Allison Sayre, MSN, WHNP-BC
Polycystic ovary syndrome (PCOS) is the most commonly diagnosed female endocrine disorder.[1] While historically viewed through a gynecological lens, PCOS is increasingly recognized as a multisystem pathology involving complex interactions between endocrine, metabolic, immune, and neurological pathways.[1] Common features include irregular menstrual cycles, ovarian cysts, elevated androgens (such as testosterone), insulin resistance, and metabolic issues.[1][2] Alongside these features are less visible but significant symptoms like mood disturbances and cognitive difficulties, including brain fog, memory lapses, and poor concentration, with emerging evidence suggesting that these neuropsychological symptoms are not just incidental, but may be driven by underlying biological mechanisms.
While self-reporting of these symptoms is valuable, researchers are now beginning to piece together evidence for the biological mechanisms that link PCOS to emotional and cognitive dysfunction. Here, we will discuss the underlying biological mechanisms linking PCOS to cognitive and psychological symptoms, and we will also examine the fascinating findings in neuroimaging.
Cognitive Symptoms in PCOS: What Patients Report
Clinical observations and patient surveys suggest that many women with PCOS experience some degree of cognitive dysfunction. The most common issues confirmed by research relate to:
- Short-term memory
- Attention span
- Executive function (planning, organizing, problem-solving)
- Verbal fluency
- Visuospatial skills (visual perception of the spatial relationships of objects)
While these symptoms are subjective and vary in severity, their prevalence across patient populations has prompted the investigation of potential biological mechanisms.[3]
Hormonal Dysregulation and the Brain
One of the primary features of PCOS is elevated levels of the typically “male” hormone, testosterone (affecting 80-90% of those with the disorder). Androgens influence brain development and function, and abnormal levels of testosterone have been linked to cognitive alterations. This makes sense, given that several brain regions involved in cognition, including the prefrontal cortex, hippocampus, and amygdala, express androgen receptors.[4]
In humans, studies comparing women with PCOS to healthy controls have found correlations between elevated androgens and poorer performance on tasks involving verbal memory, executive function, and visuospatial skills. Though causality has not been established, excess androgens remain a likely player in the cognitive effects of PCOS.[3][4]
Women with PCOS also secrete higher levels of luteinizing hormone (LH) with more frequency. LH may stimulate the secretion of additional testosterone by the ovaries, amplifying the above effects. LH levels are also independently correlated with reduced activity in brain regions associated with cognitive function and specifically, language processing.[5]
Insulin Resistance and Brain Metabolism
Another central feature of PCOS is insulin resistance (IR), affecting approximately 75% of individuals with the condition.[2] IR is a condition in which cells become less responsive to insulin, impairing glucose uptake and disrupting metabolic signaling, and it may develop or be exacerbated due to the influence of excess androgens.[5] This leads to the ongoing debate over whether insulin’s role in PCOS is symptomatic or causal in nature.[2][4]
While IR can lead to metabolic and vascular conditions that are known to interfere with cognitive function, insulin has direct effects on the brain, unrelated to these other conditions. The brain is metabolically demanding and relies heavily on glucose to fuel its function. Insulin is needed to facilitate glucose uptake as it enhances the activity of glucose transporters and supports neuronal signaling pathways involved in energy metabolism. As a result, when IR develops, the brain may experience energy deficits and disruptions in these key insulin-mediated signaling pathways.[6] Additionally, prolonged exposure to excess insulin can reduce the number of insulin receptors at the blood–brain barrier, further impairing glucose uptake. These factors may be especially relevant in PCOS, where studies have linked markers of IR to lower performance on cognitive tests, even after controlling for other variables like body mass index (BMI) and mood symptoms.[4]
Immune and Cytokine Responses
PCOS is also characterized by elevated circulating levels of cytokines and white blood cells that can cross the blood-brain barrier, negatively impacting cognitive health. These cytokines can interfere with systems associated with memory, global cognition, attention, and executive function.[4] While research on the relationship between PCOS and neuronal health is still emerging, correlations between systemic cytokine response and cognitive symptoms in PCOS populations have been documented. This suggests that imbalanced immune response may be another mechanism linking PCOS to cognitive dysfunction.
Mood and Cognitive Function
It is also important to consider the psychological comorbidities of PCOS. Women with PCOS tend to have elevated rates of stress, tension, low mood, sleep trouble, and apathy, along with lower reported scores for quality of life.[1][7] Many patients report that these worries or challenges in mood stem from changes to their appearance (hirsutism and changes to body composition), however, these mood issues can independently impair cognitive performance, as well.[1] Neurobiological changes associated with mood, such as dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, altered neurotransmitter activity, and hippocampal atrophy, can overlap with and amplify cognitive symptoms.[7] Thus, the cognitive dysfunction seen in PCOS may result from the interaction of direct physiological effects (such as hyperandrogenism, insulin resistance, and elevated cytokine response) with indirect effects mediated by an imbalanced mood.
Neuroimaging Findings
Advanced imaging techniques such as functional magnetic resonance imaging (fMRI) are beginning to reveal structural and functional brain differences in women with PCOS.
Specifically, PCOS induces functional alterations in brain regions responsible for visual working memory, such as the right middle and superior frontal gyrus.[5] An fMRI study analyzed the effects of overexposure to androgens on brain activity during working memory processing. They reported a higher activation within the right superior and inferior parietal lobes in PCOS patients (n=41) versus healthy controls (n=41) during the task, suggesting PCOS may negatively affect executive function.[5]
Studies have identified multiple physical and functional changes to the PCOS brain, including:
- Reduced total brain volume and reduced gray matter volume (accentuated in those with higher BMI scores).[1]
- Increased volume of the pituitary gland and decreased volume of the amygdala and hippocampus.[1]
- Altered white matter integrity, associated with lower cognitive performance and brain aging.[8]
- Differences in functional connectivity, showing a disruption of hypothalamic neuroplasticity.[1]
These neuroimaging findings provide additional evidence that PCOS is associated with measurable changes in brain structure and function, supporting patient reports of cognitive difficulties.
In Summary
PCOS is increasingly being recognized as a multisystem condition that extends beyond reproductive and metabolic concerns to include significant effects on brain function. Rather than stemming from a single cause, cognitive changes likely result from the cumulative effects of hormonal imbalances, insulin resistance, immune dysregulation, and mood disturbances. This intricate interplay highlights the need for a holistic understanding of PCOS as a systemic condition, and these findings call for a broader, more integrated approach to understanding and managing its diverse manifestations.
Disclaimer:
The information provided is for educational purposes only. Consult your physician or healthcare practitioner if you have specific questions before instituting any changes in your daily lifestyle including changes in diet, exercise, and supplement use.
Allison Sayre, MSN, WHNP specializes in women's health and functional medicine, blending both traditional and integrative approaches. With over 18 years of experience, she has empowered women to reclaim their health through personalized nutrition and supplementation, hormone balancing, and lifestyle modifications. She received her Bachelor of Science from Mount Carmel College of Nursing and her Master of Science from the University of Cincinnati. She has been a certified women’s health nurse practitioner since 2014 and has continued her education and training in functional medicine from both the Institute for Functional Medicine as well as the American Academy of Anti-Aging Medicine