The Animal Experimental Study Of Abnormal Uterine Bleeding Caused By Progesterone Oral Contraceptive (POC)

Objective: Marvelon is a sort of the third generation progesterone oral contraceptive (POC), the content of estrogen is further reduceded, it's major component include desogestrel (DSG) and ethinylestradiol. DSG is a new type progestogen, which posses more powerful organism activity. The contraception mechanism of marvelon is attributed to a negative feedback regulation of synthetic steroids on hypothalamic-pituitary-ovary axis. Inhibition of folliculogenesis and hence ovulation is the principal objective of marvelon. However, breakthrough bleeding (BTB) and spotting are among the most common side effects associated with POC use and their occurance is a prime determinant of whether users will continue to use it. A lots of experimental studies on mechanism of BTB have been done, but we have not got a final conclusion up to now. We observe the changes of Spague Dawlay rats uterine histology, vascular density, estrogen receptor (ER), progesterone receptor (PR) and serum concentrations of estrogen, progesterone by applying immunohistochemistry, radioimmunoassay (RIA) and computer image processing technology, so as to inquire into the mechanism of abnormal uterine bleeding.Method: Sixty healthful SD femal rats having regular sexed cycle (4-5days) were used, it included treated group (n=30) and control group (n=30),which was divided into short-term group (n=10), long-term group (n=10) and drug-stop group (n=10). Marvelon 50mg/kg (100mg marvelon dissolves in 30ml oil) was administrated to rats in treated group at 9o'clock everyday, and the same dose of oil was administrated to rats in contrastive group. We monitor the estrus cycle of SD rats by making vaginal smear regularly. The short-term group and long-term group were killed after feeding 20 days and 90 days respectively, others continued to be fed with the same dose of oil for 20 days and to be killed. Blood sample drawn from heart were used for the determination of estrogen and progesterone level by RIA, tissues were fixed through heart ascending aorta, then uterus tissues were taken quickly. After gradient alcohol dehydration, embedding and cutting into sections. We applied transmission electron microscopy and computer image procession technology, so as to observe the changes of histology, ultrastructure, ER positive cells and PR positive cells with HE staining ,as well as immunohistochemistry.Result:1.The rats'endometrium in long-term treated group were observed to be atrophied, endometrial glands scattered whose quantity and volum were decreased, the ratio of stromal area to glandular area was increased, the average density ofendometrial vascular increased and blood vessel dilatated, the ratio of stromal area to vascular area was decreased, there were notable changes between the long-term treated and long-term control group .There were no significant changes between the short-term treated and short-term control group,as well as drug-stop groups. 2.ER and PR positive cells distributed in luminal, epithelium, glandular epithelium, stroma and myometrial smooth muscle, their staining was weaken and optical density decreased in long-term treated group, there were notable changes between the long-term treated grorp and it's control group. There were no significant changes between the short-term treated and it's control group, as well as drug-stop groups. 3.The serum concentrations of estradiol and progesterone level reduced in long-term treated group, there were notable changes between the long-term treated grorp and it's control group.There were no significant changes between the short-term treated and it's control group,as well as drug-stop groups. 4.There were no notable difference between drug-stop treated group and it's control group.Conclusions: After marvelon being administered to rats for a long time, the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) is depressed during oral contraceptive use becaused of it's negative feedback regulation on hypothalamic-pituitary-ovary axis, thereb...