Relationship between menopausal hormone therapy and incidence of fractures in postmenopausal women.

OBJECTIVE: Long-term protective effects of menopausal hormone therapy (MHT) at fractures with different doses and components are controversial. We analyzed the effect of MHT on the incidence of spine and femur fractures according to MHT type, age at commencement, duration and dose of hormones in Korean women. METHOD: This retrospective study evaluated propensity score-matched patients with MHT from the Korean National Health Insurance Service database. Among women aged ≥50 years with menopause between 2004 and 2007, spine and femur fracture incidence until 2017 was analyzed in 36,446 women who had received MHT for >1 year. Estrogen-progesterone therapy (EPT), estrogen-only therapy (ET) or tibolone therapy was conducted. RESULTS: EPT significantly lowered the incidence of spine and femur fractures with a conventional dose, but not with a low dose. Tibolone significantly decreased the incidence of spine fractures in women aged 50-59 years when used for >5 years, and the incidence of femur fractures in women older than 60 years when used for >3 years. ET significantly lowered the risk of femur fractures when estradiol was used for >5 years. CONCLUSION: In menopausal women, all MHT including conventional-dose EPT, ET and tibolone tended to lower the incidence of fractures. The effects, however, varied with the type of fracture and type of MHT.

Hormone replacement therapy and myocardial infarction and stroke in postmenopausal Korean women.

OBJECTIVE: This study aimed to investigate the association of hormone replacement therapy (HRT) use, type, duration and age of commencement with myocardial infarction (MI) and stroke in postmenopausal Korean women. METHODS: This nested case-control study used data from the National Health Insurance Service database to analyze 2017 data from women aged ≥50 years and diagnosed with natural menopause between 2004 and 2007. Among 356,160 eligible women, 36,446 used HRT for ≥1 year and 319,714 did not (controls). These two groups were matched 1:1 for statistical analysis. Type and duration were categorized into three categories. RESULTS: Women who started estrogen-progestogen therapy (EPT) or estrogen therapy (ET) in their 50s, or EPT or tibolone in their ≥60s exhibited a lower stroke risk than controls. MI risk was lower among women who used tibolone - regardless of duration - or EPT or ET for 1-3 years than among controls. Stroke risk was lower with tibolone use for ≥5 years or with EPT or ET use for 1-3 years or ≥5 years than non-users. CONCLUSION: Our study may support the beneficial effect of HRT by showing that Korean postmenopausal women who used HRT at a relatively younger and healthier age had a relative benefit for MI and stroke.

Effects of Hormone Replacement Therapy on Bone Mineral Density in Korean Adults With Turner Syndrome.

BACKGROUND: Turner syndrome (TS) is a common chromosomal abnormality, which is caused by loss of all or part of one X chromosome. Hormone replacement therapy in TS is important in terms of puberty, growth and prevention of osteoporosis however, such a study has never been conducted in Korea. Therefore, the purpose of our study was to determine relationship between the starting age, duration of estrogen replacement therapy (ERT) in TS and develop a hormone replacement protocol suitable for the situation in Korea. METHODS: This is retrospective study analyzed the medical records in TS patients treated at the Severance hospital, Yonsei University College of Medicine, Seoul, Korea from 1997 to 2019. Total of 188 subjects who had received a bone density test at least once were included in the study. Korean National Health and Nutrition Examination Survey (KNHANES) was used for achieving bone mineral density (BMD) of normal control group. Student's t-test, Mann-Whitney U test, ANOVA and correlation analysis were performed using SPSS 18.0. RESULTS: Each BMD measurement was significantly lower in women with TS than in healthy Korean women. Early start and longer duration of ERT is associated with higher lumbar spine BMD but not femur neck BMD. Femur neck BMD, but not lumbar spine BMD was significantly higher in women with mosaicism than 45XO group. CONCLUSION: Early onset and appropriate duration of hormone replacement therapy is important for increasing bone mineral density in patients with Turner syndrome. Also, ERT affects differently to TS patients according to mosaicism.

Effect of catheter-directed ethanol sclerotherapy on ovarian reserve in patients with recurrent endometrioma: comparative analysis with primary endometriosis.

