Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Testosterone Is Associated with Erectile Dysfunction: A Cross-Sectional Study in Chinese Men

  • Ming Liao ,

    Contributed equally to this work with: Ming Liao, Xianghua Huang

    Affiliations Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China

  • Xianghua Huang ,

    Contributed equally to this work with: Ming Liao, Xianghua Huang

    Affiliations Urology Department, Guigang People’s Hospital, Guigang, Guangxi Zhuang Autonomous Region, People’s Republic of China, Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China

  • Yong Gao,

    Affiliations Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Fudan-VARI Center for Genetic Epidemiology, School of Life Science, Fudan University, Shanghai, People’s Republic of China

  • Aihua Tan,

    Affiliations Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Center for Metabolic Disease and Diabetes, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China

  • Zheng Lu,

    Affiliations Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China

  • Chunlei Wu,

    Affiliations Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China

  • Youjie Zhang,

    Affiliations Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China

  • Xiaobo Yang,

    Affiliations Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Department of Occupational Health and Environmental Health, School of Public Health of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China

  • Haiying Zhang,

    Affiliations Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Department of Occupational Health and Environmental Health, School of Public Health of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China

  • Xue Qin,

    Affiliations Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China

  • Zengnan Mo

    zengnanmo@hotmail.com

    Affiliations Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China

Testosterone Is Associated with Erectile Dysfunction: A Cross-Sectional Study in Chinese Men

  • Ming Liao, 
  • Xianghua Huang, 
  • Yong Gao, 
  • Aihua Tan, 
  • Zheng Lu, 
  • Chunlei Wu, 
  • Youjie Zhang, 
  • Xiaobo Yang, 
  • Haiying Zhang, 
  • Xue Qin
PLOS
x

Abstract

Background

Testosterone is essential for the regulation of erectile physiology, but the relationship between low testosterone and erectile dysfunction (ED) has not been firmly established.

Purpose

To examine the association between serum total, free and bio-available testosterone and ED in a population-based sample.

Methods

A consecutive series of 1776 men aged 20–77 participated in the routine physical examination from September 2009 to December 2009 in Guangxi, China. ED was assessed using the five-item International Index of Erectile Function (IIEF-5) questionnaire. Total testosterone (TT), sex hormone binding globulin (SHBG) and other biochemical profiles were measured. Free testosterone (FT) and bio-available testosterone (BT) were calculated based on Vermeulen’s formula. Data were collected with regard to smoking, alcoholic drinking, physical activity and metabolic syndrome.

Results

The prevalence of ED (IIEF-5<22) was 47.6%. Men with ED were significantly older, and more prone to smoke cigarettes (≥20 cigarettes/day) or drink alcohol (≥3 drinks/week), and more likely to have elevated blood pressure (P = 0.036) or hyperglycemia (P<0.001) compared with those without ED. The significant increase in SHBG with age was parallel to its increase with increasing severity of ED (P<0.001). The obscure increase in TT across the ED status was detected without significance (P = 0.418), but TT was positively associated with ED after adjustment for age [odds ratio (OR)  = 1.02, 95% CI (confidence internal): 1.00–1.04]. FT and BT were inversely associated with ED (OR = 0.14, 95%CI: 0.06–0.33; OR = 0.92 (95%CI: 0.89–0.96, respectively) in the univariate analysis, and this inverse association appeared to be independent of smoking status, alcoholic drinking, physical activity, hyper-triglyceridemia and hyperglycemia.

Conclusions

FT and BT are inversely related to worsening ED, whereas the positive association between TT and ED is most likely due to the increase in SHBG.

Introduction

Erectile dysfunction (ED) is a highly prevalent disorder among men all around the world [1][3], and possibly related to the rise in diabetes and vascular diseases [4]. Its incidence increases with age, and the ageing process in men is accompanied by a progressive decline in serum testosterone levels. Although testosterone deficiency is often found in patients presenting with ED alone, it is commonly not the principal cause [5]. Nevertheless, testosterone is increasingly considered in the clinical setting to treat ED [6], especially in those patients unresponsive to phosphodiesterase type 5 inhibitors, and often results in an improvement in sexual function [7]. Although there is some preliminary animal experimental evidence that testosterone is essential for the regulation of erectile physiology by multiple mechanisms [8], the causal relationship between low testosterone and ED has not been firmly established [5]. It is, therefore, important to further investigate the relationships between testosterone and erectile function, especially in a general population without the substantial biases inherent in patient samples.

