Menopause 'may mix up exercise reward pathways in the brain'

10:30 EDT 29 Jul 2016 | NHS

"Menopause 'crushes your motivation to exercise'," the Mail Online reports. But before you bin your gym card, the study it reports on involved rats, not women.

The female rats were genetically engineered to have either a high or low exercise capacity.

Those who had their ovaries removed to model human menopause showed lower activity on a running wheel over the following 11 weeks compared with those who hadn't.

And surprisingly the rats that had prior high exercise capacity had no protection – in fact, their activity levels declined more than the rats who'd been less active to start with.

The reason seemed to be because lack of oestrogen alters dopamine activity in the brain's motivation and reward centre.

In simplistic terms, dopamine is often described as a "feel-good" chemical and has been linked to many addictive activities, such as gambling.

The findings may give a possible explanation for why some women going through the menopause may feel less motivated to exercise.

But humans aren't genetically engineered rats, and we don't know that our biological mechanisms work in exactly the same way.  

Also, the rats were not given any type of hormone replacement therapy (HRT) to boost oestrogen levels, so these finding may not be applicable for women who choose to have HRT.

Physical activity is recommended at all stages of life, and many postmenopausal women enjoy very active lifestyles.

The best thing for people to do is to follow physical activity recommendations where possible, doing what feels comfortable for them.

Where did the story come from?

The study was carried out by researchers from the University of Missouri and the University of Kansas Medical Center, and received funding from the US National Institutes of Health.

It was published in the peer-reviewed journal, Physiology and Behavior.

The Mail's headline boldly states that the findings directly relate to menopausal women – only hidden well down in the article does it say that it involved rats.

What kind of research was this?

This animal research in genetically engineered rats aimed to see whether those bred to have high exercise capacity are better protected from losing interest in physical activity after they have their ovaries removed, compared with rats bred to have low exercise capacity.

As the researchers say, most people fail to meet physical activity recommendations. Rats bred to have high or low running capacity have also been shown to have different behaviour on a voluntary running wheel.

The researchers think this may be because of differences in dopamine pathways in a brain region called the nucleus accumbens, which control self-motivated activity and reward.  

Oestrogen has been shown to stimulate dopamine receptors and maintain activity in rats.

A loss of oestrogen from the rat's ovaries being removed – modelling human menopause – may be expected to reduce activity. This is what the researchers aimed to examine.

Animal studies can give a good insight into biological mechanisms that may be similar in humans, but we are not genetically engineered rats.

What did the research involve?

The research involved two types of rats – those bred to have either a high or low exercise capacity.

There were 40 female rats in each group, who were then randomised to either have their ovaries removed or a sham operation. 

After one week of recovery they were given access to a voluntary running wheel. Their wheel running was monitored weekly for 11 weeks.

The rats also had other assessments of body composition and blood glucose control. Their brain tissue was examined after death, paying close attention to dopamine activity in the nucleus accumbens.

What were the basic results?

The high exercise capacity rats ran more on the wheel compared with the low capacity rats.

Ovary removal significantly reduced activity in both groups compared with rats who received the sham procedure.

Strangely, while the high capacity rats who had their ovaries removed demonstrated a weekly reduction in the distance they ran on the wheel over the 11 weeks, the low capacity rats with their ovaries removed actually increased the amount they ran each week.

This meant that by the end of the 11 weeks there was no difference in running between the high and low capacity rats who had their ovaries removed. 

Brain examination showed that high capacity rats had greater dopamine activity than the low capacity rats.

Removing the ovaries was associated with increased dopamine blocking in the high capacity rats, but was linked to reduced dopamine blocking in the low capacity rats.

How did the researchers interpret the results?

The researchers concluded that the dopamine system in the brain's nucleus accumbens plays an important role in motivation to run in female rats.

High capacity rats run significantly more than low capacity rats, which is the result of a higher ratio of excitatory to inhibitory dopamine receptors.

The researchers say that despite greater inherent motivation to run, high capacity rats are not protected against the effect that ovary removal has upon dopamine activity.

It reduces the ratio of excitatory to inhibitory dopamine activity, "for which intrinsic fitness does not confer protection".


This research uses an animal model of human menopause – surgically removing the ovaries – to see what effect this would have on rats bred to have either high or low exercise capacity.  

As oestrogen has been shown to have an effect on dopamine activity in the brain's motivation centre, the researchers expected that ovary removal would have an effect on the rats' activity.

However, what was unexpected was that having prior high exercise capacity seemed to give no protection – these rats seemed to decrease their activity much more than rats that had low activity to start with.

These findings could be stretched to explain a possible reason why women who've been through natural or induced menopause (such as having their ovaries removed) may feel less motivated to exercise, particularly if they were very active previously – because of changes in dopamine activity in the brain.

However, humans are obviously not genetically engineered rats running on a wheel. Animal studies can give a good insight into biological mechanisms that may be similar in humans, but we don't know that things work exactly the same.

We also don't know whether these are permanent changes that would persist in the long term, or whether they're only short-term changes around the time of menopause. 

Overall, the findings are of interest, but they do not have any preventative or therapeutic implications.

Physical activity is recommended at all stages of life, and many postmenopausal women enjoy very active lifestyles.

Exercise can be especially important at this time, as it can help boost bone strength, which can weaken during the menopause.

The best thing for people to do is follow physical activity recommendations where possible, doing what feels comfortable for them.

For all adults, including people over 65 who are generally fit and healthy, this is at least 150 minutes of moderate aerobic activity every week (such as cycling or walking) combined with strength exercises that work all muscle groups on two or more days a week. 

Links To The Headlines

How menopause 'crushes your motivation to exercise': Brain changes mean 'many women feel less pleasure and reward from their workout in later life'. Mail Online, July 29 2016

Links To Science

Park YM, Kanaley JA, Padilla J, et al. Effects of intrinsic aerobic capacity and ovariectomy on voluntary wheel running and nucleus accumbens dopamine receptor gene expression. Physiology & Behavior. Published online June 11 2016

Original Article: Menopause 'may mix up exercise reward pathways in the brain'


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