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Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
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Association Between Long-Term Testosterone Exposure and Major Adverse Cardiovascular Events in Aging Men.

Paul J Connelly1, Samuel Owusu Achiaw2, Jocelyn M Friday2

  • 1Department of Endocrinology & Diabetes, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK.

Journal of the Endocrine Society
|October 30, 2025
PubMed
Summary

Long-term testosterone therapy in older men was linked to a 55% higher risk of major adverse cardiovascular events. This study highlights the need for more research on the cardiovascular safety of testosterone replacement therapy.

Keywords:
hypogonadismmajor adverse cardiovascular eventsretrospective cohort studytestosterone exposure

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Area of Science:

  • Endocrinology
  • Cardiology
  • Geriatrics

Background:

  • Hypogonadism is common in aging men and linked to adverse cardiometabolic outcomes.
  • Cardiovascular safety concerns regarding testosterone therapy may influence clinical decisions.
  • Testosterone therapy is a potential treatment for hypogonadism in aging men.

Purpose of the Study:

  • To investigate the association between long-term testosterone therapy and major adverse cardiovascular events (MACE).
  • To assess cardiovascular risk in men aged 51 years and older receiving testosterone therapy.

Main Methods:

  • Retrospective cohort study using linked National Health Service data.
  • Included men aged 51+ from 2012, with testosterone exposure defined by prescriptions between 2012-2016.
  • Followed participants from 2017-2022, analyzing time to first MACE (myocardial infarction, unstable angina, stroke, heart failure, CV death) using Cox models.

Main Results:

  • The study included 440 testosterone-exposed and 136,051 unexposed men.
  • Testosterone exposure was associated with a 54% increased risk of MACE in unadjusted analysis (HR: 1.54).
  • After adjustment for confounders, testosterone exposure showed a 55% increased risk of MACE (HR: 1.55).

Conclusions:

  • Long-term testosterone therapy in this real-world cohort was associated with increased cardiovascular risk.
  • Existing trials provide data on short- to medium-term safety.
  • Further long-term data is needed to fully understand the cardiovascular effects of testosterone therapy.