Corrigendum: 2023 Korean Society of Menopause - Osteoporosis Guidelines Part I.

This corrects the article on p. 1 in vol. 30, PMID: 38714490.

Effects of Rhythm Step Training on Foot and Lower Limb Balance in Children and Adolescents with Flat Feet: A Radiographic Analysis.

Background and Objectives: Owing to the recent reports regarding the efficacy of rhythm step training (RST) in lower limb muscle development and motor skill enhancement, this study aimed to evaluate the effects of RST on foot and lower limb balance in children and adolescents diagnosed with flat feet using radiographic analysis. Materials and Methods: A total of 160 children and adolescents diagnosed with flat feet from a hospital in Seoul were randomly assigned to the general flat feet training (GFFT) (n = 80) or RST (n = 80) group. Patients in both groups exercised for 50 min once a week for 12 weeks. Key variables, such as quadriceps angle (Q-angle), calcaneal pitch angle (CPA), calcaneal-first metatarsal angle (CFMA), and navicular-cuboid overlap ratio (OR) were measured before and after the intervention. Results: Significant improvements in Q-angle (p < 0.001), CPA (p < 0.001), CFMA (p < 0.001), and navicular-cuboid OR (p < 0.001) were observed in the RST group compared to the GFFT group. RST was found to be more effective in normalizing the biomechanical function of the calcaneus and improving lower limb function. Conclusions: RST significantly enhances foot and lower limb balance in children and adolescents with flat feet, suggesting its potential use as an effective intervention for this population. The study did not specifically analyze the effects of various components of rhythm training, such as music, exercise intensity, and frequency, on the outcomes. Further research is needed to determine how each of these elements individually influences the results.

Asia-Pacific consensus on long-term and sequential therapy for osteoporosis.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Adolescents diagnosed with polycystic ovary syndrome under the Rotterdam criteria but not meeting the diagnosis under the updated guideline.

STUDY QUESTION: What are the characteristics of adolescents diagnosed with polycystic ovary syndrome (PCOS) based on the 2003 Rotterdam criteria, but who do not meet the diagnosis according to the international evidence-based guideline? SUMMARY ANSWER: Adolescents who had features of PCOS but did not meet the evidence-based guideline adolescent criteria exhibited unfavorable metabolic profiles compared to controls and shared considerable metabolic and hormonal features with adolescents who did meet the adolescent criteria. WHAT IS KNOWN ALREADY: The international evidence-based PCOS guideline recommended that ultrasound should not be used for the diagnosis of PCOS in girls with a gynecological age of <8 years. Thus far, few studies have evaluated the clinical characteristics of the girls diagnosed with PCOS based on the Rotterdam criteria but who do not meet the diagnosis according to the updated guideline. STUDY DESIGN, SIZE, DURATION: This is a retrospective study, and subjects attended for care from 2004 to 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Adolescent girls with PCOS diagnosed according to the 2003 Rotterdam criteria and healthy controls. All participants were between 2 and 8 years since menarche. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 315 girls diagnosed with PCOS according to the Rotterdam criteria, those with irregular menstruation (IM)/hyperandrogenism (HA)/polycystic ovary (PCO), IM/HA, HA/PCO, and IM/PCO phenotypes accounted for 206 (65.4%), 30 (9.5%), 12 (3.8%), and 67 (21.3%) participants, respectively. According to the evidence-based guideline, 79 girls (25.1%) with the HA/PCO or IM/PCO phenotypes were not diagnosed with PCOS, and aligned to the international guideline; they were designated as the 'at-risk' group. As expected, the girls meeting the evidence-based guideline adolescent criteria showed the worst metabolic profiles (degree of generalized or central obesity, frequency of insulin resistance, prediabetes or diabetes, and metabolic syndrome) and higher hirsutism scores than the at-risk group or controls. Approximately 90% of the at-risk group were not overweight or obese, which was similar to the controls. However, they showed worse metabolic profiles, with higher blood pressure, triglyceride, and insulin resistance parameters than controls; furthermore, these profiles were similar to those of the girls meeting the adolescent criteria. The at-risk group showed similarly elevated serum LH levels and LH/FSH ratio with the girls meeting adolescent criteria. LIMITATIONS, REASONS FOR CAUTION: We could not evaluate hormonal or ultrasound parameters in controls. WIDER IMPLICATIONS OF THE FINDINGS: Compared to the conventional Rotterdam criteria, the recent international evidence-based guideline-avoiding ultrasound in PCOS diagnosis in adolescents-still gives the opportunity to identify young girls at risk, aligned to the findings in this study. A practical approach to this adolescent population would involve establishing IM or HA (with ultrasound not indicated) and designating 'at-risk' PCOS status with regular check-ups for newly developed or worsening PCOS-related symptoms or metabolic abnormalities, with subsequent reassessment including ultrasound or anti-Müllerian hormone, once 8 years post-menarche. STUDY FUNDING/COMPETING INTEREST(S): No funding was received in support of this study. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.

