Myomas are a common, benign, hormone-dependent gynecologic condition. It has been suggested that unopposed estrogen may increase the risk of myomas.1 Thus, any factor that reduces endogenous estrogen levels and increases progesterone levels may reduce the risk of uterine myomas. For example, pregnancy and oral contraceptive (OC) use decrease the risk of myomas.1,2
Diet has been associated with estrogen levels. Protection against breast and endometrial cancers by vegetable and fruit intake may be mediated by isoflavonoids, which have moderate estrogenic activity and may therefore compete with other endogenous estrogens.3 A study of postmenopausal women showed that vegetarians had lower urinary levels of estriol and total estrogens, lower plasma prolactin levels, and higher plasma levels of sex hormone-binding globulin.4 Another study of premenopausal women in the United States showed that vegetarian women had 15–20% lower plasma estrogen levels than omnivores of the same age.5,6
Little is known about the potential effect of diet on the risk of uterine myomas. To explore the potential association between diet and myoma risk, we considered data on selected food intake collected in an Italian case-control study.
Materials and Methods
Our data came from an ongoing case-control study of uterine myomas conducted in Milan, Italy.2,7 Cases included 843 women aged 54 years or less (median age 43 years, range 21–54) with histologically confirmed uterine myomas, whose clinical diagnoses dated back no more than 2 years. They were admitted to the obstetrics and gynecology clinics of the University of Milan. Indications for surgery were recurrent menorrhagia or echographic evidence of myomas larger than 10 cm in diameter. We collected data during their hospital stays.
Controls were 1557 women aged 54 years or less with comparable quinquennia of age as the cases (median age 43 years, range 21–54) who had not had hysterectomies and were admitted for acute nongynecologic, nonhormonal, nonneoplastic conditions to a network of hospitals with comparable catchment areas. Of these, 30% were admitted for traumatic conditions, 28% had nontraumatic orthopedic disorders, 18% had surgical conditions, 10% had eye disorders, and 14% had other miscellaneous illnesses such as ear, nose, and throat or dental disorders. We excluded controls if they had a confirmed or suspected history of uterine myomas.
Trained interviewers identified the cases and controls. A standard questionnaire was used to collect sociodemographic characteristics and habits; related medical history; gynecologic and obstetric data, including numbers of births, miscarriages, and induced abortions; and history of lifetime use of OCs and other female hormones. Women who reported cessation of menstrual cycles in the year of the interview were defined as postmenopausal.
Subjects were also asked about frequency of consumption per week of selected dietary items (including the major sources of retinoids and carotenoids in the Italian diet), as well as alcohol and coffee drinking in the year before interview. Subjective scores (low, intermediate, and high) were used to collect information on fat intake (butter, margarine, and oil) and consumption of whole-grain foods. Reproducibility of the questionnaire was satisfactory.8,9 Less than 2% of the cases and controls refused to be interviewed. The present report is based on data collected until June 1997.
The cutoffs for the analysis of dietary factors were based on the best possible approximation of tertiles. An estimate of the total daily average alcohol intake was derived assuming a comparable ethanol content in each type of beverage (125 mL wine = 333 mL beer = 40 mL spirits = 15 g pure alcohol). Wine accounted for more than 90% of the alcohol consumed by women in this population. To account simultaneously for the effects of several potential confounding factors, we performed unconditional multiple logistic regression with maximum likelihood fitting to obtain the odds ratios (ORs) of uterine myomas, their corresponding 95% confidence intervals (CIs), and test for trend when appropriate.10 The regression equations included terms for age, education, menopausal status, marital status, body mass index (BMI), parity, smoking, calendar year at interview, and the various food items considered, unless otherwise specified. Intake frequency was introduced also as a continuous variable. The models with the continuous coefficient give an estimate of the OR relative to an increase of one average serving per day.
Table 1 presents the distribution of cases and controls and the corresponding ORs according to selected characteristics. Women with uterine myomas were more educated, more frequently premenopausal, and less frequently smokers than controls. The risk of myomas was lower in parous than in nulliparous women, and the risk decreased with parity. No clear association emerged between BMI and the risk of myomas.
