The Effect Of Sex Hormones On Proliferation, Invasion, Apoptosis Of Endometrial Cancer Cells And The Analysis Of Evidence-based Medicine On Horemone Replacement Therapy After Operation Of Endometrial Carcinoma

Endometrial carcinoma (EC), also known as carcinoma of corpus uteri, is a common, gradually increase in the incidence of gynaecological malignancy, and its incidence is the 3rd among that of gynaecological malignancy in China, but it is the most common gynaecological malignancy in developed countries. Some studies show that the ratio of patients under 40 years old have been increasing.5%-29%of affected women are younger than 40 years.The standard definitive surgery includes total hysterectomy, bilateral salpingo-oophorectomy and pelvic and/or para-aortic lymphadenectomy. Adjuvant therapy for endometrial cancer can include systemic chemotherapy, pelvic and vault radiation, adjuvant progestogen therapy.Bilateral oophorectomy in premenopausal women causes significant adverse long-term effects in bone, heart and neurologic health as well as in quality of life. It leads to an increased risk of premature death, cardiovascular disease, cognitive impairment or dementia, parkinsonism, osteoporosis and bone fractures, and a decline in psychological well-being and sexual function. Cancer treatment has three goals:to improve the cure rate, to lenghen survival time, and to improve quality of life. The main concerns are the potential stimulation of hormone-dependent cancer and any residual endometrium. Furthermore, the controversial debate about potential long-term effects of HRT on the increased risk of breast cancer has complicated matters and consequently many physicians see HRT as being contraindicated Although HRT significantly improves quality of life of women with menopausal symptoms, it is an ongoing hotly debated subject whether HRT is safe in patients after treatment for endometrial cancer.There are few such researches at home and abroad.. Although some studies are reported on the safety of HRT in survivers with endometrial cancer in foreign countries, large prospective case-control study is still lack.It is not conclusive whether HRT will increase postoperative recurrence and Shorten the survival. Evidence-based medicine help to apply the best research evidences to clinical practice, In this study, we use evidence-based medicine methods,after the integration the raw data of Original clinical researches on HRT in endometrial cancer survierors,Meta-analysis is done about the recurrence rate. We conclude that:homogeneity test I2 index is 0%, P=0.55, Heterogeneity is low, so we select the fixed effect model analysis. The combined RR=0.32,95%CI [0.17,0.59], P=0.0002, the difference was statistically significant. Therefore, HRT used in the suivivors did not increase the recurrence rate of endometrial cancer, while its recurrence rate is lower. Meta-analysis is done about the death rate. We conclude that: homogeneity test I2 index is 0%, P=0.68, Heterogeneity is low, so we select the fixed effect model analysis. The combined RR=0.48,95%CI [0.23,1.02], P=0.05, the difference was not statistically significant. So we could not drow a conclusion whether HRT can increase mortality of endometrail cancer patients. But HRT may affect the patients death rate from reducing about 77%to increasing about 2%. There are evidence that HRT don't increase the recurrence of endometrial cancer after treatment. For the overall survival, there is no unanimous conclusion. To improve the quality of life of patients, HRT can be considered to use among early endometrial cancer suvivors without risk factors, based on successful treatment. When we should start using HRT after endometrial cancer therapy and what is the teatment options of HRT, we should need do a large prospective randomized study. This study provides us with convincing evidence.There are two types of EC:TypeⅠaccounts for about 90%of cases. It is an oestrogen-dependent cancer that tends to be endometrioid in cell type, oestrogen and progesterone receptor positive and generally presents with a lower grade. TypeⅡEC occurs mainly in postmenopausal women and is not oestrogen-dependent. It tends to be of serous papillary or clear cell type; it is more aggressive with a higher histological grade, and lacks oestrogen and progesterone receptors. The risk factors for typeⅠEC are well established and include unopposed oestrogen use and obesity. The hyperoestrogenic state in obese women can be caused by both chronic progesterone deficiency due to anovulation and enhanced peripheral conversion of androgens to oestrogens in peripheral adipose. Having a history of endometrial cancer or breast cancer are considered as a contraindication for HRT, but now there are some new ideas, for example, Breckwokdt draw a conclusin that patients with a history of breast cancer can use HRT if ER or PR is negative, because the tumor does not respond to the hormone. We know HRT include estrogen and progesterone. The current view is that:HRT consists of oestrogen which has to be combined with a progestogen in women with intact uterus to avoid the induction of proliferative endometrial changes like endometrial cancer. For the women without uterus can be only given estrogen, because progesterone may lead to increase incidence of breast cancer. According to this view, whether the endometrial cancer patients need not to use progestogen because of uterus removed? However, progesterone not only can protect the endometrium to reduce the risk of endometrial cancer, but also is an adjuvant drugs for ER-positive endometrial cancer. For these reasons, whether after the addition of progesterone made HRT is more safer for endometrial cancer? This study includes the two types of endometrial cancer cells-ER positive ishikawa cell line and ER low-expressive HEC-1A cell line. This study demonstrated that 17β-E2 did not increase the chance of endometrial cancer cell proliferation and invasion capacity. On the contrary,17β-E2 reduced the proliferation of ishikawa cell line,and accelerated the apoptosis of ishikawa cell line. The role of cisplatin does not be affected by the estrogen. Compared with estrogen group,17P-E2 plus progesterone group make the Ishikawa cell line more slowly proliferate and less invasive, but apoptosis was similar in both groups. For the HEC-1A cell line, the two groups respects similar in the proliferation, invasion and apoptosis. The results of this study tell us:Firstly, in order to improve low estrogen status and quality of life of postoperative endometrial cancer patients, estrogen replacement therapy can be considered in EC patients after operation. Secondly, because of the use of progesterone may brings much more benefits for ER-positive patients, we can consider to use estrogen plus progestin for the ER-positive patients after endometrial cancer therapy, while estrogen alone can be consider to apply for ER-negative patients. In short,we should use HRT individually to postoperative patients of EC, based on specific situation. Thirdly, we shoulld be cautious to apply HRT to postoperative patients currently, and we should fully communicate with patients because there are not adequate data of evidence-based medicine and results of basic theoretical results now.