Clinical usefulness of a low-dose maintenance therapy with transdermal estradiol gel in Japanese women with estrogen deficiency symptoms

Objectives To determine the efficacy and safety of low-dose maintenance therapy with transdermal estradiol (E2) gel in Japanese women with climacteric disorder and estrogen deficiency symptoms. Methods Women (n = 209) aged 37-59 years who had climacteric disorder or estrogen deficiency symptoms received a standard dose of transdermal E2 gel (1.8 g/day, containing E2 1.08 mg/day) for 8 weeks as induction treatment. A total of 177 women in whom the number of daily hot flushes had decreased to less than one-third of the baseline value (marked improvement) at week 8 were double-blindly randomized to receive low-dose E2 (n = 88, 0.9 g/day, containing E2 0.54 mg/day) or E2-free placebo (n = 89) for 16 weeks. Results Improvement rates in the number of daily hot flushes at the final evaluation (primary endpoint) in the low-dose E2 group (marked 90.8%, moderate 6.9%, mild 1.1%, no change 1.1%, worsening 0%) were significantly greater than in the placebo group (marked 77.0%, moderate 10.3%, mild 4.6%, no change 2.3%, worsening 5.7%) (p = 0.0097), showing an inhibitive effect on the flare-up of climacteric symptoms. The incidence of treatment-related adverse events in the low-dose group (21.6%) was similar to that in the placebo (22.5%) but was lower than that in the standard-dose treatment (32.5%). Conclusions Low-dose maintenance therapy that was half the standard dose of transdermal E2 gel (0.9 g/day) applied to women who had achieved marked improvement in the number of hot flushes at the standard dose (1.8 g/day) was demonstrated to be effective (inhibition of recurrence) and safe for the treatment of climacteric disorder and estrogen deficiency symptoms.