The use of birth control pills is widespread, but the impact of oral contraceptives on mental health remains an area of concern. Oral contraceptive pills (OCP’s) can influence mood, anxiety levels and overall mental well-being in some people. These effects are largely mediated by hormonal disruption, nutrient depletion and changes in gut microbiota. All of which can affect neurotransmitter balance, stress regulation, and inflammation.
How hormonal disruption influences mood.
OCP’s work by suppressing natural hormone production, replacing endogenous oestrogen and progesterone with synthetic versions. These synthetic hormones do not have the same effects on the brain and nervous system as hormones produced naturally. Oestrogen supports serotonin synthesis and receptor sensitivity, contributing to mood stability and cognitive function. While some synthetic oestrogens mimic these effects to a degree, they do not fully replicate the neuroprotective properties of natural oestrogen, potentially leading to altered serotonin activity.
Progesterone converts into neurosteroids such as allopregnanolone and these interact with the GABAergic system, the brain’s main inhibitory neurotransmitter network – promoting relaxation and resilience to stress. However, synthetic progestins found in OCP’s don;t have the same calming effects, and in some cases, they may even increase susceptibility to anxiety and low mood. Some women experience a worsening of symptoms similar to premenstrual dysphoric disorder (PMDD), highlighting that the disruption of natural progesterone signalling plays a role in emotional regulation.
Beyond neurotransmitter interactions, OCP’s also affect the hypothalamic-pituitary-adrenal (HPA) axis, which controls the body’s response to stress. Long-term use has been associated with increased cortisol-binding globulin, reducing the availability of free cortisol. While cortisol is often viewed negatively in relation to chronic stress, an certain level is essential for energy regulation, focus and emotional balance. Dysregulation of the HPA axis, particularly a blunted or excessive cortisol response, is a known contributor to anxiety and depressive disorders.
Nutrient depletion contributes to mental health issues.
Several nutrients associated with good mental health are known to be reduced with long-term contraceptive use. This can compromise neurotransmitter synthesis and neurological health, leading to depression, low mood or anxiety.
OCP’s lower levels of vitamin B6, folate (B9), and vitamin B12. These nutrients play crucial roles in neurotransmitter production and methylation, a biochemical process essential for good mental health and brain function. If you are susceptible to potential issues with methylation due to having an MTHFR genetic deviation then OCP’s are more likely to lead to mental health issues. Folate and vitamin B12 are also important, as they influence homocysteine metabolism; elevated homocysteine is associated with neuroinflammation and impaired cognitive function, both of which are implicated in mood disorders. Vitamin B6 is required for the synthesis of serotonin and GABA and deficiency can lead to irritability, heightened stress sensitivity, and an increased risk of depressive symptoms.
Magnesium depletion is another concern, given its essential role in stress regulation and nervous system function. Magnesium acts as a natural NMDA receptor modulator, helping to dampen excessive excitatory signalling in the brain. Chronic deficiency has been linked to heightened anxiety, poor stress resilience, and even an increased risk of depression. Similarly, zinc is often reduced with OCP use. As zinc deficiency has been correlated with increased inflammation and a greater risk of mood disorders, its depletion may contribute to the psychological side effects reported by some women on the pill.
Vitamin D levels also appear to be negatively affected by OCP use, which is relevant given its role in serotonin production and immune regulation. Low vitamin D status has been linked to depressive symptoms, fatigue, and cognitive decline, further reinforcing the need to consider nutrient status when assessing mental health changes in OCP users.
How the Pill Affects Gut Microbes and Mood
Beyond its direct impact on hormones and nutrient status, OCP use has also been associated with alterations in gut microbes, which may also impact mental well-being. The gut-brain axis is now recognised as a regulator of mood and cognition, with disturbances in gut flora contributing to neuroinflammation, altered neurotransmitter production, and increased stress sensitivity.
Research suggests that OCPs may promote dysbiosis by reducing microbial diversity and encouraging the overgrowth of certain pathogenic bacteria. This shift in gut flora can increase intestinal permeability, often referred to as “leaky gut,” allowing inflammatory molecules to enter the bloodstream. Systemic inflammation is a well-established driver of depressive and anxiety-related symptoms, suggesting that OCP-induced gut changes may contribute to mental health disturbances.
Another key mechanism by which gut bacteria influence hormonal balance is through the enzyme beta-glucuronidase, which plays a role in oestrogen metabolism. Dysbiosis can disrupt this process, leading to impaired oestrogen recirculation and potentially exacerbating hormonal imbalances that influence mood. Also, as the gut produces a significant proportion of the body’s serotonin, alterations in microbial composition may impair serotonin synthesis, further contributing to depressive symptoms.
A Case Study: The Slow Onset of Emotional Distress
For some women, the mental health effects of the pill emerge gradually, making it difficult to pinpoint the contraceptive as a contributing factor. One such case was a young woman, Sophie, who was prescribed Microgynon at the age of 19 for contraceptive purposes. Initially, she noticed little change beyond the expected cycle regulation and a slight improvement in acne. However, by her early twenties, she began experiencing persistent feelings of emotional distress, fatigue, and eventually, depressive symptoms that escalated to self-harm. Despite having no significant history of mental health issues, she found herself increasingly withdrawn, overwhelmed, and prone to intense periods of sadness that seemed disproportionate to her life circumstances.
Over the years, Sophie sought support through therapy and lifestyle changes, yet her symptoms persisted. By the time she reached 23, her low mood was accompanied by frequent anxiety, poor stress tolerance, and intrusive negative thoughts. Suspecting a biochemical imbalance, she underwent organic acid testing, which revealed very low serotonin levels, as well as significant deficiencies in key B vitamins, including B6, B9 (folate), and B12. These findings aligned with the known effects of OCP-induced nutrient depletion and neurotransmitter dysregulation.
With this insight, a targeted intervention was introduced, focusing on restoring optimal serotonin function and correcting the nutrient imbalances. Sophie began a protocol that included active B-vitamin supplementation, increased dietary intake of magnesium and zinc, and additional support for gut health. Within weeks, she reported a noticeable improvement in her mood, energy levels, and ability to cope with stress. Over several months, her symptoms of depression and anxiety gradually lifted, and she no longer experienced the overwhelming emotional lows that had been experiencing.
Sophie’s case highlights the significant biochemical changes can be occur in certain individuals. It also demonstrates that these effects are not necessarily permanent and that once the underlying imbalances are addressed, mental health will significantly improve.
The connection between OCP use and mental health is highly individual but undeniably complex. For some women, the pill has minimal psychological effects, while for others, it can contribute to mood disturbances, heightened stress sensitivity, or even depressive symptoms. The underlying mechanisms—hormonal suppression, nutrient depletion, and gut microbiota disruption—highlight the need for a more personalised approach when prescribing and monitoring hormonal contraception. However, addressing biochemical imbalances through targeted nutrition, supplementation, and gut support can lead to improvements in well-being. As our understanding of these mechanisms grows, so too does the opportunity to provide women with more informed choices about their reproductive and mental health.
