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Correlations of androgen deficiency with clinical symptoms in Taiwanese males

Abstract

The purpose of this study was to elucidate correlations between different biochemical measurements of androgen deficiency and clinical symptoms in male residents of Taiwan. An investigation of the serum biochemical markers for androgen deficiency in 650 males, including total testosterone, calculated free testosterone, and bioavailable testosterone, was conducted. Measurements of clinical symptoms were obtained using a questionnaire of the androgen deficiency in the aging male (ADAM) by St Louis University (SLQ). Correlations among the biochemical markers, correlations of the biochemical markers and age, and relationships between the biochemical markers and the SLQ were evaluated. The sensitivity and specificity of the SLQ were determined. Bioavailable and calculated free testosterone correlated better with age than did total testosterone. Eighty percent of the men had a positive SLQ, and 20% had a negative SLQ. The percentage of positive SLQ results increased with age. No statistically significant difference was noted between the biochemical markers of bioavailable and calculated free testosterone levels and the SLQ status except for men aged over 70 years. The SLQ in this study showed an acceptable sensitivity of about 80%, but the specificity was poor (about 20%). In conclusion, bioavailable testosterone and calculated free testosterone were more-closely correlated with age and may be better biochemical markers for androgen deficiency. SLQ might not be a suitable single measurement for androgen deficiency and should be used together with biochemical markers.

Introduction

Testosterone (T) is the key hormone for maintaining male characteristics. Deficiency of this hormone in middle-aged and elderly men, or so-called aging males, may cause physiological changes such as decreased body hair, skin changes, and decreased lean body mass and muscle strength. It can also cause psychological symptoms, such as depression, cognitive changes, and mood instability. Most importantly, sexual symptoms, such as erectile dysfunction (ED) and decreased libido, are associated with testosterone deficiency.1, 2, 3 Several biochemical markers including free testosterone (FT), bioavailable testosterone (BT), and sex hormone-binding globulin (SHBG) have been developed in the past few years to detect androgen deficiency. Validation of these markers has been reported, but controversies with their efficacy still exist.4, 5

Moreover, noninvasive screening questionnaires have been developed to detect populations with possible androgen deficiencies. Among the questionnaires, the questionnaire of androgen deficiency of the aging male (ADAM) developed at St Louis University (SLQ) is the commonly used one.6 The validation of this questionnaire was reported, and results have been thought to be good enough such that it can be used as a screening tool for men with androgen deficiency.6 However, the correlations between clinical symptoms and biochemical test results were weak, and doubts remained about its efficacy in Western countries.7, 8

To clarify these doubts and to investigate the ADAM in the Taiwanese population, a cross-sectional study across the entire island of Taiwan was conducted. A survey for androgen deficiency and the correlations of a clinical screening questionnaire with various biochemical markers was undertaken.

Materials and methods

Subjects

A total of 749 males aged between 40 and 80 years participated in this study in August 2004 from five medical centers distributed from north to south in Taiwan. Equal numbers of rural and urban subjects were included. Subjects were all volunteers and informed consents were obtained. Men who currently have malignant diseases or liver cirrhosis, or who were using hormones, antiandrogen or antifungal agents, or steroidal agents were excluded from this study. Six hundred and fifty men were eligible for enrollment in this study. Although the activity was open to the general population, all of the study subjects were Taiwanese males.

Hormonal measurements

Blood samples were collected and the following measurements were made. Serum albumin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, total testosterone (TT), and sex hormone-binding globulin (SHBG) were checked. Serum albumin was analyzed with a Beckman CX-7 chemistry analyzer (Global Medical Instrumentation, Ramsey, MN, USA). LH, FSH, TT, and SHBG were determined with a DPC Immulite analyzer (Diamond Diagnostics, Holliston, MA, USA). Calculated free testosterone (cFT) and bioavailable testosterone (BT) were determined using the formula of the International Society for Study of the Aging Male (ISSAM), which is available on the web (www.issam.ch).

Questionnaires

Anthropometric information including body height, body weight, and body mass index (BMI) was obtained. Data on health behaviors and the subject's current medical condition were also collected. Clinical symptoms of androgen deficiency in the aging male (ADAM) were assessed using the SLQ of ADAM.6

Statistical analysis

Data were processed with SPSS 12.0 (SPSS, Chicago, IL, USA), and one-way ANOVA was used for correlation of the variables. Correlations of the biochemical markers and age were evaluated with a linear regression test. The sensitivity (the proportion of true positives) and specificity (the proportion of true negatives) were calculated using biochemical measurements as standards.

Results

A total of 650 men were included in this study and were stratified into four categories according to age. The hormonal status of the enrolled subjects is presented in Table 1. A declining trend was noted for the biochemical markers (TT, cFT, and BT) with age. However, TT did not correlate with age, but cFT and BT correlated well with age (Figure 1). The relationship between age and cFT was −0.330 (P<0.0001), between age and BT was −0.372 (P<0.0001), and between age and TT was 0.011 (P=0.782). Correlations among TT, cFT, and BT are shown in Figure 2. cFT and BT correlated well with TT (cFT vs TT, r=0.63, P<0.0001; BT vs TT r=0.62, P<0.0001). Moreover, cFT and BT correlated with each other best (r=0.98, P<0.0001).

Table 1 Mean biochemical markers of androgen stratified into 10-year ranges
Figure 1
figure1

Correlations between the biochemical markers, total testosteron (TT), calculated free testosterone (cFT) and bioavailable testosterone (BT) with age. cFT and BT were correlated with age.

Figure 2
figure2

Correlations among the three biochemical markers, cFT, and BT were well correlated with TT.

