Nonlinear associations of bone age and basal luteinizing hormone with uterine volume in girls with central precocious puberty: a segmented regression analysis
- 1Department of Pediatric Endocrinology, Genetics and Metabolism, Fuzhou First General Hospital Affiliated with Fujian Medical University, Fuzhou Children's Hospital of Fujian Medical University
Abstract
Background: The relationships between basal luteinizing hormone (LH), bone age (BA), and uterine volume in girls with precocious puberty are conventionally treated as linear in clinical practice. Whether these associations exhibit nonlinear, threshold-dependent patterns has not been formally investigated.
Methods: This retrospective cross-sectional study included 1, 617 girls with breast development before 8 years of age, of whom 1, 008 had central precocious puberty (CPP) and 609 had premature thelarche (PT). Restricted cubic spline regression was used to test for nonlinearity in the associations of BA and ln-transformed basal LH with ln-transformed uterine volume. Where nonlinearity was confirmed, piecewise linear regression identified breakpoints at which uterine growth accelerated. CPP girls were then cross-classified by the identified thresholds to evaluate their complementary value.
Results: CPP girls had significantly greater BA advancement than PT girls (1.87 ± 1.11 vs. 1.58 ± 1.02 years, P < 0.001). In CPP girls, both BA and basal LH exhibited significant nonlinear associations with uterine volume (both P < 0.0001). A BA breakpoint was identified at 10.6 years: below this threshold, each additional year was associated with a 0.067-unit increase in ln(uterine volume); above 10.6 years, the slope increased to 0.550 (8.2-fold acceleration, P < 0.001). A basal LH breakpoint was identified at 0.67 IU/L, below which the slope was 0.107 per ln-unit and above which it rose to 0.421 (3.9-fold acceleration, P < 0.001). In PT girls, no clinically meaningful breakpoints were found. When CPP girls were stratified by both thresholds, the “Both High” subgroup (16.5%) had a median uterine volume of 2.76 mL (47.6% exceeding 3.0 mL), compared with 1.22 mL (1.4%) in the “Both Low” subgroup (58.6%).
Conclusions: The associations of BA and basal LH with uterine volume in CPP are distinctly nonlinear, with identifiable thresholds beyond which uterine growth accelerates substantially. These breakpoints are proposed as quantitative descriptors of uterine maturation tempo rather than as diagnostic cutoffs; they have high specificity but limited sensitivity, and girls with values below the thresholds require clinical follow-up. These two indicators provide complementary information for characterizing the tempo of uterine maturation.
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BibTeX
@article{yuan2026nonlinear,
title = {{Nonlinear associations of bone age and basal luteinizing hormone with uterine volume in girls with central precocious puberty: a segmented regression analysis}},
author = {Xin Yuan and Chunyan Cai and Ying Zhang and Wenyong Wu and Ruimin Chen},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1952775},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1952775/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Nonlinear associations of bone age and basal luteinizing hormone with uterine volume in girls with central precocious puberty: a segmented regression analysis
AU - Xin Yuan
AU - Chunyan Cai
AU - Ying Zhang
AU - Wenyong Wu
AU - Ruimin Chen
PY - 2026
DA - 2026/10/28
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1952775
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1952775/full
AB - Background: The relationships between basal luteinizing hormone (LH), bone age (BA), and uterine volume in girls with precocious puberty are conventionally treated as linear in clinical practice. Whether these associations exhibit nonlinear, threshold-dependent patterns has not been formally investigated. Methods: This retrospective cross-sectional study included 1, 617 girls with breast development before 8 years of age, of whom 1, 008 had central precocious puberty (CPP) and 609 had premature thelarche (PT). Restricted cubic spline regression was used to test for nonlinearity in the associations of BA and ln-transformed basal LH with ln-transformed uterine volume. Where nonlinearity was confirmed, piecewise linear regression identified breakpoints at which uterine growth accelerated. CPP girls were then cross-classified by the identified thresholds to evaluate their complementary value. Results: CPP girls had significantly greater BA advancement than PT girls (1.87 ± 1.11 vs. 1.58 ± 1.02 years, P < 0.001). In CPP girls, both BA and basal LH exhibited significant nonlinear associations with uterine volume (both P < 0.0001). A BA breakpoint was identified at 10.6 years: below this threshold, each additional year was associated with a 0.067-unit increase in ln(uterine volume); above 10.6 years, the slope increased to 0.550 (8.2-fold acceleration, P < 0.001). A basal LH breakpoint was identified at 0.67 IU/L, below which the slope was 0.107 per ln-unit and above which it rose to 0.421 (3.9-fold acceleration, P < 0.001). In PT girls, no clinically meaningful breakpoints were found. When CPP girls were stratified by both thresholds, the “Both High” subgroup (16.5%) had a median uterine volume of 2.76 mL (47.6% exceeding 3.0 mL), compared with 1.22 mL (1.4%) in the “Both Low” subgroup (58.6%). Conclusions: The associations of BA and basal LH with uterine volume in CPP are distinctly nonlinear, with identifiable thresholds beyond which uterine growth accelerates substantially. These breakpoints are proposed as quantitative descriptors of uterine maturation tempo rather than as diagnostic cutoffs; they have high specificity but limited sensitivity, and girls with values below the thresholds require clinical follow-up. These two indicators provide complementary information for characterizing the tempo of uterine maturation.
SN - 1664-2392
ER -