Effect of menopausal hormonal therapy on cardiovascular risks in Korean postmenopausal women: A nationwide cohort study.

OBJECTIVE: To evaluate the association between menopausal hormonal therapy (MHT) and the risk of cardiovascular disease (CVD), according to various regimens, dosages, routes of administration and starting ages of MHT. DESIGN: A population-based cohort study using the Korean National Health Insurance Services database. SETTING: Nationwide health insurance database. POPULATION: Women who reported entering menopause at an age of ≥40 years with no history of CVD in the national health examination. METHODS: The study population comprised 1 120 705 subjects enrolled between 2002 and 2019, categorised according to MHT status (MHT group, n = 319 007; non-MHT group, n = 801 698). MAIN OUTCOME MEASURES: Incidence of CVD (a composite of myocardial infarction and stroke). RESULTS: The incidence of CVD was 59 266 (7.4%) in the non-MHT group and 17 674 (5.5%) in the MHT group. After adjusting for confounding factors, an increased risk of CVD was observed with the administration of tibolone (hazard ratio, HR 1.143, 95% CI 1.117-1.170), oral estrogen (HR 1.246, 95% CI 1.198-1.295) or transdermal estrogen (HR 1.289, 95% CI 1.066-1.558), compared with the non-MHT group; the risk was based on an increased risk of stroke. The risk trends were consistent regardless of the age of starting MHT or the physicians' specialty. Among tibolone users, a longer period from entering menopause to taking tibolone and the use of any dosage (1.25 or 2.5 mg) were linked with a higher risk of CVD, compared with non-MHT users. CONCLUSIONS: This nationwide cohort study demonstrated an increased risk of CVD, driven mainly by an increased risk of stroke, among tibolone and oral or transdermal estrogen users, compared with that of non-MHT users.

Association between breast diseases and symptomatic uterine fibroids by using South Korean National Health Insurance database.

Both the uterus and breasts have sex hormone dependence, yet there are few studies on the association between breast disease and uterine fibroids (UFs). The purpose of this study was to investigate the incidence of benign breast disease (BBD), carcinoma in situ (CIS), and breast cancer (BC) in women treated for UFs compared to women who were not treated for UFs. This retrospective cohort study used national health insurance data from January 1st, 2011, to December 31st, 2020. We selected women between 20 and 50 years old who (1) were treated for UFs (UF group) or (2) visited medical institutions for personal health screening tests without UFs (control group). We analyzed independent variables such as age, socioeconomic status (SES), region, Charlson comorbidity index (CCI), delivery status, menopausal status, menopausal hormone therapy (MHT), endometriosis, hypertension (HTN), diabetes mellitus (DM), and dyslipidemia based on the first date of uterine myomectomy in the UF group and the first visiting date for health screening in the non-UF group. There were 190,583 and 439,940 participants in the UF and control groups, respectively. Compared with those of the control group, the RRs of BBD, CIS, and BC were increased in the UF group. The hazard ratios (HRs) of BBD, CIS, and BC in the UF group were 1.335 (95% confidence interval (CI) 1.299-1.372), 1.796 (95% CI 1.542-2.092), and 1.3 (95% CI 1.198-1.41), respectively. When we analyzed the risk of BC according to age at inclusion, UFs group had the increased risk of BCs in all age groups in comparison with control group. Women with low SES (HR 0.514, 95% CI 0.36-0.734) and living in rural areas (HR 0.889, 95% CI 0.822-0.962) had a lower risk of BC. Our study showed that women with UFs had a higher risk of BBD, CIS, and BC than those without UFs. This result suggests that women with UFs should be more conscious of BC than those without UFs. Therefore, doctors should consider recommending regular breast self-exams, mammography, or ultrasound for the early detection of BC in women with UFs.

Application of Static Headspace GC-MS Method for Selective 1,4-Dioxane Detection in Food Additives.

