Reversal of Relation Between Body Mass and Endogenous Estrogen Concentrations With Menopausal Status

For more than a decade, results from published studies have indicated that the risk of breast cancer may be lower among heavy premenopausal women than among their less obese counterparts (1-8). In heavy postmenopausal women, however, this risk is either increased or unchanged in comparison with non-obese postmenopausal women (9,10). The mechanism explaining this reversal in risk is unknown, although theoretical explanations have been proposed. Obese postmenopausal women may have ele-vated risk from higher levels of circulat-ing estrogens secondary to increased conversion of androgen to estrogen in adipose tissue (11) and a higher propor-tion of bioavailable estrogen due to the low levels of sex hormone-binding globulin (SHBG) (12,13). Obese pre-menopausal women may exhibit a greater degree of anovulation, resulting in lower levels of both progesterone and estradiol, lower breast cell division rates, and, consequently, a lower risk of breast cancer (13-15). We had the opportunity to evaluate the relation of body mass and hormonal profiles in a group of 195 community and 103 hospital control subjects from a study of endometrial cancer described elsewhere (16,17). Results of both con-trol groups were similar; therefore, the two groups were combined. Body mass index (BMI) (kg/m2) was calculated from reported current height and weight obtained during an interview. Fasting serum samples were generally drawn within 1 month of interview and prior to surgery for benign endometrial condi-tions for the hospital control subjects. Serum was extracted and separated by celite column chromatography. Estrone, estradiol, androstenedione, estrone sul-fate, progesterone, and SHBG were measured by radioimmunoassay (RIA). An enzymatic hydrolysis was performed before separation for estrone sulfate. Al-bumin-bound estradiol was assessed using ammonium sulfate precipitation, and percent-free estradiol was estimated with an equilibrium dialysis assay. The amount of free or albumin-bound estra-diol was calculated by multiplying the total estradiol concentration by the per-cent in the other fractions. Serum was