Endometriosis and Adverse Pregnancy Outcomes: A Nationwide Population-Based Study.

Endometriosis is a major cause of infertility, and considering its pathophysiology, it is expected to affect pregnancy outcomes as well. This study aimed to evaluate whether endometriosis is associated with adverse pregnancy outcomes after successful conception. Data from singleton pregnancy deliveries between January 2014 and October 2019 were obtained from the Korean Health Insurance Review and Assessment Service database. We compared the clinical characteristics and adverse pregnancy outcomes of women with and without endometriosis. A total of 1,251,597 pregnant women were enrolled; of these, 32,951 (2.6%) were assigned to the endometriosis group. Women with endometriosis had significantly more adverse pregnancy outcomes than those without endometriosis. Adverse pregnancy outcomes associated with endometriosis included preterm labor, preterm birth, preeclampsia, fetal growth restriction, placenta previa, placental abruption, antepartum and postpartum hemorrhage, and stillbirth. This study also showed an increased risk of postpartum hemorrhage, blood transfusion, uterine artery embolization, and cesarean hysterectomy in the endometriosis group compared to the non- endometriosis group. The cesarean delivery rate was significantly higher in the endometriosis group than in the non-endometriosis group, even after excluding cases of antenatal obstetric complications that could increase the risk of cesarean delivery. Women with endometriosis not only have difficulty conceiving, but also have a significantly higher risk of adverse pregnancy outcomes.

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.

Thyroid autoimmunity markers in women with polycystic ovary syndrome and controls.

This study was performed to compare the prevalence of autoimmune thyroid disease (AITD) assessed by thyroid peroxidase antibody (anti-TPO Ab) and thyroid ultrasonography (USG) in Korean women with polycystic ovary syndrome (PCOS) (n = 210) and age-matched controls (n =343). We also compared the clinical features of women with PCOS according to the presence of AITD. Patients and controls were enrolled from a population who visited a screening centre for a general health check-up. There was no difference in the frequency of anti-TPO Ab positivity between the women with PCOS and the controls (4.8% (5/104) in patients and 7.6% (18/238) in controls). The frequency of heterogeneous or hypoechoic parenchyma on USG also did not differ between the patients and controls (9.3% (11/118) in patients and 12.3% (40/325) in controls). Within the PCOS group, the subjects with AITD (who had either Ab positivity or sonographic findings compatible with thyroiditis) showed significantly higher body mass indexes, waist circumferences and homeostasis model assessment for insulin resistance levels than the patients without AITD. In conclusion, AITD was not more prevalent in women with PCOS than in controls. However, among women with PCOS, subjects with AITD showed significantly higher adiposity and insulin resistance index than those without AITD.

Prognostic influences of BCL1 and BCL2 expression on disease-free survival in breast cancer.

We investigated the prognostic influences of BCL1 and BCL2 expression on disease-free survival in breast cancer patients. BCL1 and BCL2 expression statuses were assessed by immunohistochemistry using tissue microarrays from 393 breast cancer patients. The Kaplan-Meier estimator and log-rank test were used for survival analyses. The Cox proportional hazards model was used to calculate hazard ratio (HR) and the 95% confidence interval (CI) of survival analyses. BCL1 expression revealed no impact on survival. The high BCL2 group showed superior disease-free survival compared with the low BCL2 group (p = 0.002), especially regarding local recurrence-free survival (p = 0.045) and systemic recurrence-free survival (p = 0.002). BCL2 expression was a significant prognostic factor by univariable analysis (HR, 0.528; 95% CI, 0.353-0.790; p = 0.002) and by multivariable analysis (HR, 0.547; 95% CI, 0.362-0.826; p = 0.004). High BCL2 expression was associated with higher disease-free survival in the hormone receptor (HRc)-positive and human epidermal growth factor receptor 2 (HER2)-negative (HRc(+)/HER2(-)) subtype only (p = 0.002). The high BCL2 group was associated with positive estrogen receptor (ER), positive progesterone receptor (PR), low histologic grade, and age ≤ 50 years. BCL1 expression had no prognostic impact, but BCL2 expression was a significant independent prognostic factor. High BCL2 expression was associated with higher disease-free survival, especially regarding local recurrence and systemic recurrence. The prognostic effect of BCL2 expression was effective only in the HRc(+)/HER2(-) subtype. Favorable clinicopathologic features and a strong association with the ER/PR status could partly explain the superior prognosis of the high BCL2 group. BCL2 expression could be utilized to assess the prognosis of breast cancer patients in clinical settings.

