The impact of post-warming culture duration on clinical outcomes of vitrified-warmed single blastocyst transfer cycles / 대한생식의학회지

Objective@#The objective of the study was to compare the effects of long-term and short-term embryo culture to assess whether there is a correlation between culture duration and clinical outcomes. @*Methods@#Embryos were divided into two study groups depending on whether their post-warming culture period was long-term (20–24 hours) or short-term (2–4 hours). Embryo morphology was analyzed with a time-lapse monitoring device to estimate the appropriate timing and parameters for evaluating embryos with high implantation potency in both groups. Propensity score matching was performed to adjust the confounding factors across groups. The grades of embryos and blastoceles, morphokinetic parameters, implantation rate, and ongoing pregnancy rate were compared. @*Results@#No significant differences were observed in the implantation rate or ongoing pregnancy rate between the two groups (56.3% vs. 67.9%, p=0.182; 47.3% vs. 53.6%, p=0.513). After warming, there were more expanded and hatching/hatched blastocysts in the long-term culture group than in the short-term culture group, but there was no significant between-group difference in embryo grade. Regarding pregnancy outcomes, the completion of re-expansion was faster in women who became pregnant than in those who did not for both culture durations (long-term: 2.19±0.63 vs. 4.11±0.81 hours, p=0.003; short-term: 1.17±0.29 vs. 1.94±0.76 hours, p=0.018, respectively). @*Conclusion@#The outcomes of short-term culture and long-term culture were not significantly different in vitrified-warmed blastocyst transfer. Regardless of the post-warming culture time, the degree of blastocyst re-expansion 3–4 hours after warming is an important marker for embryo selection.

The impact of post-warming culture duration on clinical outcomes of vitrified-warmed single blastocyst transfer cycles / 대한생식의학회지

Objective@#The objective of the study was to compare the effects of long-term and short-term embryo culture to assess whether there is a correlation between culture duration and clinical outcomes. @*Methods@#Embryos were divided into two study groups depending on whether their post-warming culture period was long-term (20–24 hours) or short-term (2–4 hours). Embryo morphology was analyzed with a time-lapse monitoring device to estimate the appropriate timing and parameters for evaluating embryos with high implantation potency in both groups. Propensity score matching was performed to adjust the confounding factors across groups. The grades of embryos and blastoceles, morphokinetic parameters, implantation rate, and ongoing pregnancy rate were compared. @*Results@#No significant differences were observed in the implantation rate or ongoing pregnancy rate between the two groups (56.3% vs. 67.9%, p=0.182; 47.3% vs. 53.6%, p=0.513). After warming, there were more expanded and hatching/hatched blastocysts in the long-term culture group than in the short-term culture group, but there was no significant between-group difference in embryo grade. Regarding pregnancy outcomes, the completion of re-expansion was faster in women who became pregnant than in those who did not for both culture durations (long-term: 2.19±0.63 vs. 4.11±0.81 hours, p=0.003; short-term: 1.17±0.29 vs. 1.94±0.76 hours, p=0.018, respectively). @*Conclusion@#The outcomes of short-term culture and long-term culture were not significantly different in vitrified-warmed blastocyst transfer. Regardless of the post-warming culture time, the degree of blastocyst re-expansion 3–4 hours after warming is an important marker for embryo selection.

What is the best treatment of heterotopic cervical pregnancies for a successful pregnancy outcome? / 대한생식의학회지

Heterotopic pregnancy is rare event and the risk is increased with assisted reproductive technology procedures. Heterotopic cervical pregnancy is even more unusual. We report a rare case of heterotopic cervical pregnancy that was managed successfully. A 36-year-old women who conceived by IVF-ICSI was diagnosed with heterotopic cervical pregnancy. She visited the emergency room with vaginal bleeding at 5 weeks of gestation and underwent careful intracervical gestational sac reduction with forceps under abdominal guidance the next day. The postoperative course was uneventful and with regular check-ups, the intrauterine pregnancy (IUP) progressed unremarkably through 41 weeks with delivery of a healthy newborn. We reviewed a total of 37 cases of heterotopic pregnancy that have been reported in the English language literature. There have been many attempts to eliminate the cervical embryo while preserving the IUP, and complete cervical evacuation is important in order to avoid infection, bleeding, and premature birth.

