Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men

Abstract

BackgroundAn association between testosterone therapy (TT) and cardiovascular disease has been reported and TT use is increasing rapidly.MethodsWe conducted a cohort study of the risk of acute non-fatal myocardial infarction (MI) following an initial TT prescription (N = 55,593) in a large health-care database. We compared the incidence rate of MI in the 90 days following the initial prescription (post-prescription interval) with the rate in the one year prior to the initial prescription (pre-prescription interval) (post/pre). We also compared post/pre rates in a cohort of men prescribed phosphodiesterase type 5 inhibitors (PDE5I; sildenafil or tadalafil, N = 167,279), and compared TT prescription post/pre rates with the PDE5I post/pre rates, adjusting for potential confounders using doubly robust estimation.ResultsIn all subjects, the post/pre-prescription rate ratio (RR) for TT prescription was 1.36 (1.03, 1.81). In men aged 65 years and older, the RR was 2.19 (1.27, 3.77) for TT prescription and 1.15 (0.83, 1.59) for PDE5I, and the ratio of the rate ratios (RRR) for TT prescription relative to PDE5I was 1.90 (1.04, 3.49). The RR for TT prescription increased with age from 0.95 (0.54, 1.67) for men under age 55 years to 3.43 (1.54, 7.56) for those aged ≥75 years (ptrend = 0.03), while no trend was seen for PDE5I (ptrend = 0.18). In men under age 65 years, excess risk was confined to those with a prior history of heart disease, with RRs of 2.90 (1.49, 5.62) for TT prescription and 1.40 (0.91, 2.14) for PDE5I, and a RRR of 2.07 (1.05, 4.11).DiscussionIn older men, and in younger men with pre-existing diagnosed heart disease, the risk of MI following initiation of TT prescription is substantially increased.

Testosterone therapy and cardiovascular risk

“…In the other study, Finkle et al (8). The event rate in the prescription ratio of acute MI incidence was 1.36 (95% CI 1.03-1.81).…”

“…More recent studies demonstrating that low testosterone in men is inversely associated with CV risk have led to suggestions that testosterone replacement may be beneficial (6). Safety concerns about testosterone came to the forefront after the recent publication of two observational studies suggesting associations of testosterone therapy with adverse CV outcomes (7,8). These studies were widely covered by the media, and cardiologists are likely to see patients with questions about testosterone and CV risk.…”

Testosterone and cardiovascular disease – what is the story?

“…2 A few weeks after this, the US Food and Drug Administration (FDA) announced that it was going to investigate the cardiovascular risks associated with testosterone treatment.…”

American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: A Neuroendocrine Approach to Patients With Traumatic Brain Injury

“…In men, testosterone replacement can be administered as transdermal gels, patches, buccal or subcutaneous pellets, or intramuscular injections (37). As the cardiovascular safety of testosterone replacement in older men, particularly those with cardiovascular disease, has been called into question in recent observational studies, caution is advised before considering testosterone replacement in these groups until more definitive data from clinical trials become available (48,49). Women of premenopausal age who have central hypogonadism can receive estrogen and progestin replacement (if they have an intact uterus) or estrogen replacement only (after hysterectomy), if not contraindicated, based on careful gynecologic evaluation and follow-up.…”