OBJECTIVE: Catheter-directed ethanol sclerotherapy (CDS) is known to less affect the ovarian function, with comparable efficacy. This study aims to investigate the change in ovarian reserve after catheter-directed ethanol sclerotherapy in patients with recurrent endometrioma, as compared to primary endometrioma. MATERIALS AND METHODS: Retrospective, observational study. Electronic medical records and images of patients with endometrioma who underwent CDS from August 2014 to April 2022 at a single institution were obtained. Patients aged > 18 years old and with anti-Müllerian hormone (AMH) level between 0.8 and 10.0 with regular menstruation were enrolled. Cyst diameter, laterality, AMH level, and CA-125 level before and after 1 month, 6 months, 1 year, 2 years, and 3 years of sclerotherapy were obtained. RESULTS: A total of 180 patients were fit for analysis. There was no statistical difference in age and cyst size between the two groups. Mean values of AMH in each group were 3.35 in the primary group and 3.00 in the recurrent group prior to the procedure (p = 0.347). There was no significant difference in delta value of AMH after sclerotherapy in both groups at each follow-up period. Also, this result was consistent when stratified by laterality, preprocedural AMH level, and initial size of endometrioma. No case of recurrence was reported in both groups. CONCLUSIONS: The effect of CDS on ovarian reserve is not inferior in recurrent endometrioma compared to primary endometrioma. Since sclerotherapy is known to less deteriorate the ovarian function than surgical removal of endometrioma, clinician could consider this as the first-line therapy in patients with recurrent endometrioma. CLINICAL RELEVANCE STATEMENT: Catheter-directed ethanol sclerotherapy for patients with recurrent endometrioma has similar effect on ovarian reserve compared to patients with primary endometrioma. KEY POINTS: • Secondary surgery for endometrioma has significant deleterious effect on ovarian function. • Catheter-directed sclerotherapy (CDS) for endometrioma had equally minimal adverse effect on ovarian reserve, represented as anti-Müllerian hormone (AMH), in both primary and recurrent groups. • Physicians should consider CDS for patients with recurrent endometrioma who desire to preserve ovarian function.

Therapeutic Efficacy of Catheter-directed Ethanol Sclerotherapy and Its Impact on Ovarian Reserve in Patients with Ovarian Endometrioma at Risk of Decreased Ovarian Reserve: A Preliminary Study.

STUDY OBJECTIVE: To investigate the therapeutic efficacy of catheter-directed ethanol sclerotherapy (CDS) and its effect on ovarian reserve in patients with endometrioma at risk of decreased ovarian reserve. DESIGN: Retrospective study. SETTING: Teaching hospital. PATIENTS: We evaluated 18 patients with ovarian endometrioma measuring ≥3 cm and preprocedural serum antimüllerian hormone (AMH) levels of <2 ng/mL. INTERVENTIONS: An 8.5-F catheter was inserted either transabdominally or transvaginally into the endometrioma. After aspiration, sclerotherapy with 99% ethanol was performed, with a subsequent 20-minute ethanol retention. MEASUREMENTS AND MAIN RESULTS: Ultrasonography was performed preprocedurally and 6 months after CDS to evaluate any recurrence or changes in cyst size. Furthermore, serum AMH levels, cancer antigen 125 (CA-125) levels, and the visual analog scale scores for dysmenorrhea were obtained to analyze the ovarian reserve and treatment efficacy, preprocedurally and at 6 months after CDS. The mean cyst size on ultrasonography and serum CA-125 levels decreased 6 months after CDS (p <.001 and p = .001, respectively). All patients reported a decreased visual analog scale score for dysmenorrhea (p <.001). However, the difference in serum AMH levels before and after CDS was statistically insignificant (p = .875). CONCLUSION: CDS was efficacious in reducing pain and serum CA-125 levels in patients with low AMH levels without adversely affecting their ovarian reserve.

Identification of Single Nucleotide Polymorphisms as Biomarkers for Recurrent Pregnancy Loss in Korean Women.

