Development of an ultrasonographic grading system for cystic endometrial hyperplasia in dogs.

Endometrial hyperplasia (EH) is a condition that arises due to prolonged exposure of the endometrium to unopposed oestrogen, resulting in abnormal proliferation of endometrial tissue. Atypical hyperplasia, a subtype of EH, is considered a precursor lesion for endometrial cancer (EC). Polycystic ovary syndrome (PCOS) is a recognised risk factor for the development of EH and EC due to chronic anovulation and prolonged oestrogen exposure without progesterone opposition. Despite this increased risk, current clinical guidelines do not recommend routine screening for EH or EC among asymptomatic women with PCOS. The study aims to determine the effectiveness of screening for EH and EC in women with PCOS, particularly among premenopausal women, compared with no screening, reporting the occurrence and clinical outcomes of endometrial pathology among women with PCOS. This systematic review will adhere to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive literature search will be conducted across multiple electronic databases from inception until February 2026. Two reviewers will independently perform study screening, data extraction and methodological quality assessment of the included studies. Discrepancies between reviewers will be resolved through discussion or consultation with a third reviewer. Extracted data will be summarised narratively, and where appropriate, quantitative synthesis will be performed using Joanna Briggs Institute System for the Unified Management, Assessment and Review of Information (JBI SUMARI). Heterogeneity among studies will be assessed, and subgroup and sensitivity analyses will be conducted when feasible. Ethical approval is not required for this systematic review and meta-analysis, as it will use data from previously published studies. The results of the review will be published in academic journals and presented at international conferences. CRD420251274598.

Visually Directed Hysteroscopic Biopsy in the Evaluation of Abnormal Uterine Bleeding and Postmenopausal Bleeding: A Joint Society Practice Guideline.

Treatment with NovaSure® endometrial ablation is approved for patients with heavy menstrual bleeding (HMB) without evidence of malignant or premalignant lesions. This analysis addresses the rare but clinically relevant situation in which endometrial carcinoma (EC) or atypical hyperplasia (AEH) is identified histologically after endometrial ablation in premenopausal patients. Histological evaluation of hysterectomy specimens with correlation to clinical parameters in patients undergoing hysterectomy after incidental histological diagnosis of AEH or EC following NovaSure® endometrial ablation. A retrospective single-center analysis was conducted on more than 400 patients who underwent NovaSure® endometrial ablation at our center between January 2020 and February 2025. Patients with AEH or EC for whom subsequent hysterectomy specimens were available were included. Histological evaluation was performed and independently reviewed to assess residual endometrium, residual endometrial atypia or carcinoma, and ablation-related histomorphological changes. A total of 11 patients (AEH n = 8; EC n = 3) underwent subsequent hysterectomy after NovaSure® endometrial ablation. Six out of eight patients with AEH showed no residual atypia in the hysterectomy specimens (2/8 with focal residual atypia), and no residual invasive carcinoma was detected in any of the three carcinoma cases. Histopathological analysis showed pronounced postablative changes, including necrosis, fibrosis, zonation, and vascular and lymphatic alterations. This descriptive study provides a clinicopathological characterization of patients with EC or AEH who underwent hysterectomy after endometrial ablation. In these patients, no preprocedural evidence of endometrial pathology was present, and the diagnosis was established solely through routine histopathological examination of curettage specimens obtained immediately before the ablation procedure. Histological assessment revealed pronounced changes, highlighting specific diagnostic challenges and underscoring the importance of careful patient selection and thorough diagnostic evaluation before NovaSure® ablation. Within the limitations of this study, no evidence was found that prior endometrial ablation compromises oncological outcome.

