Reassuring Data on Testosterone Safety

Volume 28, Issue 4

There have long been concerns about sex hormone replacement therapy. Estrogen replacement therapy for post-menopausal women was once thought to be safe, only to later be proven to be associated with dangerous thromboembolic complications. Testosterone, similarly, has been linked to thromboembolism in some prior studies, while other retrospective data show a potential for lower rates of adverse cardiovascular outcomes.

Given that a significant number of middle-aged and older adult men have hypogonadism and could benefit from testosterone replacement, addressing this state of clinical equipoise is worthwhile. In this week’s issue of Talking Therapeutics, we explore a new study¹ in the New England Journal of Medicine that addresses this important issue.

Talking Point: No signal for harm or benefit

This new trial included over 5000 adult men aged 45-80 with diagnosed hypogonadism. The primary endpoint was first occurrence of nonfatal stroke, death from cardiovascular cause, nonfatal myocardial infarction, or nonfatal stroke. 

Over a mean follow up period 33 months, the primary endpoint occurred in 7% of the testosterone group and in 7.3% of the placebo group. The trial also evaluated several other key safety endpoints including:

• “Pulmonary embolism occurred in the testosterone group than in the placebo group (0.9% vs. 0.5%).”
• “Nonfatal arrhythmias warranting intervention occurred in 134 patients (5.2%) in the testosterone group and in 87 patients (3.3%) in the placebo group (P=0.001).”
• “Atrial fibrillation occurred in 91 patients (3.5%) and 63 patients (2.4%), respectively (P=0.02).”
• “Acute kidney injury occurred in 60 patients (2.3%) and 40 patients (1.5%), respectively (P=0.04).”
• “Prostate cancer occurred in 12 patients (0.5%) in the testosterone group and in 11 patients (0.4%) in the placebo group (P=0.87).”

Talking Point: Patient should make the decision

These data are very informative and equip health care professionals with the requisite facts to present potential patients with a comprehensive list of pros and cons with testosterone therapy. While it is very reassuring that there appears to be no adverse cardiovascular risk with testosterone replacement, the potential risk for atrial fibrillation and acute kidney injury are concerning.

Patients should be counseled on these potential hazards prior to starting testosterone therapy, and health care providers should consider avoiding testosterone replacement therapy in patients with a history of arrhythmia or kidney failure.

Reference:

1. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular Safety of Testosterone-Replacement Therapy [published online ahead of print, 2023 Jun 16]. N Engl J Med. 2023;10.1056/NEJMoa2215025. doi:10.1056/NEJMoa2215025