The Effect of Washing and the Absence of Interindividual Transfer of Estradiol Gel

Abstract

AimThe primary objective of this study was to evaluate the extent of interindividual transfer and subsequent exposure to estradiol, estrone and estrone sulfate in non-treated postmenopausal women after repeated daily direct skin-to-skin contact with postmenopausal women treated with estradiol gel. The secondary objective was to evaluate the effect on serum estradiol, estrone and estrone sulfate concentrations of washing the application site 1 hour after estradiol gel was applied.MethodsThis was a single-center, randomized, open-label, crossover, multiple-dose study. A total of 48 healthy, postmenopausal women were assigned to either the treated (application of 1.25g of transdermal estradiol gel 0.06%) or non-treated (secondary exposure) group in matched pairs. The study comprised two treatment periods each of 14 days, separated by a washout period of 14 days. Those randomized to the treated group received estradiol gel every day in both treatment periods, but in a crossover design were further randomized to thoroughly wash (or not wash) the application site 1 hour after gel administration for the duration of one of the treatment periods. To determine the extent of transfer of estradiol gel to non-treated women, a 15-minute direct skin-to-skin contact test was conducted daily 1 hour after gel application to the treated test partner (with or without washing of the application site). Serum estradiol, estrone and estrone sulfate concentrations were measured over a 24-hour period at baseline and on day 14 of each study period to determine the extent of transfer of estradiol gel and subsequent absorption in the non-treated group, and the extent of absorption of estradiol and the effect of washing (compared with not washing) the application site after gel administration in the treated group.ResultsIn the non-treated group, mean pharmacokinetic parameters for estradiol, estrone and estrone sulfate after 14 days of daily direct skin-to-skin contact with the women treated with estradiol gel were not statistically different from baseline. In the treated group, washing the application site 1 hour after gel administration reduced the serum concentrations of estradiol, estrone, and estrone sulfate throughout the 24-hour blood sampling interval. These reductions were small but statistically significant.ConclusionInterindividual transfer of estradiol gel 1 hour after application from treated to non-treated individuals and subsequent absorption of estradiol, as determined by the area under the serum concentration-time curve and maximum serum concentration of estradiol, estrone and estrone sulfate, was not statistically significant and clinically unimportant. Washing of the application site at 1 hour after daily transdermal administration of the gel reduced the extent of absorption of estradiol in treated individuals.