Objectives
To examine the association in older men between serum reproductive hormones and cardiovascular and diabetes risk; and to determine whether reproductive hormones predict the development of cardiovascular and diabetes risk.

Methods
1705 men aged 70 years and older from the Concord Health and Ageing in Men Project were assessed at baseline (2005-2007) and 2-year follow-up (2007-2009). At baseline, testosterone (TT), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) were measured by liquid chromatography-tandem mass spectrometry, and SHBG, LH, and FSH by immunoassay. Cardiovascular and diabetes risk were defined using the National Cholesterol Education Program Adult Treatment Panel III criteria.

Results
In cross-sectional baseline data, analyses revealed significant associations between TT, SHBG, DHT, and calculated free testosterone (cFT) and cardiovascular and diabetes risk. Compared to men in the highest TT quartile, men in the lowest quartile had an unadjusted odds ratio of 3.98 (95%CI: 2.70-5.86) for cardiovascular and diabetes risk. After adjusting for age, BMI, and smoking status, TT remained associated with an odds ratio of 2.47 (95%CI: 1.60-3.81). The findings for SHBG, DHT, and cFT were similar. Statistically significant linear trends (p<0.01) across quartiles for all these hormones were observed. However, in the longitudinal analyses, there were no consistent association between any study hormones and the development of cardiovascular and diabetes risk over the two-year follow-up period.

Conclusions
Low serum TT along with SHBG, DHT, and cFT were associated cross-sectionally with cardiovascular and diabetes risk in community-dwelling older men. However, there were no longitudinal associations. This suggests that testosterone and other reproductive hormones may only be biomarkers of cardiovascular and diabetes risk and are not causally related to new onset (or incidence) of cardiovascular and diabetes risk over time.