Relationship Between Gonadal Function and Cardiometabolic Risk in Young Men With Chronic Spinal Cord Injury

Background

We reported previously that young men with chronic spinal cord injury (SCI) have a greater prevalence of testosterone deficiency compared with an age-matched, healthy control population. Young men with SCI also are at increased risk for developing cardiometabolic dysfunction after injury. It is unclear whether testosterone deficiency is associated with heightened cardiometabolic risk in men with SCI.

Objective

To investigate associations among levels of testosterone in young men with chronic SCI and surrogate markers of cardiometabolic risk.

Design

Secondary cross-sectional analysis.

Setting

Rehabilitation research centers in Washington, DC, and Miami, Florida.

Participants

Men (n = 58) aged 18-45 years with chronic (≥1 year), motor complete SCI without comorbidities or use of testosterone therapy.

Methods

Plasma concentrations of testosterone, lipids, inflammatory markers (C-reactive protein and interleukin-6), percent hemoglobin A1c, glucose, and insulin were measured in a fasting state using standard assays. A 2-hour oral glucose tolerance test and Framingham Risk Score were assessed for each subject. Body composition was assessed by dual X-ray absorptiometry scan.

Main Outcome Measurements

Surrogate markers of cardiometabolic risk among men based on the level of total testosterone (TT; ≤300, 301-500, or >500 ng/dL) and free testosterone (fT; ≤9 or >9 ng/dL). Comparisons were made between men with normal and low TT or fT.

Results

Framingham Risk Score was significantly greater in men with low fT (P < .05). Percent body fat (P < .05) and waist-to-hip ratio (P < .05) but not body mass index (P > .08), were greater in men with low TT or low fT. Men with low TT or low fT had lower high-density lipoprotein cholesterol levels (P < .05) without differences in fasting triglycerides (P > .1) or low-density lipoprotein cholesterol (P > .07). Men with low TT had greater levels of inflammatory markers C-reactive protein (P < .05) and interleukin-6 (P < .05). Men with low TT or low fT had greater fasting glucose (P < .05) and greater insulin resistance (P < .04), without differences in percent hemoglobin A1c (P > .8).

Conclusions

In young men with chronic SCI who undergo an accelerated aging process postinjury, hypogonadism is associated with an unfavorable cardiometabolic risk profile. Further research is needed to determine whether a causal relationship exists between hypogonadism and heightened cardiometabolic risk in men with SCI and whether routine screening for testosterone deficiency is warranted in this population.

Level of Evidence

IV