Objective: To compare the effects of tibolone, estriol and conventional hormone replacement therapy (HRT) on mammographic parenchymal density in postmenopausal women.
Design and setting: This was a non-randomised, prospective, longitudinal, comparative study conducted at two specialist outpatient clinics in Chile.
Patients and participants: 210 non-obese, postmenopausal women aged <65 years with a normal mammogram at baseline.
Methods: Participants received one of seven oral HRT regimens for 1 year. Treatments (daily doses) were: (i) estradiol 2mg; (ii) estradiol 2mg plus sequential medroxyprogesterone acetate (MPA) 5mg for 10 to 16 days/cycle; (iii) estradiol 2mg plus continuous MPA 2.5mg; (iv) combined equine estrogens (CEE) 0.625mg; (v) CEE 0.625mg plus sequential MPA 5mg; (vi) estriol 2mg; or (vii) tibolone 2.5mg. In addition, an age-matched group of 30 untreated control individuals was studied.
Results: Increased mammographic density occurred in 67, 57, 30, 43 and 27% of patients receiving regimens (i) to (v), respectively. No patients receiving tibolone or estriol experienced increases (both p < 0.05 vs conventional HRT). Overall, 67 of 210 treated patients [31.9%; 95% confidence interval (CI) 25.7%, 38.6%] experienced increases, compared with one of 30 controls (3.3%; 95% CI 0%, 17.2%).
Conclusions: Neither the tissue-specific agent tibolone nor the short-acting estrogen estriol induced any breast density increase. Increased breast density was more frequent with regimens containing estradiol than CEE, and with unopposed rather than opposed regimens. Tibolone (or estriol, if suitable) may be a preferable HRT for women in whom this is a concern.