Association between endogenous sex steroid hormones and inflammatory biomarkers in US men.
The cardio protective effect of estrogen in women has come under scrutiny as recent evidence from long-term trials has demonstrated negative findings. In contrast, the effect of endogenous sex hormones, specifically estrogen, on cardiovascular disease, inflammation and clotting parameters in men has not been well-studied. Men receiving androgen deprivation therapy for prostate cancer provide a unique model to study the effect of estrogen alone on inflammation and clotting factors. In a short-term randomized controlled trial of 17-beta estradiol (E(2)) versus placebo, we measured sex hormones, markers of inflammation including homocysteine (HC), C-reactive protein (CRP), interleukin-6 (IL-6) and coagulation factors including fibrinogen, plasminogen activator-inhibitor-1 (PAI-1) and anti-thrombin-III (AT-III) in 27 older men without bone metastases receiving androgen deprivation therapy or neoadjuvant treatment for prostate cancer. After 9 weeks of E(2) treatment, there was no difference in inflammation or clotting parameters between groups, but after 9 weeks of treatment AT-III increased in the E(2) treated group and decreased in the placebo group. CRP, homocysteine and IL-6 did not show any significant differences. We also evaluated the above parameters in 12 men 3 weeks after acute steroid withdrawal with androgen deprivation therapy and found no significant changes. We found an increase in AT-III in men receiving E(2) which may be related to gonadal steroid withdrawal, but no significant differences in other inflammatory or clotting factor parameters. While the current report is very preliminary in a small group of subjects, further studies are needed to determine the long-term effects of E(2) in this population of hypogonadal men.