Single-cell profiling identifies distinct hormonal, immunologic, and inflammatory signatures of endometriosis-constituting cells.

Endometriosis consists of ectopic endometrial epithelial cells (EEECs) and ectopic endometrial stromal cells (EESCs) mixed with heterogeneous stromal cells. To address how endometriosis-constituting cells are different from normal endometrium and among endometriosis subtypes and how their molecular signatures are related to phenotypic manifestations, we analyzed ovarian endometrial cyst (OEC), superficial peritoneal endometriosis (SPE), and deep infiltrating endometriosis (DIE) from 12 patients using single-cell RNA-sequencing (scRNA-seq). We identified 11 cell clusters, including EEEC, EESC, fibroblasts, inflammatory/immune, endothelial, mesothelial, and Schwann cells. For hormonal signatures, EESCs, but not EEECs, showed high estrogen signatures (estrogen response scores and HOXA downregulation) and low progesterone signatures (DKK1 downregulation) compared to normal endometrium. In EEECs, we found MUC5B+ TFF3low cells enriched in endometriosis. In lymphoid cells, evidence for both immune activation (high cytotoxicity in NK) and exhaustion (high checkpoint genes in NKT and cytotoxic T) was identified in endometriosis. Signatures and subpopulations of macrophages were remarkably different among endometriosis subtypes with increased monocyte-derived macrophages and IL1B expression in DIE. The scRNA-seq predicted NRG1 (macrophage)-ERBB3 (Schwann cell) interaction in endometriosis, expressions of which were validated by immunohistochemistry. Myofibroblast subpopulations differed according to the location (OECs from fibroblasts and SPE/DIEs from mesothelial cells and fibroblasts). Endometriosis endothelial cells displayed proinflammation, angiogenesis, and leaky permeability signatures that were enhanced in DIE. Collectively, our study revealed that (1) many cell types-endometrial, lymphoid, macrophage, fibroblast, and endothelial cells-are altered in endometriosis; (2) endometriosis cells show estrogen responsiveness, immunologic cytotoxicity and exhaustion, and proinflammation signatures that are different in endometriosis subtypes; and (3) novel endometriosis-specific findings of MUC5B+ EEECs, mesothelial cell-derived myofibroblasts, and NRG1-ERBB3 interaction may underlie the pathogenesis of endometriosis. Our results may help extend pathologic insights, dissect aggressive diseases, and discover therapeutic targets in endometriosis. © 2023 The Pathological Society of Great Britain and Ireland.

The Estimated Prevalence and Incidence of Endometriosis With the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC): A National Population-Based Study.

BACKGROUND: The incidence and prevalence of endometriosis remain unclear due to diagnostic difficulties. Especially, there has been little information regarding the population-based epidemiology of endometriosis. The purpose of this study is to estimate the prevalence and incidence of endometriosis in Korea based on the health insurance claims data. METHODS: This study is a retrospective cohort study using the Korean National Health Insurance Service-National Sample Cohort, which correspond to approximately 1 million Korean populations from 2002 to 2013. Patients aged 15-54 years were selected, and the prevalence and incidence of endometriosis were estimated by time and age groups. RESULTS: The age-adjusted prevalence rate of endometriosis also increased from 2.12 per 1,000 persons (95% confidence interval [CI], 2.01-2.24) in 2002 to 3.56 per 1,000 persons (95% CI, 3.40-3.71) in 2013. The average adjusted incidence showed no statistically significant increase. However, the age-specific incidence of the 15-19 and 20-24 years age groups increased significantly from 0.24 and 1.29 per 1,000 persons in 2003 to 2.73 and 2.71 per 1,000 persons in 2013 (R2 = 0.93 and 0.77, P < 0.001), while the incidence rate of the age group 40-44 and 45-49 years decreased from 2.36 and 1.72 per 1,000 persons in 2003 to 0.81 and 0.27 per 1,000 persons in 2013 (R2 = 0.83 and 0.89, P < 0.001). CONCLUSION: The prevalence and incidence of endometriosis in Korean women were lower than that of previous reports in high-risk population studies. Furthermore, we found a significant increase in the diagnosis of endometriosis in younger age groups.

