Therapeutic value and long-term safety of pulsed estrogen therapy

Objectives: To demonstrate equivalent efficacy for menopausal symptoms betw een Aerodiol((R)) nasal spray and reference oral estradiol therapy, and to investigate the endometrial safety and tolerability of Aerodiol in the long term. Methods: The efficacy of Aerodiol 300 mug, once daily, was compared with oral estradiol 2 mg/day in a randomized, double-blind trial. A statist ical test of noninferiority was performed on the mean absolute Kupperman in dex (KI) obtained after 14 and 23 weeks of the two treatments. Long-term sa fety was assessed in a 1-year open-label study. The initial Aerodiol dose w as 300 mug/day, and was adjusted if required. Endometrial biopsies were obt ained at inclusion and at the end of the trial and examined independently b y two pathologists. Results: In the equivalence trial, the KI improved simi larly in the Aerodiol group (n = 317) and the oral estradiol group (n = 342 ). Aerodiol was shown statistically to be at least as effective as oral the rapy (P < 0.001), but the incidences of mastalgia and withdrawal bleeding w ere significantly lower in the Aerodiol group (P < 0.01 and P < 0.001, resp ectively). In the long-term safety trial (n = 408), the rate of Aerodiol tr eatment continuation at 12 months was 85%, and there was no incidence of en dometrial hyperplasia or cancer. Aerodiol dose adaptation was performed by 29% of women. Conclusions: Aerodiol was shown to have equivalent efficacy t o reference oral estradiol therapy, but with better gynaecological acceptab ility. The endometrial safety of Aerodiol was confirmed in the long term, a nd the ability to adjust the dosage easily was of benefit to a substantial proportion of women. (C) 2001 Elsevier Science Ireland Ltd. All rights rese rved.