# Sex-specific associations between obstructive sleep apnea and thyroid hormone sensitivity in euthyroid adults

## TL;DR

This study shows that obstructive sleep apnea (OSA) is linked to reduced thyroid hormone sensitivity in women, even when hormone levels are normal, but not in men.

## Contribution

The study reveals sex-specific effects of OSA on thyroid hormone sensitivity in euthyroid adults using novel sensitivity indices.

## Key findings

- Females with OSA showed higher TFQI, PTFQI, TSHI, and TT4RI, and lower FT3/FT4 ratio compared to non-OSA females.
- OSA severity was independently associated with increased thyroid hormone sensitivity indices in females.
- No significant associations were found between OSA and thyroid hormone sensitivity in males.

## Abstract

The relationship between obstructive sleep apnea (OSA) and thyroid hormone sensitivity remains unclear. Thyroid hormone sensitivity indices may reveal subclinical hypothalamic-pituitary-thyroid (HPT) axis dysregulation beyond conventional hormone levels.

We analyzed 718 euthyroid adults who underwent overnight sleep monitoring, using thyroid‑stimulating hormone index (TSHI), thyroid feedback quantile-based index (TFQI), parametric thyroid feedback quantile-based index (PTFQI), thyrotroph T4 resistance index (TT4RI), thyrotroph T3 resistance index (TT3RI) and the ratio of free triiodothyronine to free thyroxine (FT3/FT4 ratio) to assess central and peripheral thyroid hormone sensitivity. Analysis of covariance assessed differences across OSA severity after adjusting for age and BMI. Multivariable linear regression examined associations between OSA severity and thyroid hormone sensitivity indices in sex-stratified models. Correlations between OSA-related parameters and thyroid hormones sensitivity indices were further explored using quadratic prediction plots.

Among females, OSA patients showed higher FT4 and significantly increased TFQI, PTFQI, TSHI, and TT4RI, but lower FT3/FT4 ratio compared with non-OSA. TFQI (P for trend = 0.0395) and TT4RI (P for trend = 0.0293) were positively correlated with increasing OSA severity. OSA was independently associated with elevated TFQI (β = 0.26, 95% CI 0.010–0.42, P = 0.001), PTFQI (β = 0.20, 95% CI 0.05–0.35, P = 0.011), TSHI (β = 0.24, 95% CI 0.03–0.44, P = 0.025), and TT4RI (β = 6.82, 95% CI 0.59–13.05, P = 0.033). apnea-hypopnea index (AHI), oxygen desaturation index (ODI) were significantly correlated with TT4RI (P = 0.034, 0.021, respectively). No significant associations were observed in males.

OSA is associated with impaired central and peripheral thyroid hormone sensitivity in euthyroid females, but not in males.

The online version contains supplementary material available at 10.1186/s13293-025-00821-5.

Thyroid hormone sensitivity indices reveal subtle endocrine alterations in OSA patients despite normal hormone levels.

In females, OSA was associated with elevated TFQI, PTFQI, TSHI, and TT4RI, and reduced FT3/FT4 ratio, indicating impaired thyroid hormone sensitivity despite normal hormone levels.

Females with OSA may have a higher risk of endocrine dysregulation, and more attention needs to be paid to thyroid and metabolic health in this group.

The online version contains supplementary material available at 10.1186/s13293-025-00821-5.

This study explored how the body’s sensitivity to thyroid hormones may be affected in people with obstructive sleep apnea (OSA), even when their thyroid hormone levels appear normal. We examined six indices that reflect how well the brain and body respond to thyroid hormones. These indices can reveal hidden problems in hormone regulation that standard blood tests might miss. By analyzing data from 718 adults, the study found a clear pattern in females: those with OSA showed signs of reduced thyroid hormone sensitivity. As the severity of OSA increased, several indices also increased, suggesting a disruption in how the body regulates thyroid hormones. These changes were linked to how often breathing stopped and how low oxygen levels dropped during sleep. Interestingly, none of these patterns were seen in males. These findings suggest that OSA may interfere with thyroid hormone regulation in females, even when hormone levels are technically within the normal range. Understanding this difference may help explain why females with OSA sometimes show metabolic or energy-related problems and highlights that more detailed hormone assessments may be useful for females with OSA.

The online version contains supplementary material available at 10.1186/s13293-025-00821-5.