One of the most misunderstood aspects of polycystic ovary syndrome, now increasingly reframed as Polyendocrine Metabolic Ovarian Syndrome (PMOS), is the role insulin plays in the disorder. For years, insulin resistance in PMOS was discussed primarily through the lens of diabetes risk and abnormal glucose metabolism. Yet insulin’s role in the syndrome appears to extend far beyond blood sugar alone.
What many patients, and even many clinicians outside endocrinology and reproductive medicine, may not realize is that insulin does not act uniformly across all tissues in PMOS. In some organs, insulin signaling becomes impaired. In others, it appears paradoxically preserved. This selective pattern may help explain one of the central paradoxes of the syndrome: How the same patient can simultaneously demonstrate insulin resistance and excessive ovarian androgen production.
In simplified terms, insulin appears to encounter two very different “doors” in the body. At the level of skeletal muscle and other metabolic tissues, the door becomes increasingly difficult to open. Insulin binds its receptor, but downstream signaling involved in glucose uptake becomes impaired. Glucose transporters such as GLUT4 fail to efficiently move glucose into muscle cells, and the body compensates by producing progressively larger amounts of insulin in an attempt to overcome this resistance.
At the level of the ovary, however, the story may be very different. The ovarian door may remain remarkably permissive to insulin signaling.
This distinction is critical because insulin in the ovary does far more than regulate glucose metabolism. Within ovarian theca cells, insulin acts synergistically with luteinizing hormone (LH) to stimulate androgen production. Even as skeletal muscle becomes resistant to insulin’s metabolic effects, ovarian steroidogenic pathways may continue responding to elevated circulating insulin levels. The result is a biologic mismatch: The body produces more and more insulin to compensate for metabolic resistance, while the ovary continues to “hear” insulin’s androgen-stimulating signal clearly.
Much of the public discussion surrounding PMOS focuses on insulin resistance. Far less attention is paid to what might be described as ovarian insulin permissiveness.
Emerging research suggests this selective signaling pattern may involve divergence between post-receptor insulin pathways. The phosphoinositide 3-kinase (PI3K) pathway, which mediates many of insulin’s metabolic effects including glucose uptake, appears impaired in insulin-resistant tissues. Meanwhile, signaling pathways involved in cellular growth and steroidogenesis may remain relatively preserved within ovarian tissue, allowing insulin to continue amplifying androgen production despite systemic metabolic dysfunction.
Clinically, this helps explain why many women with PMOS can demonstrate significant hyperandrogenic symptoms long before overt diabetes develops. Glucose values may remain “normal” for years while compensatory hyperinsulinemia quietly drives ovarian androgen excess, suppresses sex hormone-binding globulin production in the liver, and contributes to follicular arrest. It also helps explain why PMOS cannot be understood solely through the lens of obesity.
Some patients with PMOS are lean. Others have substantial visceral adiposity. Some exhibit profound insulin resistance, while others demonstrate more neuroendocrine-predominant phenotypes. The syndrome remains highly heterogeneous. Yet even in lean phenotypes, subtle alterations in insulin dynamics may still contribute to ovarian dysfunction in ways not always captured by routine metabolic testing.
Increasingly, researchers are also examining the evolutionary origins of these physiologic patterns. In a 2025 review published in Endocrinology, Dr. Daniel Dumesic and colleagues explored the possibility that many PMOS-associated traits may have conferred ancestral survival advantages under conditions very different from modern industrialized life.
From an evolutionary perspective, preferential abdominal fat accumulation, insulin resistance, increased androgen activity, and enhanced energy conservation may once have represented adaptive physiologic strategies during periods of food scarcity and infectious stress. Visceral and omental fat, often discussed today primarily in negative terms, likely served important survival functions. These metabolically active fat depots provide rapid mobilization of stored energy during famine and produce cytokines involved in immune regulation during infectious challenges. Increased androgen exposure may also have enhanced muscularity and physical resilience under harsh environmental conditions. In ancestral environments characterized by intermittent food availability, high physical exertion, and infectious threats, these physiologic adaptations may have promoted survival.