The effect of the look-back period for estimating incidence using administrative data.

BACKGROUND: The look-back period is needed to define baseline population for estimating incidence. However, short look-back period is known to overestimate incidence of diseases misclassifying prevalent cases to incident cases. The purpose of this study is to evaluate the impact of the various length of look-back period on the observed incidences of uterine leiomyoma, endometriosis and adenomyosis, and to estimate true incidences considering the misclassification errors in the longitudinal administrative data in Korea. METHODS: A total of 319,608 women between 15 to 54 years of age in 2002 were selected from Korea National Health Insurance Services (KNHIS) cohort database. In order to minimize misclassification bias incurred when applying various length of look-back period, we used 11 years of claim data to estimate the incidence by equally setting the look-back period to 11 years for each year using prediction model. The association between the year of diagnosis and the number of prevalent cases with the misclassification rates by each look-back period was investigated. Based on the findings, prediction models on the proportion of misclassified incident cases were developed using multiple linear regression. RESULTS: The proportion of misclassified incident cases of uterine leiomyoma, endometriosis and adenomyosis were 32.8, 10.4 and 13.6% respectively for the one-year look-back period in 2003. These numbers decreased to 6.3% in uterine leiomyoma and - 0.8% in both endometriosis and adenomyosis using all available look-back periods (11 years) in 2013. CONCLUSION: This study demonstrates approaches for estimating incidences considering the different proportion of misclassified cases for various length of look-back period. Although the prediction model used for estimation showed strong R-squared values, follow-up studies are required for validation of the study results.

Multidisciplinary Approach in Large-sized Submucosal Myoma: Hysteroscopic Myomectomy after Uterine Artery Embolization.

STUDY OBJECTIVE: To evaluate the safety and effectiveness of hysteroscopic myomectomy after uterine artery embolization (UAE) for the treatment of large-sized submucosal myomas with deep intramural invasion that are difficult to treat with 1-step hysteroscopy. DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: An academic university hospital. PATIENTS: Eight premenopausal patients with symptomatic submucosal myomas with intramural invasion. INTERVENTIONS: All of the patients after bilateral UAE underwent subsequent hysteroscopic operation 3 to 15 months after UAE. MEASUREMENTS AND MAIN RESULTS: A total of 8 patients who had a large-sized submucosal myoma with deep myometrial invasion were included. The average volume of the submucosal myomas was 87.7±39.9 cm3 as confirmed by magnetic resonance imaging, and the average patient age was 37.6 years. The mean volume reduction of the submucosal myomas was 83.3±16.4% after UAE, and no immediate complications were observed. One-step hysteroscopic myomectomy after UAE was successfully performed in all patients. Leiomyomas with hyaline degeneration were pathologically confirmed. All women showed improved symptoms, and there was no evidence of recurrence 1 year later. One patient conceived naturally and delivered a full-term baby. CONCLUSION: In premenopausal women with large-sized symptomatic submucosal myomas with deep myometrial invasion, hysteroscopic myomectomy after UAE is very effective and safe.

Effect of mistletoe on endometrial stromal cell survival and vascular endothelial growth factor expression in patients with endometriosis.

Research Question: To evaluate the effect of mistletoe on the cell viability of patients with endometriosis, the expression levels of vascular endothelial growth factor (VEGF) were measured, and the change in the expression level of VEGF following mistletoe treatment was recorded. Design: Forty reproductive-aged women with endometriosis (stage I/II [group 1, n=20], and stage III/IV [group 2, n=20]) were prospectively enrolled. Twenty women who underwent gynaecologic operations for benign conditions were selected as the control group. Both eutopic and ectopic endometrial tissues were obtained from the endometriosis patients. The endometrial tissues were cultured and the stromal cells were separated. The cells were cultured for 24 hours with peritoneal fluid from patients and controls with and without mistletoe supplementation (200 ng/mL), respectively. The MTT assay was used to assess cell viability, and VEGF expression was analysed by Western blotting and ELISA. Results: Using peritoneal fluid from endometriosis patients treated with mistletoe, we found that both eutopic and ectopic endometrial stromal cell viability increased after treatment with peritoneal fluid from patients with early-stage (I and II) endometriosis. After mistletoe treatment, the cell viability was decreased, in both eutopic and ectopic endometrial stromal cells in all stages of endometriosis. These findings were verified consistently by evaluating the expression and concentration of VEGF, a marker of angiogenesis. Conclusions: The present study showed that mistletoe can reduce the cell viability of endometrial stromal cells and the peritoneal fluid-induced elevation of VEGF in eutopic and ectopic endometrial stromal cells obtained from endometriosis patients, especially in the early stage. Mistletoe might have anti-angiogenic activity on endometrial stromal cells and thus is a potential candidate for the treatment of endometriosis.

