Bioidentical Estrogens Explained

In previous blog postings, I’ve discussed hormones that qualify as bioidentical and the power of progesterone.  Here I want to dig a little deeper into the bioidentical estrogens since they are an important, and often misunderstood, part of menopausal treatment.  Although there is only one bioidentical progestin, progesterone, there are actually 3 bioidentical estrogens.  They are estrone (E1), estradiol (E2) and estriol (E3).  They each have different levels of estrogenic activity and biological properties.

Let’s start with the middle one first – estradiol (E2).  This is the primary estrogen in the body and the most potent.   Estradiol accounts for somewhere between 10-40% of the total estrogens circulating in the body.  Estradiol is also the most widely available estrogen as a mass-produced pharmaceutical.  It comes in tablets, patches and creams.  Estradiol is very effective at treating many menopausal symptoms, especially hot flashes and vaginal dryness.  But  because estradiol is so potent, it needs to be dosed carefully.  Overdosing estradiol can lead to many unpleasant side effects like headaches, fluid retention, and break-through bleeding.  Overdosing also increases risks of endometrial and breast cancer and blood clots leading to heart attack or stroke.  Therefore it is extremely important to dose estradiol at the lowest effective dose and to make sure its activity is balanced out with the proper amount of progesterone.  One way to lower the dose of estradiol is to combine it with the less potent estrogen estriol.  I’ll discuss that more later.

Estrone (E1) is the other potent estrogen.  It accounts for 10-20% of the body’s circulating estrogens.  There are a couple of mass produced estrone containing products on the market but they are rarely used.  The main problem with estrone is that it doesn’t appear to be that effective at treating menopausal symptoms but still has many of the unwanted side effects of estradiol.  Most concerning is estrone’s ability to stimulate breast tissue growth which may lead to increased risk of breast cancer.

Finally, estriol (E3) is the weakest estrogen, meaning that it exerts a much milder estrogenic effect than estradiol or estrone.  Estriol accounts for 50-80% of circulating estrogens in the body.  Controversy has surrounded estriol in the past.  Its value was questioned by the FDA in their letters to compounding pharmacies in 2008 (see my post Answering the Critics: the FDA for more information about that).  There are no FDA approved estriol containing products, so the only place to get estriol is through a compounding pharmacy.  The interesting thing about estriol is that even though it is a weak estrogen, it appears to be effective in treating many menopausal symptoms.  Some studies have also shown that it has a higher affinity to the estrogen receptors on breast tissue that are protective against breast cancer.  I think it would be premature to say that estriol prevents breast cancer but the data we have at this point indicates that might be the case.  My experience with estriol is that it is an effective treatment with often lower side effects than the more potent estrogens.  Again, it is important to balance the effect of any of these estrogens with the appropriate dose of progesterone.

Finally, often bioidentical estrogens are prescribed in a combination – either Tri-est or Bi-est.  Tri-est is a combination of all 3 estrogens usually in a 10%/10%/80% (E1/E2/E3) ratio.  The rational behind this combination is that it mimics the normal ratio of these hormones in the body (although clearly there is variability from person to person).  Because of the safety concerns of estrone (E1) and its limited effectiveness, Tri-est had gone out of fashion.  What I see much more of now is Bi-est.  This is a combination of estradiol (E2) and Estriol (E3) in a 20%/80% (E2/E3) ratio.  This combination often relieves menopausal symptoms with a much lower exposure to the more potent estradiol.

One last note… obtaining hormone levels prior to starting any of these treatments and doing follow-up tests after starting them is an important part of finding the exact custom dose to effectively treat menopausal symptoms with the lowest risk of side effects.

I hope this information is helpful.  Please post any comments or questions.

Thank you and live well!