Previously in a sample of Korean men with lower urinary tract symptoms [9], free testosterone (FT) was correlated with erectile function, consistent with the later study [10], but total testosterone (TT) was not correlated with any of the five domains of the international Index of Erectile Function (IIEF). In terms of other previous surveys, neither correlation between TT and ED risk nor with ED severity was demonstrated in studies of Brazil [11], [12], Turkey [13], [14] and Italy [15], though low TT was associated with sexual dysfunction more often in the oldest subjects [16]. With respect to bio-available testosterone (BT), it was correlated well with the erectile function assessed by IIEF-5 score in the sample of 130 outpatients from Japan [17]. And it was reported in the Olmsted County study, the age-related decline in sexual function was due to age-related declines in levels of BT rather than TT levels [18]. It is only fairly recently that testosterone threshold for the relationship between TT and ED has been found in European Male Ageing Study (EMAS) [5]. We conclude that the frustration to clarify the relationship between testosterone and ED in previous studies is probably due to the different provenances of studied population or the underpowered sample size. Moreover, to best of our knowledge, unhealthy lifestyles such as cigarette smoking, alcoholic drinking and physical activity [19], as well as the metabolic syndrome consisting of a myriad of abnormalities including central obesity, glucose intolerance, dyslipidemia, and hypertension [20] have been associated with ED, but few studies considered these factors. It is, therefore, in order to further evaluate the relationship between testosterone and ED with the consideration of these confounders of ED, that we conducted this cross-sectional study in a large series of Chinese men from general population.

Materials and Methods

Study Population

Our analyses are based on the Fangchenggang Area Male Health and Examination Survey (FAMHES), which was designed to investigate the effects of environmental and genetic factors and their interaction with the development of age-related chronic diseases [21][23]. Briefly, the FAMHES was a population-based study conducted among non-institutionalized Chinese men aging from 17 to 88 years old in Guangxi, China. A comprehensive demographic and health survey was conducted among a consecutive series of 4303 men participating in the routine physical examination at the Medical Centre in Fangchenggang First People’s Hospital from September 2009 to December 2009. A total of 3,593 people completed the data collection interviews. There were no significant differences between these people and those who did not complete the interviews. The response rate was 83.5% [23], and all the participants provided written informed consents. The survey received the approval from ethics committee in Guangxi Medical University.

In the current cross-sectional study, participants were excluded based on the following criteria: (1) currently diagnosed with myocardial infarction, congestive heart failure, stroke, hyperthyroidism, rheumatoid arthritis, acquired immune deficiency syndrome and any kind of cancer, or with a history of pelvic trauma/surgery or suffering significant urinary tract infection; (2) in current treatment with herbal remedies, or with medication including psychotropic drugs, non-steroidal anti-inflammatory drugs, antibiotics, spironolactone, cimetidine, glucocorticoids or other steroidal drugs which might affect the testosterone level or drugs with effect on erectile physiology, such as dopamine-antagonists, diuretics and so on; (3) men without regular sexual experiences during six months preceding completion of the International Index of Erectile Function (IIEF-5) questionnaire or men with absence of sex hormones measurements; (4) who drank beer, wine or hard liquor the day before serologic examination. A flow chart indicating the process of enrolling was showed in Figure 1. We finally enrolled 1,776 men aged 20–77 years in the present study.

thumbnail
Table 1. Characteristics of the analysis sample at baseline in FAMHES*.

https://doi.org/10.1371/journal.pone.0039234.t001

Data Collection

ED was defined using the IIEF-5, a self-administered and validated instrument widely used in both clinical and epidemiologic studies [24]. The five items assess erection confidence, erection firmness, maintenance ability, maintenance frequency, and satisfaction. Each item is scored on a 5-point ordinal scale where lower values represent poorer sexual function. The IIEF-5 score ranges between 5 and 25 with lower scores indicating increased severity of ED. ED status was classified into five categories as none (IIEF-5 score 22–25), mild (17–21), moderate (12–16), and severe (5–11). Additionally, ED was defined as a dichotomous variable using a cut-off point of IIEF-5<22 (mild, moderate, and severe). This approach is similar to the definition of ED used in the Boston Area Community Health (BACH) Survey [25].

A complete physical examination including the measurement of waist circumference and blood pressure (BP) was performed on each subject. Waist circumference was measured at the midpoint between the inferior costal margin and the superior border of iliac crest on midaxillary line. BP was measured twice after resting for more than 15 min, with the mercury sphygmomanometer by well-trained nurses, and the average values were taken. Metabolic syndrome was defined based upon the updated report of National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII criteria) for Asian Americans as having three or more of the following components: (1) waist circumference at least 90 cm, (2) triglycerides at least 1.7 mmol/L, (3) high-density lipoprotein cholesterol (HDL-C) less than 1.03 mmol/L, (4) BP at least 130/85 mm Hg, (5)fasting glucose at least 5.6 mmol/l [26]. Smoking status was defined as never smoker, former smoker (cessation of smoking >6 months) and current smoker (daily smoking >6 moths) [27]. Current smokers were further divided into two groups (<20 cigarettes/day and ≥20 cigarettes/day) [28]. Physical activities were measured by weekly total activities; men with regular exercise ≥2 h/week were considered physically active [29]. Alcoholic drinkers were defined as those who had ever consumed three or more drinks (beer, wine, and hard liquor) weekly and done so for six consecutive months [30].

thumbnail
Figure 3. Testosterone and SHBG levels across ages and ED status.

