(068) Total Testosterone is Inversely Associated with C-reactive Protein Levels in Men: Findings from the Baltimore Longitudinal Study of Aging
Authors: Gurayah A , Weber A , Carto C , Ramasamy R 
Published: May 2023

Abstract

Introduction
Elevated C-Reactive Protein (CRP) and testosterone deficiency are associated with advanced age and chronic inflammatory diseases, such as cancer, obesity, diabetes, and cardiovascular disease. Further, serum CRP has proven to be a robust predictor of major adverse cardiovascular events. Testosterone decreases inflammation through several mechanisms, and testosterone replacement therapy (TRT) has been shown to consistently lower CRP levels in aging, hypogonadal men. While cross-sectional studies have shown an inverse relationship between CRP and total testosterone (TT) levels, mixed findings have been reported when individual components of metabolic syndrome and additional comorbidities are considered. Given that androgens have been implicated in anti-inflammatory pathways, we hypothesize that men with testosterone deficiency will have low CRP levels, independent of added comorbidities.

Objective
We evaluated the relationship between CRP and TT levels in men from 2004-2018 using the Baltimore Longitudinal Study of Aging.

Methods
Male participants with a documented serum TT level measured via mass spectroscopy during two separate visits &gt;3 years apart were included in our cohort. CRP, High-Density Lipoprotein (HDL), and Triglyceride levels were collected via blood specimens. Comorbidity data were documented for all participants at each follow-up visit. Patients with serum TT or CRP levels &gt;3 standard deviations from the mean of each respective variable were removed. Men with documented use of any form of TRT or a history of prostate cancer were excluded. Panel regression, a statistical technique implemented to analyze the relationship of a series of independent variables collected in pooled cross-sectional observations over time with a dependent variable, was used for univariable and multivariable modeling of CRP. P-value &lt; 0.05 was considered statistically significant.

Results
A total of 347 patients (694 visits) met the inclusion criteria of this study. The median age of our sample was 71 years with a follow-up time of 8 years (range: 3-13 years). Participants had a median CRP level of 1.03 mg/dL [0.52, 2.11] and a median TT level of 446 ng/dL [339, 560]. In terms of comorbidities, diabetes was documented most frequently, followed by congestive heart failure (CHF) and cancer (Table 1). On univariable analysis TT, cancer, and HDL were associated with a decline in CRP, while BMI, CHF, Diabetes, and Triglycerides were associated with increased CRP. Age was not associated with CRP (Table 2). On multivariable analysis, we found that increasing TT was associated with a decline in CRP levels, independent of comorbidities (p = 0.022; Table 2). The strengths of our study include having well-documented laboratory values and comorbidity information for patients at multiple visits. However, causal associations cannot be inferred due to the retrospective nature of the data.

Conclusions
We report that an increase in TT is associated with a decline in CRP levels, after controlling for components of metabolic syndrome and other related comorbidities. This finding is consistent with the anti-inflammatory effects of androgens, which decrease pro-inflammatory mediators and leukotriene biosynthesis. Our study further highlights the benefits of restoring eugonadal testosterone levels in older, hypogonadal men via hormone replacement, potentially lowering CRP levels and reducing cardiovascular risk.

Disclosure
No