Sex‐Specific and Nonlinear Associations Between Serum 25‐Hydroxyvitamin D and Sex Hormones in US Adults
- 1Anesthesia and Surgery Center of the Affiliated Hospital of North Sichuan Medical College Nanchong 637000 China
- 2Department of Otolaryngology-Head & Neck Surgery & Sleep Medicine Center West China School of Public Health and West China Fourth Hospital Sichuan University Chengdu 610041 China scu.edu.cn
Abstract
Objective: This population‐based study sought to characterize sex‐specific linear and nonlinear associations between serum 25‐hydroxyvitamin D [25(OH)D] and four circulating sex hormone markers—total testosterone, estradiol, sex hormone–binding globulin (SHBG), and free testosterone index (FTI)—in the noninstitutionalized US adult population.
Methods: We analyzed data from the 2021–2023 National Health and Nutrition Examination Survey (NHANES), including 4801 eligible participants aged 20 years and older (2169 men, 2632 women). A tiered analytical strategy was applied: weighted Spearman rank correlation for crude associations, multivariable weighted linear regression for adjusted effect estimates, restricted cubic spline (RCS) modeling for nonlinear dose–response characterization, and bootstrap resampling (500 replicates) for robustness validation.
Results: In men, crude weak positive correlations of 25(OH)D with total testosterone (r = 0.07) and SHBG (r = 0.23) were fully attenuated to nonsignificance after adjustment for BMI and waist circumference; no robust nonlinear associations were identified via RCS. In women, 25(OH)D was moderately positively correlated with SHBG (r = 0.21), and this association remained significant after full adjustment (β = 0.148, p = 0.028), corresponding to a 10.8% increase in SHBG per doubling of 25(OH)D. RCS revealed a robust J‐shaped nonlinear relationship between 25(OH)D and SHBG (p for nonlinearity < 0.001), a decline‐then‐plateau pattern for FTI (p for nonlinearity = 0.015), an approximately linear negative trend for estradiol, and only a borderline nonlinear trend for total testosterone. Bootstrap analyses confirmed the robustness of SHBG, estradiol, and FTI associations in women.
Conclusions: The association between vitamin D status and sex hormone profiles exhibits pronounced sex dimorphism. In women, SHBG most consistently correlates with 25(OH)D, showing a BMI‐independent positive association and a J‐shaped, nonlinear dose–response pattern. In men, adiposity indices (BMI and waist circumference) fully account for the crude associations of 25(OH)D with testosterone, estradiol, and SHBG.
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BibTeX
@article{han2026sexspecific,
title = {{Sex‐Specific and Nonlinear Associations Between Serum 25‐Hydroxyvitamin D and Sex Hormones in US Adults}},
author = {Yi Han and Simin Gao},
journal = {International Journal of Endocrinology},
year = {2026},
month = nov,
doi = {10.1155/ije/8944835},
url = {https://doi.org/10.1155/ije/8944835},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Sex‐Specific and Nonlinear Associations Between Serum 25‐Hydroxyvitamin D and Sex Hormones in US Adults
AU - Yi Han
AU - Simin Gao
PY - 2026
DA - 2026/11/02
JO - International Journal of Endocrinology
DO - 10.1155/ije/8944835
UR - https://doi.org/10.1155/ije/8944835
AB - Objective: This population‐based study sought to characterize sex‐specific linear and nonlinear associations between serum 25‐hydroxyvitamin D [25(OH)D] and four circulating sex hormone markers—total testosterone, estradiol, sex hormone–binding globulin (SHBG), and free testosterone index (FTI)—in the noninstitutionalized US adult population. Methods: We analyzed data from the 2021–2023 National Health and Nutrition Examination Survey (NHANES), including 4801 eligible participants aged 20 years and older (2169 men, 2632 women). A tiered analytical strategy was applied: weighted Spearman rank correlation for crude associations, multivariable weighted linear regression for adjusted effect estimates, restricted cubic spline (RCS) modeling for nonlinear dose–response characterization, and bootstrap resampling (500 replicates) for robustness validation. Results: In men, crude weak positive correlations of 25(OH)D with total testosterone (r = 0.07) and SHBG (r = 0.23) were fully attenuated to nonsignificance after adjustment for BMI and waist circumference; no robust nonlinear associations were identified via RCS. In women, 25(OH)D was moderately positively correlated with SHBG (r = 0.21), and this association remained significant after full adjustment (β = 0.148, p = 0.028), corresponding to a 10.8% increase in SHBG per doubling of 25(OH)D. RCS revealed a robust J‐shaped nonlinear relationship between 25(OH)D and SHBG (p for nonlinearity < 0.001), a decline‐then‐plateau pattern for FTI (p for nonlinearity = 0.015), an approximately linear negative trend for estradiol, and only a borderline nonlinear trend for total testosterone. Bootstrap analyses confirmed the robustness of SHBG, estradiol, and FTI associations in women. Conclusions: The association between vitamin D status and sex hormone profiles exhibits pronounced sex dimorphism. In women, SHBG most consistently correlates with 25(OH)D, showing a BMI‐independent positive association and a J‐shaped, nonlinear dose–response pattern. In men, adiposity indices (BMI and waist circumference) fully account for the crude associations of 25(OH)D with testosterone, estradiol, and SHBG.
SN - 1687-8337
SN - 1687-8345
ER -