Is compounded estriol safe?

Ask Dr. Jen

On your Instagram stories you recommend against compounded hormones, but my doctor just gave me compounded estriol. Is that safe?

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Short Take...

Compounded hormones are NOT recommended for menopausal hormone therapy (MHT), either to use transdermally (across the skin), orally (by mouth), or vaginally. There is very little data on compounded hormones in general, and people could be absorbing more than they should be taking or less. The biggest issue with compounded estriol is that it is likely ineffective, but without studies that is an educated guess. Also, there is the issue of your doctor suggesting a therapy that hasn’t been proven to be effective and isn’t recommended. What else might they not know?

Go On...

The main estrogen made by the ovary is estradiol. Transdermal estradiol is the safest option for menopausal hormone therapy (meaning estrogen that is taken after menopause that enters the blood to treat symptoms and to prevent osteoporosis). Transdermal estradiol can be given as a patch, lotion, gel, or spray that is absorbed across the skin and it can also be administered via a vaginal ring and the estrogen is absorbed into the bloodstream. These estradiol products are all standard pharmaceuticals, meaning they are made by what many people call “Big Pharma,” are approved by the Food and Drug Administration (FDA), and there is published data on safety and how well they work. We know how estradiol in these formulations is absorbed, what effects it has, and that each dose contains the amount of hormone it claims to contain. Transdermal estradiol is the lowest risk estrogen and is the gold standard for therapy, meaning unless there are compelling reasons, this is the estrogen of first choice.

In comparison estriol is the main estrogen made during pregnancy. It is made in a multi-step process that involves the fetal adrenal gland, liver, and the placenta and it spills into the maternal bloodstream. Using a fetal hormone for menopausal hormone therapy might sound weird, but we also use hormones from horse urine (Premarin). The original source of the hormone tells us nothing about safety, after all it is the estradiol made by the ovaries that gives some women breast cancer and endometrial cancer (cancer of the lining of the uterus). What matters with hormones is rigorous testing so we know if they work and the long-term safety, and we don’t have that with estriol.

Estriol is a much weaker estrogen than estradiol, with about 1% the potency. This has led some to market it as “more gentle,” but a weaker hormone is not “more gentle,” it simply stimulates estrogen receptors less than estradiol. There is no data to say the way estriol stimulates estrogen receptors is safer or lower risk. There are a few studies using pharmaceutical preparations of estriol orally and vaginally, but there isn’t enough data to make any statements about its use versus the gold standard transdermal estradiol. Should there be more testing? Sure. We may find it has a benefits we didn’t expect, but without that data all we can say is that it is a less studied estrogen for menopause. How less studied became concierge medicine in America is an essay I need to write!

There is no pharmaceutical estriol in the United States, meaning any estriol prescription is compounded at a pharmacy. A recent report from the National Academies of Sciences, Engineering and Medicine recommends against compounded hormones. They are actually technically difficult to compound and often people don’t get what they think they are getting. It turns out the testing that goes into pharmaceuticals matters. With compounded medications absorption is erratic, shelf-life unknown, and dosing imprecise. Getting this right is critical, otherwise too much or too little of a hormone can be absorbed.

As an aside, if you do get compounded estriol or estradiol the raw powder is made via a semi-synthetic process in a lab, this isn’t ground up yams, soybeans, placenta, or fetal liver. 

A compounded estriol product was tested in 2012 (it also contained estradiol, a drug combination that is often called Biest) and resulted in very low and erratic levels of estradiol in the blood. Want to guess how much estriol was detected in the blood? None. This is a concern because if you are counting on your estriol to protect your bones or treat your hot flushes it needs to actually get into your bloodstream. There is no data on how well compounded vaginal estriol might work for vaginal dryness or pain with sex related to menopause.

Currently, there is no evidence that compounded estriol (or estradiol for that matter) can do anything. Based on the sparse data it is likely an expensive placebo and any doctor who says otherwise is welcome to do the studies and get them published to support their claims. Compounded hormones are a massive industry making a lot of money, and the fact that essentially none of those profits have been diverted into studies proving the products work and are safe is disgraceful. We have an awful legacy in diethylstilbestrol (DES) of women and their children being harmed by an under tested hormone, and those who profit from compounded hormones would do well to remember that legacy.