Many readers of Natural Womanhood are familiar with the negative effects of combined oral contraceptives (COCs), commonly known as the Pill. COCs, in particular, contain both synthetic estrogen and progestin, vs the so-called “mini-Pill,” which contains only progestin. We have written extensively about how these different contraceptive pills and devices work, how the Pill affects your cyclesy el numerous side effects of contraceptives, one of which is mental health changes including depresión.
But until recently, we didn’t know por qué birth control caused these mental health effects (which, by the way, are a risk for both COCs and the mini-Pill). But recent research has found that the birth control pill can alter not only your hormonal balance, but also the balance of bacteria in your gut. This astounding link between the hormonal and gut changes behind the Pill and the combined effect on users’ brains are finally providing clues to understand the Pill’s effects on mental health.
Your brain and your “second brain” (aka your gut!)
At first glance, the gut and brain seem to have very different jobs. The former digests food and absorbs nutrients, while the latter processes thoughts, stores memories, and controls movement. Yet scientists now know they share many features and communicate more closely than once imagined.
Both the gut and the brain are packed with complex networks of cells that send and receive signals, both rely on chemical messengers called neurotransmitters, and both influence how we feel physically and emotionally. In fact, the gut contains its own network of neurons lining the intestinal tract, known as the enteric nervous system, which is sometimes called the “second brain” because it can operate independently while still talking to the brain through nerves and chemical signals [1].
For over a decade now, scientists have been studying the enteric nervous system–but each one of us is already familiar with its effects. If you’ve ever had that feeling of “butterflies in your stomach,” that’s your second brain firing!
Communication between the gut and the brain
The gut and brain are linked through what is called the gut-brain axis, a two-way communication system that uses nerves, hormones, and immune signals. One of the most important pathways is the vagus nerve, which acts like a high-speed information cable between the brain and the gut. The gut also produces and responds to many of the same neurotransmitters found in the brain, including serotonin and dopamine.
Both the gut and brain are deeply influenced by the body’s internal environment. Just as stress, diet, and infection can alter brain function, they can also shift the composition of the gut microbiome (or the community of helpful bacteria living in your gut) and change how the gut communicates with the brain. This shared sensitivity means that disruptions in gut health can affect mental health, and vice versa. Research into this connection is revealing how the gut’s microbial community, chemical messengers, and immune signals can shape brain function, influencing mood, cognition, and even risk for neurological disorders [2,3].
How does estrogen affect the gut?
This constant back-and-forth between the gut and brain does not happen in isolation. Hormones, particularly estrogen, also play an important role in the conversation. The gut microbiome helps regulate how much estrogen circulates in the body by producing enzymes that can activate or inactivate the hormone. In return, estrogen can change the makeup of the gut’s microbial community, shaping which bacteria thrive [4]. This synergistic community is even given a fancy name—the estrobolome.
The gut microbiome helps regulate how much estrogen circulates in the body by producing enzymes that can activate or inactivate the hormone. In return, estrogen can change the makeup of the gut’s microbial community, shaping which bacteria thrive.
Because estrogen affects brain regions involved in mood, memory, and cognition, any shifts in this gut-estrogen connection can also influence brain function. This three-way relationship between the gut, estrogen, and the brain is called the gut-estrogen-brain axis, and it is becoming a key focus for understanding how hormonal changes, gut health, and mental well-being are linked.
The gut-estrogen-brain axis
The gut-estrogen-brain axis works through a constant feedback loop. Bacteria in the gut can reactivate estrogen, allowing it to travel through the bloodstream and reach various organs, including the brain. Estrogen influences brain function by acting on areas that control mood, memory, and learning, and it can also affect the production of brain chemicals such as serotonin and dopamine.
At the same time, estrogen shapes which microbes live in the gut, influencing the balance of its bacterial community and how it communicates with the brain. When the gut microbiome becomes unbalanced, estrogen levels can shift, potentially changing brain function and emotional health. Understanding this relationship is important because it means that changes to hormones, gut bacteria, or brain activity can ripple through the entire system.
When the gut microbiome becomes unbalanced, estrogen levels can shift, potentially changing brain function and emotional health.
