The three estrogens: estradiol, estrone, estriol

There are three common forms of the hormone we call "estrogen" (and many many lesser variations and subvarieties). Understanding what each one is and does can be helpful in deciding which one(s) to supplement with when planning HRT.

Estradiol is the major estrogen produced by ovaries and is the strongest (the most effect for the least quantity) form. Estradiol is the "active" estrogen—the one that is capable of the fullest range of estrogen effects because it is the one that actually goes out there in our tissues and sockets into estrogen receptors and causes estrogen effects. In addition to being made by ovaries, it can also be produced by conversion from a number of precursors in the adrenal glands. It requires certain nutrients at specific levels to be metabolized properly, and it requires certain other factors to be present to determine which metabolites (some of which are considered more desirable than others) it is broken down into.

Estrone is considered a weaker form of estrogen. It is typically produced by special belly fat cells, and is the major estrogenic form found in naturally-menopausal women who are not taking HRT. It is not directly active in as many tissues was estradiol is, but can be readily converted by to estradiol for actual use. Because of this, it is considered by biochemists to more properly be thought of as an estradiol precursor (although the conversion can go both ways, meaning that estrone can also be considered a breakdown or even a storage form of estrogen). It is sometimes considered "safer" than estradiol by virtue of its weakness, but since larger quantities are required to get the same effects as a smaller quantity of estradiol as well as the fact that it is normally converted to estradiol when that form is needed, other sources consider it no more or less safe than estradiol.

Estriol is a metabolic waste product of estradiol metabolism that can still have some effects upon a limited number of estrogen receptors. It is formed in the liver and is 8% as potent as estradiol and 14% as potent as estrone. Once estriol is bound to an estrogen receptor, it blocks the stronger estradiol from acting there. Thus it is considered to have both estrogenic and antiestrogenic actions. There is also some evidence that, because it is so weak and blocks the stronger forms, estriol can be considered to have "anti-cancer" action. To take it in quantities adequate to have effects comparable to estradiol (that is, to occupy as many receptors as a needs-meeting level of estradiol), however, the risk rises to the same level with estriol as with estradiol. A particular breakdown product of estriol, 16-hydroxyestrone, is elevated in women receiving oral estriol and is associated with an increased risk of breast and cervical cancers. Estriol has also been implicated as a source of interference in lab tests for estradiol, leading to "clinically significant" testing errors. It is believed to have special efficacy for genitourinary tissues and skin generally, but that is poorly studied and results of existing research are not conclusive.

Which ones must I supplement?

This is a matter of some controversy amongst different professionals. We can start by acknowledging that there is no agreement on this, no research that says one or another is the right choice for everyone. In fact, we feel that the idea of "one right choice" is just about backwards anywhere in the context of menopausal needs.

Some folks feel that because our bodies had some percentage of all three major estrogens at some stage during our fertile life or some broad averaged out body of menopausal women typically have some other percentage of these hormones, that this represents a goal of sorts: just put everything back to that level and life will be swell. As we've tried to suggest on the matter of testing, however, what is expressed when you measure and average a whole population of women is not necessarily right for any single one of them when she's taken as an individual. We all come from different genetic backgrounds, have had different life events that have shaped our physical health and hormone exposure, and so we will continue into menopause with individual needs and capabilities. These can differ a lot from one woman to the next.

But there is also a more fundamental problem with this notion that all estrogens must be supplemented, and that's the fact that in our bodies we rely on converting one to another depending upon what's needed when. When we have a few unfilled receptors and a need for some activity on that front, we can grab up a bit of estrone, do a little biochemical slight of hand and send some fully active estradiol on its way, ready for action. When we have more estradiol kicking around in our system than we have work for it to do, we can reverse this process and downgrade it to estrone, which isn't very active and can just lounge about waiting in the unemployment line without disrupting much. When we're done with our estrogens, we metabolize them further into waste products like estriol and many others, and they gradually make their various ways out of our body.

This is our normal mechanism for handling estrogens and the capability to do so doesn't end at menopause. What does change, however, is our supply of estrogen. We don't have all that fresh estradiol flooding into our system from our ovaries, being routed to all those fertility support needs. Instead, we've geared down into post-fertile maintenance mode, with only a slow, steady trickle of estrogen to meet our basic, nonfertile needs. We don't have a surplus of estrogen so most of our estradiol is out at work in receptors, not sloshing around to be captured with testing. All that shows up now is that unemployment line grade of estrogen, our estrone, and there's not all that much of it, either. But this does not reflect a change in our needs: it's instead reflective of our situation. We still have our same old capability of inter-converting our estrogens to their needed use (whatever that capability was—some of us are better than others at the basic mechanisms and at some times we're better equipped than others with the necessary chemical co-factors like vitamins and other nutrients). So whether we put in estradiol or estrone, we're probably going to be turning our HRT to the form we need it.

And if we're putting in estriol, we're not providing for those estradiol needs, directly or indirectly. Estriol is a breakdown product, estrogen on its way out of the body. Estriol can still carry out a few actions, remember, so it does make the estradiol we make seem to go a little further. But it's not in itself a convertable contributor to estradiol, and for women who can't make enough estradiol to meet their needs for that hormone form, estriol is not going to be an effective HRT in itself. It's a dilutant, not a participant. And we'll be making it for ourselves anyway, from however much estradiol we eventually metabolize into that breakdown product.

Balancing various estrogen forms

Why do some women seem to do best on all of one or on a blend, then? That comes down to more subtle things to do with the dynamic of how their bodies handle these forms. For some women, the conversion to estrone doesn't seem to be difficult but the conversion back to estradiol may not go well. They can handle a (relative) lot of estradiol and may need a ready supply of it circulating most of the time. Other women are the opposite: too much estradiol around makes them unbearably jangly but the weaker estrone doesn't bother them and they seem to be able to make as much use of it as they need to. It seems as though some women find the accommodation to menopause, especially when it happens as rapidly as surgical meno, disruptive to their hormone handling mechanisms and they need to settle in and de-stress before they can handle these active/stored form conversions smoothly. For them, beginning with estradiol may meet their needs best.

Remember: there are no "right" answers for which estrogen(s) you might need. The right answer in choosing an HRT is getting the ones that meet your own body's needs in a way that fulfills your menopausal wellness goals. It can take some time to feel your way to the right estrogen(s) for your body's capabilities, and those capabilities may change with time. Especially in the first postop year, what works to get hormones into your body may not be the HRT you'll need or want to stay on longer term.

So don't be fooled by someone insisting that this or that HRT approach is more "natural" than another. Just because something can be measured in a population of women doesn't mean it'll suit any one woman. Just because your friend does better on an HRT that contains all estradiol doesn't mean that your body mightn't be happiest on all estrone or perhaps a combination. Just because your doctor wants you to use estriol to lower your estradiol exposure doesn't mean that you'll have none in your system. Understanding that this is a fluid situation is, yeah, a little more challenging, but in the end the answers it provides can be a lot more useful in troubleshooting why your HRT is working the way it is for you.