Let’s Talk About Estrogen
This is a basic review of estrogen. We will cover what it is, the forms of it and how you can take it as hormone therapy. Spoiler alert! How I prescribe it may surprise you. If you’ve read the FAQ, you will know that we do not insert pellets at The WoMn Clinic.
What is estrogen? Estrogen refers to a family of three hormones in the body: Estrone, Estradiol and Estriol. These are literally E1, E2 and E3 and they have to do with where and how many hydroxyl groups (OH) are located in the chemical structure.
Why does this matter? It is known that these estrogens have different abilities to stimulate the two estrogen receptors. Before you close this blog, I’m getting to it. These estrogen receptors can cause tissue to grow (alpha) or to be stable (beta). The form of estrogen that is commonly prescribed is estradiol. Estradiol activates the two receptors in a similar way and so is considered a more balanced hormone. Estrone is a metabolite of estradiol and is thought to activate the receptors that cause tissues to grow. It is thought to be more inflammatory and cause a higher risk of breast cancer. Conversely estriol has a higher affinity for the stable receptor and is thought to be more anti-inflammatory. It is usually produced by the placenta during pregnancy. Estriol is commonly used in combination with estradiol. It can also be compounded into a facial cream!
Why are you writing this blog? I am writing it to talk about estradiol. You may have heard of the Women’s Health Initiative Study. It studied horse estrogen which contains estradiol and other hormones not native to the human body. It looked at outcomes with the horse estrogen alone and in combination with a progestin. It gave the hormone to women in their 60s who had a history of hypertension. The study was designed this way because it was mainly trying to assess the effect of hormones on heart disease. These women had increased rates of heart attacks and strokes on the oral horse estrogen.
Since this study, there have been questions about whether bioidentical estradiol carries the same risk as horse estrogen if given orally. The main concern is that oral estrogen goes through the liver and so can increase the production of clotting factors.
SIDE NOTE: You should know that estrogen in the liver also causes the liver to make more HDL (good cholesterol) than LDL (bad cholesterol). Estradiol also decreases insulin resistance which allows your body to turn carbohydrate into energy rather than fat. This higher conversion of excess carbohydrate into fat is why some women have increased triglycerides in menopause. So if you have noticed your bad cholesterol and triglycerides going up and your good cholesterol staying steady or decreasing, this is why.
Back to the main event. When I started prescribing bioidentical hormones I too was alarmed by the risk of blood clots and strokes and only recommended transdermal estrogen. Truly, I tried to place my patients who had been on oral estradiol on transdermal. Women who are at increased risk for stroke and blood clots should absolutely use estradiol ONLY through the skin. I was fortunate to take a course from Neal Rouzier MD on bioidentical hormones and I was surprised that he prescribed oral estradiol. He presented the studies to back his decision.
In 2024 the green journal of the American College of Obstetrics and Gynecology released a clinical expert series on a contemporary approach to menopause care. In that article they referenced three different studies that had looked at oral estradiol use in women. The studies were the Danish osteoporosis prevention study published in 2012 that collected data from 1990 to 1993. Women were followed for 16 years and women on oral estradiol had significantly lower rates of heart attacks, heart failure or death. They also found no increased risk of thromboembolism (blood clots), cancer or stroke. They also referenced a 2022 publication in the International Society of Gynecological Endocrinology that looked at 74 articles comparing horse estrogen to oral estradiol and saw that estradiol protects better against dementia and bone fractures than horse estrogen. Estradiol also had better cardiovascular outcomes and did not have increased risk of blood clots. The last article referenced was the ELITE trial from the New England Journal of Medicine in 2016 that gave women oral estradiol and found less plaque and less coronary artery calcification in women OVER 60! No increased risk of cardiovascular events.
Are you still here? Great. I present all of these not to bore you but to give you the “receipts” of why I prescribe transdermal AND oral estradiol to my patients. Anecdotally, I have a friend who has been on oral estradiol for years and she never got diagnosed with breast cancer or have a stroke. She is also very healthy. I mention her because her daughters and her mother were all diagnosed with breast cancer but she never was and never will be.
I counsel patients about all of their options and have a detailed discussion of their medical history and assess their individual risk. I practice evidenced-based medicine and try not to practice from a point of fear. Some women prefer the patch or the cream. To those women who prefer a pill, as long as they are not at increased risk for blood clots, they can have oral estradiol, safely.
For the lawyers: the above is for general information only and not meant to be construed as medical advice. Have a good discussion on your specific health history with your menopause provider.
