Hyonjee Yoon

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.

Background: High mammographic breast density (MBD) reflects cumulative exposure to sex hormones. While it is well established that breast density declines during the menopausal transition, the association between baseline MBD and the subsequent timing of natural menopause remains underexplored. We investigated the relationship between baseline MBD and incident natural menopause in Korean women. Methods: We conducted a retrospective cohort study using the Korean National Health Insurance Service database. A total of 428,998 premenopausal women aged 40– 55 years who underwent breast cancer screening in 2009 were included. Baseline MBD was classified using the BI–RADS system. Incident natural menopause was defined by consistent self–reports across at least two subsequent screenings (2011– 2013). Multivariate logistic regression models were used to estimate odds ratios (ORs) for incident menopause, adjusting for confounders including age, BMI, and reproductive history. Results: A total of 73,599 women (17.16%) experienced natural menopause. Higher MBD was associated with progressively lower odds of incident menopause. Women with extremely dense breasts exhibited the lowest likelihood of reaching menopause (adjusted OR 0.8, 95% CI 0.77– 0.83), indicating a delayed menopausal transition. Stratified analyses revealed that the inverse association was more pronounced in women age < 50 years and those with late menarche (≥ 13 years). Conclusion: High premenopausal MBD was independently and inversely associated with the incidence of natural menopause, suggesting a potential link between dense fibroglandular tissue and variations in reproductive aging. Clinically, baseline MBD could potentially serve as a readily available indicator to evaluate reproductive aging patterns, aiding in more personalized health counseling regarding reproductive health and surveillance strategies.

Primary ovarian large cell neuroendocrine carcinoma is an extremely rare and aggressive gynecologic malignancy with poorly defined molecular characteristics and no standard treatment protocols. We present a case of pure ovarian LCNEC in a postmenopausal woman who underwent optimal cytoreductive surgery followed by platinum-based chemotherapy. Histopathologic and immunohistochemical analyses confirmed the diagnosis. Next-generation sequencing (NGS) revealed a pathogenic BRCA2 frameshift mutation (c.7177dupA), an ATM nonsense mutation, and Tier II mutations in TP53 and PTEN. The tumor exhibited homologous recombination deficiency (HRD), microsatellite instability-high (MSI-H), and an exceptionally high tumor mutational burden (TMB) of 277.49 mutations/Mb. These molecular alterations closely resemble those observed in high-grade neuroendocrine carcinomas of cervical and endometrial origin, suggesting a convergent genomic profile across gynecologic neuroendocrine carcinomas (NECs). Our findings underscore the potential of comprehensive genomic profiling in rare tumors such as ovarian LCNEC to refine diagnosis and identify candidates for biomarker-driven therapies, including PARP inhibitors and immune checkpoint inhibitors. This case supports the integration of molecular diagnostics into clinical practice and highlights the need for prospective studies incorporating molecular stratification to inform treatment strategies for rare and aggressive neuroendocrine tumors.