Indicators of lifetime endogenous estrogen exposure and risk of venous thromboembolism

Abstract

See also Sandset PM. Hormone replacement therapy and risk of venous thromboembolism -still unresolved questions. This issue, pp 68-9.Grandone E, Margaglione M. New epidemiological risk factors for venous thromboembolism (VTE) after menopause. This issue, pp 70.Summary. Background: Lifetime estrogen exposure has been related to breast cancer risk, osteoporosis, and cardiovascular disease but data on venous thromboembolism (VTE) risk are limited. Methods: Data from a hospital-based casecontrol study among 608 postmenopausal women (191 with a first episode of idiopathic VTE and 417 age-matched controls) were used to determine whether estrogen exposure, as assessed by age at menopause [classified as early(£ 45 years), normal (46-54 years) and late menopause ( ‡ 55 years)] and parity, was associated with the risk of VTE. Results: After adjustment for potential confounding variables, the risk of VTE was increased with each year's delay in the menopause [odds ratio (OR) ¼ 1.06, 95% confidence interval (CI) ¼ 1.02-1.10, P < 0.0075]. When compared with women with normal menopause used as a reference, the adjusted OR for VTE was 0.59 (95% CI ¼ 0.36-0.97) and 2.53 (95% CI ¼ 1.28-4.99) for women with early menopause and late menopause, respectively (P ¼ 0.001). Adjusted OR for VTE was also higher for women with more than two children when compared with those with less than or equal to two children (1.56, 95% CI ¼ 1.03-2.34, P ¼ 0.03). The lowest risk of VTE was observed in women with early menopause and lower parity (adjusted OR ¼ 0.60, 95% CI ¼ 0.30-1.24), the highest risk was among women with late menopause who have had more than two children (adjusted OR ¼ 3.41, 95% CI ¼ 1.46-9.25). Conclusion: These results show that the longer exposure to endogenous estrogen is associated with an increased VTE risk.

Hormone Therapy and Venous Thromboembolism Among Postmenopausal Women

“…Norpregnane derivatives are more likely to be prescribed to women with hyperestrogenic symptoms. Because there is evidence that lifetime estrogen exposure is positively related to VTE risk in postmenopausal women, 39 such prescription bias could explain in part the high VTE risk among women using transdermal estrogen combined with norpregnane derivatives. Another limitation of our study is related to the small number of subjects within progestogen subgroups, especially among users of oral estrogen.…”

Vascular Actions of Estrogens: Functional Implications

“…Perhaps the most consistent risk for estrogenic treatment and venous thrombosis is factor V Leiden. However, individuals who do not carry the mutation may be at risk for a thrombotic event, whereas those who carry it may never experience an event (Price and Ridker, 1997;Herrington et al, 2002b;Miller et al, 2006;Simon et al, 2006). The formulation of the estrogenic treatment may also be critical for increasing risk even in individuals with this mutation, as incidence of venous thrombosis was less in individuals with factor V Leiden using transdermal compared with oral estrogenic products Straczek et al, 2005).…”

Are Some Types of Hormone Therapy Safer Than Others?

“…As the authors point out, norpregnane derivatives often are used for premenopausal women, those with hyperestrogenic symptoms, or those intolerant of estrogens; thus, prescription bias might partially explain the higher risk observed in this group because higher endogenous estrogens may be linked to VTE. 8 Transdermal users in ESTHER also were older and had a longer duration of hormone use than oral users. Bias also could have arisen in the selection of controls.…”