Objective: To analyze the occurrence and distribution of high-level microsatellite instability (MSI-H) in precancerous lesions and histological subtypes of endometrial cancer, to compare the concordance rate between mismatch repair protein deficiency (dMMR) and MSI-H, to investigate the incidence of minimal microsatellite shift in the development of endometrial cancer, and to explore potential solutions for accurate MSI-H diagnosis. Methods: A total of 848 endometrial lesion samples that underwent molecular typing at the Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University from January 2023 to January 2024 were collected, including 93 cases of atypical endometrial hyperplasia (AEH) and 755 cases of endometrial carcinoma. Microsatellite status, MMR protein expression, and gene mutations (MMR, POLE, etc.) were analyzed by histology, IHC, and NGS. Microsatellite status was determined by calculating the MSI-score based on 34 microsatellite loci. An MSI-score<0.3 was defined as microsatellite stable (MSS),≥0.3 as microsatellite instability-high (MSI-H), and 0.3±0.05 as the equivocal range. Simultaneously, a visualization graph was established for minimal microsatellite shift analysis and identification. Results: The 848 lesions included 93 cases of AEH, 442 cases of low-grade endometrioid carcinoma (G1-G2), 143 cases of high-grade endometrioid carcinoma (G3), 20 cases of clear cell carcinoma, 20 cases of carcinosarcoma, 16 cases of mixed adenocarcinoma, 12 cases of dedifferentiated/undifferentiated carcinoma, and 102 cases of other types (including 94 serous carcinomas, 6 mesonephric-like adenocarcinomas, and 2 gastric-type mucinous adenocarcinomas). The results showed that the incidence of dMMR in AEH was 4.3%, and MSI-H was 3.2%, significantly lower than the 24.9% and 23.0% in endometrial cancer, respectively (P<0.001). All the 102 cases of other types, including serous carcinoma, were pMMR/MSS. The overall concordance rate between dMMR and MSI-H was 90.6%, but it varied between 75% and 100% across different stages and histological subtypes. In molecular subtyping, the concordance rate was 75% for AEH and carcinosarcoma, 87.5% for dedifferentiated/undifferentiated carcinoma, 91.5% for high-grade endometrioid carcinoma, and 100% for other high-grade carcinomas, while the POLE-mutated subtype had the lowest concordance rate of 66.7%, significantly lower than the 93.1% overall concordance rate for the MSI-H subtype (P<0.001). In MSI-H cases, up to 84.5% of endometrial cancer cases exhibited minimal microsatellite shift in at least one locus, with 67.8% showing shifts in≥3 loci. Through analysis of 34 microsatellite loci and visualization, 20 cases (11.5% of 174 MSI-H cases) were identified as borderline (MSI-score=0.3±0.05), considered diagnostically challenging. Among these, MLH1-/PMS2- co-loss accounted for 12/20 cases, with half (6/12) harboring MLH1 mutations; isolated MSH6 loss accounted for 6/20 cases, with 5 of these harboring MSH6 mutations. The 20 minimal shift MSI-H cases shared all pathological features of typical MSI-H endometrial cancer. Conclusions: The incidence and distribution of MSI-H show significant differences across histological subtypes between endometrial precancerous lesions and endometrial carcinomas. The overall concordance between dMMR and MSI-H is good, but varies across different disease stages, histological types, and molecular subtypes. Minimal microsatellite shift is commonly detected in MSI-H cases, and some cases are difficult to interpret due to their classification within the equivocal range. Increasing the number of microsatellite loci, combined with visualization graph comparison and integration of mismatch repair protein immunophenotype and histological features, can effectively improve the accuracy of MSI-H interpretation.

ObjectiveTo develop a comprehensive predictive model incorporating multi-dimensional parameters for the accurate preoperative stratification of endometrial hyperplasia subtypes.MethodsA retrospective cohort study was conducted involving 1822 patients with endometrial lesions. We gathered candidate variables spanning demographic, reproductive, hematological, hepatic and renal, coagulation, ultrasonographic, and pathological domains. Utilizing a two-step feature selection approach (variance thresholding combined with lasso regression), we constructed and compared three logistic regression models.ResultsSixteen key features were identified, encompassing pathological, clinical, and inflammatory indicators. Especially, the integrated model (Model 3) demonstrated the highest diagnostic efficacy, with an AUC of 0.923 (training set: sensitivity 87.2%, specificity 85.6%) and 0.905 (validation set: sensitivity 84.5%, specificity 83.2%), significantly outperforming the single-domain model.ConclusionThe predictive model, developed based on multidimensional clinical indicators, effectively categorized the preoperative subtypes of endometrial hyperplasia, thereby offering a practical tool for clinical decision-making and underscoring the pivotal role of inflammation in the progression of pathological lesions.

