OR25-04 Factors Affecting Testosterone Concentrations In Men: Individual Participant Data Meta-analyses From The Androgens In Men Study

Abstract Disclosure: R.J. Marriott: None. K. Murray: None. L. Antonio: None. S. Bhasin: None. A.S. Dobs: None. D.J. Handelsman: None. G.J. Hankey: None. R. Haring: None. A.M. Matsumoto: None. C. Ohlsson: None. E.S. Orwoll: None. D.M. Vanderschueren: None. G.A. Wittert: None. F.C. Wu: None. B.B. Yeap: None. Different factors modulate circulating testosterone in men, impacting interpretation of reference ranges. We aimed to clarify factors associated with variations in sex hormone concentrations by conducting individual participant data (IPD) meta-analyses of prospective cohort studies of adult men with total testosterone measured using mass spectrometry. The Androgens In Men Study protocol was submitted to PROSPERO (23 July 2019), registered (20 November 2019; CRD42019139668) and published (BMJ Open 2020; 10: e034777). A systematic review (14 June-31 December 2019) identified prospective cohort studies (BMJ Open 2021; 11: e048013). IPD data were requested. Cross-sectional analyses related total testosterone (measured using mass spectrometry), sex hormone binding globulin (SHBG), luteinising hormone (LH), dihydrotestosterone (DHT) and estradiol (also measured using mass spectrometry) concentrations to sociodemographic, lifestyle, and health factors. Summary curves and effect estimates with 95% confidence intervals (CIs) were obtained using two-stage random-effects IPD meta-analyses. Summary estimates were obtained from 11 studies (25,149 men). There was a non-linear association of testosterone with age, with negligible change among men aged 17-70 years (1SD increase about age 43.5, from 35.7 to 51.3 years -0.27 nmol/L, CI -0.71 to 0.18) and decreasing testosterone with age for men >70 years (1SD increase about age 84.5, from 76.7 to 92.3 years -1.55 nmol/L, CI -2.05 to -1.06). Testosterone was inversely associated with BMI (1SD increase about 27.5 kg/m2, from 25.5 to 29.6 kg/m2 -2.42 nmol/L, CI -2.70 to -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 excluded zero. SHBG increased with age (per SD increase in age 11.3 nmol/L, CI 9.0 to 13.6) and decreased with BMI (per SD increase in BMI -5.9 nmol/L, CI -6.9 to -5.0). There was little change in mean LH with age in men <70 years (1SD increase in age 0.10 IU/L, CI -0.08 to 0.28), but an increase in LH with age in men ≥70 years (1SD increase in age 4.14 IU/L, CI 3.71 to 4.56). DHT and estradiol were less prominently associated with these factors. 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. Presentation Date: Saturday, June 17, 2023