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In the zebrafish model, it was discovered that BMAL1 can bind to crucial E-box elements in the VEGF promoter and activate its activity (Fig

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Studies have found vaginal estradiol administration to result in 10 fold higher serum levels compared to the same dose orally.10 One study that looked at 2mg and 0.2mg estradiol vaginally found the higher dose resulted in a rapid serum level of 530pg/mL whereas the 0.2mg dose increased serum level to 80pg/mL, with the 80pg/mL being similar to serum levels noted in other studies consistent with a 2mg oral dose.10,12 Transdermal estradiol may vary by application type, but one study of the gel found that treatment with 1.5mg estradiol transdermal gel produced similar levels to 2mg estradiol orally or 0.2mg vaginally, suggesting about 75% of the dose is needed transdermally as compared to orally.10 The package inserts for oral and transdermal estradiol products do not specify monitoring timelines, though transdermal estradiol has been shown to take as long as 12 to 14 days to reach steady state in some studies whereas oral estradiol achieves steady state more quickly at around 5-6 days.13 Specific information on pharmacokinetics for estradiol administered buccally were unavailable, though, one study reported steady state had been achieved after two weeks of treatment