Progression to prediabetes or diabetes in young Korean women with polycystic ovary syndrome: A longitudinal observational study.

OBJECTIVE: To investigate changes in glycaemic status in women with polycystic ovary syndrome (PCOS). DESIGN: Longitudinal observational study. PATIENTS: Women with PCOS who underwent baseline and follow-up screening tests for diabetes (n = 262). Four patients with type 2 diabetes (T2DM) at baseline and 6 patients who were taking drugs at the final follow-up were excluded. MEASUREMENTS: Changes in glycaemic classification based on fasting glucose, haemoglobin A1c and oral glucose tolerance test. RESULTS: The median length of follow-up was 2.9 years. The mean age and body mass index in the normoglycaemia group (n = 202) were 23.0 years and 21.6 kg/m2 , while it was 23.6 years and 22.9 kg/m2 in the prediabetes group (n = 50). In the normoglycaemia group, 38 (18.8%) and 2 (1.0%) developed prediabetes and T2DM, respectively. In the prediabetes group, 22 (44.0%) remained in the same category, 6 (12.0%) developed T2DM, while 22 (44.0%) achieved normoglycaemia. The incidence rate of T2DM was 9.3 per 1,000 person-years, which was significantly higher than that of the female population of similar age, and the incidence was higher in women with fasting glucose ≥ 5.6 mmol/L at baseline than in women with < 5.6 mmol/L. CONCLUSIONS: About 20% of normoglycaemic women had developed prediabetes or T2DM after a median time of 2.9 years. Meanwhile, nearly half of prediabetes women achieved normoglycaemia. Higher baseline fasting glucose levels were associated with an increased incidence of T2DM. Our results are the first to evaluate glycaemic status changes using all three parameters in patients with PCOS.

Association Between Polycystic Ovary Syndrome and the Polymorphisms of Aryl Hydrocarbon Receptor Repressor, Glutathione-S-transferase T1, and Glutathione-S-transferase M1 Genes.

OBJECTIVE: To investigate the association between the aryl hydrocarbon receptor repressor (AhRR) C/G polymorphisms and glutathione-S-transferase M1 (GSTM1) and GSTT1 null mutation and the risk of polycystic ovary syndrome (PCOS) in Korean women. METHODS: This was a case-control study of 478 women with PCOS and 376 aged-matched healthy controls. Genotyping of the AhRR C/G polymorphism and GSTM1 and GSTT1 were performed using real-time PCR analysis and multiplex PCR, respectively. RESULTS: The genotype distribution of the AhRR C/G polymorphisms and GSTM1/GSTT1 null mutations did not differ between women with PCOS and controls. Using the wild-type combined AhRR CC and GSTT1 present genotype as a reference, the odds that a woman had PCOS were 1.54 (95% CIs 1.04-2.29) times higher if she had a combined AhRR CG or GG and GSTT1 null genotype. The odds that a woman had PCOS was 1.48 (95% CIs 1.08-2.04) times higher if she had a combined GSTM1/GSTT1 null genotype compared with the wild-type combined GSTM1/GSTT1 present genotype. However, there were no significant associations between the risk of PCOS and any combined AhRR and GSTM1. CONCLUSIONS: Our data suggest that a combined AhRR CG or GG and GSTT1 null genotype or a combined GSTT1/GSTM1 null genotype might be associated with an increased risk of PCOS.

Metachronous Sporadic Sextuple Primary Malignancies Including Bilateral Breast Cancers.

Multiple primary malignancies are defined as the presence of more than one malignant neoplasm with a distinct histology occurring at different sites in the same individual. They are classified as synchronous or metachronous according to the diagnostic time interval of different malignancies. Diagnosis of multiple primary malignancies should avoid misclassification from multifocal/multicentric tumors or recurrent/metastatic lesions. In multiple primary malignancies, with increase in the number of primary tumors, the frequency rapidly decreases. Here, we report an exceptionally rare case of a woman who was diagnosed with metachronous sporadic sextuple primary malignancies including bilateral breast cancers (gastric cancer, ovarian Sertoli-Leydig cell tumor, left breast cancer, thyroid cancer, right breast cancer, and rectal neuroendocrine tumor). The sextuple primary malignancies in this case involved 5 different organs: the stomach, ovary, thyroid, rectum, and bilateral breasts. Further studies are needed to elucidate the current epidemiologic status of patients with multiple primary malignancies.