Efficient detection methods must be developed for 1,4-dioxane due to its suspected status as a human carcinogen, which is highly mobile in food and environmental resources. In this regard, this experiment has been conducted to develop reliable and selective detection and measurement methods by using static headspace (SH) isolation, followed by gas chromatography-mass spectrometry (GC-MS). A new method was developed for determining the spiked 1,4-dioxane contents in a polyethylene glycol 600 (PEG 600). The optimal condition for SH-GC-MS was discussed. The representative ions of 1,4-dioxane and 1,4-dioxane-d8 in the SIM mode of MS are 88 and 96, respectively, and the peaks of the SIM mode were separated and confirmed. The linear range for the method covers 0.25 to 100 mg/L with a coefficient of determination (R2) ≥ 0.999. The method applicability was demonstrated by spike recovery across a variety of food additives (i.e., chlorine bitartrate, choline chloride, polysorbate 20 and 60, and PEG 1000). All spike recovery from the tested samples was in the range of 89.50-102.68% with a precision of 0.44-11.22%. These findings suggest a new analytical method for food safety inspection, and could be applicable for ensuring the safety of foods and environmental and public health on a broad scale.

The increased risk of colorectal cancer in the women who underwent hysterectomy from the South Korean National Health Insurance Database.

BACKGROUND: Several population-based studies and observational studies have shown that oophorectomy is associated with an increased risk of colorectal cancer (CRC), and hormone replacement therapy has been associated with a reduction in the risk of colorectal cancer. This study was carried out to investigate whether hysterectomy, which may affect the levels of female hormones, is associated with a risk of cancer of the specific gastrointestinal tract. METHODS: This population-based retrospective cohort study was conducted using insurance data provided by the Health Insurance Review and Assessment Service (HIRA) from January 1, 2007, to December 31, 2020. The hysterectomy group included 40- to 59-year-old women who underwent hysterectomy with uterine leiomyoma or uterine endometriosis from January 1, 2011, to December 31, 2014. The control group included women aged 40 to 59 years who visited medical institutions for medical examination from January 1, 2011 to December 31, 2014. RESULTS: The hysterectomy and non-hysterectomhy groups comprised 66,204 and 89,768 subjects, respectively. The median ages in the non-hysterectomy group and hysterectomy group were 48 (range: 43-53) and 46 (range: 44-49) years, respectively. In the unadjusted results of the analysis, all colorectal cancer (CRC) increased in the hysterectomy alone group (HR 1.222, 95% confidence interval (CI) 1.016-1.47, p = 0.033), sigmoid colon cancer increased in the hysterectomy alone group (HR 1.71, 95% CI 1.073-2.724, p = 0.024), and rectal cancer increased in the hysterectomy with adnexal surgery group (HR 1.924, 95% CI 1.073-2.724, p = 0.002). The adjusted results showed that all CRC increased in the hysterectomy alone group (HR 1.406, 95% CI 1.057-1.871, p = 0.019), colon cancer increased in the hysterectomy alone group (HR 1.523, 95% CI 1.068-2.17, p = 0.02), and rectal cancer increased in the hysterectomy with adnexal surgery group (HR 1.933, 95% CI 1.131-3.302, p = 0.016). The all-cause mortality of GI cancer increased in the hysterectomy alone group (HR 3.495, 95% CI 1.347-9.07, p = 0.001). CONCLUSIONS: This study showed that the risk of all CRC increased in women who underwent hysterectomy compared with women who did not. In particular, the risk of rectal cancer was significantly higher in the women who underwent hysterectomy with adnexal surgery than in the controls. There was no association between hysterectomy and other GI cancers.

Skin cancer risk of menopausal hormone therapy in a Korean cohort.

Conflicting studies exist on the association between menopausal hormone therapy (MHT) and skin cancers, such as melanoma and non-melanoma skin cancer (NMSC). This retrospective cohort study aimed to evaluate the risk of skin cancer from MHT using data from 2002 to 2019 from the National Health Insurance Service in South Korea. We included 192,202 patients with MHT and 494,343 healthy controls. Women > 40 years who had menopause between 2002 and 2011 were included. Patients with MHT had at least one MHT for at least 6 months and healthy controls had never been prescribed MHT agents. We measured the incidence of melanoma and NMSC. Melanoma developed in 70 (0.03%) patients with MHT and 249 (0.05%) controls, while the incidence of NMSC was 417 (0.22%) in the MHT group and 1680 (0.34%) in the controls. Tibolone (hazard ratio [HR] 0.812, 95% confidence interval [CI] 0.694-0.949) and combined oestrogen plus progestin by the manufacturer (COPM; HR 0.777, 95% CI 0.63-0.962) lowered the risk of NMSC, while other hormone groups did not change the risk. Overall, MHT was not associated with melanoma incidence in menopausal Korean women. Instead, tibolone and COPM were associated with a decrease in NMSC occurrence.

