Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Dec 20:15:1501257.
doi: 10.3389/fimmu.2024.1501257. eCollection 2024.

Sex hormone imbalance and rheumatoid arthritis in American men: a cross-sectional analysis from NHANES 2011-2016

Pengfei Wen #  1 , Yidian Wang #  1 , Mingyi Yang  1 , Xincun Qiao  1 , Peng Yang  1 , Shouye Hu  1 , Lin Liu  1 , Zhi Yang  1
Affiliations

Sex hormone imbalance and rheumatoid arthritis in American men: a cross-sectional analysis from NHANES 2011-2016

Pengfei Wen et al. Front Immunol. .

Abstract

Background: Emerging evidence suggests that sex hormones, particularly testosterone and sex hormone-binding globulin (SHBG), play a critical role in the pathophysiology of Rheumatoid arthritis (RA). However, the precise relationship between these hormonal factors and RA risk in men remains underexplored.

Methods: We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016. A total of 3,110 male participants were included after excluding those with missing data on testosterone, SHBG, RA, or key covariates. Serum testosterone and SHBG levels were measured, and RA status was determined based on self-reported physician diagnosis. Multivariate logistic regression models were used to assess the association between testosterone, SHBG, and RA. Restricted cubic spline (RCS) regression was applied to explore nonlinear relationships. Subgroup and interaction analyses were performed to assess effect modifications by age, race/ethnicity, body mass index (BMI), hypertension, and poverty-income ratio (PIR).

Results: Of the 3,110 men analyzed, 191 were diagnosed with RA. Low testosterone levels (<300 ng/dL) were significantly associated with increased RA risk (OR = 2.30, 95% CI: 1.65-3.21, p < 0.001), and elevated SHBG levels (>57 nmol/L) were also associated with a higher risk of RA (OR = 1.65, 95% CI: 1.14-2.39, p = 0.008). RCS analysis indicated a nonlinear relationship between testosterone, SHBG, and RA risk, with sharp increases in RA risk at the lower ends of testosterone and SHBG levels. Interaction analyses revealed that age, race/ethnicity, hypertension, and PIR significantly modified the relationship between these hormonal factors and RA, while BMI did not exhibit any significant interaction.

Conclusion: This study provides evidence that low testosterone and high SHBG levels are associated with an increased risk of RA in men. These associations are nonlinear and modified by factors such as age, race/ethnicity, hypertension, and PIR. Our findings highlight the importance of considering hormonal status in RA risk assessment and suggest potential avenues for targeted therapeutic strategies aimed at hormonal regulation.

Keywords: NHANES; SHBG; cross-sectional study; hormonal regulation; rheumatoid arthritis; testosterone.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of participant selection.
Figure 2
Figure 2
Determination of the association between testosterone and rheumatoid arthritis by restricted cubic spline (RCS) regression analysis.
Figure 3
Figure 3
Determination of the association between SHBG and rheumatoid arthritis by restricted cubic spline (RCS) regression analysis.
Figure 4
Figure 4
Verification of the association between testosterone, SHBG, and rheumatoid arthritis by subgroup analyses and interaction analyses.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Wen P, Ma T, Zhang B, Hao L, Wang Y, Guo J, et al. . Identifying hub circadian rhythm biomarkers and immune cell infiltration in rheumatoid arthritis. Front Immunol. (2022) 13:1004883. doi: 10.3389/fimmu.2022.1004883 - DOI - PMC - PubMed
    1. Brown P, Pratt AG, Hyrich KL. Therapeutic advances in rheumatoid arthritis. BMJ. (2024) 384:e070856. doi: 10.1136/bmj-2022-070856 - DOI - PubMed
    1. Di Matteo A, Bathon JM, Emery P. Rheumatoid arthritis. Lancet. (2023) 402:2019–33. doi: 10.1016/S0140-6736(23)01525-8 - DOI - PubMed
    1. Gravallese EM, Firestein GS. Rheumatoid arthritis - common origins, divergent mechanisms. N Engl J Med. (2023) 388:529–42. doi: 10.1056/NEJMra2103726 - DOI - PubMed
    1. Wen P, Luo P, Zhang B, Wang Y, Hao L, Wang J, et al. . Hotspots and future directions in rheumatoid arthritis-related cardiovascular disease: A scientometric and visualization study from 2001 to 2021 based on Web of Science. Front Med (Lausanne). (2022) 9:931626. doi: 10.3389/fmed.2022.931626 - DOI - PMC - PubMed

LinkOut - more resources