Preventive effect of oral estetrol in a menopausal hot flush model.
OBJECTIVE
To evaluate the efficacy of estetrol (E(4)) in alleviating hot flushes in an experimental animal model considered representative for menopausal vasomotor symptoms.


METHODS
Recording of the thermal responses in the tail skin of morphine-dependent ovariectomized rats after morphine withdrawal by administration of naloxone. Six groups of rats were treated orally for 8 days as follows: vehicle (negative) control; E(4): 0.1, 0.3, 1.0 and 3.0 mg/kg/day; and, as active (positive) control, ethinylestradiol 0.3 mg/kg/day. On day 8, tail skin temperature was recorded at baseline and for 60 min at 5-min intervals following naloxone administration. Results In control animals, tail skin temperature increased sharply by about 4.5 degrees C after naloxone treatment and reverted to baseline by 60 min. Estetrol suppressed the tail skin temperature increase in a dose-dependent fashion. The highest dose of E(4) tested (3 mg/kg/day) was equipotent to a 10-fold lower dose of ethinylestradiol. Both fully suppressed tail skin temperature changes.


CONCLUSIONS
Estetrol is effective in alleviating hot flushes in an experimental animal model considered representative for studying menopausal hot flushes (vasomotor symptoms). In this model, the potency of estetrol is 10-fold lower compared to ethinylestradiol.
Holinka
C F
CF
PharmConsult, New York, NY, USA.
Brincat
M
M
Coelingh Bennink
H J T
HJ
D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004953:Estetrol / Q000627:therapeutic use*; D005260:Female; D019584:Hot Flashes / Q000517:prevention & control*; D006801:Humans; D023421:Models, Animal; D008954:Models, Biological; D009020:Morphine / Q000009:adverse effects; D009270:Naloxone / Q000494:pharmacology; D010052:Ovariectomy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012881:Skin Temperature / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
D009270:Naloxone; D009020:Morphine; D004953:Estetrol