Delayed diagnosis of gestational diabetes mellitus and perinatal outcomes in women with large for gestational age fetuses during the third trimester.

OBJECTIVE: We evaluated the incidence of newly diagnosed gestational diabetes mellitus (GDM) during the 3rd trimester in women with suspected large for gestational age (LGA) fetuses on ultrasound and assessed their perinatal outcomes. METHODS: A retrospective cohort study was performed. Singleton pregnant women with suspected LGA on the 3rd trimester ultrasound and whose results of GDM screening at midpregnancy had been normal were enrolled. All participants were retested with 100-g oral glucose tolerance test (OGTT) within 2 days after diagnosis of LGA. We compared perinatal outcomes between the newly diagnosed with GDM group and the non-GDM group. RESULTS: Among 169 pregnant women, 13% (23/169) were newly diagnosed with GDM. The women in the GDM group had a higher HbA1c level at diagnosis (5.8 vs. 5.3, P<0.01) and earlier gestational age at delivery (38.0 vs 38.9 weeks of gestation, P=0.003) than those in the non-GDM group. The rate of cesarean delivery (CD) was significantly higher in the GDM group than that in the non-GDM group (73.9%, vs. 49.3%, P=0.028) with similar proportions for the indications of CD except CD on maternal request (CDMR). The CDMR rate was higher in the GDM group than nonGDM group (41.2% vs. 23.6%) but it did not reach statistical significance. There were no significant differences in the obstetrical and neonatal complications between the two groups. CONCLUSION: Among pregnant women with suspected LGA, 13% were newly diagnosed with GDM in late pregnancy. Nonetheless, there were no differences in the perinatal outcomes between women with newly diagnosed GDM and those without GDM. However, concerns over shoulder dystocia appear to increase CD rates in the GDM group.

Influence of Androgen Receptor on the Prognosis of Breast Cancer.

We investigated the prognostic influence of androgen receptor (AR) on breast cancer. AR status was assessed using immunohistochemistry with tissue microarrays from 395 operable primary breast cancer patients who received curative surgery. The Kaplan-Meier estimator was used to analyze the survival rates and a log-rank test was used to determine the significance of the differences in survival. The Cox proportional hazards model was used to calculate the hazard ratio (HR) and the 95% confidence interval (CI) of survival. There were 203 (51.4%) subjects with a low expression of AR, and 192 patients (48.6%) with a high expression rate. The high AR expression group showed superior overall survival (p = 0.047) and disease-free survival (p = 0.004) when compared with the low AR expression group. The high AR expression group showed superior systemic recurrence-free survival when compared with the low AR expression group (p = 0.027). AR was an independent prognostic factor for both overall survival (HR, 0.586; 95% CI, 0.381-0.901; p = 0.015) and disease-free survival (HR, 0.430; 95% CI, 0.274-0.674; p < 0.001). A high AR expression was a significant favorable prognostic factor only in the subgroups with positive hormone receptors (HRc) and negative human epidermal growth factor receptor 2 (HER2) when considering disease-free survival (p = 0.026). The high AR expression group was significantly associated with superior overall survival and disease-free survival when compared with the low AR expression group with breast cancer patients. AR was a significant independent prognostic factor for both overall survival and disease-free survival. The prognostic impact of AR was valid in the HRc(+)/HER2(-) subtype when considering disease-free survival. These findings suggest the clinical usefulness of AR as a prognostic marker of breast cancer in clinical settings.

Impact of the newly recommended antral follicle count cutoff for polycystic ovary in adult women with polycystic ovary syndrome.

