Historically, medical research has predominantly focused on males, leaving health conditions affecting females in the dark.
Consequently, though around half of the world’s population will experience menopause, it’s still a relatively mysterious transition.
Because people are, on average, living longer and because females tend to live longer than males, females will make up the majority of the aging population.
So, tackling questions about menopause has never been more timely.
Scientists are starting to gain more insight into menopause — including ZOE’s scientists — but we sorely need more research.
Gut bacteria and menopause
Scientists have found that a thriving, diverse gut microbiome is linked to many aspects of health.
Here, we’ll focus on how your gut microbiome changes during menopause and how that might influence disease risk and symptoms during the transition.
But because menopause is under studied, and gut microbiome science is in its infancy, the evidence so far is patchy.
With that caveat, let’s dive in.
Your microbiome through time
Over the course of your life, your gut microbiome changes. One of the greatest shifts comes at a young age, when you first switch from milk to food.
Later, as you reach adolescence, there’s another significant change. At this point, the gut microbiome of females — but not males — becomes more adult-like.
Experts believe these changes are driven by female sex hormones, which help shape your gut microbiome throughout life.
Hormonal differences may help explain the differences between the gut microbiomes of men and women during adulthood.
When you reach menopause — 1 year after your last period — your ovaries have stopped producing sex hormones, which include progesterone and estrogen.
Because sex hormones affect your gut bacteria, and because hormone levels change, it makes sense that there might be changes in your gut microbiome during this time.
The reduction in estrogen, in particular, drives many of the symptoms associated with menopause, including hot flashes, night sweats, vaginal dryness, and mood changes.
It’s also responsible for the increased risk of certain health conditions, like heart disease and osteoporosis.
During the menopause transition and beyond, some people take hormone replacement therapy (HRT), which raises levels of sex hormones and can help reduce symptoms and disease risk.
So, how do gut bacteria influence levels of sex hormones?
Gut microbes and sex hormones
As we mentioned, sex hormones appear to influence the makeup of your gut microbiome.
But the relationship between gut bacteria and hormones is a two-way street.
Gut bacteria also influence the amount of hormones in your blood. To understand how they do this, we’ll have to get into the weeds a little bit.
The main estrogens in your body are estrone, estriol, and estradiol. When they reach your liver, they’re metabolized.
As part of this process, they’re irreversibly attached to other compounds. This means that they can’t affect the cells and tissues of your body as they normally would.
Once they’re bound up, they’re sent to your gut and pooped out. In other words, the liver removes them from your bloodstream.
But, once in your gut, some bacteria can “recycle” estrogens. These bacteria can unbind the compounds from estrogens, allowing them to reenter your blood supply.
It’s a similar story for other hormones, including progesterone and androgens, which include testosterone.
So, it seems that hormones help feed some species of gut bacteria. And in return, gut bacteria help them pass back into your bloodstream to be reused.
Although studies into the gut microbiome and hormone levels are few and far between, some have produced interesting findings.
One example is a small, carefully designed study in Austria. It included 16 women who were taking hormonal contraceptives. These drugs tend to reduce levels of estradiol and progesterone.
Generally, a more diverse gut microbiome is a healthy gut microbiome. The scientists found that decreases in these hormones were linked to reduced gut microbiome diversity.
There were also changes in the relative abundance of some types of bacteria.
For instance, hormonal contraceptives were associated with lower numbers of Eubacterium, some of which are considered “good” gut bugs, like E. eligens.
The researchers also showed that levels of bacteria fluctuated throughout the participants’ menstrual cycles — further evidence of hormones’ influence over gut bacteria.
Overall, the evidence suggests that the two-way street between hormones and gut bacteria runs like this: Higher levels of estrogen and progesterone boost gut bacteria diversity by feeding them.
And at the same time, greater gut bacteria diversity means more hormones are recycled and sent back into circulation.
Postmenopausal women have very low levels of estrogens and progesterone. So, recycling by your gut bugs might play an even greater part in determining the levels of these hormones in your blood.
And there are other ways that sex hormones and gut bacteria might interact.
Having a thriving population of bacteria in your gut is good news. However, if these microbes or the chemicals they produce make it into your bloodstream, it can be bad news. This is called translocation.
To stop this from happening, the lining of your gut has numerous methods of defense. Your intestinal epithelium — a thin layer of cells that lines your intestines — is a major player.
But sometimes, these defensive barriers are breached, allowing gut bacteria or their products to translocate.
When this happens, it can cause inflammation, which is linked to all manner of health conditions, including heart disease, cancer, and diabetes.
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There’s some evidence — although mostly in animal and laboratory studies — that sex hormones help sure up your gut lining.
