Objective: To evaluate impact of different postmenopausal hormone therapy (HT) regimens and raloxifene on mammographic breast density.

Design: Open, randomised, comparative clinical trial.

Setting: Women were recruited through local newspapers and posters. They were examined at the Departments of Haematology, Gynaecology, and Radiology in a University Hospital.

Population: A total of 202 healthy postmenopausal women between the age of 45 and 65 years.

Methods: Women were randomly assigned to receive daily treatment for 12 weeks with tablets containing low-dose HT containing 1 mg 17 beta-estradiol + 0.5 mg norethisterone acetate (NETA) (n = 50), conventional-dose HT containing 2 mg 17 beta-estradiol and 1 mg NETA (n = 50), 2.5 mg tibolone (n = 51), or 60 mg raloxifene (n = 51). Mammographic density was determined at baseline and after 12 weeks by an automated technique in full-field digital mammograms.

Main outcome measures: Mammographic density was expressed as volumetric breast density estimations.

Results: Mammographic breast density increased significantly and to a similar degree in both the conventional- and low-dose HT groups. A small reduction in mammographic breast density was seen in the raloxifene group, whereas those allocated to tibolone treatment only showed minor changes.

Conclusions: Our findings demonstrated a significant difference in impact on mammographic breast density between the regimens. Although these results indicate a differential effect of these regimens on breast tissue, the relation to breast cancer risk remains unresolved.