Enhancing Cervical Cancer Screening: Review of p16/Ki-67 Dual Staining as a Promising Triage Strategy.

Cervical cancer, primarily caused by high-risk human papillomavirus (HR-HPV) types 16 and 18, is a major global health concern. Persistent HR-HPV infection can progress from reversible precancerous lesions to invasive cervical cancer, which is driven by the oncogenic activity of human papillomavirus (HPV) genes, particularly E6 and E7. Traditional screening methods, including cytology and HPV testing, have limited sensitivity and specificity. This review explores the application of p16/Ki-67 dual-staining cytology for cervical cancer screening. This advanced immunocytochemical method allows for simultaneously detecting p16 and Ki-67 proteins within cervical epithelial cells, offering a more specific approach for triaging HPV-positive women. Dual staining and traditional methods are compared, demonstrating their high sensitivity and negative predictive value but low specificity. The increased sensitivity of dual staining results in higher detection rates of CIN2+ lesions, which is crucial for preventing cervical cancer progression. However, its low specificity may lead to increased false-positive results and unnecessary biopsies. The implications of integrating dual staining into contemporary screening strategies, particularly considering the evolving landscape of HPV vaccination and changes in HPV genotype prevalence, are also discussed. New guidelines and further research are necessary to elucidate the long-term effects of integrating dual staining into screening protocols.

Effect of collagen endometrial patch loaded with adipose-derived mesenchymal stem cells on endometrial regeneration in rats with a thin endometrium.

Background: This study aimed to investigate the effects of a collagen endometrial patch (EM patch) loaded with adipose-derived mesenchymal stem cells (ADSCs) on endometrial regeneration in a rat model with thin endometrium. Materials and methods: Thin endometrium was induced in female rats and divided into treatment groups as outlined: control, group 1(G1), local injection of ADSCs into the uterus, group 2 (G2), an EM patch without ADSCs, group 3 (G3), and an EM patch loaded with ADSCs, group 4 (G4). The rats were euthanized at either two weeks or four weeks after modeling and treatment followed by histological and biochemical analyses to examine the regenerative effects on the injured endometrium. Results: Transplantation of the ADSC-loaded EM patch significantly promoted endometrial proliferation and increased the luminal epithelial area. Two weeks after treatment, the mean number of von Villebrand factor (vWF)+ or cluster of differentiation (CD) 31+-stained blood vessels was significantly higher in G4 than in G1 and G2. The mRNA and protein expression levels of TGF-ß and FGF2 were significantly upregulated in G4 compared to those in the control. G4 exhibited significantly increased LIF mRNA levels and immunoreactivity compared with the other groups at both two weeks and four weeks after treatment. Cell tracking after ADSCs treatment revealed the presence of a substantial number of ADSCs grafted in the uterine tissues of G4, whereas a low number of ADSCs that were focally clustered were present in G2. Conclusion: Transplantation of EM patches loaded with ADSCs resulted in the histological and biochemical restoration of an injured endometrium. The strategic integration of EM patches and ADSCs holds significant promise as an innovative therapeutic approach for effectively treating impaired endometrial conditions.

Dienogest in endometriosis treatment: A narrative literature review.

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.

Perceptions and Knowledge of Women Regarding Contraception and Current Trends in Contraceptive Use in Korea.

