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PMOS proposed as developmental disorder shaped by gene-environment and epigenetic mechanismsNew framework explains how polycystic ovary syndrome develops in women
Frontiers in MedicinePublished October 29, 2026DOI ↗Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease
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Key Takeaway
Interpret the PMOS developmental framework as hypothesis-generating, not practice-changing.
This publication is a review that combines a proposed pathogenetic framework for polyendocrine metabolic ovarian syndrome (PMOS) with discussion of the 2023 International Evidence-based Guideline for PCOS. It is not a primary trial and reports no sample size, intervention, comparator, or follow-up.
The authors propose that PMOS is a developmental disorder consistent with the developmental origin of health and disease (DOHaD) theory, involving gene-environment interactions and epigenetic mechanisms. This is a theoretical model rather than a tested causal pathway.
The review also summarizes biological rationale relevant to the 2023 International Evidence-based Guideline for PCOS, including the use of anti-Müllerian hormone, postponing diagnosis until after puberty, and healthy lifestyle behaviors. No effect sizes, absolute numbers, or statistical comparisons are reported.
No limitations, adverse events, or funding and conflict of interest information are reported. The authors caution that the review discusses theoretical frameworks and guidelines, not primary clinical trial data.
For practice, the guideline-related content on AMH, timing of diagnosis, and lifestyle behaviors may be informative, but the PMOS pathogenetic framework should be treated as hypothesis-generating rather than practice-changing.
How this fits prior evidence
This review extends prior coverage of PMOS as a multi-layered network of endocrine, metabolic, and immune dysfunction by proposing a developmental DOHaD framework involving gene-environment and epigenetic mechanisms. Like the prior follicular arrest model, this pathogenetic account is hypothesis-generating rather than practice-changing. The guideline discussion is separate from prior observational findings on resting energy expenditure, microglia as candidate contributors, prepregnancy HOMA-IR and pregnancy outcomes, and dry eye symptoms, and does not confirm or contrast those results directly.
Living with polycystic ovary syndrome (PCOS) can feel like a complex puzzle. New research helps piece that puzzle together by looking at how the condition starts. Experts now suggest that the condition may be a developmental disorder. This means it could begin early in life because of how genes and the environment interact with each other.
This theory is based on the idea that early life experiences and environmental factors can leave lasting marks on how the body functions. By looking at these early stages, doctors hope to better understand why some women develop the condition while others do not. This perspective focuses on the underlying biology of the body's development.
While this research provides a helpful framework for understanding the roots of the condition, it is important to remember that these are theoretical models. The findings are based on a review of existing guidelines and biological theories rather than new clinical trials. These ideas help shape how doctors think about the condition and how they might approach care for women of reproductive age.
What this means for you:
New research suggests polycystic ovary syndrome may begin during early development through gene and environment interactions.
Common questions
What causes polycystic ovary syndrome?
New research suggests the condition may be a developmental disorder. This means it could be caused by interactions between a person's genes and their environment during early development. This theory helps doctors understand the underlying biological reasons why the condition occurs in women of reproductive age.
What are the current guidelines for treating PCOS?
The 2023 International Evidence-based Guideline for PCOS includes several key points. These include the use of anti-Müllerian hormone, the practice of waiting until after puberty to make a diagnosis, and the importance of maintaining healthy lifestyle behaviors for those affected.
Polycystic ovary syndrome (PCOS) is the most common reproductive and endocrine disorder affecting women in their reproductive age. PCOS is characterized by clustering of reproductive disturbances, including, but not limited to, hypothalamus-pituitary-ovarian axis dysfunction, chronic anovulation, excess androgen, and subfertility. PCOS extends beyond reproductive dysfunction to involve metabolic, endocrine, and cardiometabolic abnormalities. Therefore, it has recently been redefined as polyendocrine metabolic ovarian syndrome (PMOS). Despite the evolution of diagnostic criteria for PMOS in recent decades, there persists a knowledge gap regarding its origins and pathophysiology. Genetic studies have identified candidate genes associated with PMOS, but genetic factors alone cannot account for its varied phenotypes. The diverse phenotypes observed in PMOS instead point to a complex gene-environment interaction, thereby paving the way for epigenetic mechanisms to explain this heterogeneous trait. Emerging evidence suggests that epigenetic alterations during critical developmental periods, particularly in utero and during puberty, may contribute to the reproductive, metabolic, and endocrine manifestations of PMOS. These observations may re-frame PMOS as a developmental disorder that follows the developmental origin of health and disease (DOHaD) theory. In this review, we propose a comprehensive framework to address the complexity of PMOS pathogenesis and phenotypes. We investigated how environmental exposures during critical windows may shape the epigenome and contribute to PMOS development. The review also examines the biological rationale of the 2023 International Evidence-based Guideline for PCOS, including the use of anti-Müllerian hormone, postponing diagnosis until after puberty, and recommendations for healthy lifestyle behaviors.
