Abstract P084: Sex Differences In Testosterone On Interleukin-6 At Baseline And In Response To Mental Stress

Abstract

Introduction: Young and middle-aged women with ischemic heart disease are a high-risk group for morbidity and mortality particularly after a myocardial infarction (MI). This group exhibits higher concentrations of the inflammatory cytokine interleukin-6 (IL-6) at baseline and in response to mental stress compared to men. The reasons for these differences are unknown; however, sex hormones may play a role. While testosterone has been shown to have anti-inflammatory effects among men; the role of testosterone on inflammatory cytokines among women has been understudied, and no research has examined the influence of testosterone on IL-6 response to stress. Hypothesis: Among young and middle-aged patients with a recent MI, higher concentrations of testosterone have anti-inflammatory effects among men at baseline and in response to mental stress; but are associated with greater inflammation among women. Methods: We studied 269 patients 61 years old or younger who were hospitalized for a MI in the previous 8 months. We measured plasma IL-6 (pg/mL) before and 90 minutes after mental stress (speech task). Inflammatory response was defined as the difference between IL-6 levels 90-minutes post mental stress and resting values. Serum free testosterone (pg/mL) was measured before mental stress. Differences across sex and time were examined with mixed models for repeated measures after natural log-transformation of IL-6. Results: The mean age was 51 years (range: 26-61); 48% were women and 64% African American. Mean values of free testosterone among men and women were 12.6 pg/mL (range: 0.9-29.0) and 1.8 pg/mL (range: 0.3-15.6), respectively. After adjusting for demographic factors (age, race, income), lifestyle and medical history (BMI, hypertension, diabetes, depression) and medication use, the association of testosterone with the IL-6 response to stress differed by sex (p for testosterone-by-sex-by-time interaction = 0.06). Among men, higher levels of testosterone were associated with lower concentrations of IL-6 at rest (β = -0.04; p = <.0001), but was attenuated after stress (β = -0.001; p = 0.93). This change in slopes across time or inflammatory response for men was significant (p = <.0001). In contrast, among women, higher levels of testosterone tended to be associated with higher IL-6 at rest (β = 0.04; p = 0.07) and after stress (β = 0.04; p = 0.14), indicating no change between time points or inflammatory response to stress (p=0.75). Conclusions: Among young and middle-aged survivors of a recent MI, higher concentrations of free testosterone are associated with lower inflammation among men, but with an opposite trend of higher inflammation among women.