Higher levels of sex hormone-binding globulin were associated with androgen deficiency in men, independent of total testosterone level, researchers in Italy reported.

“The first-line assessment for the evaluation of gonadal status in men with features of androgen deficiency is total testosterone, as indicated by all current guidelines and recommendations,” Mario Maggi, MD, of the department of experimental, clinical and biomedical sciences at the University of Florence, and colleagues reported. “However, they all report that [total testosterone] could provide misleading information in conditions known to alter SHBG.”

The researchers performed a cross-sectional observational study of 2,622 men who were treated at an outpatient clinic for sexual dysfunction. All patients were interviewed using ANDROTEST, a 12-item screening test for hypogonadism in patients with sexual dysfunction. Researchers recorded biochemical and clinical biomarkers, and used higher ANDROTEST scores as a marker of more severe symptoms of hypogonadism. They also used prostate-specific antigen and hematocrit as surrogate markers of testosterone bioactivity.

Researchers observed a positive association between age and SHBG, whereas SHBG was negatively correlated with BMI (P < .0001). Total testosterone, however, was negatively correlated with both age and BMI (P < .0001).

SHBG was significantly associated with ANDROTEST score after the researchers adjusted for lifestyle and total testosterone (P < .0001), and higher SHBG was negatively associated with prostate-specific antigen as well as hematocrit (both P < .0001). Lower levels of SHBG were also associated with a poorer metabolic profile regardless of total testosterone level, the researchers wrote.

“This indicates that besides a hypogonadism due to an impaired [testosterone] production, a hypogonadism due to a lower biological activity of [testosterone] does exist,” the researchers wrote. “Hence, the evaluation of SHBG levels, together with [total testosterone], in men suspected to be hypogonadal, can provide useful information on their gonadal status.” – by Andy Pohamus