Association of Early Hysterectomy With Risk of Cardiovascular Disease in Korean Women.

Importance: Women who undergo surgical hysterectomy before natural menopause may have an earlier increase in hematocrit and storage iron levels than those who continue menstruation, thereby increasing the risk of cardiovascular disease (CVD) at ages younger than usually seen. Examining this issue may provide important implications for women's cardiovascular health to both physicians and patients. Objective: To evaluate the association of hysterectomy with the risk of incident CVD among women before age 50 years. Design, Setting, and Participants: In this Korean population-based cohort study, 135 575 women aged 40 to 49 years were evaluated from January 1, 2011, to December 31, 2014. After propensity score matching in covariates including age, socioeconomic status, region, Charlson Comorbidity Index, hypertension, diabetes, dyslipidemia, menopause, menopausal hormone therapy, and adnexal surgery before inclusion, 55 539 pairs were included in the hysterectomy and nonhysterectomy groups. Participants were followed up until December 31, 2020. Data analysis was conducted from December 20, 2021, to February 17, 2022. Main Outcomes and Measures: The primary outcome was an incidental CVD, a composite of myocardial infarction, coronary artery revascularization, and stroke. The individual components of the primary outcome were also evaluated. Results: A total of 55 539 pairs were included; median age in the combined groups was 45 (IQR, 42-47) years. During median follow-up periods in the hysterectomy group of 7.9 (IQR, 6.8-8.9) years and nonhysterectomy group of 7.9 (IQR, 6.8-8.8) years, the incidence of CVD was 115 per 100 000 person-years for the hysterectomy group and 96 per 100 000 person-years for the nonhysterectomy group. After adjusting for confounding factors, the hysterectomy group had an increased risk of CVD compared with the nonhysterectomy group (hazard ratio [HR], 1.25; 95% CI, 1.09-1.44). The incidences of myocardial infarction and coronary artery revascularization were comparable between the groups, whereas the risk of stroke was significantly higher in the hysterectomy group (HR, 1.31; 95% CI, 1.12-1.53). Even after excluding women who underwent oophorectomy, the hysterectomy group had higher risks of CVD (HR, 1.24; 95% CI, 1.06-1.44). Conclusions and Relevance: The findings of this cohort study suggest early menopause owing to hysterectomy was associated with increased risks for a composite of CVD, particularly stroke.

Risk of Gestational Diabetes and Pregnancy-Induced Hypertension with a History of Polycystic Ovary Syndrome: A Nationwide Population-Based Cohort Study.

OBJECTIVE: To evaluate the risks of developing gestational diabetes (GDM) and pregnancy-induced hypertension (PIH) in women with polycystic ovary syndrome (PCOS) using data from Korea's National Health Insurance Service. METHOD: The PCOS group comprised women aged 20 to 49 years diagnosed with PCOS between 1 January 2012, and 31 December 2020. The control group comprised women aged 20 to 49 years who visited medical institutions for health checkups during the same period. Women with any cancer within 180 days of the inclusion day were excluded from both the PCOS and control groups, as were women without a delivery record within 180 days after the inclusion day, as well as women who visited a medical institution more than once before the inclusion day due to hypertension, diabetes mellitus (DM), hyperlipidemia, DM in pregnancy, or PIH. GDM and PIH were defined as cases with at least three visits to a medical institution with a GDM diagnostic code and a PIH diagnostic code, respectively. RESULTS: Overall, 27,687 and 45,594 women with and without a history of PCOS experienced childbirth during the study period. GDM and PIH cases were significantly higher in the PCOS group than in the control group. When adjusted for age, SES, region, CCI, parity, multiple pregnancies, adnexal surgery, uterine leiomyoma, endometriosis, PIH, and GDM, an increased risk of GDM (OR = 1.719, 95% CI = 1.616-1.828) was observed among women with a history of PCOS. There was no increase in the risk of PIH among women with a history of PCOS (OR = 1.243, 95% CI = 0.940-1.644). CONCLUSION: A history of PCOS itself might increase the risk of GDM, but its relationship with PIH remains unclear. These findings would be helpful in the prenatal counseling and management of patients with PCOS-related pregnancy outcomes.