Panels A and B. Changes of TT, SHBG, FT, BT by each decade of age; Panels C and D. Association of TT, SHBG, FT, BT with ED status. P value is obtained by one-way analysis of variance (ANOVA). Student-Newman-Keuls test is used for multiple comparisons; asterisk in panels A and B stands for P<0.05 compared with the 20–30 yr age group, whereas in panels C and D stands for P<0.05 compared with the none-ED group. Dots represent median values of sex hormones, while bars represent the 25–75th percentiles. Abbreviations: ED, erectile dysfunction; SHBG, sex hormone-binding globulin; TT, total testosterone; FT, free testosterone; BT, bioavailable testosterone. Testosterone value.

https://doi.org/10.1371/journal.pone.0039234.g003

thumbnail
Table 2. Association between testosterone and ED in the multivariate regression analysis .

https://doi.org/10.1371/journal.pone.0039234.t002

thumbnail
Table 3. Subgroup analysis of association between ED and FT, BT in the univariate binary logistic models.

https://doi.org/10.1371/journal.pone.0039234.t003

Serum Assay

The description of the laboratory test has been previously reported in detail [21], [22]. Briefly, about 10 ml overnight fasting venous blood specimens were collected between 8∶00 and 11∶00 in the morning and were transported frozen to the testing center of Department of Clinical Laboratory at the First Affiliated Hospital of Guangxi Medical University in Nanning in two hours, which were centrifuged within 15 to 25 minutes and stored at −80C until analysis. Triglycerides, HDL-c, and serum glucose were measured enzymatically on a Dimension-RxL Chemistry Analyzer (Dade Behring, Newark, DE) in the Department of Clinical Laboratory at the Fangchenggang First People’s Hospital. Serum TT and sex hormone binding globulin (SHBG) were measured with electrochemiluminescence immunoassay on COBAS 6000 system E601(Elecsys module) immunoassay analyzer (Roche Diagnostics, GmbH, Mannheim, Germany) with the same batch of reagents, and the inter-assay coefficient of variation was 3.6% and 4.4%, respectively. BT and FT were calculated from a validated formula based on equilibrium-binding theory suggesting good agreement with laboratory assay [31], [32].

Statistical Analysis

All statistical analyses were performed using SPSS version 18.0 software (SPSS Inc., Chicago, IL, USA). The continuous variables were examined by Shapiro-Wilks test. Sex hormones including TT, FT, BT and SHBG, not conforming to a normal distribution, were logarithmically transformed in the following analysis, whereas the back-transformed values were reported. Categorical variables were presented with frequencies and proportions. Baseline characteristics were compared between cases (ED) and controls (non-ED) with Mann–Whitney u-test and χ2 test where appropriate. The sample was divided into four groups according to each decade of age: 20–30 (N = 540), 31–40 (N = 682), 41–50 (N = 346), ≥51–60 (N = 198). ED status was classified into four categories as none (N = 931), mild (N = 621), moderate (N = 169), and severe (N = 55). Changes of testosterone and SHBG levels across the four age groups or ED status were evaluated by one-way analysis of variance (ANOVA), thus Student-Newman-Keuls test was used for multiple comparisons. Correlations of age with sex hormones including TT, FT, BT and SHBG were examined via Spearman correlation analyses. When IIEF-5 score was used as a continuous variable to indicate the increased severity of ED, the linear regression models were used to assess the association between testosterone and IIEF-5. Analyses were repeated in the binary logistic regression models when ED was defined as a dichotomous variable using a cut-off point of IIEF-5<22. Both the linear regression and the binary logistic regression were constructed in unadjusted, age-adjusted and multivariate adjusted models. The multivariate adjusted model included the following covariates: age, smoking status, alcoholic drinking, physical activity, hypertriglyceridemia, hyperglycemia, elevated BP, low HDL-C and central obesity. Statistical tests were two-tailed, and a P value<0.05 was considered statistically significant.

Results

General Characteristics of the Studied Sample

Characteristics of the 1,776 men in our study were presented in Table 1. There were 47.6% of men with ED (IIEF-5<22). Between the ages of 20 and 77, the prevalence of mild ED increased from 28.7% to 42.3%, moderate ED increased from 6.5% to 24.2%, and severe ED increased from 1.7% to 10.1%. As showed in Figure 2, prevalence of ED increased with age.

The median age of ED group was 40 (Table 1). Men in ED group were significantly older than men in non-ED group (P<0.001). The proportion of men with smoking or drinking showed very little differences between ED group and non-ED group (P = 0.050, P = 0.018). The proportion of men with regular exercise ≥2 h/week did not show significant difference between ED group and non-ED group (P = 0.922). Regarding the components of metabolic syndrome, men with ED were more prone to have elevated BP (P = 0.036) and hyperglycemia (P<0.001).

