Dienogest in endometriosis treatment: A narrative literature review / 대한생식의학회지

Endometriosis is characterized by the implantation of endometrial cells outside the uterus. This hormone-dependent disease is highly prevalent among women of reproductive age. Clinical symptoms of endometriosis include dysmenorrhea, pelvic pain, and infertility, which can negatively impact the overall quality of life of those affected. The medical treatment of endometriosis serves as an important therapeutic option, aimed at alleviating pain associated with the condition and suppressing the growth of endometriotic lesions. As such, it is employed as an adjuvant therapy following surgery or an empirical treatment after the clinical diagnosis of endometriosis. Dienogest, a fourth-generation progestin, has received approval for the treatment of endometriosis in many countries. A growing body of evidence has demonstrated its efficacy in managing endometriosis-associated pain, preventing symptoms, and reducing lesion recurrence. In this review, we examine the clinical efficacy, safety, and tolerability of dienogest in treating endometriosis. We also provide updated findings, drawing from clinical studies that focus on the long-term use of this medication in patients with endometriosis.

What is the link between endometriosis and adiposity?

Endometriosis is defined by the presence of extrauterine endometrial tissue and presents with symptoms of dysmenorrhea, chronic pelvic pain, and impaired fertility. This condition often follows a chronic progressive course with favorable recurrence, even after surgical or medical treatment. The etiology or exact pathophysiology of endometriosis remains to be clarified, although it is thought to be a complex and multifactorial disease. Prior epidemiological or population-based studies have reported several risk factors related to endometriosis, such as environmental, menstrual, habitual, and lifestyle factors. Moreover, anthropometry has been found to be significantly associated with the diagnosis of endometriosis, as a lower body mass index is associated with an elevated risk of endometriosis. Here, we review studies that have examined the association between body size and the risk of endometriosis and discuss the clinical and biological significance of the relationship between adiposity and endometriosis.

Contraception in the COVID-19 pandemic: recommendations from the Korean society of contraception and reproductive health

Coronavirus disease 2019 (COVID-19) is associated with a systemic inflammatory response that activates coagulation in symptomatic patients. In addition, a rare form of thrombosis has been reported in people who received the COVID-19 vaccine, most of whom were women younger than 50 years of age. Considering that hormonal contraceptive methods widely used by women of childbearing age increase the risk of thrombosis, the development of guidelines for the use of hormonal contraceptives in the era of the COVID-19 pandemic is necessary. In this context, the Korean Society of Contraception and Reproductive Health provides guidelines for issues regarding contraception and reproductive health during the pandemic.

Machine Learning Approaches to Identify Factors Associated with Women's Vasomotor Symptoms Using General Hospital Data

Background@#To analyze the factors associated with women's vasomotor symptoms (VMS) using machine learning. @*Methods@#Data on 3,298 women, aged 40–80 years, who attended their general health check-up from January 2010 to December 2012 were obtained from Korea University Anam Hospital in Seoul, Korea. Five machine learning methods were applied and compared for the prediction of VMS, measured by the Menopause Rating Scale. Variable importance, the effect of a variable on model performance, was used for identifying the major factors associated with VMS. @*Results@#In terms of the mean squared error, the random forest (0.9326) was much better than linear regression (12.4856) and artificial neural networks with one, two, and three hidden layers (1.5576, 1.5184, and 1.5833, respectively). Based on the variable importance from the random forest, the most important factors associated with VMS were age, menopause age, thyroid-stimulating hormone, and monocyte, triglyceride, gamma glutamyl transferase, blood urea nitrogen, cancer antigen 19-9, C-reactive protein, and low-density lipoprotein cholesterol levels. Indeed, the following variables were ranked within the top 20 in terms of variable importance: cancer antigen 125, total cholesterol, insulin, free thyroxine, forced vital capacity, alanine aminotransferase, forced expired volume in 1 second, height, homeostatic model assessment for insulin resistance, and carcinoembryonic antigen. @*Conclusion@#Machine learning provides an invaluable decision support system for the prediction of VMS. For managing VMS, comprehensive consideration is needed regarding thyroid function, lipid profile, liver function, inflammation markers, insulin resistance, monocyte count, cancer antigens, and lung function.

