CASE-CONTROL STUDY OF ENDOGENOUS STEROID-HORMONES AND ENDOMETRIAL CANCER

Background: It has been suggested that identified risk factors for end ometrial cancer operate through a single etiologic pathway, i.e., expo sure to relatively high levels of unopposed estrogen (estrogen in the absence of progestins). Only a few studies, however, have addressed th is issue directly. Purpose: We assessed the risk of developing endomet rial cancer among both premenopausal and postmenopausal women in relat ion to the circulating levels of steroid hormones and sex hormone-bind ing globulin (SHBG). The independent effect of hormones was assessed a fter adjustment for other known risk factors. Methods: The data used i n the analysis are from a case-control study conducted in five geograp hic regions in the United States. Incident cases mere newly diagnosed during the period from June 1, 1987, through May 15, 1990. The case pa tients, aged 20-74 years, were matched to control subjects by age, rac e, and geographic region. The community control subjects were obtained by random-digit-dialing procedures (for subjects 20-64 years old) and from files of the Health Care Financing Administration (for subjects greater than or equal to 65 years old). Additional control subjects wh o were having a hysterectomy performed for benign conditions were obta ined from the participating centers. Women reporting use of exogenous estrogens or oral contraceptives within 6 months of interview were exc luded, resulting in 68 case patients and 107 control subjects among pr emenopausal women and 208 case patients and 209 control subjects among postmenopausal women. The hormone analyses were performed on blood sa mples obtained from case patients or from hysterectomy control subject s before surgery. The odds ratios (ORs) and 95% confidence intervals ( CIs) were estimated by use of an unconditional logistic regression ana lysis after we controlled for matching variables and potential confoun ders. All P values were two-sided. Results: High circulating levels of androstenedione were associated with 3.6-fold and 2.8-fold increased risks among premenopausal and postmenopausal women, respectively, afte r adjustment for other factors (P for trend = .01 and < .001, respecti vely). Risks related to other hormone fractions varied by menopausal s tatus. Among postmenopausal women, a reduced risk was associated with high SHBG levels and persisted after adjustment was made for obesity a nd other factors (OR = 0.51; 95% CI = 0.27-0.95). High estrone levels were associated with increased risk (OR = 3.8; 95% CI = 2.2-6.6), alth ough adjustment for other risk factors (particularly body mass index) diminished the effect (OR = 2.2; 95% CI = 1.2-4.4). Albumin-bound estr adiol (E(2)), a marker of the bioavailable fraction, also remained an important risk factor after adjustment was made for other factors (OR = 2.0; 95% CI = 1.0-3.9). In contrast, high concentrations of total, f ree, and albumin-bound E(2) were unrelated to increased risk in premen opausal women. In both premenopausal and postmenopausal groups, risks associated with obesity and fat distribution were not affected by adju stment for hormones. Conclusion: High endogenous levels of unopposed e strogen are related to increased risk of endometrial cancer, but their independence from other risk factors is inconsistent with being a com mon underlying biologic pathway through which all risk factors for end ometrial cancer operate. Implications: Further research should focus o n alternative endocrinologic mechanisms for risk associated with obesi ty and body fat distribution and for the biologic relevance of the inc reased risk associated with androstenedione in both premenopausal and postmenopausal disease.