I began full menopause by the age of 41, so I have been taking hormone replacement therapy (estrogen and progesterone) to try to minimize the effects that lower estrogen levels may have on my long-term health. My gynecologist wanted me to take estrogen in the form of a patch due to concerns that oral forms may increase risk for cardiovascular issues. But the patch proved to be difficult to keep on my skin for a full week, and I began experiencing some breakthrough bleeding. The patch was also much more expensive than pills. What is the data about the risks of the patch versus the pill form of estrogen for this type of use?
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There is a reason doctors have preferred to give women estrogen through the skin instead of as pills in menopause. It is a little bit technical, but bear with me. When we take anything in by mouth — pills, food, or supplements — we absorb nutrients or medication through the walls of our intestine into our bloodstream. That blood then passes through the liver. In the liver, the molecules of the medication may be dramatically altered, and much of the drug may be metabolized before the medication then moves through the circulation to act on the rest of the body. This is called first-pass metabolism.
One theory regarding why the women in the Women’s Health Initiative (WHI) study had a higher risk for breast cancer and cardiovascular disease is that first-pass metabolism was altering the oral estrogen and progesterone they were given in some way that was biologically important. Medications that enter the body through the skin go directly into the systemic circulation without passing through the liver first. As a result, since the WHI was published, the general consensus was that estrogen patches and gels were safer than oral estrogen.
Has this theory been borne out in the literature? Yes and no. In a review that included 51 studies conducted between 1990 and 2021, the authors found that there was no difference between oral and transdermal estrogen when it came to bone health, glucose metabolism, cholesterol, breast cancer, endometrial disease, or cardiovascular risk.
The only difference they noted was an increased risk of blood clots. Ten of the 51 studies included in the review looked at the risk of blood clots. Only two found that the risk of blood clots was increased in women taking oral estrogen compared with women taking transdermal estrogen. One of the included studies took their analysis a step further. They looked at women at high risk for blood clotting due to two common genetic mutations. Again, the risk of blood clots was higher with oral estrogen than transdermal estrogen.
In that study, the risk of blood clots was about four times as high in women taking oral estrogen as in women taking transdermal estrogen. However, the total number of blood clots in the group taking oral estrogen was still small.
If you are not at an increased risk of blood clots, it would be reasonable to consider an oral alternative. However, there are several different transdermal options to consider as well. If a once-weekly patch isn’t working, a twice-weekly patch that needs to stay in place for only three to four days may work better for you. Cleaning the area well with rubbing alcohol can help patches adhere better. There is also an estrogen gel, called Divigel, that is applied to the skin on the thigh daily.
One final tip related to drug costs — and it works with any brand-name drug: Go to the manufacturer’s website, usually “drugname.com”, and download a coupon to reduce your co-pay. I have yet to find a brand-name drug that doesn’t offer a savings coupon, and many are quite generous.
The takeaway: There is a slight increase in blood clots among women taking oral estrogen as compared with women taking transdermal estrogen, but the safety profile of both formulations is otherwise quite similar.
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