Endometriosis is a puzzling disease with little known about its true prevalence, its distribution in the population, or its risk factors. Estimates of the frequency of endometriosis vary widely. The disorder is encountered in 7–10% of actively menstruating women, with a suspected prevalence as high as 22% in asymptomatic women and 30% in women with subfertility . Women with the disease may have progressive dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility . Given this relatively high prevalence and the significant morbidity associated with this disease, endometriosis poses a significant public health problem .
Advances in understanding the epidemiology of endometriosis have lagged behind other diseases because of methodological problems related to disease definition and control selection. Nevertheless, a better picture of epidemiology of endometriosis has emerged over the past few decades . Research has associated family history with an increased risk of developing the disease . Recently, the results of a genome-wide association study showed that women with two different genetic variants were more likely to develop endometriosis . Other nonmodifiable risk factors include history of autoimmune diseases and menstrual characteristics such as length of cycle, cycle regularity, early age at menarche, and heaviness of menstrual flow [4,7,8]. The association between modifiable risk factors such as exercise habits, cigarette use, alcohol consumption, and caffeine intake with endometriosis has also been studied, but further research is indicated as results have been inconsistent in these areas [4,7,9]. These risk factors seem to be compatible with the central importance of retrograde menstruation influenced by outflow obstruction that might affect its amount, immune factors that might affect its ability to be cleared, or with hormonal stimuli that might affect its growth .
The basic epidemiology of endometriosis among Egyptian women did not draw the attention of many researchers. Given the fact that the majority of the Egyptian women are suffering in silence , this study aimed to investigate some risk factors that correlated with endometriosis among a sample of women in Alexandria.
Materials and methods
Study design and settings
This case–control study was conducted in the University Maternity Hospital and in some private hospitals in Alexandria, Egypt, between September 2005 and March 2007.
Women eligible for the cases in this study were those who were diagnosed by operative laparoscopy as having endometriosis and attending the previously mentioned hospitals. Every case diagnosed as having endometriosis was matched for age and residence by two hospital-based controls that were diagnosed with unrelated minor conditions at the outpatient clinics of the hospital. Cases continued to be recruited until the sample size summed up to 110 surgically confirmed cases of endometriosis and 220 age-matched control women.
Data collection methods
Informed consents were obtained before the interview from all women who were willing to participate in the study. A structured interview was performed using a predesigned questionnaire to collect data on sociodemographic background and some risk factors previously reported to be associated with endometriosis such as reproductive variables, menstrual characteristics, and medical history. Study participants were subjected to weight and height measurements to calculate the body mass index (BMI), defined as weight (kilogram) divided by height (meter). Cases were interviewed at the postoperative ward just before discharge from the hospital. Controls were interviewed at the waiting areas of the outpatient clinics. The study was approved by the ‘Ethics Committee’ of the High Institute of Public Health.
All the statistical analyses were carried out using SPSS version 13 (SPSS, Chicago, Illinois, USA). The significance of the association between all potential risk factors and the presence of endometriosis was assessed using either Pearson's χ2 test or Fisher's exact test (computed with Monte Carlo estimation, when needed) for the categorical variables, or the Student t-test for the continuous variables. Crude odds ratios (ORs) along with 95% confidence intervals (CI) were also calculated. A logistic regression analysis was performed in which all significant associations by univariate analysis were adjusted with some potential confounders (identified from the literature). In all the tests used in this study, a probability of less than 0.05 was considered statistically significant.
The age of women ranged from 16 to 43 years, with a mean age of 27.9±6.8 and 27.4±6.4 years for cases and controls, respectively. Ever-married women constituted 71.8% of patients versus 66.4% of controls. University graduates constituted the highest percentages of both groups (76.4 and 70% of cases and controls, respectively), with insignificant differences between both groups. A comparatively large proportion of the sampled women were working for cash (41.8 and 45% for cases and controls, respectively).
Some reproductive characteristics of the study participants are shown in Table 1. Among ever-married women, the proportion of women who had been pregnant before was significantly higher in controls than in cases (74.7 and 35.4%, respectively, P<0.01). Among parous women, the proportion of women who had their first pregnancy before the age of 25 years was also significantly higher in the controls than in the cases (61.5 and 35.7%, respectively, P<0.01). Moreover, the proportion of women who breastfed their infants was significantly higher in the controls than in the endometriosis group (91.7 vs.71.4%, P<0.05). A significantly higher proportion of parous women in the endometriosis group than controls reported suffering from current infertility (78.6 vs. 9.2%, respectively; P<0.01).
