Comparison of screening questionnaires for the diagnosis of hypogonadism
Introduction
Serum testosterone levels decline with age in both cross-sectional [1], [2] and longitudinal studies [3], [4], [5], [6]. Because of the increase in sex hormone binding globulin with age, there is an even greater decline in the unbound hormone measured either as free testosterone [7], [8] or bioavailable testosterone (BT) [8], [9], [10], [11]. In some older men, serum testosterone concentrations decrease to levels below the accepted range of normal in young men and these older men are classified as hypogonadal.
Epidemiological studies have suggested that the age-related decline in testosterone is associated with a decline in libido [12], loss of muscle mass and strength [13], [14], [15], functional decline [16], and decrease in some cognitive abilities [17], [18], [19]. Intervention studies have reported that testosterone replacement may enhance libido [20], [21], improve lean body mass and increase muscle strength [22], [23], [24], [25], [26] and improve some aspects of cognition [27], [28], [29], [30].
Recent reviews and “consensus panel” reports have suggested that rather than depend purely on a statistically based biochemical definition of hypogonadism, the definition of hypogonadism should depend on both biochemical and functional criteria [1], [31], [32], [33], [34]. At present, however, because of age-related and disease-related symptoms, it is unclear which symptoms are most clearly related to hypogonadism as men age.
Three screening tests utilizing symptoms and/or epidemiological factors have been developed to detect hypogonadism [35], [36], [37]. Two of these tests have undergone some degree of validation [35], [36] and the ADAM questionnaire has undergone independent validation [37]. There is a clear need for a direct comparison of these three screening tests.
In this study, we have examined the relationship between the three screening tests and bioavailable testosterone (BT) as the biochemical “gold standard” for hypogonadism [38], [39], as well as other measures of serum androgens including the calculated free testosterone index (CFT) of Vermeulen et al. [39] and total testosterone.
Section snippets
Methods
One hundred and fourty eight males aged 23–80 years (mean 53.3 ± 1.1 years) were interviewed, filled out questionnaires and had blood obtained between 8 and 11 a.m. The St. Louis University ADAM questionnaire [35], the Massachusetts Male Aging Survey (MMAS) [36] and the Aging Male Survey (AMS) [37] were administered. In addition a series of questions were asked in a questionnaire format to be answered yes or no. The questions were: Do you have night sweats? Do you have hot flashes? Do you have
Results
Table 1 provides the sensitivity and specificity of the ADAM, MMAS and AMS for hypogonadism defined as a BT < 70 ng/dl. Both the ADAM and AMS had high sensitivity, viz. 97 and 83%, whereas the sensitivity for the MMAS was 60%. The specificity for ADAM was 30%, MMAS was 59% and AMS was 39%. For the ADAM-positive individuals, the mean BT was 92 ± 4 ng/dl and for the negative 147 ± 9 ng/dl (p < 0.0002). The CFT also distinguished between ADAM positive and ADAM negative (p < 0.01). (data not shown) Total
Discussion
This study suggests that the ADAM and AMS are superior to the MMAS as a screening tool for hypogonadism as they have high sensitivity. This is in keeping with the two previous validation studies for the ADAM [35], [40]. The specificity of these questionnaires is relatively low as has previously been seen with the ADAM. It is recognized that depression, as well as a number of symptoms commonly seen in older persons with disease states will confound the attempt to use a symptom questionnaire for
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