BACKGROUND: Single nucleotide polymorphisms (SNPs) are reportedly associated with repeated abortion. Thus, genetic analysis based on race is the key to developing accurate diagnostic tests. This study analyzed the genetic polymorphisms of recurrent pregnancy loss (RPL) patients among Korean women compared to the controls. METHODS: In 53 women of RPL group and 50 controls, the genetic analysis was performed. The genotype distribution and allele frequency were analyzed statistically for the difference between the two groups. The association between each SNP marker and RPL risk was analyzed. RESULTS: The genotypes of LEPR, endothelial nitric oxide synthase (eNOS), KDR, miR-27a, miR-449b, and tumor necrosis factor-alpha (TNF-α) were analyzed using odds ratio (OR) with 95% confidence intervals (CIs). Only the AG genotype of miR-449b (A>G) polymorphism showed significant association with the risk of RPL when compared to the AA genotype (OR, 2.39). The combination of GG/AG+GG/CA+AA genotypes for eNOS/miR-449b/TNF-α was associated with 7.36-fold higher risk of RPL (OR, 7.36). The GG/AG+GG combination for eNOS/miR-449b showed 2.43-fold higher risk for RPL (OR, 2.43). The combination of AG+GG/CA+AA genotypes for miR-449b/TNF-α showed a significant association with the risk of RPL (OR, 7.60). From the haplotype-based analysis, the G-G-A haplotype of eNOS/miR-449b/TNF-α and the G-A haplotype of miR-449b/TNF-α were associated with increased risk of RPL (OR, 19.31; OR, 22.08, respectively). CONCLUSION: There is a significant association between the risk of RPL and miR-449b/TNF-α combination, and therefore, genetic analysis for specific combined genotypes can be an important screening method for RPL in Korean women.

Cytokines in culture media of preimplantation embryos during in vitro fertilization: Impact on embryo quality.

Cytokine support of embryonic development includes promotion of implantation and protection of blastomeres from cell stress and apoptosis. Correlations between embryo quality and concentrations of specific cytokines in culture media of human embryos have been investigated for many years. The aim of this study was to assess the concentrations of cytokines in preimplantation embryo culture media and to investigate their relationships with embryo quality and in vitro fertilization (IVF) outcomes. Seventy-two samples were obtained from 39 infertile couples undergoing IVF or intracytoplasmic sperm injection treatment between October 2018 and May 2019. Each embryo was cultured separately, and the embryo culture medium was collected 72 h after fertilization. Before embryo transfer on day 3, a morphological evaluation of each embryo was performed. Cytokine concentrations of each culture medium were analyzed for 23 selected cytokines using the Multiplex Cytokine/Chemokine Panel II Assay (Merck Millipore®). The results were categorized into two groups (top-quality and non-top-quality embryos). The median age of the 39 patients was 34 years. Nine of 23 cytokines were quantified and compared between the top-quality embryo group and non-top-quality embryo group. Among the nine cytokines, CCL15, CCL27, and CXCL-12 were significantly elevated in the top-quality embryo group. These results suggested that specific cytokines measured in human embryo culture media can be used to predict embryo quality and IVF outcomes.

Comparison of the therapeutic efficacy and ovarian reserve between catheter-directed sclerotherapy and surgical excision for ovarian endometrioma.