PURPOSE: This study aimed to investigate the perceptions and behaviors of Korean women of reproductive age in regards to contraception counseling. MATERIALS AND METHODS: The study sample was collected in Korea and comprised 1011 women aged 20-44 years and 150 obstetrics and gynecology (OB/GYN) doctors. Participants completed online questionnaires assessing their current methods of contraception, knowledge of and satisfaction with contraceptive methods, and willingness to learn about and use other contraceptive methods. RESULTS: Women used condoms (74.2%), natural methods (cycle control or withdrawal, 52.4%), and combined oral contraceptives (COCs) (36.9%) more frequently than long-acting reversible contraception (LARC) methods, such as hormone-releasing intrauterine system (IUS) (4.5%), copper-intrauterine devices (3.3%), and subdermal implants (1.4%). Although the proportion of women who used LARC was low, those who used hormone-releasing IUS or subdermal implants reported high levels of satisfaction. The findings revealed discordant results between women and OB/GYN doctors regarding the initiation and quality of information provided by doctors about contraception and overall satisfaction with counseling. Most women (83.1%) expressed a desire to have more information about various contraceptive methods. More than 60% of women reported a willingness to use LARC, such as hormone-releasing IUS or subdermal implants, when provided with detailed information in counseling. CONCLUSION: The majority of Korean women are familiar with condoms and natural methods, but lack knowledge about alternative contraceptive methods, including LARC. Women who used LARC reported higher levels of satisfaction than those who used other methods.

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.

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.

Artificial intelligence approaches to the determinants of women's vaginal dryness using general hospital data.

The aim of this study is to analyse the determinants of women's vaginal dryness using machine learning. Data came from Korea University Anam Hospital in Seoul, Republic of Korea, with 3298 women, aged 40-80 years, who attended their general health check from January 2010 to December 2012. Five machine learning methods were applied and compared for the prediction of vaginal dryness, measured by a Menopause Rating Scale. Random forest variable importance, a performance gap between a complete model and a model excluding a certain variable, was adopted for identifying major determinants of vaginal dryness. In terms of the mean squared error, the random forest (1.0597) was much better than linear regression (17.9043) and artificial neural networks with one, two and three hidden layers (1.7452, 1.7148 and 1.7736, respectively). Based on random forest variable importance, the top-10 determinants of vaginal dryness were menopause age, age, menopause, height, thyroid stimulating hormone, neutrophils, years since menopause, lymphocytes, alkaline phosphatase and blood urea nitrogen. In addition, its top-20 determinants were peak expiratory flow rate, low-density lipoprotein cholesterol, white blood cells, monocytes, cancer antigen 19-9, creatinine, eosinophils, total cholesterol, triglyceride and amylase. Machine learning presents a great decision support system for the prediction of vaginal dryness. For preventing vaginal dryness, preventive measures would be needed regarding early menopause, the thyroid function and systematic inflammation.Impact StatementWhat is already known on this subject? Only a few studies have investigated the risk factors of vaginal dryness in middle-aged women. More research is to be done for finding its various risk factors, identifying its major risk groups and drawing its effective clinical implications.What do the results of this study add? This study is the first machine-learning study to predict women's vaginal dryness and analyse their determinants. The random forest could discuss which factors are more important for the prediction of vaginal dryness. Based on random forest variable importance, menopause age was the most important determinant of vaginal dryness and their association was discovered to be negative in this study. Vaginal dryness was closely associated with the height, rather than the body weight or body mass index. The importance rankings of blood conditions related to systematic inflammation were within the top-20 in this study: neutrophils, lymphocytes, white blood cells, monocytes and eosinophils.What are the implications of these findings for clinical practice and/or further research? Machine learning presents a great decision support system for the prediction of vaginal dryness. For preventing vaginal dryness, preventive measures would be needed regarding early menopause and systematic inflammation.

Misperception of body weight and associated socioeconomic and health-related factors among Korean female adults: A nationwide population-based study.

