Serum Oestradiol Concentrations Following Single-Dose Administration of Oestradiol Acetate Intravaginal Rings (IVRs) Delivering 50, 75 and 100 mg/Day Oestradiol in Healthy Post-Menopausal Women

Abstract

JOURNAL OF THE BRITISH MENOPAUSE SOCIETY, Supplement S3, zoor metabolism. The oral contraceptive containing ethinylestradiol and the progestin norethisterone acetate did not elicit a higher D-ring metabolism, which is considered to increase breast cancer risk. For the oral contraceptive containing dienogest a significant decrease of the ratio in favour of the antiestrogenic oestradiol metabolite was observed. Introduction. Oestrogen replacement therapy is well established for treating the systemic (vasomotor) and local (urogenital atrophy) symptoms associated with the menopause. Previously, intravaginal oestradiol (E z) administration was only able to treat local symptoms, while oral or transdermal products were required to provide sufficient quantities of E z to treat systemic and local symptoms. An intravaginal ring (IVR) using the E z prodrug, oestradiol acetate (EA), was developed to provide sufficient E z to treat both local and systemic symptoms. Methods. Three studies were conducted to characterise the pharmacokinetics of E z and oestrone (E l ) following administration of EA-IVR single-doses to healthy postmenopausal women. In Study 1, EA-IVRs providing nominal doses of 50 mg and 75 mg for 14 days and 100 mg Ez/day for 12 weeks were administered to 12 subjects according to an escalating-dose design. In Study 2, EAIVRs providing 100 mg~/day were administered to 12 subjects for three days. In Study 3, EA-IVRs providing 50 mg~/day were administered to 26 subjects for 13 weeks. Serum~and E I concentrations were determined by enzyme-linked fluorescent assay or GCIMS methods. Results. The E z concentration-time profile was characterised by rapid~absorption (mean tmax <1 h) followed by a short E z distribution phase (rapidly decreasing serum E z concentrations) followed by relatively constant serum E z concentrations to the end of the 12-13 week dosing interval. Average serum E z concentration (Cavg) values following 50 mg, 75 mg, and 100 mg Ez/day for 14 days were 172.5, 201.5 and 292.9 pmol/L, respectively. Cavg values after 12-13 weeks treatment were 149.7 (50 mg Ez/day) and 280.4 pmollL (100 mg Ez/day). Serum E] concentrations were similar to but generally lower those for E z. The EA-IVR was generally well tolerated. Conclusions. Average serum E z concentrations following single-dose EA-IVR administration (approximately 150-280 pmollL) are likely to be effective in treating both the systemic and local symptoms of oestrogen deficiency.

The effect of a novel vaginal ring delivering oestradiol acetate on climacteric symptoms in postmenopausal women

“…Use of the 17β‐oestradiol ester improves solubility in the ring polymer. This improved solubility provides release rates equivalent to 50 or 100 μg/day oestradiol over a three month period, resulting in mean serum oestradiol concentrations of approximately 150 and 280 pmol/L, respectively 19 . These mean serum concentrations that are achieved are similar to those yielded by the oestradiol transdermal patch 14 .…”

The effect of a novel vaginal ring delivering oestradiol acetate on climacteric symptoms in postmenopausal women

“…Use of the 17hoestradiol ester improves solubility in the ring polymer. This improved solubility provides release rates equivalent to 50 or 100 Ag/day oestradiol over a three month period, resulting in mean serum oestradiol concentrations of approximately 150 and 280 pmol/L, respectively 19 . These mean serum concentrations that are achieved are similar to those yielded by the oestradiol transdermal patch 14 .…”