Among women whose LMPs occurred at age 45 or older, the risk for endometrial cancer also increased with increasing adult BMI (Table 2) but not to the same extent as that seen in women whose LMPs occurred at a younger age. Change in BMI from age 18 to adult showed a similar but attenuated pattern to that in women with an earlier age at LMP.
Because the age at LMP variable in this study combines women who currently are menstruating with women who have stopped menstruating, we further stratified our analyses by menopausal status (Table 3). With one exception, the analysis showed that the risk for endometrial cancer increased with increasing BMI. Among women with LMP before age 45, the risk estimates were similar regardless of menopausal status. Among women with LMP at age 45 and older, being overweight or obese had little effect on endometrial cancer risk for premenopausal or perimenopausal women, whereas risk estimates for postmenopausal women were significantly elevated.
In summary, endometrial cancer risk was increased for women whose BMIs were class I or II–III obese as adults, at age 18, or at both periods. In addition, risk increased for women who were normal weight at age 18 and classified as overweight or obese as adults. This study found a statistically significant interaction between BMI and age at LMP and showed that women who had their LMPs before age 45 had the highest risk of developing endometrial cancer associated with being overweight or obese.
The strengths of this study include a large number of endometrial cancer cases, a population-based methodology, and a review of the original pathology diagnosis by a panel of experts. Previous studies of endometrial cancer among younger women had fewer cases of cancer and were conducted at single facilities.11,19 For example, Henderson and others had 31 patients who weighed at least 190 lb each, and La Vecchia and others had 29 premenopausal patients who had BMIs of 25 or higher.11,19 A separate panel of expert pathologists assessed diagnoses independent of the community pathologists, thereby reducing potential misclassification. Previous analyses from the Cancer and Steroid Hormone study indicated that diagnoses of endometrial cancer made by community pathologists were not as reproducible as were ovarian cancer diagnoses.22
The limitations of this study are that the data were collected in the early 1980s, that the measures for determining BMI were self-reported, and that the measures for menstrual history were self-reported. Although we acknowledge the potential concern about the vintage data, weight and height have been longstanding measures for overweight assessment and the questions used to obtain self-reported information have changed little since data collection for the Cancer and Steroid Hormone study.28 Additionally, we know of no physiologic or clinical trends that would change the relationship between BMI and endometrial cancer. The BMIs for women in the case group may have been lower than expected because of possible weight loss from cancer treatment or the cancer itself, but the questionnaire attempted to minimize this bias by asking for “usual adult weight.” Because bias and unreliability in self-reports increase directly with the magnitude of overweight status,29 more recent studies address the potential biases related to self-reported current weight with weight and height verification using scales, tape measures, and trained personnel.5,15 We were unable to verify the self-reported weight and height. In addition, the study did not collect other anthropometric measures such as waist or hip circumference or subscapular measures. Furthermore, previous research has shown that overweight women with predominant central adiposity may be at greater risk for endometrial cancer than overweight women with predominant gynecoid adiposity.3 We had no information on adipose distribution. Age at LMP may be biased because bleeding secondary to the cancer could not be distinguished in the analysis from menstrual bleeding. This may have yielded a shorter time since LMP, an older LMP age, and the misclassification of women who were perimenopausal or naturally menopausal as premenopausal. Given the magnitude of the relative risks, these limitations are unlikely to have affected the findings materially.
Postmenopausal women who report a younger age at LMP and, therefore, a younger age at menopause may be more likely to have irregularities in their menstrual cycles, which may be related to endocrine abnormalities.1 Some of the endocrine abnormalities related to endometrial cancer risk are the same as those for polycystic ovary syndrome, such as chronic hyperinsulinemia, low insulin-like growth factor binding protein-1, low sex hormone-binding globulin, elevated androgens, and lack of luteal-phase progesterone production.1 Kaaks and others hypothesize that the presence of menstrual cycle irregularities or elevated androgen levels may change the relationship between BMI and endometrial cancer among premenopausal women because obesity causes elevated androgens and chronic anovulation.1 Women in our study with class II–III obesity might be more likely to have chronic anovulation leading to extended menstrual cycles and to report early menopause more often. We do not have the data to quantify chronic anovulation.
Our study agrees with other studies—being overweight or obese increases endometrial cancer risk, and the risk increases as BMI increases. One earlier study showed that being overweight in childhood or adolescence increased the risk for endometrial cancer,30 but that study used different BMI definitions and results may not be comparable. Another study that looked at BMI at different ages reported no effect,31 but a small sample size may have contributed to this conclusion. Weight loss has been shown to bring endocrine levels to a normal state to help menstrual cycles return to normal.1
The rapidly increasing prevalence of overweight and obese children, adolescents, and adults in the United States32,33 is of public health and clinical concern because obesity is a risk factor for several chronic disease conditions, including endometrial cancer. Current trends show that, although endometrial cancer trends are decreasing in women older than 50 years, they are increasing in women younger than 50 years.34 The high risk that we observed in this study underscores the need for clinicians to counsel young women on the benefits of maintaining or achieving a normal weight throughout childbearing years and before entering menopause. Maintaining or achieving normal weight affects the risk for endometrial cancer, other reproductive functions, and other chronic conditions, including diabetes and cardiovascular disease.35
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