Cross-sectional association of endogenous steroid hormone, sex hormone-binding globulin, and precursor steroid levels with hemostatic factor levels in postmenopausal women.

Publication Type:

Journal Article


Journal of thrombosis and haemostasis : JTH (2016)


BACKGROUND: Oral use of exogenous estrogen/progestin alters hemostatic factor levels. The influence of endogenous hormones on these levels is incompletely characterized.

OBJECTIVES: Our study aimed to test whether, among postmenopausal women, high levels of estradiol (E2), estrone (E1), testosterone (T), dehydroepiandrosterone-sulfate (DHEAS), DHEA, and androstenedione, and low levels of sex hormone-binding globulin (SHBG), are positively associated with measures of thrombin generation (TG), normalized activated protein C sensitivity ratio (nAPCsr), and factor VII activity (FVIIc), and negatively associated with antithrombin activity (ATc) and total protein S antigen (PSAg).

METHODS: This Heart and Vascular Health study cross-sectional analysis included 131 postmenopausal women without a prior venous thrombosis who were not currently using hormone therapy. Adjusted mean differences in TG, nAPCsr, FVIIc, ATc, and PSAg levels associated with differences in hormone levels were estimated using multiple linear regression. We measured E2, E1, total T, DHEAS, DHEA, and androstenedione levels by mass spectrometry, SHBG levels by immunoassay, and calculated free T.

RESULTS: One pg/mL higher E1 levels were associated with 0.24% lower PSAg levels (p<.0001), and one ug/mL higher DHEAS levels with 40.8 nM lower TG peak values (p<.0001) and 140.7 nMxMin lower TG endogenous thrombin potential (ETP) (p<.0001). After multiple comparisons correction that declared statistical significance at p<0.00069, there was no significant evidence of other associations.

CONCLUSIONS: As hypothesized, higher E1 levels were associated with lower levels of the natural anticoagulant, PSAg. Contrary to hypotheses, higher DHEAS levels were associated with differences in TG peak and ETP that suggest less generation of thrombin. This article is protected by copyright. All rights reserved.