OBJECTIVES: To compare the efficacies of catheter-directed sclerotherapy (CDS) with 99% ethanol and surgery for ovarian endometrioma and their impact on the ovarian reserve. METHODS: From January 2011 to June 2019, 71 patients who underwent surgical excision (n = 51) or CDS (n = 20) for symptomatic ovarian endometriomas were reviewed. To analyze the effect on the ovarian reserve, serum anti-Müllerian hormone (AMH) levels were compared before and after the procedure. Symptoms, serum cancer antigen 125 (CA-125), lesion size, recurrence, hospitalization, and complications were reviewed retrospectively. RESULTS: During a mean follow-up of 22.3 months (range, 6 to 94 months), no significant difference in symptom relief was found between CDS and surgery (95.0% [19/20] and 92.2% [47/51], respectively, p > 0.999). The hospital stay was shorter with CDS than with surgery (2.6 ± 0.6 days and 4.1 ± 0.5 days, respectively, p < 0.001). There was no significant difference in serum AMH levels before and after CDS (2.3 (interquartile range (IQR) 1.1-5.3) ng/mL and 2.6 (IQR 0.9-4.9) ng/mL, respectively, p = 0.243), but there was a significant decrease in serum AMH in the surgery group (3.0 (IQR 1.3-5.5) ng/mL and 1.6 (IQR 0.7-3.2) ng/mL, respectively, p < 0.001). CA-125 decreased in both CDS and surgery groups (p = 0.001 and < 0.001, respectively). Two minor complications occurred in the surgery group, while no complication was observed in the CDS group. CONCLUSIONS: The therapeutic efficacy of CDS appears to be comparable to that of surgical resection for ovarian endometrioma. Ovarian function was well-preserved, and a shorter hospital stay was required in patients who underwent CDS. KEY POINTS: • There was no significant difference in symptom relief between CDS and surgery (95.0% [19/20], 92.2% [47/51], respectively, p >0.999). • No significant difference in serum AMH levels was seen before and after CDS (2.3 (1.1, 5.3)* ng/mL, 2.6 (0.9, 4.9)* ng/mL, respectively, p = 0.243), whereas serum AMH levels significantly decreased after surgical resection (3.0 (1.3, 5.5)* ng/mL, 1.6 (0.7, 3.2)* ng/mL, respectively, p <0.001). *Median (25 quartiles, 75 quartiles) • The hospitalization period was shorter with CDS than with surgery (2.6 ± 0.6 days, 4.1 ± 0.5 days, respectively, p <0.001).

Vulvar Crohn's disease in an adolescent diagnosed after unsuccessful surgical treatment.

BACKGROUND: This case report presents a case of Vulvar Crohn's disease (VCD) in an adolescent, that is an uncommon manifestation of Crohn's disease (CD) without gastrointestinal symptoms. Before treating CD itself with proper medication, vulvar abscess continued to recur without improvement. CASE PRESENTATION: We report the case of an 18-year-old woman with VCD. After treatment with azathioprine 50 mg daily and mesalazine 1 g three times daily, vulvar lesions resolved after 6 weeks. We collected electronic medical data on patient characteristics, and evaluated findings of physical examinations, pelvic MRI, and biopsy specimen obtained from gastroduodenoscopy/colonoscopy. CONCLUSIONS: VCD is a rare manifestation of CD that may be misdiagnosed in the absence of gastrointestinal symptoms leading to delayed treatment. If a patient has an unexplained vulvar inflammatory lesion and with repeated failed surgical treatment, gynecologists should consider the possibility of a VCD.

Korean red ginseng induces extrinsic and intrinsic apoptotic pathways in MCF-7 breast cancer cells and MCF-10A non-malignant breast cells.

BACKGROUND: Among non-hormonal treatments, herbal products are frequently used by women. Korean red ginseng (KRG) is one of the popular herbal medicines. KRG could be one option for relieving menopausal symptoms. However, there are still concerns about the safety for long-term use. In order to be used for alleviating menopausal symptoms, the safety of KRG on breast must be ensured. The purpose of this study was to investigate the effects of KRG on breast cells. METHODS: MCF-7 and MCF-10A cells were treated with different concentrations of KRG extracts for 48 h. Cell viability was evaluated by MTT assay, and apoptosis by flow cytometry. The expression of apoptosis-related proteins was determined by western blot analysis and estrogen receptor (ER) affinity by ER binding assay. RESULTS: KRG extract inhibited growth and induced apoptosis of both MCF-7 and MCF-10A cells in dose-dependent manner. KRG extract increased the expression of pro-apoptotic proteins BAX, BAK, and BAD and decreased the expression of anti-apoptotic proteins Bcl-2 and Bcl-XL in both cells. The expressions of Fas and FasL were increased in lower doses, but decreased in higher doses in both cells. Activities of caspase-3, -8 and -9 increased in MCF-10A, while caspase-8 and -9 showed increase in MCF-7. Competition of KRG to E2 was significant in MCF-7 as KRG dose increased, whereas ER binding was hardly shown in MCF-10. CONCLUSION: KRG induced apoptosis via extrinsic and intrinsic pathway in MCF-7 breast cancer cells and MCF-10A non-malignant cells. KRG may be safely used with regard to breast cancer risk in postmenopausal women to reduce the vasomotor symptoms.

