Lifetime Weight History and Endometrial Cancer Risk by Type of Menopausal Hormone Use in the NIH-AARP Diet and Health Study

Abstract

Obesity and menopausal estrogen therapy are established risk factors for endometrial cancer. However, the joint effects of obesity and menopausal hormone therapy on endometrial cancer risk are incompletely understood. We addressed this issue in a cohort of 103,882 women ages 50 to 71 years at baseline in 1995 to 1996. During a median of 4.6 years, which contributed to a total of 455,304 person-years of follow-up through 2000, 677 cases of endometrial cancer were ascertained. Both baseline body mass index (BMI) and adult weight gain were associated with increased endometrial cancer risk. The multivariate relative risk (RR) comparing obese with normal weight women (BMI >30 versus <25 kg/ m 2 ) was 3.03 [95% confidence interval (95% CI), 2.50-3.68]. Compared with women with stable weight (gained or lost <5 kg) between age 18 and baseline, women who gained z20 kg had a RR of 2.75 (95% CI, 1.96-3.86). Menopausal hormone therapy significantly modified the relations of BMI (P interaction < 0.001) and adult weight gain (P interaction = 0.004) to endometrial cancer risk. Compared with normal weight, the RRs for obesity were 5.41 (95% CI, 4.01-7.29) among women who never used menopausal hormone therapy, 2.53 (95% CI, 1.21-5.30) among former menopausal hormone therapy users, and 1.44 (95% CI, 1.00-2.05) among current users. Compared with a stable weight between age 18 and baseline, the RRs for weight gain of z20 kg among never users and ever users of menopausal hormone therapy were 5.35 (95% CI, 3.01-9.52) and 1.43 (95% CI, 0.96-2.15), respectively. We conclude that both current adiposity and adult weight gain are associated with substantial increases in the risk of endometrial cancer, with relations particularly evident among never users of menopausal hormone therapy. (Cancer Epidemiol Biomarkers Prev 2007;16(4):723 -30)

Body Mass and Endometrial Cancer Risk by Hormone Replacement Therapy and Cancer Subtype

“…The association between BMI and risk of endometrial cancer among women who never used HT was linear across the entire range of BMI examined. Although these findings are generally similar to other studies that examined risk among never-users (8,31,34), these studies did not examine the finer strata of normal weight women or the interactions by HT were not obvious (32). In contrast, BMI was not clearly related to endometrial cancer risk among ever E + P users.…”

“…As indicated in a comprehensive review (5), whether the positive relationship between BMI and endometrial cancer exists at lower BMI levels has been unclear. In the European Prospective Investigation on Cancer study (31), obesity (BMI z 30) was associated with increased risk but overweight (BMI, 25-29 versus <25) was not, whereas in the NIH-AARP Diet and Health Study (8), overweight women (BMI, 25-29 versus <25) were at increased risk. Our results for the overweight category were of borderline significance (BMI, 25-29.9; RR, 1.40; 95% CI, 0.99-1.96) compared with healthy weight women (defined as BMI of 22.5-25).…”

“…Most of the 57 case-control and 24 prospective cohort analyses published to date (6,8,(31)(32)(33) show an unequivocal association between BMI and endometrial cancer. As indicated in a comprehensive review (5), whether the positive relationship between BMI and endometrial cancer exists at lower BMI levels has been unclear.…”

“…Previous studies suggest that progestins in estrogen plus progestin (E + P) attenuate risks associated with estrogen, but that this protection may vary by body fatness (7). A recent prospective study found that obese women who exclusively used E + P had a borderline, nonsignificant higher risk of endometrial cancer compared with normal weight women (8).…”

Body Mass Index, Hormone Replacement Therapy, and Endometrial Cancer Risk: A Meta-Analysis

“…Three studies (33,34,39) stratified analyses according to never versus ever HRT use and the Million Women Study (52) reported the number of cases in women on combined HRT across BMI categories giving an analyzed total cases of 2,253. Associations were stronger for never users compared with ever users of any HRT preparation (Fig.…”