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
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. © The Author(s), under exclusive licence to Springer Nature B.V. 2025.
Centre of Research Impact and Outcome, Chitkara University, Punjab, Rajpura, 140417, India; Faculty of Data Science and Information Technology, INTI International University, Nilai, Malaysia; One Health Centre (COHERD), Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education, Wardha, India; Marwadi University Research Center, Department of Microbiology, Faculty of Science, Marwadi University, Gujarat, Rajkot, 360003, India; Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Karnataka, Bangalore, India; Department of Chemistry, Sathyabama Institute of Science and Technology, Tamil Nadu, Chennai, India; Department of Pharmacology, IMS and SUM Hospital, Siksha ‘O’ Anusandhan (Deemed to be University), Odisha, Bhubaneswar, 751003, India; Department of Pharmacy, Chandigarh Pharmacy College, Chandigarh Group of Colleges-Jhanjeri, Punjab, Mohali, 140307, India; School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India; University of Cyberjaya, Persiaran Bestari, Cyber 11, Selangor Darul Ehsan, Cyberjaya, 63000, Malaysia; University Center for Research and Development, Chandigarh University, Punjab, Mohali, India; Medical Laboratories Techniques Department, AL-Mustaqbal University, Babil, Hillah, 51001, Iraq; IES Institute of Pharmacy, IES University, Madhya Pradesh, Bhopal, 462044, India; New Delhi Institute of Management, Tughlakabad Institutional Area, New Delhi, India; Department of Microbiology, Graphic Era (Deemed to Be University), Clement Town, Dehradun, 248002, India; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P. O. Box 10219, Riyadh, 11433, Saudi Arabia; Department of Paediatrics, Dr. D. Y. Patil Medical College Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed-to-be-University), Pimpri, Maharashtra, Pune, 411018, India; Department of Public Health Dentistry, Dr. D. Y. Patil Medical College Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed-to-be-University), Pimpri, Maharashtra, Pune, 411018, India; Department of Medicine, Korea Universtiy, Seoul, South Korea; Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, India; South Asia Infant Feeding Research Network (SAIFRN), Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India; Faculty of Mathematics and Natural Sciences, Universitas Negeri Padang, Padang, Indonesia