Comparison of Extraction Methods and Extraction Optimization in Aqueous Two-Phase System for Ethyl Carbamate Analysis in Model Systems for Maesil Wine.

Ethyl carbamate (EC) is a known carcinogen, and therefore its intake is regulated internationally. The objectives of this study were to compare the EC recovery yields under different liquid-liquid extraction (LLE) conditions and to investigate the optimum conditions of the aqueous two-phase system (ATPS) for EC extraction. Our results showed that for the LLE method, addition of 15% NaCl improved the EC yield by 15%, and dichloromethane as the extraction solvent showed a slightly higher yield (about 5%) than chloroform. However, there was little difference in the yield when mixing was performed using an ultrasonic bath compared to a vortex mixer. Using response surface methodology with central composite design to analyze the ATPS results, optimal extraction was found to occur at 21.5°C for 2.8 h in the sample containing 70% alcohol and 15% phosphate, showing a recovery yield of 75.64%. This information can be applied to alcoholic beverages and other fermented food products to analyze EC with better extraction methods, depending on the types of food.

Incidence of bowel injury during gynecologic surgery for benign indications: A nationwide cross-sectional study of cases from 2009 to 2018.

OBJECTIVE: To investigate the incidence and risk factors of intestinal injury during gynecologic surgery for benign diseases, based on a national database. METHOD: The study cohort was generated by extracting patients with operation codes for benign gynecologic diseases from the Health Insurance Review & Assessment Service National Inpatient Sample from 2009 to 2018. After analyzing the incidence of bowel injury during gynecologic surgery, a multivariate analysis was performed to identify the associated risk factors for bowel injury. RESULTS: Among 81 451 patients who underwent gynecologic surgery for benign diseases, the incidence of bowel injury was 6.14 per 1000 women. The risk of bowel injury decreased with laparoscopy (odds ratio [OR] 0.54; 95% confidence interval [CI] 0.41-0.69; P < 0.001) and increased with subtotal hysterectomy (OR 2.83; 95% CI 1.79-4.46; P < 0.001) and adnexectomy (OR 2.83; 95% CI 1.93-4.16; P < 0.001). Old age, higher Charlson comorbidity index, low socioeconomic status, and a higher clinic grade were associated with a higher risk of bowel injury. CONCLUSION: This study revealed the incidence of bowel injury during benign gynecologic surgery in a Korean national population-based cohort. The risk of bowel injury increased with open surgery, subtotal hysterectomy, and adnexectomy.

Incidence and risk of venous thromboembolism according to primary treatment type in women with endometrial cancer: a population-based study.