Robotic single-site versus multi-port myomectomy: a case-control study.

BACKGROUND: This study aimed to evaluate the compatibility of robotic single-site (RSS) myomectomy in comparison with the conventional robotic multi-port (RMP) myomectomy to achieve successful surgical outcomes with reliability and reproducibility. METHODS: This retrospective case-control study was performed on 236 robotic myomectomies at a university medical center. After 1:1 propensity score matching for the total myoma number, total myoma diameter, and patient age, 90 patients in each group (RSS: n = 90; RMP: n = 90) were evaluated. Patient demographics, preoperative parameters, intraoperative characteristics, and postoperative outcome measures were analyzed. RESULTS: The body mass index, parity, preoperative hemoglobin levels, mean maximal myoma diameter, and anatomical type of myoma showed no mean differences between RSS and RMP myomectomies. The RSS group was younger, had lesser number of myomas removed, and had a smaller sum of the maximal diameter of total myomas removed than the RMP group. After propensity score matching, the total operative time (RSS: 150.9 ± 57.1 min vs. RMP: 170 ± 74.5 min, p = 0.0296) was significantly shorter in the RSS group. The RSS group tended to have a longer docking time (RSS: 9.8 ± 6.5 min vs. RMP: 8 ± 6.2 min, p = 0.0527), shorter console time (RSS: 111.1 ± 52.3 min vs. RMP: 125.8 ± 65.1 min, p = 0.0665), and shorter time required for in-bag morcellation (RSS: 30.1 ± 17.2 min vs. RMP: 36.2 ± 25.7 min, p = 0.0684). The visual analog scale pain score 1 day postoperatively was significantly lower in the RSS group (RSS: 2.4 ± 0.8 days vs. RMP: 2.7 ± 0.8 days, p = 0.0149), with similar consumption of analgesic drugs. The rate of transfusion, estimated blood loss during the operation, and length of hospital stay were not different between the two modalities. No other noticeable complications were observed in either group. CONCLUSIONS: Da Vinci RSS myomectomy is a compatible option with regard to reproducibility and safety, without significantly compromising the number and sum of the maximal diameter of myomas removed. The advantage of shorter total operative time and less pain with the same amount of analgesic drugs in RSS myomectomy will contribute to improving patient satisfaction.

Changes in the Expression of TBP-2 in Response to Histone Deacetylase Inhibitor Treatment in Human Endometrial Cells.

Histone deacetylase inhibitors (HDACi) induce apoptosis preferentially in cancer cells by caspase pathway activation and reactive oxygen species (ROS) accumulation. Suberoylanilide hydroxamic acid (SAHA), a HDACi, increases apoptosis via altering intracellular oxidative stress through thioredoxin (TRX) and TRX binding protein-2 (TBP-2). Because ROS accumulation, as well as the redox status determined by TBP-2 and TRX, are suggested as possible mechanisms for endometriosis, we queried whether SAHA induces apoptosis of human endometrial cells via the TRX-TBP-2 system in endometriosis. Eutopic endometrium from participants without endometriosis, and ectopic endometrium from patients with endometriosis, was obtained surgically. Human endometrial stromal cells (HESCs) and Ishikawa cells were treated with SAHA and cell proliferation was assessed using the CCK-8 assay. Real-time PCR and Western blotting were used to quantify TRX and TBP-2 mRNA and protein expression. After inducing oxidative stress, SAHA was applied. Short-interfering TRX (SiTRX) transfection was performed to see the changes after TRX inhibition. The mRNA and protein expression of TBP-2 was increased with SAHA concentrations in HESCs significantly. The mRNA TBP-2 expression was decreased after oxidative stress, upregulated by adding 2.5 µM of SAHA. The TRX/TBP-2 ratio decreased, apoptosis increased significantly, and SiTRX transfection decreased with SAHA. In conclusion, SAHA induces apoptosis by modulating the TRX/TBP-2 system, suggesting its potential as a therapeutic agent for endometriosis.