Combined oral contraceptives introduce additional synthetic hormones
So what do oral contraceptives have to do with any of this? Recently, scientists have been interested in how oral contraceptive use might influence this gut-estrogen-brain connection. As stated earlier, combined oral contraceptives (COCs) contain synthetic forms of estrogen and progesterone which disrupt the body’s natural hormone patterns; this is how they prevent pregnancy, as well as reduce symptoms of reproductive issues like uterine fibroids or heavy menstrual bleeding. But by changing the body’s estrogen levels, COCs may also affect the gut microbiome and the signals it sends to the brain. The synthetic hormones can likewise alter the microbial community, which may change how much estrogen is available to circulate in the body.
By changing the body’s estrogen levels, COCs may also affect the gut microbiome and the signals it sends to the brain. The synthetic hormones can likewise alter the microbial community, which may change how much estrogen is available to circulate in the body.
A recent article en Contemporary OB/GYN resumido the research on how COCs alter the gut microbiome and in turn affect mental health [5]. Interestingly, side effects of long term COCs include ambos mood disorders (like depression) and gastrointestinal (GI) symptoms. And while you may only think of antibiotics as medicines that disrupt your gut, recent evidence suggests COCs also have the ability to disrupt the composition of bacteria living in your gut [5]. This led researchers to wonder whether the synthetic estrogen from the Pill was changing the gut microbiome and therefore affecting patients’ moods. To do this, they compiled existing human and animal studies from a literature search in PubMed.
Research suggests that women using hormonal contraceptives may experience changes in the diversity and activity of gut bacteria. COC users have reduced types of certain bacteria compared to non-users, and this disruption could have effects on various health outcomes. For example, there is a potential increased risk of developing or relapsing Crohn’s disease (CD) in women taking COCs, with risk increasing with the length of COC use and becoming insignificant upon discontinuation [6]. COCs may also alter intestinal permeability, a factor in CD pathogenesis (e.g., a study which examined sex differences in gastrointestinal (GI) barrier function found oral contraceptive users had the highest intestinal permeability when compared to women with natural menstrual cycles and men [7]). (This effect appears limited to estrogen-containing oral contraceptives, and does not include the progestin-only “mini-Pill.”)
All these changes can affect gut barrier function, allowing inflammatory signals or neurotransmitter precursors to reach the brain more easily. Remember that the bacteria in the gut are responsible for producing many of the neurotransmitters that reach the brain, so this hormonal contraception-induced dysbiosis can disrupt the balance of these neurotransmitters, potentially leading to mental health complications [5].
Additional research supporting the gut-estrogen-brain connection
Since a landmark Danish study published in 2016, which found a “small but real” increased risk of depression and antidepressant use with hormonal birth control (particularly in adolescents), we’ve known the mental health risks of hormonal birth control are indeed real. The same research group also linked hormonal contraception use to increased suicide attempts and suicides, highlighting the extremely serious nature of the birth control-mental health connection [8]. But again, until recent research on the gut and its connection to the brain was discovered, the mechanism behind birth control’s effects on mental health were unknown.
Further underscoring the connection between gut health and mental health, the Contemporary OB/GYN review article explained several animal studies that have shown that gut microbiome disruption or antibiotic-mediated dysbiosis can lead to depressive-like behaviors, which can be reversed by probiotics [9,10,11,12]. Likewise, a 2020 systematic review of human studies found a correlation between decreased diversity in gut microbiome and depression diagnoses [13].
However, conflicting research does exist: One longitudinal study following 10 healthy premenopausal women (aged 16-40) who started oral contraceptives between January 2015 and August 2018 demonstrated no significant change in the gut microbiome diversity or composition. However, this study did identify marginal changes in the function of the gut microbiome, and the type of COC used in this study was not evaluated [14].
Lo esencial
Changes in your “second brain” could certainly explain why some individuals report mood changes, increased anxiety, or depressive symptoms while on birth control, though the effects vary widely between people. Not all studies find strong links, and many factors, like the type of contraceptive, hormone dose, and an individual’s existing gut microbiome, likely influence outcomes.
Still, the gut-estrogen-brain axis highlights how hormones, gut microbes, and brain function are closely interconnected. Hormonal birth control can disrupt this delicate balance by altering estrogen levels and changing gut microbial activity, and this may contribute to the mood changes some women experience.
This is just one of several ways these medications may impact the body, alongside effects on gut microbes, hormone regulation, and reproductive health. While some people use these methods safely, the emerging research highlights the importance of considering natural fertility awareness methods, which avoid introducing synthetic hormones and allow the body’s own systems to function without interference.
