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International Urology and Nephrology

09-01-2025 | Prostate Cancer | Urology – Review

Exploring the link between sex hormone-binding globulin levels and prostate cancer risk: a comprehensive systematic review and meta-analysis

Authors: Prakasini Satapathy, Shilpa Gaidhane, Ashok Kumar Bishoyi, Subbulakshmi Ganesan, Karthikeyan Jayabalan, Swati Mishra, Manpreet Kaur, Ganesh Bushi, Muhammed Shabil, Rukshar Syed, Sonam Puri, Sunil Kumar, Sabah Ansar, Sanjit Sah, Diptismita Jena, Zaid Khan, Quazi Syed Zahiruddin, Khang Wen Goh

Published in: International Urology and Nephrology

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Abstract

Background

Sex hormone-binding globulin (SHBG) plays a critical role in regulating androgen bioavailability and has been hypothesized to influence prostate cancer risk, though existing evidence is inconsistent. This systematic review and meta-analysis aimed to evaluate the association between SHBG levels and prostate cancer risk.

Methods

A comprehensive search was conducted across PubMed, Embase, and Web of Science for studies published up to December 1, 2024. Observational studies assessing SHBG levels and prostate cancer risk were included. Effect sizes were pooled using random-effects meta-analysis. Heterogeneity was evaluated using the I2 statistic, and quality assessment was performed using the Newcastle–Ottawa Scale. Statistical analysis was performed using R software version 4.4.

Results

Sixteen studies, including 720,298 participants and 90,799 prostate cancer cases, were analyzed. The pooled odds ratio (OR) for prostate cancer risk per unit increase in SHBG was 0.907 (95% CI 0.799–1.030), indicating no statistically significant association. Substantial heterogeneity was observed among the included studies (I2 = 79%; P < 0.0001). Subgroup analyses showed no significant variation in effect sizes by study design. However, a Mendelian randomization analysis conducted in 140,254 European-descent males, including 79,148 prostate cancer cases, suggested a modest protective effect of higher SHBG levels, with an OR of 0.944 (95% CI 0.897–0.993). Sensitivity analyses confirmed the robustness of the pooled findings.

Conclusion

This meta-analysis showed a complex relationship between SHBG levels and prostate cancer risk. While overall findings do not support a statistically significant association, higher SHBG levels may confer a protective role in specific contexts. Further research is needed to elucidate mechanisms, reduce heterogeneity, and validate SHBG as a biomarker for risk stratification.
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Metadata
Title
Exploring the link between sex hormone-binding globulin levels and prostate cancer risk: a comprehensive systematic review and meta-analysis
Authors
Prakasini Satapathy
Shilpa Gaidhane
Ashok Kumar Bishoyi
Subbulakshmi Ganesan
Karthikeyan Jayabalan
Swati Mishra
Manpreet Kaur
Ganesh Bushi
Muhammed Shabil
Rukshar Syed
Sonam Puri
Sunil Kumar
Sabah Ansar
Sanjit Sah
Diptismita Jena
Zaid Khan
Quazi Syed Zahiruddin
Khang Wen Goh
Publication date
09-01-2025
Publisher
Springer Netherlands
Published in
International Urology and Nephrology
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-025-04370-z

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