Efficacy and tolerability of pulsed estrogen therapy: a 12-week double-blind placebo-controlled study in highly symptomatic postmenopausal women.
OBJECTIVE
To confirm the efficacy and safety of pulsed estrogen therapy, a transient daily hormone exposure, for climacteric symptoms in highly symptomatic postmenopausal women.


METHODS
In this multicenter, double-blind, parallel-group study, early postmenopausal women with at least seven moderate to severe vasomotor symptoms per day were randomized to receive intranasal estradiol, 150 or 300 microg/day, or placebo, for 12 weeks. The primary outcome measure was the mean daily number of moderate to severe vasomotor symptoms, as recorded in patient diaries.


RESULTS
A total of 165 patients were randomized. The mean daily number of moderate to severe vasomotor symptoms decreased significantly more (p < 0.001) in the 150-microg/day (-7.86) and 300-microg/day (-9.39) groups than in the placebo group (-5.22). The decrease reached significance more rapidly with the 300-microg/day dose (from week 2) than with the 150-microg/day dose (from week 8). The rate of emergent adverse events with both doses was similar to that with placebo.


CONCLUSIONS
Pulsed estrogen therapy, achieved by intranasal estradiol 150 microg/day and 300 microg/day, significantlyreduced the incidence of moderate to severe vasomotor symptoms, compared with placebo. The 300-microg/day dose demonstrated a greater and more rapid therapeutic effect, with no clinically significant difference in tolerability, compared with the 150-microg/day dose, and therefore offers the best efficacy/safety ratio when initiating treatment with intranasal estradiol.
Rozenbaum
H
H
Clinique de l'Essonne, Evry Cedex, France.
Chevallier
O
O
Moyal
M
M
Durand
G
G
Perineau
M
M
This
P
P
D000281:Administration, Intranasal; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005602:France; D019584:Hot Flashes / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D020551:Pulse Therapy, Drug; D012720:Severity of Illness Index; D016896:Treatment Outcome
D004958:Estradiol