Study Proliferation And Inhibition Of Endometrium During Postmenopausal Hormone Replacement Therapy

Hormone replacement therapy (HRT) is an effective method which has been used widely to relieve menopausal symptoms and reduce the risk of both osteoporosis and cardiovascular disease. Since estrogen replacement therapy was found to cause a higher risk of endometrial hyperplsia and cancer, but by addition of progestogen can prevent endometrium from stimulation with estrogen. Large doses of progestogen could induce clinical and metabolic side effects, it is desirable to find the minimum dosage neccesory to inhibit the endometrial hyperplasia. Although many studies have been reported,but no definitive answer yet. We designed a series of experiments choosing estradiol valerate and medroxyprogesterone representing as estrogen and progestogen and mitotic rate , PCNA index as markers hoping to solve this problem.This study was divided into two parts: animal experiment and clinical study. Animal experiment(1) The first part used OVX rats as models. Five dosages of E₂V 40, 200, 400, 600, 800μg/Kg were given orally for 24 hours. Both mitotic rate and PCNA index showed linear increase with increase in E₂V dosage.(2) The second part served as normal control. Rats were selected randomly according to metaestrous ,diestrous ,proestrous and estrous. The mitotic rate and PCNA index of the endometrium during different stages were examined , and the results showed both markers were at a lower level during estrous.(3) The third part showed clearly the difference in endometrial mitotic rate and PCNA index when 800μg/Kg estradiol valerate was given alone for a short period of 6 days or in combination with progestogen. There were almost no mitosis and PCNA staining in the OVX control group. In the treated group with estrogen only, mitotic rate and PCNA index showed a rise in the first three days then dropped to a low level on the fourth day, but rise again the 5th day. When MPA was added, both markers reduced to a low level in the luminal and glandular epithilum.(4) In the fourth part, imitating the usual clinical continuous and cyclic regimen. E₂V : MPA were given continuously for 21 days to four groups in the ratio of 1:0.1,...