Potential roles of aquaporin 9 in the pathogenesis of endometriosis.

Aquaporins (AQPs) are involved in cell migration, proliferation and carcinogenesis in tumor development and physiologic inflammatory processes, but their associations with endometriosis have not been fully evaluated. In this study, tissue samples were obtained from women undergoing laparoscopic surgery for endometriosis and other benign conditions. Analysis of expressions of AQP subtypes in eutopic and ectopic endometrium of patients with endometriosis (Eu-EMS and Ect-EMS, respectively) and eutopic endometrium of control patients without endometriosis (Eu-CTL) were performed using the NanoString nCounter System and western blotting. Human endometrial stromal cells (HESCs) were cultured and transfected with the siRNA of the AQP of interest. Among the AQP1-9 subtypes, endometrial expression of AQP2 and AQP8 was significantly increased, whereas AQP9 expression was significantly decreased in the Eu-EMS group compared to the Eu-CTL group. Comparison of expression of AQP2, AQP8 and AQP9 among Eu-EMS, Ect-EMS and Eu-CTL groups revealed significant differences for only AQP9. Expression of AQP9 in the Eu-EMS group was decreased compared with that in Eu-CTL. After transfection of AQP9 siRNA in HESCs, expressions of MMP2 and MMP9 were significantly elevated. Increased expression of phosphorylated ERK 1/2 and phosphorylated p38 MAPK proteins after transfection was also confirmed using western blot analysis. Increased migration and invasion potentials of HESCs after transfection were determined by migration and wound healing assays. These findings suggest that AQP9 may be involved in the pathogenesis of endometriosis and warrant further investigation as a potential therapeutic target for treating endometriosis.

Effect of deflazacort on pregnancy outcome in kidney transplant patients: should we change the immunosuppressant before conception?

BACKGROUND: Despite the good prognosis in patients with transplant organs, limited evidence is available on how immunosuppressants affect pregnancy. The aim of this study was to determine whether immunosuppressant use affects the pregnancy outcome and to identify whether there is any need to change the immunosuppressant before the patient tries to conceive. METHODS: This retrospective cohort study included women with previous kidney transplantation history who visited the Department of Obstetrics and Gynecology for either infertility or antenatal care between January 2005 and May 2016. A total of 40 cases (36 women) met the inclusion criteria. Statistical analyses were performed using SAS version 9.4. RESULTS: There were no differences in the immunosuppressant regimen between the pregnant and non-pregnant groups (never-pregnant+miscarriage) (P = 0.73). Individual immunosuppressant use was significantly different in terms of pregnancy outcome among the never-pregnant, miscarriage, and clinical pregnancy groups (azathioprine, P = 0.01; deflazacort, P < 0.0001). Only deflazacort use differed significantly between the clinical pregnancy and non-pregnant groups (P = 0.003). After adjusting for factors that may affect pregnancy outcome, deflazacort use remained significantly associated with a decreased odds ratio for clinical pregnancy (P = 0.02). Cox regression analysis also showed that deflazacort use was the only remaining factor that could hinder the success of clinical pregnancy (P = 0.03). CONCLUSIONS: Our study suggests that the type of immunosuppressive regimen may not affect the success of clinical pregnancy. However, deflazacort may decrease the possibility of clinical pregnancy in women with kidney transplant when they try to conceive.

Use of the Endometriosis Fertility Index to Predict Natural Pregnancy after Endometriosis Surgery: A Single-Center Study.