BACKGROUND: Current prophylaxes and treatments for venous thromboembolism (VTE) in women with gynecologic cancer are mainly guided by studies on solid cancers because studies in gynecologic cancer did not provide sufficient data. Large-scale studies evaluating the incidence and risk of VTE according to therapeutic modality may guide prophylaxis and treatment of VTE in gynecologic cancer. This study was performed to determine the incidence and risk of VTE according to primary treatment type in Korean women with endometrial cancer. METHODS: We selected 26,256 women newly diagnosed with endometrial cancer between 2009 and 2018 from the Korean Health Insurance Review and Assessment Service database. During the total follow-up period and first six months after primary treatments initiation, the incidence and risk of VTE were evaluated according to primary treatment type, that is, no treatment, surgery, radiotherapy, chemotherapy, or hormone therapy. RESULTS: VTE occurred in 136 per 10,000 women during the total follow-up period and in 54 per 10,000 women during the first six months with the highest frequency in women that underwent chemotherapy. During the first year, the monthly incidence of VTE decreased with time among women that underwent no treatment, surgery, or hormone therapy and remained unchanged in those that received radiotherapy or chemotherapy. Compared with women that received no treatment, VTE risk, especially of PE significantly increased in women that underwent chemotherapy (VTE: hazard ratio (HR), 2.334; 95% CI, 1.38-3.949; P = 0.002) (PE: HR, 2.742; 95% CI, 1.424-5.278; P = 0.003) or hormone therapy (VTE: HR, 2.073; 95% CI, 1.356-3.17; P = 0.001) (PE: HR, 2.086; 95% CI, 1.19-3.657; P = 0.01) during the total follow-up period and women that underwent only chemotherapy during the first six months (VTE: HR, 2.532; 95% CI, 1.291-4.966; P = 0.007) (PE: HR, 3.366; 95% CI, 1.496-7.576; P = 0.003). CONCLUSIONS: In this cohort study, the incidence and risk of VTE were highest in women with endometrial cancer that underwent chemotherapy as a primary treatment. Notably, the incidence of VTE decreased over time in women that received no treatment, surgery, or hormone therapy. This study can help guide therapies for prophylaxis and treatment of VTE in women with endometrial cancer.

Dienogest and the Risk of Reoperation in Endometriosis.

BACKGROUND: This retrospective cohort study aimed to determine whether there is a difference in reoperation rates between patients who used dienogest (DNG) and patients who did not use DNG. METHODS: Using Health Insurance Review and Assessment Service (HIRA) data generated between 1 January 2010 and 30 June 2018, we identified women with an endometriosis diagnosis code who used GnRH agonists after gynecological surgery. Among them, women prescribed DNG were selected as the DNG group, and those who did not receive DNG were selected as the control group. A survival analysis of the reoperation between the two groups was performed. RESULTS: DNG and control groups were extracted from 9735 people each. The reoperation rates were 0.4% and 0.6% in the DNG and control groups, respectively, without adjusting. In the Cox proportional risk analysis, DNG use increased the reoperation rate {hazard ratio (HR), 1.599; 95% confidence interval (CI), 1.005-2.545}. The site of endometriosis and the number of GnRH agonist injections were not associated with reoperation (HR, 1.008; 95% CI, 0.739-1.374; HR, 1.062; 95% CI, 0.690-1.635). In the subgroup survival analysis, according to the period between the last GnRH agonist injection and the first DNG dose, DNG did not increase the reoperation rates up to 9 months (~3 months: HR, 0.968; 95% CI, 0.551-1.699; 4~6 months: HR, 1.094; 95% CI, 0.58-2.063; 7~9 months: HR, 2.419; 95% CI, 0.735-7.962), but DNG increased the reoperation rate from 10 months onwards (10~12 months: HR, 3.826; 95% CI, 1.164-12.579 and ~13 months: HR, 8.436; 95% CI, 4.722-15.072). CONCLUSIONS: Women who used DNG had a higher endometriosis reoperation rate than women who did not use DNG. However, the initiation of DNG treatment within nine months after the last GnRH agonist injection did not affect the endometriosis reoperation rate.

Incidence and risk factors of VTE in patients with cervical cancer using the Korean national health insurance data.

This study investigated incidence and risk factors for venous thromboembolism (VTE) in patients with cervical cancer. We selected 49,514 patients newly diagnosed with cervical cancer from the Korean Health Insurance Review and Assessment Service databases. During the total follow-up period and first 6 months after initiation of primary treatments, incidence of VTE, and association of risk factors with VTE occurrence were evaluated according to primary treatments or no treatment, surgery, radiotherapy, and chemotherapy. VTE occurred in 1.15% of patients with cervical cancer. Regardless of the period after initiation of primary treatments, and of VTE, the incidence of thromboembolism was highest in chemotherapy. During the first 12 months, monthly incidence of VTE was highest in chemotherapy and decreased with time in all primary treatments. Compared with no treatment, VTE risk significantly increased for all primary treatments (surgery: HR 1.492; 95% CI 1.186-1.877) (radiotherapy: HR 2.275; 95% CI 1.813-2.855) (chemotherapy: HR 4.378; 95% CI 3.095-6.193) and for chemotherapy during the first 6 months (HR 3.394; 95% CI 2.062-5.588). In this cohort study, incidence and risk of VTE in patients with cervical cancer were the highest when chemotherapy was the primary cancer treatment, and incidence of VTE decreased with time.

