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Hello. This is Dr JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital. 

I’d like to talk with you about a recent report in the British Medical Journal (BMJ) on different forms of contemporary menopausal hormone therapy and risks for cardiovascular disease (CVD). 

This is a very large-scale and comprehensive study from Sweden that looked at more than 900,000 women, including more than 77,000 users of hormone therapy. The women were aged 50-58 years and the study leveraged the nationwide register system, where they have information on prescription medications as well as health outcomes that can be linked. 

This study looked at the different forms of hormone therapy: oral vs transdermal, estrogen with and without a progestogen, and also tibolone (which is not available in the United States). The endpoints included myocardial infarction (MI), total ischemic heart disease, stroke, a composite of CVD, as well as venous thromboembolism (VTE). 

They found that tibolone was associated with the greatest increased risk for CVD; there was actually an increase in both ischemic heart disease and stroke as well as composite CVD. They did not see an increased risk for VTE. This may be related to the unique pharmacologic profile of tibolone, which has estrogenic, progestogenic, and androgenic properties. 

The estrogens tested in the estrogen plus progestin and estrogen alone formulations were not conjugated equine estrogen as tested in the Women’s Health Initiative (WHI) and HERS trials, but mostly oral or transdermal estradiol. With combination estrogen plus progestin, they saw a small (about 20%) increase in ischemic heart disease, similar to what was seen in the WHI. And they saw about a doubling in the risk for VTE, also similar to what was seen in the WHI. With estrogen alone there was no increase in ischemic heart disease or MI, but there was about a 50% increase in VTE — again, similar to the WHI findings. 

With transdermal estradiol (transdermal forms of estrogen), in contrast, there was no clear increase in any of these CVD outcomes. In fact, there was a borderline reduction in both MI and composite CVD. 

So overall, this study suggests greater cardiovascular safety with transdermal compared with oral estrogen. This would be expected, given the first-pass metabolism and increased clotting associated with oral estrogens. 

On the basis of a large body of evidence, we know that for women in early menopause who have bothersome vasomotor symptoms, if they’re healthy, oral or transdermal estrogen could be used according to the preference of the woman. But this study suggests that, especially in women who do have cardiovascular risk factors, it may be very reasonable to lean toward the use of transdermal over oral estrogen among those who are choosing to use hormone therapy. 

We certainly need more research on transdermal estradiol, micronized progesterone, and these contemporary formulations that are being used. But in the meantime, this study in the BMJ does provide very useful information for women and their clinicians.