Both FT and BT were inversely correlated with age (both r = −0.482, P<0.001). Although TT was inversely correlated with age as well (r = −0.169, P<0.001), its reduction across the age groups was relatively small in absolute terms (Figure 3). Both FT and BT gradually increased with advancing age (P<0.001), parallel to its decrease with increasing severity of ED (P<0.0 01). Similarly, SHBG gradually increased with advancing age (P<0.001), parallel to its increase with increasing severity of ED (P<0.0 01). However, the significant decrease of TT across the age (P<0.0 01) groups was not parallel with its obscure increase across the ED status (P = 0.418).

Association between Testosterone and ED

Table 2 presented the unadjusted, age-adjusted, and multivariate adjusted association between TT, FT, BT and ED. TT was inversely associated with IIEF-5 after adjusting for age [β = −0.05; 95% confidence interval (CI): −0.08, −0.03], and it was associated with a risk of ED in the age-adjusted model [odds ratio (OR)  = 1.02, 95% CI: 1.00–1.04]. After adjusting the following variables including smoking status, alcoholic drinking, physical activity, hypertriglyceridemia, hyperglycemia, elevated BP, low HDL-C and central obesity, the positive association between ED and TT remained significant.

FT and BT were positively associated with IIEF-5 scores (β = 3.81 and 95%CI: 2.29–5.34, β = 0.16 and 95%CI: 0.09–0.22, respectively), however, the positive associations were not statistically significant after adjusting for age (Table 3). In the unadjusted model of binary logistic regression analysis, FT was associated with ED with an OR of 0.14 (95%CI: 0.06–0.33), and BT was associated with ED with an OR of 0.92 (95%CI: 0.89–0.96). The inverse associations between FT, BT and ED were still observed in subgroup analysis (Table 3); however, in men with elevated BP, low HDL-C or central obesity, the association was detected without statistical significance.

Discussion

The present study in a large series of Chinese men from general population reveals that serum levels of FT and BT are decreased with age, whereas TT do not change much with age presumably because the SHBG increases as well. FT and BT are inversely related to worsening ED, whereas the positive association between TT and ED is most likely due to the increase in SHBG.

The ED prevalence of our studied sample was 47.6%, closed to the prevalence of 49.4% in the primary care setting [4], 52% in Massachusetts Male Aging Study (MMAS) [33] and 47% in BACH Survey [25]. The IIEF-5 instrument was previously used in China [34], and it was reported that among Chinese men above 40 the prevalence of ED was 40.2% [3]. Additionally, the BACH survey has demonstrated the contribution of modifiable lifestyle factors (physical activity, smoking, and alcohol consumption) to the prevalence of ED [25]. Consistent with the results from BACH [28], we have reported that heavy smokers (≥20 cigarettes/day) had a significantly increased risk of ED than never smokers [23], which had some implications in the present study. Moreover, previous studies have reported that current smokers, alcoholic drinkers had a higher level of FT, and physical activity was positively associated with FT [27], however, in the subgroup analysis of our study, the effect of these lifestyles did not attenuate the inverse association between ED and FT or BT. Similarly, the inverse association between ED and FT or BT appeared to be independent of hypertriglyceridemia and hyperglycemia, whereas in groups with elevated BP, low HDL-C or central obesity, it might be underpowered to detect the relatively small associations observed in other groups.

Concerning the changes of testosterone levels across age, FT or BT rather than TT appeared to be more correlated with age [9]. We explained that TT did not change much with age probably because SHBG went up with age [9], [18]. It has been reported that serum testosterone levels gradually fall with advancing age, whereas SHBG levels increase with age and present a rapid increase in the old [35], consistent with the current study. Along these lines, although FT and BT were decreased among the aged men, the unbound testosterone may have a high probability to combine with SHBG because the elevation of SHBG level showed an enhanced rate when these men got older. Thus the net result of these changes of unbound testosterone and SHBG is to present that TT did not change much with age. Moreover, TT levels in many aged men were very closed to those found in young healthy subjects [36], which might indirectly support this result from present study. Additionally, we observed that the increase of SHBG across ED status paralleled with its increase with age, thus the positive association of SHBG with ED might be a reflection of age. However, we observed that the association of TT with ED and its association with age showed a reverse direction, thus the positive association between TT and ED was probably due to the increase in SHBG.

It has been widely accepted that circulating testosterone is partly bound to SHBG with high affinity, so that testosterone levels are strongly related to SHBG concentrations [37]. In addition, genetic variants in the SHBG locus have been associated with a substantial variation in testosterone concentrations, and the SHBG polymorphism could affect testosterone binding to SHBG [38]. Although the association between TT and ED in the current study was independent of age, the possibility of SHBG interaction could not be ruled out. As shown in our study, both TT and SHBG were gradually increased across the ED status, although the increase in TT was relatively small in absolute terms. Moreover, it is critical to highlight that although the positive association between TT and ED remained statistically significant after adjusting the putative confounders, the magnitude of this association was modest.

