Endometrial safety and tolerability of AERODIOL (R) (intranasal estradiol)for 1 year

Objective: the purpose of this study was to assess the endometrial safety a nd patient acceptability of a pulsed estrogen therapy provided by S21400 (i ntranasal 17 P-estradiol) in the treatment of postmenopausal symptoms. Desi gn: postmenopausal women (n = 408) entered an open-label, community based, multicentre trial. Patients received S21400 plus sequential (> 90% of patie nts) or continuous progestogen. Treatment was initiated with a standard dai ly dose of 300 mug but dose adaptation was possible every 3 months from 150 to 600 mug daily. Endometrial biopsies were performed at entry and at 12 m onths, and bleeding patterns were recorded at 3-monthly intervals throughou t the trial. Results: 71% of patients received 300 mug per day S21400 throu ghout the study, 3% had their dose decreased, 19% had their dose increased and 7% had their dose both decreased and increased. Three hundred and eleve n biopsies were obtained after 12 months of treatment, there were no cases of endometrial hyperplasia. The 95% confidence interval [CI] for the rate o f incidence was 0-1.2%. Cyclical bleeding occurred in 82% of sequential tre atment cycles. Unexpected bleeding occurred in 5% of the treatment cycles. Presence of unexpected bleeding varied according to the treatment regimen, 15 and 4% of the cycles with combined continuous and sequential regimen, re spectively. Unexpected bleeding was mostly spotting. Nasal treatment was we ll accepted. Nasal symptoms (itching sensation, rhinorrhea and sneezing) we re mostly mild in intensity and they led to treatment withdrawal in approxi mately 3% of patients. The rate of treatment continuation was 85% at 1 year . Conclusions: S21400, in combination with continuous or sequential progest ogen, exhibits good endometrial safety and patient acceptability in postmen opausal women. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.