Bioequivalence of a 17 beta-estradiol hydroxypropyl-beta-cyclodextrin complex in postmenopausal women

Five postmenopausal women received single doses of a 0.675 mg estradiol hydroxypropyl-beta-cyclodextrin (estradiol-HP beta CD) sublingual tablet by the sublingual and oral route. A single dose of a 1 mg micronized estradiol tablet was given orally for comparison. Blood samples were obtained over 48 hours for measurement of estradiol, estrone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations. Sublingual administration produced faster and significantly higher peak estradiol concentrations than after oral administration of either estradiol-HP beta CD or micronized estradiol. The concentration-time area under the curve of estradiol after sublingual estradiol-HP beta CD was also significantly larger than after oral administration of either estradiol-HP beta CD or micronized estradiol, reflecting a larger estradiol bioavailability. The estradiol/estrone concentration ratio after sublingual estradiol-HP beta CD revealed a predominance of estradiol for the first 2 hours after the dose, followed by an estrone predominance. Both oral doses produced a predominant delivery of estrone to the systemic circulation. There was not difference in time-averaged LH suppression between the three phases. However, estradiol-HP beta CD sublingually produced greater FSH suppression than oral micronized estradiol.