For instance, a lab study showed that estradiol protects mucus-producing cells in the intestinal epithelium against injury. And a study using rats and human tissue found that activating estrogen receptors helped reduce translocation.
Plus, a study in pregnant participants found that progesterone made their gut linings less “leaky.”
There’s little direct evidence that menopause is associated with gut barrier integrity. But some research does suggest that translocation of microbes from your intestines happens more often during menopause.
At this stage, scientists don’t know to what extent translocation influences symptoms and disease risk during menopause. But it’s certainly an area worth researching.
A role in bone health?
So, we’ve seen that gut bacteria can “recycle” estrogen, and a drop in sex hormone levels might increase the chance of translocation.
But links between gut bacteria and menopause don’t stop there. Next, let’s talk about bones.
As estrogen levels drop off, the risk of developing osteoporosis increases. Osteoporosis is a condition that makes bones weaker, which increases the risk of fractures.
Perhaps surprisingly, gut bacteria play a part in maintaining good bone health.
And some early research suggests that manipulating the gut microbiome with probiotics might help keep bones strong.
What are isoflavones?
Certain plants contain phytoestrogens. These include isoflavones, which are found in soy.
Some gut bacteria can convert isoflavones into estrogen-like compounds, which can bind to estrogen receptors. In other words, these compounds can act like estrogen.
But the story gets a little complicated: When estrogen levels in your body are high, these estrogen-like compounds appear to block the action of estrogen.
But when levels of estrogen are low — as they are during the menopause transition and beyond — these compounds work in a similar way to estrogen.
And research suggests that consuming soy isoflavones might help reduce the risk of some menopause symptoms, including hot flashes, by mimicking estrogen’s action.
So, once again, gut bacteria might help restore some of the activity associated with sex hormones in people experiencing menopause.
What’s changing in the gut microbiome?
We’ve seen how gut bacteria might influence the levels of sex hormones, but what are the specific changes to the gut microbiome during this time of life?
Only a few studies have investigated this question. Most of these were relatively small, and the results are mixed.
To make sense of the findings, a review from April 2022 looked at 10 studies on menopause, sex hormones, and gut bacteria.
In five of these studies, the scientists found a decrease in gut bacteria diversity after menopause or in women with low estrogen levels.
And three of the 10 studies found that after menopause, women’s gut microbiomes were more similar to men's than premenopausal women's.
Some of the studies also found changes in the levels of certain gut bacteria. For instance, after menopause, people tended to have lower levels of Firmicutes and Ruminococcus.
And they had higher levels of Butyricimonas, Dorea, Prevotella, Sutterella, and Bacteroides.
However, as the authors explain, we don’t really know what these changes mean for health. At this stage, it’s not clear whether these shifts are good or bad. But we do have some clues.
For instance, Ruminococci ferment fiber in your gut and produce short-chain fatty acids (SCFAs), which benefit your health in a number of ways. So, having fewer of these might not be a good thing.
Also, as the authors of the review explain, “Dorea, Prevotella, and Sutterella have all been previously associated with obesity in multiple studies.” So, an increase in these may negatively impact health.
But they also note that Prevotella’s impact on health is still up for debate. We simply don’t know enough about how individual gut bacteria influence health to understand what these changes mean.
In November 2022, ZOE scientists published one of the largest studies to date to investigate gut bacteria during menopause.
We took data from more than 1,000 women as part of our PREDICT 1 study.
Our scientists found that postmenopausal women had increased levels of bacteria associated with inflammation and obesity.
Does HRT undo the changes?
By this point, you might be wondering whether HRT, which increases levels of sex hormones, might undo these changes.
There simply hasn’t been much research into it. However, one study provides a hint. Researchers recruited females under 40 whose ovaries had stopped producing hormones.
These individuals had particularly high levels of Eggerthella, compared with healthy participants. The authors explain that Eggerthella may be linked to widespread inflammation.
And when the participants received estradiol hormone therapy, levels of Eggerthella dropped.
But these participants weren’t postmenopausal, and the researchers only focused on one bacterium. Overall, we simply don’t know how HRT influences the gut microbiome yet.
The evidence so far suggests that menopause affects your gut microbiome. But at this stage, we don’t know what that means for your health.
And although hormones seem to play a direct role in these changes, other factors might also be important.
For instance, as the authors of a review explain, progesterone influences the immune system and the speed at which food travels through your gut.
With less progesterone in your body, changes to your immune system and gut transit time could play a part in changing your gut microbiome.
So, we’ll end this feature as we began: We need to carry out much, much more research into menopause.
But, in the meantime, there are things you can do today to help bolster your gut microbiome, whatever stage of life you’re in. If you want to improve the health of your gut and its microbial visitors, ZOE has some advice.
And, if you’re interested in learning which bacteria are in your gut, start by taking our free quiz.
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