Background: Misperception of body weight is associated with various psychological and health problems, including obesity, eating disorders, and mental problems. To date, female-specific risk factors, including socioeconomic or health-related lifestyle features, or their indicative performance for the misperception in Asian women according to age groups remain unknown. Objectives: To investigate the prevalence and associated risk factors for the mismatch in self-perceived body weight and evaluated the classification performance of the identified risk factors across age groups in female adults. Methods: We analyzed data of 22,121 women (age 19-97 years) from the 7-year Korea National Health and Nutrition Examination Survey dataset (2010-2016). We evaluated self-perceived body weight of the participants with their actual weight using the body mass index cut-off and grouped them by age: early adulthood (19-45), middle adulthood (46-59), and late adulthood (≥60). Logistic regression was conducted in each age group based on their weight misperception. The classification performance of the identified risk factors was evaluated with a bagging tree ensemble model with 5-fold cross-validation. Results: 22.2% (n=4,916) of the study participants incorrectly perceived their body weight, of which 14.1% (n=3,110) and 8.2% (n=1,806) were in the underestimated and overestimated groups. Among the age groups, the proportion of participants who misperceived their body weight was highest in late adulthood (31.8%) and the rate of overestimation was highest in early adulthood (14.1%). We found that a lower education level, absence of menopause, perception of themselves as unhealthy, and efforts for weight management were significantly associated with the overall misperception (overestimation or underestimation) of body weight across age groups. Based on the identified risk factors, the highest area under the receiver operating curve (AUROC) and accuracy of the best classification model (weight overestimation in all participants) were 0.758 and 0.761, respectively. Adding various associated lifestyle factors to the baseline model resulted in an average increase of 0.159 and 0.135 in AUROC for classifying weight underestimation and overestimation, respectively. Conclusions: Age, education level, marital status, absence of menopause, amount of exercise, efforts for weight management (gain, loss, and maintenance), and self-perceived health status were significantly associated with the mismatch of body weight.

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.

Risk of type 2 diabetes is increased in nonobese women with polycystic ovary syndrome: the National Health Insurance Service-National Sample Cohort Study.

OBJECTIVE: To investigate the relationship between polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus (T2DM) in Korean women. DESIGN: Longitudinal case-control study. SETTING: Not applicable. PATIENT(S): PCOS patients aged 15 to 44 years (n = 1,136) and control individuals (n = 5,675), matched 1:5 by age group, income, and region of residence. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): The occurrence of T2DM. RESULT(S): In the PCOS and control groups, 15.7% and 14.4%, respectively, were obese (body mass index ≥25 kg/m2). The incidence rate of T2DM was 15.84/1,000 and 5.80/1,000 person-years in the PCOS and control groups, respectively. The unadjusted hazard ratio (HR) of T2DM in women with PCOS was 2.6-fold higher than that in control individuals. Women with PCOS still had a higher HR of T2DM than did control individuals after adjustment for body mass index, family history of T2DM, physical exercise level, and total cholesterol. PCOS was significantly associated with T2DM in women both with and without obesity. CONCLUSION(S): PCOS is independently associated with an increased incidence of T2DM in both obese and nonobese women. Screening for T2DM should be considered for both obese and nonobese women with PCOS in Korea.

Comparison of various menopausal symptoms and risk factor analysis in Korean women according to stage of menopause.

OBJECTIVE: To determine the prevalence and severity of menopausal symptoms and their related risk factors among middle-aged Korean women according to their reproductive stages. METHODS: This cross-sectional study included 3039 Korean women, aged 45-65 years, who attended their routine health checkup. Their scores from the Menopause Rating Scale (MRS) were compared and participants were categorized into four groups according to stage of menopause: premenopause, early menopause (≤2 years from their last menstruation), mid-menopause (2-8 years), and late menopause (>8 years). RESULTS: The mean age of the participants was 52.81 ± 5.39 years, and 98.5 % of them reported one or more symptoms included in the MRS. The most common symptom was physical/mental exhaustion, experienced by 86.7 % of participants. The prevalence of moderate to severe symptoms, including vasomotor symptoms, heart discomfort, sleep problems, sexual problems, vaginal dryness, and joint/muscular discomfort, increased in the early menopausal period. This increased in the late menopausal period compared with its prevalence at premenopause. The prevalence of moderate to severe psychological symptoms, heart discomfort, and sleep problems followed a U-shaped trend after menopause: high at early menopause, low at mid-menopause, and high again at late menopause. A low level of physical exercise was an independent risk factor for a high total MRS score; however, the menopausal stages, age, and weight were also variously associated with menopausal symptoms. CONCLUSIONS: Several menopausal symptoms remain severe, or are aggravated, until the late menopausal period among Korean women. More attention is warranted to manage these symptoms in postmenopausal women.