Incidence and risk of venous thromboembolism according to primary treatment in women with ovarian cancer: A retrospective cohort study.

OBJECTIVE: This study aimed to investigate incidence and risk for venous thromboembolism (VTE) according to primary treatment in women with ovarian cancer. METHODS: We selected 26,863 women newly diagnosed with ovarian cancer between 2009 and 2018 from the Korean Health Insurance Review and Assessment Service databases. During the total follow-up period and the first six months after initiation of primary treatments, incidence and risk of VTE were evaluated according to primary treatment as no treatment, surgery, radiotherapy, or chemotherapy. RESULTS: The mean follow-up period was 1285.5±6 days. The VTE incidence was highest in women who underwent chemotherapy (306 per 10,000 women). Among women who underwent surgery, VTE was highest in surgery with neoadjuvant chemotherapy (536 per 10,000 women), followed by surgery with adjuvant chemotherapy (360 per 10,000 women) and surgery alone (132 per 10,000 women). During the first 12 months, monthly incidence of VTE decreased. Compared with women with no treatment, risk of VTE significantly increased in women undergoing chemotherapy (HR 1.297; 95% CI, 1.08-1.557; P = 0.005) during the total follow-up period and decreased in women undergoing surgery (HR 0.557; 95% CI, 0.401-0.775; P<0.001) and radiotherapy (HR 0.289; 95% CI, 0.119-0.701; P = 0.006) during the first six months. Among women who underwent surgery, VTE risk significantly increased in surgery with neoadjuvant chemotherapy (HR 4.848; 95% CI, 1.86-12.632; P = 0.001) followed by surgery with adjuvant chemotherapy (HR 2.807; 95% CI, 1.757-4.485; P<0.001) compared with surgery alone during the total follow-up period and in surgery with neoadjuvant chemotherapy (HR 4.223; 95% CI, 1.37-13.022; P = 0.012) during the first six months. CONCLUSIONS: In this large Korean cohort study, incidence and risk of VTE were highest in women with ovarian cancer who underwent chemotherapy and surgery with neoadjuvant chemotherapy as a primary cancer treatment. Incidence of VTE decreased over time.

Postoperative outcomes of natural orifice transluminal endoscopic surgery-assisted vaginal hysterectomy and conventional laparoscopic-assisted vaginal hysterectomy: a comparative study.

OBJECTIVE: The present study aimed to determine the differences in outcomes between natural orifice transluminal endoscopic surgery-assisted vaginal hysterectomy (NAVH) and conventional laparoscopy-assisted vaginal hysterectomy (LAVH). METHODS: We retrospectively reviewed the charts of patients who between July 2012 and September 2015, were diagnosed as having benign uterine disease such as uterine myoma, endometriosis, or adenomyosis and managed via NAVH or LAVH in a single-center (Eulji University Hospital). Data such as age, body weight, height, parity, operation time, intra/post-operative complications, and uterus weight were obtained from the clinical charts. NAVH and LAVH recipients were matched 1:3 in terms of baseline characteristics, and the 2 groups were compared regarding surgical outcomes. RESULTS: Of the 160 patients with benign uterine disease included in the present study. Forty received NAVH and remaining 120 received LAVH. There were significant differences between the groups regarding operation time and hemoglobin change. Notably, although the operation time was shorter for LAVH, hemoglobin change was lower for NAVH. Additionally, although maximum hospitalization duration was shorter for LAVH, the average length of hospitalization was similar between NAVH and LAVH. There were no significant differences between the groups in terms of other variables. CONCLUSION: NAVH may become a new alternative surgical method of choice for hysterectomy, as it represents a clinically feasible and safe approach; moreover is superior to LAVH in terms of bleeding loss.