Development of a Model for the Prediction of Treatment Response of Uterine Leiomyomas after Uterine Artery Embolization.

Background: Uterine artery embolization (UAE) is one of the minimally-invasive alternatives to hysterectomy for treatment of uterine leiomyomas. There are various factors affecting the outcomes of UAE, but these have only been sporadically studied. Study Objective: To identify factors associated with the efficacy of UAE for the treatment of uterine leiomyoma, and to develop a model for the prediction of treatment response of uterine leiomyomas to UAE. Study design: A retrospective cohort study (Canadian Task Force Classification II-2) Patients: One hundred ninety-eight patients with symptomatic uterine leiomyomas. Intervention: UAE Measurements and Main Results: Among 198 leiomyoma patients who were treated with UAE, 104 who underwent pelvic magnetic resonance imaging (MRI) with diffusion-weighted imaging were selected for developing prediction model. Variables that were statistically significant from the univariate analysis were: location of leiomyoma, total number of lesions, sum of leiomyomas diameters, T2 signal intensity of largest leiomyoma, and T2 leiomyoma:muscle ratio. After a logistic regression analysis, leiomyoma location and T2 signal intensity of the largest leiomyoma were found to be statistically significant variables. Using intramural myomas defined as controls, submucosal leiomyomas showed a greater response to UAE with an odds ratio of 7.6904. The odds ratio of T2 signal intensity with an increase in signal intensity of 10 was 1.093. Using these two variables, we developed a prediction model. The AUC in the prediction model was 0.833, and the AUC in the validation set was 0.791. Conclusion: We identified that submucosal leiomyomas and those leiomyomas that show high signal intensity on T2-weighted imaging will exhibit a greater response to UAE. Prediction models are clinically helpful in selecting UAE as an appropriate treatment option for managing uterine leiomyoma.

Analysis of MED12 Mutation in Multiple Uterine Leiomyomas in South Korean patients.

Uterine leiomyomas are one of the most common benign gynecologic tumors, but the exact causes are not completely understood. In 2011, through DNA sequencing, MED12 mutation was discovered in approximately 71% of uterine leiomyomas. Several recent studies confirmed the high frequency of MED12 mutation in uterine leiomyoma. Nevertheless, no study has been done on MED12 mutation in the case of patients with multiple leiomyomas in a patient. The purpose of this study was to investigate the frequency of MED12 mutations in uterine leiomyomas of South Korean patients. In addition, we examined MED12 mutation in multiple leiomyomas in the same patients. Uterine leiomyoma tissues were obtained from symptomatic women who underwent hysterectomy or myomectomy for medically indicated reasons. We collected 60 uterine leiomyomas from 41 women. Tumor size ranged from 1 to 12cm. Patients' ages ranged from 25 to 55 years with an average of 38.4 years. Of the 60 tumors, 40 (66.67%) displayed MED12 mutation. Among the 41 patients, 14 patients had multiple leiomyomas and we analyzed those multiple leiomyomas. Three of them had the same mutations. Five of them, each leiomyoma had a different mutation. Two of them did not have mutation. Four of them had both mutation-positive and mutation-negative leiomyomas. In conclusion, we confirmed the high frequency of the MED12 mutation in uterine leiomyomas of South Korean patients. We also identified various MED12 mutation status in patients with multiple leiomyomas. This suggests that in a given patient, different tumors may have arisen from different cell origins and therefore it is supposed that occurrence of multiple leiomyoma in a single patient may not be caused by intrauterine metastasis or dissemination.

