Agnethe Berglund, Claus Højbjerg Gravholt, Kirstine Stochholm
The Journal of Clinical Endocrinology & Metabolism, Volume 110, Issue 9, September 2025, Pages 2556–2564
https://doi.org/10.1210/clinem/dgae912
Abstract
Context
Few studies have reported on males with 45,X/46,XY mosaicism. Most studies stem from pediatric settings, and knowledge of natural history and long-term health outcomes are therefore lacking.
Objective
To describe long-term health outcomes in males with 45,X/46,XY in comparison to the general population.
Design
A national population-based registry study.
Setting
A public uniform healthcare system.
Patients and Controls
All males in Denmark diagnosed with 45,X/46,XY mosaicism from 1960–2016 (n = 135) and 1:100 age-matched males from the background population.
Main Outcome Measures
Hospital diagnoses, prescribed medication, and surgery codes were analyzed using a Cox proportional hazards regression model yielding hazard ratios (HRs).
Results
45,X/46,XY was associated with an increased overall risk of being referred to the hospital [HR = 1.6, confidence interval (CI): 1.3–1.9], undergoing surgery (HR = 1.8, CI: 1.4–2.2), and being prescribed medication (HR = 1.2, CI: 1.03–1.5). This risk applied to 15/18 diagnostic groups, 6/14 medication groups, and 10/16 surgery groups. Diagnoses with increased HRs included diabetes, thyroid disorders, obesity, hypertension, ischemic heart disease, osteoporosis, and inflammatory bowel disease. Half of all 45,X/46,XY males (69/135) had ≥1 diagnosis related to the genitourinary system, and nearly one-third (39/135) underwent urogenital surgery.
Conclusion
45,X/46,XY mosaicism in males impacts long-term health significantly. The morbidity pattern includes a wide range of diseases, most known to occur at increased frequencies in Turner syndrome. The study underscores the importance of identifying these males and following them with systematic screening as in Turner syndrome.