Redefining PCOS: A Shift from the Ovaries to the Brain
Dr Aleisha Moore, author of a recent highly downloaded Journal of Neuroendocrinology Early Career Perspective article, summarises the paper's key findings. Journal of Neuroendocrinology currently has a call for papers for a Special Issue on polycycstic ovary syndrome. If you feel your research would fit, please take a look at the requirements on the journal webpage. Deadline 31 July 2026.
For many years, polycystic ovary syndrome (PCOS) was primarily considered a disorder that originated in and affected the ovaries. However, recent shifts in perspective now view PCOS not as a single disorder but as several phenotypically distinct subtypes, each of which may arise from different genetic or environmental etiologies and require targeted treatment approaches.
In my recent review published in the Journal of Neuroendocrinology, titled "Neuroendocrine Mechanisms Responsible for Elevated Gonadotrophin-Releasing Hormone (GnRH) and Luteinizing Hormone (LH) Pulses in Polycystic Ovary Syndrome," I detail the neuroendocrine phenotype of PCOS. Recent reports estimate that this subtype accounts for ~25% of the PCOS population (Gao et al., Nature Medicine, 2025). It is defined by elevated pulsatile Luteinising Hormone (LH) secretion that drives ovarian testosterone secretion and disrupts ovarian function. Elevated LH pulsatility arises from an impaired ability of ovarian steroid hormones to suppress GnRH pulsatile secretion from neurons in the hypothalamus. Therefore, the way the neuroendocrine subtype likely develops lies in brain circuits that control Gonadotropin-releasing hormone (GnRH) release rather than in primary changes at the ovary.
Most current therapies mainly target ovarian symptoms, such as using birth control pills to regulate cycles or medications to induce ovulation. However, these methods have significant limitations: many patients face challenges with treatment adherence, treatments must be adjusted based on life stage and fertility goals, and they do not address the underlying changes in brain circuitry that drive the syndrome’s symptoms.
Approaches that correct or prevent the underlying changes in the brain leading to excess LH secretion and reproductive dysfunction offer a promising direction for individualised care for PCOS patients with the neuroendocrine subtype. This review highlights that combined clinical studies and basic research using animal models, together with advanced neuroscience techniques to study deep-brain hypothalamic networks, have identified multiple cell populations that may promote GnRH/LH release in PCOS. One crucial group identified is KNDy neurons, a group of neurons in the hypothalamus central to the hormonal control of reproduction. These neurons produce three neuropeptides that are vital for reproductive capacity (Kisspeptin, Neurokinin B and Dynorphin) and have been identified as a key component of the GnRH/LH pulse generator. There is increasing evidence supporting the role of KNDy neurons in the development of LH hypersecretion in PCOS, and drugs that target KNDy neuron activity show promise in reducing LH pulse secretion, and therefore potentially preventing ovarian dysfunction, in clinical trials.
Together, this review highlights a rapidly advancing research area and a promising new therapeutic approach that could break a long-standing stagnation in the development of PCOS treatments. Ongoing efforts to identify key abnormalities in PCOS and to develop strategies that specifically target brain circuits with long-term treatments are essential. Additionally, increased funding from agencies will be vital to achieve the goal of providing targeted, precision medicine for this group of patients, who have historically received less support.