Endometrioid Adenocarcinoma Arising from Endometriosis of the Uterine Cervix: A Case Report

Endometrioid adenocarcinoma arising from endometriosis of the uterine cervix is rare in premenopausal woman. We describe here a patient with this condition and review the clinical and pathological features of these tumors. A 48-yr-old woman complaining of severe dysmenorrhea was referred for investigation of a pelvic mass. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Histological examination revealed an endometrioid adenocarcinoma directly adjacent to the endometriosis at the uterine cervix, with a transition observed between endometriosis and endometrioid adenocarcinoma. The patient was diagnosed as having endometrioid adenocarcinoma arising from endometriosis of the uterine cervix and underwent postoperative chemotherapy. Gynecologists and pathologists should be aware of the difficulties associated with a delay in diagnosis of endometrioid adenocarcinoma arising from endometriosis when the tumor presents as a benign looking endometrioma.

A case of small cell carcinoma of pulmonary type of ovary associated with huge mucinous cystadenocarcinoma / 대한산부인과학회지

Small cell carcinoma of ovary is extremely rare. This neoplasms compose predominantly or exclusively of small round cells with scant cytoplasm. There are two types of primary small cell carcinoma of ovary described in the literature : the hypercalcemic type and the pulmonary type. The first 11 patients with a primary ovarian small cell carcinoma of the pulmonary type were described by Eichorn et al. in 1992. The prognosis of this tumor is very poor and only limited data on the treatment of this tumor type are available. In the present case report, we describe a patient with the pulmonary type of small cell carcinoma associated with huge mucinous cystadenocarcinoma with a brief review of the concerned literatures.

Massive Perivillous Fibrin Deposition in Placenta

Massive perivillous fibrin deposition (MFD) is a rare condition characterized by heavy accumulation of fibrin in intervillous or perivillous spaces encasing villi throughout the placenta. This condition may cause varying degrees of placental insufficiency, leading to a significantly increased risk of intrauterine growth retardation, intrauterine death, and pre-term delivery. However, the objective criteria for the diagnosis of MFD have not been clearly established. We report a case of MFD associated with intrauterine growth retardation and preterm premature rupture of membranes.

An analysis of the risk factors for metabolic syndrome affecting stress urinary incontinence in korean middle-aged and older women / 대한산부인과학회지

OBJECTIVE: The purpose of this study was to identify the relationship between metabolic syndrome and stress urinary incontinence. METHODS: Based form 362 case, the risk factors including the parameters of metabolic syndrome for stress urinary incontinence (SUI) were analyzed retrospectively: body mass index (BMI), hypertension, insulin resistance, triglyceride, HDL-cholesterol. RESULTS: The risk for metabolic syndrome were associated positively with SUI. Women with the risks for metabolic syndrome had 2.503 times of the odds for SUI compared without the risks for metabolic syndrome (95% CI 1.28-4.87, p<0.001). The independent risk factors for SUI were BMI (OR 3.574 ; 95% CI 0.09-0.31, p<0.001) and insulin resistance (OR 2.563 ; 95% CI 0.04-0.31, p=0.011) by multivariate analysis. CONCLUSION: Our results suggested that metabolic syndrome was the important factor of the stress urnary incontinence. And we confirmed the need for the treatment of metabolic disturbance and the prevention of metabolic syndrome aimed at correcting hormonal-metabolic disturbance in middle-aged and older women with SUI.

Study on consecutive light microscopic changes of tumor cells and apoptotic index observed in serial cervical biopsies during neoadjuvant chemotherapy with 5-fluorouracil and cisplatin in locally advanced cervical cancer / 부인종양