Effect of helixor A on natural killer cell activity in endometriosis.

BACKGROUND AND AIM: NK cells are one of the major immune cells in endometriosis pathogenesis. While previous clinical studies have shown that helixor A to be an effective treatment for endometriosis, little is known about its mechanism of action, or its relationship with immune cells. The aim of this study is to investigate the effects of helixor A on Natural killer cell (NK cell) cytotoxicity in endometriosis MATERIALS AND METHODS: We performed an experimental study. Samples of peritoneal fluid were obtained from January 2011 to December 2011 from 50 women with endometriosis and 50 women with other benign ovarian cysts (control). Peritoneal fluid of normal control group and endometriosis group was collected during laparoscopy. Baseline cytotoxicity levels of NK cells were measured with the peritoneal fluid of control group and endometriosis group. Next, cytotoxicity of NK cells was evaluated before and after treatment with helixor A. NK-cell activity was determined based upon the expression of CD107a, as an activation marker. RESULTS: NK cells cytotoxicity was 79.38±2.13% in control cells, 75.55±2.89% in the control peritoneal fluid, 69.59±4.96% in endometriosis stage I/II endometriosis, and 63.88±5.75% in stage III/IV endometriosis. A significant difference in cytotoxicity was observed between the control cells and stage III/IV endometriosis, consistent with a significant decrease in the cytotoxicity of NK cells in advanced stages of endometriosis; these levels increased significantly after treatment with helixor A; 78.30% vs. 86.40% (p=0.003) in stage I/II endometriosis, and 73.67% vs. 84.54% (p=0.024) in stage III/IV. The percentage of cells expressing CD107a was increased significantly in each group after helixor A treatment; 0.59% vs. 1.10% (p=0.002) in stage I/II endometriosis, and 0.79% vs. 1.40% (p=0.014) in stage III/IV. CONCLUSIONS: Helixor A directly influenced NK-cell cytotoxicity through direct induction of CD107a expression. Our results open new role of helixor A as an imune modulation therapy, or in combination with hormonal agents, for the treatment of endometriosis.

Comparison of the inhibitory effect of gonadotropin releasing hormone (GnRH) agonist, selective estrogen receptor modulator (SERM), antiprogesterone on myoma cell proliferation in vitro.

Uterine myomas are the most common gynecologic tumor in women of reproductive age. Treatment options of uterine myomas consist of surgical, medical and interventional therapy such as uterine artery embolization or myolysis. Given that it is the most common type of tumor in women of reproductive age, the treatment of uterine myomas must prioritize uterine conservation. There are several drugs for medical treatment of uterine myoma such as gonadotropin releasing hormone (GnRH) agonist, selective estrogen receptor modulator (SERM) and antiprogesterone. The objective of this study was to compare the effect of GnRH agonist, SERM, and antiprogesterone in the treatment of uterine myomas in vitro. The effect of drugs was evaluated through the cell viability assay in cultured leiomyoma cells, western blot analysis of proliferating cell nuclear antigen (PCNA), and BCL-2 protein expression. As a result, mifepristone single-treated group represents the most significant reduction in myoma cell viability and proliferation. When pretreated with leuprolide acetate, raloxifene shows more significant reduction in myoma cell viability and proliferation than mifepristone. This study suggests one of the possible mechanisms how medications act on uterine myoma, especially at the molecular level.

Prevalence, incidence, and treatment trends of adenomyosis in South Korean women for 15 years: A national population-based study.

