The Clinical Research Of Estrogen And Progesterone Vaginally Sequential Administration On Endometrial Receptivity In Amenorrhea Patients

ObjectiveEndometrial receptivity is the ability of endometrium receiving embryo, and it can be strictly restricted by time and space. Vaginal administration is a special therapy method in female, which has many advantages including quick absorption, direct function, low-use dose and high efficiency. Dydrogesterone is trans-progesterone which has similar molecular structure with endogenous progesterone, and there is no relevant research about its vaginal administration. Central or ovarian amenorrhea patients have low serum level of estrogen and progesterone, which induces dysplasia of uterus and endometrium so as to decrease endometrial receptivity. Our purpose was to determine the efficacy of estrogen and progesterone vaginally sequential administration on endometrial receptivity in amenorrhea patients by means of the comparison between vaginal and oral medication.MethodsTwelve central or ovarian amenorrhea patients were included in the study. They were random divided into two groups, administrated orally (Group A) or vaginally (Group B) sequential estrogen and progesterone separately. The former 14 days were given 17β-estrogen, and the latter 14 days were given 17β-estrogen and dydrogestrone simultaneously. After 14 days and 21 days of therapy, therapeutic effect and endometrial receptivity were evaluated by serum hormones, endometrial morphology, histology and hormone receptors expression. Serum samples were assayed to determine estradiol (E2), progesterone (P) and sex hormone-binding globulin (SHBG) concentrations so as to compare the hormones’content and activity. With the use of transvaginal ultrasonography, endometrial thickness, endometrial and subendometrial blood flow pattern and parameters which contained peak systolic velocity (PSV), pulsatility index (PI) and resistance index (RI) of uterine arteries were inspected. Endometrium were obtained by uterine cavity organizations suckers from the corpus of the uteri, which accompanied with the tissue sectioning, staining and software analysis to compare the development of glands and intercellular substances. The expression of estrogen receptor (ER) and progesterone receptor (PR) were determined by immunohistochemistry and semiquantitative method.Results1. The concentrations of E2 in Group B were statistically higher than Group A (P<0.05), with no significant difference in that of P and SHBG (P>0.05).2. The uterine size in Group B were bigger than Group A, and the endometrial thickness of two groups were both higher than treatment before (P<0.05). No statically differences were found in the endometrial thickness, PSV, PI, RI among groups at the 21 days of therapy (P>0.05). The endometrial blood pattern in Group B was better than Group A, but had no statically criteria.3. At the 14th day, endometrium in Group A were in the middle proliferative phase and one in Group B were in the late proliferative phase. At the 21st day, endometrium in Group A were in the early secretory phase and one in Group B were in the middle proliferative phase. Both at the 14th and 21st days of treatment, the endometrial glandular area, perimeter, glandular mean diameter, glandular lumens area, constituent ratio of glands and lumens in Group B were higher than Group A, and constituent ratio of mesenchyme was opposite. In the 14th day of therapy, the average height and constituent ratio of glandular epithelia in Group B were higher than Group A, whereas the 21st was the opposite. The results above had statically significances (p<0.05).4. ER and PR expression in two groups both decreased at the 21st day, which was consistent with menstrual cycle. ER expression of Group B in the glandular epithelia cells and interstitial cells were statistically higher than Group A (P<0.05), whereas PR had no significant difference.Conclusions1. It was the low-dose estrogen vaginal administration that increased serum E2 level observably and had high bioactivity. Dydrogestrone was trans-progesterone, which couldn’t be measured in serum, but the histology results revealed that it could promote excretive reversion of endometrium perfectly.2. Without excessive endometrial growth, estrogen and progesterone vaginal administration play a better role in promoting the development of uterine than oral usage. Estrogen and progesterone vaginally sequential administration didn’t change the endometrial and subendometrial blood flow, which might have something to do with the limitation of two-dimensional ultrasound.3. Estrogen and progesterone vaginally sequential administration had better efficacy in glandular proliferation and excretion than orally, and the morphology was in accordance with menstrual period. The influence of orally therapy was latter than menstrual cycle.4. Estrogen and progesterone vaginally sequential administration increased ER expression, but high serum E2 level didn’t influence PR expression in the glandular epithelial cells during the implantation window.