Several investigations have documented that sustained delivery of estrogen can modulate or sustain normal female reproductive functions. However, the literature is lacking scientific evidence regarding the mechanism of estrogen and neuropeptide Y antagonist (NPY) effect on the hypothalamic-pituitary-gonadal axis. The objective of this study was to explore the role of sustained delivery of estrogen and its effects on reproductive unction compared to an antagonist such as NPY. A total of twenty adult female rats (OVX, n=15; intact control, n=5) were divided into five groups (intact control, OVX, sham, OVX + estrogen, and OVX + NPY). Animals in two groups were surgically implanted with a TCP delivery device loaded with estrogen or NPY. Vaginal smears and body weights (BW) were evaluated at baseline and at two weeks post implantation. At the end of two weeks, all animals were euthanized and vital and reproductive organs were retrieved for histopathological evaluation. The results revealed differences in BW between intact control and OVX animals. Furthermore, there was statistical difference (P<0.05) in BW between OVX and OVX + NPY animals. Vaginal smear evaluation revealed that estrogen exposure induced estrus cyclic activities as compared to OVX and sham animals. The animals exposed to sustained delivery of NPY triggered moderate cyclic activities compared to intact control animals. There were no significant differences (P<0.5) in vital organ wet weights among and between animals in all groups. Overall this study proved the capability of TCP to release estrogen and NPY at sustained levels, which resulted inpathophysiological changes in female reproductive organs.