AIMS: Our objective was to predict natural pregnancy after endometriosis surgery using the endometriosis fertility index (EFI). METHODS: A retrospective medical records review was conducted, examining patients surgically treated for endometriosis at a single center in Korea between January 2009 and February 2015. In total, 68 women attempting natural conception were analyzed by assessing age, preoperative serum CA-125, body mass index, revised American Fertility Society (rAFS) stage, EFI, and pregnancy outcome. Kaplan-Meier estimates and log-rank tests were used to generate cumulative natural pregnancy rate curves based on an EFI cut-point. A receiver-operating characteristic (ROC) curve was plotted for EFI. RESULTS: Seventy-seven patients attempted conceptions, resulting in 33 natural and 9 assisted conceptions. Excluding assisted conceptions, the mean EFI scores of 68 women who were not pregnant and pregnant were 5.43 ± 0.36 and 6.88 ± 0.28 respectively. The relation between EFI and natural pregnancy was significant (cumulative overall pregnancy rate, p = 0.006), whereas rAFS stage was not (univariate logistics, p = 0.853). The cut-point for maximum natural pregnancy outcomes was 6 (area under ROC curve = 0.710, 95% CI 0.586-0.835). CONCLUSION: The EFI is a reliable staging system for predicting natural pregnancy after endometriosis surgery. EFI scores can be used to guide postoperative treatment of women with endometriosis.

MiR-150-5p May Contribute to Pathogenesis of Human Leiomyoma via Regulation of the Akt/p27Kip1 Pathway In Vitro.

Uterine leiomyoma is found in ~50-80% of women of a reproductive age and is the most common reason for hysterectomy. Recently, posttranscriptional gene silencing by microRNAs (miRs) has been reported as a mechanism for regulating gene expression stability in the pathogenesis of uterine leiomyomas. In this study, miR microarray analysis of leiomyomas and paired myometrial tissue revealed numerous aberrantly expressed miRs, including miR-150. In functional assays, transfection with miR-150 mimic resulted in decreased migration and fibrosis, implying an inhibition of leiomyoma growth. To identify the target genes of miR-150 in leiomyoma, gene set analysis and network analysis were performed. To overcome the limitations of in silico analysis, changes in expression levels of hallmark genes in leiomyoma after transfection with a miR-150 mimic were also evaluated using qRT-PCR. As a result, the Akt/p27Kip1 pathway was presumed to be one of the target pathways of miR-150. After transfecting cultured leiomyoma cells with the miR-150 mimic, expression levels of its target gene Akt decreased, whereas those of p27Kip1 increased significantly. Our results suggest that miR-150 affects the cell cycle regulation in uterine leiomyoma through the Akt/p27Kip1 pathway.

Role of B-Cell Translocation Gene 1 in the Pathogenesis of Endometriosis.

Estrogen affects endometrial cellular proliferation by regulating the expression of the c-myc gene. B-cell translocation gene 1 (BTG1), a translocation partner of the c-myc, is a tumor suppressor gene that promotes apoptosis and negatively regulates cellular proliferation and cell-to-cell adhesion. The aim of this study was to determine the role of BTG1 in the pathogenesis of endometriosis. BTG1 mRNA and protein expression was evaluated in eutopic and ectopic endometrium of 30 patients with endometriosis (endometriosis group), and in eutopic endometrium of 22 patients without endometriosis (control group). The effect of BTG1 downregulation on cellular migration, proliferation, and apoptosis was evaluated using transfection of primarily cultured human endometrial stromal cells (HESCs) with BTG1 siRNA. BTG1 mRNA expression level of eutopic and ectopic endometrium of endometriosis group were significantly lower than that of the eutopic endometrium of the control group. Migration and wound healing assays revealed that BTG1 downregulation resulted in a significant increase in migration potential of HESCs, characterized by increased expression of matrix metalloproteinase 2 (MMP2) and MMP9. Downregulation of BTG1 in HESCs significantly reduced Caspase 3 expression, indicating a decrease in apoptotic potential. In conclusion, our data suggest that downregulation of BTG1 plays an important role in the pathogenesis of endometriosis.

Catheter-directed Sclerotherapy for Ovarian Endometrioma: Short-term Outcomes.

