Hormone Replacement Therapy Does Not Increase Incidence of Heart Attack, Stroke, According to New England Journal of Medicine Study

A study reported in the July 13, 2023, issue of the New England Journal of Medicine found that men receiving testosterone HRT and a placebo group had a comparable incidence of major cardiovascular events during a 22-month period.¹

The randomized, double-blind trial included men between the ages of 45 and 80 years with low testosterone levels who had preexisting cardiovascular disease or had a high risk of the disease. A gel containing testosterone was applied daily by 2,596 men and 2,602 men received a placebo gel.

Cardiovascular events—which included nonfatal heart attacks and strokes as well as death from cardiovascular causes—impacted 7% of the men who received testosterone (hormone replacement therapy) and 7.3% of the placebo group.

Deaths from cardiovascular causes were 16% lower and deaths from any cause were 2% lower among men who received hormone replacement therapy compared to the placebo. Some of the other results were mixed, though: pulmonary embolism (blood clot in a lung) occurred among 0.9% of men who received hormone replacement therapy and 0.5% of the placebo group, atrial fibrillation (a type of abnormal heart rhythm) occurred among 3.5% of the hormone replacement therapy group and 2.4% of the placebo group, and acute kidney injury was observed among 2.3% and 1.5% of the hormone replacement therapy and placebo groups, respectively.

The authors noted that a meta-analysis published in The Lancet Healthy Longevity failed to find an association between hormone replacement therapy and the risk of venous thromboembolism (blood clots in the veins), and that an association between hormone replacement therapy and a decrease in the incidence of atrial fibrillation was revealed by another study.

The findings may offer some comfort to men considering hormone replacement therapy who were concerned about a possible elevated risk of heart disease. “Controlled trials have shown that the use of testosterone in older men improves sexual function, increases volumetric and areal bone mineral density, corrects unexplained anemia, and moderately reduces depressive symptoms,” Dr. A. Michael Lincoff, MD and colleagues wrote.

Apply What You’ve Learned: Testosterone

• Testosterone is a sex hormone made by men and, in lesser amounts, by women. Testosterone is vital for normal male sexual development and function. Levels of the hormone decline in both men and women during aging. Obesity, diabetes and other factors are also associated with lower-than-normal testosterone levels in men.²
• Symptoms of low testosterone include decreased sexual desire and activity, erectile dysfunction, low energy and mood swings.³ Regular blood testing of testosterone and other hormone levels is advisable to determine whether testosterone replacement could be beneficial and to guide the amount of testosterone administered.
• Forms of testosterone replacement therapy include intramuscular injections, transdermal gels and patches, orally administered capsules or lozenges, subdermal implants (pellets) and nasal formulas. A healthcare provider can help determine whether an individual is an appropriate candidate for testosterone replacement and which testosterone product to prescribe.
• Nonprescription options to support healthy male hormone balance include pomegranate, cacao seed, DHEA and pregnenolone.⁴,⁵

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References:

1. Lincoff AM et al. N Engl J Med. 2023 Jul 13;389(2):107-117. ↩︎
2. Dhindsa S et al. Diabetes Care. 2018 Jul;41(7):1516-1525. ↩︎
3. García-Cruz E et al. Actas Urol Esp (Engl Ed). 2020 Jun;44(5):294-300. ↩︎
4. Sreeramaneni PGA et al. J Diet Suppl. 2023;20(3):411-427. ↩︎
5. Li Y et al. Exp Gerontol. 2020 Nov;141:111110. ↩︎