Associations of Serum Testosterone and Sex Hormone-Binding Globulin With Incident Cardiovascular Events in Middle-Aged to Older Men.


Journal

Annals of internal medicine
ISSN: 1539-3704
Titre abrégé: Ann Intern Med
Pays: United States
ID NLM: 0372351

Informations de publication

Date de publication:
Feb 2022
Historique:
pubmed: 28 12 2021
medline: 15 4 2022
entrez: 27 12 2021
Statut: ppublish

Résumé

The influence of testosterone on risk for cardiovascular events in men is uncertain. Previous observational studies of sex hormones and incident cardiovascular disease in men have reported inconsistent findings, limited by cohort sizes and different selection criteria. To analyze associations of serum total testosterone and sex hormone-binding globulin (SHBG) with incident cardiovascular events in men. Cohort study. UK Biobank prospective cohort. Community-dwelling men aged 40 to 69 years. Testosterone and SHBG were assayed, and free testosterone was calculated. Cox proportional hazards regression was done, with outcomes of incident myocardial infarction (MI), hemorrhagic stroke (HS), ischemic stroke (IS), heart failure (HF), and major adverse cardiovascular events (MACE), adjusted for sociodemographic, lifestyle, and medical factors. Of 210 700 men followed for 9 years, 8790 (4.2%) had an incident cardiovascular event. After adjustment for key variables, lower total testosterone concentrations (quintile 1 vs. quintile 5) were not associated with incident MI (fully adjusted hazard ratio [HR], 0.89 [95% CI, 0.80 to 1.00]), HS (HR, 0.94 [CI, 0.70 to 1.26]), IS (HR, 0.95 [CI, 0.82 to 1.10]), HF (HR, 1.15 [CI, 0.91 to 1.45]), or MACE (HR, 0.92 [CI, 0.84 to 1.00]). Men with lower calculated free testosterone values had a lower incidence of MACE (HR, 0.90 [CI, 0.84 to 0.97]). Lower SHBG concentrations were associated with higher incidence of MI (HR, 1.23 [CI, 1.09 to 1.38]) and lower incidence of IS (HR, 0.79 [CI, 0.67 to 0.94]) and HF (HR, 0.69 [CI, 0.54 to 0.89]), but not with HS (HR, 0.81 [CI, 0.57 to 1.14]) or MACE (HR, 1.01 [CI, 0.92 to 1.11]). Observational study; single baseline measurement of testosterone and SHBG. Men with lower total testosterone concentrations were not at increased risk for MI, stroke, HF, or MACE. Calculated free testosterone may be associated with risk for MACE. Men with lower SHBG concentrations have higher risk for MI but lower risk for IS and HF, with causality to be determined. Western Australian Health Translation Network, Medical Research Future Fund, and Lawley Pharmaceuticals.

Sections du résumé

BACKGROUND BACKGROUND
The influence of testosterone on risk for cardiovascular events in men is uncertain. Previous observational studies of sex hormones and incident cardiovascular disease in men have reported inconsistent findings, limited by cohort sizes and different selection criteria.
OBJECTIVE OBJECTIVE
To analyze associations of serum total testosterone and sex hormone-binding globulin (SHBG) with incident cardiovascular events in men.
DESIGN METHODS
Cohort study.
SETTING METHODS
UK Biobank prospective cohort.
PARTICIPANTS METHODS
Community-dwelling men aged 40 to 69 years.
MEASUREMENTS METHODS
Testosterone and SHBG were assayed, and free testosterone was calculated. Cox proportional hazards regression was done, with outcomes of incident myocardial infarction (MI), hemorrhagic stroke (HS), ischemic stroke (IS), heart failure (HF), and major adverse cardiovascular events (MACE), adjusted for sociodemographic, lifestyle, and medical factors.
RESULTS RESULTS
Of 210 700 men followed for 9 years, 8790 (4.2%) had an incident cardiovascular event. After adjustment for key variables, lower total testosterone concentrations (quintile 1 vs. quintile 5) were not associated with incident MI (fully adjusted hazard ratio [HR], 0.89 [95% CI, 0.80 to 1.00]), HS (HR, 0.94 [CI, 0.70 to 1.26]), IS (HR, 0.95 [CI, 0.82 to 1.10]), HF (HR, 1.15 [CI, 0.91 to 1.45]), or MACE (HR, 0.92 [CI, 0.84 to 1.00]). Men with lower calculated free testosterone values had a lower incidence of MACE (HR, 0.90 [CI, 0.84 to 0.97]). Lower SHBG concentrations were associated with higher incidence of MI (HR, 1.23 [CI, 1.09 to 1.38]) and lower incidence of IS (HR, 0.79 [CI, 0.67 to 0.94]) and HF (HR, 0.69 [CI, 0.54 to 0.89]), but not with HS (HR, 0.81 [CI, 0.57 to 1.14]) or MACE (HR, 1.01 [CI, 0.92 to 1.11]).
LIMITATION CONCLUSIONS
Observational study; single baseline measurement of testosterone and SHBG.
CONCLUSION CONCLUSIONS
Men with lower total testosterone concentrations were not at increased risk for MI, stroke, HF, or MACE. Calculated free testosterone may be associated with risk for MACE. Men with lower SHBG concentrations have higher risk for MI but lower risk for IS and HF, with causality to be determined.
PRIMARY FUNDING SOURCE BACKGROUND
Western Australian Health Translation Network, Medical Research Future Fund, and Lawley Pharmaceuticals.

