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expert reaction to study looking at HRT and depression during the menopause

A study published in JAMA Network Open looks at use of Hormone Replacement Therapy (HRT) and depression during menopause in a cohort of Danish women.


Prof Matt Sydes, Professor of Clinical Trials & Methodology, MRC Clinical Trials Unit (CTU), UCL, said:

“This is not a randomised controlled trial.  It isn’t possible to tell whether the factors that drive the decision to start hormone therapy are connected to the outcomes of interest here.  What drives the choice to visit the family doctor and the joint decision to start HRT?  Could mood disturbance be part of this?  The rate of prior depression appears much lower in the non-hormone therapy group than the hormone therapy group.  If people are already on anti-depressants for prior depression, how does this impact the choice to start HRT or the chances of a subsequent diagnosis of depression?  There are previous randomised trials of HRT.  What have they reported on subsequent depression, or what could they link to national records to find out?”


Prof Ciara McCabe, Professor of Neuroscience, Psychopharmacology and Mental Health, University of Reading, said:

“It is unclear how the authors can separate out any peri/menopause mood changes from Hormone Therapy mood changes.  Many women begin taking Hormone Therapy precisely because of negative changes in their mood which fits with the report that the incidence of depression was greatest after initiation and then gradually declined.  If Hormone Therapy was causing the depression I wonder why the depression would gradually decline with continued Hormone Therapy use.”


Prof David Curtis, Honorary Professor, UCL Genetics Institute, UCL, said:

“This is an observational study which finds that women prescribed systemic hormone replacement therapy (HRT) were more likely to receive a hospital diagnosis of depression soon afterwards.  While this might be because HRT increases depression risk, we would also see this if women with more severe menopausal symptoms were more likely to be prescribed HRT but also more likely to become depressed.  Alternatively, women who were developing depression might complain of exacerbated menopausal symptoms and be prescribed HRT, but only later be diagnosed with depression at a hospital.  So overall I’m afraid I don’t think study can really throw any light as to whether or not HRT has any effect on depression risk.”



‘Association of Hormone Therapy With Depression During Menopause in a Cohort of Danish Women’ by Marie K. Wium-Andersen et al. was published in JAMA Network Open at 15:00 UK time on Tuesday 1 November 2022.

DOI: 10.1001/jamanetworkopen.2022.39491



Declared interests

Prof Matt Sydes: “No financial or scientific conflicts to declare.”

Prof Ciara McCabe: “None.”

Prof David Curtis: “I have no conflict of interest to declare.”

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