Safety profile of a fixed formulation containing 2 mg estradiol valerate and 2 mg dienogest (Lafamme (R)) for continuous combined hormone replacementtreatment in postmenopausal women

The fixed formulation containing 2 mg estradiol valerate and 2 mg dienogest (Lafamme(R)) has been developed for continuous hormone replacement therapy (HRT). In this paper, the clinical safety data on this drug are summarized with regard to endometrial safety, bleeding pattern, efficacy and tolerabi lity. For the various clinical trials, healthy postmenopausal women (phase I studies) and postmenopausal women with a clinical indication for hormone replacement therapy (HRT) (phases II and III) were enrolled. All women who had started treatment were included in the safety assessment (safety popula tion). At least 22,920 treatment cycles of 28 days each were observed, whic h is equivalent to 1,763 woman-years. Adverse events (AEs) documented in al l studies were assessed according to conventional criteria. In two key stud ies, endometrial biopsies were performed. With regard to endometrial safety , the histological findings showed an atrophic endometrium in nearly 90% of the women. No hyperplastic endometrium was found in any of the women. A to tal of 1,834 women treated with Lafamme(R) experienced AEs which were asses sed as related to the study medication. Predominant were AEs concerning the reproductive system (40.7% of the women), the central and peripheral nervo us systems (10%) and the gastrointestinal system (6.7%). In total, 116 seri ous adverse events (SAEs) were documented, of which 29 were assessed as bei ng related to the treatment. Both the kinds and the rates of adverse reacti ons documented for Lafamme(R) are already recognized in, and characteristic of, orally administered estrogen/progestogen combinations for continuous H RT (C) 2001 Prous Science. All rights reserved.