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Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study

Sweetland S, Beral V, Balkwill A, Liu B, Benson VS, Canonico M, Green J, Reeves GK, for the Million Women Study Collaborators.

J Thrombosis Haemostasis 2012;10:2277-86

Background: Current use of menopausal hormone therapy (HT) increases venous thromboembolism (VTE) risk and the formulations used may affect risk.

Methods: 1,058,259 postmenopausal UK women were followed by record linkage to routinely collected National Health Service hospital admission and death records. HT use and risk of VTE was examined using Cox regression to estimate relative risks (RRs) and 95% confidence intervals (CIs).

Results: During 3.3million years of follow-up, 2200 women had an incident VTE, diagnosed 1.5 years, on average, after last reporting HT use. RRs in current versus never users at last reporting varied by HT formulation: risk was significantly greater for oral estrogen-progestin than oral estrogen-only therapy (RR=2.07 [95%CI:1.86-2.31] versus 1.42 [1.21-1.66]), with no increased risk with transdermal estrogen-only therapy (0.82 [0.64-1.06]). Among users of oral estrogen-progestin, HT risk varied by progestin type, with significantly greater risks for preparations containing medroxyprogesterone acetate than other progestins (2.67 [2.25-3.17] versus 1.91 [1.69-2.17];P(heterogeneity) =0.0007). Current users of oral HT at last reporting had twice the risk of VTE in the first two years after starting than later (P(heterogeneity) =0.0006). Associations were similar for deep vein thrombosis with and without pulmonary embolism. Over five years, 1 in 660 never users of HT were admitted to hospital for (or died from) pulmonary embolism, compared to 1 in 475 current users of oral estrogen-only HT,1 in 390 users of estrogen-progestin HT containing norethisterone/norgestrel, and 1 in 250 users of estrogen-progestin HT containing medroxyprogesterone acetate.

Conclusions: VTE risk varied considerably by HT formulation, being greatest in users of oral estrogen-progestin HT, especially formulations containing medroxyprogesterone acetate. © 2012 International Society on Thrombosis and Haemostasis.