Back to Search Start Over

Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men: Individual Participant Data Meta-analyses.

Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men: Individual Participant Data Meta-analyses.

Authors :
Yeap, Bu B.
Marriott, Ross J.
Dwivedi, Girish
Adams, Robert J.
Antonio, Leen
Ballantyne, Christie M.
Bauer, Douglas C.
Bhasin, Shalender
Biggs, Mary L.
Cawthon, Peggy M.
Couper, David J.
Dobs, Adrian S.
Flicker, Leon
Handelsman, David J.
Hankey, Graeme J.
Hannemann, Anke
Haring, Robin
Hsu, Benjumin
Martin, Sean A.
Matsumoto, Alvin M.
Source :
Annals of Internal Medicine; Jun2024, Vol. 177 Issue 6, p768-781, 21p
Publication Year :
2024

Abstract

The relationship between testosterone and related hormones and cardiovascular and mortality outcomes is debated. The authors of this study obtained individual patient–level data from 9 cohort studies and aggregate data from 11 studies in total. These data enabled them to describe the associations of testosterone, sex hormone–binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone (DHT), and estradiol with all-cause mortality, cardiovascular death, and incident cardiovascular events while accounting for other cardiac risk factors. Background: Whether circulating sex hormones modulate mortality and cardiovascular disease (CVD) risk in aging men is controversial. Purpose: To clarify associations of sex hormones with these outcomes. Data Sources: Systematic literature review to July 2019, with bridge searches to March 2024. Study Selection: Prospective cohort studies of community-dwelling men with sex steroids measured using mass spectrometry and at least 5 years of follow-up. Data Extraction: Independent variables were testosterone, sex hormone–binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone (DHT), and estradiol concentrations. Primary outcomes were all-cause mortality, CVD death, and incident CVD events. Covariates included age, body mass index, marital status, alcohol consumption, smoking, physical activity, hypertension, diabetes, creatinine concentration, ratio of total to high-density lipoprotein cholesterol, and lipid medication use. Data Synthesis: Nine studies provided individual participant data (IPD) (255 830 participant-years). Eleven studies provided summary estimates (n = 24 109). Two-stage random-effects IPD meta-analyses found that men with baseline testosterone concentrations below 7.4 nmol/L (<213 ng/dL), LH concentrations above 10 IU/L, or estradiol concentrations below 5.1 pmol/L had higher all-cause mortality, and those with testosterone concentrations below 5.3 nmol/L (<153 ng/dL) had higher CVD mortality risk. Lower SHBG concentration was associated with lower all-cause mortality (median for quintile 1 [Q1] vs. Q5, 20.6 vs. 68.3 nmol/L; adjusted hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.95]) and lower CVD mortality (adjusted HR, 0.81 [CI, 0.65 to 1.00]). Men with lower baseline DHT concentrations had higher risk for all-cause mortality (median for Q1 vs. Q5, 0.69 vs. 2.45 nmol/L; adjusted HR, 1.19 [CI, 1.08 to 1.30]) and CVD mortality (adjusted HR, 1.29 [CI, 1.03 to 1.61]), and risk also increased with DHT concentrations above 2.45 nmol/L. Men with DHT concentrations below 0.59 nmol/L had increased risk for incident CVD events. Limitations: Observational study design, heterogeneity among studies, and imputation of missing data. Conclusion: Men with low testosterone, high LH, or very low estradiol concentrations had increased all-cause mortality. SHBG concentration was positively associated and DHT concentration was nonlinearly associated with all-cause and CVD mortality. Primary Funding Source: Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668) [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00034819
Volume :
177
Issue :
6
Database :
Complementary Index
Journal :
Annals of Internal Medicine
Publication Type :
Academic Journal
Accession number :
177927937
Full Text :
https://doi.org/10.7326/M23-2781