Table 2 shows the medical history of the studied sample. Nearly equal percentage of both cases and controls reported a positive history of allergic conditions (32.7 and 34.1%, respectively, P>0.05). Only 2.7% of cases compared with 3.2% of controls reported a history of autoimmune diseases (P>0.05). Significantly higher proportion of cases than controls (29.1 vs. 16.6%, P<0.01) reported a history of irritable bowel syndrome (IBS). A history of reproductive tract outflow obstruction was reported by six women with endometriosis compared with none of the controls (6.4 vs. 0.0%, P<0.01).
Table 3 illustrates the menstrual characteristics of the participants. A significant trend for women with endometriosis to have an earlier menarche compared with controls was detected, with 21.8% of patients compared with 11.4% of controls reported as experiencing early menarche (defined as ≤11 years) (P<0.05). A significant trend for women with endometriosis reporting having shorter menstrual cycles was also identified, with 41.8% of cases compared with 24.5% of the control group having menstrual cycles of 27 days or less (P<0.001). With regard to the cycle regularity, there was a statistically significant excess of patients (40.9%) than controls (24.5%) whose menstrual cycles were irregular (P<0.05).
Table 4 shows the distribution of cases and controls by their family history. A statistically significant excess proportion of patients than controls reported having one or more female relatives with endometriosis (10.9 vs. 5%, respectively, P<0.001). Among women who had a positive family history of endometriosis, 25% of patients compared with 18.1% of controls reported having a sister with the disease.
Table 5 shows that patients weighed significantly less than controls [mean weight±standard deviation (SD), 64.3±10.2 vs. 67.2±8.9 kg, respectively, P<0.01]. However, insignificant difference was found between the two groups regarding their mean heights (height±SD; 1.62±0.04 vs. 1.61±0.03 m, respectively, P>0.05). As for the BMI, women with endometriosis had significantly lower mean BMI±SD (24.44±3.69 kg/m2) than those of the control group (25.72±2.93 kg/m2) (P<0.05). Women with endometriosis were significantly less likely to be overweight than controls (36.4 vs. 51.9%, respectively, P<0.05).
Table 6 illustrates the results of the stepwise logistic regression analysis of the significant variables related to endometriosis by univariate analysis among cases and controls. Gravidity was inversely associated with the risk of endometriosis with nulligravidae being four times more likely to develop endometriosis than those with a history of gravidity [adjusted odds ratio (AOR)=4.0, 95% CI (2.2–7.6)].
With regard to the menstrual factors, cycle length was inversely associated with the risk of endometriosis, in which short cycles (≤27 days) were associated with approximately six times increase in risk of endometriosis [AOR=6.1, 95% CI (2.9–12.8)], and cycles of 28 to less than 30 days were associated with a 3.5 times increase in risk of developing endometriosis [AOR=3.52, 95% CI (1.69–7.62)]. Women with irregular cycles were three times more likely to develop endometriosis than women with regular cycles [AOR=3.5, 95% CI (1.89–6.71)]. Similarly, a nearly two-fold increase in risk of developing endometriosis was observed among women with a history of IBS [AOR=1.9, 95% CI (1.03–3.87)].
With regard to BMI, being overweight was associated with approximately 50% decrease in risk of developing endometriosis [AOR=0.4, 95% CI (0.26–0.85)]. However, obesity was associated with approximately two times increase in risk of developing endometriosis. Yet, this increase in risk was not statistically significant [AOR=1.7, 95% CI (0.73–4.30)]. Women who had one or more relatives with endometriosis were 1.2 times more likely to develop endometriosis [AOR=1.21, 95% CI (0.19–0.43)].
In this study, on the basis of the findings of the univariate analysis, nine variables were found to have a significant association with endometriosis and they were introduced into the logistic regression model. After adjusting for the possible confounders, the final best model showed that history of gravidity, menstrual cycle length, BMI, history of IBS, menstrual cycle regularity, and positive family history of endometriosis were the independent variables associated with developing endometriosis.
