title: Effect of prolonged use of high dose of tibolone on the vagina of ovariectomized rats.
abstract: The aim of this study was evaluate the effect of prolonged use of high dose of tibolone on the vagina of ovariectomized rats. Bilateral ovariectomy was performed on 14 rats weighing 250 g. Thirty days later, vaginal smears were collected verifying the menopause status by anoestrus cytology. Rats were divided randomly into groups: experimental rats (n = 9) received 1 mg tibolone/day orally and control rats (n = 6) received placebo (carboxymethylcellulose). After 150 days, all rats were sedated and euthanized by cervical displacement. The vagina was removed, fixed in 10% buffered formalin, sampled and processed for paraffin embedding. Histological sections were stained with haematoxylin and eosin, picrosirius red, periodic acid Schiff (PAS) and PAS-diastase, and Weigert's resorcin-fuchsin. Cell proliferation was analysed by immunohistochemistry to detect Ki67. Histomorphometric analyses were performed for epithelial thickness, per cent area of collagen fibres and blood vessels, mast cells and Ki67-positive nuclei per mm of basal membrane. Means and standard error of means were calculated, and data were compared using the Mann-Whitney test, with significance level at P < 0.05. In the vagina, epithelial thickness, number of Ki67-positive nuclei per mm of basal membrane, number of vessels and number of mast cells were significantly higher in the tibolone group when compared with the control group. Furthermore, the content of glycogen and glycoproteins in the vaginal epithelium was modified by tibolone. Tibolone administered in high dose and for a long period has a trophic effect, reversing vaginal atrophy, and has no dysplastic or neoplastic effect in the vagina of ovariectomized rats.
authors.affiliation: Department of Pathology, UFF, Niterói, RJ, Brazil. helenebiomed@yahoo.com.br
authors.forename: Helene Nara
authors.initials: HN
authors.lastname: Henriques
authors.forename: Ana Carolina Bergmann
authors.initials: AC
authors.lastname: de Carvalho
authors.forename: Porphirio José
authors.initials: PJ
authors.lastname: Soares Filho
authors.forename: José Augusto Soares
authors.initials: JA
authors.lastname: Pantaleão
authors.forename: Maria Angélica
authors.initials: MA
authors.lastname: Guzmán-Silva
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D020249:Hormone Replacement Therapy; D023421:Models, Animal; D009652:Norpregnenes / Q000494:pharmacology*; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects; D014621:Vagina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*
chemical_list: D020847:Estrogen Receptor Modulators; D006023:Glycoproteins; D009652:Norpregnenes; D006003:Glycogen; C027385:tibolone