Validation of an Arabic ADAM questionnaire for androgen deficiency screening in the Arab community

Abstract

Background. It is well documented that testosterone levels decline with age, this decline is associated with symptoms which could be assessed denoting androgen deficiency. We investigated the validity of an Arabic version of the Saint Louis University androgen deficiency in ageing men (ADAM) questionnaire to screen for androgen deficiency in Saudi and non Saudi Arabic speaking men.

Methods. It was a cross sectional study of ambulatory community-based Arabic Saudi men recruited from Volunteers in Riyadh city, Capital of Saudi Arabia, aged 18–80 years. Seven hundred thirty men agreed to fill the Arabic ADAM questionnaire, they were invited to a morning blood sample for total testosterone and sex hormone binding globulin and those who agreed to complete the whole study were only 407 men. Low serum bioavailable testosterone (BT) levels (androgen deficiency) were defined as <10th percentile of serum BT levels in young healthy Saudi men (18–30 years).

Results. Cronbach's Alpha of 0.71 (n = 730) showed a good internal consistency of the Arabic ADAM questionnaire. Among participants, 18.2% and 77.6% had low serum BT levels and a positive ADAM questionnaire, respectively. The prevalence of positive ADAM and low serum BT is increasing with age. The Arabic ADAM questionnaire had a high sensitivity of 86.5%, a low specificity of 24.3%, and positive predictive values (+PVs) and negative (−PVs) of 20.3% and 89%, respectively.

Conclusion. The Arabic ADAM questionnaire has a very good sensitivity but very low specificity for screening of androgen deficiency in Saudi men, therefore biological confirmation is needed especially when clinical symptoms of androgen deficiency are present.

Keywords:

• Ageing males
• androgen deficiency
• testosterone level
• Arabic screening test
• ADAM

Introduction

Although it is well known that total testosterone (TT) levels decline by 1% to 2% annually in men starting at the age of 40 years, the clinical significance of this decline is still unknown [1]. Several cross-sectional [2–6] and longitudinal studies [7–9] have shown a decrease in testosterone levels with ageing in men. This finding has equally been observed in elderly men in good health. Ageing in males is accompanied by a series of signs and symptoms, reminiscent of androgen deficiency in young adults [10–15], such as decrease in muscle mass and strength, increase in abdominal, mainly visceral, fat with insulin resistance and atherogenic lipid profile, decrease in libido and sexual hair, osteopenia, decrease in cognitive performance, insomnia, excessive sweating and decrease in general well-being, and it is tempting to relate these symptoms to the age associated decrease in androgen levels.

Morley et al. [16,17] validated a 10-question screening questionnaire for androgen deficiency in ageing men (ADAM) in two studies of white men. This St. Louis University ADAM questionnaire contained questions covering areas on libido, energy, strength/endurance, height loss, enjoyment of life, sadness in mood, erectile dysfunction, sports performance, sleepiness after dinner, and work performance. Serum bioavailable testosterone (BT) levels were used as the biochemical gold standard in these studies [16,17], and mean serum BT, but not TT, levels were significantly lower in those who answered positively, when compared to those who answered negatively, in eight of the 10 questions [17]. In the first study, the Saint Louis University ADAM questionnaire had 88% sensitivity and 60% specificity in detecting androgen deficiency by the low serum BT level (<71 ng/dl) standard. In the second study, the sensitivity and specificity of this questionnaire were 97% and 30%, respectively.

To our knowledge and in the view of literature review, the ADAM questionnaire was not used before in Arabic language, we thought it would be helpful to test for and to have a validated Arabic form of this tool to be used in Arabic language populations for screening for androgen deficiency.

Subjects and methods

Translation and Back-Translation of the Arabic version of the ADAM Questionnaire.

ADAM questionnaire was translated from English into Arabic by a bilingual professional translator. The Arabic version's content validity was assessed and amendments were made as indicated. This draft of Arabic ADAM questionnaire was then back-translated to English independently by three bilingual professionals. The three back-translated English versions were then assessed and compared with the original English version. The final version of the Arabic ADAM questionnaire was administered to 14 Saudi men (mean age 54 ± 9.9 years) and then again within 10 days to assess the test–retest reliability.

