Sex hormones are influential in setting the tone of immune responses and estradiol exhibits a particularly strong influence that varies across the life cycle in women. Although largely anti-inflammatory and protective, estradiol can have divergent effects and the influence and availability of estradiol changes with aging, most notably with the menopause transition.  Furthermore, exposure to stressors can impact the functions of sex hormones.  Women living with HIV (WLH) may be more vulnerable to the effects of stress and trauma exposure on the interactions of stress hormones and sex hormones on inflammatory pathways due to the constant systemic challenge of living with HIV. The proposed studies will further our understanding of the biology of aging, and specifically the prognosis of WLH, and characterize the link between immunosenescence and endocrinesenescence. The planned research will define estrogen deficiency at both the systemic and receptor level and evaluate the extent to which global variation in these parameters predicts pro-inflammatory pathways in WLH.  We will conduct clinical interviews to assess trauma exposure and trauma-related hyperarousal to examine how these factors interact with HIV to exacerbate estrogen deficiency and inflammation.  Furthermore, we will characterize the influence of trauma exposure and estrogen receptor function on inflammation at molecular level in WLH. Overall, the data generated from this proposal will provide critical information about the influence of estradiol signaling in the inflammation in WLH.  Because trauma exposure and its related adverse mental health outcomes (i.e. posttraumatic stress disorder; PTSD) are poorly controlled in WLH, and PTSD has dangerous implications for HIV pathogenesis and transmission, it is of critical importance to identify the effects of trauma and PTSD comorbid with HIV in order to titrate the most effective treatment approaches for this complex comorbidity.