title: Clinical usefulness of a low-dose maintenance therapy with transdermal estradiol gel in Japanese women with estrogen deficiency symptoms.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Mizunuma
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage* / Q000009:adverse effects; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D005782:Gels; D019584:Hot Flashes / Q000188:drug therapy*; D006801:Humans; D007564:Japan; D008593:Menopause; D008875:Middle Aged; D010919:Placebos
chemical_list: D005782:Gels; D010919:Placebos; D004958:Estradiol