Participants

The study was conducted in the city of Riyadh, Kingdom of Saudi Arabia. It was a cross sectional study of ambulatory community-based Saudi and non Saudi Arabic speaking men recruited from volunteers in King Khalid University Hospital, relatives of patients, men from a university-based family medicine clinic and men attending outpatient clinics for minor illnesses, i.e. sore through, common cold, abdominal colic, simple eye, or ear infection. The latter group constituted less than 3% of our sample. The inclusion criteria included Arabic ethnicity, living in the community, age between 18 and 80 years. The exclusion criteria included the presence of cancer; known hypogonadism, depression, heart or renal diseases and the use of sex hormone or medications that would impact erectile function or libido.

Study tools

All participants who fulfilled the inclusion and didn't fulfill exclusion criteria were invited to participate in the study. An interview questionnaire was administered by trained interviewers; It includes socio-demographic data (age, education, and marital status) in addition to the Arabic ADAM questionnaire. A positive Saint Louis ADAM questionnaire was defined as a positive answer to question 1, question 7, or to three of the other questions [16,17]. The Arabic tool was not self administered as some of the participants were unable to read and write.

Hormone measurements

An early morning non fasting blood sample was collected from all participants to control for diurnal variation in hormone level. Serum free and BT concentrations were obtained by the calculation based on the measured serum TT, sex hormone-binding globulin (SHBG), and albumin concentrations, and was done according to the method by Sodergard et al [18], this calculator was developed by the Hormonology Department, University Hospital of Ghent, Belgium [19]. Studies showed that there is excellent correlation between free testosterone calculated by this method and free testosterone concentration obtained by equilibrium dialysis [20]. Both serum TT and SHBG concentrations were measured on an automated immunoassay analyzer. Reagents were used according to the manufacturer's instructions and the analytical performance was within the manufacturer's specifications. The principle of measurement for serum TT was based on a solid-phase, competitive chemiluminescent enzyme immunoassay. The principle of measurement for SHBG was based on a solid-phase, two-site chemiluminescent immunometric assay. Serum albumin concentrations were measured on an automated analytical chemistry system, Modular Analytics (Roche Diagnostics, Mannheim, Germany), based on a colorimetric method using Bromocresol Green (BCG) dye binding. The reagent was used according to the manufacturer's instructions and the analytical performance was within the manufacturer's specifications. The 10th percentile of BT for men in the lowest age group (20–30) was used as the cut off point for androgen deficiency.

Statistical analysis

Cronbach scale reliability analyses was used to assess the internal consistency of the Arabic ADAM questionnaire on the whole sample (n = 730). The test–retest reliability of the Arabic ADAM questionnaire was analyzed by using the Pearson correlation coefficient of the two scores on 17 Saudi men, and the differences between the two scores were compared by the paired t test. The relationships of serum TT and BT levels with age were analyzed by using Pearson correlation analyses. Participants were classified into two groups by their serum BT levels into the low (<4.2 nmol/l) and non-low BT (>4.2 nmol/l) groups. The sensitivity, specificity, positive predictive value (+PV), and negative predictive value (−PV) of the Arabic version of the Saint Louis University ADAM questionnaire to detect men with low versus non-low BT levels was calculated. Similarly, the sensitivity, specificity, +PV, and −PV of each question in the Arabic ADAM questionnaire was calculated.

Results

Reliability of the Arabic ADAM questionnaire

Cronbach's Alpha of 0.71 (n = 730) showed a good internal consistency of the Arabic ADAM questionnaire. The test–retest reliability of the Arabic ADAM questionnaire (n = 17) was also good (Pearson correlation coefficient or r = 0.81, p < 0.001, two-tailed) with no significant difference between the test and retest ADAM scores (mean ± standard error of the mean 1.34 ± 0.36 vs. 1.4 ± 0.45; p = 0.33, paired t-test, two-tailed).

