Association of Free Testosterone With Hypogonadal Symptoms in Men With Near-normal Total Testosterone Levels

Abstract

To investigate the association between hypogonadal symptoms and free testosterone (FT) levels in men with near-normal total testosterone (T) levels (250-350ng/dL) and to determine whether a discriminatory threshold for FT exists below which hypogonadal symptoms become more prevalent. We reviewed the charts of 3167 men who presented to an outpatient men's health clinic. Two hundred thirty-one men had symptoms of "low testosterone" and serum testosterone levels between 250 and 350ng/dL. We evaluated hypogonadal symptoms using the Androgen Deficiency in the Adult Male (ADAM) and quantitative ADAM (qADAM) questionnaires. Serum levels of T and sex hormone-binding globulin were collected on the same day that men completed their questionnaires. We used linear regression to determine whether a threshold of FT exists for hypogonadal symptoms. We performed univariate and multivariable analyses to evaluate factors that predicted a low FT level. The median age was 43.5years, and the median testosterone and FT levels were 303ng/dL and 6.3ng/dL, respectively. Prevalence and severity of hypogonadal symptoms (ADAM and qADAM) were similar between men with low (<6.4ng/mL) and normal FT levels. There was an association between age and 3 of the 10 hypogonadal symptoms (decreased enjoyment in life, sadness, and deterioration of work performance) with a low FT on a univariate analysis. Only younger age was positively associated with FT on multivariable analysis. We did not observe a relationship between hypogonadal symptoms and FT in men with near-normal testosterone levels. Symptom-specific FT thresholds could not be defined, as age remains an important confounder.