476 Evaluation of the in vitro percutaneous absorption of progesterone, testosterone, estriol and estradiol topical compounded formulations

Abstract

The safety, effectiveness and use of compounded bioidentical hormone replacement therapy has been questioned by the US Food and Drug Administration in the light of the recently published study report by The National Academies of Sciences, Engineering and Medicine. An in vitro study was conducted to evaluate the human skin percutaneous absorption of commonly prescribed bioidentical hormones using the Franz Skin Finite Dose Model. A topical compounded cream (VersaBase Cream) and gel (VersaBase Anhydrous HRT) were prepared for progesterone 100 mg/g, testosterone 1 mg/g, and estriol/estradiol [50%/50%] 2 mg/g. The 6 formulations were applied to the outer surface of ex vivo skin mounted in Franz diffusion chambers (9 tissues/formulation) to evaluate the total absorption, rate of absorption and skin content of the bioidentical hormones. The topical creams and gels for progesterone and testosterone exhibited similar mean flux profiles, characterized by a rise in skin percutaneous absorption to a peak at approximately 7 hrs (progesterone) and 5 hrs (testosterone) after dose application, followed by a slow decline in flux over time (24 hrs). The estrogens did not show a peak rise but instead a steady mean flux that increased slightly over the study time. Overall, the total absorption of the bioidentical hormones was higher for the topical gels in comparison to the creams. The total recovery (receptor medium, skin content and surface wash) of the bioidentical hormones varied from 87-97%. This study demonstrates that the bioidentical hormones penetrate through the skin (stratum corneum, epidermis and dermis) upon application of the topical compounded creams and gels. These results are important evidence to support the effectiveness of compounded bioidentical hormone replacement therapy since the in vitro model used has proven to accurately predict in vivo permeation kinetics.