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.

Restoration of Vaginal Epithelial Atrophy in Ovariectomized Rats with Sex Steroid Hormones

“…The decrease in vaginal epithelium layers rendered it susceptible to abrasion. Previous studies in animals [16,24,25] and human studies [26] were in agreement with our findings. The decrease in vaginal epithelium thickness would make it vulnerable to bacterial infection [27] and more easily to be torn.…”

“…Results from previous studies were similar and supported data obtained in the current study [16,24]. However, administration of progesterone (1 mg/kg/day) alone for 4 weeks to OVX rats in the present study failed to retain the structure of vaginal tissues from degradation induced by ovariectomy.…”

“…Similar findings were reported by previous study [16]. However a divisive study [29] showed that estrogen treatment in women decreased collagen content compared to placebo treatment.…”

“…Ten measurements were used for each image and the average epithelial thickness was calculated. Images of histological sections were taken under a final magnification of x400 and analyzed using Image-Pro Plus 4.5 software (Media Cybernetics, Silver Spring, MD,USA) [16].…”

“…Eight images for each slide of vaginal sections stained with Masson trichrome were used and a 100-point grid mask was applied to count the average per cent area of collagen fibers per group [16].…”