Recently, the EMAS demonstrated that there was a testosterone threshold for the relationship between TT and ED [5], [39]. TT was associated with worse sexual functioning at concentrations of 8 nmol/l or less, whereas the relationship came to a plateau at TT levels over 8 nmol/l [5]. This finding was consistent with the evidence from the animal trials that androgen requirement for sexual behavior was less than the amount normally present [40], [41] Moreover, evidences from a meta-analysis also suggested that such a testosterone threshold on sexual function might exist in men [42]. Nevertheless, the EMAS group also suggested that the relationship between testosterone and sexual function might be different in older compared with younger men [5]. In this case, our study based on a relatively young population might emerge with some important values. We found FT or BT was inversely related to worsening ED in these patients, and suggested the threshold effect between TT and ED take into account the increase in SHBG.

Although the strength of the present study was characterized by its large sample size and its provenience from general population, some important limitations must be recognized. The cross-sectional nature of the study does not allow identifying the causality but only the associations. The FAMHES population was of southern Chinese Han ethnicity, thus the extrapolation to other ethnic groups should be done with caution. In addition, our studied sample was a very young population (for instance, compared to MMAS). Although IIEF-5 is a validated instrument for ED assessment widely used in both clinical and epidemiologic studies, the definition of ED according to an IIEF-5 score of <22 is blunt when considering Yes versus No statistics. It might result in extremely mild ED being considered a Yes, lumped together with very different and more debilitating ED of score 5. Nevertheless, it has been recently reported that men with mild ED have similar risk factors to a general ED clinical trial population [43]. Although previous study observed a higher prevalence of psychogenic ED in younger patients and organic ED in older patients [15], there were insufficient evidence identifying the putative prevalent component for ED in our study. Although there were no significant differences with respect to the ED prevalence between subjects who participated in the study and those who did not, not all the men responding to the questionnaire had voluntarily measured their sex hormones levels, so that selection bias might still exist because our response rate of hormones measurement was 67.6%. Although the mass spectrometry-based methods [e.g. gas chromatography-mass spectrometry (GC-MS)] with improved accuracy and precision in serum testosterone measurements has been recommended in studies of male sexual function [44], serum testosterone in the present study was measured with electrochemiluminescence immunoassay [31], [32]. TT levels were quite high in our population, and we have limited information on the causes of these unexpectedly high TT levels, which were probably due to other sexual behaviors rather than ED [42], such as increased frequency of autoeroticism or masturbation [45], and high prevalence of extramarital affairs [46].

This cross-sectional study was conducted in a large series of Chinese men from general population. Serum levels of FT and BT were decreased with age, whereas TT did not change much with age presumably due to the increase in SHBG. BT and FT were inversely related to worsening ED. The positive association between TT and ED is most likely due to the increase in SHBG, thus the threshold effect between TT and ED needs further investigation.

Acknowledgments

We express our sincere thanks to the local research teams from Fangchenggang First People’s Hospital, Fangchenggang, China, for their contribution to the survey.

Author Contributions

Conceived and designed the experiments: ZM ML XH. Performed the experiments: XQ ZL CW YZ ML. Analyzed the data: XY HZ ML. Contributed reagents/materials/analysis tools: YG AT. Wrote the paper: ZM ML XH.

