How does PMOS impact brain health?
According to the 2024 study on Associations of PCOS with Indicators of Brain Health at Midlife, individuals with PMOS exhibit lower cognitive performance and lower white matter integrity at midlife,
PMOS is one of the most common, most profound and most overlooked health conditions affecting individuals assigned female at birth. It is a multi-system disorder which impacts hormonal, menstrual, reproductive/maternal, cardio-metabolic, oncological, mental/neurological, sexual and immune system health. In this article we explore the link between PMOS and Brain Health.
At its core, PMOS is associated with abnormal functioning of the system of hormones that connects the hypothalamus, the pituitary and the ovaries (the HPO-axis).[1] As a result, PMOS is associated with hyperandrogenism (HA) or androgen excess (AE), elevated levels of androgens in individuals assigned female at birth.
Elevated androgens disrupt the way that adipose tissue metabolizes glucose. The adipose tissue produces less adiponectin, a hormone that helps with insulin sensitivity and inflammation, and more leptin, a hormone that causes you to feel hungry in efforts to maintain enough fat stores for long-term health. As a result, 65-70% of individuals with PMOS develop insulin resistance (IR).[2] In another study insulin resistance was shown to affect up to 95% of individuals with PMOS who are overweight and up to 75% of individuals who are lean.[3]
Initially, the pancreas compensates for insulin resistance by producing more insulin resulting in hyperinsulinemia.[4] Eventually, the pancreas is no longer able to produce enough insulin to maintain healthy levels of blood sugar and the individual develops hyperglycemia, or high blood sugar.[5] Uncontrolled high blood sugar eventually leads to prediabetes and/or type 2 diabetes; more than 50% of individuals with PMOS develop type 2 diabetes before the age of 40.[6]
Insulin resistance is also linked to Alzheimer’s disease with it sometimes referred to as “type 3 diabetes”;[7] individuals with PMOS may be at up to 2x the risk of developing dementia[8] with some mild cognitive impairment starting in mid-life.[9]
The underlying cause of PMOS is a result of a complex interaction of genetic, epigenetic and environmental factors.[10] Genetic factors relate to how individual or groups of genes are implicated in health and disease.[11] The genetic link underlying PMOS is far more complex than a single inherited gene and genetic factors explain less than 10% of PMOS heritability.[12] Epigenetic factors relate to how genes are expressed or function, in response to the environmental factors within the womb or later in life.[13] Environmental factors include lifestyle, diet, stress / trauma and exposure to endocrine-disruptors,[14] natural or man-made chemicals that may mimic, block or interfere with the body’s hormones.[15]
Biological children of mothers with PMOS are therefore exposed in utero (within the womb) to elevated levels of androgens.[16] Although the specific mechanisms are not well understood, this exposure to elevated androgens is believed to alter the development and functioning of certain parts of the brain.[17][18][19] Individuals with PMOS are therefore 1.7-2.3x more likely to have a child with attention-deficit hyperactivity disorder (ADHD) and have an increased likelihood of having ADHD themselves.[20][21][22]
Biological children of mothers with PMOS can also be exposed in utero to elevated levels of glucose and insulin. This exposure results in a number of genetic variations, changes in protein levels and the production of toxins.[23][24] A number of these mechanisms are believed to result in impaired neuronal connectivity, the extent to which neurons are connected through neural networks. This impaired neuronal connectivity negativity impacts cognition, the “mental action or process of acquiring knowledge and understanding through thought, experience and the senses”,[25] thereby increasing the risk of ASD in offspring. Individuals with PMOS are 35% more likely to have a first child with autism spectrum disorder (ASD)[26] and have an increased likelihood of having autism themselves.[27][28]
No explicit link has firmly been established between PMOS and premenstrual dysmorphic disorder (PMDD),[29] an extreme form of premenstrual syndrome (PMS) with significant mental and physical impairments in the week leading up to menses, the onset of a period, and then improvement in or absence of symptoms in the intervening weeks.[30] However, individuals with PMOS have a significantly increased likelihood of having autism and/or attention deficit hyperactivity disorder or ADHD. While only 3-9% of the population experience PMDD,[31] one study found that 46% of women with ADHD and 92% of those with autism have a diagnosis of PMDD.[32]
PMOS can result in a very large burden of disease on the individual which varies and can compound across lifespan:
Challenges with academic attainment, with individuals <0.5 as likely to complete a university level education;[33]
Challenges with professional attainment, with a 25% higher risk of disability and employment days;[34]
Social withdrawal;
Sexual health issues (4x), reporting lower satisfaction and lower sexual function;[35][36][37]
Relationship problems; and
3x as likely to experience “very poor” or “poor” health in the mid-40s.[38]
Individuals with PMOS have increased risk of developing mental health conditions, including:
Depression and anxiety, with particularly high rates amongst young women;[39][40]
Attempted suicide;[41][42]
Eating disorders, spanning binge eating disorder, night eating syndrome, bulimia nervosa and anorexia nervosa;[43][44][45] and
Post-partum depression (also known as perinatal depression), a mood disorder which may be experienced by pregnant or postpartum women.[46]
Individuals with PMOS are at 1.5x increased risk of developing post-traumatic stress disorder (PTSD)[47] although it is unclear whether there is a causal relationship and, if so, whether PMOS causes PTSD, PTSD causes PMOS or both.[48] Potential mechanisms linking PMOS and PTSD include shared genetic variants,[49] dysregulation of the hypothalamic-pituitary-adrenal axis (HPA-axis),[50] higher prevalence of adverse childhood experiences or trauma,[51] changes in appearance that can lead to poor self-esteem and psychological distress and increased prevalence of mental health conditions.
Individuals with epilepsy are 1.5x as likely to exhibit PMOS symptoms and have heightened levels of androgens.[52] Epilepsy is a disorder of the brain characterized by seizures, short alterations to normal brain activity.[53] Seizures are believed to interfere with the balance of the hypothalamic-pituitary-ovarian (HPO) axis.[54][55] Anti-seizure medications (ASMs) or anti-epileptic drugs (AEDs) may also cause abnormalities with PMOS-like symptoms due to interference with the functioning of the HPO axis.[56]
Overall risk factors for brain health include:[57]
Insulin resistance;
Hypertension (high blood pressure);
Hyperglycemia (high blood sugar);
Dyslipidemia (high cholesterol);
Increasing age;
Family history of dementia;
Having diabetes;
Having Down syndrome;
Untreated vision or hearing loss;
Use of tabacco;
High alcohol consumption;
Having a high body mass index (BMI);
Having sleep apnea or other sleep disturbances;
Lack of consumption of fruits and vegetables;
Use of certain medications that might worsen memory such as diphenhydramine, oxybutynin and sedatives;
Exposure to air pollution;
Suffering from depression; and
Experiencing traumatic brain injury.
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Complications - Brain