Comparison of Hormone Levels in Nipple Aspirate Fluid of Pre- and Postmenopausal Women: Effect of Oral Contraceptives and Hormone Replacement

Abstract

The effects of ovarian suppression by oral contraceptives as well as hormone replacement therapy were studied on hormone levels and on products of hormone action in nipple aspirate fluid (NAF) from breasts of pre- and postmenopausal women. Multiple samples per subject revealed high consistency (intraclass correlation coefficients) for all products measured. Compared with premenopausal women, NAF progesterone was much lower in postmenopausal women, but NAF androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate concentrations were not different. With oral contraceptive use, estradiol, estrone sulfate, and progesterone levels were similarly lower in serum and NAF. In postmenopausal women, NAF estradiol and estrone sulfate were not significantly less than those in premenopausal women, nor were epidermal growth factor or cathepsin D levels, but IL-6 was elevated. Despite corresponding changes in hormones in serum and NAF over time, correlations based on simultaneous sampling were not significant. It is concluded that: 1) potential precursors of estradiol remain at comparable levels in the breast after menopause; 2) local synthesis is important for maintenance of estradiol levels in NAF of postmenopausal women but less important for progesterone; and 3) changes in the serum parameters are accurately reflected in NAF, but only after a matter of days. These findings provide additional validation for the physiological relevance of NAF hormone levels as potential breast cancer risk markers.

Soy Isoflavones for Breast Cancer Risk Reduction—Response

“…When results in the present study are compared with our previous publications, it is true that estradiol concentrations in NAF have been consistently, but not significantly, lower in postmenopausal women than in premenopausal women. The number of postmenopausal subjects in our 2010 and 2004 publications was 18 in each (1,2). The higher postmenopausal NAF estradiol concentrations in the present study (3), although unexpected, can be attributed to chance when the sample size is small, as it was here, with 8 NAF-yielding postmenopausal subjects in the soy group.…”

Dietary Intake of Lactose as a Strong Predictor for Secretor Status of Nipple Aspirate Fluid in Healthy Premenopausal Nonlactating Women

“…Several studies have attempted to link NAF secretor status with breast cancer risk, but with mixed results (16,20). This is not surprising based on our observations that some of the reproductive factors associated with being secretors increase whereas others decrease the risk for breast cancer.…”

Patterns of Sex Steroid Hormones in Nipple Aspirate Fluid during the Menstrual Cycle and after Menopause in Relation to Serum Concentrations

“…One possibility is that, even in premenopausal women, local biosynthesis of estrogens in the breast contributes significantly to the levels in the breast. There is good evidence of local biosynthesis of estrogens in breast tissue of postmenopausal women: a number of studies have shown that the steroid precursors required for estradiol synthesis are present in breast tissue (6,7), and high estrogen concentrations exist in NAF (8) and breast tissue (4)(5)(6)9) of postmenopausal women in the presence of dramatically lower concentrations of estrogens in plasma.…”