Effects Of High-Dose Progestogen On Development Of Ovariectomized Rats' Uterus

ObjectiveThis study aimed to examine the effects of high-dose progestogen on endometrium and smooth muscles in ovariectomized rats in contrast to other hormone therapies and to explore the feasibility of treating hypoplasia of uterus with high-dose progestogen.MethodsExperimental animals: Fortyeight 30-to 35-day-old female Wistar rats with an average weight of 150 g underwent bilateral ovariectomy under general anesthesia. They were randomized into six groups: Group SHAM, sham operation group; Group OVX, ovariectomy group; Group E, estrogen replacement therapy group; Group P₁, low-dose progesterone replacement therapy group; Group P₂, medium-dose , progesterone replacement therapy group; Group P₃, high-dose progesterone replacement therapy group. Group P₃ had 18 rats and each of the other groups had 6 rats.Operation methods: Group SHAM only underwent on-off of abdomen and the other groups bilateral oophorectomy. After operations, Group SHAM and Group OVX were administered with placebo; Group E, benzogynestry 20μg.kg^-1.d^-1 by hypodermic injection; Group P₁, luteohormone 1mg.kg^-1.d^-1; Group P₂, luteohormone5mg.kg^-1.d^-1; Group P₃, luteohormone 25mg.kg^-1.d^-1.Observation of indexes: After four weeks of successive administration, bodieswere weighed and the concentrations of estrogen and progestogen in blood serum were examined by radioimmunoassay; uterus weights were measured and uterus indexes (uterus weight / body weight) were calculated; histological morphology of each layers of uterus were observed on HE staining uterus slices and thickness of endomeu^ number of glandulas ^ thickness of myometrium> morphous and diameter of myometrial smooth muscle cell were examined respectively. In addition, uterus indexes, myometrium thickness and myocytic diameters of six rats from Group P3 were measured respectively on the first, second and fourth weekend. Results1. Uterus indexes: the uterus indexes of Group OVX decreased significantly in contrast to that of Group SHAM. Compared with Group OVX, the other experimental groups had higher uterus indexes except for Group Pi which had no variety in uterus indexes. The augments of Group E and Group P3 were significant(P<0.05). The uterus indexes of Group P3 increased with the prolonging administration period.2. Obvious uterus atrophia, thinner endometria and myometrium, fewer and straighter glandulas were observed in Group OVX. Compared with Group OVX, of the other experimental groups except for Group Pi, endometria thickened, the number of glandulas increased, myometrium thickened and myometrial smooth muscle cell diameter increased. Compared with Group P2, the muscularis thickness and myocytic diameters of Group P3 rose significantly(P<0.05), but endometria thickness and glandula quantities of Group P3 rose slightly without statistic significance. The myometrium thickness and myometrial smooth muscle cell diameters of Group P3 increased with the extended administration period. The effects of progestogen on uterus weight increment, muscularis development and myocytes hypertrophy were intensified with the augment of its dose from Group Pi, Group P2to Group P3 as a sequence.Conclusions1. Single administration of high-dose progestogen can induce uterus weight and uterus indexes to increase, muscularis to thicken, smooth muscle to turn into hypertrophy and endometria to present secretive-phase-like appearance.2. The effects of progestogen on developing uterus of hypoplasia is positively correlated with doses and administration period of progestogen.