OBJECTIVE: Adenomyosis is associated with female infertility worldwide. With improvements in imaging methods, such as pelvic magnetic resonance imaging, the diagnosis and treatment of adenomyosis have changed. This study aimed to evaluate the overall prevalence, incidence, and treatment trends of adenomyosis in South Korea using data from the Korean National Health Insurance Service Database (NHIS). METHODS: Data were collected from the Korean NHIS, a population-based complete enumeration database. A total of 678 641 women aged 11-55 years diagnosed with adenomyosis (N80.0 ICD-10 code) from the database from 2002 to 2016 were enrolled. After applying a one-year look-back method, 629 592 patients were analyzed to estimate the prevalence, incidence, and treatment trends of adenomyosis. RESULTS: The overall prevalence during the study period was 3.86 per 1000 people. The prevalence of adenomyosis has increased from 1.42 per 1000 individuals in 2002 to 7.50 per 1000 individuals in 2016. The crude annual incidence rate of adenomyosis was 1.62 per 1000 people in 2003, which increased to 4.12 per 1000 people in 2016. In addition, the proportion of uterus-preserving surgeries in adenomyosis treatments has increased from 7.51% to 21.29% over 15 years. CONCLUSION: The prevalence and incidence of adenomyosis in South Korea increased between 2002 and 2016. Furthermore, the proportion of uterus-preserving surgeries and progestin prescriptions for adenomyosis treatment has increased. We expect that our findings will raise awareness of the necessity for fertility preservation through earlier diagnosis and proper management of patients with adenomyosis.

Efficacy of Dexmedetomidine vs. Remifentanil for Postoperative Analgesia and Opioid-Related Side Effects after Gynecological Laparoscopy: A Prospective Randomized Controlled Trial.

Remifentanil is widely used for intraoperative analgesia, but often causes remifentanil-induced hyperalgesia (RIH) and related side effects. Dexmedetomidine, a non-opioid analgesic, has been used as an alternative to remifentanil to prevent RIH. We aimed to investigate the effect of dexmedetomidine on postoperative recovery after gynecological laparoscopy. Ninety-six adult patients undergoing elective gynecological laparoscopy were randomly assigned to the dexmedetomidine or remifentanil groups. The primary outcome was the pain score at 30 min after surgery. The secondary outcomes were intraoperative adverse events (hypotension and bradycardia) and postoperative opioid-related side effects (nausea, vomiting, requirement for rescue analgesics, and shivering). We also performed an ancillary cytokine study to evaluate oxidative stress, one of the causes of RIH. Compared with the remifentanil group, the dexmedetomidine group had lower pain scores at 30 min after surgery (4.0 ± 1.9 vs. 6.1 ± 2.0, mean ± SD, p < 0.001) and lower incidence of intraoperative hypotension and postoperative nausea, vomiting, and shivering. Furthermore, the proportion of patients requiring rescue analgesics was significantly lower in the dexmedetomidine than in the remifentanil group (25% vs. 66.7%, p < 0.001). Cytokine levels did not differ between the groups. Dexmedetomidine showed a better analgesic effect with minimal opioid-related side effects and is considered superior to remifentanil for intraoperative analgesia.

Correlation between MRI Features of Adenomyosis and Clinical Presentation.

This study aimed to explore the correlation between MRI features, clinical risk factors, and symptoms associated with adenomyosis. Overall, 112 patients with pathologically confirmed adenomyosis were included in this retrospective study. MRI findings and clinical presentation, including visual analog scale (VAS) scores, cancer antigen 125 (CA-125) and hemoglobin levels, and parity, were analyzed. Additionally, 131 patients undergoing active surveillance were included to validate the MRI parameters and clinical presentations. Associations between MRI parameters and adenomyosis-related clinical presentations were assessed. Patients with operated adenomyosis were younger and had larger lesions, which were more frequently of the diffuse type and posterior localization, coexisting ovarian endometriosis, deep infiltrating endometriosis, myometrial cysts, and diffusion restriction than the non-operated lesions (p < 0.05). Patients with operated adenomyosis also exhibited higher VAS scores and CA-125 levels, and nulliparity was more common in this group (p < 0.05). In contrast, patients with non-operated adenomyosis showed a higher frequency of entire localization and fibroids (p < 0.05). Among the MRI parameters, size and classification were associated with the VAS and CA-125 levels. Myometrial cysts were associated with CA-125 levels. Classification was also associated with hemoglobin levels, and posterior localization was associated with parity. We identified a significant correlation between MRI features and clinical presentation in patients with adenomyosis.

Fractional CO2 Laser Treatment Is Safe and Effective for the Management of Genitourinary Syndrome of Menopause in Korean Women.

