Liao PW, Wu CC, Chen KC, et al. testosterone Threshold for Increased Cardiovascular Risk in Middle-Aged and Elderly Men: A Locally Weighted Regression Analysis. J Sex Med. http://www.jsm.jsexmed.org/article/S1743-6095(16)30459-3/abstract INTRODUCTION: Although testosterone deficiency has a well-known association with increased risk of cardiovascular disease (CVD), the threshold remains to be determined. AIM: To investigate whether there is a discriminatory testosterone level below which the CVD risk increases. METHODS: The study included 876 men 45 to 74 years old who underwent a general health checkup. The Framingham Risk Score was used to estimate the 10-year CVD risk; a high-sensitivity C-reactive protein (hsCRP) level of at least 1 mg/L was considered an indicator of increased CVD risk. Aging symptoms and sexual function were evaluated with the Aging Males' Symptom Scale. MAIN OUTCOME MEASURES: Locally weighted regression was performed to determine the testosterone threshold for Framingham CVD risk and increased hsCRP. RESULTS: The mean age was 56.6 +/- 7.0 years. The mean total testosterone level was 394.3 +/- 115.7 ng/dL. The mean 10-year Framingham CVD risk was 16.6 +/- 10.7%, and 169 (19.3%) had increased hsCRP. The locally weighted regression showed that total testosterone levels of 440 and 480 ng/dL were associated with increased Framingham CVD risk and an increased probability of increased hsCRP, respectively. Men with sexual dysfunction (poor sexual performance, decreased morning erection, and loss of libido) had significantly greater CVD risk. Their risk appeared to increase at a relatively higher testosterone level, and it reached a plateau at a testosterone level of 300 to 350 ng/dL. In contrast, the risk in those with no or less sexual dysfunction remained low at a higher testosterone level, and a threshold level of 425 to 475 ng/dL was associated with increased CVD risk. A similar pattern and threshold were identified in the analyses of the relation between testosterone and hsCRP. CONCLUSION: These data showed that a testosterone threshold of 440 ng/dL was associated with increased Framingham 10-year CVD risk in middle-aged and elderly men. Poor sexual performance, decreased morning erection, and loss of libido had an impact on the testosterone threshold for CVD risk. The threshold level was higher in men with sexual dysfunction. Further study is required to evaluate the validity of these testosterone thresholds for CVD risk.