Endometriosis Is Associated with Adverse Pregnancy Outcomes: a National Population-Based Study.

Pregnancy and neonatal outcomes in women diagnosed with endometriosis were investigated using data collected from the Korea National Health Insurance Claims Database and the National Health Screening Program for Infants and Children. A total of 3,778,561 women who gave birth between 2007 and 2015 were identified, and 1,938,424 primiparous women and their newborns were included in this study. Women with a diagnosis of endometriosis had a significantly higher incidence of multiple pregnancy, cesarean section, breech presentation, postpartum hemorrhage, placental abruption, placenta previa, and stillbirth than women without endometriosis (P < 0.0001). The rates of preterm birth and low birth weight were also increased in women with endometriosis (P < 0.0001). After adjusting for age, the estimated risks of these outcomes remained significant. Women previously diagnosed with endometriosis have an increased risk of adverse pregnancy and neonatal outcomes. Particular attention and information regarding these conditions should be provided to women with endometriosis during the preconception or antenatal periods.

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 cells or C-X-C motif chemokine 12 (CXCL12) treatment improve thin endometrium in a mouse model.

Successful implantation and pregnancy is dependent on sufficient endometrial growth during each reproductive cycle. Here, we report the therapeutic effect of either bone marrow-derived cells (BMDCs) or the stem cell chemo-attractant C-X-C motif chemokine 12 (CXCL12) on endometrial receptivity in a murine ethanol induced thin endometrium model. Endometrial epithelial area was significantly increased in mice treated with BMDCs, CXCL12, or by co-treatment with both compared with PBS-treated controls. Ki-67 and CD31 immunoreactivity was significantly higher in mice treated with either BMDCs, CXCL12, or both. The mRNA expression levels of endometrial receptivity markers leukemia inhibitory factor, interleukin-1ß, and integrin beta-3 were increased in mice treated with either BMDCs, CXCL12, or both. The mRNA levels of matrix metalloproteinase-2 and -9 were significantly decreased by BMDCs but not by CXCL12. Pregnancy rates and litter size were increased after either treatment. Both BMDCs and CXCL12 displayed a comparable efficacy on endometrial regeneration in mice with thin endometrium. Our findings indicate the potential therapeutic effects of BMDCs and CXCL12 on infertility related to thin endometrium. Bone marrow-derived cells and CXCL12 displayed a comparable efficacy on endometrial regeneration in mice with thin endometrium.

Assessment of patient-reported outcomes (PROs): treatment satisfaction, medication adherence, and quality of life (QoL) and the associated factors in postmenopausal osteoporosis (PMO) patients in Korea.

Patient-reported outcomes (PROs) provide practical guides for treatment; however, studies that have evaluated PROs of women in Korea with postmenopausal osteoporosis (PMO) are lacking. This cross-sectional, multi-center (29 nationwide hospitals) study, performed from March 2013 to July 2014, aimed to assess PROs related to treatment satisfaction, medication adherence, and quality of life (QoL) in Korean PMO women using osteoporosis medication for prevention/treatment. Patient demographics, clinical characteristics, treatment patterns, PROs, and experience using medication were collected. The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) (score-range, 0-100; domains: effectiveness, side effects, convenience, global satisfaction), Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS) (score-range, 0-8), and EuroQol-5 dimensions questionnaire (index score range, - 0.22 to 1.0; EuroQol visual analog scale score range, 0-100) were used. To investigate factors associated with PROs, linear (treatment satisfaction/QoL) or logistic (medication adherence) regression analyses were conducted. A total of 1804 patients (age, 62 years) were investigated; 60.1% used bisphosphonate, with the majority (67.2%) using weekly medication, 27.8% used daily hormone replacement therapy, and 12.1% used daily selective estrogen receptor modulator. Several patients reported gastrointestinal (GI) events (31.6%) and dental visits due to problems (24.1%) while using medication. Factors associated with the highest OS-MMAS domain scores were convenience and global satisfaction. GI events were associated with non-adherence. TSQM scores for effectiveness, side effects, and GI risk factors were significantly associated with QoL. Our study elaborately assessed the factors associated with PROs of Korean PMO women. Based on our findings, appropriate treatment-related adjustments such as frequency/choice of medications and GI risk management may improve PROs.

