Comparison of efficacy and local tolerability of estradiol metered-dose transdermal spray to estradiol patch in a network meta-analysis

<b>Objectives:</b> Transdermal hormone replacement therapy is preferred for menopausal vasomotor symptoms. Our purpose was to compare the efficacy and local tolerability of a patch and a metered-dose transdermal spray that have never been directly compared. <b>Method:</b> The relative change in the number of hot flushes between baseline and week 12 was selected as an efficacy indicator and the frequency of local skin reactions as a tolerability indicator. A network meta-analysis was performed to compare efficacy. Application site tolerability was compared descriptively. <b>Results:</b> Overall 46 studies were identified. In the efficacy analysis, eight active treatment arms and a placebo arm were determined based on the estradiol daily dose (from 14 μg to 50 μg). All but one had a significantly higher effect on relative change in the number of hot flushes than did the placebo. We found no evidence for different efficacy of the patch and the metered-dose transdermal spray. The latter performed better in terms of local skin reactions. <b>Conclusion:</b> The patch and the metered-dose transdermal spray seem to have the same efficacy on vasomotor symptoms in estradiol hormone replacement. The local tolerability of the metered-dose transdermal spray is favorable.