OBJECTIVE: To determine the effects of neoadjuvant chemotherapy (5-fluorouracil plus cisplatin) on tumor cell morphology and apoptosis by analyzing the consecutive changes of apoptotic index (AI) and histology observed in the serially obtained cervical cancer tissues during the chemotherapy. METHODS: Cervical cancer tissues were obtained by punch biopsy just before starting the each cycle of neoadjuvant chemotherapy from five patients with locally advanced disease (stage IIb-IIIb), but previously untreated squamous cell carcinoma of uterine cervix. All patients were treated with three cycles of 5-fluorouracil (1,000 mg/m2 at day #1-5) and cisplatin (60 mg/m2 at day #1) at 3 weeks interval. All H & E stained cervical cancer tissue slides were scored for apoptotic index and observed for microscopic changes of tumor cells by a pathologist. RESULTS: After the first cycle of chemotherapy, AI was significantly increased (from 2 times to 8 times). And widespread injury to cytoplasm was observed and followed by karyorrhexis and karyolysis of nucleus of tumor cells. The size of tumor nests was reduced and it was also noted that fibrosis and infiltration of inflammatory cells were increased. The parts of tumor nests were replaced by mature squamous cells and the changes in nuclear morphologic features pointing in a more differentiated direction. But after the second cycle of chemotherapy, only one patient showed an increase in AI by 1.2 times over that after the first cycle of chemotherapy. The rest showed slight decreases in AI compared to that after the first cycle of chemotherapy. In addition, fewer microscopic morphologic changes of tumor cells induced by chemotherapy were observed after the second cycle of chemotherapy compared to those after the first cycle of chemotherapy. CONCLUSION: We found that AI hardly increased or rather decreased, and that microscopic changes of tumor cells were fewer after the second cycle of neoadjuvant chemotherapy compared to the situation after the first cycle of chemotherapy. Thus, we could deduce that chemoresistance might rapidly develop in cervical cancer cells after the first cycle of neoadjuvant chemotherapy using 5-fluorouracil and cisplatin. So we need to consider this problem when we treat the locally advanced cervical cancer patients with neoadjuvant chemotherapy using 5-fluorouracil and cisplatin.

Female adnexal tumor of probable Wolffian origin: A Case Report / 대한산부인과학회지

Female adnexal tumors of probable Wolffian origin (FATPWO) were first reported in 1973 and the disease is a rare clinical entity. They are often found in the leaves of the broad ligament, ovary and paravaginal tissue. We report a 40-year-old woman who presented with both adnexal masses filling the pelvic cavity which were hard and fixed on palpation, and the masses were radiologically diagnosed as both ovarian fibroma-thecomas on the CT scan. The left adnexal mass was surgically excised and pathologically proved to be fibroma, the left adnexal mass was excised and pathologically proved to be FATPWO.

An Analysis of the Metabolic Syndrome and the Clinicopathologic Prognostic Factors Affecting Survival in Patients with Uterine Endometrial Cancer / 대한산부인과학회지

OBJECTIVE: We aimed to evaluate the metabolic syndrome and the clinicopathologic prognostic factors of endometrial cancer results from 35 surgically staged patients and to find out those novel prognostic factors. METHODS: This study is based on 35 endometrial cancer patients. Difference of survival rate in the following histologic parameters and parameter of metabolic syndrome was analyzed: age, body mass index (BMI), hypertension, insulin resistance, triglyceride, HDL-cholesterol, FIGO stage, tumor grade, myometrial invasion, cervical involvement, adnexal metastasis, and lympho-vascular space invasion (LVSI). Concerning lymph node involvement, the ratio of metastatic lymph node to dissected lymph node (metastatic ratio: MR) was calculated in total pelvic lymph node. MR was divided into less than 0.5 to more than 0.5. In each group, 5-year survival rate (5YSR) was analyzed and compared. RESULTS: The overall 5YSR for all 35 patients was 78.8%. The 5YSR for insulin resistance and normal insulin tolerance were 94.1%, 33.6% (p=0.009). LVSI, adnexal metastasis and MR of pelvic lymph node were independent prognostic factors for the endometrial cancer patients. CONCLUSION: Our results suggested that there was a relationship between insulin resistance and endometrial cancer and we confirmed the need for the treatment of metabolic disturbance and the prevention of metabolic syndrome aimed at correcting hormonal-metabolic disturbance in endometrial cancer patients. The MR of pelvic lymph node is thought that one of the most important prognostic factor of the endometrial cancer.

Ex vivo expansion of umbilical cord blood-derived T-lymphocyte with autologous cord blood plasma / 대한산부인과학회지

