Estrogen and mood

Schiff: Dr. Berga, you’ve looked at serotonergic changes for effects on cognition, but changes in serotonin also suggest effects on mood. Would you recommend estrogen for a woman who’s become depressed, and under what circumstances would you try it?

Berga: The real question is: if a woman is depressed premenopausally and her depression becomes worse after menopause, should you give her estrogen as an adjunct to an SSRI? The data on that question are not abundant, but a recent study did show a marked reduction in depression in long-term users of ERT.¹² Another study of depression has shown that SSRIs work better in women and that tricyclics work better in men.¹³ And there is evidence that some SSRIs don’t work in the absence of estrogen in women.¹⁴ If you put all these data together, you’ve got a pretty good argument for combining estrogen with SSRIs in women suffering either an exacerbation or a new onset of depression at the time of menopause. The psychiatrists who specialize in postpartum depression also now want to give estrogen along with SSRIs, so it’s an idea that’s gaining currency.

Nachtigall: I think what we’d all like to know is how much the loss of estrogen at menopause contributes to depression, particularly new-onset depression. I see many women who have never been depressed before, except perhaps postpartum. Now suddenly they’re at menopause and they’re depressed. As you said, Dr. Schiff, it’s difficult to sort out menopausal effects in a clinical study because there are so many things going on in a woman’s life at that time. These women may have prolonged sleep latency or insomnia, they’re having hot flushes and vaginal discomfort, and they may be having trouble at home or at work. But they’ve handled a lot of problems up until this point in their lives and have not been depressed, so I’m inclined to think estrogen deprivation is at least partly responsible.

We have other good drugs now for depression. But estrogen is certainly something to consider as part of the therapy.*

Schiff: Have you found that a lot of women who start HRT say they feel better, and that their mood improves?

Nachtigall: Absolutely.

Schiff: Dr. Sarrel, is there any support for this effect of estrogen in the psychiatric literature?

Sarrel: Yes. Data published within the past 12 months indicate quite clearly that estrogen, particularly estradiol, has beneficial effects on the brain in patients with anxiety disorders and even in major clinical depression.¹⁵ In the treatment of patients who have become psychotic postpartum, estradiol has now been demonstrated to stop the psychosis. So estradiol’s actions in the brain are very positive from a psychiatric standpoint.

Schiff: Returning to the issue of continuance, then, why do women discontinue a therapy in such high numbers if it’s making them feel better?

Nachtigall: They stop because of side effects, but also because they hear bad things about hormones on the television news or from some friend or relative. So, in answer to your question, I say many women stop not because of fear of cancer or fear of breakthrough bleeding but because of fear itself. And the media now supply that 24 hours a day. However, if they’re getting good support from their health-care providers, they’re less likely to stop for either of these reasons. That’s why women in clinical trials have much higher continuance rates than women from the general population.

* Postmenopausal hormone therapy is indicated for treatment of vasomotor symptoms and vaginal atrophy and for prevention of osteoporosis. No other uses are currently FDA-approved.