Estrogen Pill vs. Estrogen Cream or Patch - Which Works Best?

The Delivery System Makes All the Difference When it Comes to Hormones

One of the issues up on the radar screen in natural hormone replacement therapy is whether taking estrogen in the oral (pill form) or transdermal (skin cream or patches) works best. (It's already very clear that progesterone cream works better than progesterone pills.) A few studies have been published showing that oral estrogen increases levels of C-reactive protein (CRP), a marker of inflammation that is associated with heart disease.

The Voices of Experience
Jane Murray M.D., who specializes in natural hormone replacement therapy in her medical practice in Kansas City, decided to test this for herself after she noticed that her patients who used estradiol patches seemed to be doing better than those taking pills. She first tested an elderly patient who had been on a small dose of Premarin for many years. When her blood tests showed high CRP levels, Dr. Murray suggested she switch to a patch. After three months on the patch, the patient was tested again, and her CRP levels were normal. According to Dr. Murray, “That was my index case that woke me up to the fact that this is a real and clinically relevant phenomenon. Since then I’ve had other patients with the same result, so I now routinely recommend patches or cream over pills. I have noticed that my overweight patients who are insulin resistant are more sensitive to the CRP-elevating effects of oral estrogen. This may be why we’ve gotten such conflicting reports over the years about estrogen’s effects on heart disease.”

Oral Estrogens Associated with Low Sex Drive
Dr. Murray continues, “I also found that patients on oral hormones tended to have more problems with low libido or sex drive. When I researched this I found that oral hormones stimulate the liver to make proteins, including SBHG [serum binding hormone globulin], which binds to hormones and makes them inactive. When I tested hormone levels in my patients I found that when they were put on oral hormones their SBHG went way up and their free testosterone went way down, which accounts for the low libido. I found this to be true with oral hormone replacement hormones and with birth control pills. When I switched these women to the birth control patches their libido came back.”

Dr. Randolph Weighs In on Oral Estrogens
C.W. (Randy) Randolph, M.D. of Jacksonville Beach, Florida has had similar results in his busy natural hormone therapy practice, and adds that compared to transdermal estrogens, oral estrogens increase the risk of thromboembolic events [strokes and blood clots]. He points out that the liver proteins created by oral estrogens also raise blood pressure, raise triglyceride levels, and suppress thyroid function. Because he is a pharmacist as well as a physician, Dr. Randolph makes his own transdermal hormone gels. He usually recommends that women begin with a combination of 0.75 mg of estradiol and 1.5 mg of estriol daily, and then adjust according to salivary hormone level tests and symptoms.

Ylikorkala O, Evio S, Effects of hormone therapy and alendronate on C-reactive protein, E-selectin, and sex hormone-binding globulin in osteoporotic women, Fertil Steril. 2003 Sep;80(3):541-5.

Kawano H, Yasue H, Effects of transdermal and oral estrogen supplementation on endothelial function, inflammation and cellular redox state, Int J Clin Pharmacol Ther. 2003 Aug;41(8):346-53.

Frohlich M, Muhlberger N, Markers of inflammation in women on different hormone replacement therapies, Ann Med. 2003;35(5):353-61.