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

ABSTRACT

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.

Key words::

• HORMONE REPLACEMENT THERAPY
• LOW-DOSE MAINTENANCE THERAPY
• CLIMACTERIC SYMPTOMS
• TRANSDERMAL ESTRADIOL
• RANDOMIZED CONTROLLED STUDY

ACKNOWLEDGEMENTS

The author gratefully acknowledges the dedicated efforts of the following institutions: Kotoni Ladies Clinic (Hokkaido), Gorinbashi sanka fujinka syonika hospital (Hokkaido), Hoyukai Sapporo Clinic of Obstetrics & Gynecology (Hokkaido), Tonan Hospital KKR Sapporo Medical Center (Hokkaido), Iesaka sanka fujinka clinic (Gunma), Toranomon Women's Clinic (Tokyo), Akazawa ladies Clinic (Tokyo), Kichijouji ladies clinic (Tokyo), Kondo Women's Hospital (Kanagawa), Yoshimura Ladies clinic (Osaka), Osaki Clinic (Osaka), Medical Corporation Ishihara Clinic (Kyoto), Women's wellness ginza clinic (Tokyo), and Kosugi Clinic (Tokyo).

Conflict of interest The author was previously involved in this study as an external medical expert and has no conflicts of interest to report.

Source of funding This study was sponsored by Shiseido Company, Limited. The author received editorial assistance from Shiseido Company, Limited.