The average weekly frequencies of consumption of selected dietary items and the corresponding ORs of uterine myomas are reported in Table 2. Consumption of milk, liver, carrots, eggs, cheese, whole-grain foods, butter, margarine, and oil was not associated with uterine myomas. No association emerged between uterine myoma risk and the intake of coffee, tea, or total alcohol consumption. Women with uterine myomas reported more frequent consumption of beef, other red meat, and ham and less frequent consumption of green vegetables, fruit, and fish. The multivariate ORs in the upper tertiles were 1.7 (95% CI 1.4, 2.2) for beef and other red meat, 1.3 (95% CI 1.0,1.6) for ham, 0.5 (95% CI 0.4,0.6) for green vegetables, and 0.8 (95% CI 0.6,1.0) for fruit. The protective effect of fruit appeared weaker than that of vegetables. An inverse trend in myoma risk was observed also for fish consumption; the OR for the highest versus least frequent intake was 0.7 (95% CI 0.6, 0.9).
All of the food groups associated with uterine myomas in Table 2 were included in a multiple logistic regression equation to allow for a mutual confounding effect. For the highest level of consumption, the association of beef and other red meat (OR 1.8; 95% CI 1.4,2.3), ham (OR 1.2; 95% CI 1.0,1.5), and green vegetables (OR 0.5; 95% CI 0.4, 0.7) with myoma risk was confirmed. The ORs for an increase of one serving per day in these food groups associated with myoma risk are shown in Table 3. The ORs were 1.8 for beef and red meat consumption, 1.9 for ham, and 0.6 for green vegetables.
We found a moderate association between the risk of uterine myomas and the consumption of beef, other red meat, and ham, whereas a high intake of green vegetables seems to have a protective effect. A limitation of this study is that we collected information only on the frequency of intake, with no quantitative estimate of portion size, of a few indication foods. Therefore, no estimate of the total caloric intake could be obtained.11 However, we were unable to explain the results in term of obvious information bias because the possible relation between diet and uterine myomas was unknown to the interviewers and probably to most of the subjects interviewed. Further, a specific attempt was made to collect dietary information before the first diagnosis of myomas. A major effect of selection bias is unlikely because we excluded from the control group women admitted to the hospital for chronic conditions and for any digestive-tract diseases that could have produced long-term modification of the diet. Control subjects were asked specifically about their history of myomas and were excluded if they had a confirmed or possible history of the disease.
Control subjects did not undergo ultrasound examinations, which can be considered a limitation of the study, but this potential misclassification mechanism could only underestimate any difference between the cases and controls. The choice of other control groups, such as a group of women who had hysterectomies for indications other than uterine myomas, could be criticized also because the controls would be a selected group and would have conditions with potentially similar etiologic correlates. With reference to confounding, socioeconomic status, measurement of body weight, and reproductive and hormonal correlates of uterine myomas did not explain the results.
The intake of green vegetables, fruit, and fish may be a general indicator of more health-oriented attitudes toward diet and other lifestyle habits. However, greater attention to health may also favor the diagnosis of myomas, producing an underestimate of the real association. Social determinants of gynecologic surgery also are well recognized. Surgery for myomas or other benign neoplastic conditions, such as benign breast disease and ovarian cysts, is more frequent in more educated women of higher social classes12 and may reflect the greater attention that better-educated women pay to relatively minor health problems.
Hormonal factors are a potential link between diet and uterine myomas because the risk may be increased by exposure to unopposed estrogen.1 Along this line of reasoning, ever smoking, which has been associated with lower concentrations of estradiol,13 was inversely related to the risk of myomas.14 The association between levels of estrogen, diet, and breast and endometrial cancers15,16 also may help us understand the effect of dietary factors on the risk of uterine myomas. For breast and endometrial cancers, a direct association with the frequency of consumption of meat and ham was observed in this Italian population, whereas protection was conferred by high intake of vegetables and fruits.16,17 Thus, a number of dietary indicators or correlates seem to be shared by breast and endometrial cancers and uterine myomas.
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