Letter by Micheletti and Chevallier Regarding Article, “Hormone Therapy and Venous Thromboembolism Among Postmenopausal Women: Impact of the Route of Estrogen Administration and Progestogens: The ESTHER Study”
To the Editor:
We read with interest the report by Canonico and colleagues1 that shows a differential association of oral and transdermal estrogen with venous thromboembolism (VTE) risk among postmenopausal women. In addition, their data suggest that norpregnane derivatives may be thrombogenic (with a 4-fold-increased VTE risk), whereas micronized progesterone and pregnane derivatives appear safe with respect to thrombotic risk.
First, we note that in 2 groups, oral estrogens and norpregnane derivatives, the authors reached conclusions about increased VTE risk notwithstanding odds ratios with very large confidence intervals that showed a great deal of heterogeneity. Could they give us the odds ratio variance and the probability value obtained with another statistical test for comparison of qualitative variables?
When progestins were studied, the route of estrogen administration was not shown, whereas an increased VTE risk was noted with oral estrogen. In this case, what type of progestin was involved?
The exposure time to estrogen has not been mentioned. The probability of VTE occurrence is the strongest in the first year of hormone exposure2; in this respect, what can justify the cutoff point being fixed at 5 years?
The results do not appear to be in concordance with the already available data about hemostasis and nomegestrol acetate, and in our opinion, no biological plausibility has ever been found to explain the results of this case-control study.3 Nomegestrol acetate has very strong antigonadotropic and antiestrogenic actions, so it is used particularly in premenopausal women with strong hyperestrogenic symptoms, and hyperestrogenemia is by itself an important VTE risk factor.
Although the results are interesting, we believe that more randomized trial data are needed before conclusions can be made about the thrombogenic properties of nomegestrol acetate.
Drs Micheletti and Chevallier are employed by Laboratoire Théramex, Merck Serono.
Canonico M, Oger E, Plu-Bureau G, Conard J, Meyer G, Levesque H, Trillot N, Barrellier MT, Wahl D, Emmerich J, Scarabin PY; Estrogen and Thromboembolism Risk (ESTHER) Study Group. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation. 2007; 115: 840–845.