Low dose of transdermal estradiol gel for treatment of symptomatic postmenopausal women: a randomized controlled trial.
OBJECTIVE
To investigate safety and efficacy and identify the lowest effective dose of a new transdermal estradiol (E2) gel for relief of menopausal symptoms in a population of postmenopausal women.


METHODS
This study was a randomized, double-blind, placebo-controlled, multicenter, parallel-group study. Postmenopausal women with at least 60 hot flushes per week applied 0.87 g/d (n=136), 1.7 g/d (n=142), or 2.6 g/d (n=69) E2 gel or placebo gel (n=137) topically for 12 weeks. The changes from baseline in hot flush frequency and severity at 4 and 12 weeks and changes from baseline in vaginal atrophy symptoms at 12 weeks were examined.


RESULTS
With increasing E2 doses, mean trough serum E2 increased from 17 to 29 pg/mL. By weeks 3-5, E2 gel reduced moderate-to-severe hot flush rate by at least seven hot flushes per day (P<.001) and reduced the severity score (P<.01). The numbers needed to treat for benefit for an 80% and 100% decrease in hot flush number were 3.2 and 6.3 for the 0.87-g/d group and 1.3 and 2.3 for the 2.6-g/d group. At week 12, vaginal pH was more acidic and vaginal maturation index more mature compared with placebo (P<.001). The lowest dose improved most bothersome vulvovaginal atrophy symptoms (P<.05). Estradiol gel was well tolerated at the site of application and produced no unexpected adverse effects. The 0.87 g/d dose produced fewest adverse events.


CONCLUSIONS
The 0.87 g/d dose of this new transdermal E2 gel, which delivers an estimated 0.0125 mg E2 daily, delivered the lowest effective dose for treatment of vasomotor symptoms and vulvovaginal atrophy in a population of postmenopausal women.


BACKGROUND
ClinicalTrials.gov, www.clinicaltrials.gov, NCT00391417.


METHODS
I.
Simon
James A
JA
George Washington University, Washington, DC, USA.
Bouchard
Celine
C
Waldbaum
Arthur
A
Utian
Wulf
W
Zborowski
Joanne
J
Snabes
Michael C
MC
D000279:Administration, Cutaneous; D001284:Atrophy; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D005782:Gels; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D014621:Vagina / Q000187:drug effects / Q000473:pathology; D014666:Vasomotor System / Q000187:drug effects*; D014844:Vulva / Q000187:drug effects / Q000473:pathology
D005782:Gels; D004958:Estradiol