Endometriosis is an important gynecologic disease
affecting reproductive-age women (
Phytoestrogens stimulate sex hormone-binding globulin
(SHBG) production in the liver (
With regard to the role of inflammatory, immunologic and hormonal factors in the pathogenesis of this disease, we hypothesized that phytoestrogen intake can reduce the risk of endometriosis. Our study evaluated the association between dietary phytoestrogen intake and endometriosis risk using a food frequency questionnaire (FFQ).
Between May 2016 and February 2017, the present case-control study was conducted on 156 infertile women in clinic Arash Hospital, Tehran, Iran. The sample size was determined using the information obtained from a pilot study with 20 patients and the following formula: all infertile women who underwent diagnostic laparoscopy during the period of the study were allocated. The case group consisted of 78 endometriosis women for whom the disease was confirmed by laparoscopy and histology examinations. Control group included 78 infertile women with a normal pelvis. Women in the two groups were comparable in demographic and personal characteristics.
Inclusion criteria were as follows: i. Age between 15-45 years, ii. The absence of a history of chronic disease (such as cancer, diabetes, stroke, heart disease, etc.), iii. Being from Iranian race, iv. Not being pregnant, v. Not using medications affecting food absorption, appetite and basal metabolism of the body, and vi. No smoking and vii. Lack of mental retardation.
The medical Ethics Committee of Tarbiat Modares University approved the study (IR.TMU.REC.1395.358) also, before enrolment of the participants, a written informed agreement was obtained from each one. In the beginning, a socio-demographic questionnaire including questions about socioeconomic status, age, smoking, education, habitat, and ethnicity was completed by women, then participants’ dietary information was obtained using FFQ.
Dietary data were collected using FFQ as a validated
semi-quantitative questionnaire with 147 food items.
Trained dietitians questioned participants regarding their
intake frequency for each food item consumed during
the past year on a daily, weekly, or monthly basis; all
these were converted to daily intakes. Then, by applying
the manual for household measures, portion sizes of
the consumed food were transformed to grams (
Statistical analysis of data was performed by using Statistical Package for Social Science (SPSS, version 21, SPSS Inc., Chicago, IL, USA). Odds ratio [adjusted for age, total energy intake, body mass index (BMI), educational level, and income], with 95% confidence intervals (95% CIs) were calculated using logistic regression models to assess the strength of the associations between the phytoestrogen intake and the risk of endometriosis. Dietary phytoestrogen, isoflavin, lignan, and coumestrol intake was categorized into quartile categories, based on the distribution of control subjects. To calculate the linear trend in the odds of dietary variable quartile, median factor score of each quartile was entered into the logistic regression analysis, and the lowest quartile of intake was used as the reference category for all regression analyses. T test, Mann-Whitney, and chi-square were used to compare other variables. A P value below 0.05 was considered statistically significant.
Table 1 compares the demographic characteristics of healthy women and subjects with endometriosis. There were no statistically significant differences in the women’s age, BMI, parity, educational, marital status, occupation, income, and age at menarche between the two groups.
Demographic and anthropometric characteristics of women with and without endometriosis
|Characteristic||Case group||Control group||P value|
|Age (Y)*||31.01 ± 6.56||29.35 ± 7.00||0.13|
|<25||50 (64.1)||50 (64.9)|
|25-29.9 (overweight)||24 (30.8)||23 (29.9)|
|≥30 (obese)||4 (5.1)||4 (5.2)|
|Lower than university||42 (53.8)||38 (49.4)|
|University||36 (46.2)||39 (50.6)|
|Age at menarche***||13.49 ± 2.38||13.35 ± 1.64||0.70|
|Unmarried||22 (28.2)||21 (27.3)|
|Married or cohabiting||56 (71.8)||56 (72.7)|
|Parous||32 (41)||42 (54.6)|
|Nulliparous||46 (59)||35 (45.5)|
|Housewife||61 (78.2)||68 (88.3)|
|Employed||17 (21.8)||9 (11.7)|
*; Values are given as mean ± SD and compared using Student’s t test, **; Values are given as a number (%) and compared using Chi-squared test, ***; Values are given as mean ± SD and compared using Mann-Whitney test, and BMI; Body mass index.
