Endometriosis can only be diagnosed by invasive procedures such as laparoscopic or laparotomy exploration. We constructed a non-invasive predictive model based on medical history and hematological indexes (blood routine, serum tumor markers examination) that can diagnose endometriosis in ovarian cyst patients. We found association between the CA-125, CA-19-9, age, partus matures, menstrual episodes, history of hysteroscopy, dysmenorrhea and blood routine test with endometriosis, but no single characteristic predicted endometriosis with a high accuracy. Our study supported the retrograde menstruation theory because the history of hysteroscopy is shown to be associated with an increase in risk of developing endometriosis.
Our study confirmed the belief that an increased frequency of and duration of menstruations is associated with endometriosis [14, 15]. Dysmenorrhea was the main symptom of endometriosis infertile women (46.92%) with endometriosis and the mechanism of dysmenorrhea in endometriosis lie in increased production of prostaglandins (PGs)[16]. Moreover, BMI showed a negative correlation with the presence of endometriosis, as was reported previously[17]. Obesity is often associated with long menstrual cycles, a factor that reduce the risk of endometriosis. It is considered that the reduction of the frequency of menstrual episodes counterbalances the relative hyperestrogenism of women[18].
Endometriosis is rare before the menarche and tends to decrease after the menopause. Studies conducted in women under age of 45 years suggested that the frequency of endometriosis increases with age until menopause[19]. While Fuldeore, M. J, et al [2] reported that the average age of women with endometriosis in their study was 37.8 years compared to 33.8 years women without endometriosis (p < 0.0001), it is possible that incidence of endometriosis increases as women age increases which can be because of the hormonal changes that occur during peri-menopause[20].
Screening for the diagnosis of patients with clinical suspicion of endometriosis is based on serum CA-125 which have been confirmed in many studies. Shen, A et al [21] reported that endometriosis is significantly associated with elevated serum CA-125 concentrations, confirmed CA-125 as an auxiliary biological marker in endometriosis diagnosis. Some studies[22, 23] did not agree with this finding and showed that the diagnosis of endometriosis on CA-125 alone is not accurate, mainly in relation to their sensitivity, Hirsch, M, et al[23] reported that CA-125 with a cut-off of ≥ 30 u/ml has a sensitivity of 0.57, which did not meet the criteria for a triage test, and international guidelines do not recommend CA-125 testing in women with suspected endometriosis[24]. However, in the study we find model 1 which consisted of CA-125 alone predicted endometriosis with high sensitivity (81.6%) and predicted the absence of endometriosis with a specificity of 83.5%. Nevertheless the timing of blood collection for CA-125 is uncontrolled because it’s a retrospective design, the relationship with the menstrual cycle is known to affect this test[25].
The study shows an inverse association between the number of mature delivery and endometriosis, but no association between the number of abortions and endometriosis has been found. This has also been observed in many studies of endometriosis[14, 26]. Parazzini, F, et al [26]reported that the risk of endometriosis decreased with increasing number of births, compared with nulliparous women, the OR of endometriosis at stage 1 was 0.1 (95% CI 0.1, 0.2) in women reporting two or more births was respectively 0.1 (95% CI 0.1, 0.3), 0.2 (95% CI 0.1, 0.4).
It has been reported that [27] reproductive history may influence hormonal milieu, Estradiol levels is higher among nulliparous women than among parous women, whereas androgen levels have an opposite effect, and reproductive history may influence the volume of endometrial cells released into the peritoneal cavity. The other studies revealed that CA-19-9 can be used to discriminate between patients with or without endometriosis, and it is correlation to severity of the disease, their results showed that CA-19-9 was significantly associated with advanced stage (stage III and IV) endometriosis[10]. Our results is in concordance with a former study that the mean levels of CA-19-9 are significantly elevated compared with the control group.
Endometriosis is associated with increased inflammatory activity which is an important stimulant for platelets[28], suggest platelet indices is an important and effortless hematological parameter that can be useful in evaluation of endometriosis[29, 30]. Evsen, M. S et al reported that platelets count in patients with peritoneal endometriosis were found to be higher from the control group (p = 0.038)[30], particularly more apparent in advanced stage peritoneal endometriosis. Monocytes also was also implicated as prognostic factor of inflammatory response but there is no evidence supporting that monocyte count is associated with endometriosis, our study shows that it is a protective factor for endometriosis, further study should be done to confirm this finding. This model provides guidance about confirmation of endometriosis. CA-125 can be useful in directing the diagnosis of the disease, and clinical history, tumor marker and routine blood tests increase the diagnosis of endometriosis more accurately. For instance, a peri-menopause woman with multiple reproductive history and irregular menstruation, has a higher chance of containing endometriosis, and if CA-125 is quite high, ovarian cysts would be appropriate to confirm the presence of the disease.