Whether differences in sex hormones influence cancer risk in men remains uncertain. We aimed to clarify the association of circulating testosterone, sex hormone-binding globulin (SHBG), and related hormones with risks of cancer death, incident cancer, and incident prostate cancer by means of individual participant data (IPD) meta-analyses.
A systematic review of the literature using MEDLINE, Embase, OpenGrey, and Mednar was conducted from date of database inception till July 22, 2019, with bridge searches using MEDLINE till Jan 21, 2026. Prospective cohort studies comprising 1000 or more community-dwelling men with testosterone concentrations measured using mass spectrometry and a follow-up of 5 years or more were included. Two-stage random-effects meta-analyses were performed, controlling for baseline age, previous cancer, BMI, marital status, alcohol consumption, smoking status, physical activity, hypertension status, and diabetes status. Risk of bias was assessed using the Newcastle-Ottawa method. This study was prospectively registered with PROSPERO (CRD42019139668).
Ten studies provided IPD (24 510 men; 276 931 participant-years; 2847 cancer deaths), and one provided aggregate data (1535 men; 184 cancer deaths). Five studies provided IPD for incident prostate cancer (12 280 men; 151 373 participant-years; 918 events). Lower total testosterone concentrations were associated with higher risk of cancer death (median of first vs median of fifth quintile [Q1:Q5] hazard ratio [HR] 1·18, 95% CI 1·04-1·34), as were lower dihydrotestosterone concentrations (Q1:Q5 1·21, 1·06-1·38), the risk increasing with testosterone concentrations less than 8.6 nmol/L. SHBG and luteinising hormone concentrations were non-linearly associated with risk of cancer death (lowest risk: SHBG Q3:Q5 HR 0·81, 95% CI 0·68-0·97; luteinising hormone Q2:Q5 0·73, 0·59-0·90). Men with very low baseline testosterone concentrations had a higher risk of incident cancer, the risk increasing with concentrations less than 7.3 nmol/L. Lower SHBG or lower luteinising hormone concentrations were associated with higher risk of incident prostate cancer (Q1:Q5 HR 1·28, 95% CI 1·07-1·54; Q1:Q5 1·45, 1·13-1·86); testosterone was not associated with this outcome. Estimates of I2 indicated negligible to moderate heterogeneity across most analyses.
Lower total testosterone or dihydrotestosterone concentrations in men were associated with a higher risk of cancer death, and mid-range SHBG or luteinising hormone concentrations were associated with a lower risk. Men with lower SHBG or luteinising hormone concentrations had an associated higher risk of incident prostate cancer. Sex hormones could serve as biomarkers for cancer risk, warranting further investigation of these observed associations.
Medical Research Future Fund; Government of Western Australia; Lawley Pharmaceuticals.
The lancet. Healthy longevity. 2026 Jun 19 [Epub ahead of print]
Ross J Marriott, Kevin Murray, Leen Antonio, Robert J Adams, Christie M Ballantyne, Douglas C Bauer, Shalender Bhasin, Mary L Biggs, Peggy M Cawthon, David J Couper, Adrian S Dobs, Leon Flicker, Nele Friedrich, David J Handelsman, Graeme J Hankey, Anke Hannemann, Calvin H Hirsch, Benjumin Hsu, Sean A Martin, Alvin M Matsumoto, Claes Ohlsson, Terence W O'Neill, Eric S Orwoll, Thomas G Travison, Dirk Vanderschueren, Robin Wilkening, Gary A Wittert, Frederick C W Wu, Bu B Yeap
School of Population and Global Health, The University of Western Australia, Perth, WA, Australia., Laboratory of Clinical and Experimental Endocrinology, Katholieke Universiteit (KU) Leuven, Leuven, Belgium., Adelaide Institute for Sleep Health, Flinders University, Adelaide, SA, Australia., The Texas Heart Institute, Baylor College of Medicine, Houston, TX, USA., Division of General Internal Medicine, University of California San Francisco, San Francisco, CA, USA., Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA., San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA., Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Division of Endocrinology, Diabetes and Metabolism, School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Medical School, The University of Western Australia, Perth, WA, Australia; Western Australian Centre for Health and Ageing, The University of Western Australia, Perth, WA, Australia., Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany., ANZAC Research Institute, The University of Sydney, Sydney, NSW, Australia., Medical School, The University of Western Australia, Perth, WA, Australia; Perron Institute for Neurological and Translational Science, Perth, WA, Australia., University of California Davis School of Medicine, Sacramento, CA, USA., Marcus Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA., Freemasons Centre for Men's Health and Wellbeing, School of Medicine, University of Adelaide, Adelaide, SA, Australia., Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA; Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA., Centre for Bone and Arthritis Research at the Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Göteborg, Sweden., NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, UK., Oregon Health and Science University, Portland, OR, USA., School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Open Science, Swiss National Science Foundation, Bern, Switzerland., Division of Endocrinology, Diabetes and Gastroenterology, School of Medical Sciences, University of Manchester, Manchester, UK., Medical School, The University of Western Australia, Perth, WA, Australia; Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, WA, Australia. Electronic address: .