HRT and Cardiovascular Risks

A recent study published in the European Heart Journal (Lokkegaard, et al EHJ, Sept. 30, 2008) brings to light new information regarding hormone replacement therapy and risk of myocardial infarction. Previously, studies have shown that HRT is associated with an increase in MI risk in the first year after initially starting therapy (NEJM 2003;349:523-534).
Participants in the landmark Women's Health Initiative Study were randomly assigned to receive conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day) or placebo with a planned follow up of 15 years. The study was stopped after 5 years because of a higher rate of MI in the first year and a high rate of MI in the 6 months after stopping therapy.
Women with symptoms related to menopause are often left confused as to what is the best choice of treatment. In many cases the doctors have been confused as well.The recommendation after the Women's Health Initiative was released was "don't start it, don't stop it."
The findings of the recent Danish trial emphasize that the mode of HRT appears to be the key to increased MI risk. If HRT is given continuously and orally, combined with progestins, as in the WHI study, there is the highest risk of MI. In comparison, if the HRT is given via a transdemal or transvaginal route the risk of MI is almost 40 percent lower than in the group taking the oral preparation and not different than non-users of HRT.
These results were consistent even when the groups were analyzed by age, although there was a higher risk of MI with women who started HRT at a younger age. Importantly, using oral HRT is acceptable and associated with a low risk of MI if it is given in a cyclical nature (estrogen every day with 7 to 10 days of progestogen each month).
The take-home point from the recent study is that when HRT is indicated, the preferred mode should be transdermal, transvaginal or in a combined cyclical mode as described above.