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Association between body fat distribution and androgen deficiency in middle-aged and elderly men in China

Abstract

The objective of the present study was to examine the association between body fat distribution and total testosterone (TT) and free testosterone (FT) levels among middle-aged and elderly men. A total of 922 male residents aged 40–70 years from a community in Shanghai, China, participated in the study. Their waist circumference (WC), waist-height ratio (WHtR), body mass index (BMI), and TT and FT concentrations were measured. Logistic regression models were used to estimate testosterone deficiency risk on the basis of anthropometric indices. BMI, WC and WHtR were all associated with TT deficiency. The participants in the highest quartiles of above-mentioned anthropometric indices had the highest risk of TT deficiency (BMI: odds ratio (OR)=4.40, 95% confidence interval (CI)=2.69–7.19; WC: OR=3.47, 95% CI=2.14–5.60; WHtR: OR=2.89, 95% CI=1.76–4.76). WC and WHtR were associated with FT deficiency. The participants in the highest quartiles had the highest risk of FT deficiency (WC: OR=1.87, 95% CI=1.18–2.97; WHtR: OR=1.67, 95% CI=1.04–2.66). The association between BMI and FT deficiency was not statistically significant (OR=1.21 for the highest quartile, 95% CI=0.78–1.87). Our study demonstrated that both general and abdominal obesity were associated with TT deficiency, whereas only abdominal obesity was found to be associated with FT deficiency.

Introduction

Androgens have important roles in sexual development and functions for both men and women. Testosterone is the most important androgen, as it is crucial for the development and maintenance of male sexual function.1 It was also reported to be associated with other health effects including decreased muscle mass and strength,2 diminished bone mineral density,3 hip fracture,4 impaired spatial cognition5 and coronary atherosclerosis,6 among many others.7, 8, 9

Three domains of testosterone can be measured, which are total testosterone (TT), free testosterone (FT) and bioavailable testosterone (BT). TT is present in the blood with the majority being specifically bound to sex hormone-binding globulin and non-specifically bound to albumin, and a small fraction remaining ‘free’. Free and albumin-bound testosterone are referred to as BT, which is available to the tissues for biological actions. Although BT is a good measure of androgenicity, the measurement of BT is more complex and labor intensive than TT and FT, and, therefore, is less used in epidemiological studies.

Most cross-sectional and several available longitudinal studies on influencing factors of testosterone level demonstrated a gradual linear age-related decrease in levels of FT, and to a lesser extent in TT, after the fourth decade.7, 9, 10, 11 Severe alcohol consumption was reported to be related to lower levels of TT and FT,7, 12, 13 whereas current smoking was found to be related to higher levels of TT and FT.14

Obesity is another factor that may be related to testosterone levels9, 15 in males. In the studies on the health effects of obesity, body fat distribution has been found to be related to a number of outcomes,16, 17, 18 with a pattern that abdominal obesity has higher risk than general obesity. However, evidences on the associations between body fat distribution and TT and FT levels were uncertain. Both general and abdominal obesity were reported to be associated with TT and FT levels in several studies, however, these findings were limited only in Caucasian population.15, 19, 20 Asian population generally has higher body fat percentage than do Caucasians of the same age, sex and body mass index (BMI),21 which may produce different effect on testosterone level from Caucasians. Therefore, in the present study, we examined the association of TT and FT with body fat distribution in 922 community dwelling men aged 40–70 years in China.

Subjects and Methods

Participants

This was a cross-sectional study of Chinese men recruited from a community in Shanghai, China. Those who were: (1) living in the community, (2) aged 40–70 years, (3) able to provide written informed consent and (4) without history of hypogonadism, or medication history of sex hormones or any other steroid compound were eligible for the present study. Residents’ registry system of the community was used to identify the potential participants. Eligible male residents were then invited by trained interviewers to participate in the study, and read an informed consent form before enrollment. The study was approved by the institutional review boards of all participating institutes and performed in accordance with the Declaration of Helsinki Principles.

In-person interview

Information on demographic characteristics and Aging Males’ Symptoms scale were collected through in-person interview. Demographic characteristics, including age, education, work status, smoking, alcohol consumption and history of diseases, were obtained by trained interview in an open room. Aging Males’ Symptoms scale, including psychological, somatic and sexual dimension, was conducted in a separate room.

Anthropometric measures

Height and weight were measured by calibrated scales in light clothing following standard procedure. WC was measured at the umbilical level22 with subjects standing and breathing normally. BMI was calculated as weight (kg) divided by height squared (m2). Waist–height ratio (WHtR) was calculated by dividing waist (cm) by height (cm).

