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. 2021 Jun 23:12:683226.
doi: 10.3389/fendo.2021.683226. eCollection 2021.

Sex Steroids and Osteoarthritis: A Mendelian Randomization Study

Yi-Shang Yan  1 , Zihao Qu  2   3 , Dan-Qing Yu  1   4 , Wei Wang  2   3 , Shigui Yan  2   3 , He-Feng Huang  1
Affiliations

Sex Steroids and Osteoarthritis: A Mendelian Randomization Study

Yi-Shang Yan et al. Front Endocrinol (Lausanne). .

Abstract

Objective: Sex steroids are thought to contribute to the pathogenesis of osteoarthritis (OA). This study investigated the causal role of sex steroids in site- and sex-specific OA and risk of joint replacement surgery using the Mendelian randomization (MR) method.

Methods: Instrumental variables for estradiol, dehydroepiandrosterone sulfate, testosterone (T), and dihydrotestosterone (DHT) were selected. We used the inverse variance weighting (IVW) approach as the main MR method to estimate causal effects based on the summary-level data for OA and joint replacement surgery from genome-wide association studies (GWAS).

Results: A positive causal association was observed between serum T level and risks of hip OA (odds ratio [OR]=1.558, 95% confidence interval [CI]: 1.193-2.034; P=0.001) and hip replacement (OR=1.013, 95% CI: 1.008-1.018; P=2.15×10-8). Serum DHT level was also positively associated with the risk of hip replacement (OR=1.011, 95% CI: 1.006-1.015; P=4.03×10-7) and had potential causality with hip OA (OR=1.398, 95% CI: 1.054-1.855; P=0.020).

Conclusions: Serum T and DHT levels may play causal roles in the development of hip OA and contribute to the risk of hip replacement, although the underlying mechanisms require further investigation.

Keywords: Mendelian randomization; dehydroepiandrosterone sulfate; dihydrotestosterone; estradiol; osteoarthritis; testosterone.

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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
Causal effects of sex steroids on the risk of overall OA. The estimated effects, 95% confidence intervals and p-values of associations were contained. Effect, the combined causal effect; CI, confidence interval; P value, p-value of the causal estimate.
Figure 2
Figure 2
Causal effects of sex steroids on the risk of OA of hip and knee. The estimated effects, 95% confidence intervals and p-values of associations were contained. Effect, the combined causal effect; CI, confidence interval; P value, p-value of the causal estimate.
Figure 3
Figure 3
Causal effects of sex steroids on the risk of OA in single sex. The estimated effects, 95% confidence intervals and p-values of associations were contained. Effect, the combined causal effect; CI, confidence interval; P value, p-value of the causal estimate.
Figure 4
Figure 4
Causal effects of sex steroids on the risk of joint replacement of hip and knee. The estimated effects, 95% confidence intervals and p-values of associations were contained. Effect, the combined causal effect; CI, confidence interval; P value, p-value of the causal estimate.
See this image and copyright information in PMC

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