Table 2 summarizes the ORs for endometriosis by daily phytoestrogen intake according to quartile of intake. We observed inverse associations between consumption of phytoestrogen (OR: 0.68; 95% CI: 0.51-0.91, P-trend=0.01) and total isoflavones (OR: 0.38; 95% CI: 0.33-0.83; P-trend=0.002) and endometriosis risk, but this difference was more related to formononetin (OR: 0.57; 95% CI: 0.27-0.97; P-trend=0.04) and glycitein (OR: 0.68; 95% CI: 0.67-0.98; P-trend=0.04).
High consumption of lignan was associated with a lower risk of endometriosis (OR: 0.49; 95% CI: 0.46- 0.52; P-trend=0.01). Among the sub type of lignan, only secoisolariciresinol (OR: 0.54; 95% CI: 0.36-0.77; P-trend=0.01), lariciresinol (OR: 0.64; 95% CI: 0.32- 0.74, P-trend=0.02) and matairesinol (OR: 0.30; 95% CI: 0.22-0.52; P-trend=0.003) were related to reduced risk of endometriosis. The intake of coumestrol in the third quartile was associated with reduced risk of endometriosis (OR: 0.38; 95% CI: 0.15-0.96; P-trend=0.15).
Table 3 demonstrates an association between the sub-type of phytoestrogen in each food group and risk of endometriosis. Among food groups, only isoflavin (OR: 0.48; 95% CI: 0.44-0.63), lignan (OR: 0.66; 95% CI: 0.62-0.94), coumestrol (OR: 0.64; 95% CI: 0.51-0.99) and phytoestrogen (OR: 0.46; 95% CI: 0.38-0.83) in dairy products and coumestrol in fruits (OR: 0.69; 95% CI: 0.03-0.77) were associated with endometriosis.
Adjusted odds ratios (OR) of endometriosis and corresponding 95% confidence intervals (CI) according to the subtype of phytoestrogen intake
|Quartile, OR (95% CI)*|
BMI; Body mass index and *; Odds ratio adjusted for age, energy intake, BMI, educational level, and income. Quartile 1 used as the reference category.
Adjusted odds ratios (OR)* of endometriosis and corresponding 95% confidence intervals (CI) according to phytoestrogen from the dietary item
|Food group||Isoflavones||Coumestrol||Lignans||Total phytoestrogens|
|Cereals and breads||0.99(0.86-1.04)||0.99(0.01-3.24)||0.94(0.87-1.01)||0.96(0.92-1.01)|
BMI; Body mass index and *; Odds ratio adjusted for age, energy intake, BMI, educational level, and income.
Our findings suggest that higher intake of phytoestrogen such as isoflavin, lignan, and coumestrol is associated with a reduced risk of endometriosis. All subtypes of phytoestrogen in dairy products and coumestrol in fruits were related to reduced endometriosis risk.
Recently, some studies discussed associations between
phytoestrogen and endometriosis. One of such studies
Results of some studies demonstrated that dietary
consumption of phytoestrogens was associated with
reduced risk of endometrial, breast, colorectal and prostate
It was indicated that increased urinary excretion of
phytoestrogen was associated with decreased CRP levels
Animal studies showed that ginstein has an antiproliferative effect on mammary tissue in rats exposed
to prepubertal estrogens (
Regarding the effect of phytoestrogens on inflammatory,
immunological and hormonal factors, phytoestrogen
consumption can reduce the risk of endometriosis.
Bioavailability, absorption, and estrogenic characteristics
of phytoestrogens are dependent on the compound’s
bioactivity, which metabolized in to compounds by
intestinal microflora (
A limitation of this study was the problem of convincing the participants to answer many questions. Also, as it was a case-control study, the probability of selection and recall bias including under- and over-reporting of the specific food items might have affected our results.
Phytoestrogens have a major impact on the level of hormones, and immune and inflammatory markers; thus, it can play an important role in the control and prevention of many diseases. Due to the inflammatory nature of endometriosis and the effect of hormones on the progression of the disease, the role of phytoestrogens consumption in the progression and regression of the disease should be assessed in future works.