Lightning Talk + Poster ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Associations of testosterone and sex hormone-binding globulin with risks of cancer death, incident cancer, and incident prostate cancer in men. Individual participant data meta-analyses. (#490)

Ross J Marriott 1 , Kevin Murray 1 , Leen Antonio 2 , Shalender Bhasin 3 , Adrian S Dobs 4 , Leon Flicker 5 , David J Handelsman 6 , Graeme J Hankey 5 , Robin Wilkening 7 , Alvin M Matsumoto 8 , Claes Ohlsson 9 , Eric S Orwoll 10 , Dirk Vanderschueren 2 , Hubert Vesper 11 , Gary A Wittert 12 , Frederick CW Wu 13 , Bu B Yeap 5 14
  1. School of Population and Global Health, University of Western Australia, Perth, WA, Australia
  2. Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
  3. Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
  4. School of Medicine, Johns Hopkins University, Baltimore, United States
  5. The Medical School, University of Western Australia, Perth, WA, Australia
  6. ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia
  7. School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia
  8. Department of Medicine, University of Washington School of Medicine, Seattle, United States
  9. Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Goteborg, Sweden
  10. Oregon Health and Science University, Portland, United States
  11. National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, United States
  12. School of Medicine, University of Adelaide, Adelaide, SA, Australia
  13. School of Medical Sciences, University of Manchester, Manchester, United Kingdom
  14. Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, WA

Aims

Whether differences in sex hormones relate to cancer, particularly prostate cancer, risk in men remains uncertain. We sought to clarify associations of testosterone and sex hormone-binding globulin (SHBG) with cancer risk via individual participant data (IPD) meta-analyses of major prospective cohort studies of community-dwelling men with testosterone measured using mass spectrometry.

Methods

Eligible studies were identified via systematic literature review to July 2019, with bridge searches to March 2024. Ten studies provided IPD (24,510 men; 276,931 participant-years; 2847 cancer deaths), 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). Two-stage random effects meta-analyses controlled for age, prior cancer, BMI, marital status, alcohol, smoking, physical activity, hypertension and diabetes.

Results

Men with baseline testosterone at or below the lowest quintile median (Q1; 8.2 nmol/L), had higher risk of cancer death relative to Q5 (Q1:Q5 hazard ratio [HR]=1.15, 95% confidence interval [CI]=1.01-1.31). Baseline testosterone was not associated with risk of incident non-fatal and fatal cancer, nor incident prostate cancer. SHBG was non-linearly associated with risk of cancer death (Q3:Q5 HR=0.79, 95%CI=0.66-0.95; Q4:Q5 HR=0.85, 95%CI=0.76-0.96). SHBG was not associated with incident non-fatal and fatal cancer. Men with lower baseline SHBG had higher risk of incident prostate cancer (Q1:Q5, HR=1.31, 95%CI=1.08-1.60; Q2:Q5 HR=1.26, 95%CI=1.04-1.52). Relative heterogeneity was negligible to moderate (estimates of I2 had 95%CI from 0.0-65.4%). Summary estimates from IPD were robust to the inclusion of aggregate data. 

Conclusion

Men with lower testosterone concentrations had higher risk, and men with mid-range SHBG lower risk, of cancer death. Testosterone was not associated with prostate cancer risk, while men with lower SHBG had a higher risk of incident prostate cancer. Testosterone and SHBG are biomarkers for cancer risk. The association between SHBG and prostate cancer risk merits further evaluation.