“Pharmacokinetic and Pharmacodynamics of Three Doses of Oestriol in Healthy Postmenopausal Women Following Continuos Vaginal Ring Delivery for 21 Days”

Abstract

In healthy postmenopausal women receiving treatment with a vaginal ring at continuous delivery rates of 0.125 (Test 1), 0.250 (Test 2), or 0.500 mg day–1 (Test 3) for 21 days, the AIMSE evaluated the oestriol pharmacokinetics, pharmacodynamics, and safety. METHODS One application of Tests 1, 2, or 3 was given to each of the thirty-one individuals. The technique of liquid chromatography coupled tandem mass spectrometry was used to ascertain the oestriol plasma concentration. The pharmacodynamics were evaluated by measuring serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin, as well as maturation value (MV) and vaginal pH. To assess safety, adverse events, endometrial thickness, and local tolerability were considered. RESULTS: For the area under the plasma concentration (AUC) curve up to the most recent measurement, the 90% confidence interval of the coefficient/slopeβwas 0.5997–1.174%, for the AUC extrapolated to infinity, it was 0.5838–1.115%, and for the maximum plasma concentration, it was 0.2408–0.943%. The dose proportionality was unavoidable for maximum plasma concentration, although a statistically significant departure from proportionality was seen for AUC. Higher delivery rates were associated with a more noticeable decline in the FSH and LH curves; however, sex hormone-binding globulin did not exhibit this behaviour. For each formulation, the treatment's impact on vaginal pH and MV was comparable. Every product had a 70–80% rise in MV, and there was a shift in the distribution of parabasal, intermediate, and superficial cells in Favor of superficial cells. During treatment, the vaginal pH readings significantly dropped. Endometrial thickness was not affected in a dose-dependent manner. FINAL VERDICT Each formulation produced the ideal amount of local impact by releasing enough oestriol. On the other hand, there was no variation in the surrogate parameters for clinical efficacy between formulations. For FSH and LH, however, a dose-dependency was well shown. The product was safe and well-tolerated.