Boston, MA - A new analysis of data from the Nurses' Health Study suggests that hormone therapy (HT) is associated with an increased risk for stroke, regardless of the treatment strategy or the timing of treatment initiation [1].

The researchers found an increased risk of about 40% with estrogen alone and 30% with estrogen plus progestin, "a finding that is nearly identical to that of the Women's Health Initiative," they write. Stroke risk increased with increasing doses of oral conjugated estrogen.

"In younger women, with lower stroke risk, the attributable risk of stroke owing to hormone use is modest and might be minimized by lower doses and shorter treatment duration," the researchers, with first author Dr Francine Grodstein (Harvard Medical School, Boston, MA), add.

Their results are published in the April 28, 2008 issue of the Archives of Internal Medicine.

A previous analysis from the Nurses' Health Study showed an increased risk for stroke with current use of hormone therapy of about 35%, the authors write. Results from the Women's Health Initiative, a randomized trial of hormone therapy in postmenopausal women, also showed a 30% to 40% increased risk with therapy either with estrogen alone or estrogen combined with progestin.

The risks in that trial appeared similar for both younger and older women, they write, but the trial included only a few women who were recently menopausal, when hormone therapy is used most often in the clinical setting, so the risk for these women is still unclear.

In the current study, they write, "we examined the most critical current questions regarding stroke risk: we explored the timing of HT initiation and further examined varying estrogen doses, since we had limited power to address these questions in the previous analyses." They also looked at the relationship with stroke type.

The Nurses' Health Study is a prospective observational study including 121 700 women who were between the ages of 30 and 55 in 1976. Subjects were followed with biennial questionnaires, including information on menopause and postmenopausal hormone use, as well as cardiovascular risk factors and cardiovascular diagnoses.

They found a significant increased risk for stroke in women currently taking HT, whether it was estrogen alone or estrogen plus progestin.

The increased risk was seen for women initiating HT at young ages or near menopause or at older ages or more than 10 years after menopause, they note. Short-term use of less than five years, initiated at younger ages, was not associated with a clear increase in stroke risk; they note, however, "this apparently null result was based on a small number of cases."

The incidence of stroke was relatively low in younger women, they write; the attributable risk in women aged 50 through 54 indicated approximately an additional two cases of stroke per 10 000 women per year taking hormones.

There was also a strong and statistically significant relationship between the dose of oral conjugated estrogen and stroke risk, the authors add (p for trend <0.001).

"In summary, our findings in the Nurses' Health Study indicate that HT is associated with an increased risk of stroke, regardless of the hormone regimen or the timing of HT initiation," the authors conclude. "However, in younger women, who are at lower absolute risk of stroke, the attributable risk of stroke owing to hormone use is modest, and our data suggest that risk might be further minimized by lower doses and shorter duration of treatment."

A randomized trial, the Kronos Early Estrogen Prevention Study (KEEPS), is currently under way, evaluating the effect of five years of HT vs placebo in 720 women aged 42 to 58 years, randomized within 36 months of their final menstrual period, and may provide further data on the effect and safety of this treatment in younger women.