Experts call for caution over study linking menopausal depression to oral hormones: ScienceAlert

A study linking data from a collection of national population and health registers in Denmark showed that postmenopausal women who received oral hormone therapy were more likely to receive a hospital diagnosis of depression soon after.

The researchers reported that the risk was highest in women aged 45 to 50 and in the first few years after starting hormone therapy, but the association gradually decreased over time.

But international experts outside the study talk about the limitations of population-based studies like this one — which bring into relief how little is known about menopause and depression — especially when hormone treatments can be incredibly effective for some women experiencing perimenopausal depression.

“Many women start taking hormone therapy precisely because of negative mood changes – which fits with the report that the incidence of depression was higher after starting and then gradually declined,” says neuroscientist Ciara McCabe from the University of Reading.

With this kind of study, it’s simply not possible to separate depression-related mood changes from any medication-related changes, nor to see what precipitated the use of hormone therapy.

“This is not a randomized controlled trial. It is not possible to say whether the factors driving the decision to start hormone therapy are associated with the outcomes we are interested in here,” says Matt Sydes of the UK Medical Research Council. Clinical trial Unit in London.

Psychiatrist Jayashri Kulkarni of Monash University in Australia, an expert in perimenopausal depression, shares the concern that large population studies like these “may be misinterpreted by women and their clinicians, leading to potentially worse outcomes for women who already struggle with menopausal depression and need hormone therapy.”

Dramatic reductions in hormone prescriptions in response to confusion about women’s health studies have happened in the past, such as in the early 2000s. “So many women have suffered as a result,” Kulkarni told ScienceAlert.

Being a retrospective observational study, there’s a lot that the Danish data set doesn’t capture – which serves as a good reminder of the limitations of these kinds of epidemiological studies, so let’s take a look.

Kulkani says the study lumps all estrogen hormone treatments together, when, for example, some forms of estrogen designed to treat menopausal hot flashes don’t reach the brain and so would have little effect on mood.

Fluctuating hormone levels in the brain affect mood, and menopause drugs—containing synthetic versions of the sex hormones estrogen and progesterone, either alone or in combination—work to stabilize these fluctuations.

The study also only had data on hospitalized cases of depression, and without capturing the finer details of the depression the women experienced and their personal histories, it says nothing about other factors affecting their mental health.

“It doesn’t take into account the very important nuances of diagnosing depression … nor the wide variation in forms of hormone treatments or the frequent fluctuations in mental health due to menopause,” Kulkarni told ScienceAlert.

As Kalkani pointed out to ScienceAlert, the diagnosis of depression has changed substantially in the two decades covered by the study, from 1995 to 2017.

And many new drugs for menopause hormones have been developed and continue to be developed, he says.

Depression is also a spectrum condition, occurring in many forms, associated with individual life events, and responding differently to treatment.

“Women have a whole range of differences in what symptoms they have, what’s going on [after their diagnosis] and what are the causes. For many women, trauma is the biggest factor that creates depression.”

Simply put, Kulkarni says these types of retrospective studies that examine decades of data are not the type of research needed to move the field forward.

It’s clinical trials that carefully diagnose depression and follow women through treatment, determining type, timing and dose, and neuroscience studies that look at how hormones affect the brain that will help better understand menopausal depression and the most effective treatments. for women, Kulkani explains.

“Research in this area is desperately needed – but what is really needed is a large, prospective, detailed clinical trial,” comparing hormonal treatments with standard antidepressants.

And that’s the biggest issue here that risks being overlooked: women’s health in general, but menopause in particular, is woefully understudied. The vast majority of people with depression also do not receive the minimum treatment they need.

As Kulkarni writes in the recent Nature Outlook In perspective, getting a depression diagnosis can be especially difficult for women, mainly because depression in women is so misunderstood.

This is a reflection of the systemic sexism that permeates biomedical research and which in turn affects the care women receive, she says.

“Many health professionals do not recognize menopause as the underlying causative factor in women with midlife depression and therefore do not prescribe hormone therapy,” Kulkarni writes.

“A large part of clinicians’ reluctance to prescribe [hormone therapy] for menopausal depression is the lack of knowledge about menopause – particularly how it affects the brain.”

For some women, trans men and non-binary people, menopause could be the first time they are diagnosed with depression. Others with a previous history of depression may experience a resurgence of depressive symptoms during menopause.

Either way, the incidence of depression peaks in the years around menopause. Suicide rates too. But menopausal depression is often diagnosed years later, if at all.

Complicating matters is the fact that psychological symptoms such as mood changes can precede physical symptoms of menopause by up to five years.

Clearly, much more research is needed to delve into the complexities of menopause and depression – and much more funding is needed to make this research a reality.

The study was published in JAMA Network Open.

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