Adult granulosa cell tumor is a rare ovarian cancer with less aggressive behavior than epithelial ovarian cancer. However, recurrence occurs in up to 30% of patients and is challenging to manage, as treatment options are limited. Additionally, adult granulosa cell tumor has been linked to synchronous endometrial pathology, including endometrial hyperplasia and cancer, but the impact of these abnormalities on surgical decision-making and survival outcomes remains unclear. To evaluate how coexisting endometrial abnormalities influence surgical management and overall survival, and to examine the association between surgical extent (conservative vs complete staging) and recurrence in patients with adult granulosa cell tumor. This retrospective cohort study included all patients diagnosed with histologically confirmed ovarian adult granulosa cell tumor in Denmark between January 2007 and December 2021. Analyses were first conducted in the comprehensive nationwide Danish cohort, and results were subsequently compared in a combined analysis including data from a Dutch adult granulosa cell tumor cohort (January 2000-December 2021). Surgical procedures were categorized as complete staging (including hysterectomy, bilateral salpingo-oophorectomy, omental and peritoneal biopsies, and peritoneal washings) or less extensive surgery with clinical staging. Abnormal uterine bleeding and endometrial pathology were identified, and their associations with surgical extent and International Federation of Gynecology and Obstetrics stage were assessed. Progression-free survival was compared with surgical extent and International Federation of Gynecology and Obstetrics stage. A total of 252 Danish and 195 Dutch patients (n=447) were included, with median follow-up times of 7.2 and 3.2 years, and recurrence rates of 18% and 42%, respectively. In the Danish cohort, abnormal uterine bleeding and endometrial hyperplasia were associated with receiving less extensive surgery (odds ratio=0.35, 95% confidence interval: 0.18-0.66 and odds ratio=0.39, 95% confidence interval: 0.19-0.76). Furthermore, abnormal uterine bleeding, endometrial hyperplasia, and endometrial cancer were each associated with lower International Federation of Gynecology and Obstetrics stage at diagnosis of adult granulosa cell tumor (odds ratio=0.32, 95% confidence interval: 0.15-0.64; odds ratio=0.28, 95% confidence interval: 0.12-0.6; and odds ratio=0.16, 95% confidence interval: 0.01-0.94, respectively). In the Danish cohort, overall survival was not affected by endometrial cancer (hazard ratio=0.8, 95% confidence interval: 0.21-3.16). No difference in progression-free survival was observed between patients undergoing complete staging and those managed conservatively (hazard ratio=1.37, 95% confidence interval: 0.65-2.88). International Federation of Gynecology and Obstetrics stage IC (hazard ratio=9.4, 95% confidence interval: 4.0-22.29) and stage II-III (hazard ratio=8.4, 95% confidence interval: 2.9-24.17) had higher rates of recurrences compared with those with International Federation of Gynecology and Obstetrics stage IA or IB. Analyses of the combined Danish and Dutch cohorts demonstrated estimates consistent with those observed in the Danish cohort. The presence of abnormal uterine bleeding, endometrial hyperplasia, and endometrial cancer was associated lower International Federation of Gynecology and Obstetrics stage, suggesting that these factors facilitate earlier detection of adult granulosa cell tumor without adversely affecting overall survival. Complete surgical staging is not associated with improved progression-free survival in patients with adult granulosa cell tumor. Higher International Federation of Gynecology and Obstetrics stage (IC or higher) was, as expected, associated with an increased rate of recurrence compared to stage IA and IB.

Clinical application of photodynamic therapy in endometrial hyperplastic diseases: a review.

Cystic endometrial hyperplasia in dairy goats: morphological changes and expressions of estrogen receptor-α and progesterone receptor.

Longitudinal trajectories of anxiety and depression in patients with endometrial cancer or atypical endometrial hyperplasia undergoing fertility-sparing treatment.

Risk of endometrial carcinoma in patients with atypical endometrial hyperplasia in a population of predominantly racial and ethnic minorities, a single institution study.

Prolonged conservative treatment of women with atypical endometrial hyperplasia and early endometrial carcinoma: A systematic review and meta-analysis.

To investigate oncological and reproductive outcomes in patients with mismatch repair-deficient (MMRd) endometrial endometrioid carcinoma (EEC) or atypical endometrial hyperplasia (AEH) undergoing fertility-preserving treatment to inform clinical management of this molecular subtype. Clinical and pathological data from 14 patients with MMRd EEC or AEH who received fertility-preserving treatment at Peking Union Medical College Hospital from January 2020 to December 2023 were retrospectively analyzed. The mean age at diagnosis of the patients was 33.6 ± 4.2 years. Loss of MLH1/PMS2 expression was the most common immunohistochemical abnormality, followed by loss of MSH6, MSH2/MSH6, and PMS2 expression. Among the 12 patients who underwent germline genetic testing, pathogenic/likely pathogenic germline variants in MMR genes were identified in three patients. During the follow-up period (median 34.5 months, range 26-117 months), seven patients achieved complete remission (CR), with a median time to CR of 8 months. The recurrence rate among these patients was 57.1%, and the median time to recurrence was 11 months. Nine patients underwent surgery after treatment failure or recurrence, with postoperative pathology revealing histologic upgrading and/or metastasis in eight patients. Two patients successfully conceived through assisted reproductive technology and achieved live births. Patients with MMRd EEC or AEH undergoing fertility-preserving treatment demonstrated relatively low remission rates, high recurrence rates, and suboptimal reproductive outcomes. Careful risk assessment and close surveillance for recurrence are warranted for patients desiring fertility.

