The effect of a change in the dose of trimegestone on the pattern of bleeding in estrogen-treated post-menopausal women: 6 month extension of a dose-ranging study.

BACKGROUND Abnormal bleeding pattern is one major reason for non-compliance with hormone replacement therapy (HRT) in post-menopausal women. We have previously documented that the dose of trimegestone is the main determinant of the pattern of bleeding in women treated with estradiol (E(2)) and sequential combined trimegestone administered in four doses. The objectives of this study were to test the effect of changing the dose of trimegestone and the duration of treatment on the pattern of bleeding in these women who then entered a 6 month extension phase where a single dose of trimegestone was given sequentially combined with E(2). METHODS The menstrual diaries of 134 post-menopausal women who completed a dose-ranging study of trimegestone and then entered a 6 month extension phase were analysed. In the 6 month extension study, all women were given one dose of trimegestone (0.25 mg) in a sequential fashion (day 15-28) combined with continuous E(2) (2 mg/day). RESULTS Women who had received trimegestone 0.25 mg/day during the first 6 months experienced no change in the bleeding pattern in the 6 month extension. Women who had been treated with 0.5 mg/day dose experienced earlier onset, and more prolonged bleeding (P < 0.0001) following the change to 0.25 mg/day. Women who previously received trimegestone doses of 0.05 and 0.1 mg experienced a later onset of bleeding, which was lighter and of shorter duration (P < 0.001) during the extension phase as compared with the first 6 months. CONCLUSION The dose of trimegestone, and not the duration of treatment, appears to be the important determinant of the pattern of bleeding in post-menopausal women on this HRT regimen.