STUDY QUESTION: What is the impact of the newly recommended antral follicle count (AFC) cutoff for polycystic ovary (PCO) on the diagnostic status of polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Among patients with phenotypes requiring the presence of PCO for diagnosis, approximately half (48.2%) were excluded from having PCOS based on the new AFC cutoff, although these excluded women had worse metabolic and hormonal profiles than the controls and were indistinguishable from the remaining patients with regard to major hormonal and metabolic parameters. WHAT IS KNOWN ALREADY: In the Rotterdam criteria, PCO is defined as either 12 or more follicles measuring 2-9 mm in diameter or an increased ovarian volume >10 cm3. Recently, an international PCOS guideline development group recommended an AFC threshold for PCO of ≥20 in adult women when using transducers with a high-resolution frequency, including 8 MHz. STUDY DESIGN, SIZE, DURATION: The current study used a case control design. PARTICIPANTS/MATERIALS, SETTING, METHODS: PCOS was diagnosed according to the Rotterdam criteria. Ultrasonography examinations were conducted with wide band frequency (5-9 MHz) transvaginal transducers and the centre frequency was 8 MHz. In patients who show both irregular menstruation and hyperandrogenism (HA), a diagnosis of PCOS can be made irrespective of the ovarian criteria change. Patients who were diagnosed according to HA and PCO (n = 86) or irregular menstruation and PCO (n = 443) were initially included among a total of 1390 adult women with PCOS (aged 20-40 years). Regardless of the AFC, if the ovarian volume is ≥10 cm3, a diagnosis of PCO can still be made. Thus, only patients who had an ovarian volume of <10 cm3 were analysed. Subjects who had an AFC of 12-19 and an ovarian volume <10 cm3 were designated as the 'low AFC group' (n = 255) and were the main focus of the study because they were excluded from having PCOS based on the new cutoff. Subjects with an AFC ≥20 and an ovarian volume <10 cm3 were designated as the 'high AFC group' (n = 101). A total of 562 premenopausal women without PCOS were enrolled as controls. MAIN RESULTS AND THE ROLE OF CHANCE: Among patients with irregular menstruation and PCO or HA and PCO phenotypes, approximately half (48.2%, 255/529) were excluded from having PCOS, which corresponded to one-fifth (18.3%, 255/1390) of the total adult patients. However, compared to the control group, these excluded women had worse metabolic profiles and were more androgenised. Notably, they were indistinguishable from the 'high AFC group' with regard to major hormonal and metabolic parameters (BMI and diabetic classification status, and the prevalence of insulin resistance, metabolic syndrome and HA). LIMITATIONS, REASONS FOR CAUTION: We cannot exclude the possibility of inter- and intraobserver variation in the evaluation of AFC. WIDER IMPLICATIONS OF THE FINDINGS: With the newly recommended follicle count cutoff, a substantial proportion of women with PCOS might be classified as not having PCOS despite visiting a hospital due to irregular menstruation or hyperandrogenic symptoms. A practical approach to them would involve controlling the menstrual or hyperandrogenic symptoms in hand and regularly evaluating them regarding newly developed or worsening PCOS-related symptoms or metabolic abnormalities. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a grant from the Seoul National University Hospital Research Fund (No. 2520140090), Republic of Korea. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: Not applicable.

Long-term prognostic effect of hormone receptor subtype on breast cancer.

PURPOSE: To determine the long-term prognostic role of hormone receptor subtype in breast cancer using surveillance, epidemiology, and end results (SEER) database. METHODS: Data of 810,587 female operable invasive breast cancer patients from SEER database with a mean follow-up period of 94.2 months (range, 0-311 months) were analyzed. Hormone receptor subtype was classified into four groups based on estrogen receptor (ER) and progesterone receptor (PR) statuses: ER(+)/PR(+), ER(+)/PR(-), ER(-)/PR(+), and ER(-)/PR(-). RESULTS: Numbers of subjects with ER(+)/PR(+), ER(+)/PR(-), ER(-)/PR(+), ER(-)/PR(-), and unknown were 496,279 (61.2%), 86,858 (10.7%), 11,545 (1.4%), 135,441 (16.7%), and 80,464 (9.9%), respectively. The ER(+)/PR(+) subtype showed the best breast-cancer-specific survival, followed by ER(+)/PR(-), ER(-)/PR(+), and ER(-)/PR(-) subtypes in the respective order (all p < 0.001). Survival difference among hormone receptor subtypes was maintained in subgroup analysis according to anatomic stage, race, age group, and year of diagnosis. Hormone receptor subtype was a significant independent prognostic factor in multivariable analyses (p < 0.001). Hazard ratios of ER(+)/PR(-), ER(-)/PR(+), and ER(-)/PR(-) for breast-cancer-specific mortality risk were 1.419 (95% confidence interval [CI] 1.383-1.456), 1.630 (95% CI 1.537-1.729), and 1.811 (95% CI 1.773-1.848), respectively, with ER(+)/PR(+) as reference. CONCLUSION: Hormone receptor subtype is a significant independent prognostic factor in female operable invasive breast cancer patients with long-term effect. The ER(+)/PR(+) subtype shows the most favorable prognosis, followed by ER(+)/PR(-), ER(-)/PR(+), and ER(-)/PR(-) subtypes in the respective order. Prognostic impacts of hormone receptor subtypes are also maintained in subgroup analysis according to anatomic stage, race, age, and year of diagnosis.