Characteristics of study participants

The 730 men who agreed to an interview during the study period (October 2008 through May 2009) were also invited for an early morning blood sampling. The conditional response rate for this group was 55%, with 407 men completing the full study. Table I illustrates the characteristics of the ambulatory community based Saudi men. Their mean age was 43.6 ± 14.9, and most of them (89%) were married. The proportion of men in the age groups; 20–30, 31–50, 51–70 and 71 and more years were 23.6%, 45.2%, 26.8% and 4.4%, respectively. Both serum BT and TT levels had negative correlations with age, yet the correlation with was very weak and non significant with TT (BT: r = −0.388, p = 0.00 and TT: r = −0.08, p = 0.889).

Table I.  Characteristics of the study sample.

Personal characteristics	N (730)	%
Age in years
20–30 years	165	22.5
31–50 years	332	45.6
51–70 years	196	26.9
≥71 years	37	5.0
Marital status
Married	650	89
Not married	80	11
Educational achievement
Primary or less	89	12.2
Preparatory	135	18.5
Secondary and higher	506	69.3

Among participants, 18.2% and 77.6% had low serum BT levels and a positive ADAM questionnaire, respectively. The prevalence of positive ADAM and low serum BT is increasing with age. An interesting figure was noticed in the age group 71 years and over where ADAM questionnaire was positive in 98.6% of the participants while serum BT level was low in almost 28% of the same age group (Table II). The Arabic ADAM questionnaire had a high sensitivity of 86.5%, a low specificity of 24.3%, and +PVs and −PVs of 20.3% and 89%, respectively (Table III). It appears from the same table that the tope five questions which had the highest sensitivity and −ve predictive values were questions number 2,3,7,8 and 1, respectively. Their specificity was satisfactory (39%–54.59%). Although questions numbers 4,6, and number 5 had the lowest sensitivity; 12.1%, 27.4% and 39.2%, respectively. The mean serum BT and not TT levels were significantly lower for those who gave positive answers in comparison with those who gave negative answers in six out of 10 questions i.e. 1,2,3,7,8,10.

Table II.  Prevalence of low serum bioavailable testosterone levels and positive Arabic ADAM questionnaire in Saudi men.

Age group, y (n = 407)	Low serum BT level %	Non-low serum BT level %	p	Positive ADAM questionnaire %	Negative ADAM questionnaire % (n = 730)	p
20–30 (96)	8.3	91.7		67.6	32.4 (165)
31–50 (184)	16.8	83.2		74.5	25.5 (332)
51–70 (109)	27.5	72.5		88.1	11.9 (196)
≥71 (18)	27.8	72.2	<0.001	98.6	1.4 (37)	<0.001

Table III.  Validity measures for Arabic ADAM questionnaire and its individual question in Saudi men.

Question	Sensitivity (%)	Specificity (%)	+PV (%)	−PV(%)
1. Do you have a decrease in libido (sex drive)?	66.2	54.5	24.4	87.9
2. Do you have a lack in energy?	71.2	43.2	21.8	87.1
3. Do you have a decrease in strength and/or endurance?	71.6	44.7	22.5	87.6
4. Have you lost height?	12.5	88	18.8	82
5. Have you noticed a decreased ‘enjoyment of life’?	39.2	61.4	18.6	81.8
6. Are you sad and/or grumpy?	27.4	70.8	17.4	81.3
7. Are your erections less strong?	70.3	39	20.4	85.5
8. Have you noted a recent deterioration in your ability to play sports?	70.8	42.9	21.2	87.2
9. Are you falling asleep after dinner?	50.7	53.2	19.3	83
10. Has there been a recent deterioration in your work performance?	55.4	57.7	22.5	85.3
Positive Arabic ADAM questionnaire	86.5	24.3	20.3	89

Discussion

Aging is a complex process. In males, from the fourth decade onwards the total serum testosterone (TT) levels are decreased, especially the serum levels of the so-called BT, whereas the serum levels of SHBG are increased. This androgen deficiency in males does not always cause symptoms. In symptomatic males a detailed history is required supported by screening questionnaires for androgen deficiency, followed by a clinical examination; the serum levels of T and SHBG should also be determined. In patients with normal serum levels of T and increased SHBG serum levels, free testosterone, obtained by calculation from the T and SHBG levels, is a reliable and simple index of BT to show the presence of androgen deficiency [21].