Effects of corticotropin-releasing hormone on the expression of adenosine triphosphate-sensitive potassium channels (Kir6.1/SUR2B) in human term pregnant myometrium.

OBJECTIVE: Corticotropin-releasing hormone (CRH) is a crucial regulator of human pregnancy and parturition. Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels are important for regulating myometrial quiescence during pregnancy. We investigated regulatory effects of different concentrations of CRH on KATP channel expression in human myometrial smooth muscle cells (HSMCs) in in vitro conditions. METHODS: After treating HSMCs with different concentrations of CRH (1, 10, 102, 103, 104 pmol/L), mRNA and protein expression of KATP channel subunits (Kir6.1 and SUR2B) was analyzed by reverse transcription-polymerase chain reaction and western blot. We investigated which CRH receptor was involved in the reaction and measured the effects of CRH on intracellular Ca2+ concentration when oxytocin was administered in HSMCs using Fluo-8 AM ester. RESULTS: When HSMCs were treated with low (1 pmol/L) and high (103, 104 pmol/L) CRH concentrations, KATP channel expression significantly increased and decreased, respectively. SUR2B mRNA expression at low and high CRH concentrations was significantly antagonized by antalarmin (CRH receptor-1 antagonist) and astressin 2b (CRH receptor-2 antagonist), respectively; however, Kir6.1 mRNA expression was not affected. After oxytocin treatment, the intracellular Ca2+ concentration in CRH-treated HSMCs was significantly lowered in low concentration of CRH (1 pmol/L), but not in high concentration of CRH (103 pmol/L), compared to control. CONCLUSION: Our data demonstrated the regulatory effect was different when HSMCs were treated with low (early pregnancy-like) and high (labor-like) CRH concentrations and the KATP channel expression showed significant increase and decrease. This could cause inhibition and activation, respectively, of uterine muscle contraction, demonstrating opposite dual actions of CRH.

Uterine rupture in pregnancies following myomectomy: A multicenter case series.

OBJECTIVE: The purpose of this case series was to retrospectively examine records of cases with uterine rupture in pregnancies following myomectomy and to describe the clinical features and pregnancy outcomes. METHODS: This study was conducted as a multicenter case series. The patient databases at 7 tertiary hospitals were queried. Records of patients with a diagnosis of uterine rupture in the pregnancy following myomectomy between January 2012 and December 2014 were retrospectively collected. The uterine rupture cases enrolled in this study were defined as follows: through-and-through uterine rupture or tear of the uterine muscle and serosa, occurrence from 24+0 to 41+6 weeks' gestation, singleton pregnancy, and previous laparoscopic myomectomy (LSM) or laparotomic myomectomy (LTM) status. RESULTS: Fourteen pregnant women experienced uterine rupture during their pregnancy after LSM or LTM. Preterm delivery of less than 34 weeks' gestation occurred in 5 cases, while intrauterine fetal death occurred in 3, and 3 cases had fetal distress. Of the 14 uterine rupture cases, none occurred during labor. All mothers survived and had no sequelae, unlike the perinatal outcomes, although they were receiving blood transfusion or treatment for uterine artery embolization because of uterine atony or massive hemorrhage. CONCLUSION: In women of childbearing age who are scheduled to undergo LTM or LSM, the potential risk of uterine rupture on subsequent pregnancy should be explained before surgery. Pregnancy in women after myomectomy should be carefully observed, and they should be adequately counseled during this period.

Graves Disease Is Associated With Endometriosis: A 3-Year Population-Based Cross-Sectional Study.

