Efficacy and tolerability of transdermal 17 beta-estradiol in patients with climacteric symptoms: dose titration according to individual choice

Abstract

The aim of this open-label, multicenter study was to determine the efficacy and tolerability of four doses of transdermal 17 beta-estradiol (25, 50, 75, and 100 μg/d) in postmenopausal women and to evaluate the effectiveness of individually and pragmatically adjusted doses, following up and down titration of the initial dose. After a 2-week washout period, women began the first cycle of treatment with transdermal 17 beta-estradiol 50 μg/d. After 1 month, women could choose to continue, decrease, or increase that dose, according to their perception of effectiveness and tolerance. After cycle 2, women had another opportunity to alter their dose. A total of 77% (176 of 228) of patients completed all three treatment cycles, and 199 were considered suitable for evaluation on a per-protocol basis. After 1 month, a total of 47% of women chose to stay on a fixed 50-μg/d dose, 23% increased to 75 μg/d, and only 1 chose to increase to 100 μg/d; 18% decreased to 25 μ/d; and 11%, after initial modification, returned to the initial 50-μg/d dose. The climacteric symptom of hot flushes was the main indicator of effectiveness. At baseline, all women had a similar daily number of hot flushes, which was significantly reduced from 6.9 ± 5.0 at baseline to 1.1 ± 3.6 at the end of cycle 3. By titration group, patients who chose to maintain their treatment on a fixed dose or to decrease had a significantly greater reduction in hot flushes at cycles 1 and 2 compared with the other groups. Nevertheless, when mean scores on a 100-mm visual analog scale for hot flushes and nocturnal sweating were combined, results showed that at the end of cycle 3, the therapeutic effect was similar for all titration groups. Mild or minor adverse events were reported by 56% (128 of 228) of patients; in 79% of patients (101 of 128), these events were considered related to the study drug. Breast sensitivity (29%; 65 of 228) and skin reactions (20%; 46 of 228) were the most commonly reported side effects. An increased number of adverse effects were reported by patients who increased their dose. These results suggest that women are able to adapt hormone replacement therapy dose themselves, according to their initial (1 month) individual response to treatment in terms of effectiveness and tolerance, with no significant loss of therapeutic benefit.