The present study was undertaken to validate an Arabic tool (ADAM questionnaire) for screening of androgen deficiency in Saudi community which is characterized by high percentage of marriage and multiple wives. Different studies conducted in many countries supported the fact that TT and BT are significantly and negatively correlated with age [22–24], the current study found a negative and significant correlation between age and BT, yet the correlation with TT was non significant and very weak.

Many cut-offs were used in multiple studies for detecting androgen deficiency depending on testosterone and bio-available testosterone concentration in their community and its frequency distribution in the younger age group. In our study, we used 4.2 nmol/l of biotestosterone (BT) as the cut-offs for androgen deficiency, which was equivalent to 10th percentile of BT level in the younger Saudi age group (20–30 years age). In the present study, we found the translated Arabic ADAM questionnaire had good content validity, internal consistency (as reflected by a Cronbach of 0.71), and test–retest reliability.

The Arabic ADAM questionnaire was found to have a high sensitivity (86.5%) to identify aging males with low free testosterone levels and very low specificity (24.3%); A low specificity was also detected with the original Saint Louis University ADAM questionnaire [16], and other studies [17,25,26]. The recent study conducted in Southern region of Santiago de Chile revealed that ADAM tool rendered a 83% sensitivity and only 19.7% specificity in the detection of partial androgen deficiency [27]. The top five questions with high sensitivity in the Arabic ADAM questionnaire (∼70%) to detect low BT levels were ‘lack in energy’, ‘decreased in strength’, ‘less strong erection’, ‘recent deterioration in ability to play sport’ and ‘decreased libido’. The same questions were found to have the highest validity, except for decreased ability to play sport, in the Chinese ADAM questionnaire [26]. The low specificity of the Arabic ADAM questionnaire could be explained by that, some symptoms included in the tool can be caused by depression and other diseases, apart from androgen deficiency in men [16,17,28]. This low specificity makes the ADAM questionnaire couldn't be used as a surrogate to serum free testosterone testing for detecting androgen deficiency in men. The prevalence of low serum BT level in age group 71 years and over is low (27.8%), this could be ascribed to the lower percent of study participants included in this age group (4.4%). Statistically significant differences in the mean serum BT levels were observed between those who gave positive answers and those who gave negative answers in six questions; these are; sex drive, lack in energy, decrease strength, less strong erection, decrease ability to play sport and deterioration in work performance. These findings agreed with the previous study [17], which showed significant differences in serum BT but not TT levels between the two groups in eight of 10 questions including the six questions in our present study, and with the Chinese study [26] in which ‘loss of height’ was significantly different instead of ‘decreased ability to play sport’ which was detected in our study. The difference between our study and the other studies might be related to some cultural differences between societies.

The recent consensus recommendations endorsed by the Internal Society of Andrology, International Society for the study of the Ageing Male, and European Assembly of Andrology didn't recommend for generalized population screening for androgen deficiency [29,30]. However, screening for hypogonadism would be useful in high risk patients i.e. patients with obesity, patients with HIV, patients with cardiovascular disease, and patients with long term corticosteroids, for monitoring testosterone therapy and planning and executing clinical trials of androgen replacement, particularly in our Arabic community and developing countries where an Arabic tool is strongly needed.

Some limitations of this study should be acknowledged. First, only 55% of the participants completed the blood sample survey. The second, is the number of study sample in the age group above 71 years which was very few (only 18 persons, 4.4%).

Conclusion

The Arabic ADAM questionnaire has a very good sensitivity, but because of its very low specificity; it may be used only as a screening tool for hypogonadism in our Arabic community in high risk patients, and not for general population, especially when clinical symptoms might indicate androgen deficiency, yet biological confirmation is essentially required. Further community based studies are strongly recommended to explain and to investigate the age-related changes of serum androgen levels in healthy Saudi Men.

Acknowledgements

This work was funded by the Princess Al-Johara Al-Ibrahim Cancer Research Center, Prostate cancer research unit, King Saud University, Riyadh, KSA.