Estrogenic uterovaginal effects of oral estetrol in the modified Allen-Doisy test.
OBJECTIVE
To evaluate the effect of estetrol (E(4)) on vaginal cornification and uterine wet weight in the ovariectomized rat.


METHODS
Adult female rats served as experimental animals. Six groups of ovariectomized rats (eight per group) were treated orally once daily for 7 days as follows: vehicle (negative) control; E(4): 0.1, 0.3, 1.0 and 3.0 mg/kg/day, and ethinylestradiol 0.05 mg/kg/day as active (positive) control. Vaginal lavages were obtained daily and uterine wet weight was determined on day 7.


RESULTS
Vaginal cornification was observed by day 5 in all rats at all E(4) doses and in the animals receiving ethinylestradiol, but not in the control rats. The onset of cornification with E(4) was dose-dependent. After 7 days' treatment, the two highest E(4) doses (1.0 and 3.0 mg) induced statistically significant higher uterine wet weight compared to vehicle.


CONCLUSIONS
Estetrol has estrogenic effects on the vagina and on the uterus of ovariectomized rats. The potency of E(4) is approximately 20-fold lower compared to ethinylestradiol.
Heegaard
A-M
AM
Nordic Bioscience, Herlev, Denmark.
Holinka
C F
CF
Kenemans
P
P
Coelingh Bennink
H J T
HJ
D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004953:Estetrol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011897:Random Allocation; D051381:Rats; D007507:Therapeutic Irrigation; D014599:Uterus / Q000187:drug effects* / Q000473:pathology*; D014621:Vagina / Q000187:drug effects* / Q000473:pathology*
D004953:Estetrol