Male Sexual Dysfunction Hypogonadal Symptoms Are Associated With Different Serum Testosterone Thresholds in Middle-aged and Elderly Men Ranjith Ramasamy, Nathan Wilken, Jason M. Scovell, Jason R. Kovac, and Larry I. Lipshultz OBJECTIVE
METHODS
RESULTS
CONCLUSION
To determine the association between hypogonadal symptoms and total serum testosterone levels in middle-aged and elderly men (aged >40 years), and to identify whether there exists a clear-cut discriminatory threshold of total testosterone below which the probability of hypogonadal symptoms increases. We retrospectively reviewed the charts of 360 men who presented to an outpatient men’s health clinic with a chief complaint of low testosterone. Sexual, psychological, and physical symptoms were evaluated using the androgen deficiency in the aging male (ADAM) questionnaire. Serum levels of total testosterone were collected on the same day on which men completed their ADAM questionnaires. We performed the univariate (t test, chi-square, and binary logistic regression) and multivariate analyses (binary logistic regression) to evaluate the total testosterone threshold and the symptoms that predicted a low-testosterone level. A cluster of symptoms: 1 sexual (decreased libido), 1 psychological (decreased energy), and 3 physical (decreased strength or endurance, decreased ability to play sports, and falling asleep after dinner) were most associated with total serum testosterone levels of 300 ng/dL. The threshold testosterone serum levels that were associated with an increased prevalence of these hypogonadal symptoms ranged from 320 to 375 ng/dL. On multivariate analysis, age, but not symptoms on the ADAM questionnaire, predicted a total testosterone level of 300 ng/dL in our population. Our findings support our clinical experience that many men with serum testosterone levels between 300 and 400 ng/dL can still experience hypogonadal symptoms. Our finding that multiple symptom-specific testosterone thresholds exist supports earlier studies showing that different functional testosterone levels exist for various hypogonadal symptoms.6,7 A large general population of men aged between 40 and 79 years was evaluated in the European Male Aging Study.4 The European Male Aging Study identified erectile dysfunction as the most prevalent symptom in men with testosterone level 300 ng/dL) with age and ADAM questionnaire responses
Age Do you have decreased libido? Do you have a lack of energy? Do you have a decrease in strength or endurance? Have you noticed a decreased “enjoyment in life”? Are you sad and/or grumpy? Are your erections less strong? Has there been a recent deterioration in your work performance? Are you falling asleep after dinner? Have you noticed a recent deterioration in your ability to play sports? Have you lost height?
Odds Ratio
95% Confidence Interval
P Value
0.96 1.14 1.85 2.09 1.28 1.44 0.68 2.10 1.83 1.76 0.97
0.94-0.97 0.91-2.16 1.22-2.82 1.37-3.20 0.83-2.00 0.91-2.27 0.43-1.07 1.25-3.52 1.20-2.80 1.14-2.72 0.56-1.66
300 ng/dL) with age and ADAM questionnaire responses
Age Do you have a lack of energy? Do you have a decrease in strength or endurance? Has there been a recent deterioration in your work performance? Are you falling asleep after dinner? Have you noticed a recent deterioration in your ability to play sports?
Odds Ratio
95% Confidence Interval
P Value
0.95 1.22 1.70 1.12 1.46 0.90
0.93-0.98 0.65-2.30 0.90-3.24 0.56-2.26 0.85-2.50 0.47-1.70
300 ng/dL. Therefore, we suggest that although the symptom of erectile dysfunction may be a good indicator of low testosterone in community-dwelling men, it is a poor indicator for identifying low testosterone in men >40 years of age presenting to a men’s health clinic. This finding suggests that appropriate age and population-based questions need to be identified before treating hypogonadism. Previous studies analyzing the association between testosterone threshold and symptoms have varied findings. Wu et al4 found that only sexual symptoms are associated with testosterone levels. Contrast to these data, Lackner et al3 found that hypogonadal symptoms correlate with age rather than testosterone levels, and that on univariate analysis there was only a correlation between psychological symptoms and testosterone levels. In this study, no symptoms were predictive of low testosterone on multivariate analysis. Neither of these studies used the often-used ADAM questionnaire. In our study, on multivariate analysis no question on the ADAM questionnaire predicted a testosterone level 300 ng/dL. Importantly, increasing age was the only predictive factor for low-testosterone levels. These findings are not surprising given other clinical data. Although testosterone has been shown to be important in erectile function,2,4 age-related factors affecting vasculature are likely more important in age-related erectile dysfunction.8 The interesting finding that a positive mood predicted an increasing age has been shown in multiple studies outside the field of urology.9 Despite the associations that have been shown in UROLOGY 84 (6), 2014
other studies between hypogonadal symptoms and testosterone levels,4,6,7 our data suggest that the strength of these relationships at a cutoff of 300 ng/dL may be nondiagnostic. There exists a proportion of men with low “normal” serum testosterone levels >300 ng/dL who experience hypogonadal symptom suggesting that the commonly used cutoff of 300 ng/dL for biochemical hypogonadism may not be appropriate. Our study has both strengths and limitations. We minimized heterogeneity by surveying men as they were seen consecutively and by excluding men who had received androgenic anabolic steroids and TST in the previous 6 weeks. Men aged 40 years visiting a men’s health clinic, symptoms of decreased libido, decreased energy, decreased strength and endurance, decreased ability to play sports, and falling asleep after dinner were 1381
the conditions most frequently associated with low total serum testosterone levels. The threshold level of serum testosterone for these hypogonadal symptoms ranged from 320 to 375 ng/dL. Consequently, we propose the existence of unique thresholds at which hypogonadal symptoms become increasingly prevalent. Rather than using solitary predefined levels of serum testosterone (ie,
