NEW KINETIC DATA ON ESTRADIOL IN LIGHT OF THE VAGINAL RING CONCEPT

The principal estrogen produced by the functioning premenopausal ovary is 17 beta-estradiol. At the point of irreversible ovarian failure, a t menopause, the production of estradiol decreases dramatically, which results in circulating serum levels less than 120 pmol/l. It is impor tant to recognise the pharmacokinetic and metabolic outcomes associate d with dosage and route of delivery of estrogen. One of the most promi sing methods of administering estrogen replacement therapy (ERT) for l ocal effects is the estradiol vaginal ring designed for a controlled c ontinuous low release (7.5 mu g estradiol/24 h) over a period of 90 da ys. The present study was undertaken to characterise the basal endogen ous turnover of estradiol in postmenopausal women. Information on the disposition of estradiol after an intravenous dose formed the base of the kinetic model. The rate of extent of absorption df estradiol was a ssessed after ring application. Individual serum concentrations of est radiol were analysed without subtraction of the basal estradiol levels . The results indicate a rapidly eliminated compound (plasma clearance 2 l/min) with a distribution of approximately 50 1, resulting in an e fficient half-life of about 20 min. The endogenous production was high ly variable (< 1-44 mu g/24 h). The steady-state estradiol levels foll owing ring application did not increase and were well within the norma l basal estradiol range seen in untreated women. In light of the prese nt findings, the low daily dose, the low availability of estradiol acr oss the vaginal wall and the controlled local delivery, favour the use of the estradiol vaginal ring.