This study evaluates the efficacy and safety of fractional CO2 lasers for treating genitourinary syndrome of menopause (GSM) in Korean women. The patients received three laser applications at an interval of 4 weeks each. The severity of GSM symptoms was assessed using a visual analog scale (VAS) at baseline and at every visit. The objective scale was measured using the vaginal health index score (VHIS) and Vaginal Maturation Index (VMI) after completion of the laser procedure. During each procedure, the patients' pain in the VAS score was recorded. In the last visit, patients evaluated their satisfaction with the laser therapy using a 5-point Likert scale. Thirty women completed all the study protocols. After two sessions of laser therapy, some GSM symptoms (vaginal dryness and urgency) and VHIS improved significantly. After completion of the treatment, all GSM symptoms improved (p < 0.05), and the VHIS further increased significantly (VHIS at baseline, 8.86 ± 3.2 vs. V3, 16.83 ± 3.15, p < 0.001). The average satisfaction was 4.3. This study shows that fractional CO2 laser treatment is effective and safe for Korean women with GSM. Further studies are needed to confirm these results and assess the long-term effects of laser therapy.

Robotic surgery in Gynecology: the present and the future.

Since its introduction, laparoscopic surgery has been often preferred over open surgery in obstetrics and gynecology due to its advantages, such as less bleeding, lower incidence of adhesions, reduced postoperative pain, short hospital stay, and quick return to daily life. However, in the case of complex surgeries, laparoscopy presented some limitations. Nonetheless, since the 1980s, medical robots have been introduced to overcome the technical limitations of laparoscopy and start a new age for minimally invasive surgery. In this review, we explore the indications and advantages and disadvantages of robotic surgery in the field of gynecology, and try to assess the recent trend of robotic surgery.

Body Composition and Bone Mineral Density in Postmenopausal Women with Advanced Knee Osteoarthritis Undergoing Surgical Treatment.

OBJECTIVES: This study aimed to demonstrate the bone mineral density (BMD) and body composition in postmenopausal women with knee osteoarthritis (OA) who underwent surgical treatment, such as total knee arthroplasty, osteotomy, or meniscectomy. METHODS: A total of 254 women with OA aged 50 years who underwent surgical treatment were enrolled in this study. We evaluated obesity-related factors, muscle components, and BMD using dual-energy X-ray absorptiometry. RESULTS: No significant differences were noted in the BMD of the hip joint between the symptomatic side of the leg with knee OA and the contralateral side. However, when comparing the BMD of each component, the results indicated a significantly higher BMD in the obesity group based on body mass index (BMI). When defining sarcopenic obesity (SO) using various indicators of obesity (BMI, the estimated visceral adipose tissue area, android/gynoid ratio, and total body fat percentage), the prevalence of SO in the OA group who underwent surgical treatment ranged from 22.0% to 49.6%. CONCLUSIONS: This study investigated obesity-related factors in patients with advanced knee OA who underwent surgery, revealing a high prevalence of overweight/obese individuals, the presence of SO, and a complex relationship between obesity, body composition, and bone density, highlighting the potential protective effects of weight-bearing on bone health while exploring the impact of sarcopenia on bone density differences in the context of OA. Depending on various definitions of obesity, diverse proportions of SO in patients with OA have been observed, and further detailed research is required to understand its impact on the condition.

A Recent Review of the Management of Postmenopausal Symptoms in Breast Cancer Survivors.

The treatment strategy for postmenopausal symptoms resulting from estrogen deficiency in breast cancer survivors receiving endocrine therapy should differ from that in normal women. Several nonhormonal pharmacological therapies can be used to treat vasomotor symptoms. Cognitive-behavioral therapy can help alleviate psychophysiological symptoms, including depression and sleep disorders. Topical vaginal estrogen and moisturizers may aid in treating genitourinary symptoms. Additionally, chronic conditions must be individually managed. Prevention of osteoporosis should always be included in the management, and physicians should be alert to possible cardiovascular risk and cognitive function changes.

Comparison of the Right and Left Femur Bone Mineral Densities in Postmenopausal Women.