METHODS
RESULTS
CONCLUSION
To determine the association between hypogonadal symptoms and total serum testosterone levels in middle-aged and elderly men (aged >40 years), and to identify whether there exists a clear-cut discriminatory threshold of total testosterone below which the probability of hypogonadal symptoms increases. We retrospectively reviewed the charts of 360 men who presented to an outpatient men’s health clinic with a chief complaint of low testosterone. Sexual, psychological, and physical symptoms were evaluated using the androgen deficiency in the aging male (ADAM) questionnaire. Serum levels of total testosterone were collected on the same day on which men completed their ADAM questionnaires. We performed the univariate (t test, chi-square, and binary logistic regression) and multivariate analyses (binary logistic regression) to evaluate the total testosterone threshold and the symptoms that predicted a low-testosterone level. A cluster of symptoms: 1 sexual (decreased libido), 1 psychological (decreased energy), and 3 physical (decreased strength or endurance, decreased ability to play sports, and falling asleep after dinner) were most associated with total serum testosterone levels of 300 ng/dL. The threshold testosterone serum levels that were associated with an increased prevalence of these hypogonadal symptoms ranged from 320 to 375 ng/dL. On multivariate analysis, age, but not symptoms on the ADAM questionnaire, predicted a total testosterone level of 300 ng/dL in our population. Our findings support our clinical experience that many men with serum testosterone levels between 300 and 400 ng/dL can still experience hypogonadal symptoms. Our finding that multiple symptom-specific testosterone thresholds exist supports earlier studies showing that different functional testosterone levels exist for various hypogonadal symptoms.6,7 A large general population of men aged between 40 and 79 years was evaluated in the European Male Aging Study.4 The European Male Aging Study identified erectile dysfunction as the most prevalent symptom in men with testosterone level 300 ng/dL) with age and ADAM questionnaire responses
Age Do you have decreased libido? Do you have a lack of energy? Do you have a decrease in strength or endurance? Have you noticed a decreased “enjoyment in life”? Are you sad and/or grumpy? Are your erections less strong? Has there been a recent deterioration in your work performance? Are you falling asleep after dinner? Have you noticed a recent deterioration in your ability to play sports? Have you lost height?
Odds Ratio
95% Confidence Interval
P Value
0.96 1.14 1.85 2.09 1.28 1.44 0.68 2.10 1.83 1.76 0.97
0.94-0.97 0.91-2.16 1.22-2.82 1.37-3.20 0.83-2.00 0.91-2.27 0.43-1.07 1.25-3.52 1.20-2.80 1.14-2.72 0.56-1.66
300 ng/dL) with age and ADAM questionnaire responses
Age Do you have a lack of energy? Do you have a decrease in strength or endurance? Has there been a recent deterioration in your work performance? Are you falling asleep after dinner? Have you noticed a recent deterioration in your ability to play sports?
Odds Ratio
95% Confidence Interval
P Value
0.95 1.22 1.70 1.12 1.46 0.90
0.93-0.98 0.65-2.30 0.90-3.24 0.56-2.26 0.85-2.50 0.47-1.70
300 ng/dL. Therefore, we suggest that although the symptom of erectile dysfunction may be a good indicator of low testosterone in community-dwelling men, it is a poor indicator for identifying low testosterone in men >40 years of age presenting to a men’s health clinic. This finding suggests that appropriate age and population-based questions need to be identified before treating hypogonadism. Previous studies analyzing the association between testosterone threshold and symptoms have varied findings. Wu et al4 found that only sexual symptoms are associated with testosterone levels. Contrast to these data, Lackner et al3 found that hypogonadal symptoms correlate with age rather than testosterone levels, and that on univariate analysis there was only a correlation between psychological symptoms and testosterone levels. In this study, no symptoms were predictive of low testosterone on multivariate analysis. Neither of these studies used the often-used ADAM questionnaire. In our study, on multivariate analysis no question on the ADAM questionnaire predicted a testosterone level 300 ng/dL. Importantly, increasing age was the only predictive factor for low-testosterone levels. These findings are not surprising given other clinical data. Although testosterone has been shown to be important in erectile function,2,4 age-related factors affecting vasculature are likely more important in age-related erectile dysfunction.8 The interesting finding that a positive mood predicted an increasing age has been shown in multiple studies outside the field of urology.9 Despite the associations that have been shown in UROLOGY 84 (6), 2014
other studies between hypogonadal symptoms and testosterone levels,4,6,7 our data suggest that the strength of these relationships at a cutoff of 300 ng/dL may be nondiagnostic. There exists a proportion of men with low “normal” serum testosterone levels >300 ng/dL who experience hypogonadal symptom suggesting that the commonly used cutoff of 300 ng/dL for biochemical hypogonadism may not be appropriate. Our study has both strengths and limitations. We minimized heterogeneity by surveying men as they were seen consecutively and by excluding men who had received androgenic anabolic steroids and TST in the previous 6 weeks. Men aged 40 years visiting a men’s health clinic, symptoms of decreased libido, decreased energy, decreased strength and endurance, decreased ability to play sports, and falling asleep after dinner were 1381
the conditions most frequently associated with low total serum testosterone levels. The threshold level of serum testosterone for these hypogonadal symptoms ranged from 320 to 375 ng/dL. Consequently, we propose the existence of unique thresholds at which hypogonadal symptoms become increasingly prevalent. Rather than using solitary predefined levels of serum testosterone (ie,
