Trimegestone: expanding therapeutic choices for the treatment of the menopause

Trimegestone is a novel norpregnane progestin, which has a potent progester one receptor and very low androgen receptor affinities but no detectable af finity to oestrogen receptor. Trimegestone has been developed for use in co njunction with oestrogen for postmenopausal hormone replacement therapy (HR T). The dose of trimegestone required for endometrial safety was optimised in a dose ranging study. Oral trimegestone was administered at 0.05, 0.1, 0 .25 and 0.5 mg/day, days 15 - 28 along with continuous oral micronised oest radiol at 2 mg daily. The majority of women in the four dose groups experie nced relief of climacteric symptoms by the end of the third treatment cycle . The incidence of pre-menstrual tension-like symptoms was low and did not differ between the four dose groups. After 6 months of treatment, the bleed ing pattern showed a clear dose-dependent modulation such that the higher t he dose of trimegestone administered the more predictable was the day of on set of bleeding and the shorter and lighter the bleeding episodes became. T his was further confirmed in another study comparing trimegestone in 0.5 an d 0.25 mg doses to norethisterone acetate, where women on the 0.5 mg dose e xperienced more favourable bleeding pattern compared with the lower dose of 0.25 mg or to norethisterone acetate. In the dose ranging study, 96% of en dometrial specimens obtained at the end of the study had secretory changes. The lipoprotein profile measured at baseline, 3 and 6 months during the do se ranging study confirmed the fact that trimegestone, irrespective of the dose, did not negate the beneficial effects of oestrogen on lipids. Conclus ion: trimegestone is an effective and well-tolerated new progestin, which d oes not negate the beneficial effects of oestrogen on lipids.