Hormone measures

Fasting blood samples were drawn in the morning between 0800 and 0900 hours, and were stored at −70 °C until they were assayed by the clinical laboratory of Changhai Hospital in Shanghai, China. Both TT and FT were measured by a Chemiluminescence method (instruments and test agents were manufactured by the Beckmann Co., Bremen, German). The performance of TT and FT assay followed a standardization process to ensure that favorable results can be duplicated from a previous test. For TT, the intra- and interassay coefficients of variation varied from 1.1% to 4.3% and 1.5% to 7.8%, respectively. The intra- and interassay coefficients of variation of FT measurements ranged from 0.9% to 3.5% and 1.4% to 6.9%, respectively. The laboratory was accredited to ISO15189 with regard to sample collection, transport and test.

Statistical analyses

TT deficiency was defined as TT concentration ≤12 nmol/1 as recomended,23 which was close to 25th percentile of TT in our data. There is no universally accepted threshold for FT deficiency. We used 25th percentile (0.37 nmol 1−1) of the study population as the reference value for FT deficiency in the present paper.

We compared participant characteristics according to TT and FT categories by χ2 tests. Pearson correlations (r) were conducted among the anthropometric indices.

The risk of TT or FT deficiency was evaluated by quartiles of BMI, WC and WHtR. The 25th, 50th and 75th percentile were 22.92, 24.78 and 26.73 (kg m−2) for BMI, 82.00, 88.00 and 94.00 (cm) for WC and 0.48, 0.52 and 0.55 for WHtR. We used logistic regression models to compute odds ratios (ORs) and 95% confidence intervals (CIs) for both TT deficiency and FT deficiency after potential confounders were adjusted.

We also assessed the risks of TT and FT deficiency by combined general and abdominal ‘obesity’ after BMI, WC and WHtR were categorized by their 50th.

We repeated the above analysis among those with androgen deficiency symptoms (score ≥27),24 those aged more than 55 years or those with chronic diseases, in which the variation of testosterone concentration was divergent from the group as a whole.7, 18, 25, 26

As type 2 diabetes is associated with a moderately high prevalence of hypogonadism,27 and may influence testosterone levels through mechanisms other than body fat, we did a sensitivity analysis with type 2 diabetes added to the logistic regression models separately.

Data analyses were performed using SAS, version 8.1 (SAS Institute, Inc., Cary, NC, USA).

Results

The age of the subjects ranged from 40 to 70 years. The distributions of TT and FT deficiency according to demographic characteristics were shown in Table 1. Those aged 60–70 years had higher rate of FT deficiency compared with their younger counterpart. The percentages of FT and TT deficiency were similar across work status, smoking and alcohol drinking. Men with TT or FT deficiency were more likely to have a history of chronic diseases.

Table 1 Distribution of total testosterone and free testosterone deficiency by demographic characteristics

In the correlation analysis of anthropometric indices, BMI was moderately correlated with WC (r=0.42, P<0.01) and WHtR (r=0.43, P<0.01).WC was strongly correlated with WHtR (r=0.98, P<0.01).

Both general and abdominal obesity were associated with TT deficiency. Participants in the upper quartiles of BMI, WC and WHtR had a higher percentage of TT deficiency. Compared with the first quartile of BMI, ORs (95% CIs) of TT deficiency were 1.71 (1.02, 2.88) for the second, 2.43(1.47, 4.01) for the third and 4.40 (2.69, 7.19) for the fourth quartile after potential confounders including age, smoking, drinking, work status and chronic diseases were adjusted. The associations between TT deficiency with WC and WHtR showed the similar trend (Table 2).

Table 2 Odds ratios with 95% confidence intervals for total testosterone and free testosterone deficiency according to quartiles of anthropometric indices

Abdominal obesity as measured by WC and WHtR was associated with FT deficiency. Compared with the first quartile of WC, the ORs (95% CIs) of FT deficiency were 1.49 (0.93, 2.38) for the second, 1.47(0.93, 2.33) for the third, and 1.87(1.18, 2.97) for the fourth quartile after potential confounders were adjusted. The association between WHtR and FT deficiency was similar to WC, whereas the association between BMI and FT deficiency was not statistically significant (Table 2).

Risks of TT and FT deficiency by combined BMI and WC status were reported in Table 3. Those with higher BMI (>50th) had a statistically significant higher risk of TT deficiency regardless of their WC status (ORs were 2.08 and 2.71). Statistically significant higher risk of FT deficiency was only observed among those with both higher BMI (>50th) and higher WC (>50th; OR=1.53; 95% CI=1.07–2.19). The results were similar when replacing WC with WHtR (Table 3).