OBJECTIVE: The objective of this study was to establish a clinically applicable culture system by investigating the use of autologous cord blood plasma (ACBP) instead of fetal bovine serum (FBS) for the ex vivo expansion of umbilical cord blood (UCB) T-lymphocytes. METHODS: Fresh UCB mononuclear cell (MNC) fractions were isolated by Ficoll-Hypaque density centrifugation. The nonadherent MNC fractions were then cultured with the anti-CD3 antibody 5 microgram/mL plus IL-2 175 U/mL in the presence of 10% FBS, 10% ACBP or homologous cord blood plasma (HCBP). On day 8, proliferation rate, cell surface markers, cytotoxic assay of UCB T-lymphocytes according to the medium supplemented with FBS, ACBP or HCBP were evaluated. RESULTS: Proliferation studies demonstrated a significant increase in the proliferative ability of UCB T-lymphocytes incubated in anti- CD3 and IL-2 irrespective of the medium supplemented with FBS or ACBP. In the FBS supplemented medium, expressions of the activated T-lymphocytes were increased significantly after culture: CD3+CD8+, CD3+CD25+, CD3+CD38+, and CD45RO+ (p<0.05). Also in the ACBP supplemented medium, expressions of the activated T-lymphocytes were increased significantly after culture: CD3+ CD8+, CD3+CD25+, and CD45RO+ (p<0.05). In the HCBP supplemented medium, expressions of the activated T-lymphocytes were increased significantly after culture as in the ACBP: CD3+CD8+, CD3+CD25+, and CD45RO+ (p<0.05). Of the activated T-lymphocytes, increase of cytotoxic CD3+CD8+ cells increased significantly in the ACBP and HCBP groups compared to FBS group (p<0.05). CONCLUSION: These findings support the feasibility of ex vivo expansion of umbilical cord blood T-lymphocytes in the medium supplemented with autologous cord blood plasma, instead of fetal bovine serum, for future adoptive cellular immunotherapy.

Vascular Endothelial Growth Factor and Angiopoietin-1 and -2 mRNA Expressions in Invasive Cervical Carcinoma / 대한산부인과학회잡지

OBJECTIVE: This study was aimed to investigate the vascular endothelial growth factor (VEGF) mRNA and angiopoietin (Ang) -1 and -2 mRNA expressions between cervical cancer and normal cervix, and to assess the relationships among their expression and other prognostic factors of invasive cervical cancer. METHODS: The tissues were obtained from 34 patients with cervical cancer and 14 patients with normal cervix undergoing hysterectomy. Total RNA was extracted and reverse transcribed into cDNA. RT-PCR and QC-PCR was performed to evaluate VEGF and Ang-1 and -2 mRNA expressions. Clinicopathologic factors of cervical cancer were reviewed with the patient's charts and results were analyzed with Mann-Whitney U test, Spearman correlation test and logistic regression analysis. RESULTS: VEGF, Ang-1 and -2 mRNA expression in cervical cancer was higher than that in normal cervix (p<0.05) and there were significant correlations between Ang-2 mRNA expression and VEGF mRNA expression in all stage of cervical cancer (p<0.05). A definite correlation was found between VEGF mRNA expression and clinical stage, SCC-Ag levels, lymph node metastasis of cervical cancer (p<0.05). Also, There was significant correlation among Ang-2 mRNA expression and clinical stage, tumor sizes, SCC-Ag levels, lymph node metastasis of cervical cancer (p<0.05). Ang-1 mRNA expression was significantly correlated with clinical stage of cervical cancer (p<0.05). CONCLUSION: The expression of VEGF mRNA, Ang-1 and -2 mRNA could be associated with the progression and metastasis of cervical cancer and might have a role as prognostic parameters in cervical cancer.

Expression of Matrix Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-2 Compared with ER and PR Expressions in the Endometriosis and Adenomyosis / 대한산부인과학회잡지

OBJECTIVE: This study was aimed to investigate the role of matrix metalloproteinase-2 (MMP-2) and inhibitor of metalloproteinase-2 (TIMP-2) for pathogenesis of endometriosis and adeonomyosis by the comparison of their expressions with those of ER (nuclear estrogen receptor) and PR (nuclear progesterone receptor) according to menstrual cycle. METHODS: Twenty seven cases of endometriosis, twenty four cases of adenomyosis,and twenty four cases of normal endometrium were classified by menstrual cycle (proliferative phase, early to mid secretory phase, and late secretory phase to menstrual period) and immunohistochemical study for ER, PR, MMP-2 (72 kD, gelatinase A), and TIMP-2 and Western immunoblotting for MMP-2 and TIMP-2 were performed. RESULTS: The results revealed increased expressions of MMP-2 and TIMP-2 in the epithelial cells of endometriosis throughout cycle compared with uterine endometrium. Expression of MMP-2 and TIMP-2 was weak in adenomyosis. In the epithelium of endometriosis, MMP-2 and ERrevealed a statistical significance each other (p<0.01). Expression of MMP-2 and TIMP-2 in both epithelium and stromal cells of endometriosis of stage 4 was higher than that of stage 1-3 and the expression of MMP-2 in epithelium and stage were statistically significance (p<0.05). PR expression tended to being reduced in both epithelial and stromal cells of endometriosis compared with normal uterine endometrium, except for late secretory phase. Expression of estrogen and progesterone receptors was weak in adenomyosis. By Western immunoblotting study, MMP-2 expression in endometriosis was higher than normal reproductive endometrium. CONCLUSION: The results suggest that the increased expression of MMP-2 associated with the ER expression in epithelium of endometriosis compared with normal endometrium is closely related with the pathogenesis and progression of the endometriosis. Adenomyosis may be associated with different mechanism such as invagination of basal layer of endometrium.