References

  1. 1. Corona G, Lee DM, Forti G, O’Connor DB, Maggi M, et al. (2010) Age-related changes in general and sexual health in middle-aged and older men: results from the European Male Ageing Study (EMAS). J Sex Med 7: 1362–1380.G. CoronaDM LeeG. FortiDB O’ConnorM. Maggi2010Age-related changes in general and sexual health in middle-aged and older men: results from the European Male Ageing Study (EMAS).J Sex Med713621380
  2. 2. Golden SH, Robinson KA, Saldanha I, Anton B, Ladenson PW (2009) Clinical review: Prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive review. J Clin Endocrinol Metab 94: 1853–1878.SH GoldenKA RobinsonI. SaldanhaB. AntonPW Ladenson2009Clinical review: Prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive review.J Clin Endocrinol Metab9418531878
  3. 3. Bai Q, Xu QQ, Jiang H, Zhang WL, Wang XH, et al. (2004) Prevalence and risk factors of erectile dysfunction in three cities of China: a community-based study. Asian J Androl 6: 343–348.Q. BaiQQ XuH. JiangWL ZhangXH Wang2004Prevalence and risk factors of erectile dysfunction in three cities of China: a community-based study.Asian J Androl6343348
  4. 4. Grover SA, Lowensteyn I, Kaouache M, Marchand S, Coupal L, et al. (2006) The prevalence of erectile dysfunction in the primary care setting: importance of risk factors for diabetes and vascular disease. Arch Intern Med 166: 213–219.SA GroverI. LowensteynM. KaouacheS. MarchandL. Coupal2006The prevalence of erectile dysfunction in the primary care setting: importance of risk factors for diabetes and vascular disease.Arch Intern Med166213219
  5. 5. O’Connor DB, Lee DM, Corona G, Forti G, Tajar A, et al. (2011) The Relationships between Sex Hormones and Sexual Function in Middle-Aged and Older European Men. J Clin Endocrinol Metab 96: E1577–E1587.DB O’ConnorDM LeeG. CoronaG. FortiA. Tajar2011The Relationships between Sex Hormones and Sexual Function in Middle-Aged and Older European Men.J Clin Endocrinol Metab96E1577E1587
  6. 6. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, et al. (2010) Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 95: 2536–2559.S. BhasinGR CunninghamFJ HayesAM MatsumotoPJ Snyder2010Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline.J Clin Endocrinol Metab9525362559
  7. 7. Traish AM, Guay AT (2006) Are androgens critical for penile erections in humans? Examining the clinical and preclinical evidence. J Sex Med 3: 382–404; discussion 404–387. AM TraishAT Guay2006Are androgens critical for penile erections in humans? Examining the clinical and preclinical evidence.J Sex Med 3: 382–404; discussion 404–387
  8. 8. Traish AM, Goldstein I, Kim NN (2007) Testosterone and erectile function: from basic research to a new clinical paradigm for managing men with androgen insufficiency and erectile dysfunction. Eur Urol 52: 54–70.AM TraishI. GoldsteinNN Kim2007Testosterone and erectile function: from basic research to a new clinical paradigm for managing men with androgen insufficiency and erectile dysfunction.Eur Urol525470
  9. 9. Ahn HS, Park CM, Lee SW (2002) The clinical relevance of sex hormone levels and sexual activity in the ageing male. BJU Int 89: 526–530.HS AhnCM ParkSW Lee2002The clinical relevance of sex hormone levels and sexual activity in the ageing male.BJU Int89526530
  10. 10. Basar MM, Aydin G, Mert HC, Keles I, Caglayan O, et al. (2005) Relationship between serum sex steroids and Aging Male Symptoms score and International Index of Erectile Function. Urology 66: 597–601.MM BasarG. AydinHC MertI. KelesO. Caglayan2005Relationship between serum sex steroids and Aging Male Symptoms score and International Index of Erectile Function.Urology66597601
  11. 11. Rhoden EL, Teloken C, Sogari PR, Souto CA (2002) The relationship of serum testosterone to erectile function in normal aging men. J Urol 167: 1745–1748.EL RhodenC. TelokenPR SogariCA Souto2002The relationship of serum testosterone to erectile function in normal aging men.J Urol16717451748
  12. 12. Rhoden EL, Teloken C, Mafessoni R, Souto CA (2002) Is there any relation between serum levels of total testosterone and the severity of erectile dysfunction? Int J Impot Res 14: 167–171.EL RhodenC. TelokenR. MafessoniCA Souto2002Is there any relation between serum levels of total testosterone and the severity of erectile dysfunction?Int J Impot Res14167171
  13. 13. Muezzinogu T, Gumus B, Temeltas G, Ari Z, Buyuksu C (2007) A relationship of sex hormone levels and erectile dysfunction: which tests should be done routinely? Yonsei Med J 48: 1015–1019.T. MuezzinoguB. GumusG. TemeltasZ. AriC. Buyuksu2007A relationship of sex hormone levels and erectile dysfunction: which tests should be done routinely?Yonsei Med J4810151019
  14. 14. Kocoglu H, Alan C, Soydan H, Ates F, Adayener C, et al. (2011) Association between the androgen levels and erectile function, cognitive functions and hypogonadism symptoms in aging males. Aging Male 14: 207–212.H. KocogluC. AlanH. SoydanF. AtesC. Adayener2011Association between the androgen levels and erectile function, cognitive functions and hypogonadism symptoms in aging males.Aging Male14207212
