For many years, anti-Müllerian hormone (AMH) was viewed primarily as an ovarian marker. Clinicians used it to estimate ovarian reserve, assess follicular activity, and counsel patients regarding reproductive aging and fertility treatment response. In polycystic ovary syndrome, now increasingly reframed as polyendocrine metabolic ovarian syndrome (PMOS), AMH levels were often recognized as elevated, largely because of the increased number of small arrested follicles characteristic of the condition.

But emerging evidence suggests AMH may not simply reflect the syndrome. It may help sustain it.

One of the central neuroendocrine abnormalities in PMOS involves disruption of pulsatile gonadotropin-releasing hormone (GnRH) secretion at the level of the hypothalamus. Under normal physiologic conditions, GnRH is not released continuously. Instead, it is secreted in carefully timed pulses, almost like a metronome coordinating the reproductive axis. These pulses stimulate the anterior pituitary to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH), hormones that in turn regulate ovarian follicular development, ovulation, and steroid hormone production.

The timing matters profoundly. If GnRH is secreted in a normal pulsatile rhythm, pituitary receptors have time to recover, recycle, and remain sensitive to signaling. But if GnRH secretion becomes excessively rapid or sustained, the downstream hormonal balance changes. In PMOS, this altered pulsatility often favors LH predominance relative to FSH, contributing to ovarian androgen excess and impaired follicular maturation.

The reproductive system, in many ways, depends on rhythm. At the center of this rhythm lies an intricate hypothalamic network often referred to as the KNDy neuron system. These neurons, located primarily within the arcuate nucleus of the hypothalamus, function as part of the pulse generator controlling GnRH secretion. Their name derives from the three neuropeptides they express: kisspeptin, neurokinin B, and dynorphin.

Kisspeptin functions as a major activator of GnRH neurons, effectively helping initiate pulsatile reproductive signaling. Neurokinin B appears to amplify and propagate the signal within the neuronal network, acting almost like an accelerator that helps sustain the pulse. Dynorphin, in contrast, serves as an inhibitory counterbalance, applying a braking mechanism that terminates the pulse and allows the system to reset before the next cycle begins.

The result is a highly coordinated oscillatory system. One way to conceptualize this is as a biologic metronome. Kisspeptin initiates the rhythm. Neurokinin B steps on the accelerator. Dynorphin applies the brakes. The pulses rise and fall in carefully regulated intervals, allowing the pituitary and ovary to respond appropriately.

In PMOS, however, this rhythm appears increasingly dysregulated. Many patients with PMOS demonstrate accelerated GnRH pulsatility and persistently elevated LH secretion. This altered neuroendocrine pattern is believed to contribute directly to excessive androgen production within ovarian theca cells. Yet for many years, the origin of this abnormal pulsatility remained poorly understood.

Emerging research has raised the possibility that AMH itself may participate directly in this process. In a landmark 2016 study published in Nature Communications, Paolo Giacobini and colleagues demonstrated that a substantial subset of GnRH neurons express anti-Müllerian hormone receptor type 2 (AMHR2), both in mice and humans. The investigators further showed that AMH could directly increase GnRH neuronal firing activity and stimulate LH pulsatility and secretion.

This finding was important because it suggested AMH may exert effects far beyond the ovary itself. Rather than functioning solely as a passive biomarker of follicular activity, AMH may also act centrally at the level of the hypothalamus, influencing the very pulse generator that governs reproductive hormone secretion.

The implications are potentially profound. In many patients with PMOS, circulating AMH levels are elevated because of the accumulation of small antral follicles. If elevated AMH simultaneously enhances GnRH neuronal activity and increases LH pulsatility, a self-reinforcing neuroendocrine loop may emerge. Increased LH stimulates ovarian androgen production. Hyperandrogenism contributes to follicular arrest. Follicular arrest increases the number of small follicles producing AMH. Elevated AMH may then further amplify GnRH pulsatility and LH predominance.

The metronome speeds up.

Importantly, this remains an evolving area of investigation rather than fully settled clinical doctrine. PMOS is highly heterogeneous, and it remains unclear to what extent AMH-driven neuroendocrine amplification contributes across all phenotypes of the syndrome. Much of the mechanistic work exploring AMH signaling at the hypothalamic level remains preclinical or translational. Nevertheless, the findings offer an intriguing framework for understanding why elevated LH pulsatility and androgen excess persist in many patients.

The concept also helps explain why PMOS cannot be understood solely as an ovarian disorder. The ovary is clearly involved, but increasingly appears to operate within a larger neuroendocrine network involving the hypothalamus, pituitary, insulin signaling pathways, adipose tissue, inflammatory mediators, and ovarian steroidogenesis. What emerges is less a problem of a single organ and more a dysregulation of communication between multiple physiologic systems.

The evolutionary perspective introduced in recent PMOS literature further deepens this discussion. Human reproductive systems evolved under conditions where energy availability, physical activity, infection risk, and survival pressures differed dramatically from modern environments. Neuroendocrine systems capable of rapidly adjusting reproductive function in response to metabolic signals may once have conferred important survival advantages. In contemporary environments characterized by caloric abundance, sedentary behavior, sleep disruption, and chronic metabolic stress, however, these same adaptive systems may become maladaptive.

This may help explain why PMOS so often sits at the intersection of reproduction and metabolism. It also highlights why simplistic narratives surrounding the condition are increasingly inadequate. PMOS is not merely a disorder of “bad ovaries,” nor can it be reduced solely to insulin resistance, obesity, or infertility. Rather, it appears to involve complex interactions between metabolic and neuroendocrine signaling systems that reinforce one another over time.

For patients, this evolving understanding may also carry emotional significance. Many individuals with PMOS have long sensed that the syndrome affected far more than their menstrual cycles alone. Mood fluctuations, appetite changes, energy dysregulation, weight shifts, sleep disruption, and reproductive dysfunction often coexist in ways that feel deeply interconnected. Modern neuroendocrine research increasingly suggests that these experiences may reflect real physiologic network disturbances rather than isolated symptoms occurring by coincidence.

The challenge moving forward is translating these mechanistic insights into clinically meaningful care. Future therapies may increasingly target neuroendocrine signaling pathways, metabolic inflammation, insulin dynamics, or hypothalamic regulation alongside traditional reproductive interventions. Precision medicine approaches may ultimately identify which physiologic drivers dominate in specific PMOS phenotypes.

But perhaps the most important shift is conceptual. The reproductive axis is not static. It is rhythmic, adaptive, metabolically sensitive, and deeply interconnected with the rest of human physiology. And in PMOS, the problem may not simply be that the reproductive metronome exists, but that the signals controlling its tempo have become amplified beyond their normal range.

If AMH can influence the very neurons that regulate reproductive rhythm, then perhaps one of the most important lessons of PMOS is that the ovary is not acting alone. What appears on ultrasound may be only the visible endpoint of a much larger conversation occurring between the brain, metabolism, inflammation, adipose tissue, and the reproductive system itself.

And that raises an important question: if the reproductive metronome is being driven by signals originating far beyond the ovary, should we still think of PMOS primarily as a reproductive disorder, or as a whole-body physiologic condition with reproductive consequences?

This broader view of fertility, one that sees reproduction as deeply connected to metabolism, environment, nutrition, inflammation, and overall health, is also a central theme of my work. Because fertility is rarely the story of a single organ. It is often the story of how multiple physiologic systems communicate, adapt, and sometimes fall out of sync.

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.