[Effect of tibolone on endometrium of castrated rats].
OBJECTIVE
to evaluate the effect of long-term use of a high dose of tibolone on the morphology of the endometrium of castrated female rats.


METHODS
fifteen female Wistar rats, aged eight weeks and weighting about 250 g were used. All the female rats were submitted to bilateral oophorectomy and 30 days afterwards, vaginal cytology was collected, to verify the menopause status. The female rats were randomly divided in two groups. The Treatment Group (n=9) received 1 mg of tibolone/day orally; the Control Group (n=6) received a solution of carboxymethylcellulose vehicle. After 20 weeks of treatment, all the animals were sedated and sacrificed by cervical dislocation. The uterus was removed and fixated in 10% buffer formaldehyde. Both uterine horns were divided in three regions (proximal, medial and distal) and processed to be included in paraffin. Histological sections, stained with hematoxylin-eosin were submitted to morphological and morphometrical analysis. The following parameters have been analyzed: thickness of the endometrial superficial epithelium, thickness of the endometrium stroma, endometrial area, absolute number of endometrial glands and number of glands/endometrial area. The data obtained were compared by the t-Student test.


RESULTS
in the Tibolone Group, the uteri were well developed and there was a significant increase (p<0.01) of all the histomorphometric parameters. In some cases, the cylindrical epithelium became stratified, pavimentous and covered the internal portions of the glands, as well as of the endometrium cavity. Rats from the Control Group presented uterine atrophy. There were few tubular-like glands and scarce intercellular substance. Glands were covered by cubic epithelium which extended itself to the endometrial cavity.


CONCLUSIONS
high doses of tibolone, given for long periods of time to castrated female rats, have an estrogenic effect which can be dose-dependent, causing proliferation in the endometrium and causing changes in the cell differentiation (squamous metaplasia), but do not lead to hyperplasia.
Pantaleão
José Augusto Soares
JA
Universidade Federal Fluminense, Niterói, RJ, Brasil.
Henriques
Helene Nara
HN
de Carvalho
Ana Carolina Bergmann
AC
Pollastri
Carlos Eduardo
CE
Soares Filho
Porphirio José
PJ
Guzmán-Silva
Maria Angélica
MA
D000818:Animals; D004717:Endometrium / Q000187:drug effects*; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage*; D005260:Female; D009652:Norpregnenes / Q000008:administration & dosage*; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; C027385:tibolone