  15. 15. Corona G, Mannucci E, Mansani R, Petrone L, Bartolini M, et al. (2004) Aging and pathogenesis of erectile dysfunction. Int J Impot Res 16: 395–402.G. CoronaE. MannucciR. MansaniL. PetroneM. Bartolini2004Aging and pathogenesis of erectile dysfunction.Int J Impot Res16395402
  16. 16. Corona G, Mannucci E, Ricca V, Lotti F, Boddi V, et al. (2009) The age-related decline of testosterone is associated with different specific symptoms and signs in patients with sexual dysfunction. Int J Androl 32: 720–728.G. CoronaE. MannucciV. RiccaF. LottiV. Boddi2009The age-related decline of testosterone is associated with different specific symptoms and signs in patients with sexual dysfunction.Int J Androl32720728
  17. 17. Tsujimura A, Matsumiya K, Matsuoka Y, Takahashi T, Koga M, et al. (2003) Bioavailable testosterone with age and erectile dysfunction. J Urol 170: 2345–2347.A. TsujimuraK. MatsumiyaY. MatsuokaT. TakahashiM. Koga2003Bioavailable testosterone with age and erectile dysfunction.J Urol17023452347
  18. 18. Gades NM, Jacobson DJ, McGree ME, St Sauver JL, Lieber MM, et al. (2008) The associations between serum sex hormones, erectile function, and sex drive: the Olmsted County Study of Urinary Symptoms and Health Status among Men. J Sex Med 5: 2209–2220.NM GadesDJ JacobsonME McGreeJL St SauverMM Lieber2008The associations between serum sex hormones, erectile function, and sex drive: the Olmsted County Study of Urinary Symptoms and Health Status among Men.J Sex Med522092220
  19. 19. Christensen BS, Gronbaek M, Pedersen BV, Graugaard C, Frisch M (2011) Associations of unhealthy lifestyle factors with sexual inactivity and sexual dysfunctions in Denmark. J Sex Med 8: 1903–1916.BS ChristensenM. GronbaekBV PedersenC. GraugaardM. Frisch2011Associations of unhealthy lifestyle factors with sexual inactivity and sexual dysfunctions in Denmark.J Sex Med819031916
  20. 20. Chughtai B, Lee RK, Te AE, Kaplan SA (2011) Metabolic syndrome and sexual dysfunction. Curr Opin Urol 21: 514–518.B. ChughtaiRK LeeAE TeSA Kaplan2011Metabolic syndrome and sexual dysfunction.Curr Opin Urol21514518
  21. 21. Lu Z, Gao Y, Tan A, Yang X, Zhang H, et al. (2012) Increased high-sensitivity c-reactive protein predicts a high risk of lower urinary tract symptoms in chinese male: Results from the fangchenggang area male health and examination survey. Prostate 72: 193–200.Z. LuY. GaoA. TanX. YangH. Zhang2012Increased high-sensitivity c-reactive protein predicts a high risk of lower urinary tract symptoms in chinese male: Results from the fangchenggang area male health and examination survey.Prostate72193200
  22. 22. Tan A, Gao Y, Yang X, Zhang H, Qin X, et al. (2011) Low serum osteocalcin level is a potential marker for metabolic syndrome: results from a Chinese male population survey. Metabolism 60: 1186–1192.A. TanY. GaoX. YangH. ZhangX. Qin2011Low serum osteocalcin level is a potential marker for metabolic syndrome: results from a Chinese male population survey.Metabolism6011861192
  23. 23. Wu C, Zhang H, Gao Y, Tan A, Yang X, et al. (2012) The Association of Smoking and Erectile Dysfunction: Results From the Fangchenggang Area Male Health and Examination Survey (FAMHES). J Androl 33: 59–65.C. WuH. ZhangY. GaoA. TanX. Yang2012The Association of Smoking and Erectile Dysfunction: Results From the Fangchenggang Area Male Health and Examination Survey (FAMHES).J Androl335965
  24. 24. Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Pena BM (1999) Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res 11: 319–326.RC RosenJC CappelleriMD SmithJ. LipskyBM Pena1999Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction.Int J Impot Res11319326
  25. 25. Kupelian V, Araujo AB, Chiu GR, Rosen RC, McKinlay JB (2010) Relative contributions of modifiable risk factors to erectile dysfunction: results from the Boston Area Community Health (BACH) Survey. Prev Med 50: 19–25.V. KupelianAB AraujoGR ChiuRC RosenJB McKinlay2010Relative contributions of modifiable risk factors to erectile dysfunction: results from the Boston Area Community Health (BACH) Survey.Prev Med501925
  26. 26. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, et al. (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112: 2735–2752.SM GrundyJI CleemanSR DanielsKA DonatoRH Eckel2005Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement.Circulation11227352752
  27. 27. Shiels MS, Rohrmann S, Menke A, Selvin E, Crespo CJ, et al. (2009) Association of cigarette smoking, alcohol consumption, and physical activity with sex steroid hormone levels in US men. Cancer Causes Control 20: 877–886.MS ShielsS. RohrmannA. MenkeE. SelvinCJ Crespo2009Association of cigarette smoking, alcohol consumption, and physical activity with sex steroid hormone levels in US men.Cancer Causes Control20877886
  28. 28. Kupelian V, Link C, McKinlay J (2007) Association between smoking, passive smoking, and erectile dysfunction: results from the Boston Area Community Health (BACH) Survey. Eur Urol 52: 416–422.V. KupelianC. LinkJ. McKinlay2007Association between smoking, passive smoking, and erectile dysfunction: results from the Boston Area Community Health (BACH) Survey.Eur Urol52416422
  29. 29. Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, et al. (2003) International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 35: 1381–1395.CL CraigAL MarshallM. SjostromAE BaumanML Booth2003International physical activity questionnaire: 12-country reliability and validity.Med Sci Sports Exerc3513811395
