Summary of CHMP’ s Opinion The CHMP noted that the applicant had provided the following arguments to support the endometrial safety of Activelle 0.5 mg/ 0.1 mg: a. the proliferative effect of unopposed oestrogens on the endometrium is dose-dependant, b. this proliferative effect of unopposed oestrogens is time-dependant, especially for high oestrogen doses, c. continuous combined therapy over long duration is more protective that sequential therapy in the prevention of endometrial hyperplasia or carcinoma.