Increased stroke risk may be associated with oral estrogen, but not transdermal forms
Up to 3,000 strokes per year per million hormone therapy users could be avoided by encouraging them to change from oral to transdermal estrogens and from synthetic progestins to micronized progesterone, the study concluded.
Oral, but not transdermal, forms of estrogen are associated with increased stroke risk in postmenopausal women, according to a new study, which suggests for the first time that the type of concomitant progestogen may play a role in this outcome.
Researchers used data from the French national health system in a nested case/control study to examine the role of estrogens and progestogens in ischemic stroke. Results were published online on June 2 by Stroke.
The researchers compared 3,144 women ages 51 to 62 years with a first hospitalization between 2009 and 2011 for a stroke to a control sample of 12,158 healthy women who had never been hospitalized, matching the groups for age and ZIP code. All women had no personal history of cardiovascular disease or contraindication to hormone therapy.
Overall hormone therapy use was similar among cases and controls (6.2% vs. 6.8%, respectively; P=0.19). The researchers classified hormone therapy users according to route of estrogen administration (oral or transdermal) and type of concomitant progestogen (progesterone, pregnane derivatives, norpregnane derivatives, and nortestosterone derivatives).
Stroke risk was increased for oral estrogen (odds ratio [OR], 1.58; 95% CI, 1.01 to 2.49) but not transdermal estrogen (OR, 0.83; 95% CI, 0.56 to 1.24). The association with oral estrogen increased with the dose of hormone therapy (P<0.01 for linear trend), but there was no dose-effect relation with transdermal estrogen use.
For the progestogens, only users of norpregnane derivatives had higher stroke risk (OR, 2.25; 95% CI, 1.05 to 4.81). In this group, 85% of the patients used nomegestrol acetate, and an analysis restricted to this molecule yielded similar results (OR, 2.85; 95% CI, 1.15 to 7.06).
The study authors noted limitations to their work, such as lack of data on medication adherence, incomplete data on risk factors and comorbidities, and the retrospective nature of their analysis. They also noted the potential for indication bias in terms of why the women received a particular route of estrogen or type of progestogen.
“Based on these observations, ≤3,000 cases of these pathologies per year per million [hormone therapy] users could be avoided by encouraging them to change from oral to transdermal estrogens and from synthetic progestins to micronized progesterone,” the study authors wrote. “Nevertheless, data from randomized controlled trials are needed to confirm these results.”