Elevated LH predicts ischaemic heart disease events in older men: the Health in Men Study.

Context: Hypogonadism in men is associated with insulin resistance, elevations in pro-inflammatory cytokines and fibrinogen, and an atherogenic lipid profile. However, it is uncertain whether the age-related decline in testosterone is associated with ischaemic heart disease (IHD) events.

Objective: To determine whether testosterone and its associated hormones, sex hormone-binding globulin (SHBG) and LH, predict IHD events in older men.

Design: Prospective cohort study.

Methods: Between 2001 and 2004, 3637 community-dwelling men aged 70-88 years underwent a clinical assessment of cardiovascular risk factors and biochemical assessment of testosterone, SHBG and LH. Free testosterone was calculated using mass action equations. Participants were followed until December 2008 using electronic record linkage to capture IHD events (hospital admission or death).

Results: Mean follow-up was 5.1 years. During this period, 618 men (17.0%; 95% confidence interval (CI) 15.8, 18.3%) experienced an event, of which 160 were fatal. Men with higher baseline total or free testosterone levels experienced fewer IHD events (hazard ratio (HR)=0.89; 95% CI 0.82, 0.97 and HR=0.86; 95% CI 0.79, 0.94 for each one s.d. increase in total and free testosterone respectively). These associations were maintained after adjustment for age and waist:hip ratio but did not persist after adjustment for prevalent IHD or other cardiovascular risk factors. SHBG was not associated with IHD events. In contrast, higher LH levels were associated with reduced event-free survival in both univariate (HR=1.15; 95% CI 1.08, 1.22) and adjusted analyses (HR=1.08; 95% CI 1.01, 1.15).

Conclusions: Dysregulation of the hypothalamic-pituitary-gonadal axis may be a risk factor for IHD. Further studies of men with either elevated LH or low testosterone are warranted.