Harman · The Journal of clinical endocrinology and metabolism 2001 · longitudinal cohort study · n=890

Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging.

Cited 2692 times in the scientific literature.

Level 3 - non-randomized controlled study

Longitudinal cohort study assessing repeat serum measurements over time using mixed-effects modeling.

PubMed 11158037 · doi:10.1210/jcem.86.2.7219 · record verified 2026-08-26

What was done

Total testosterone (T) and sex hormone-binding globulin (SHBG) were measured by radioimmunoassay in stored serum samples from 890 men in the Baltimore Longitudinal Study on Aging. Mixed-effects models were used to analyze longitudinal changes in total T and free T index (T/SHBG) while controlling for date-of-sampling effects, body mass index, and medication use.

What was found

Significant, independent longitudinal declines were observed for both total T (-0.124 nmol/L per year) and free T index (-0.0049 nmol T/nmol SHBG per year). Total T, but not free T index, also decreased with increasing body mass index, while beta-blocker use was associated with higher levels of both. The incidence of hypogonadal levels based on total T criteria was approximately 20% in men over 60, 30% in men over 70, and 50% in men over 80 years of age, with higher percentages when free T index criteria were used.

Why it matters

It demonstrates that declines in bioavailable and total testosterone are driven by aging per se rather than solely by age-related chronic diseases or medications, establishing that biochemical hypogonadism becomes common in advanced age.

Limits

Participants were drawn from the Baltimore Longitudinal Study on Aging, a cohort typically healthier and of higher socioeconomic status than the general population. Stored samples exhibited date-of-sampling artifactual effects requiring statistical adjustment, and clinical symptoms of hypogonadism were not correlated with the biochemical thresholds in the abstract.

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