madman
Super Moderator
Abstract
INTRODUCTION AND OBJECTIVES:
Total testosterone (TT) measurement is widely used to diagnose male hypogonadism (MH). However, TT may be normal despite androgen deficiency when sex hormone-binding globulin (SHBG) is elevated, a condition often associated with ageing and chronic comorbidities. This study evaluated the prevalence and clinical determinants of men presenting normal TT but low calculated free testosterone (cFT), focusing on the influence of age-related SHBG elevation.METHODS:
A prospective study included 266 men with a diagnosis of ED, who were screened for MH. They underwent at least two simultaneous morning measurements of TT, SHBG and albumin, performed at least one week apart, allowing for the calculation of cFT using the Vermeulen formula. Low TT, low cFT, and elevated SHBG were defined as <345 ng/dL, <6.5 ng/dL, and >50 nmol/L, respectively. Patients presenting normal TT but low cFT were classified as having "false-negative TT." A ROC analysis was performed to assess the predictive ability of age for elevated SHBG.RESULTS:
Mean age was 59.4 + 10.1 years. Mean TT was 448 ÷ 190.8 ng/dL; 33.1% had low TT. Elevated SHBG and normal TT with low cFT were observed in 98 (38.6%) and 36 (13.5%) participants, respectively. Men with elevated SHBG and men with normal TT with low CFT were significantly older (p<0.001). In linear regression analysis, among all variables entered (age, hepatic disease, hyperthyroidism, anticonvulsant use, levothyroxine, HIV status, and smoking history), age was the only significant independent predictor of TT-cFT discordance (p<0.001). ROC analysis showed that age had a modest ability to predict TT-cFT discordance (AUC = 0.686). The optimal cut-off point was approximately 61 years (sensitivity of 67% and specificity of 62%). Prevalence of elevated SHBG was markedly higher among patients receiving anticonvulsant therapy (p = 0.004) and those with chronic liver disease (p = 0.006). Of all 36 patients with normal TT and low cFT, only 16.7% were smokers, 2.8% had HIV infection, and 8.3% had hepatic disease.CONCLUSIONS:
Normal TT do not reliably exclude MH in older men. Age-related increases in SHBG can conceal reduced FT, leading to false-negative biochemical findings. Incorporating SHBG measurement and CFT calculation into the initial diagnostic assessment of men aged ≥60 years may enhance diagnostic accuracy and reduce the underdiagnosis.