Synchronous Multiple Primary Malignant Neoplasm Involving the Uterine Endometrium and Ovary / 대한산부인과학회잡지

Multiple primary malignant neoplasm means that more than 2 cancers are independently developed in one individual. In general, the neoplasms are diagnosed simultaneously or within 6 month interval. Simultaneous presentation of carcinomas involving ovary and uterus is not a common event and presents a diagnostic dilemma when they are of the same histology. We experienced a rare case of multiple primary malignant neoplasm involving the uterine endometrium and the ovary synchronously. Thus we report this case with a review of literatures.

Microbiologic and Molecular Genetic Analysis of Lactobacillus spp. Isolated from Vagina of Korean Women and A Pilot Clinical Study on the Treatment of Vaginitis using the Best Lactobacillus Strain KLB 46 / 대한산부인과학회잡지

OBJECTIVE: The aim of this study was to analize the biologic and molecular genetic characteristics of Lactobacillus spp. isolated from vagina of Korean healthy women and to perform a pilot clinical study on the treatment of vaginitis using the best Lactobacillus strain KLB 46. METHODS: Vaginal specimens were obtained from 205 Korean women with healthy vaginal ecosystems. 155 lactobacillus strains were used for catalase test, cell surface hydrophobicity (CSH) test and antimicrobial activity test. Also we identified the species prevalence by PCR-RFLP analysis of 16S rDNA gene and performed the minimal inhibitory concentrationtest using14 antibiotics to determine their patterns of antibiotic susceptibility. A pilot clinical trial of 8 bacterial vaginosis, 1 trichomonas vaginitis and 6 atrophic vaginitis using Lactobacillus crispatus KLB 46 was done by vaginal instillation (10(10)-10(11) cells/mL). RESULTS: 155 lactobacilli strains were isolated and all isolates showed high CSH and 61% of the isolates had higher CSH. L. acidophilus and L. crispatus were the most prevalent species by PCR-RFLP analysis of their 16S rDNA gene. And PCR-RFLP analysis suggested that KLB 46 was L. crispatus. The clinical study showed that the vaginal epithelial adherence rate was high as 77% for bacterial vaginosis and 33.3% for atrophic vaginitis. CONCLUSION: The predominating lactobacilli were L. crispatus and L. acidophilus in Korean women's vaginas. Although further study would be needed, L. crispatus KLB 46 is a good candidate of suitable probiotics for bacterial vaginosis.

A Case of Primitive Neuroectodermal Tumor of the Uterus / 대한산부인과학회잡지

Primitive neuroectodermal tumor (PNET) is a rare tumor derived from fetal neuroectodermal cells. These tumors occur in the central nervous system and peripheral locations, but the occurrence of primitive neuroectodermal tumors located in the uterus is extremely rare. We present a 53-year-old woman with primitive neuroectodermal tumor of the uterus confirmed by immunohistochemical staining. We have experienced one case of PNET of the uterus and wish to report with brief review of concerned literature.

