Poster Presentation ESA-SRB-APEG-NZSE 2022

Testosterone concentrations in men: Individual Participant Data meta-analyses from the Androgens In Men Study. (#314)

Ross J Marriott 1 , Kevin Murray 1 , Leen Antonio 2 , Shalender Bhasin 3 , Adrian S Dobs 4 , David J Handelsman 5 , Graeme J Hankey 6 , Robin Haring 7 , Alvin M Matsumoto 8 , Claes Ohlsson 9 , Eric S Orwoll 10 , Dirk Vanderschueren 11 , Gary A Wittert 12 , Frederick C Wu 13 , Bu B Yeap 6 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. ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia
  6. Medical School, University of Western Australia, Perth, WA, 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. Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
  12. Freemasons Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, South Australia, Australia
  13. School of Medical Sciences, University of Manchester, Manchester, United Kingdom
  14. Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, WA, Australia

Background

Different factors modulate circulating testosterone in men, impacting interpretation of reference ranges. By conducting an individual participant data (IPD) meta-analysis of major cohort studies measuring testosterone accurately, we aimed to clarify sex hormone concentrations and factors associated with these in men.

Methods

Systematic literature searches (June-December 2019) identified prospective cohort studies of adult men with total testosterone measured using mass spectrometry. IPD data were requested. Cross-sectional analyses related total testosterone, sex hormone binding globulin (SHBG), luteinising hormone (LH), dihydrotestosterone (DHT) and estradiol concentrations to sociodemographic, lifestyle, and health factors. Summary curves and summary effect estimates with 95% confidence intervals (CIs) were obtained using two-stage random-effects IPD meta-analyses (PROSPERO: CRD42019139668).

Findings

Summary estimates were obtained from 11 studies (25,364 adult men). There was a non-linear association of testosterone with age, with negligible change among 17-70 year olds (per SD increase age -0.27 nmol/L, CI -0.71,0.18) and decreasing testosterone with age for men >70 years (-1.24 nmol/L, CI -1.61,-0.87). Testosterone was inversely associated with BMI (per SD increase BMI -2.42 nmol/L, CI -2.70,-2.13). Testosterone concentrations were lower for men who: were married/de facto (-0.57 nmol/L); undertook ≤75 minutes vigorous physical activity/week (-0.51 nmol/L); former smokers (-0.34 nmol/L); had hypertension (-0.53 nmol/L), cardiovascular disease (-0.35 nmol/L), cancer (-1.39 nmol/L), or diabetes (-1.43 nmol/L); all CIs <0.0. SHBG increased with age and decreased with BMI, while LH increased non-linearly with age. DHT and estradiol were less prominently associated with these factors.

Interpretation

Multiple factors are associated with variation in male testosterone and SHBG concentrations, with evidence of primary impairment of testicular hormone production after age 70 years. Interpretation of testosterone results in individuals needs to account for these factors, especially age >70 years, BMI, diabetes and cancer. Further research is needed to determine health impacts of declining testosterone in older men.