Androgen deficiency could be detected using the hormonal study, and 122 (19%) subjects had low TT levels (using a cutoff value of <11 nmol/l), 209 (32%) had low cFT levels (using a cutoff value of <0.23 nmol/l), and 159 (24%) had low BT levels (using a cutoff value of <5 nmol/l).1 The distribution of males with androgen deficiency was stratified into four categories by age (Table 2).

Table 2 Distributions of men with androgen deficiency in different age groups

There were 521 (80%) subjects with positive clinical symptoms of ADAM as surveyed by the SLQ and 129 (20%) with negative SLQ results. Trends of an increasing positive rate with increased age and a negative rate decreasing with age were noted (Table 3). The relationship between the SLQ and androgen deficiency is shown in Table 4. The SLQ could only be used to screen men with androgen deficiency aged over 70 years. No statistically significant difference was elucidated for the biochemical markers between men with positive and negative SLQ results.

Table 3 Distribution of ADAM questionnaire results stratified by age
Table 4 Correlations between biochemical markers of androgen deficiency and SLQ in 10-year ranges

The sensitivity of the SLQ in this study was 75.4% for TT, 81.5% for cFT, and 81.8% for BT, but the specificity was 18.6% for TT, 21.1% for cFT, and 20.2% for BT. According to SLQ questions 1 and 7, 55% of the men in this study had decreased libido and 61% had ED. We also found a trend of an increasing prevalence of these two symptoms with increasing age.

Discussion

This cross-sectional study enrolled 650 males aged between 40 and 80 years from different regions of Taiwan. As such, these data are representative of the current hormonal status of men living in Taiwan. The prevalence of androgen deficiency was 9–32% based on the biochemical measurements evaluated in this study. This result is comparable with previous studies in a group of men aged below 70 years, but is low for men aged over 70 years.9, 10, 11

Controversies still exist over the determination of ideal biochemical measurements for people with androgen deficiency. Serum TT is a less-expensive and simpler biochemical measurement for aging males with androgen deficiency. However, a poor correlation between TT and age has been reported,12 similar to that demonstrated in this study. cFT and BT are better parameters, but the procedure is time consuming and the costs are relatively higher.5, 12 However, Christ-Crain et al.13 reported no good correlations between BT and TT. We used all three of these parameters for the screening test to verify their correlations. In this study, the TT level did not correlate with age, but cFT and BT correlated better with age. However, TT showed good correlations with cFT and BT. Accordingly, cFT and BT correlated well with TT, and a correlation with age was also noted. In checking men with possible androgen deficiency, cFT and BT are better and more-reasonable biochemical markers, as was reported by Morley et al.6 and Tsujimura et al.12

The ADAM questionnaire of St Louis University had been used as a noninvasive screening tool to detect possible androgen deficiency in aging males. Morley et al.6 validated this questionnaire with BT, and they concluded that the SLQ showed high sensitivity, acceptable specificity, and good intrarater reliability. Since then, the questionnaire had been used to define symptoms of ADAM. However, Christ-Crain et al.13 reported that testosterone did not have a statistically significant correlation with the SLQ, although the study population they evaluated was small. In the present study, there was neither a statistically significant correlation between the biochemical parameters and SLQ except for men aged over 70 years. The SLQ may have its role in screening patients with symptoms of androgen deficiency, but it should not be the only tool used to survey men with these symptoms.

For questions 1 and 7 of the SLQ surveying sexual dysfunction, we found that 55% of middle-aged to elderly men in Taiwan have decreased libido, and 61% have ED. Trends of increasing prevalences of decreased libido and ED with age were also demonstrated. When comparing the status of ED and decreased libido, the biochemical markers did not differentiate men with or without symptoms except for men older than 70 years of age. The biochemical study results showed no correlations with androgen deficiency. These results support the fact that the etiology of ED and decreased libido are multifactorial and possibly not influenced by a single factor. Androgen deficiency as the main factor causing ED was only found in a small fraction of patients.14, 15, 16

Sensitivity of the SLQ has previously been validated by Morley et al.6 to be 88%, with a specificity of 60%. The sensitivity of the SLQ in this study was around 80% for the different biochemical markers, which is similar to the report by Morley et al.;18 however, the specificity was only around 20%. Furthermore, there were more enrolled subjects in this study and they were community-based, while in the previous study, subjects were confined to physicians. Our results may be more comprehensive and may suggest that the questionnaire should not be the sole tool used in screening for androgen deficiency.

The prevalence of androgen deficiency being similar in this study to studies conducted in Western countries might imply that no differences exist between races.6, 17, 18, 19 However, the lack of a correlation between androgen deficiency and the SLQ might be a racial factor, and further large surveys among different races should be carried out to elucidate this observation.

Conclusions

BT and cFT are better parameters than TT for detecting androgen deficiency. BT and cFT correlate well with TT, but the correlation is best between cFT and BT. No correlations between the SLQ and biochemical measurements were found except in men aged over 70 years of age. Biochemical testing cannot adequately reflect ED and decreased libido. The SLQ may not be a convincing single screening test for men with androgen deficiency, and biochemical measurements should be done simultaneously.

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Acknowledgements

This study was in part financially supported by the Taiwanese Association of Andrology.

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Correspondence to T I S Hwang.

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Lin, Y., Hwang, T., Chiang, H. et al. Correlations of androgen deficiency with clinical symptoms in Taiwanese males. Int J Impot Res 18, 343–347 (2006). https://doi.org/10.1038/sj.ijir.3901417

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Keywords

  • androgen deficiency
  • testosterone
  • bioavailable testosterone
  • calculated free testosterone

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