The Clinical Significance of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) in Pretreatment Evaluation of Invasive Cervical Cancer / 대한산부인과학회잡지

OBJECTIVE: This study aimed to evaluate the clinical significance of CT or MRI in detecting parametrial invasion, pelvic or para-aortic lymph node metastasis. We also evaluated whether IVP, cystoscopy and sigmoiodoscopy could be replaced by CT or MRI. METHODS: The medical records of 130 patients with invasive cervical cancer who were histologically diagnosed from Jan 1994 to Feb 1999 at MokDong Hospital were reviewed. We compared the results of physical examination, CT or MRI, and surgical finding in detecting the prarmetiral invasion and pelvic or para-aortic LN metastasis. We also compared the results of IVP, cystoscopy, sigmoidoscopy with the finding of CT or MRI. Fishers exact test was used and p<0.05 was regarded as statistically significant. RESULTS: CT or MRI were clinically significant in detecting parametrial invasion, pelvic or para-aortic LN metastasis, ureter, bladder and rectosigmoid invasion (p<0.005). In detecting parametrial invasion and pelvic or para-aortic LN metastasis, the positive predictive value of CT or MRI were 33.3%, 70% and the negative predictive value were 98%, 91.5%, respectively. In detecting ureter, bladder, and rectosigmoid invasion, the positive predictive value of CT or MRI were 62.5%, 26% and 17% and the negative predictive value were 98%, 100% and 100%, respectively. CONCLUSION: CT or MRI can provide useful information as to parametrial invasion and pelvic or para- aortic lymph node metastasis. CT or MRI can substitude for IVP, cystoscopy, sigmoidoscopy. And only if bladder and rectosigmoid invasion is suspected on MRI, we must perform cystoscopy and sigmoidoscopy to confirm the invasion. Because CT is either superior or equal to IVP in evaluation of the urinary tract, it is not necessary to perform IVP when CT is performed.

A Case of Malignant Mixed Mullerian Tumor of Uterus after Tamoxifen Therapy for Breast Cancer / 대한산부인과학회잡지

Tamoxifen is widely used for the treatment of breast cancer and currently proposed for preventive strategies. However. there is evidence that tamoxifen may affect other hormone sensitive organs, such as uterus and ovary. It has been documented that tamoxifen treatment is associated with development of endometrial polyp, endometrial hyperplasia, ovarian and endometrial cancer. Uterine malignant mixed mullerian tumor is a neoplasm which apparently arises from undifferentiated mullerian stroma and is composed of a mixture of malignant epithelial and stromal component. We report a case of malignant mixed mullerian tumor of uterus which was developed in a patient treated with tamoxifen for 5 years following a modified radical mastectomy due to breast cancer.

A Relationship with the Hormone Replacement Therapy and Breast Density in Postmenopausal Women / 대한산부인과학회잡지

OBJECTIVE: To determine the frequency and degree on change in mammographic densities, and calcification in the breast tissue, during different types of hormone replacement therapy and to evaluate the factors that play a role on the breast cancer. METHOD: A retrospective review of 268 cases menopausal women for HRT group and 52 cases menopausal women for unmatched control group. Mammographic evaluations for the distribution of breast densities and calcification, new solid mass and cyst in four different type of HRT were performed each every year during 5 years. The significant increase of breast densities and calcifications and new formation of neoplasm were taken with breast sonogram. 10 cases were biopsied for the confirmation of maliganancy. RESULT: Compared with the conrol groups, the hormone user group have a significant increase in the breast densitiy for 5 years (p0.05). Among 10 cases in suspicious malignancy, 9 cases were confirmed to the malignancy by biopsy. CONCLUSION: The results of this study revealed that not only progesterone combined HRT but also estrogen only HRT significantly increased mammographic density. There is no relationship on the calcification and HRT in this study. The annual checking of mammography is necessary to HRT.

A Relationship with the Hormone Replacement Therapy and Breast Density in Postmenopausal Women / 대한산부인과학회잡지

OBJECTIVE: To determine the frequency and degree on change in mammographic densities, and calcification in the breast tissue, during different types of hormone replacement therapy and to evaluate the factors that play a role on the breast cancer. METHOD: A retrospective review of 268 cases menopausal women for HRT group and 52 cases menopausal women for unmatched control group. Mammographic evaluations for the distribution of breast densities and calcification, new solid mass and cyst in four different type of HRT were performed each every year during 5 years. The significant increase of breast densities and calcifications and new formation of neoplasm were taken with breast sonogram. 10 cases were biopsied for the confirmation of maliganancy. RESULT: Compared with the conrol groups, the hormone user group have a significant increase in the breast densitiy for 5 years (p0.05). Among 10 cases in suspicious malignancy, 9 cases were confirmed to the malignancy by biopsy. CONCLUSION: The results of this study revealed that not only progesterone combined HRT but also estrogen only HRT significantly increased mammographic density. There is no relationship on the calcification and HRT in this study. The annual checking of mammography is necessary to HRT.