PsychEducation.org (home)                                                                                                                    Hormones and Mood

Basic Information About Estrogen in Psychiatry
(June 2005)

You'd think Psychiatry would know more about this.  Everyone knows estrogen has something to do with mood, right? It's amazing how little we know about this.  While I'm trying to find research that might guide us clinicians in knowing what to do with estrogen in Psychiatry (measure it? ask OB-Gyn's to start birth control or other forms of hormone replacement? learn how to do so safely ourselves?), here are some basics that seem relevant.

First, if you're thinking about estrogen as a hormone therapy, there is a 2005 10-page guide, compiled by the Centers for Disease Control (the authors are all women, as are those at the hospital system which reviewed the guide -- see page 2). They start with some really common-sense questions to help you determine whether hormone therapies are wise, for you. As you know, there are risks involved, just as there are with most of the mood medications we routinely use. This guide will help you evaluate those risks compared to the benefits you might be looking for. 

For basic information about estrogen therapy, from what appears to me to be a responsible organization, see Project Aware. Their volunteer, non-profit site is quite large, so remember when you're done, if you'd like more on the research on estrogen use in Psychiatry (such as there is), come on back.  Here is my collection of relevant research for a psychiatrist interested in mood and anxiety. When there is enough here to write an organized story, I'll be back. At this point these are only "very suggestive" studies, not "tells you what to do" research, except for one conclusion at the bottom.   

Theme One: The basis of estrogen effects on mood is likely to be extremely complex, not simple

In a recent review on of the brain chemistry of reproductive hormones in women,Genazzani the following estrogen effects were described: 

The moral of the story: there is no simple way to explain "here's how estrogen affects mood".  While you will often see the implication "too little estrogen leads to depression", and the related claim "estrogen can be a treatment for depression", you should keep in mind that this is a dramatic simplification of a complex relationship, most of which we don't understand. 

Theme Two: Too much estrogen may also be bad, perhaps associated with anxiety/agitation

However, even though the effects of estrogen on the brain are clearly very complex, we psychiatrists are still faced with the fact that something about estrogen and progesterone clearly affects mood.  For many women, the relationship is so obvious, they want to know if there isn't some way to treat what appears to be the problem, namely their changing hormone levels. After all, if that's the cause, why not treat the cause, rather than the symptoms? 

Two studies have shown that estrogen can treat depression in perimenopausal women: first came a study from Harvard showing that an estrogen patch worked;Soares and more recently smaller study from UCLA with similar results.Morgan  (There is also an "open trial", meaning no control group, from HarvardCohen). However, as soon as you think about estrogen in this role, you have to think about the risks of estrogen. See that 10-page guide from the CDC for a good summary.  It gets pretty tricky evaluating the risks versus the benefits; this excellent guide starts by asking you questions about what is most important to you in your health care.  

But even something so seemingly simple as raising the estrogen levels we know are falling during perimenopause runs into some problems. One research team found that in women with severe mood/anxiety symptoms (so-called borderline personality disorder, an unfortunate term and very complex condition), there was in increase in symptoms when they went on birth control pills, though only if they already had a high level of estrogen.DeSoto  Might they have been getting too much estrogen overall this way? Or perhaps the sudden increase was the problem? 

Similarly, that UCLA study above included three women whose estrogen levels went up a lot when taking Premarin, and they actually got a little worse, including an increase in their anxiety scores in particular. Unfortunately, measuring estrogen levels when using Premarin is not practical when using this form.  So we don't know the actual blood levels in this study.  I thought this pattern was very interesting though. Here are two key graphs from their data. Careful, though: I'm going to offer you my interpretation of these results, and there could be something I'm misunderstanding. These are very new results (June 2005).

Note that zero, no change, is in the middle of these scales. So if increasing estrogen levels helped treat depression in these women, you'd expect that their diamonds would fall in the lower right side -- right?  Raise the estrogen, lower the depression score. As you can see, it wasn't entirely that way, although there was enough of a result to be statistically significant. To me, the result that might be especially useful to Psychiatry right now, even though it was only two women, are the two diamonds in the upper right.  These women had a large increase in their estrogen level, and their depression scores got worse.

In particular, what got worse was anxiety, as shown in the same kind of graph system for their anxiety subscale scores (part of the same depression scale that asks about anxiety):

Again you see that for the few women whose estrogen level went up quite a bit, their anxiety got worse. For now, then, here's my conclusion about estrogen replacement, which is much simpler than trying to answer the question "does it work for depression?" or "is it worth the risk?". Any woman with high anxiety who's taking estrogen replacement needs her estrogen level checked. If she's taking Premarin, she should talk with her doctor about switching to estradiol so that her level can be checked (because you can't do so on Premarin; here's a description of that problem). According to my OB-Gyn colleagues, in their experience "women seem to feel best when their estrogen level is between 50 and 100". One said he tried to shoot for 75. For now, if anxiety is a problem and the level is higher than 150 or so (in one of my patients switched over to estradiol at what was thought to be an equivalent dose, it was 400), then you should talk to your doctors about trying a lower dose.