Abstract

INTRODUCTION AND OBJECTIVES: To investigate the association between hypogonadal symptoms and calculated free testosterone levels in men with near normal total testosterone levels (250 e 350ng/dL). We also attempted to determine whether there exists a clear-cut discriminatory threshold of free testosterone below which hypogonadal symptoms become more prevalent. METHODS: We retrospectively reviewed the charts of 3,167 men who presented to an outpatient men’s health clinic. Of these men, 231 men had a T value between 250 e 350 ng/dL with a chief complaint of “low testosterone”. Men using testosterone or other androgenic anabolic steroids (AAS) within 6 months of the time of the survey were excluded. We also excluded men who had presented with a primary diagnosis of infertility, Kleinfelter syndrome, or secondary hypogonadism after appropriate assessment of history and endocrine evaluation with gonadotropins. We evaluated hypogonadal symptoms using the Androgen deficiency in Aging Male (ADAM) questionnaire and quantitative ADAM questionnaire. Serum levels of total testosterone, sexhormone binding globulin (SHBG) were collected on the same day that men completed their questionnaires. FT levels were calculated using the Vermeulen formula. We used locally weighted linear regression to identify threshold levels of FT below which the probability of a symptom increased above the background prevalence in the overall study population. We subsequently performed univariate (t test, chi-square) and multivariate analyses (ordinal logistic regression) to evaluate factors that predicted a low free testosterone level. RESULTS: The mean age of the 231 men was 48.4 þ 16.2 y, and the mean T level and FT levels were 292 þ 36 ng/dL, and 6.7 þ 1.26 ng/dL respectively. Significant associations between free testosterone levels and a number of androgen deficiency symptoms were seen at FT levels of 5.0 e 7.0 ng/dL, but multiple logistic regression analysis revealed confounding effects with age. Of the 10 hypogonadal symptoms, the probability of having psychological (decreased energy and sadness) and physical (decreased strength, falling asleep after dinner and deterioration of work performance) symptoms was associated with FT on a univariate analysis. However, on multivariable analysis, only younger age correlated positively with higher FT. CONCLUSIONS: Hypogonadal symptoms in men with near normal total testosterone levels can be associated with a free testosterone level. Symptom-specific free testosterone thresholds could not be defined, as age remains an important confounder.

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