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The Association of Reproductive Hormone Levels and All-Cause, Cancer, and Cardiovascular Disease Mortality in Men.

CONTEXT
Testosterone (T) levels have been associated with mortality, but controversy exists.


OBJECTIVE
Our objective was to investigate associations between serum levels of total T, SHBG, free T, estradiol, LH and FSH, and subsequent mortality with up to 30 years of follow-up.


DESIGN
This was a prospective cohort study consisting of men participating in four independent population-based surveys (MONICA I-III and Inter99) from 1982 to 2001 and followed until December 2012 with complete registry follow-up.


SETTING AND PARTICIPANTS
A total of 5350 randomly selected men from the general population aged 30, 40, 50, 60, or 70 years at baseline participated.


MAIN OUTCOMES AND MEASURES
All-cause mortality, cardiovascular disease (CVD) mortality, and cancer mortality were the main outcomes.


RESULTS
A total of 1533 men died during the follow-up period; 428 from CVD and 480 from cancer. Cox proportional hazard models revealed that men in highest LH quartile had an increased all-cause mortality compared to lowest quartile (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.14-1.53). Likewise, increased quartiles of LH/T and estradiol increased the risk of all-cause mortality (HR, 1.23; 95% CI, 1.06-1.43; HR, 1.23; 95% CI 1.06-1.43). No association to T levels was found. Higher LH levels were associated with increased cancer mortality (HR, 1.42; 95% CI, 1.10-1.84) independently of smoking status. Lower CVD mortality was seen for men with T in the highest quartile compared to lowest (HR, 0.72; 95% CI, 0.53-0.98). Furthermore, negative trends were seen for SHBG and free T in relation to CVD mortality, however insignificant.


CONCLUSION
The observed positive association of LH and LH/T, but not T, with all-cause mortality suggests that a compensated impaired Leydig cell function may be a risk factor for death by all causes in men. Our findings underpin the clinical importance of including LH measurement in the diagnostic work-up of male patients seeking help for possible androgen insufficiency.