Gynecologic Tumors and Precursor Lesions, Including p53-Aberrant Atypical Hyperplasia-like Endometrial Lesions, in Li-Fraumeni Syndrome.

To evaluate the impact of therapeutic regimens and visceral fat dynamics on complete remission (CR) rates in fertility-preserving management of atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC), and identify modifiable predictors of treatment efficacy. This interim analysis is based on data from an ongoing, prospective, open-label randomized controlled trial (RCT; Chinese Clinical Trial Registry ChiCTR2200067099). Conducted in accordance with the pre-specified study protocol, the analysis included the first 73 enrolled participants, who were randomized to either: (1) GnRH-a combined with daily letrozole, or (2) high-dose oral progestins (medroxyprogesterone acetate or megestrol acetate). All patients received standardized lifestyle interventions (diet and exercise). The exploratory aim was to assess the association between early changes in body composition-measured using the InBody 770 analyzer over 12 weeks-and treatment response. Multivariate logistic regression analyses were performed to assess the association between treatment outcomes and changes in weight and body fat distribution. At this interim analysis, 73 patients were enrolled, including 31 patients with AEH (42.5%) and 42 patients with EC (57.5%). After 12 weeks of treatment, 40 patients achieved complete remission, while 33 cases did not. After implementing positive education and lifestyle interventions, patients experienced reductions in weight and indicators of body fat distribution after 12 weeks of treatment. The gonadotropin-releasing hormone agonist plus aromatase inhibitors (GnRH-a+AIs) group showed a significantly higher complete response rate than the megestrol acetate/medroxyprogesterone acetate (MA/MPA) group (75.6% vs. 28.1%; risk difference: 0.48, 95% CI:0. 27-0.68). After adjustment for covariates, each 1 cm increase in baseline hip circumference was associated with 7.187-fold higher odds of complete response rate (OR = 7.19, 95% CI: 1.03-50.41, p = 0.047). Conversely, progestin therapy (vs. GnRH-a+AIs) was associated with 92.7% lower odds of CR rate (OR = 0.07, 95% CI: 0.02-0.35, p = 0.001). Furthermore, reduction in visceral fat area (per 1 cm2 decrease) was associated with 35.9% higher odds of complete response (OR = 1.36, 95% CI: 1.02-1.81, p = 0.034). Conversely, progestin therapy (vs. GnRH-a+AIs) was associated with 89.2% lower odds of CR rate(OR = 0.108, 95% CI: 0.015-0.773, p = 0.027). Treatment regimen selection critically influences therapeutic outcomes in fertility-sparing management. Our study shows that reducing visceral fat area substantially improves treatment efficacy, making it a key indicator for predicting treatment effects.

Rationale:Adenomyosis and simple endometrial hyperplasia are common benign gynecological conditions. However, atypical presentations with extreme endometrial thickening and associated diagnostic challenges have rarely been reported.Patient concerns:A 27-year-old woman presented with a 13-year history of menstrual irregularity and endometrial thickness of 7.0 cm on ultrasonography. Magnetic resonance imaging (MRI) revealed an enlarged uterus and a 7.9 cm intrauterine mass (T1 isointense, T2 hyperintense, diffusion-weighted imaging high signal) with junctional zone interruption.Interventions:Taking into account the patient’s reproductive needs and the fact that hysteroscopy couldn’t completely remove the contents of the uterine cavity, an open surgery was used for diagnosis and treatment.Diagnoses:Pathological examination led to the diagnosis of adenomyosis combined with non-atypical endometrial hyperplasia.Outcomes:After 6 months of postoperative gonadotropin-releasing hormone agonist (GnRH-a) treatment, the patient achieved regular menstruation. During 10 years of follow-up, she had 2 natural pregnancies and delivered 2 full-term infants via cesarean section.Lessons:This case highlights that adenomyosis can present with an extremely thickened endometrium, an intrauterine mass and the absence of typical dysmenorrhea. Combined surgery and GnRH-a can achieve long-term symptom control and successful pregnancies, supporting fertility-preserving management in similar young patients.

