Effects of drospirenone and norethisterone acetate combined with estradiol on mammographic density and proliferation of breast epithelial cells-A prospective randomized trial.

ABSTRACT

OBJECTIVE: There are no previous data on the influence of drospirenone (DRSP) in combination with estradiol (E2) on the breast in postmenopausal women. The objective of this study was to evaluate the effect of DRSP or norethisterone acetate (NETA) in continuous combination with E2 on two surrogate markers for breast cancer - mammographic breast density and proliferation of breast epithelial cells - in healthy postmenopausal women. STUDY DESIGN: 120 healthy, naturally postmenopausal women were randomized to either 2 mg of DRSP or 0.5 mg of NETA in continuous combination with 1 mg of oral E2. The women underwent mammography and fine-needle aspiration biopsy of the breast at baseline and after six months of treatment. MAIN OUTCOME MEASURES: Digitized mammographic breast density and breast cell proliferation. RESULTS: There was a significant increase in mammographic breast density after treatment in both groups (median increase 5.5% for E2/DRSP and 2.3% for E2/NETA, respectively, p < 0.001), but with no significant difference between groups. The proliferation of breast epithelial cells also increased in both groups (p < 0.001, respectively), with a significantly larger increase in the E2/DRSP group than in the E2/NETA group (2.5% versus 0.7%, respectively, p < 0.05). Systolic blood pressure had decreased significantly after 6 months of treatment in the E2/DRSP group (p < 0.05) but not in the E2/NETA group. CONCLUSIONS: Breast density increased to a similar degree with E2/DRSP and E2/NETA. Proliferation of breast epithelial cells also increased significantly in both groups but was slightly more pronounced in the E2/DRSP group.