Endocrine Abstracts

Background: Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a congenital anomaly characterized by uterovaginal agenesis in 46,XX females. The current literature on MRKHS is dominated by single-center cohorts/case-series and population-based evidence is warranted. We aimed to identify a large nationwide cohort and investigate the patient characteristics and mortality of MRKHS patients in Denmark.

Methods: To identify individuals with putative MRKH, we searched the Danish National Patient Registry (DNPR) from 1977 to 2023 for patients with uterovaginal agenesis/aplasia/hypoplasia diagnosis codes among women with no record of pregnancy or abortion. We retrieved karyotype data from the Danish Cytogenetic Central Registry. For initial case prioritization, we reviewed their complete DNPR diagnosis/procedure history, followed by case validation and characterization through medical records. The validated cohort was finally uploaded to Statistics Denmark, allowing us to investigate long-term outcomes in MRKHS vs matched comparators.

Results: We identified a total of 1449 individuals in the DNPR search. We excluded 829 individuals based on DNPR history and another 47 patients based on cytogenetic data (XY females, n = 44; monosomy X, n = 3). Medical records were retrieved from 438/586 eligible patients, confirming the diagnosis in 278. Median (IQR) age at diagnosis was 17.6 (16.4-19.3) years. Patients typically presented with primary amenorrhea (n = 252, 90.6%) but also abdominal pain (n = 76, 27.3%) and dyspareunia (n = 60, 21.6%). Type I (isolated) and type II (with extragenital anomalies) were found in 113 (56.8%) and 86 (43.2%), respectively, while 77 had insufficient data for classification. The most common extragenital feature was renal anomalies, identified in 64 (33.3%) of 192 patients, who had a renal exam. Karyotype information was available for 232 patients of which 220 (94.8%) had a normal 46,XX karyotype. Median (IQR) follow-up time after the date of MRKHS diagnosis was 18.6 (9.3-32.0) years. MRKHS was associated with increased mortality (HR 3.03, 95% CI:1.57-5.87), particularly for type 2 (HR 3.80, 95% CI:1.32-10.97), while no association was found restricted to type 1 (HR 1.53, 95%CI: 0.34-6.95).

Conclusions: Through nationwide registry data and diagnosis validation, we have established a population-based MRKHS cohort, constituting a valuable resource for epidemiological MRKHS research. Type 2 MRKHS was found to be associated with increased mortality.