Amber asked
What is the best method for taking Estrace (estradiol-17ß)? My Doctor didn't have an opinion. I've read sublingual?
Answer
Estrace (estradiol) is not recommended to be taken sublingually (i.e. under the tongue) as it is not intended for that route of administration. Estrace, and the associated generic products, are not manufactured as sublingual tablets and are not designed to dissolve quickly and uniformly under the tongue. This could result in inconsistent dosing and local irritation.
Having said that, some practitioners DO recommend their patients take Estrace under the tongue for reasons we will discuss below. There is some controversy regarding whether or not estradiol in general is more effective dosed sublingually versus orally.
Estradiol Sublingual Studies
Estradiol is known to have low bioavailability, meaning it is not absorbed well. It is extensively metabolized in the gastrointestinal tract and undergoes "first pass metabolism" in the liver, further reducing drug concentrations.
To combat the effects of oral dosing, Estrace tablets are "micronized", helping to decreases the first-pass effects in the liver and increase the low bioavailability. However, even micronized versions of estradiol such as Estrace, still only have an overall bioavailability of 5-10% of original dose.
Multiple studies show positive results when dosing estradiol under the tongue versus swallowing the medication. One small study showed that sublingual administration resulted in much quicker absorption versus oral administration and also resulted in significantly higher estradiol levels than oral dosing. Another study concluded that the estradiol used in Estrace (17 beta-estradiol) is more highly absorbed sublingually when compared to oral dosing.
So while studies show that estradiol is in fact better absorbed sublingually, there aren't any studies on the overall effect this has on individuals and if it is safe. More extensive, larger scale studies need to be undertaken.
Sublingual Dosing Considerations
Sublingual dosing of medication offers several advantages over oral dosing, perhaps most importantly is the increased absorption versus oral dosing. Sublingual administration of certain medications allow the drugs to be absorbed directly to the bloodstream, bypassing the GI tract and eliminating "first pass metabolism".
Unfortunately, Estrace tablets and associated generics are not manufactured to be taken sublingually. While the actual drug molecule (estradiol) may be a good candidate for sublingual dosing, the drug vehicle used in this case (i.e. the tablet) is not.
Sublingual tablets are designed and manufactured to dissolved under the tongue quickly and efficiently and allow the drug to be absorbed consistently. A variety of factors influence this such as:
- Particle size of the medication
- "Wetting time" of the tablet
- Disintegration time
- Dissolution time
- Content uniformity of the drug
- Hardness of the tablet
- Friability (tendenacy of a tablet to chip or break)
- Stability of the product
- Texture
- Taste masking
There are a lot of considerations to take into account when manufacturing a consistent, effective and well tolerated sublingual product. When it comes to Estrace, we would be particularly concerned about content uniformity of the drug, disintegration time, dissolution time and taste masking.
As Estrace isn't manufactured as a sublingual tablet, the product will not completely dissolve under the tongue and will, over time, create a mass of non-dissolved powder. This could result in much of the drug not being absorbed appropriately. Quick disintegration and dissolution are critically important for proper drug absorption under the tongue.
In addition, the longer it takes to dissolve, the more chance you have of swallowing parts of the dose, resulting in inconsistent and fluctuating dosing. Sublingual tablets are designed to promote the retention of the drug under the tongue while the Estrace tablets are not.
Can Estrace Be Dosed Sublingually?
As discussed above, Estrace is recommended to be swallowed to ensure consistent dosing. While initial studies show that sublingual dosing does result in higher levels of estradiol, more studies are needed to further evaluate all aspects of this route of administration. Remember, Estrace tablets are not designed to be placed under the tongue, potentially causing some of the issues discussed above.
Having said all this, some doctors do recommend Estrace to be dosed under the tongue due to the perceived benefits. In any case, be sure that you and your doctor agree on your dosing regimen and discuss how the medication is working for you and if you are experiencing any side effects.
