Emory University School of Medicine, Atlanta, GA, 30322, USA.
Pharmacology Department, Emory University, Atlanta, GA, 30322, USA.
J Endocrinol Invest. 2024 Mar;47(3):523-533. doi: 10.1007/s40618-023-02163-8. Epub 2023 Aug 30.
Klotho is a pleotropic hormone involved in a multitude of biological processes necessary for healthy aging, and affords protection from adverse events such as cardiovascular disease, inflammation, and various cancers. Emerging evidence suggests that klotho is also an important component of biochemical pathways that regulate hormone balance, which may include those pathways governing testosterone production and men's sexual health, though data are limited and results are mixed.
Using a cohort of 767 men from the NHANES 2015-2016 survey cycle, we set out to quantify the association between serum klotho levels and serum testosterone levels, as well as clinical markers of men's sexual health (e.g., testosterone:estrogen ratio, bioavailable testosterone, and free testosterone).
Multivariable linear and logistic regression models while controlling for potential confounders were constructed to quantify the relationship between serum klotho and testosterone, as well as between serum klotho and odds of low testosterone (serum testosterone < 300 ng/dL).
A positive association was observed between serum klotho and testosterone (β = 0.18, p = 0.04). Serum klotho levels were also stratified into quartiles, and we observed statistically significant increases in testosterone for increasing quartile level of klotho using the first quartile as the reference group (β = 90.51, p = 0.001, β = 106.93, p = 0.002, β = 95.33, p = 0.03 for quartiles 2, 3, and 4, respectively). The average testosterone values by quartiles of klotho were 306.9 ng/dL, 390 ng/dL, 409.3 ng/dL, and 436.6 ng/dL, respectively. We modeled important proxies for sexual health including bioavailable and free testosterone, the testosterone:estradiol ratio, and C-reactive protein. Men in the second quartile of klotho had a significantly lower odds of an abnormal testosterone:estradiol ratio compared to the first quartile [OR = 0.18, 95% CI = (0.03, 0.98)].We observed null associations between continuous serum klotho and odds of low testosterone [OR = 1.0, 95% CI = (1.0, 1.0)], and when stratified by quartile, we observed a significant decrease in the odds of low testosterone for individuals in the second quartile of klotho compared to the first quartile [OR = 0.21, 95% CI = (0.05, 0.91)]. In addition, C-reactive protein was inversely associated with testosterone in men (β = - 4.65, p = 0.001), and inversely associated with quartiles of klotho (β = - 2.28, p = 0.04, β = - 2.22, p = 0.04, β = - 2.28, p = 0.03, for quartiles 2, 3, and 4, respectively).
Our findings support previous studies suggesting a role for klotho in testosterone levels and sexual function among men. Future studies are warranted to corroborate these findings, determine clinical significance, and elucidate potential mechanisms underlying these associations.
Klotho 是一种多功能激素，参与许多对健康衰老至关重要的生物学过程，并能预防心血管疾病、炎症和各种癌症等不良事件。新出现的证据表明，klotho 也是调节激素平衡的生化途径的重要组成部分，其中可能包括调节睾丸激素产生和男性性健康的途径，尽管数据有限，结果喜忧参半。
我们使用来自 NHANES 2015-2016 调查周期的 767 名男性队列，旨在量化血清 klotho 水平与血清睾丸激素水平以及男性性健康的临床标志物（例如，睾丸激素：雌激素比值、生物可利用睾丸激素和游离睾丸激素）之间的关联。
构建了多变量线性和逻辑回归模型，同时控制了潜在的混杂因素，以量化血清 klotho 与睾丸激素之间以及血清 klotho 与低睾丸激素（血清睾丸激素<300ng/dL）之间的关系。
观察到血清 klotho 与睾丸激素之间存在正相关关系（β=0.18，p=0.04）。我们还将血清 klotho 水平分为四分之一，我们观察到 klotho 水平升高的四分位数与 klotho 水平升高的四分位数相比，睾丸激素水平显著升高（β=90.51，p=0.001，β=106.93，p=0.002，β=95.33，p=0.03） 分别为 2、3 和 4 分位数）。klotho 四分位数的平均睾丸激素值分别为 306.9ng/dL、390ng/dL、409.3ng/dL 和 436.6ng/dL。我们建立了重要的性健康代理指标，包括生物可利用和游离睾丸激素、睾丸激素：雌二醇比值和 C 反应蛋白。与第一四分位数相比，klotho 第二四分位数的男性异常睾丸激素：雌二醇比值的可能性显著降低[OR=0.18，95%CI=（0.03，0.98）]。我们观察到连续血清 klotho 与低睾丸激素的几率之间存在零关联[OR=1.0，95%CI=（1.0，1.0）]，并且当按四分位数分层时，与第一四分位数相比，klotho 的第二四分位数的男性低睾丸激素的几率显着降低[OR=0.21，95%CI=（0.05，0.91）]。此外，C 反应蛋白与男性睾丸激素呈负相关（β=-4.65，p=0.001），与 klotho 四分位数呈负相关（β=-2.28，p=0.04，β=-2.22，p=0.04，β=-2.28，p=0.03），分别为 2、3 和 4 分位数）。
我们的研究结果支持先前的研究表明 klotho 在男性睾丸激素水平和性功能中的作用。需要进一步的研究来证实这些发现，确定临床意义，并阐明这些关联背后的潜在机制。