The regression model uncovered an inverse association between endometriosis and gravidity, menstrual cycle length, and being overweight. Positive association was showed in women who reported irregular cycles, positive history of IBS, and those who had one or more relatives with endometriosis.
This study showed an inverse association between menstrual cycle length and the risk of endometriosis. This could be explained as the higher likelihood of pelvic contamination from menstrual endometrial material — the reflux hypothesis. This result was supported by earlier observations linking endometriosis risk to short cycles (≤27 days) [4,7,11,12]. Moreover, Darwish et al. , in their first epidemiological study of the prevalence and risk factors of endometriosis among Egyptian women, reported that women with endometriosis had significantly short cycles of 27.7±3.6 years than women in other groups. Other researchers failed to confirm the association between short menstrual cycles and endometriosis [14,15].
Although epidemiological studies showed less consistent evidence on cycle regularity [4,12], this study showed that women with irregular cycles were more likely to develop endometriosis than those with regular cycles. Consistent with the present findings, Signorello et al.  found that women with irregular cycles were at a greatly increased risk of developing endometriosis. Other studies failed to confirm the association between endometriosis and menstrual cycle pattern [13,14,17].
With regard to the family history, this study showed that women who had one or more relatives with endometriosis were 1.2 times more likely to have endometriosis than controls. There is good evidence that women with endometriosis are more likely to have a mother or sister with the disease than controls [4,18]. A higher frequency of endometriosis in first-degree relatives of affected women has also been reported in studies from Norway and Italy [19,20]. These findings, however, should be considered cautiously because recall bias cannot be excluded. Cases of endometriosis might tend to recall a family history of the disease more accurately than controls. Accordingly, considering positive family history as a risk for endometriosis would not be affirmed until the results of the ongoing genetic studies in this field will be published in details.
The study also showed that gravidity was inversely associated with the risk of endometriosis, and nulligravidae were more likely to report endometriosis than those with a history of gravidity. In agreement with the present findings, many clinical and epidemiological data suggested an inverse association between gravidity and the risk of developing endometriosis [4,11,15,21].
There is a difficulty in sorting out the relationship between childbearing and endometriosis. Although disruption of pelvic anatomy and ovarian function leading to infertility may clearly be a consequence of endometriosis, it is also reasonable to propose that delayed childbearing could also be a cause of endometriosis . Clearly, the association between childbearing and endometriosis could not be addressed in those studies in which cases are defined on the basis of presenting a complaint of infertility; however, the question can be addressed in which pelvic pain or mass is the complaint .
This study also showed that a history of IBS was associated with endometriosis. This may be explained in terms of diagnostic bias, as some women with chronic pelvic pain symptoms may be misdiagnosed as having IBS. Some studies were in agreement with the present findings and have reported an association between IBS and endometriosis [22,23]. On the contrary, a wide-scale survey for diseases correlated with endometriosis failed to confirm this association .
This study uncovered a weak inverse association between BMI and endometriosis. The logistic model showed that being overweight was associated with approximately 50% decreased risk of developing endometriosis. This finding is supported by findings of other anthropometric studies that observed weak inverse associations between endometriosis and BMI with overweight women suggested to be at a lower risk of endometriosis [16,25,26]. It is worth mentioning that, in studying any disease that causes pain or discomfort, changes in the appetite as a result of the disease should be acknowledged as a possible source of bias when considering body weight and BMI as risk factors.
An important limitation of this study is that the sample size was not large enough to obtain comprehensive results on possible risk factors. However, this could be attributed to the difficulty in recruiting cases of endometriosis diagnosed by operative laparoscopy as having the disease. Moreover, the present findings need to be cautiously interpreted. In case of all case–control studies, appropriate control selection is difficult, because factors that might influence which affected women are diagnosed could be related to exposures of interest. Our control group comprises a heterogeneous group of women, but all have been reported to be free of the disease.
Conclusion and recommendations
Nulliparity and short and irregular menstrual cycles were significant risk factors for developing endometriosis. A weak association between reported family history of endometriosis and history of IBS and the development of endometriosis was also observed. Health education of women to raise their awareness about endometriosis-related factors should be a priority to ensure early diagnosis of the disease. The study also suggests the need to stimulate professional education on possible risk factors of the disease, perhaps by creating continued medical education programs.
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