PMOS- Part 1 Diagnosis and Root Causes
PCOS (Polycystic Ovarian Syndrome) has gotten a long overdue rebrand and a new name to better reflect what is going on in the body. The condition formerly known as PCOS is now called PMOS or Polyendocrine Metabolic Ovarian Syndrome. This is significant because 10% of women have this condition and it has significant comorbidities and chronic disease risk. It is the most common endocrine condition affecting fertility. The name game confusion is due to the fact you DO NOT actually need to have the findings of cysts on the ovaries for the diagnosis. The new name is more reflective of the pathophysiology and thus will increase awareness and earlier diagnosis which can improve outcomes and reduce progression of other associated comorbid conditions (ideally). So the new name omits “cysts” and captures the involvement of the endocrine and metabolic pathways involved in addition to the ovaries.
Diagnostic Criteria
The most commonly used diagnostic checklist calls for two out of the three criteria:
- Reduced ovulation and anovulatory cycles – meaning there are menstrual irregularities and skipped menstrual cycles suggesting ovulation is not occurring each month. Cycles tend to be greater than 35 days long and often fewer than 8 cycles per year.
- Clinical findings or lab findings of excess androgens – this is basically signs of too much testosterone which could be acne, hair growth on face or abdomen / chest, hair loss in a female pattern baldness and lab values of elevated testosterone or other androgens.
- Polycystic ovaries or multiple follicles on ultrasound.
In order to diagnose PMOS- in addition to meeting these criteria, other conditions which can cause similar symptoms should be ruled out- such as thyroid conditions and adrenal hyperplasia and elevations in prolactin. Historically this was thought to be a disorder of the ovaries but in actuality it is a multisystem endocrine imbalance involving insulin, the androgens such as testosterone, the brain and the ovaries!
Pathophysiology of PMOS
Understanding the systems involved is important in the functional medicine model as we always want to take the root cause and personalized approach when possible. PMOS has diversity in how it presents and seems to be multifactorial when it comes down to causative factors. Not all patients have the outward signs of excess testosterone, just like not all patients have cysts on the ovaries. Anovulation is not always a defining feature either. Just like snowflakes, each patient with PMOS might “look different” outwardly, on paper, in the lab and diagnostic data. What is common among all patients is the following:
Hyperinsulinemia– There is a bidirectional relationship between the excess insulin produced by the pancreas and the testosterone excess in PMOS. This is one of the key signals driving a feed forward cycle of testosterone production in the ovaries and progression toward insulin resistance which then causes more insulin production.
Hyperandrogenism– In patients with PMOS, the feedback loop that contributes to the follicle on the ovary maturing is disrupted in part due to the amplification of Luteinizing Hormone by the excess insulin. This balance is critical for ovulation. The “arrested follicles” and the anovulation contribute to the infertility issues common with PMOS. These immature follicles sometimes form cysts hence the former name of the condition.
Insulin Resistance and Metabolic Dysfunction– Insulin resistance plays a central role in PMOS. As a result of the hyperinsulinemia again there is a bidirectional relationship between that and insulin resistance. The more insulin produced by the pancreas, the more resistant cells become and then the pancreas compensates by ratcheting up production even more. The insulin stimulates the testosterone production- so you can see how this takes on a snowball effect once the delicate balance is disrupted. We know that insulin resistance is associated with a host of other medical risks and conditions including obesity, hypertension, metabolic associated liver disease , heart disease, diabetes and elevated cholesterol……just to name a few. This is why it is critical to catch the diagnosis early and intervene.
Associated Symptoms and Diagnoses
The diagnosis of PMOS does not mean the affected person will have all of these signs and symptoms – but the risk is higher for developing the following:
Infertility
Obesity
Blood sugar elevations
Diabetes Type 2
Hypertension
Hyperlipidemia
Metabolic Associated Steatohepatic Disease
Coronary Artery Disease
Depression
Anxiety
Acne
Alopecia
Hirsuitism
Root Causes of PMOS
In the functional medicine model we often try to identify when possible root causes, antecedents, triggers and mediators of the problem. Like many things PMOS is multifactorial.
Genetics and Epigenics
Researchers have identified several genes in twin studies and in Genome Wide Association Data (GWAS) suggesting genetic predispositions influenced by lifestyle and environmental exposures. Most of these genes have something to do with hormones and hormone receptors and enzymes in the brain and ovaries.
Gestational Exposures
It is suspected that prenatal exposures to higher levels of AMH (Anti-Muellerian Hormone), androgens and endocrine disrupting chemicals all may contribute to a higher risk of PMOS in the adult. In addition, growth restriction and low birth weight may also have some association.
Lifestyle Factors
Lifestyle factors and environmental exposures that contribute to insulin resistance and obesity are risk factors leading to the feed forward cycle of hyperinsulinemia. This is important as if lifestyle factors are a root cause of the pathophysiology this means that these are actionable items for the treatment. The most studied relate to dietary patterns, physical activity, sleep / circadian rhythm and stress. As with any issue related to the neuroendocrine system all of these factors matter when it comes to homeostasis and optimal functioning of the human body.
There is an association between dietary patterns that have high glycemic impact (high carbohydrates and low fiber basically) as well as diets that are associated with fat accumulation and obesity. Not surprisingly, sedentary lifestyle is also associated with higher risk of PMOS.
Microbiome Influence
Not surprisingly that there is an association between PMOS and the quality of the microbiome. Seems like everything is influenced by the symbiotic relationship between the commensal or friendly gut bacteria and risk of chronic disease. It turns out that the gut microbiota influence hormone signaling in a variety of ways related to gut permeability, inflammatory signaling and bile acid metabolism related to liver function.
Mitochondrial Health
It is understood now that the mitochondria are not just the “powerhouse” energy producers of the cell but play a much larger role in insulin sensing and the development of insulin resistance than previously thought. Therefore anything that dysregulates the function of the mitochondria can impact insulin resistance. This includes factors such as infection and trauma. Mitochondrial dysfunction in the cells of the ovary affect the function in hormone balance and inflammation which are part of the pathophysiology.
Environmental Factors
Endocrine disrupting chemicals seem to be implicated in the pathophysiology of PMOS. The ones best studied are substances such as Bispenol-A (BPA), Parabens and Triclosan. These particular toxicants have been found to have a negative impact on the metabolic and endocrine function of the ovaries. These are ubiquitous in the environment and commonly found in plastics, cosmetics, food, soap, toothpaste and pharmaceuticals. There is no doubt that these are part of our total body burden of environmental exposures and may be increasing risk of PMOS in those more susceptible.
References:
Prosperi S, Chiarelli F. Insulin resistance, metabolic syndrome and polycystic ovaries: an intriguing conundrum. Front Endocrinol (Lausanne). 2025 Oct 1;16:1669716. doi: 10.3389/fendo.2025.1669716. PMID: 41103651; PMCID: PMC12520869.
Sanchez-Garrido MA, Tena-Sempere M. Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies. Mol Metab. 2020 May;35:100937. doi: 10.1016/j.molmet.2020.01.001. Epub 2020 Feb 5. PMID: 32244180; PMCID: PMC7115104.
Thomas G Gulliams PhD. The Standard Monograph Series PCOS Volume 20 No. 2
