Hormone therapy and VTE risk

Hormone therapy and VTE risk

The different drug formulations of menopausal hormone therapy (HT) may determine the risk of venous thromboembolism (VTE), according to a new study. It is known that combined estrogen-progesterone therapy has a higher risk of VTE than estrogen-only therapy, and oral therapy has a higher risk than transdermal therapy. Now, a follow-up study from the Million Women Study with more than 3.3 million patient-years of follow-up looks at the varying risks of different HT combinations. The risk of VTE was again found to be significantly higher for combination estrogen-progesterone therapy compared to estrogen-only therapy (relative risks [RR] = 2.07 [95% confidence intervals (CI) 1.86-2.31] vs 1.42 [1.21-1.66]). Transdermal estrogen-only therapy resulted in no excess risk for VTE (RR 0.82 [0.64-1.06]). Among users of combination estrogen-progesterone, the risk of VTE varied by progestin type with significantly greater risk for preparations containing medroxyprogesterone compared to other progestins (2.67 [2.25-3.16] vs 1.91 [1.69-2.17]; P heterogeneity = 0.0007). The risk of VTE was significantly higher (2 times the risk) in the first 2 years after starting combination HT than later years. Five-year risks for pulmonary embolism (PE), both fatal and nonfatal, were calculated as: 1 in 664 for never users of hormone therapy, 1 in 475 for current users of oral estrogen-only, 1 in 390 for users of estrogen-progesterone containing norethisterone/norgestrel, and 1 in 250 for users of estrogen-progestin therapy containing medroxyprogesterone. The authors conclude that VTE risk varies considerably by HT formulation and is greatest in users of oral estrogen-progesterone therapy containing medroxyprogesterone. One case of PE could be avoided for every 1295 current users of oral HT if estrogen-only rather than estrogen-progesterone was used. Among combined HT users, one PE in 700 women could be avoided by use of a progestin other than medroxyprogesterone (J Thromb Haemost published online Sept. 10, 2012. doi: 10.1111/j.1538-7836.2012.04919.x). These data follow on the Women's Health Initiative, which also showed a higher risk of breast cancer for combination hormone replacement therapy vs estrogen-only therapy, but this risk is offset by the risk of endometrial cancer in women with an intact uterus on unopposed estrogen.