Testosterone levels have been related to carotid atherosclerosis but not stroke in women. Two cross-sectional population-based studies have shown lower prevalence of carotid atherosclerosis in postmenopausal women with higher testosterone levels. 9, 10 In the present study, higher testosterone levels were associated with reduced odds of intraplaque hemorrhage in women, but no association was noted for incident stroke. 3 Similarly, in a meta-analysis of the 2 prior studies of testosterone levels and risk of ischemic stroke, no association between testosterone levels and stroke in women was observed. 4 The timing hypothesis postulates differential effect and risk associated with estrogen exposure in women based on underlying subclinical atherosclerosis or time since menopause. The work by Glisic et al3 further strengthens these biological underpinnings, finding a nearly 2-fold increased risk of stroke for detectable estradiol levels among women with established carotid atherosclerosis, but a weaker, nonsignificant association for women without. This is consistent with biological studies showing that exogenous estrogen treatment in apolipoprotein E–deficient mice inhibited the development of early atherosclerosis including initiation of fatty plaques but did not inhibit intraplaque hemorrhage or progression of established lesions. 11 Time since menopause having a differential impact based on cardiovascular disease is generally less supported for stroke than for coronary heart disease. For exogenous estrogen use, Grodstein et al12 found no evidence of differences in the increased risk of stroke associated with postmenopausal hormone therapy based on time since menopause or age at initiation. Similarly, in the Women’s Health Initiative, initiation of hormone therapy within 10 years of menopause was associated with a 77% significantly increased risk of stroke, even though a reduced risk of coronary heart disease was observed in this group. 13 In men, testosterone levels decrease with age, and lower testosterone levels have been associated with several cardiovascular risk factors. 14 However, in cross-sectional analyses in the Atherosclerosis Risk in Communities Study, plasma testosterone levels were not associated with mean carotid intimal–medial thickness in men, 14 consistent with the lack of association for testosterone and carotid plaque features in the current study. 3 In contrast, several studies have observed an inverse relationship between testosterone levels and stroke in men. Among men aged≥ 70 years, higher testosterone levels were associated with reduced risk of stroke. 15 In the Copenhagen City Heart Study, low testosterone levels were associated with a 34% increased risk of ischemic stroke, which seemed to be partially mediated by obesity and hypertension. 4 In a meta-analysis of 4 studies examining sex hormones and ischemic stroke in men, 4 lower testosterone levels (< 10th percentile) were associated with increased risk of ischemic stroke (hazard ratio, 1.43; 95% confidence interval, 1.21–1.70), whereas no association was observed for estradiol levels. 3 In the current study, in contrast, no association of testosterone levels with incident stroke was observed for men with or without established carotid atherosclerosis. 3 Further research is needed to evaluate whether low testosterone levels are a risk marker or a true effector of risk. Sex differences in the association of endogenous hormones and carotid atherosclerosis and stroke may not be surprising, but further research is needed to understand how hormones differentially affect men and women. What are the intermediate biological mechanisms? How might risk be …