Machine Learning Approaches to Identify Factors Associated with Women's Vasomotor Symptoms Using General Hospital Data

Background@#To analyze the factors associated with women's vasomotor symptoms (VMS) using machine learning. @*Methods@#Data on 3,298 women, aged 40–80 years, who attended their general health check-up from January 2010 to December 2012 were obtained from Korea University Anam Hospital in Seoul, Korea. Five machine learning methods were applied and compared for the prediction of VMS, measured by the Menopause Rating Scale. Variable importance, the effect of a variable on model performance, was used for identifying the major factors associated with VMS. @*Results@#In terms of the mean squared error, the random forest (0.9326) was much better than linear regression (12.4856) and artificial neural networks with one, two, and three hidden layers (1.5576, 1.5184, and 1.5833, respectively). Based on the variable importance from the random forest, the most important factors associated with VMS were age, menopause age, thyroid-stimulating hormone, and monocyte, triglyceride, gamma glutamyl transferase, blood urea nitrogen, cancer antigen 19-9, C-reactive protein, and low-density lipoprotein cholesterol levels. Indeed, the following variables were ranked within the top 20 in terms of variable importance: cancer antigen 125, total cholesterol, insulin, free thyroxine, forced vital capacity, alanine aminotransferase, forced expired volume in 1 second, height, homeostatic model assessment for insulin resistance, and carcinoembryonic antigen. @*Conclusion@#Machine learning provides an invaluable decision support system for the prediction of VMS. For managing VMS, comprehensive consideration is needed regarding thyroid function, lipid profile, liver function, inflammation markers, insulin resistance, monocyte count, cancer antigens, and lung function.

Vasomotor Symptoms: More Than Temporary Menopausal Symptoms

Vasomotor symptoms (VMS), such as hot flashes and night sweating, are classic menopausal symptoms experienced by a majority of perimenopausal and postmenopausal women. VMS have received a great deal of attention due to their relationship with cardiometabolic risk. Further, accumulating evidence indicates that VMS are associated with an increased risk of several chronic diseases, including metabolic syndrome, type 2 diabetes mellitus, nonalcoholic fatty liver diseases, and osteoporosis in perimenopausal and postmenopausal women. These findings suggest VMS as biomarkers of impaired cardiometabolic conditions rather than just temporary symptoms in menopausal women, warranting further studies to confirm the casual relationship of VMS with these diseases and the exact underlying mechanism in this context.

Vasomotor Symptoms: More Than Temporary Menopausal Symptoms

Vasomotor symptoms (VMS), such as hot flashes and night sweating, are classic menopausal symptoms experienced by a majority of perimenopausal and postmenopausal women. VMS have received a great deal of attention due to their relationship with cardiometabolic risk. Further, accumulating evidence indicates that VMS are associated with an increased risk of several chronic diseases, including metabolic syndrome, type 2 diabetes mellitus, nonalcoholic fatty liver diseases, and osteoporosis in perimenopausal and postmenopausal women. These findings suggest VMS as biomarkers of impaired cardiometabolic conditions rather than just temporary symptoms in menopausal women, warranting further studies to confirm the casual relationship of VMS with these diseases and the exact underlying mechanism in this context.

Bone marrow-derived stem cells contribute to regeneration of the endometrium / 대한생식의학회지

Stem cells are undifferentiated cells capable of self-renewal and differentiation into various cell lineages. Stem cells are responsible for the development of organs and regeneration of damaged tissues. The highly regenerative nature of the human endometrium during reproductive age suggests that stem cells play a critical role in endometrial physiology. Bone marrow-derived cells migrate to the uterus and participate in the healing and restoration of functionally or structurally damaged endometrium. This review summarizes recent research into the potential therapeutic effects of bone marrow-derived stem cells in conditions involving endometrial impairment.

