Objective: To compare the effects of transferring from low-dose, transdermal estrogen to raloxifene with a phase of alternate-day raloxifene therapy with or without low-dose transdermal estrogen on patient satisfaction, endometrial changes, and overall safety in healthy, postmenopausal women previously administered hormone therapy.
Design: Healthy postmenopausal women were randomized to one of two treatment groups: raloxifene + low-dose, transdermal estrogen (RLX+E) and raloxifene + placebo (RLX+P). The study consisted of four equal phases of 8 weeks each: Phase I (low-dose, transdermal estrogen, 25 microg/day), phase II (double-blind, alternate-day raloxifene 60 mg + low-dose, transdermal estrogen or placebo patch), phase III (alternate-day RLX 60 mg + placebo patch), and phase IV (raloxifene 60 mg/day + placebo patch). Primary endpoints included patient satisfaction, endometrial changes, overall safety, and quality of life.
Results: Sixty women were randomized in this study. Baseline characteristics were similar between the two treatment groups. For the primary analysis (phase II to phase IV, inclusive), there were no significant differences between the therapy sequences for patient satisfaction, endometrial thickness, or quality of life. In the therapy comparison phase (phase II), mean change in patient satisfaction score was 3.2 mm (SD = 16.2) for RLX+E and -17.1 mm (SD = 38.7) for RLX+P (P = 0.003), whereas mean change in endometrial thickness was 0.8 mm (SD = 2.7) for RLX+E and -0.9 mm (SD = 1.5) for RLX+P (P = 0.021). The RLX+P group showed a significantly greater increase in vasomotor events, with a mean score change of 1.7 (SD = 1.9) compared with a mean score change of 0.2 (SD = 1.8) in the RLX+E group (P = 0.005). There were no statistically significant differences between the two therapy groups in the reporting of treatment-emergent adverse events.
Conclusion: Gradual conversion to raloxifene from low-dose estrogen, with a progression from 60 mg every alternate day to 60 mg/day, is a viable option in potentially symptomatic, postmenopausal women.