Comparative uterine effects on ovariectomized rats after repeated treatment with different vaginal estrogen formulations.
OBJECTIVE
Topical estrogen therapy is recommended for the treatment of vaginal atrophy. This study was designed to compare the uterotrophic effects of a new estrogen vaginal formulation (0.005% estriol vaginal gel) and other existing topical treatments (Ovestinon(®) and Colpotrofin(®)).


METHODS
Each one of the studied formulations was administered intravaginally to groups of ovariectomized rats with cytologically confirmed vaginal atrophy. The doses were adjusted by animal weight according to human dosage. After daily treatment for 14days, the animals were sacrificed and their vaginas and uteri removed. All uteri were weighted. Uteri and vaginas were fixed for histological evaluation.


RESULTS
All three active formulations proved to be very effective in the cytological reversal of vaginal atrophy. However, they differ in their effects in the uteri. Ovestinon(®) and Colpotrofin(®) produced a significant increase in uterine weight, myometrial and endometrial thickness as well as histological modifications in the endometrium suggestive of estrogenic activity. Conversely, animals treated with 0.005% estriol vaginal gel, did not show significant weight increase or any other macroscopical or microcospical modifications of the uteri, an effect comparable to placebo.


CONCLUSIONS
There are significant differences in the uterotrophic effect of three different topical estrogen formulations as tested in a rat model of vaginal postmenopausal atrophy. While the three formulations were equally effective in reversing vaginal atrophy, only the newly developed ultra-low dose 0.005% estriol vaginal gel has proved to lack any significant estrogenic effect on the uterus.
Farma-Cros Ibérica, SL, C/ Castilla-La Mancha 7, Pol. Ind. Camporrosso, 02520 Chinchilla de Montearagón, Albacete, Spain. jlb.farmacros@telefonica.net
Juan
J
López-Belmonte
Concepción
C
Nieto
José
J
Estevez
Juan L
JL
Delgado
Jaime Moscoso
JM
del Prado
D000282:Administration, Intravaginal; D000818:Animals; D001284:Atrophy / Q000188:drug therapy / Q000209:etiology; D004717:Endometrium / Q000187:drug effects / Q000473:pathology; D004958:Estradiol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004964:Estriol / Q000009:adverse effects / Q000627:therapeutic use; D004967:Estrogens / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D009215:Myometrium / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D014591:Uterine Diseases / Q000139:chemically induced* / Q000473:pathology; D014599:Uterus / Q000187:drug effects* / Q000473:pathology; D014621:Vagina / Q000187:drug effects* / Q000473:pathology; D014623:Vaginal Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology
D004967:Estrogens; D004958:Estradiol; D004964:Estriol; C013657:promestriene