Lowest effective transdermal 17beta-estradiol dose for relief of hot flushes in postmenopausal women: a randomized controlled trial.
OBJECTIVE
To investigate the efficacy of micro-dose transdermal estrogen in relieving menopausal vasomotor symptoms.


METHODS
A randomized, double-blind, placebo-controlled, multi-center trial. Healthy postmenopausal women with at least seven moderate or severe hot flushes per day for at least 1 week, or at least 50 per week, applied transdermal patches with a nominal delivery of 0.023 mg/d 17beta-estradiol and 0.0075 mg/d levonorgestrel (low-dose E2/levonorgestrel; n=145), 0.014 mg/d E2 (micro-dose; n=147), or placebo (n=133) for 12 weeks. The coprimary efficacy variables were the mean changes from baseline in frequency and severity of moderate and severe hot flushes at the week 4 and 12 endpoints.


RESULTS
At the week 12 endpoint, mean weekly frequencies of moderate and severe hot flushes were significantly reduced compared with placebo with low-dose E2/levonorgestrel (-51.80; P<.001) and micro-dose E2 (-38.46; P<.001). Severity scores were also significantly reduced with both treatments compared with placebo. At week 12 endpoint, 41.3% of women receiving micro-dose E2 were treatment responders (75% or more reduction from baseline in hot flush frequency; P=.003 compared with 24.2% placebo). In this group, the mean reduction in moderate and severe hot flushes from baseline was approximately 50% after 2, 70% after 4, 90% after 8, and 95% after 12 weeks. There were no differences between active treatments and placebo regarding adverse events.


CONCLUSIONS
Micro-dose E2 (0.014 mg/d) was clinically and statistically significantly more effective than placebo in reducing the number of moderate and severe hot flushes, with a 41% responder rate, supporting the concept of the lowest effective dose.


BACKGROUND
ClinicalTrials.gov, www.clinicaltrials.gov, NCT00206622
Bachmann
Gloria A
GA
University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA. gloria.bachmann@umdnj.edu
Schaefers
Matthias
M
Uddin
Alkaz
A
Utian
Wulf H
WH
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D017698:Postmenopause / Q000502:physiology*; D014666:Vasomotor System / Q000187:drug effects*
D003280:Contraceptives, Oral, Synthetic; D004958:Estradiol; D016912:Levonorgestrel