Purpose To evaluate the effectiveness of catheter-directed sclerotherapy (CDS) with 95% ethanol in patients with primary or recurrent ovarian endometriomas. Materials and Methods In this prospective study, 14 participants (mean age, 32 years; range, 20-44 years) who underwent CDS for ovarian endometrioma from March 2015 to December 2017 were evaluated. Diagnosis was based on symptoms and imaging studies. To assess the impact of CDS on ovarian reserve, serum anti-Müllerian hormone (AMH) was measured before CDS and 6 months after CDS. Serum cancer antigen 125 (CA-125) levels were also measured at the same time points. Follow-up US was performed 1, 3, and 6 months after CDS and biannually thereafter to monitor potential cyst size change and recurrence. Comparison of AMH, CA-125, and cyst size before and after CDS was performed by using the paired t test or Wilcoxon signed-rank test. Results Mean endometrioma size decreased from 5.8 cm ± 2.2 to 1.1 cm ± 1 (P ˂ .001). During a mean follow-up of 12.7 months (range, 6.1-23.0 months), there were no recurrences of endometrioma. Pain was relieved in all participants, with a decrease in serum CA-125 level (P = .001). There was no difference in serum AMH level before and 6 months after CDS, indicating well-preserved ovarian function (4.29 ng/mL ± 2.47 vs 4.36 ng/mL ± 1.94, respectively; P > .875). There were no procedure-related complications. Conclusion Catheter-based sclerotherapy with 95% ethanol can lead to better short-term clinical outcomes and well-preserved ovarian function for patients with endometriomas. © RSNA, 2018.

Pectinase-treated Panax ginseng protects heat stress-induced testicular damage in rats.

Testicular hyperthermia is well studied to cause impaired spermatogenesis. In the present study, the protective effect of enzymatically modified (pectinase-treated) Panax ginseng (GINST) against intermittent sub-chronic heat stress-induced testicular damage in rats was investigated. Male Sprague-Dawley rats were divided into four groups: normal control (NC), heat-stressed control (HC), heat-stressed plus GINST-100 mg/kg/day (HG100) and heat-stressed plus GINST-200 mg/kg/day (HG200) treatment groups. GINST (100 and 200 mg/kg/day) was mixed separately with a regular pellet diet and was administered orally for 8 weeks starting from 1 week before heat exposure. Parameters such as organ weight, blood chemistry, sperm kinetic values, expression of antioxidant enzymes, spermatogenesis molecules and sex hormone receptors levels were measured. Data revealed that kidney and epididymis weight were significantly (P < 0.05) decreased with heat stress and recovered by GINST treatment. Further, the altered levels of blood chemistry panels and sperm kinetic values in heat stress-induced rats were attenuated when GINST was administered (P < 0.05). Furthermore, the expression levels of antioxidant-related enzymes (GSTM5 and GPX4), spermatogenesis-related proteins (CREB1 and INHA) and sex hormone receptors (androgen receptor, luteinizing hormone receptor and follicle-stimulating hormone receptor) were reduced by heat stress; however, GINST treatment effectively ameliorated these changes. In conclusion, GINST was effective in reducing heat-induced damage in various male fertility factors in vivo and has considerable potential to be developed as a useful supplement in improving male fertility.

Common Causes of Postmenopausal Bleeding in Korean Women: 10-Year Outcomes from a Single Medical Center.

The common causes of postmenopausal bleeding (PMB), according to the data from the western world, are atrophy, hormone replacement therapy (HRT), endometrial cancer, etc. We conducted a retrospective study to assess whether the causes of PMB in Korean postmenopausal women are similar to those already known. This retrospective study used 10-year medical records (March 2005 to December 2014) of 792 PMB women in the Yonsei University Health System. The data were divided into 2 categories by 5-year intervals to compare the differences between the 2 periods. The most common cause of PMB in Korean women was atrophy (51.1%). Polyps and HRT were the second, followed by anticoagulant medications, cervical cancer, and endometrial cancer. The proportion of patients with cervical cancer significantly decreased during the second half of the decade (8.7% vs. 5.2%; P = 0.048). Although no significant change was noted for HRT, its rank was higher during the latter 5-year period. Only the most common cause of PMB was the same as the conventional data. Interestingly, the proportion of patients with cervical cancer decreased during the latter half of the decade, reflecting the changes in the nation's cancer prevalence rate, while the use of HRT increased.