Dose-ranging studies of a novel intranasal estrogen replacement therapy

Abstract
Objectie: To study the efficacy and tolerability of Aerodiol®, a novel intranasal estradiol spray, and to determine
an appropriate dose range. Methods: An exploratory, parallel-group, dose-finding study was followed by a large-scale,
double-blind, placebo-controlled study. In the exploratory study, 134 postmenopausal women were allocated to
receive a daily dose of 100 – 900 g of Aerodiol for 12 weeks. Efficacy was determined by an overall assessment of
estrogenization. In the placebo-controlled study, 420 postmenopausal women were randomized to receive 100, 200,
300, or 400 g of Aerodiol, or oral estradiol 1 or 2 mg, or placebo, daily for 12 weeks. Efficacy was assessed by the
Kupperman Index and the number of hot flushes per day after 12 weeks. Results: In the exploratory study, the level
of estrogenization was sufficient for 23% of women in the 100 g/day group, excessive for 36% of the 900 g/day
group, and good for more than 80% of women receiving 200 – 600 g/day. In the placebo-controlled study, the
Kupperman Index at week 12 was significantly lower than placebo (P 0.01) for all Aerodiol groups except the 100
g/day group. The efficacy of Aerodiol 300 g/day was similar to oral estradiol 2 mg/day. The variability in exposure
to estradiol was lower with Aerodiol than with oral estradiol. Aerodiol therapy was well tolerated in both studies.
Premature withdrawals were approximately equally distributed among treatment groups in the placebo-controlled
study. Conclusions: Aerodiol was effective in reducing climateric symptoms at doses between 100 and 600 g/day.
Treatment was well tolerated and well accepted. A dose of 300 g/day is recommended for initiating hormone
replacement therapy. © 2001 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Dose-ranging studies; Intranasal estrogen replacement therapy

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