Background: The benefit of oestrogen therapy for menopause symptoms is well recognised. However, the means of delivery currently available have disadvantages, including variable bioavailability, intestinal and hepatic first-pass effects, and dermatological reactions. An intranasal 17beta-oestradiol spray, S21400, which bypasses such drawbacks, has been developed. We studied the efficacy and tolerability of S21400 in the treatment of postmenopausal symptoms.
Methods: In this double-blind study, 420 postmenopausal women were randomly allocated to receive intranasal placebo or S21400 in doses of 100 microg, 200 microg, 300 microg, or 400 microg, or oral oestradiol valerate in doses of 1 mg or 2 mg, daily for 12 weeks. The primary outcomes were the Kupperman Index (KI) and the incidence of hot flushes. Tolerability assessments included rhinoscopy and ciliary function tests.
Findings: S21400 dose-dependently decreased KI (p<0.001), with a lowest effective dose of 300 microg/day at 4 weeks (p<0.05) and 200 microg/day at 12 weeks (p<0.01). The incidence of hot flushes decreased by a maximum of 75% (S21400 lowest effective dose 200 microg/day at 4 weeks and 100 microg/day at 12 weeks). S21400 increased serum oestradiol exposure dose-dependently, to concentrations similar to those achieved with oral oestradiol 1-2 mg, with lower intra-patient and inter-patient variability. There was no significant difference in ear, nose, and throat function or adverse events between the S21400 and the placebo or oral oestradiol groups, except for a greater incidence of sneezing and application site reaction (99% mild or moderate) in the S21400 groups. S21400 was thought to be effective and convenient by the patients, and compliance was high.
Interpretation: Intranasally administered 17beta-oestradiol is significantly better than placebo; its effectiveness at reducing menopausal symptoms is similar to that of oral oestradiol and is also well-tolerated. Intranasal administration avoids first-pass metabolism and provides a reproducible, easily adjustable dosing mechanism that represents a new option for hormone replacement therapy.