Complete vaginal outlet stenosis in a patient with Sheehan’s syndrome

We present a case of complete vaginal stenosis in a woman diagnosed with Sheehan’s syndrome. The patient delivered at full-term 5 months prior, and experienced massive postpartum bleeding at that time. During evaluation of persistent amenorrhea, we found that her vaginal orifice was completely adhesive and obstructed. Prior to corrective surgery, we managed the patient with an oral contraceptive to induce uterine bleeding into the vaginal outflow tract. After three cycles of an oral contraceptive, we could confirm that there was no stenotic lesion in the vaginal cavity as a hematocolpos was created. Adhesiolysis with scar revision for the vaginal stenosis was successfully performed; it was found that the lesion was limited to only the distal part of the vaginal outlet. Complete vaginal stenosis in reproductive age women with hypopituitarism has not been reported. The artificial induction of hematometrocolpos before surgery was useful in determining the extent of the stenotic lesion, and assured safety.

Outcome of posterior transvaginal mesh kit / 대한산부인과내시경학회지

OBJECTIVE: The objective of this study is to report outcomes of apical and posterior pelvic organ prolapse repair using posterior transvaginal mesh kit. METHODS: Thirty four consecutive patients with apical or posterior pelvic organ prolapse over pelvic organ prolapse quantification (POP-Q) stage 2 were repaired by posterior transvaginal mesh kit at the Korea University Guro Hospital between July 2007 and June 2011. Postoperative follow-up visits were scheduled at 1, 6 months after surgery, with question about side effects and POP-Q exam. RESULTS: Thirty four consecutive patients who underwent posterior transvaginal mesh kit had completed 6 month follow up. The demographics are the mean age 65.9+/-8.6 years, the mean body mass index 26.4+/-3.0 kg/m2 and the mean parity 3.6+/-1.5. Overall anatomic cure rates of apical pelvic organ prolapse and rectocele were 91.7%, 92.6%, respectively. The Ap, Bp scores improved significantly after operation (p<0.01). No patient presented healing abnormality. CONCLUSION: Posterior transvaginal mesh kit is effective and safe for treatment of apical and posterior pelvic organ prolapse.

Microarray Analysis of Gene Expression During Differentiation of Human Mesenchymal Stem Cells Treated with Vitamin E in vitro into Osteoblasts

OBJECTIVE: Supplementation with vitamin E is able to protect bone against free radical-induced elevation of bone-resorbing cytokines. We examined gene expression by microarray analysis during the differentiation of human mesenchymal stem cells treated with vitamin E into osteoblasts in vitro. METHODS: Human bone marrow stem cells were cultured in osteogenic differentiation medium and vitamin E was added. A colorimetric immunoassay for the quantification of cell proliferation was used to measure osteoblast differentiation. Gene expression was analyzed using a microarray technique. We also used a real time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: It was found that vitamin E enhanced cell proliferation when compared to cells cultured in media without vitamin E. We focused on 68 genes which are related to osteogenesis and osteoclastogenesis. Alkaline phosphatase, transforming growth factor-beta 1, fibroblast growth factor receptor 1, matrix metalloproteinase 2, muscle segment homeobox 2, bone morphogenetic protein 1, biglycan, vascular endothelial growth factor B, dentin sialophosphoprotein, cartilage oligomeric matrix protein, runt-related transcription factor 2, fibroblast growth factor receptor 3, and SMAD2 were upregulated > 2-fold compared to the control. Conversely, osteopetrosis-associated transmembrane protein 1, microphthalmia-associated transcription factor, and epidermal growth factor receptor were downregulated > 2-fold compared to the control. Vitamin E produced a 1.5-fold increase in the expression of runt-related transcription factor 2 and transforming growth factor-beta 1 as determined by real time RT-PCR. CONCLUSION: Vitamin E had a positive effect on the gene expressions regarding osteogenic differentiation of mesenchymal stem cells.

