Endometriosis is defined as the presence of functioning endometrial glands and stromal cells outside the endometrial cavity, affecting 5-15% of women of child-bearing age, among whom 30-50% develop infertility [1,2]. Many theories have been proposed to explain the pathophysiologic development of endometriosis; however, the etiology of the disease is still unclear [3,4]. Most researchers agree that endometriosis is an estrogen-dependent chronic inflammatory process in the pelvic cavity. Accordingly, endometriosis is associated with pelvic pain and infertility, especially in the case of ovarian endometrioma, which directly affects the ovarian reserve [5].

The major risk factors based on such estrogen-dependent features of endometriosis include increased estrogen exposure frequently leading to early menarche, prolonged duration of menstrual flow, shorter menstrual cycle interval, and nulliparity [1,6,7]. One of the factors that could influence physiologic estrogen activity and exposure is the dietary pattern of a patient, which is a valuable, modifiable factor not only for disease management but also for prevention when well understood [1,8]. A number of studies have been published, although they reported rather inconclusive data. Some studies have reported that a plant-based and high-fiber diet increases estrogen excretion and decreases the concentration of bioavailable estrogen. However, the effects of vegetable consumption on the risk of ovarian endometrioma are unknown [1,9-11]. Moreover, studies investigating the association between red meat consumption and the risk of endometrioma development have reported contradictory results [12].

When evaluating the relationship between certain diets and diseases, it is important to note that the effect of diet on the hormone levels or inflammatory status of the body could be influenced by the cooking method, storage techniques, and/or management of food resources (e.g., use of pesticides) [13]. Because of such variables, the precise evaluation of the relationship between dietary patterns and the occurrence of a specific disease requires statistical analysis based on a homogeneous population with a shared culinary culture. Thus, this case-control study investigated the dietary patterns of Korean women diagnosed with ovarian endometrioma (histologically confirmed after laparoscopic surgery) compared with patients with other benign ovarian cysts with surgical and histologic confirmation.

In this study of a homogeneous population of Korean women living in a local city with a shared culinary culture, the dietary intake of calcium was significantly lower in the endometrioma group. Moreover, although statistical significance was not reached, the dietary intakes of vitamin D, iron, and zinc were relatively lower in the endometrioma group than in the control group. Our data did not provide supporting evidence for a relationship between endometriosis and any of the other nutrients or food groups examined, except for calcium, vitamin D, iron, and zinc.

The lower intakes of calcium in our patients with endometrioma are partially consistent with previously reported data from different ethnicities and population pools. Harris et al. [17] reported that calcium, vitamin D, and magnesium intakes from food sources were inversely related to endometriosis. In their study, participants with a higher quintile intake of calcium from food sources had a lower risk of endometriosis, with a trend of statistical significance. Moreover, Trabert et al. [1] suggested inverse associations between endometriosis and dairy product intake or calcium intake from food sources, although the difference was not statistically significant (odds ratio, 0.7; 95% confidence interval, 0.4-1.2). The authors suggested the ability of calcium and vitamin D to downregulate growth-promoting factors, such as insulin-like growth factor-I, and to upregulate negative growth factor regulators, such as transforming growth factor β. Further-more, according to their study, dietary factors such as dairy products and several specific nutrients may be related to the physiologic processes associated with endometriosis through their effects on systemic inflammation. The association between vitamin D and endometrioma seems more complicated to analyze than the association of other nutrients with endometrioma. As mentioned earlier, the dietary intake of vitamin D was inversely related to endometriosis, although only a small proportion of vitamin D is obtained from dietary sources [17]. Nevertheless Ciavattini et al. [18] also reported that a relatively high proportion of women with ovarian endometrioma showed hypovitaminosis D. Similarly, Abbas et al. [19] observed that vitamin D treatment induced a reduction in the endometriosis cyst dimension in a rat model. To clarify the role of vitamin D in endometriosis, further studies are urgently required.

In our study, the dietary intake of zinc was also lower in the endometrioma group (median [IQR] = 11.40 [9.36-13.94] mg in the case group and 14.24 [9.04-18.13] mg in the control group, P=0.198). Similar patterns were observed in the study by Messalli et al. [20], who reported that patients with endometriosis presented a lower serum zinc concentration than the control group (1,010±59.24 μg/L vs. 1,294±62.22 μg/L, P<0.05). They also suggested that zinc interferes in the pathogenic processes of endometriosis, such as inflammation and immunity.

Other important dietary factors known to be related to the risk of endometriosis development are red meat, trans fats, and omega-3 fatty acids. Large studies have been conducted to reveal such relationships, and their results have shown that increased intakes of red meat and trans fats, and decreased intake of omega-3 fatty acids were related to an increased risk of endometriosis [2,8,21]. In our study, the intake of animal fat and protein showed no difference between the 2 groups. Such results may be due to the small number of patients included in this study; however, they could also result from the inclusion in the current study of an East Asian population with eating habits that differ from those of Western populations analyzed in previous studies. Traditionally, Asian populations are known to consume lower amounts of meat than their Western counterparts. Although the general dietary patterns have been showing similarities worldwide, owing to the increasing cultural exchanges and the faster and easier internal trades of food products, the daily eating habits still considerably differ across different countries [22,23]. Thus, the red meat consumption in our Korean population may have been too low to present any significant effect on the risk of endometriosis, compared with previous data from Western populations. Moreover, the current study was conducted in a local port city in South Korea, where the population had easy and frequent access to fish products containing omega-3 fatty acids. Accordingly, both the case and control groups had been exposed to and consumed higher levels of omega-3 fatty acids than the general population, which could have affected the results of the current study.

The current study had several limitations. As this was a retrospective study that reviewed previously obtained medical records, the baseline characteristics of the patients were limited to 9 categories for the risk factors of endometrioma. Although such categories included major risk factors, more detailed features of the patients still need to be investigated in future studies. In addition, most studies evaluating population dietary patterns in association with endometriosis use self-questionnaires; thus, some of the data are vulnerable to recall bias. However, in our study, all questionnaires were completed by medical professionals who had been educated about the purpose and outline of the study. In addition, in epidemiologic studies, the diagnosis or exclusion of endometriosis is typically determined solely by evaluating the patients’ medical records. In our study, all patients were diagnosed with or ruled out from having endometriosis by laparoscopic surgery and histologic confirmation, thus obtaining a more precise medical status for each patient.

Other limitations include the potentially compromised effects of a single nutrient according to the cooking method, even with the same amount of ingredients. Such variations are difficult to standardize in epidemiologic studies. However, it may be important to implement in certain areas in persons with similar lifestyles, and our study included a homogeneous population of only Korean women and local area residents.

Finally, the number of patients included in the present study was relatively small. To offset the size limitation, all patients included in the study were surgically diagnosed with the ovarian pathology (endometrioma or a benign ovarian cyst), with histologic confirmation, and every food frequency questionnaire interview was supervised by a medical professional. Additionally, to our knowledge, this is the first study to analyze the effect of dietary patterns on the risk of endometriosis in a Korean population.

In summary, the risk of endometriosis is significantly associated with a lower intake of calcium, and despite being statistically insignificant, lower intakes of vitamin D, magnesium, and zinc were observed in patients with ovarian endometrioma. Further studies including a larger number of patients on a nationwide scale with detailed statistical analysis of significant nutrients are urgently required to determine the link between dietary patterns and the risk of endometriosis, to enable the establishment of patient education programs and lifestyle consultation on population-based strategies for preventing the disease.