Diseases with sex-dependent expressions may have an etiology in prenatal sex hormone exposure, specifically prenatal androgens. This study examined the relationship between prenatal hormone exposure (as evidenced by the 2D4D ratio), with life stress as a potential moderator/mediator, and adult depressive and/or physical health symptoms. Participants were n = 137 undergraduates from diverse backgrounds. Results indicated a more masculine 2D4D ratio was associated with poorer health in males, but the 2D4D ratio seemed to have little explanatory power for female physical/mental health. In males, a lower ratio (i.e., more masculine) ratio was linked to clinical cutoff scores for depression, higher levels of life stress, and greater depression scores. In addition, the relationship was mediated by life stress, indicating the link between a more masculine ratio and depression was dependent on levels of life stress. The 2040 ratio was also moderated by life stress, such that at high levels of stress a more masculine ratio was associated with more physical symptoms. Overall, while life stress seemed to have the largest impact on physical and mental health for female participants, a more masculine ratio emerged as a risk factor for men, but was strongly governed by the context of reported stress levels. (C) 2017 Elsevier Ltd. All rights reserved.