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

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.

Moderate to severe vasomotor symptoms are risk factors for non-alcoholic fatty liver disease in postmenopausal women.

OBJECTIVE: To evaluate the association between vasomotor symptoms (VMS) and non-alcoholic fatty liver disease (NAFLD) in postmenopausal women. METHODS: This cross-sectional study included 1793 Korean postmenopausal women aged 45-65 years who attended a routine health check at a Korean institution from January 2010 to December 2012. Their scores on the Menopause Rating Scale were used to assess VMS. Moderate to severe VMS included ratings of moderate, severe, and very severe. NAFLD was diagnosed by abdominal ultrasound among those who indicated that their ethanol intake was less than 70 g/week. RESULTS: The mean age of these participants was 54.51 ± 4.74 years and the mean duration of menopause was 5.36 ± 4.41 years. A total of 602 (33.6%) women reported mild VMS while 435 (24.3%) reported moderate to severe VMS. The prevalence of NAFLD differed significantly according to the severity of VMS (none, 31.7%; mild, 34.9%; moderate to severe, 39.1%; p = 0.037). Levels of the liver enzymes alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase were significantly higher in women with moderate to severe VMS than in those without VMS. Logistic regression analysis revealed that moderate to severe VMS were significantly associated with the risk of NAFLD (OR: 1.50, 95% CI: 1.10-2.03) after adjusting for age, years since menopause, central obesity, alcohol use, smoking, exercise, and insulin resistance. CONCLUSIONS: Moderate to severe VMS are associated with NAFLD and worse liver function profiles in otherwise healthy postmenopausal women. Further longitudinal studies are needed to investigate casual relationships and underlying mechanisms.

Effectiveness of Dienogest for Treatment of Recurrent Endometriosis: Multicenter Data.

This study aimed to assess whether dienogest (DNG) is also effective in patients with recurrent endometriosis based on multicenter data of 121 women who were clinically diagnosed as having recurrent endometriosis and treated for more than 24 weeks with DNG (2 mg daily). We evaluated the changes in endometriosis-associated pain scores (visual analog scale [VAS]), serum cancer antigen 125 (CA-125) levels, and endometrioma sizes following DNG medication in these women along with adverse events associated with DNG medication. The mean duration of DNG treatment was 57.80 (24.08) weeks, and during continuation of DNG, the mean VAS score was 5.03 (1.73) at baseline and significantly decreased to 2.46 (1.32) at 24 weeks after taking DNG. In subgroup analysis, the trend of pain-related symptoms was compared between the symptom-only recurrence group and the recurrent endometrioma group. In both groups, the pain scores decreased significantly during the first 24 weeks but remained relatively unchanged thereafter. Moreover, the size of recurrent endometriomas and CA-125 levels also decreased significantly compared to baseline. The mean size of recurrent endometriomas was 3.77 (1.59) cm in diameter and decreased to 2.74 (1.53) cm after 24 weeks of DNG treatment ( P for trend < .001). The mean CA-125 level was 80.04 U/mL at baseline and significantly decreased to 33.11 U/mL after taking DNG for 24 weeks and lasted until 72 weeks ( P for trend = .0288). Overall, 51 (42.15%) patients reported adverse events, and the most common one was irregular bleeding pattern (29.75%, 36/121). In conclusion, DNG was found to be effective in reducing the size of endometriomas and provided symptomatic relief in this cohort of women with recurrent endometriosis.