Conventional-dose hormone therapy (HT) and tibolone, but not low-dose HT and raloxifene, increase markers of activated coagulation

Eilertsen, Anette Løken; Qvigstad, Erik; Andersen, Trine Opstad; Sandvik, Leiv; Sandset, Per Morten

doi:10.1016/j.maturitas.2006.04.012

Cited by 30 publications

(35 citation statements)

References 137 publications

(151 reference statements)

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“…The unavailable information on estrogens doses was also a limitation of our study. Although increasing doses of estrogens may increase the coagulation activation, 43 observational studies have suggested no significant difference in thrombotic risk by estrogen dose. 12,19,20,22,23 However, studies with high level of evidence comparing estrogen doses effect on thrombotic risk are still lacking.…”

Section: Canonico Et Almentioning

confidence: 99%

Postmenopausal Hormone Therapy and Risk of Idiopathic Venous Thromboembolism

Canonico

Fournier

Carcaillon

et al. 2010

ATVB

238

125

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Objective-Oral estrogen therapy increases venous thromboembolism risk among postmenopausal women. Although recent data showed transdermal estrogens may be safe with respect to thrombotic risk, the impact of the route of estrogen administration and concomitant progestogens is not fully established. Methods and Results-We used data from the E3N French prospective cohort of women born between 1925 and 1950 and biennially followed by questionnaires from 1990. Study population consisted of 80 308 postmenopausal women (average follow-up: 10.1 years) including 549 documented idiopathic first venous thromboembolism. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional models. Compared to never-users, past-users of hormone therapy had no increased thrombotic risk (HRϭ1.1; 95% CI: 0.8 to 1.5). Oral not transdermal estrogens were associated with increased thrombotic risk (HRϭ1.7; 95% CI: 1.1 to 2.8 and HRϭ1.1; 95% CI: 0.8 to 1.8; homogeneity: Pϭ0.01). The thrombotic risk significantly differed by concomitant progestogens type (homogeneity: PϽ0.01): there was no significant association with progesterone, pregnanes, and nortestosterones (HRϭ0.9; 95% CI: 0.6 to 1.5, HRϭ1.3; 95% CI: 0.9 to 2.0 and HRϭ1.4; 95% CI: 0.7 to 2.4). However, norpregnanes were associated with increased thrombotic risk (HRϭ1.8; 95% CI: 1.2 to 2.7). Conclusions-In this large study, we found that route of estrogen administration and concomitant progestogens type are 2 important determinants of thrombotic risk among postmenopausal women using hormone therapy. Transdermal estrogens alone or combined with progesterone might be safe with respect to thrombotic risk.

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Section: Canonico Et Almentioning

confidence: 99%

Postmenopausal Hormone Therapy and Risk of Idiopathic Venous Thromboembolism

Canonico

Fournier

Carcaillon

et al. 2010

ATVB

238

125

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“…Two studies consistently showed that tibolone would have the same or a less deleterious effect on F1+2 and DDimers than did CEE or E2 combined with NETA [55,56,[59][60][61]. By contrast, data were more controversial regarding the comparison of the effects of tibolone and estrogens combined with NETA on APCr.…”

Section: Tibolonementioning

confidence: 99%

“…By contrast, data were more controversial regarding the comparison of the effects of tibolone and estrogens combined with NETA on APCr. While tibolone might more induced APCr than did estradiol and estriol, it could have less effect on haemostasis than did CEE [55,[59][60][61]. With regards to other progestogens, one study has investigated the differential effect of tibolone and CEE combined with micronized progesterone on haemostasis and showed that increase in F1+2 was more pronounced among HT users compared to tibolone ones [57].…”

Section: Tibolonementioning

confidence: 99%

Progestogens and venous thromboembolism among postmenopausal women using hormone therapy

2011

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Hormone therapy (HT) is the most effective treatment for correcting menopausal symptoms after menopause. HT initially consisted of estrogens alone and progestogens were secondly added to estrogens for preventing the risk of endometrial cancer associated to estrogens use. Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is a major harmful effect of HT. It is now well known that oral and transdermal estrogens are differentially associated with VTE risk but progestogens may be another important determinant of the thrombotic risk among HT users. Both randomized controlled trials and metaanalysis of observational studies suggested that the VTE risk was higher among users of estrogens plus progestogens than among users of estrogens alone. With respect to the different pharmacological classes of progestogens, there is evidence for a deleterious effect of medroxyprogesterone acetate on VTE risk. In addition, observational studies showed that norpregnane derivatives were significantly associated with an increased VTE risk whereas micronized progesterone could be safe with respect to thrombotic risk. The effect of tibolone on VTE risk remains uncertain. In conclusion, progestogens may have differential effects on VTE risk according to the molecules and therefore represent an important potential determinant of the thrombotic risk among postmenopausal women using estrogens. Progestogens and VTE Finale version3/21

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“…Studies evaluating the effects of tibolone on the coagulation system are sparse and showed discordant results (Eilertsen et al 2006). Either potentially favorable effects or no changes were observed in some risk markers for venous thromboembolism, whereas other markers showed procoagulatory changes.…”

Section: Effects On Coagulationmentioning

confidence: 99%

Cardiovascular Effects of Tibolone: A Selective Tissue Estrogenic Activity Regulator

Campisi

Marengo

2007

Cardiovascular Drug Reviews

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Traditionally, it was accepted that long-term hormone replacement therapy (HRT) has a cardiovascular beneficial effect in postmenopausal women with and without coronary artery disease (CAD). However, randomized trials in postmenopausal women have not shown any benefit in either primary or secondary prevention of cardiovascular events. Therefore, these findings have raised the question of whether traditional HRT (i.e., estrogen and progesterone) has a cardioprotective effect in women at risk for or with established CAD. Concerns about the use of conventional HRT have led to a search for alternatives. Tibolone is a synthetic compound with estrogenic, androgenic, and progestogenic properties that relieves climacteric symptoms and prevents postmenopausal bone loss. Tibolone possesses a tissue-selective mechanism of action that differs from that of estrogen and/or progestogen. Unlike these compounds, tibolone's metabolites play a central role in its mode of action. Tibolone is widely used for HRT. However, its clinical impact on cardiovascular disease is still under study. The current review focuses on the effects of tibolone on the cardiovascular system and discusses clinical investigations with this compound in postmenopausal women.

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Conventional-dose hormone therapy (HT) and tibolone, but not low-dose HT and raloxifene, increase markers of activated coagulation

Abstract: Our data suggest that low-dose HT is associated with less activation of coagulation than conventional-dose HT. This finding may be of clinical importance since randomized clinical trials showing increased risk of thrombosis have utilized conventional-dose HT.

Cited by 30 publications

References 137 publications

Postmenopausal Hormone Therapy and Risk of Idiopathic Venous Thromboembolism

Postmenopausal Hormone Therapy and Risk of Idiopathic Venous Thromboembolism

Progestogens and venous thromboembolism among postmenopausal women using hormone therapy

Cardiovascular Effects of Tibolone: A Selective Tissue Estrogenic Activity Regulator

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