Older women who have used hormone therapy after menopause may see their depressive symptoms rise slightly faster over the years than men of the same age, according to a new study of healthy older adults published in the journal BMC Medicine1. The difference was small, and when the women using hormones were compared with women who never used them, the gap was not clear enough to rule out chance1.
What the study found
Researchers followed 585 people with an average age of 71.6 years, drawn from the Harvard Aging Brain Study and related studies1. None of them had memory or thinking problems when they joined, a group researchers call “cognitively unimpaired”1. Just over half, 58.3 percent, were women1.
Among the women, 42 percent said they were using, or had used, hormone therapy after menopause1. This treatment is commonly used for menopause symptoms such as hot flashes and night sweats, and for depressive symptoms1.
Over time, women who had used hormone therapy reported greater increases in depressive symptoms than men of the same age, and this was statistically significant, meaning it was unlikely to be chance alone1. The link held even after the researchers took into account whether people had a past history of depression1.
But the more natural comparison, women who used hormones versus women who did not, did not reach statistical significance1. In the group as a whole, the authors concluded, female users and non-users did not differ in how their depression scores changed, and the contrast with men should be read with that in mind1.
How the study worked
Mood was measured with the Geriatric Depression Scale, a questionnaire made for older adults1. At the start, 7 percent of the women scored in the mild to moderate range, between 11 and 19 points1. The researchers then used statistical models to track how each person’s score changed over time in relation to hormone therapy use1.
Hormone use was self-reported: people said whether they used it now or had used it before1.
A clue from brain scans
The researchers also looked at white matter hyperintensities, small areas of change in the brain’s wiring that show up on scans and that the authors describe as white matter lesions1. The amount of these changes seemed to shape the link between hormone therapy and mood1. In women with a large volume of them, hormone users reported greater depressive symptoms over time than men, but again not compared with women who did not use hormones1.
The authors said the findings point to the need to study which menopause treatment factors may affect depressive symptoms in older women, and how this relates to white matter lesions1.
What it does not show yet
- Cause and effect. This was an observational study, meaning researchers watched what happened rather than giving people a treatment. It cannot establish that hormone therapy causes worsening mood1.
- A large effect. The differences were described as subtle1.
- A difference from other women. The comparison between women who used hormones and women who did not was not statistically significant, either overall or among those with more white matter changes1.
- Who it applies to. The group was mostly older and free of memory problems, so the results may not carry over to younger women going through menopause now1.
The available coverage does not say which type of hormone therapy women used, at what age they started, or for how long. It also does not report the exact length of follow-up. These details matter, because earlier research suggests type and timing can make a difference (see below).
Who is behind it
The paper is titled “Longitudinal associations of hormone therapy and depressive symptoms in cognitively unimpaired older women”1. Its authors include K. A. Lopez Garcia, listed first, along with Reisa Sperling, Rachel Buckley and Gillian Coughlan, listed last1. It appeared as an early, peer-reviewed accepted version of the article, meaning the final edited version may still change1. The sources available to Biohack do not say who funded the work or whether the authors reported any conflicts of interest.
Biohack read this study through a news write-up rather than the paper itself. Some of the statistical figures in that write-up appear to have mismatched signs, so this article reports the findings in words rather than repeating every number.
How it fits with earlier research
Research on hormone therapy and mood has pointed in different directions, often depending on who was studied and when they started treatment.
Studies that also found a link with more depressive symptoms
The Canadian Longitudinal Study on Aging, a large national study, looked at depression and hormone therapy in women aged 45 to 642. After adjusting for factors such as age, income, weight, smoking, drinking and social support, women using hormone therapy had 1.21 times greater odds of depressive symptoms2. The same project found that early menopause, before age 40, was linked with 1.45 times greater odds of depressive symptoms than menopause between 45 and 552. Like the new study, this was observational.
Trials that found mood benefits around menopause
Placebo-controlled trials, where some women get a dummy treatment for comparison, have looked at women closer to menopause. In a one-year trial at the University of North Carolina, women aged 45 to 60 in or just after the menopause transition received either estradiol through the skin with progesterone, or a placebo3. Seventeen percent of the hormone group developed clinically significant depression, compared with 32 percent of the placebo group3. The study was funded by the National Institutes of Health3. Its lead researcher said the results did not mean every woman in perimenopause should be prescribed hormone therapy3.
The KEEPS-Cog trial gave recently postmenopausal women estrogen and progesterone by mouth (220 women), estradiol through the skin with progesterone by mouth (211 women), or a placebo (262 women) for up to four years4. The pill form was linked with improvements in anxiety and depression symptoms, while the skin form did not benefit mood4. Neither form changed thinking skills4.
The timing question
Researchers have proposed a “critical window” idea: that hormone therapy may act differently depending on how close to menopause it starts4. Results from the Women’s Health Initiative showed that estrogen started in women 65 or older did not improve thinking or lower dementia risk4. The new study adds data from a much older group, average age 71.6, but the coverage does not say when these women began treatment1.
What to watch next
- The final paper. The fully edited version in BMC Medicine may add details on hormone type, timing and follow-up length1.
- Brain scan subgroups. Further work is needed to learn whether white matter health picks out a group of women whose mood follows a different path on hormone therapy in later life1.
- Trials in older women. Most placebo-controlled mood trials so far have been in women around menopause43, not in women in their 70s.
This article reports research findings and is not medical advice. Decisions about hormone therapy are best made with a doctor who knows a person’s full history.
