To address this knowledge gap and provide a more profound understanding of the relationship between visceral obesity and TD, we conducted this population-based study to investigate the correlation between WWI and TD, utilizing data from the National Health and Nutrition Examination Survey (NHANES). Was the first to propose a novel adiposity index called weight-adjusted-waist index (WWI), designed for assessing central obesity, with the formula WC/weight1/2. However, testosterone deficiency (TD) is an exceedingly common condition in males afflicting approximately 30% of men aged 40 to 79 years, whose incidence rose with aging and some prevalent medical conditions, such as obesity, diabetes, and hypertension . Maintaining normal testosterone levels is crucial for regulating a range of males’ physiological functions, including male reproduction and sexual functions, cardiovascular health, metabolic processes, and psychological cognitive functions 2–6. Nonetheless, its undesirable performance in distinguishing between lean and fat body masses as well as fat distribution has drawn increasing attention in the recent studies32,33.
Previous studies have explored the relationship between body mass index (BMI) and testosterone levels, indicating that obese individuals tend to have lower testosterone levels . This investigation firstly unveiled a negative linear association between WWI and total testosterone levels, coupled with a positive linear relationship with the prevalence of TD in U.S. male adults aged 20 years and older. Weighted multivariable linear regression and logistic regression analyses were employed to investigate the relationships between WWI and total testosterone levels, and the risk of TD, respectively. The correlation between the WWI and testosterone levels might be explained by the fact that the WWI is an obesity index and reflects abdominal fat mass28. Our study was in line with previous studies and revealed a negative relationship between the WWI and serum total testosterone levels and a positive relationship with testosterone deficiency, which remained robust after adjusting for other confounders. Esmaeili etal.23reported that the hip circumference, waist circumference, waist-to-hip ratio, and waist-to-height ratio were negatively related to serum testosterone levels.
Most cross-sectional and the several available longitudinal studies have demonstrated a gradual linear age-related decrease in levels of FT, and to a lesser extent in TT, after the fourth decade.12, 13, 27, 51, 52, 53, 54 Consistent with these previous findings, an inverse relationship between age and cFT levels was seen in our cohort and this also remained significant after adjusting for BMI, WC or WHt ratio. A causal association of ageing and adiposity with lower serum testosterone levels could involve changes at the level of the hypothalamus, pituitary or testes. The regression and standard coefficients for the univariate linear regression relationships of TT with age, BMI, WC, Ht, WHt ratio and SHBG are shown in Table 4. The regression and standard coefficients for the univariate linear regression relationships of cFT with age, BMI, WC, Ht and WHt ratio are shown in Table 3. The regression and standard coefficients for the univariate linear regression relationships of SHBG with age, BMI, WC, Ht and WHt ratio are shown in Table 2. Linear regression analysis was performed to assess the relationship of TT, cFT, SHBG and LH with age, BMI, WC, Ht and WHt ratio.
In this study, the data of a total of 29,902 participants from 2011–2012, 2013–2014, and 2015–2016 NHANES cycles were analyzed. Approved by the National Center for Health Statistics (NCHS) Research Ethics Review Board, NHANES were performed in accordance with the Declaration of Helsinki, and informed consents were signed by all the participants included in the survey. In addition to undesirable sexual symptoms, including decreased libido and erectile dysfunction, testosterone deficiency also increases the risk of developing osteoporosis, diabetes, metabolic syndrome, and cognitive decline, as well as cardiovascular and all-cause mortality7,8,9,10,11. Testosterone is a steroid hormone mainly produced by the Leydig cells and regulated by the hypothalamic‒pituitary‒gonadal axis, and it is the primary hormone involved in the development and maintenance of secondary male characteristics1,2,3.
The WWI may serve as a useful tool to screen out those who are at risk of developing testosterone deficiency. When the WWI was greater than 9.486 cm/√kg, the WWI and increased risk of developing testosterone deficiency were significantly positively correlated. Furthermore, the influence of potential confounders, including established hypogonadism status, spironolactone use, and dietary factors, cannot be entirely eliminated despite a number of pertinent confounders have been adjusted in this study. With the sample weights being considered, the results are representative and can generally be applied to the whole population of the United States. In the present study, the interactions of the WWI with the eGFR and hypertension status were significant. Waist circumference is better correlated with abdominal obesity, while it is highly correlated with BMI, and is limited in its ability to be used as a measurement independent of BMI17. Since it was first proposed in 1972, BMI has been a longstanding and widely used measurement for assessing obesity31.
Table 3 lists the subgroup analyses stratified by age, BMI, diabetes, and hypertension, considering WWI as a continuous variable. The mean age of participants was 46.74 ± 0.35 years, demonstrating a statistical increase with higher WWI quartiles. The study population was categorized into quartiles of WWI, denoted as Q1 (8.54–10.34 cm/√kg), Q2 (10.34–10.90 cm/√kg), Q3 (10.90–11.44 cm/√kg), and Q4 (11.44–12.96 cm/√kg). Similarly, details regarding the NHANES laboratory methodology for testosterone determination can be found on the official NHANES website.
A positive association between WWI and risk of TD was also identified in all three models. All subgroup analyses were performed in Model 2 with age, race, education, PIR, BMI, marital status, smoking, alcohol consumption, hypertension, and diabetes adjusted The positive relationship between the risk of TD and WWI quartiles remained stable in most subgroups, except for the BMI subgroup.
Ht was determined by a stadiometer calibrated to the nearest 0.1 cm and weight was measured on scales calibrated to 0.1 kg to calculate BMI (ratio of body weight in kg to height in m2).26 WC was measured, according to WHO guidelines, at the midpoint distance between the costal margin and iliac crest in the mid-axillary line on the dominant side.26 WHt ratio was calculated by dividing waist (cm) by height (cm). Subjects were also excluded if they had a BMI ≥35 kg m−2 because of the documented association of severe obesity with hypogonadotrophic hypogonadism.16, 17, 18 We investigated whether WC was a better predictor of testosterone than BMI in our cohort and, given increasing evidence of the value of indexing WC to height (Ht) as waist-to-height ratio (WHt ratio),19, 20, 21 we also examined the utility of WHt ratio for prediction of the testosterone level. We have examined the relationships of age, adiposity and testosterone levels in ageing men with symptoms consistent with hypoandrogenism but who were otherwise in good health. Additionally, we compared the strength of the associations between WWI, BMI, WC, and weight with total testosterone levels and the risk of TD, thereby enriching the data and expanding its clinical applicability. Firstly, this is the largest study to date and the first to investigate the relationship between WWI and both testosterone levels and the risk of TD. This may be because participants with higher BMI are more likely to engage in physical exercise and dietary control to reduce their weight, which can increase testosterone levels, thereby weakening the observed association. This study provides new ideas for future studies exploring the relationship between obesity and total testosterone level as well as TD.

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