Low Testosterone May Increase Mortality Risks in Men

A new review of research found that men with testosterone levels below a specific level had a higher risk of early death from cardiovascular disease and other causes.

According to the American College of Physicians (ACP), men experience a gradual decline in testosterone levels as they age. For example, starting in their mid-30s, testosterone levels drop at an average rate of 1.6 percent per year.

In the United States, approximately 20% of men over age 60 years, 30% over age 70, and 50% over age 80 have low testosterone or "low T."

Healthcare providers typically diagnose low T when a man's testosterone levels fall below 300 ng/dL. The condition can cause symptoms including low energy, erectile dysfunction, depression, and an increase in body fat.

Still, health experts have concerns over whether testosterone therapy could raise the risk of cardiovascular-related events like heart attack or stroke. While a recent study found no associations between testosterone replacement and heart attack risks, the health effects of male sex hormones remain unclear.

In a new meta-analysis published on May 13 in Annals of Internal Medicine, researchers reviewed studies published up to July 2019 and sporadic research papers to March 2024 to clarify whether testosterone levels impacted heart-related and other mortality outcomes in men.

Specifically, they used 11 studies with at least a 5-year follow-up that included male participants who had sex hormones measured using mass spectrometry. The team looked at several hormones that circulate in a man's body, including testosterone, luteinizing hormone (LH), dihydrotestosterone (DHT), estrogen, and sex hormone–binding globulin (SHBG).

They also adjusted for various health and lifestyle factors such as physical activity, cholesterol levels, and smoking status.

After analyzing the data, the team found that only men with very low total testosterone levels had higher risks for all-cause and cardiovascular-related mortality.

Specifically, men with baseline testosterone levels below 213 ng/dL, LH concentrations above 10 IU/L, or estrogen levels below 5.1 pmol/L had higher rates of death from all causes.

What's more, men with testosterone concentrations below 153 mg/dL had a higher risk of dying from cardiovascular disease.

Further analysis revealed that a higher concentration of circulating SHBG was linked to an elevated risk for all-cause mortality and was slightly associated with heart-related deaths.

The team also found the risks for all-cause and cardiovascular disease mortality were higher in men with low or very high DHT levels. However, only those with very low DHT concentrations had a higher risk of experiencing a cardiovascular event.

In addition, men with very high LH or very low estrogen concentrations had an increased risk for all-cause mortality.

The results suggest that sex hormones play complex roles in men's overall health.

"This is, to our knowledge, the first IPDMA of major prospective cohort studies using mass spectrometry sex steroid assays, which clarifies previous inconsistent findings on the influence of sex hormones on key health outcomes in aging men," the study's authors wrote.

Is testosterone replacement therapy safe?

In an editorial accompanying the study, Bradley D. Anawalt, M.D., a Professor of Medicine at the University of Washington School of Medicine, explains that testosterone replacement therapy has been a controversial topic among scientists and health experts for decades.

The debate centers around whether testosterone therapy to raise hormone levels into the normal range increases the risk for stroke, heart attack, cardiovascular death, and all-cause mortality among men with low T.

Anawalt notes that the primary finding in this study was that high testosterone concentrations were not associated with increased cardiovascular death and all-cause mortality, but low serum total testosterone concentrations at baseline were.

"It is tempting to hypothesize that testosterone therapy might have cardiovascular benefits solely in patients with very low concentrations of serum total testosterone," Anawalt wrote.

According to the Endocrine Society, testosterone therapy is only recommended for men with low T who are also experiencing symptoms. While it's generally safe, risks associated with testosterone replacement include acne, obstructive sleep apnea, elevated red blood cell count, and prostate or breast enlargement.

Moreover, men with specific health conditions like prostate cancer, untreated sleep apnea, or blood clots should not use testosterone treatments.

Additionally, testosterone therapy is not FDA-approved to improve athletic performance, boost strength, or enhance physical appearance. Men using the hormone to increase their otherwise normal testosterone levels could be putting their health at risk.

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