OBJECTIVES: Bone mineral density (BMD) is measured in the hip and posteroanterior spine; moreover, according to the 2019 International Society for Clinical Densitometry guidelines, unilateral hip can be used. This study aimed to determine whether there is a difference between the BMD of both the femurs in postmenopausal women. METHODS: A total of 343 postmenopausal women were enrolled in this study from January 1, 2010, to December 31, 2019 at a single tertiary hospital. By using the Hologic® Horizon W DXA System, the femur and spine BMD was measured; BMD was recorded in g/cm². Following regions were analyzed in both the femurs: the femur neck, the trochanter area, and total femur. RESULTS: Mean age at imaging was 62 ± 9.7 years, and significant difference in the total BMD of both the femurs (P = 0.003) was observed. In secondary analysis, patients with osteoporosis showed significant contralateral BMD discrepancies in trochanter and total proximal femur BMD (P = 0.041 and P = 0.011, respectively). However, in women with normal BMD, no significant difference between the right and left femur BMD was observed. Furthermore, measurement of solely the unilateral hip can lead to a 16.9% of underdiagnosis in postmenopausal women. CONCLUSIONS: In conclusion, it is necessary to check BMD in both hips, particularly in patients suspected of osteoporosis.

Reproductive Life Span and Severe Hypoglycemia Risk in Postmenopausal Women with Type 2 Diabetes Mellitus.

BACKGROUND: Estrogen promotes glucose homeostasis, enhances insulin sensitivity, and maintains counterregulatory responses in recurrent hypoglycemia in women of reproductive age. Postmenopausal women with type 2 diabetes mellitus (T2DM) might be more vulnerable to severe hypoglycemia (SH) events. However, the relationship between reproductive factors and SH occurrence in T2DM remains unelucidated. METHODS: This study included data on 181,263 women with postmenopausal T2DM who participated in a national health screening program from January 1 to December 31, 2009, obtained using the Korean National Health Insurance System database. Outcome data were obtained until December 31, 2018. Associations between reproductive factors and SH incidence were assessed using Cox proportional hazards models. RESULTS: During the mean follow-up of 7.9 years, 11,279 (6.22%) postmenopausal women with T2DM experienced SH episodes. A longer reproductive life span (RLS) (≥40 years) was associated with a lower SH risk compared to a shorter RLS (<30 years) (adjusted hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.69 to 0.80; P for trend <0.001) after multivariable adjustment. SH risk decreased with every 5-year increment of RLS (with <30 years as a reference [adjusted HR, 0.91; 95% CI, 0.86 to 0.95; P=0.0001 for 30-34 years], [adjusted HR, 0.80; 95% CI, 0.76 to 0.84; P<0.001 for 35-39 years], [adjusted HR, 0.74; 95% CI, 0.68 to 0.81; P<0.001 for ≥40 years]). The use of hormone replacement therapy (HRT) was associated with a lower SH risk than HRT nonuse. CONCLUSION: Extended exposure to endogenous ovarian hormone during lifetime may decrease the number of SH events in women with T2DM after menopause.

A novel technique for myometrial defect closure after robot-assisted laparoscopic adenomyomectomy: A retrospective cohort study.

OBJECTIVE: To introduce our novel technique for myometrial defect closure after adenomyomectomy. MATERIALS AND METHODS: A retrospective cohort study. A total of 40 patients with adenomyosis who visited our clinic between October 2012 and January 2018 were recruited. Of those 34 patients were eligible for analysis. RESULTS: The mean thickness of the affected uterine wall before surgery was 4.02 cm ± 1.11, dropping to 2.37 cm ± 0.84 postoperatively. This led to a mean drop of 41% in the thickness of the affected wall, which was found to be significant using a paired t-test (p < 0.0001). The mean preoperative pain score was 8.68 ± 1.12, while the postoperative mean was 0.06 ± 0.34. The mean preoperative CA 125 was 121.73 ± 117.29, dropping to 6.95 ± 2.60 postoperatively. This was found to be significantly lower using both the Wilcoxon Signed Rank and Sign tests (p = 0.0156). CONCLUSION: Myometrial defect closure in a layer-by-layer fashion after robot-assisted laparoscopic adenomyomectomy is a reproducible technique. This uterine conserving method was effective in reducing our patients' pain. It may be the solution to maintaining adequate myometrial wall thickness, uterine layer alignment, and endometrial integrity.