Accelerating Decline in Serum Testosterone across Birth Cohorts: A Systematic Review and Meta-Regression Analysis

Studies have reported declines in male reproductive health including declines in spermatogenesis and endocrine function. This study aims to determine the extent of these potential changes in total testosterone levels and to assess how much of these changes can be explained by shifts in relative body weight and other contributing factors.

PubMed was searched for relevant studies, and those reporting quantitative values of testosterone in healthy men ages ≥18 were included. Studies involving participants with cancer, chronic comorbidities, or diagnosed hypogonadism were excluded. The review protocol was registered on PROSPERO (CRD420251069558).

Overall, 345 studies were selected with a total of 169,493 subjects. The mean±standard deviation age and body mass index were 37.4±4.2 years and 24.0±3.4 kg/m², respectively. The findings suggested a possible accelerating decline in testosterone across successive birth cohorts. The estimated slopes were β=-2.49 (95% confidence interval [CI] -3.73, -1.26) for men born ≥1903, β=-2.66 (95% CI -3.95, -1.36) for ≥1925, β=-3.16 (95% CI -4.73, -1.59) for ≥1950, and β=-3.73 (95% CI -31.86, 33.76) for ≥1975. The decline was steeper among younger men, with β=-3.55 (95% CI -5.56, -1.53) ng/dL/y for those <30 years (p<0.0001), compared with β=-2.95 (95% CI -5.67, -0.23) ng/dL/y for ages 30 to 40 years (p=0.029) and -0.72 (95% CI -2.40, 0.96) ng/dL/y for men ≥40 years (p=0.392), and in individuals with normal weight (β=-3.07 [95% CI -4.98, -1.17] ng/dL/y) (p=0.002) than in those with overweight/obesity (β=-1.96 [95% CI -3.63, -0.29] ng/dL/y) (p=0.022).

These results indicate that declining testosterone levels have increasingly affected younger men with normal weight. The rate of decline was steeper in more recent birth cohorts, suggesting a possible acceleration of this trend across generations.