The Association between Components of the Metabolic Syndrome and Bone Mineral Density

OBJECTIVE: The aim of this study was to evaluate the association between the components of the metabolic syndrome (MS) and bone mineral density (BMD). METHODS: We conducted a retrospective cross-sectional analysis for 128 men (mean age 50.4 +/- 8.3 years) and 391 women (mean age 46.9 +/- 11.6 years) in Korea University Guro Hospital, Korea. Height (cm), weight (kg), waist circumference (cm), and blood pressure (mmHg) were measured. Fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C), and triglycerides were measured. BMD at the total hip and lumbar spine was measured by dual X-ray densitometry. All participants completed a standardized questionnaire including medical history, smoking history, alcohol consumption, physical activity and menopausal status. RESULTS: Women with MS had lower BMD at lumbar and total hip sites (0.937 +/- 0.136 g/cm2, P-value 0.010; 0.875 +/- 0.113 g/cm2, P-value 0.045, respectively) than did women without MS. These differences at the spine and femoral neck were persisted after adjusting for age, body mass index, menopause status, alcohol consumption, smoking and physical activity. However, no significant differences in BMD were found in men between those with and without MS. In linear regression analyses, waist circumferences were highly associated with BMD at lumbar and total hip sites in women (beta -0.003, P-value < 0.001; beta -0.001, P-value 0.001, respectively). However, no significant differences were found in men between BMD and components of the MS. CONCLUSION: Among components of MS, waist circumference was associated with BMD in women. But no association was found in men. Women with MS had lower BMD than did women without MS.

Barium Stimulates the Expression of Osteogenic Genes in Human Mesenchymal Stem Cells into Osteoblasts in vitro / 대한폐경학회지

OBJECTIVES: The purpose of this study was to determine the effect of barium on gene expression in differentiation of human mesenchymal stem cells into osteoblasts in vitro. METHODS: Human bone marrow stem cells were cultured for 0~14 days in osteogenic differentiation medium with strontium chloride (SrCl2) and barium chloride (BaCl2). Alkaline phosphatase (ALP) activity staining was the method selected for measuring osteoblast differentiation. Total ribonucleic acid (RNA) was extracted after 1, 3, 7, and 14 days, and analysis of runt-related transcription factor 2/core-binding factor alpha 1 (Runx2/Cbfa1), bone morphogenetic protein-2 (BMP-2), and bone sialoprotein (BSP) gene expression was performed by real-time reverse transcriptase (RT)-polymerase chain reaction (PCR). RESULTS: Barium and strontium had a superior enhancing effect on cell proliferation when compared to cells cultured in media without strontium or barium. BaCl2 produced a 2-fold increase in the expression of Runx2/Cbfa1 at 14 days. SrCl2 (0.1~0.3 mM) produced a 2-fold increase in the expression of Runx2/Cbfa1 at 14 days. Barium produced a 1.5-fold increase in the expression of BMP-2 on days 1 or 3. Expression of BSP was increased 1.5~1.7- and 2-fold on days 1 and 14 by barium and strontium, respectively. CONCLUSION: Barium-like strontium is considered one of the important factors in inducing mesenchymal stem cells to differentiate into osteoblasts with further enhancement on bone formation.

Relationship between Metabolic Syndrome and Bone Mineral Density in Middle-aged Women / 대한폐경학회지

OBJECTIVES: To determine the relationship between metabolic syndrome (MS) and bone mineral density (BMD) in middle-aged women. METHODS: Three hundred eight premenopausal women were included in this study, including 268 women without MS and 40 women confirmed to have MS according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria. Clinical markers including anthropometric parameters, the serum lipid profile, and glucose level were determined and analyzed with the BMD at the lumbar spine and femoral neck. RESULTS: There was no significant difference in femoral neck or lumbar BMD between the controls and women with MS. In correlation tests, the body mass index (BMI) showed a significant association with the femoral (r = 0.209, P < 0.001) and lumbar BMD (r = 0.176, P = 0.002). In addition, the waist circumference (WC) was also significantly correlated with the femoral (r = 0.142, P = 0.012) and lumbar BMD (r = 0.113, P = 0.048). CONCLUSION: The BMI and WC showed a significant positive association with the femoral and lumbar spine BMD in premenopausal women. Further studies with a large population will be needed to elucidate the combined effect of MS on BMD in middle-aged women.

