In recent posts on combination HRT, we've looked at how progestins affect breast cancer risk. Now let's consider an HRT risk more related to estrogen — venous thrombosis.
When an estrogen is taken orally, it is promptly metabolizied by the liver, stimulating a variety of liver enzymes. One effect of this liver activity is an increase in clotting factors.
Older women whose blood clots too easily have greater risks for heart disease, stroke and blood clots in the legs or the lung.
Our biggest study on hormone replacement, the Women's Health Initiative, looked only at an oral estrogen. The clinical trial arm of the WHI was stopped in 2002 because of increased risk of heart disease, stroke and venous thromboembolism.
In recent years, transdermal estrogen has become widely available. A big question is whether delivering estrogen through the skin has less impact on the clotting system, making it safer.
The ESTHER study, conducted in France between 1995 and 2005, compared transdermal and oral estrogen use in women with venous thromboembolism.
Compared to women not using HRT, women on transdermal estrogens had no increased risk of clot-related problems. Women on oral estrogen, however, had a 4 times greater risk.
Last year, a British Medical Journal report combined results from 17 studies on HRT and thromboembolism risk. They found a 2.5 greater risk with oral estrogen. Again, women on transdermal estrogen had about the same risk as women not on HRT.
With combined HRT, it also appears progestins like norethindrone add to thrombotic risk, while progesterone does not.
So if you are considering HRT for menopausal symptoms, what's the safest regimen? Given the current information, I recommend the lowest dose transdermal estrogen that helps your symptoms along with cyclic Prometrium. If you've had a hysterectomy, you can skip the Prometrium.
Taking HRT this way for less than three years should relieve menopausal symptoms and be relatively safe for most women.