Women with endometriosis and dysmenorrhea are increasingly recognized as having systemic comorbidities beyond pelvic disease, but large-scale data on endocrine and metabolic comorbidities across a broad menstrual-related disorders population remain limited. Using the Japan Medical Data Center Claims Database, we conducted a nationwide cross-sectional study of women aged under 40 years enrolled in 2023. Women with confirmed diagnoses of endometriosis (ICD-10: N80) and/or dysmenorrhea (N94.4 or N94.6) were classified as the menstrual-related disorders group (n = 257,897); those without such diagnoses were the control group (n = 3,183,032). The primary outcomes were the frequencies of thyroid-related diagnoses (hypothyroidism [E03], non-toxic goiter [E04], hyperthyroidism [E05], thyroiditis [E06], and other thyroid disorders [E07]) and dyslipidemia (E78). Stratified analyses were performed according to prescription for low-dose estrogen-progestin preparations (LEP) or dienogest (DNG). All thyroid-related diagnoses were recorded more frequently among women with menstrual-related disorders than among controls. Hypothyroidism was identified in 2.1% of women with menstrual-related disorders versus 0.8% of controls (prevalence ratio [PR] 2.46; 95% CI 2.39-2.54); the corresponding PR was 3.11 (95% CI 2.99-3.24) in the endometriosis subgroup (n = 96,863). Dyslipidemia was recorded in 5.2% of women with menstrual-related disorders versus 1.4% of controls (PR 3.73; 95% CI 3.66-3.80; prevalence difference +3.78 percentage points). The endometriosis subgroup consistently showed the highest frequencies. These associations remained statistically significant after adjustment for age using the Mantel-Haenszel method (adjusted PR 1.45-3.02 across all comparisons), although adjusted estimates were consistently lower than crude estimates. Among women with menstrual-related disorders, hypothyroidism was more frequent in those without LEP/DNG prescriptions (3.4%) than in those with prescriptions (1.5%), whereas dyslipidemia frequencies were similar (5.2% vs. 5.1%). These findings indicate that young Japanese women with menstrual-related disorders have substantially higher frequencies of thyroid-related diagnoses and dyslipidemia than controls, particularly those with endometriosis. Surveillance bias, age confounding, and confounding by indication cannot be excluded because of the cross-sectional claims-based design.

BackgroundStress is linked to irregular menstrual cycles in adults, but little research has examined this relationship in adolescents. Adolescents may be particularly vulnerable because their menstrual cycles are still developing and more variable.ObjectivesTo investigate the association of stress and irregular menstrual cycle characteristics in adolescents during the COVID-19 pandemic using data from the Clue menstrual cycle tracking app.DesignWe surveyed 13-18-year-old Clue app users (N = 6,486) in the United States about their perceived stress and linked responses to app-recorded menstrual cycle data.MethodsUsing mixed-effects models, we analyzed the association of overall stress and changes in stress during the pandemic with cycle and period length, dysmenorrhea, heavy flow, and three aspects of irregularity: short, long, and variable cycles.ResultsAdolescents reporting high perceived stress had higher odds of reporting dysmenorrhea (adjusted odds ratio [aOR] = 1.1, 95% confidence interval [CI]: 1.1-1.2, p = 0.001), and short cycles (<21 days) (aOR = 1.4, 95% CI: 1.1-1.8, p = 0.003), and had slightly longer periods (β = 0.1 days, 95% CI: 0.0-0.3, p=0.007) compared to those reporting low stress. Adolescents reporting that their stress levels had become much worse during the COVID-19 pandemic also had higher odds of reporting dysmenorrhea (aOR = 1.1, 95% CI: 1.1-1.2, p<0.001), and heavy flow (aOR = 1.2, 95% CI: 1.1-1.3, p<0.001) compared to those whose stress levels had not increased. Stronger associations between COVID-19 stress and report of dysmenorrhea were observed in users menstruating for <4 years (interaction p-value = 0.008).ConclusionIncreases in COVID-19 pandemic-related stress may have impacted adolescents' cycle characteristics, particularly among adolescents menstruating for <4 years.

KAT6B/A::KANSL1 fusion-positive uterine mesenchymal neoplasms are rare and may show overlapping endometrial stromal and smooth muscle features. We report a 47-year-old woman with regular menses, no dysmenorrhea, and a 7-year history of a presumed uterine fibroid. She underwent laparoscopic myomectomy at an outside hospital in November 2024. The fragmented specimen was interpreted as an endometrial stromal tumor with smooth muscle differentiation, but the tumor-myometrium interface could not be assessed, and an endometrial stromal nodule could not be distinguished from low-grade endometrial stromal sarcoma. Subsequent pelvic magnetic resonance imaging showed postoperative changes, possible residual leiomyomas, and heterogeneous enhancement at the uterine fundus. Pelvic computed tomography showed heterogeneous uterine enhancement without definite extrauterine disease. Because the original specimen was fragmented and a potentially malignant uterine mesenchymal neoplasm could not be excluded, completion hysterectomy with bilateral salpingo-oophorectomy was performed. The hysterectomy specimen contained multiple residual intramyometrial nodules with marked regional heterogeneity. One component showed fascicular smooth muscle morphology and diffuse desmin and h-caldesmon expression, whereas other nodules showed tongue-like myometrial infiltration, focal intravascular growth, spiral arteriole-like vessels, and diffuse ER, PR, CD10, and SMA expression. Whole-transcriptome sequencing identified an in-frame KAT6B::KANSL1 fusion involving KAT6B exon 3 and KANSL1 exon 11. Because the tumor expressed ER and PR, postoperative letrozole was administered for 30 days, after which surveillance was selected following review of the final pathologic and molecular findings. At 8 months after completion surgery, no clinical or radiologic recurrence was detected; this limited follow-up does not permit conclusions regarding long-term biological behavior or endocrine treatment benefit.