The aim of this cross-sectional study was to compare the prevalence of thyroid diseases between women with and without endometriosis.We established the endometriosis group according to diagnosis codes, surgery codes, and gonadotropin-releasing hormone agonist codes using the Korean Health Insurance Review and Assessment Service-National Inpatients Sample (HIRA-NIS) from 2009 to 2011. Four controls were randomly matched to each endometriosis case. Thyroid disease cases were selected using the thyroid disease diagnosis code (E0X).Among the 1,843,451 women sampled, 5615 had endometriosis; 22,460 controls were matched to the endometriosis cases. After adjustment for age and sampling year, Graves disease was associated with endometriosis (odds ratio [OR]: 2.52; 95% CI: 1.30-4.88; P < 0.01), while hypothyroidism was not (OR: 1.17; 95% CI: 0.90-1.52; P = 0.25). Autoimmune hypothyroidism was also not associated with endometriosis (OR: 1.61; 95% CI: 0.88-2.94; P = 0.12).This study revealed an association between Graves disease and endometriosis.

[A case of Crohn's disease having normal delivery after infliximab treatment during early pregnancy].

Infliximab is a chimeric IgG1 monoclonal antibody to tumor necrosis factor (TNF)-a used in the treatment of steroid refractory or dependent Crohn's disease (CD). Patients with active CD are more likely to experience stillbirth, preterm labor, or small for gestational aged babies. The safety of administering infliximab in pregnant patients is not well documented. A 25-year-old woman, who was diagnosed with small bowel CD three years ago, was admitted to our hospital due to the aggravation of abdominal pain. She had been treated with mesalazine, azathioprine and intermittent steroid for three years. After admission, she did not respond to steroid therapy, we decided to try infliximab. After the administration of infliximab, epigastric pain was relived and Crohn's disease activity index score decreased significantly. However after the fourth infusion of infliximab, the patient became aware that she was ten gestational weeks old pregnancy state After then, infliximab was stopped and maintained by mesalazine. The patient gave birth to a healthy baby via normal vaginal delivery without the recurrence of CD. This case suggests that infliximab administration is safe during the early period of pregnancy. Thus, we report this case with a review of literature.

Gonadotropin-releasing hormone-agonist induces apoptosis of human granulosa-luteal cells via caspase-8, -9 and -3, and poly-(ADP-ribose)-polymerase cleavage.

Gonadotropin-releasing hormone-agonist (GnRH-Ag) used in controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) has been known to directly affect apoptosis of human ovarian cells, but its mechanism is not clearly understood. Therefore, the purpose of the present study was to investigate whether caspase-8, -9, and -3 activation and poly-(ADP-ribose)-polymerase (PARP) cleavage are involved in the mechanism by which GnRH-Ag induces apoptosis in human granulosa-luteal cells. The prospective study was conducted in the research institute and clinical fertility center of university hospital. Human granulosa-luteal cells collected from IVF-ET patients were cultured and treated with 10-6 M GnRH-Ag or saline as a control. To access apoptosis in the cells, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay and DNA fragmentation analysis were preformed 24 h after treatment. Activity of caspase-8, -9, and -3 in the cells was examined using a fluorogenic substrate. Caspase-8, -9, and -3 activation and PARP cleavage were analyzed by Western blot. DNA fragmentation in the cells increased at concentrations over 10-6 M GnRH-Ag. In TUNEL assays, the rate of apoptotic cell formation in GnRH-Ag treatment increased significantly compared with that of saline treatment (p < 0.05). The activity of caspase-8, -9 and, -3 investigated using a fluorogenic substrate increased only in the apoptotic cells. In Western blot analysis, cells treated with GnRH-Ag revealed an increase in active forms of caspase-8, -9, and -3 compared with saline treatment. In addition, cleavage of PARP also increased in cells treated with GnRH-Ag. These results suggest that activation of caspase-8, -9, and -3 and cleavage of PARP might be involved in apoptosis of human granulosa-luteal cells induced by GnRH-Ag.

A case of ovarian pregnancy after ipsilateral partial salpingectomy.

We present a case report of an ovarian pregnancy after ipsilateral partial salpingectomy. A 19-year-old woman was admitted with vaginal bleeding and right lower abdominal pain. She had a history of right partial salpingectomy caused by a tubal pregnancy. The pregnancy test result was positive, and a right adnexal mass was identified by ultrasonography. Laparoscopy revealed a right ovarian pregnancy. Thus the possibility of ipsilateral ectopic pregnancy should be considered even when the patient has a history of salpingectomy total or partial.