Associations of Endogenous Estradiol and Testosterone Levels With Plaque Composition and Risk of Stroke in Subjects With Carotid Atherosclerosis

Abstract

TE was associated with presence of vulnerable carotid plaque as well as increased risk of stroke in women, whereas no consistent associations were found for TT in either sex.

Sex Differences in Sex Hormones, Carotid Atherosclerosis, and Stroke

“…In this issue, Glisic et al 3 examine the relationship of endogenous sex hormone levels and carotid plaque composition, as well as incident stroke, in >2100 older men and women in the Rotterdam Study. Notably, presence of carotid atherosclerosis (carotid intimal-medial thickness of >2.0 mm on carotid screening) was more common among men than women in the study.…”

“…No relationship was observed for total testosterone and carotid plaque composition features in men. 3 Endogenous hormones were also related to incident stroke in women. Among women with carotid plaque, those with detectable total estradiol levels had a nearly 2-fold increased risk of stroke during a median follow-up of 10 years.…”

“…No association between total estradiol and risk of stroke was noted in men, and no associations were observed for total testosterone with incident stroke in either men or women. 3 Notable strengths of the study include a well-characterized, cohort-based, population study; use of magnetic resonance imaging for analysis of carotid plaque composition; and exclusion of exogenous hormone therapy users. Although testosterone levels were measured via chromatography-tandem mass spectroscopy, the gold standard, estradiol was measured by immunoassay, which has particularly low sensitivity in postmenopausal women and prevented the investigators from examining estradiol as a continuous variable in women.…”

“…Postmenopausal women have markedly lower estradiol and testosterone levels than men of roughly the same age. 3,4 After the cessation of estrogen production by the ovaries, estrogen biosynthesis takes place in peripheral tissues, especially adipose, through aromatase conversion of androgens in postmenopausal women. Although absolute levels of both estradiol and testosterone are lower in postmenopausal women than men, the estradiol to testosterone ratio is >6-fold higher in women than in men.…”

“…4 In addition to the association with atherosclerotic features, higher endogenous estrogens may also contributed to thrombotic risk through association with lower levels of the natural anticoagulant protein S antigen. 8 Glisic et al 3 add to this body of evidence by showing that higher estradiol levels are associated with high-risk carotid plaque features, as well as a 2-fold increased risk of stroke in women with established carotid atherosclerosis.…”