Individual testosterone decline and future mortality risk in men.

Area of Science:

• Endocrinology and Aging Research
• Cardiovascular Epidemiology
• Longevity Studies

Background:

• Male aging is associated with declining testosterone (TS) levels, but the impact of age-related TS changes on overall health and mortality remains unclear.
• Variability in testosterone decline among men suggests potential links between hormone dynamics and health outcomes.
• Understanding these associations is crucial for assessing health risks in aging male populations.

Purpose of the Study:

• To investigate the association between intra-individual changes in serum testosterone and related hormones (SHBG, free TS, LH) over a ten-year period and subsequent mortality.
• To determine if the rate of age-related decline in testosterone levels impacts all-cause, cardiovascular disease (CVD), or cancer mortality.
• To assess the relationship between hormone level changes and mortality risk, independent of baseline hormone concentrations.

Main Methods:

• Longitudinal study of 1167 men aged 30-60 years from the Danish MONICA study, with baseline (MONICA1) and 10-year follow-up (MONICA10) assessments.
• Mortality follow-up for up to 18 years using national registry data linked via unique personal identification numbers.
• Cox proportional hazard models were employed to analyze the association between intra-individual hormone changes and mortality outcomes.

Main Results:

• A total of 421 men (36.1%) died during the follow-up period.
• Men experiencing the most significant decline in total testosterone (bottom 10th percentile) exhibited a 1.60-fold increased risk of all-cause mortality compared to the reference group (10th-90th percentile).
• No significant associations were found between testosterone decline and cause-specific mortality (CVD or cancer).

Conclusions:

• A pronounced age-related decline in total testosterone is independently associated with higher all-cause mortality rates in men.
• The baseline testosterone level did not influence the observed association between testosterone decline and mortality risk.
• These findings underscore the clinical relevance of monitoring testosterone dynamics in aging men for mortality risk assessment.