Background: Unscheduled bleeding in postmenopausal women on hormone replacement therapy (HRT) represents a common but poorly characterised clinical challenge. Whilst endometrial cancer affects approximately 9% of women with unexplained postmenopausal bleeding, existing evidence in HRT users is largely restricted to women under 60 years and short-duration regimens, leaving a critical evidence gap in contemporary all-age clinical practice. Whether the same investigative urgency is warranted for HRT users experiencing unscheduled bleeding as for women with unexplained postmenopausal haemorrhage remains unresolved. Objectives: To determine the diagnostic yield of endometrial cancer and hyperplasia amongst postmenopausal women presenting with unscheduled bleeding whilst on HRT, and to explore potential associations with HRT regimens and clinical risk factors. Methods: This retrospective observational study analysed 343 postmenopausal women presenting with unscheduled bleeding whilst on HRT at a single tertiary centre between September 2023 and February 2024. All patients underwent transvaginal ultrasound and endometrial sampling according to institutional protocol. Descriptive statistics were used to characterise outcomes, with exploratory analyses of potential risk factors. Given the symptomatic and selected nature of this cohort, all proportions represent the diagnostic yield within an investigated population rather than population-level incidence estimates. Results: Amongst 343 women (mean age 56.2 ± 7.4 years), nine cases (2.6%) of endometrial abnormalities were identified: four malignancies (1.2%), four endometrial hyperplasia without atypia (1.2%), and one complex atypical hyperplasia (0.3%). Only five cases (1.5%) required surgical intervention. All four endometrial cancers were Stage IA (FIGO 2009; three Grade 1, one Grade 2; no LVSI), corresponding to Stage IA2mNSMP under FIGO 2023. None required adjuvant therapy. Strikingly, 88.9% of all abnormal cases occurred within two years of HRT initiation, with no endometrial pathology identified amongst the 45 women using systemic HRT for more than five years-a temporal pattern not previously reported. Conclusions: In this retrospective all-age NHS cohort, the diagnostic yield of endometrial cancer was 1.2% in HRT users with unscheduled bleeding, with only 1.5% requiring surgical intervention. All cancers were early-stage (FIGO 2009 Stage IA; FIGO 2023 Stage IA2mNSMP) and required no adjuvant therapy. A previously unreported temporal clustering of pathology within the first two years of HRT initiation generates a hypothesis that early unscheduled bleeding may unmask pre-existing rather than HRT-induced endometrial abnormalities. These observations are hypothesis-generating and should not be interpreted as evidence of endometrial safety. These findings apply specifically to symptomatic women presenting for investigation and cannot be generalised to asymptomatic HRT users. Prospective validation in larger cohorts with baseline endometrial assessment is required before any clinical conclusions can be drawn. What This Study Adds: (1) A real-world cancer detection proportion of 1.2% in an all-age contemporary NHS cohort. (2) A previously undescribed temporal pattern with pathology clustering within two years of HRT initiation and no pathology in long-term users (n = 45), generating a testable hypothesis about pre-existing versus HRT-induced disease. (3) Dual FIGO 2009/2023 staging demonstrating that molecular classification added no treatment-discriminatory value in this early-detection context.

Endometrial carcinogenesis involves complex interactions between hormonal signaling and the local immune microenvironment. While atypical endometrial hyperplasia is a recognized precursor to carcinoma, the spatial and phenotypic evolution of immune and hormonal markers during progression remains incompletely characterized. A retrospective cohort of 150 endometrial specimens, including hyperplasia without atypia (n=40), hyperplasia with atypia (n=40), endometrioid carcinoma (n=40), and serous carcinoma (n=30), was analyzed using immunohistochemistry for CD3, CD4, CD8, FOXP3, CD68, CD163, estrogen receptor (ER), and progesterone receptor (PR). Digital whole-slide imaging and QuPath were applied to quantify immune cell densities in intratumoral and peritumoral compartments. Correlations between immune markers and hormonal receptors were evaluated, and a subgroup of 27 paired hyperplasia-carcinoma cases was analyzed separately. CD3+ and CD8+ T-cell densities increased progressively from hyperplasia to carcinoma (P<0.001), with hyperplastic lesions demonstrating predominant peritumoral localization consistent with immune exclusion. FOXP3+ regulatory T cells were enriched in neoplastic lesions, particularly in ER/PR-positive tumors. CD8+ intratumoral and peritumoral densities showed significant inverse correlations with ER and PR expression (both r=-0.76, P<0.001), whereas FOXP3+ infiltration correlated positively with ER and PR (r=0.64, P<0.001). M2 CD163+ macrophages demonstrated an inverse association with ER (r=-0.49, P<0.01), while M1 CD68+/iNOS macrophages showed no statistically significant correlations. In the paired subgroup, higher peritumoral than intratumoral CD8+ densities persisted, indicating residual immune exclusion despite malignant transformation. Endometrial neoplastic progression is characterized by a transition from peritumoral immune exclusion in hyperplasia to increased intratumoral immune infiltration in carcinoma, although this shift is not universal. Hormone receptor-positive tumors exhibit enrichment of FOXP3+ regulatory T cells and CD163+ macrophages, suggesting hormone-linked immune suppression. These findings highlight combined immune-hormonal biomarkers as potential indicators of progression risk and support further investigation of integrated immunomodulatory and hormone-targeted therapeutic strategies.

