Efficacy Evaluation of Estradiol on Hot Flushes in Postmenopausal Women:
a Model-based Meta-analysis
Abstract
Aims: To evaluate the efficacy of estradiol in the treatment of
menopausal hot flushes in women, quantify its efficacy characteristics
as well as the placebo effect, and explore the influencing factors to
establish an efficacy scale for the development of drugs for the
treatment of menopausal hot flushes. Data and methods: A literature
search was conducted to include clinical studies on estradiol for the
treatment of menopausal hot flushes. Data of demographics, dose,
administration route and efficacy were extracted and used to construct
an efficacy model. Model simulations were used to obtain the efficacy in
different populations with different doses and administration routes.
Results: Seventeen studies, including 17 groups of placebo (1698
subjects) and 29 groups of estradiol (3013 subjects) with daily doses of
estradiol ranging from 0.01 to 2 mg, were included. There were
significant effects of administration route (oral or transdermal),
ethnicity (Caucasian or Asian) and duration of menopause on model
parameters. The efficacy was higher in non-Asians than in Asians, and
weaker in menopausal women with > 60 weeks of menopause
than < 60 weeks. The placebo effect was higher for shorter
menopause duration, with a time to ED50 of 3.15 weeks for Asian and 1.96
weeks for non-Asians. Conclusion: The standard longitudinal efficacy
scales of estradiol on menopausal hot flushes were constructed, and no
difference was found in the efficacy of estradiol in Asians and
non-Asians. The standard efficacy of estradiol in this study could
inform the efficacy evaluation in new drug development.