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. CONCLUSION: 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.