Pathophysiological changes associated with sustained delivery of estrogen and estrogen plus progesterone by TCPL...

The specific objective of this investigation was to study the role of sustained delivery of estrogen (E), or estrogen plus progesterone (E + P) on the histologic and biochemical changes associated with the reproductive organs of adult female rats as a model. Adult Sprague Dawley female rats were randomly divided into three equal groups (n = 3). Group I animals were left as intact controls, group II were implanted with TCPL loaded with E (release rate: 8 pg/ml), and group III animals were implanted with TCPL loaded with E + P. Data obtained from this study have shown that: (i) TCPL delivery system is capable of releasing E, and P + E at a sustained level for four weeks. (ii) The amounts of E or E + P released from TCPL capsules resulted in pathophysiological changes at the reproductive organ levels. (iii) Data obtained showed a slight decrease in total body weights following implantation of E filled TCPL devices. In contrast, no significant difference was observed in total body weights between rats treated with E + P and the control rats. (iv) The results demonstrate that the uterine weights obtained from E and E + P treated animals were significantly higher than the uterine weights obtained from the control animals. Unlike uterine weights, the wet weights of ovaries were remarkably regressed in all E and E + P treated animals in comparison to the control animals. Ultrastructurally, suppression of theca cells as well as inhibition of proliferative activity of granulosa cells were observed in the ovaries of the animals that received E alone in comparison to P + E and the control group. (v) Histological findings revealed changes in vaginal smears and the vaginal, fallopian tube and endometrial epithelium. This was evidenced microscopically by the hypertrophic, papillary projections, cytoplasmic vacuolation (fluid retention) and a decrease in ovarian follicles in animals exposed to sustained delivery of E in comparison to control and E + P groups. Overall, our observations of the results of this study suggest that sustained levels of P + E by TCPL capsules were able to regulate fertility regardless of suppression of endogenous levels of the ovarian hormones.