The Effect of Pomegranate on Depression, Anxiety, and Food Intake in Ovariectomized Rats / 대한폐경학회지

OBJECTIVES: To determine whether or not pomegranate extract can affect depression, anxiety, and food intake in ovariectomized rats. METHODS: Seventy-nine female Sprague-Dawley rats were divided into six groups: A, no operation and no drug intake; B, sham operation and distilled water; C, ovariectomy and distilled water; D, ovariectomy and 10% dilute pomegranate extract; E, ovariectomy and 20% dilute pomegranate extract; and F, ovariectomy and 40% dilute pomegranate extract. Beginning 2 days after surgery, drugs were administrated for 4 weeks. After that, the rats were subjected to the elevated plus maze (EPM) test and forced swim test (FST). RESULTS: The 10% pomegranate extract had a lower % closed arm entry frequency in the EPM test. A pomegranate dose-dependent decrease in the duration of immobility duration in FST was shown. Pomegranate did not reverse ovariectomy-related hyperphagia and weight gain. CONCLUSION: Pomegranate extract improved depression and anxiety in a postmenopausal model with ovariectomized rats.

Prophylactic Hypogastric Artery Ballooning in a Patient with Complete Placenta Previa and Increta

Abnormal attachment of the placenta (Placenta accreta, increta, and percreta) is an uncommon but potentially lethal cause of maternal mortality from massive postpartum hemorrhage. A 33-yr-old woman, who had been diagnosed with a placenta previa, was referred at 30 weeks gestation. On ultrasound, a complete type of placenta previa and multiple intraplacental lacunae, suggestive of placenta accreta, were noted. For further evaluation of the placenta, pelvis MRI was performed and revealed findings suspicious of a placenta increta. An elective cesarean delivery and subsequent hysterectomy were planned for the patient at 38 weeks gestation. On the day of delivery, endovascular catheters for balloon occlusion were placed within the hypogastric arteries, prior to the cesarean section. In the operating room, immediately after the delivery of the baby, bilateral hypogastric arteries were occluded by inflation of the balloons in the catheters previously placed within. With the placenta retained within the uterus, a total hysterectomy was performed in the usual fashion. The occluding balloons were deflated after closure of the vaginal cuff with hemostasis. The patient had stable vital signs and normal laboratory findings during the recovery period; she was discharged six days after delivery without complications. The final pathology confirmed a placenta increta.

The Effect of Pomegranate on Postmenopausal Syndrome: A Randomized, Double-blind, Placebo-controlled Trial / 대한폐경학회지

OBJECTIVES: To investigate the safety and effect of pomegranate extract on postmenopausal syndrome. METHODS: One hundred twelve women participated in a randomized, double-blind, placebo-controlled trial conducted in a tertiary university hospital in Korea. Women were treated with pomegranate extract or placebo for 12 weeks. The primary end point was menopausal symptoms, which were evaluated based on the Kupperman Index. The secondary end point was the serum estradiol (E2, pg/ml) level. Statistical analysis was performed. RESULTS: Menopausal symptoms as the Kupperman Index were significantly improved in the pomegranate group compared to placebo during the 12 weeks of intervention (P < 0.0001). Melancholia did not differ between the two groups. There was also no difference in serum E2 levels. There were no differences between the two groups in age, body weight, height, systolic and diastolic blood pressures, serum white and red blood cell counts, and fasting blood glucose, hemoglobin, aspartic transaminase, alanine transaminase, total cholesterol, triglycerides, high- and low-density lipoprotein-cholesterol, creatinine, and E2 levels. The side effects of pomegranate extract were negligible. CONCLUSION: Pomegranate extract is safe and effective in the treatment of menopausal symptoms. Further studies on whether or not the beneficial effect of pomegranate extract is due to the estrogen component are needed.