  30. 30. Lee AC, Ho LM, Yip AW, Fan S, Lam TH (2010) The effect of alcohol drinking on erectile dysfunction in Chinese men. Int J Impot Res 22: 272–278.AC LeeLM HoAW YipS. FanTH Lam2010The effect of alcohol drinking on erectile dysfunction in Chinese men.Int J Impot Res22272278
  31. 31. Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84: 3666–3672.A. VermeulenL. VerdonckJM Kaufman1999A critical evaluation of simple methods for the estimation of free testosterone in serum.J Clin Endocrinol Metab8436663672
  32. 32. Ly LP, Sartorius G, Hull L, Leung A, Swerdloff RS, et al. (2010) Accuracy of calculated free testosterone formulae in men. Clin Endocrinol (Oxf) 73: 382–388.LP LyG. SartoriusL. HullA. LeungRS Swerdloff2010Accuracy of calculated free testosterone formulae in men.Clin Endocrinol (Oxf)73382388
  33. 33. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB (1994) Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 151: 54–61.HA FeldmanI. GoldsteinDG HatzichristouRJ KraneJB McKinlay1994Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study.J Urol1515461
  34. 34. Hao ZY, Li HJ, Wang ZP, Xing JP, Hu WL, et al. (2011) The prevalence of erectile dysfunction and its relation to chronic prostatitis in Chinese men. J Androl 32: 496–501.ZY HaoHJ LiZP WangJP XingWL Hu2011The prevalence of erectile dysfunction and its relation to chronic prostatitis in Chinese men.J Androl32496501
  35. 35. Araujo AB, Esche GR, Kupelian V, O’Donnell AB, Travison TG, et al. (2007) Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab 92: 4241–4247.AB AraujoGR EscheV. KupelianAB O’DonnellTG Travison2007Prevalence of symptomatic androgen deficiency in men.J Clin Endocrinol Metab9242414247
  36. 36. Vermeulen A (1993) The male climacterium. Ann Med 25: 531–534.A. Vermeulen1993The male climacterium.Ann Med25531534
  37. 37. Gooren LJ (1996) The age-related decline of androgen levels in men: clinically significant? Br J Urol 78: 763–768.LJ Gooren1996The age-related decline of androgen levels in men: clinically significant?Br J Urol78763768
  38. 38. Ohlsson C, Wallaschofski H, Lunetta KL, Stolk L, Perry JR, et al. (2011) Genetic determinants of serum testosterone concentrations in men. PLoS Genet 7: e1002313.C. OhlssonH. WallaschofskiKL LunettaL. StolkJR Perry2011Genetic determinants of serum testosterone concentrations in men.PLoS Genet7e1002313
  39. 39. Wu F, Tajar A, Beynon J, Pye S, Silman A, et al. (2010) Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 363: 123–135.F. WuA. TajarJ. BeynonS. PyeA. Silman2010Identification of late-onset hypogonadism in middle-aged and elderly men.N Engl J Med363123135
  40. 40. Damassa DA, Smith ER, Tennent B, Davidson JM (1977) The relationship between circulating testosterone levels and male sexual behavior in rats. Horm Behav 8: 275–286.DA DamassaER SmithB. TennentJM Davidson1977The relationship between circulating testosterone levels and male sexual behavior in rats.Horm Behav8275286
  41. 41. Armagan A, Kim NN, Goldstein I, Traish AM (2006) Dose-response relationship between testosterone and erectile function: evidence for the existence of a critical threshold. J Androl 27: 517–526.A. ArmaganNN KimI. GoldsteinAM Traish2006Dose-response relationship between testosterone and erectile function: evidence for the existence of a critical threshold.J Androl27517526
  42. 42. Isidori AM, Giannetta E, Gianfrilli D, Greco EA, Bonifacio V, et al. (2005) Effects of testosterone on sexual function in men: results of a meta-analysis. Clin Endocrinol (Oxf) 63: 381–394.AM IsidoriE. GiannettaD. GianfrilliEA GrecoV. Bonifacio2005Effects of testosterone on sexual function in men: results of a meta-analysis.Clin Endocrinol (Oxf)63381394
  43. 43. Lee JC, Benard F, Carrier S, Talwar V, Defoy I (2011) Do men with mild erectile dysfunction have the same risk factors as the general erectile dysfunction clinical trial population? BJU Int 107: 956–960.JC LeeF. BenardS. CarrierV. TalwarI. Defoy2011Do men with mild erectile dysfunction have the same risk factors as the general erectile dysfunction clinical trial population?BJU Int107956960
  44. 44. Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H (2007) Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab 92: 405–413.W. RosnerRJ AuchusR. AzzizPM SlussH. Raff2007Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement.J Clin Endocrinol Metab92405413
  45. 45. Corona G, Ricca V, Boddi V, Bandini E, Lotti F, et al. (2010) Autoeroticism, mental health, and organic disturbances in patients with erectile dysfunction. J Sex Med 7: 182–191.G. CoronaV. RiccaV. BoddiE. BandiniF. Lotti2010Autoeroticism, mental health, and organic disturbances in patients with erectile dysfunction.J Sex Med7182191
  46. 46. Fisher AD, Corona G, Bandini E, Mannucci E, Lotti F, et al. (2009) Psychobiological correlates of extramarital affairs and differences between stable and occasional infidelity among men with sexual dysfunctions. J Sex Med 6: 866–875.AD FisherG. CoronaE. BandiniE. MannucciF. Lotti2009Psychobiological correlates of extramarital affairs and differences between stable and occasional infidelity among men with sexual dysfunctions.J Sex Med6866875