The problem is that modern environments bear little resemblance to the environments in which these systems evolved. Today, caloric abundance coexists with unprecedented physical inactivity. Human metabolism evolved for persistence hunting, food scarcity, and continuous movement. Modern life often consists of prolonged sitting, ultra-processed caloric excess, sleep disruption, and chronic psychosocial stress layered onto ancient metabolic circuitry designed for survival rather than abundance. The same physiologic tendencies that may once have protected against starvation may now contribute to progressive visceral adiposity, chronic hyperinsulinemia, inflammatory amplification, and cardiometabolic disease.
As Dumesic and colleagues note, PMOS may reflect a mismatch between ancient adaptive physiology and contemporary environmental conditions. The syndrome represents not simply reproductive dysfunction, but a broader tradeoff between survival and reproduction shaped across evolutionary time.
Importantly, this evolutionary framing should not be interpreted fatalistically, nor should it be used to romanticize the syndrome. PMOS remains associated with significant reproductive, metabolic, cardiovascular, and psychological burdens. But understanding the condition through a systems and evolutionary lens may help shift the conversation away from simplistic narratives centered solely on willpower or body size.
Many patients with PMOS have spent years being told to “just lose weight,” often without acknowledgment of the biologic forces influencing appetite regulation, insulin signaling, fat distribution, androgen activity, and metabolic efficiency. A systems-based framework does not eliminate personal responsibility for health behaviors, but it does provide a more physiologically grounded understanding of why weight regulation and metabolic health may be particularly complex in this population.
It also reframes treatment itself. Metformin, inositol, GLP-1 receptor agonists, nutritional interventions, resistance training, sleep optimization, and movement are increasingly understood not as isolated “weight loss tools,” but as interventions targeting interconnected metabolic and neuroendocrine pathways. Emerging therapies may eventually allow clinicians to tailor treatment according to dominant physiologic drivers in specific PMOS phenotypes rather than approaching all patients through a single uniform framework.
At its core, PMOS may represent a condition in which ancient survival circuitry collides with modern environmental reality. And perhaps nowhere is that contradiction more visible than in insulin itself: resisted in one tissue, amplified in another, simultaneously protecting survival while quietly driving dysfunction.
This is one of the central themes I explore throughout my book, The Quest for Fertility. Many patients arrive believing their struggles stem from a lack of willpower, poor choices, or a personal failure to do what seems to work for everyone else. Yet the science increasingly suggests a far more complex story, one involving metabolism, hormones, neuroendocrine signaling, genetics, environment, and evolutionary biology.
Understanding these interconnected systems does not eliminate personal responsibility for health. Rather, it allows us to replace blame with biology and frustration with understanding.
Perhaps the most important question is this: If PMOS is fundamentally a disorder of interconnected systems rather than simply a disorder of the ovary, how should that change the way we diagnose it, treat it, and talk about it with our patients?
Oluyemisi (Yemi) Famuyiwa is a double board-certified reproductive endocrinologist, infertility specialist, and obstetrician-gynecologist, and the founder and medical director of Montgomery Fertility Center in Rockville, Maryland. There she provides personalized fertility care and advanced reproductive treatments, including IVF, fertility preservation, donor egg IVF, recurrent implantation failure management, and male fertility services.
She completed her residency in obstetrics and gynecology at Georgetown University Hospital and her fellowship in reproductive endocrinology and infertility at the National Institutes of Health. She serves as an associate clinical professor at George Washington University School of Medicine and Health Sciences and is an attending physician at Holy Cross Hospital.
A nationally recognized fertility expert, educator, and advocate, Famuyiwa is dedicated to advancing reproductive health through patient care, research, public education, and mentorship. She hosts the Fertile Talks podcast, where she explores fertility, women’s health, lifestyle medicine, and reproductive wellness with experts and patients alike, and she is a frequent speaker on fertility, nutrition, epigenetics, environmental health, and reproductive longevity. She is the author of The Quest for Fertility: A Comprehensive Approach to Fertility Preparation, an evidence-based guide that empowers individuals and couples to optimize their reproductive health and navigate their fertility journey with confidence. Her research includes work in the Journal of Clinical Endocrinology and Metabolism examining the role of insulin-like growth factors and sex steroid regulation in reproductive tissues.
Famuyiwa has been recognized as a Castle Connolly Top Doctor, one of America’s Most Honored Doctors, a Top Black Doctor, and an Exceptional Woman in Medicine. She shares updates on Linktree, LinkedIn, YouTube, Facebook, Instagram, and X. Her articles on fertility, women’s health, and reproductive medicine can be found on KevinMD.