Identifiants

pubmed: 34958606
doi: 10.7326/M21-0551
doi:

Substances chimiques

Sex Hormone-Binding Globulin 0
Testosterone 3XMK78S47O

Types de publication

Journal Article Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

159-170

Subventions

Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn

Auteurs

Bu B Yeap (BB)

Medical School, University of Western Australia, and Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Western Australia, Australia (B.B.Y.).

Ross J Marriott (RJ)

School of Population and Global Health, University of Western Australia, Perth, Western Australia, Australia (R.J.M., K.M.).

Leen Antonio (L)

Laboratory of Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium (L.A., D.V.).

Suchitra Raj (S)

Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Western Australia, Australia (S.R.).

Girish Dwivedi (G)

Medical School, University of Western Australia, Harry Perkins Institute of Medical Research, and Fiona Stanley Hospital, Perth, Western Australia, Australia (G.D.).

Christopher M Reid (CM)

School of Population Health, Curtin University, Perth, Western Australia, Australia (C.M.R.).

Bradley D Anawalt (BD)

Department of Medicine, University of Washington School of Medicine, Seattle, Washington (B.D.A.).

Shalender Bhasin (S)

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (S.B.).

Adrian S Dobs (AS)

Division of Endocrinology, Johns Hopkins University School of Medicine, Baltimore, Maryland (A.S.D.).

David J Handelsman (DJ)

Anzac Research Institute, Concord Hospital, University of Sydney, Sydney, New South Wales, Australia (D.J.H.).

Graeme J Hankey (GJ)

Medical School, University of Western Australia, Perth, Western Australia, Australia (G.J.H., P.E.N.).

Robin Haring (R)

School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia, and Faculty of Applied Public Health, European University of Applied Sciences, Rostock, Germany (R.H.).

Alvin M Matsumoto (AM)

Department of Medicine, University of Washington School of Medicine, and Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington (A.M.M.).

Paul E Norman (PE)

Medical School, University of Western Australia, Perth, Western Australia, Australia (G.J.H., P.E.N.).

Terence W O'Neill (TW)

Centre for Epidemiology Versus Arthritis, University of Manchester, and National Institute for Health Research Manchester Biomedical Research Centre, Manchester University National Health Service Foundation Trust, Manchester, United Kingdom (T.W.O.).

Claes Ohlsson (C)

Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, and Region Vastra Gotaland, Sahlgrenska University Hospital, Gothenburg, Sweden (C.O.).

Eric S Orwoll (ES)

Oregon Health & Science University, Portland, Oregon (E.S.O.).

Dirk Vanderschueren (D)

Laboratory of Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium (L.A., D.V.).

Gary A Wittert (GA)

Freemasons Centre for Men's Health and Wellbeing, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia (G.A.W.).

Frederick C W Wu (FCW)

Division of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, University of Manchester, Manchester, United Kingdom (F.C.W.).

Kevin Murray (K)

School of Population and Global Health, University of Western Australia, Perth, Western Australia, Australia (R.J.M., K.M.).

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Classifications MeSH