
The currently available medical treatments for endo-
metriosis seem to be equally effective. It is estimated
that about 80% - 85% of patients have improvement in
their symptoms [5]. Interestingly, severity of symptoms
does not correlate well with the extent of the disease [3],
although, in a well conducted study of 63 women a
benefit from conservative surgery seemed to be greater
in those with the most severe disease [8]. Unfortunately,
there were only two participants in the group with severe
disease, so limited data might hinder us to draw firm
conclusion. In general, we know little about possible
environmental and individual factors that can negatively
influence the efficacy of different therapeutic modalities.
The present paper deals with change in pelvic pain
and quality of life outcomes during combined surgical
and medical treatment period in endometriosis patients,
in relation to certain individual factors that might influ-
ence the effectiveness of therapy. The instrument we
used to evaluate efficacy was a detailed questionnaire
filled out twice by eligible and consenting patients.
In our study, the overall rate of improvement in qual-
ity of life was identified in almost three quarters of the
final study cohort (73.7%), and this is in line with other
data [5]. Similarly to earlier observatio ns [2,3], we could
not find any correlation between the revealed extent of
the disease and its impact on personal quality of life and
pain scores reported by the patients. Moreover, no sig-
nificant relation could be identified between these study
end points and sociodemographic variables, such as
marital status, level of education, number of previous
pregnancies and births.
However, we found a striking relation between smoker
status and pain relief, as well as overall improvement of
quality of life. Those who were regular smokers in our
study reported significantly less improvement in these
fields. An explanation to this finding could be provided
by a relatively new hypothesis raising, that, dioxin, the
most toxic of the organochlorines, is associated with an
observed increase in endometriosis in the developed
world [1]. Dioxins (2,3,7,8-tetrachlorodibenzo-p-dioxin;
TCDD) and dioxin-like chemicals cause a large variety
of pathologies including immune dysfunction, carcino-
genesis, developmental and reproductive abnormalities.
Most of these toxic effects are mediated by aryl hydro-
carbon receptor (AhR, also called th e dioxin receptor), a
ligand-activated transcription factor [9]. Recent investi-
gation demonstrated that cigarette smoke contains high
levels of agonists for AhR and markedly activates the
dioxin signali n g pat h way [1 0] .
The association of endometriosis with organochlori-
nes, specifically polychlorinated biphenyls (PCBs) that
are not dioxinlike, was firs t re p o rt ed from Germany [11].
Also, a letter from Belgian gynecologists suggested that
the higher prevalence of endometrio sis at infertility clin-
ics in Belgium could be caused by the relatively high
TCDD concentration in the Belgian population [12]. In
1976, an explosion in Seveso, Italy exposed the sur-
rounding population to among the highest levels of
TCDD recorded in humans. The “Seveso Women’s
Health Study” addressed the relation between TCDD
exposure and endometriosis and found a doubled but
statistically nonsignificant risk for endometriosis in
women with higher serum TCDD levels [13]. In nude
mice, Bruner and coworkers demonstrated an augment-
ing effect of TCDD on the development of arteficial
endometrial lesions [14]. Also, in a rat model, it was
shown that the environmental pesticide methoxychlor,
which can be metabolized to a chemical with high affin-
ity for the estrogen receptor, had the same ability as es-
trogen to promote the growth of endometrial implants
[15]. Methoxychlor is an example of synthetic or-
ganochlorines, a large and complex group of synthetic
organic compounds containing chlorine atoms. The
presence of chlorine tends to make the chemicals more
stable. In fact, certain organochlorines, such as dioxins
are extremely persistent and bioaccumulative [1]. Al-
though in a study by Wilson et al. it was demonstrated
that the maximum daily exposure estimates of dioxins
deriving from mainstream cigarette smoke are below the
current WHO Tolerable Daily Intake range of 1 - 5 pg/kg
bw/day [16], because of the highly bioaccumulative
properties of the organochlorines we need to be cautious
when interpreting these data.
More is known about the mechanism of toxicity of
dioxin than of almost any other chemical. It binds to the
Ah receptor, which functions as a ligand-activated tran-
scription factor [9]. Dioxin disturbs homeostasis, it is a
known human carcinogen and is toxic to multiple organ
systems [17]. Dioxins are reproductive and develop-
mental toxicants, as well as being neurotoxic and im-
munotoxic [18,19]. Cytokines such as tumor necrosis
factor and interleukins (IL) 1β and 6 have also been
shown to be induced by dioxin exposure [20,21]. TCDD
has been shown to be an immune sup pressant in multiple
systems and was also recently suggested to cause auto-
immunity in a mouse model [22]. Moreover, TCDD sup-
presses T-cell-mediated B-cell responses. It also causes a
block in T-cell maturation and is associated with thymic
atrophy at high doses in all species investigated [1].
These mechanisms might all contribute to the develop-
ment and maintenance of endometriosis.
In some studies endometriosis was inversely related to
cigarette smoking, however the available data were in-
A. Koppan et al. / Health 3 (2011) 571-576
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
sufficient to clarify this point [23-26]. Moreover, these
studies had different end points and they did not focus
on improvement in general condition and pain after
therapy in endometriosis patie nts earlier reporting pelvic
pain. Also, in the study by Mato rras et al., only a trend to
a protective effect of smoking was detected [26]. Miss-
mer et al. observed a complex relation with cigarette
smoking [27]. The rate of endometriosis was not linearly
associated with past smoking dose. However, the rela-
tion with current smoking differed by case-infertility
status. Among women who had never reported infertility,
cigarette smoking was directly associated with risk.
However, when cases were concurrently infertile, cur-
rent smoking was associated with reduced risk.
Based on our results, we can conclude, that regular
smoking might have a disadvantageous impact on the
success rate of combined surgical and medical therapy
for endometriosis re lated pelvic pain. Although there are
several studies focusing on the patomechanism of en-
dometriosis with regard to smoking, to our knowledge,
this is the first report dealing with a possible correlation
between therapy issues and smoking in this field. Even
though our data passed strict statistical analyses, consid-
ering their limited amount, we consider this work as a
preliminary one to initiate specially aimed international
studies to further clarify the issue.
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