Predicting low testosterone in aging men: a systematic review

Abstract

Background: Physicians diagnose and treat suspected hypogonadism in older men by extrapolating from the defined clinical entity of hypogonadism found in younger men. We conducted a systematic review to estimate the accuracy of clinical symptoms and signs for predicting low testosterone among aging men.

Methods: We searched the MEDLINE and Embase databases (January 1966 to July 2014) for studies that compared clinical features with a measurement of serum testosterone in men. Three of the authors independently reviewed articles for inclusion, assessed quality and extracted data.

Results: Among 6053 articles identified, 40 met the inclusion criteria. The prevalence of low testosterone ranged between 2% and 77%. Threshold testosterone levels used for reference standards also varied substantially. The summary likelihood ratio associated with decreased libido was 1.6 (95% confidence interval [CI] 1.3-1.9), and the likelihood ratio for absence of this finding was 0.72 (95% CI 0.58-0.85). The likelihood ratio associated with the presence of erectile dysfunction was 1.5 (95% CI 1.3-1.8) and with absence of erectile dysfunction was 0.83 (95% CI 0.76-0.91). Of the multiple-item instruments, the ANDROTEST showed both the most favourable positive likelihood ratio (range 1.9-2.2) and the most favourable negative likelihood ratio (range 0.37-0.49).

Interpretation: We found weak correlation between signs, symptoms and testosterone levels, uncertainty about what threshold testosterone levels should be considered low for aging men and wide variation in estimated prevalence of the condition. It is therefore difficult to extrapolate the method of diagnosing pathologic hypogonadism in younger men to clinical decisions regarding age-related testosterone decline in aging men.

Figure 1:

Literature search and study selection. ADAM = Androgen Deficiency in Aging Males, AMS = Aging Males’ Symptoms, MMAS = Massachusetts Male Aging Study.

Figure 2:

Receiver operating characteristics of individual findings. The figure has a point for each of the individual reported sensitivities and specificities for the studies included in the review. Findings for combinations are plotted in greys and black, for sexual function in red and orange, for activities in greens, for mood in browns, for signs of low testosterone in blues and for body mass index in purple. The area of each circle is proportional to the sample size used to calculate the findings. The diagonal line shows where sensitivity equals the complement of specificity (i.e., 1 – specificity), which indicates that a clinical feature added little change to the diagnostic probability of low testosterone. The particular sign or symptom for any point can be located by referring to Figure 3, which uses the same colour coding. ADAM = Androgen Deficiency in Aging Males, AMS = Aging Males’ Symptoms, BMI = body mass index, MMAS = Massachusetts Male Aging Study, Sex fn = sexual function, T = testosterone.

Figure 3:

Display of kappa values for each study. For each finding, the square shows the estimated kappa value between the 2 dichotomous variables “low testosterone” and “positive sign or symptom”; horizontal lines show the 95% confidence intervals, and the area of each square is proportional to the estimated variance of the kappa value. Each sign or symptom is plotted in a different colour, with similar signs and symptoms sharing the same colour family (see Figure 2). ADAM = Androgen Deficiency in Aging Males, AMS = Aging Males’ Symptoms, BMI = body mass index, ED = erectile dysfunction, MMAS = Massachusetts Male Aging Study, T = testosterone.