Association between testosterone and serum soluble α-klotho in U.S. males: a cross-sectional study

Abstract

Purpose Testosterone plays a crucial role in males, and the deficiency of testosterone leads to multiple adverse health conditions. Klotho is a recently discovered protein encoded by antiaging gene klotho. Both the levels of testosterone and klotho change with aging, so the relationship between them is worth exploring. The purpose of this study was to investigate whether total testosterone is associated with serum klotho levels in U.S. males aged 40–79 years. Methods Included in this study were 3750 male participants from the 2011 to 2016 National Health and Nutrition Examination Survey, aged 40–79 years with included information on klotho and sex hormones. The sex steroid hormone levels and klotho concentrations were assayed in laboratories using the recommended methods according to Nutrition Examination Survey guidelines. The association between sex hormones and klotho was calculated using multivariate linear regression models after adjustment for several possible confounding variables. Results Among the 3750 participants, the total testosterone concentration was 399.048 ± 184.780 ng/dL, and the testosterone deficiency prevalence was 1160 (30.942%). The geometric mean of serum klotho levels was 791.000 pg/mL. In the adjusted models, klotho increased 0.165 pg/mL for every 1 ng/dL increase of total testosterone (p = 0.004). In addition, estradiol (β 2.232; 95% CI 0.588–3.876; p = 0.032) and sex hormone-binding globulin (β 2.013; 95% CI 1.173–2.583; p = 0.002) were also positively associated with klotho concentrations. Conclusion This study reported a significant association between klotho and sex hormones in the U.S. male population. The levels of klotho in men increased with total testosterone, estradiol and sex hormone-binding globulin levels, which may have implications for future research and clinical practice.

Sexually dimorphic renal expression of Klotho is directed by a kidney-specific distal enhancer responsive to HNF1b

“…Recent studies show no significant difference between the levels of soluble Klotho in the serum, 73 though high testosterone has also been associated with high soluble Klotho levels. 74 The disparities might be caused by different assays used to measure serum Klotho.…”

Association between anemia and serum Klotho in middle-aged and older adults

“…Furthermore, Our stratified analysis found that low levels of serum Klotho were associated with a higher risk of developing anemia more significantly in men and diabetic patients. A study using a sample of 3750 men aged 40-79 years in the USA found a positive correlation between total testosterone and S-Klotho levels [ 20 ]. The role of androgens in stimulating erythropoiesis has been well established since the 20th century, and the testosterone produced by the testes is the main circulating androgen in men.…”

Non-linear dilution adjustment of exemplary urine arsenic Part II: Sex- and Age-specific Differences

“…Serum levels of m-KL tend to be female-dominant throughout life, [54][55][56] while estrogen, testosterone, and sexual hormone binding protein (SHBG) were all positively correlated with serum m-KL also in men. 57 Besides, there is strong evidence for a mediating role of estrogen in the m-KLinduced inhibition of NaPT-II, causing enhanced excretion of PO4and iAsV. 58,59 Contrary results with age-associated increased %iAs and decreased %DMA in a smaller study population of an arseniasis-hyperendemic area in Taiwan suggest possible regional differences in the age-dependency of TWuAs composition.…”