This study aimed to compare the diagnostic performance of 3-mm, 4-mm, and 5-mm trans-vaginal ultrasound endometrial thickness thresholds for detecting endometrial neoplasia and to determine the optimal clinical cutoff. In this prospective cohort study, 1170 women aged ≥50 years referred for endometrial evaluation between February 2014 and October 2020 were included, with follow-up through January 2021. All participants underwent trans-vaginal ultrasound performed by certified sonographers across 4 ultrasound units within a large academic medical center with an ethnically diverse patient population. Diagnostic accuracy measures (including sensitivity, specificity, positive predictive value, and negative predictive value) were calculated for each endometrial thickness threshold. The McNemar test was used to compare diagnostic performance across cutoffs. The main outcome was the detection of endometrial cancer or hyperplasia. Among the 1170 eligible women, 82 (7.0%) had endometrial cancer and 42 (3.6%) had hyperplasia. Analyses were limited to 975 cases with a clearly visualized endometrial stripe. Sensitivity for endometrial neoplasia detection was 100%, 97.8%, and 90.2% for the 3-, 4-, and 5-mm thresholds, respectively, while specificity was 9.5%, 16.1%, and 24.4%. Sensitivity and negative predictive value did not differ significantly between the 3- and 4-mm thresholds (p =.16 and p =.40); however, both metrics were significantly higher for the 3- and 4-mm thresholds compared with the 5-mm threshold (p =.005 and p =.01). The 4-mm cutoff demonstrated significantly higher specificity and positive predictive value compared with the 3-mm cutoff (p <.001). Both the 3-mm and 4-mm endometrial thickness thresholds provided excellent sensitivity for excluding endometrial neoplasia. The 4-mm cutoff achieved greater specificity, minimizing unnecessary invasive procedures, and may represent the optimal threshold for clinical application.

The work was performed to assess the relationship of single-nucleotide polymorphisms (SNPs), which determine the concentration of sex hormones (confirmed in previously performed genome-wide studies (GWASs)), with the risk of endometrial hyperplasia (EH). The objects of the study were 1493 women, of which 520 individuals had EH; the control group consisted of 973 women. Nine SNPs that were GWAS-associated with the level of sex hormones were investigated. The correlations of SNPs that determine the level of sex hormones with EH risk were found: minor polymorphic variants rs11031002 (allele A: OR = 0.45–0.50) and rs11031005 (allele C: OR = 0.05–0.53) of the FSHB gene were associated with a low risk of developing the disease, and the TT*rs11031002-rs11031005 FSHB haplotype, at a level of statistical significance (p = 1 × 10−11) exceeding the GWAS “standard”, increases the EH risk by more than 2.5 times (OR = 2.84). The 16 multilevel SNP interaction exploratory models of nine considered loci were EH-associated (padj-perm < 0.001). Two loci, T>A rs11031002 and T>C rs11031005 FSHB, play a fundamental role in these models (100% and 75% of models, respectively), and two more loci, C>G rs112295236 SLC22A10 and C>A rs117585797 ANO2, are part of more than 30% of all models. Sex hormone-level genetic determinants are involved in numerous EH-significant hormone-mediated molecular pathways (regulation of gene transcription, processes of embryogenesis and development, regulation of metabolism, differentiation and maturation of the epithelium, TGFβ pathway, fat cell differentiation, etc.). In conclusion, for the first time, it was found that the genetic polymorphisms that determine an organism’s sex hormone levels are associated with EH.