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.

Background/Objectives: Uterine leiomyomas are the most common benign gynecological tumors in women of reproductive age and are often associated with localized symptoms. However, emerging evidence suggests a link between uterine leiomyomas and systemic conditions such as cardiovascular disease (CVD), particularly myocardial infarction (MI) and ischemic stroke (IS). This study aimed to investigate the relationship between uterine leiomyomas and the risk of CVD events in young women aged 20–39 years using a large, nationwide, population-based cohort. Methods: This retrospective cohort study analyzed data from the National Health Insurance Service database of South Korea of 2,581,700 women aged 20–39 years who underwent health screening between 2009 and 2012. Uterine leiomyomas were identified using International Code of Disease, 10th Edition codes. CVD events (MI and IS) were defined according to hospital claims and radiological data. Multivariate hazard ratios (HRs) were calculated to evaluate the association between leiomyomas and CVD after adjusting for confounders (age, lifestyle factors, comorbidities, and body mass index). Results: In all, 58,812 were diagnosed with uterine leiomyomas, and 25,063 underwent surgical treatment. During the follow-up period, MI occurred in 115 women (0.21%) and IS in 82 women (0.15%) in the leiomyoma group, compared with 3107 cases of MI (0.12%) and 2240 cases of IS (0.09%) in the non-leiomyoma group. The leiomyoma group demonstrated a higher incidence rate of CVD (IR: 0.63 vs. 0.39 per 1000 person-years). After adjusting for confounding factors such as age, lifestyle, comorbidities, and body mass index (BMI), the hazard ratio (HR) for MI was 1.32, indicating a statistically significant increase in cardiovascular risk. The risk of CVD was lower in women who underwent surgical treatment; however, when specifically analyzing the occurrence of MI and IS, no statistically significant differences were observed between the two groups. Conclusions: Uterine leiomyomas are associated with an increased risk of MI and IS in young women. Surgical treatment itself may be associated with additional cardiovascular risks. Further research is needed to develop strategies to mitigate these risks and elucidate the underlying mechanisms.

Background/Objectives: Uterine leiomyomas (ULs) and breast fibroadenomas (FAs) are the most common benign tumors in women, both arising in hormone-responsive mesenchymal tissues and often co-occurring during reproductive years. Despite their shared hormonal sensitivity and frequent MED12 mutations, their downstream molecular evolution remains poorly characterized. This study aimed to investigate whether ULs and FAs, though initiated by similar genetic alterations, diverge in their oncogenic trajectories, thereby addressing the molecular basis for their distinct clinical behaviors. Methods: We performed whole-exome sequencing (WES) on 15 uterine leiomyomas and 7 publicly available fibroadenomas with matched normal controls to compare somatic mutations, copy number alterations (CNAs), and mutational signatures. All UL samples were derived from Korean patients who underwent surgical treatment at a tertiary hospital between 2017 and 2019. Somatic variants were analyzed using MuTect2 and Strelka2. FACETS was used to estimate copy number changes in individual samples, and GISTIC2 to identify recurrent and statistically significant copy number alterations across patient cohorts. Mutational processes were inferred using SigProfiler. Microsatellite instability status was determined with MSIsensor2. The study was approved by the Institutional Review Board (UC17SNSI0092). Results: Comparative whole-exome sequencing of 15 ULs and 7 FAs from matched tumor-normal samples in an East Asian cohort confirmed both tumor types harbor identical MED12 p.G44D mutations, establishing shared molecular initiation. However, post-initiation evolution diverged dramatically: ULs exhibited chromosomal instability with 15 copy number amplifications, 6 of which affected oncogenes, but relatively modest point mutations. In contrast, FAs remained chromosomally stable but hypermutated, harboring 1.47× more variants than ULs despite lower tumor purity. Notably, one histologically benign FA harbored multiple loss-of-function mutations plus an EGFR gain-of-function mutation typically associated with malignant breast cancer, challenging traditional benign-malignant classifications. Conclusions: Despite sharing a common initiating mutation in MED12, ULs and FAs evolve through fundamentally distinct genomic pathways. UL evolves through chromosomal instability, whereas FA evolves through a mutator phenotype, with important implications for understanding tumor biology and molecular-based risk stratification. These findings support a paradigm of tissue-specific oncogenic evolution and underscore the potential clinical utility of genomic profiling in distinguishing benign tumors with atypical molecular features.

Background: Hyperprolactinemia is a common endocrine disorder with significant reproductive and systemic implications. This study aimed to investigate the nationwide epidemiological trends, longitudinal shifts in pharmacological treatment, and the temporal associations of concurrent conditions and long-term sequelae in Korean women with claims-based hyperprolactinemia. Methods: A nationwide, population-based retrospective cohort study was conducted using data from the Health Insurance Review & Assessment Service (HIRA) of South Korea from 2009 to 2021. Female patients aged 10–59 years with hyperprolactinemia diagnostic claims were evaluated. We analyzed annual prevalence, incidence, diagnostic procedures, and dopamine agonist prescription patterns. Associated clinical conditions were classified into two categories based on the timing of their diagnosis relative to hyperprolactinemia: concurrent or underlying conditions present at baseline, and long-term complications that developed during the follow-up period. Results: A total of 95,616 female patients were identified after applying the selection criteria. The prevalence and incidence of hyperprolactinemia peaked among women in their early thirties, with an absolute peak at age 32. A significant pharmacological paradigm shift was observed: bromocriptine was the predominant therapy during the early study period, but cabergoline prescriptions surpassed bromocriptine in 2017. Regarding clinical work-ups, only 5.3% of the entire cohort underwent a sella magnetic resonance imaging (MRI). Regarding associated clinical conditions, reproductive disorders such as infertility (28.0%) and polycystic ovary syndrome (24.8%) showed high overall prevalence but low incidence of new diagnoses during the follow-up period. Conversely, among the patients affected by bone disorders, more than 60% of the total osteoporosis and osteopenia cases were diagnosed subsequent to the initial hyperprolactinemia diagnosis. Significant post-diagnosis incidence was also observed for metabolic disorders, including dyslipidemia and diabetes mellitus. Conclusions: Hyperprolactinemia in Korean women is highly concentrated in the peak reproductive years. The shift toward cabergoline reflects evolving clinical guidelines and improved drug accessibility. Our findings highlight that while reproductive issues often present concurrently, bone loss and metabolic complications frequently emerge as post-diagnosis sequelae. Therefore, clinical management should extend beyond prolactin normalization to include proactive, multidisciplinary screening for skeletal and metabolic health.