La is an inevitable stage of women’s lives that not only produces hot flashes or a change in metabolism that makes it difficult to maintain weight, muscle mass or bone strength. Mental health is one of the most affected aspects during this period. Hormone replacement therapy (HRT) is one of the most used resources to alleviate physical symptoms or improve mood, but the complexity of the effects of menopause and the diversity of its effects on each woman make it impossible to offer general solutions.
Today, a team of researchers led by Barbara Sahakian, from the University of Cambridge, publishes a study, based on data from nearly 125,000 women from the United Kingdom Biobank, in which the effects of menopause and the use of HRT on three factors are analyzed: mental health, in particular anxiety and depression, sleep quality, and brain structure, based on resonance images with which the volume of gray matter in key areas for memory was measured. and emotional regulation. The results are striking, although their interpretation requires caution.
Regarding the impact on mental health, they saw that menopause was related to more anxiety, depression and sleep problems, something predictable. The surprise came when comparing women who received HRT with those who did not receive it. The medicated group had worse mental health indicators and were more likely to have consulted a doctor for anxiety or depression.
This relationship between hormone therapy and worse health outcomes was also seen in the analysis of a subgroup of more than 10,000 women who had MRIs. As expected, postmenopausal women had less gray matter than premenopausal women in the hippocampus, responsible for forming and storing memories, or the cingulate cortex, a key part of the brain in regulating emotions or attention. What was striking was that, among menopausal women, the reduction was greater among those who had received HRT.
Finally, unlike mood or general brain structure, in tests of cognitive ability, such as memory, there were no differences between premenopausal and menopausal women, whether they took hormones or not, and HRT improved the reaction speed in menopausal women, which is a little less than in younger women.
The authors do not say that their results show that hormone therapy worsens women’s mental health or shrinks their gray matter. The study is observational and takes a snapshot of a specific moment, it does not follow the women by measuring their health over time. It cannot, therefore, establish a cause and effect relationship. The question that arises in studies like this is whether HRT worsens mental health or brain atrophy or whether women with worse depressive or insomnia symptoms are more likely to be prescribed hormones.
To address this question, the researchers did a new analysis in which they compared the mental health histories of women who were not using HRT at the beginning of the study, but who did start taking it at a later evaluation. The analysis of 7,000 women revealed that those who started HRT had already consulted their doctors more for nervousness, anxiety or depression before starting than those who never used the therapy. “This suggests that the observed association is mainly explained by women with pre-existing psychiatric symptoms being more likely to be prescribed HRT, and not necessarily by HRT being the cause of worsening mental health,” the Cambridge team writes.
Clinical guidelines recommend considering HRT to alleviate depressive symptoms linked to menopause, something that could explain, at least in part, this association. For Rafael Romero, director of the Laboratory of Neuroimaging and Brain Networks at the University of Seville and co-author of the study, his results also suggest that, despite these guideline recommendations, “hormonal therapy is not the best treatment for depression and anxiety.” “It may be more advisable to offer other treatments before hormonal therapy, such as exercise or an improvement in diet and, in more severe cases, a specific pharmacological treatment for depression or anxiety,” he points out.
Francisco Carmona, director of the Endometriosis Unit at the Hospital Clinic of Barcelona and scientific director of Women’s, who was not involved in the study, believes that this type of work is interesting, but that the results should not be used to reject HRT. “There was a time when it was considered good for all women and then for none. Now we are in a trend of greater caution, which I think these results reinforce. We know that HRT cannot be universal, but it can be good for some women, individualizing the treatment and giving it in well-controlled medical environments,” she explains.
Silvia P. González, spokesperson for the Spanish Association for the Study of Menopause (AEEM), is more critical of the results. “The conclusions are too strong for a study with many biases,” he says. “They say that hormone therapy does not seem to mitigate the negative effects of menopause on mental health, but, really, with what they present, you cannot say that they do not,” he continues. “To be able to say that hormonal treatment is not useful at a neurological level, you would need a study with a prospective design and homogeneous groups and with the same type of hormonal therapy, because now we know that it is not hormonal therapy for menopause but hormonal therapies, and that perhaps depending on the route, the dose, the type of hormone…”, he adds. “When a study of this size is presented, it may give us the feeling that the conclusions are going to be very solid, but if the study is done poorly, it doesn’t have to be,” he emphasizes.
The authors of the study, the largest to have investigated the effects of menopause and HRT on mental health and brain structure, do not consider that their results suggest that hormone therapy should be abandoned, but they do recall the complex relationship between menopause, mental health and hormone treatment. On the one hand, their data show that menopause affects the structure of the brain and increases the risk of emotional problems. Furthermore, they consider that hormone therapy is not a happy pill for all women and remember that its most proven effects are in the relief of physical symptoms such as hot flashes. In any case, they suggest that the decision to start this type of treatment should be individualized.
Barbara Sahakian also comments on another finding that may help understand other health problems. “The regions where they saw the differences [en el volumen de la materia gris] “They are among those who are usually affected by Alzheimer’s,” she points out. “Menopause could make these women more vulnerable. Although that is not all, it may help explain why we see almost twice as many cases of dementia in women as in men,” he adds.
To overcome the limitations of this study, Carmona and Romero agree that it would be interesting to do another prospective study that could establish causal relationships and with a design that would allow a good understanding of the effect of hormones on gray matter volume, depression or anxiety.
