Estrogen therapy is a key part of menopause management, helping relieve hot flashes, night sweats, vaginal dryness, and mood changes that come from declining hormone levels. While estrogen can be taken in pill form or through the skin (as a patch, gel, or cream), research increasingly shows that how you take estrogen makes a big difference in safety. For many women, using estrogen through the skin—known as transdermal estrogen—is a safer and more natural way to restore balance.
One of the biggest differences between oral and transdermal estrogen is how the body processes it. When estrogen is swallowed in pill form, it must pass through the liver first before entering the bloodstream. This “first-pass” effect triggers the liver to make more clotting factors and certain inflammatory proteins. As a result, oral estrogen increases the risk of blood clots (deep vein thrombosis and pulmonary embolism), especially in women over 50 or those with other risk factors like obesity, smoking, or a family history of clotting disorders.
Transdermal estrogen, on the other hand, is absorbed directly through the skin and goes straight into the bloodstream—bypassing the liver. Because it does not stimulate liver production of clotting factors, it has not been shown to increase the risk of venous thromboembolism (VTE). Large observational studies, including the Women’s Health Initiative follow-up research and European Menopause Society data, confirm that women using estrogen patches or gels have a significantly lower risk of blood clots compared to those taking estrogen pills.
In addition to reducing clot risk, transdermal estrogen appears to have a more favorable effect on inflammation and metabolism. Oral estrogen can raise levels of C-reactive protein (CRP), an inflammatory marker linked to heart disease. Transdermal estrogen does not raise CRP and tends to maintain healthier triglyceride and blood sugar levels. It also provides more stable hormone levels throughout the day, which some women find leads to smoother symptom control and fewer mood swings.
For many women seeking hormone replacement therapy, transdermal estrogen offers the benefits of symptom relief without the risk of oral estrogen. While each woman’s situation is unique and should be discussed with a healthcare provider, using estrogen through the skin is often the preferred option for safety and overall well-being. This is the form I use with the many women for whom I treat with hormone replacement therapy. And for optimal balance, I always use natural progesterone along with transdermal estrogen. These two hormones have a balancing effect on one another.
