Randomized comparison of intranasal and transdermal estradiol

Abstract

Objective: To compare the efficacy and patient acceptability of intranasal versus transdermal 17β-estradiol (E2) delivery systems for postmenopausal symptoms. Methods: Postmenopausal women were randomly assigned to intranasal 17β-E2, 300 μg daily ( n = 176) or transdermal 17β-E2 (delivering 50 μg/day), two patches per week ( n = 185) for 12 weeks, followed by a 4-week period with the alternate treatment. Efficacy was compared between groups using the Kupperman Index and vasomotor symptoms at week 12. Patient acceptability was compared by patient choice of administration route and by questionnaire at week 16. Results: Intranasal and transdermal therapy produced significant reductions in the Kupperman Index and in the occurrence of hot flushes and night sweats at week 12. Alleviation of climacteric symptoms was statistically equivalent in the two treatment groups ( P < .001). The difference between groups in the Kupperman Index score of −0.5 ± 0.9 (95% confidence interval −2.3, 1.3) was within the predetermined interval of equivalence. Both therapies were well tolerated with similar adverse event rates, except for moderate and severe mastalgia which was significantly less frequent with intranasal E2 (7.2%) than with the patch (15.5%, P = .02). Sixty-six percent of patients chose to continue the intranasal therapy and 34% the transdermal therapy ( P < .001). Satisfaction was greater with intranasal therapy at week 16 ( P < .001). Conclusion: Intranasal and transdermal estrogen delivery systems had equivalent efficacy and similar safety profiles. Intranasal therapy was the patients’ choice for long-term treatment.