Table 3 Odds ratio with 95% confidence intervals for total testosterone and free testosterone deficiency according to combined general and abdominal obesity indexes

To test the sensitivity of associations between anthropometric indices and TT and FT deficiency, we conducted subgroup analysis among those with androgen deficiency symptoms, those aged more than 55 years and those with chronic disease, and obtained similar results. Similar associations were also observed when type 2 diabetes was added to the logistic regression models (data not shown).

Discussion

In this cross-sectional study of middle-aged and elderly men, we found general obesity as measured by BMI was associated with an increased risk of TT deficiency, whereas abdominal obesity as measured by WC or WHtR was associated with increased risks of both TT and FT deficiency. Although a stronger association with TT deficiency was found in BMI than WC and WHtR, the difference is small and likely not clinically consequential. In view of the above results about TT and FT, the abdominal obesity conferred overall greater risk of testosterone deficiency than general obesity. The results did not change in subgroup analysis.

Studies15, 19, 20 on anthropometric indices and fat distribution in Caucasian population showed both general and abdominal obesity were associated with TT and FT level. In our study, both general and abdominal obesity were associated with TT. Whereas only abdominal obesity was associated with FT. Most individuals with general obesity also have abdominal obesity. However, it is reported that some individuals, especially Asians, may have abdominal obesity without general obesity.28, 29 This may explain the disparity between general obesity and abdominal obesity in our study.

Multiple biologic mechanisms have been implicated in mediating the adverse health effects of excess adiposity. However, the exact pathways are unknown.30 An increased abdominal fat accumulation is largely caused by the accumulation of visceral fat. Visceral fat may be more sensitive to lipolysis, compared with subcutaneous fat, thereby preferentially increasing circulating free fatty acid levels.30 Other proposed mechanisms involve secretion of adipokines, which may differ by fat storage site.30

The study of Allan et al.20 showed that WHtR was a good predictor of FT, and WC was a good index for predicting FT if height was included in the same model. The study population of Allan’s was 55 years and older and with symptoms consistent with hypoandrogenism, which was comparable with our subgroup analysis in participants aged 55 years and older and those with androgen deficiency symptoms. However, we did not find stronger association between WHtR and FT than WC and FT. In our study, WHtR was very highly correlated to WC, which is true in other Asian population studies.31, 32 In other words, the contribution of height to WC is small, and therefore the predicting capacity of WHtR and WC is similar.

Our study has several strengths. The first was the large sample size, which raised the power of statistical analysis. Second, the population-based design ruled out the possible selection bias in hospital-based study. A further strength was blood samples, which were collected in a uniform manner, and the time period was restricted to 0800–0900 hours, as testosterone levels have a diurnal variation, with higher levels of TT and FT occurring in the morning.33

Certain limitations should be considered. One limitation of our study is the cross-sectional design, which constrains our ability to establish causality between fat distribution and testosterone. Another limitation is that chronic diseases may have affected men’s willingness to participate in the survey. We evaluated the effect of this potential bias using a subgroup analysis in subjects with chronic diseases, and obtained the same results as the whole population. In addition, we used Chemiluminescence method for the assay of TT and FT, which has been widely used in epidemiology studies.34, 35 This assay may provide a little less accurate measurement compared with Mass Spec, and lead to inaccurate classifications of TT and FT. However, the misclassifications are likely to be nondifferential, and the effect of such misclassification, if any, would have attenuated the observed association.

In conclusion, we found that higher measures of both general and abdominal adiposity confer a greater risk of TT deficiency in middle-aged and elderly men, regardless of the index chosen, and higher measures of abdominal adiposity confer greater risk of FT deficiency. The results need to be replicated in other Asian studies, especially in longitudinal studies.

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Acknowledgements

The project was supported by the Major Scientific Research Proposal of the Science and Technology Commission of Shanghai Municipality (grant number 09DJ1400400) and Shandong Provincial Education Department Scholarship for Domestic visiting scholar.

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Correspondence to Y Sun or M Miao.

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Ren, Y., Wang, B., Liu, X. et al. Association between body fat distribution and androgen deficiency in middle-aged and elderly men in China. Int J Impot Res 26, 116–119 (2014). https://doi.org/10.1038/ijir.2013.48

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Keywords

  • fat distribution
  • middle-aged and elderly men
  • testosterone

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