Older age, diabetes, cancer among factors linked to lower testosterone concentrations

Key takeaways:

• Reduced testosterone is associated with poor health outcomes in aging men.
• When interpreting testosterone measurements, physicians should account for age, BMI and the presence of diabetes or cancer.

After age 70 years, researchers found that having a higher BMI and the presence of certain conditions such as diabetes and cancer were associated with lower testosterone concentrations.

“Lower testosterone concentrations are associated with a range of poor health outcomes in aging men, including higher risks for diabetes, dementia, and death, with some evidence for causation with respect to diabetes,” Ross J. Marriott, PhD, a research fellow at the University of Western Australia School of Population and Global Health, and colleagues wrote in Annals of Internal Medicine.

However, it is unknown whether decreased testosterone is natural to male aging or reflects “functional inhibition resulting from age-related comorbid conditions,” they added.

“Sociodemographic, lifestyle, and behavioral factors and medical comorbid conditions have been associated with differences in testosterone concentrations in previous individual studies, with uncertainty over the consistency and magnitude of such associations,” the researchers wrote.

So, the researchers conducted a systematic review and meta-analysis of 11 studies that included individual participant data on 21,074 men as well as aggregate data on 4,075 men to better understand factors associated with variations in testosterone concentrations. They used mass spectrometry to measure levels of total testosterone, testosterone-dihydrotestosterone and estradiol, and immunoassays to measure sex hormone-binding globulin (SHBG) and luteinizing hormone (LH).

Marriott and colleagues reported no significant differences in mean testosterone levels until after age 70 years, during which testosterone concentrations decreased (standard difference [SD] = –1.55 nmol/L; 95% CI, –2.05 to –1.06) and LH levels increased (change per SD increase = 4.14 IU/L; 95% CI, 3.71-4.56), indicating impaired testicular function.

Testosterone concentrations were also lower in men who:

• had a higher BMI (SD = –2.42 nmol/L; 95% CI, –2.7 to –2.13);
• had at most 75 minutes of vigorous physical activity per week (mean difference [MD] = –0.51 nmol/L; 95% CI, –0.9 to –0.13);
• were married (MD = –0.57 nmol/L; 95% CI, –0.89 to –0.26); and
• formerly smoked (MD = –0.34 nmol/L; 95% CI, –0.55 to –0.12).

Medical conditions that were linked to reduced testosterone concentrations included:

• cancer (MD = –1.39 nmol/L; 95% CI, –1.79 to –0.99);
• CVD (MD = –0.35 nmol/L; 95% CI, –0.55 to –0.15);
• hypertension (MD = –0.53 nmol/L; 95% CI, –0.82 to –0.24); and
• diabetes (MD = –1.43 nmol/L; 95% CI, –1.65 to –1.22).

The researchers noted that the decrease in testosterone concentrations among men aged older than 70 years was “less apparent in the subgroup of men free of hypertension, diabetes, CVD, cancer, COPD, lipid-lowering medication use, and elevated creatinine levels.”

In addition, they wrote that SHBG increased with age and was so pronounced that “further investigation is warranted to explore whether this might alter the bioavailability of testosterone to access target tissues,” they wrote.

Marriott and colleagues added that the findings “may be relevant for the evaluation of men with suspected hypogonadism.”

“In any individual man, sociodemographic, lifestyle, and medical factors should be considered when interpreting a testosterone result, particularly when that result is closer to the lower bound of the reference interval,” they wrote. “These factors should also be considered as potential confounders in analyses evaluating the associations of testosterone concentrations with health outcomes in men.”