The Effect of Pomegranate on Postmenopausal Syndrome: A Randomized, Double-blind, Placebo-controlled Trial / 대한폐경학회지

OBJECTIVES: To investigate the safety and effect of pomegranate extract on postmenopausal syndrome. METHODS: One hundred twelve women participated in a randomized, double-blind, placebo-controlled trial conducted in a tertiary university hospital in Korea. Women were treated with pomegranate extract or placebo for 12 weeks. The primary end point was menopausal symptoms, which were evaluated based on the Kupperman Index. The secondary end point was the serum estradiol (E2, pg/ml) level. Statistical analysis was performed. RESULTS: Menopausal symptoms as the Kupperman Index were significantly improved in the pomegranate group compared to placebo during the 12 weeks of intervention (P < 0.0001). Melancholia did not differ between the two groups. There was also no difference in serum E2 levels. There were no differences between the two groups in age, body weight, height, systolic and diastolic blood pressures, serum white and red blood cell counts, and fasting blood glucose, hemoglobin, aspartic transaminase, alanine transaminase, total cholesterol, triglycerides, high- and low-density lipoprotein-cholesterol, creatinine, and E2 levels. The side effects of pomegranate extract were negligible. CONCLUSION: Pomegranate extract is safe and effective in the treatment of menopausal symptoms. Further studies on whether or not the beneficial effect of pomegranate extract is due to the estrogen component are needed.

The effect of pomegranate on postmenopausal syndrome in ovariectomized rats / 대한산부인과학회지

OBJECTIVE: To determine whether or not pomegranate extract can affect postmenopausal syndrome in ovariectomized rats. METHODS: Seventy-nine female Sprague-Dawley rats were used: A, no intervention; B, sham operation and distilled water; C, ovariectomy and distilled water; D, ovariectomy and 10% dilute pomegranate; E, ovariectomy and 20% pomegranate; and F, ovariectomy and 40% pomegranate. The study samples were obtained 4 weeks later. The following parameters were investigated for analyses: the thickness of urogenital epithelium, tail skin temperature, serum levels of sex hormones, lipid profile, homocysteine, and thiobarbituric acid reactive substances. RESULTS: 20% pomegranate had a transient thickening effect of bladder epithelial layer. There was an intermittent lowering effect of tail skin temperature of pomegranate extract, however, it was not consistent. There were lowering effect in serum homocysteine and elevating effect in serum high density lipoprotein-cholesterol. Pomegranate did not reverse post-ovariectomy reduced sex hormone levels. CONCLUSION: Pomegranate extract showed a tendency to reverse ovariectomy-related urothelial changes. Also pomegranate had a serum homocysteine-lowering effect.

Perinatal Outcomes in Pregnant Women with Impaired Glucose Tolerance (IGT) Proven through 100 g Oral Glucose Tolerance Test (OGTT) / 대한주산의학회잡지

OBJECTIVE: To compare the perinatal outcomes of pregnant women with 100 g oral glucose tolerance test (OGTT) proven impaired glucose tolerance (IGT), with normal control and gestational diabetes mellitus (GDM) groups. METHODS: 159 pregnant women who had visited our medical center between March 2002 and March 2004, positive (> or = 140 g) for 50 g OGTT were included in this study. IGT was defined by the presence of one abnormal 100 g OGTT glucose value, and they were compared with the control group, and the GDM group(with at least 2 abnormal glucose values). The maternal and neonatal outcomes were assessed among three groups. RESULTS: Even though familial history of DM was significantly higher in the IGT and GDM group (p4 kg) and hypoglycemia was significantly increased in GDM group than other groups. The difference in the frequency of i) large for gestational age birthweight (>90 percentile) ii) preterm delivery, iii) APGAR score (1-min and 5-min), iv) shoulder dystocia, and v) congenital anomalies among the three groups was not notable-however, the incidence of neonatal hyperbilirubinemia was significantly higher and duration of NICU admission is significantly longer in the IGT group, compared to the control group (p95%) ii) infections (genitourinary and surgical wounds) in the three groups, the prevalence of preeclampsia was significantly higher in the IGT (p=0.018) and GDM group (p=0.023), compared with the control group. CONCLUSION: Neonatal hyperbilirubinemia, as well as maternal preeclampsia were significantly elevated in the IGT group. The results obtained thus far demonstrate the possibility of the need for active perinatal care with therapeutic intervention in pregnant women with IGT.