Why menstrual cycle irregularities belong in brain research.

Menstrual irregularities are not merely reproductive anomalies; they often serve as key clinical indicators of broader disruptions across endocrine, metabolic and neural systems. Behaviors such as restrictive eating, excessive physical activity and psychosocial stress are strongly associated with disruptions to menstrual cycle patterns 5 , with cycle cessation or shortening frequently serving as an early sign of physiological strain. In many cases, a persistent emerging pattern of irregular menstruation is the first observable symptom of an underlying condition, such as a thyroid disorder, polycystic ovary syndrome (PCOS) or endometriosis, all of which are increasingly recognized for their impact on brain structure, function and mental health 6 – 8 . Furthermore, dysmenorrhea (painful menstrual periods) is strongly linked to (pelvic and non-pelvic) chronic pain and associated brain-imaging findings 9 . However, research is scarce because these conditions have been overlooked for decades. Recognizing menstrual cycle irregularities as meaningful clinical signals creates a critical opportunity for early intervention in disrupted body systems. At the same time, this recognition must be balanced with caution to avoid over-pathologizing menstrual variation, as intra-individual variability in factors such as the length oftime between menstrual periods is common in healthy individuals. Further, many individuals with conditions such as PCOS live healthy and fulfilling lives with appropriate support and care.

Advancing the science of menstrual cycle irregularities and brain health will require interdisciplinary collaboration and innovative research design. Longitudinal studies that integrate neuroimaging, endocrine profiling and comprehensive health assessments will be critical to elucidating the mechanisms that link menstrual disruptions to neurological outcomes. Large-scale epidemiological studies, particularly those that include racially, socioeconomically and hormonally diverse populations, are also needed to capture the full spectrum ofmenstrual variability. Importantly, reproductive health must be assessed using standardized, validated tools that allow consistent characterization of cycle patterns across studies and clinical settings. In clinical practice, greater awareness of the neurological implications of menstrual cycle irregularities is urgently needed. Routine integration of cycle tracking and reproductive history into health assessments could facilitate the early detection of endocrine or neurobiological dysfunction and mental health conditions, enabling timely intervention. Hormonal contraceptives, widely used for both health and lifestyle reasons, complicate this landscape. Although they are essential for many individuals, these medications can obscure symptoms of underlying conditions, such as PCOS, endometriosis or thyroid dysfunction, particularly when initiated during adolescence, before the emergence of overt reproductive pathology. Understanding how hormonal contraceptives affect the brain remains an important frontier. These medications directly alter the hormonal milieu that shapes mood, cognition and neuroplasticity, yet their neurobiological impact remains understudied. A precision medicine approach that considers individual hormonal profiles, reproductive history and neurological vulnerabilities will be essential for tailoring treatment and supporting cognitive and emotional health in those with menstrual-related conditions. Finally, dismantling the stigma surrounding menstruation and menstrual cycle irregularities is critical. Promoting open, inclusive dialogue empowers individuals to seek care and advocate for their health. By addressing cultural barriers and clinical blind spots, we can ensure that reproductive physiology is recognized not as a niche concern but as a fundamental aspect ofcomprehensive, evidence-based healthcare for all. Advancing the understanding of brain–hormone interactions in the context of menstrual irregularities may also lay the groundwork for broader insights into how hormonal fluctuations — whether diurnal, seasonal or lifestyle driven — shape brain function and structure across sexes and life stages. The implications of this work thus extend well beyond reproductive health, offering a roadmap for future research on the endocrine foundations of brain health more broadly.

Neuroimaging studies have observed complex and dynamic fluctuations in both brain structure and brain function across the regular menstrual cycle, including changes in gray matter volume and thickness, functional network organization, neural reactivity to stimuli and brain chemistry. These neural shifts closely track cyclical patterns of ovarian hormones, such as pre-ovulatory estradiol peaks and post-ovulatory progesterone surges 1 . By contrast, individuals with irregular cycles often lack these predictable hormonal rhythms because of disruptions in the HPG axis ( Fig. 1 ). Endocrine disorders such as PCOS, endometriosis and thyroid dysfunction can disrupt the balance of estrogen, progesterone and androgens, potentially leading to distinct alterations in brain architecture and function. Despite growing interest in the brain–endocrine relationship and convincing preliminary evidence that irregular menstrual cycles shape brain functional and structural dynamics in unique ways, individuals with menstrual cycle irregularities remain chronically under-represented in research. Although their exclusion is often justified as a means for minimizing hormonal variability, it introduces a sampling bias, one that sidelines a substantial proportion ofthe population and limits insight into the full spectrum of menstrual cycle physiology and its effects on the brain.

The dynamic, bidirectional relationship between menstrual cycles and brain health demands a more integrated, biologically informed approach to research and clinical care. Menstrual irregularities are not peripheral concerns; they are neuroendocrine signals that may reflect, and contribute to, broader disruptions in brain function and resilience. Addressing this intersection requires dismantling of methodological exclusions, embracing of menstrual cycle variability in scientific inquiry and fostering of interdisciplinary collaboration. With the integration of advanced neuroimaging, longitudinal hormonal profiling and inclusive clinical frameworks, the full spectrum of menstrual cycle–brain interactions can begin to be uncovered. These insights will pave the way for more personalized and equitable care, recognizing the menstrual cycle not only as a reproductive metric but also as a vital sign of neurological health.

A growing field of research that has provided some early insight into the bidirectional relationship between menstrual irregularities and brain health is brain injury. Concussions have emerged as a substantial disruptor of menstrual cycle regularity. Female individuals who sustain a concussion are at an increased risk of developing menstrual cycle disturbances, including delayed cycles, missed periods and complete amenorrhea 13 . These effects can persist for months after injury, reflecting long-term perturbations in neuroendocrine function. Rather than being peripheral symptoms, these disruptions may be physiological signals of central nervous system strain. This physiological response may parallel the temporary cessation of menstruation seen in the postpartum period, an evolutionary adaptation whereby elevated prolactin levels suppress ovulation and menstruation, allowing the body to allocate resources toward lactation and infant care. Similarly, in the context of concussion, menstrual disruptions may reflect a reallocation of physiological resources toward neurological repair and survival. The influence of the menstrual cycle on brain injury outcomes is equally compelling. Hormonal fluctuations may shape both vulnerability to concussion severity and recovery trajectories. For example, concussions sustained during the luteal phase — when progesterone is elevated — are associated with more-severe symptoms and prolonged recovery than those that occur during the follicular phase. These findings implicate the HPG axis in modulating post-injury outcomes 14 , emphasizing that concussion recovery is shaped not only by biomechanical factors but also by hormonal state. Additionally, hormonal contraceptive use may mitigate some of these effects by stabilizing hormone levels and supporting recovery 15 . Just as concussions can disrupt menstrual patterns, pre-existing hormonal conditions such as PCOS or endometriosis may shape how individuals experience and recover from brain injury. In contrast, male individuals lack a similarly visible, cyclic biomarker of hormonal disruption, which highlights the unique potential of menstrual health as a window into neuroendocrine function in female individuals. Findings from concussion research illustrate the delicate balance between the brain and endocrine system as an indicator of overall health, underscoring the need for personalized brain-injury management.

The menstrual cycle is governed by a complex neuroendocrine feedback loop between the brain and body. As such, brain health not only is influenced by hormones but also plays a central role in regulating them. Psychiatric conditions such as premenstrual dysphoric disorder (PMDD) and postpartum depression are causally linked to fluctuations in sex hormones. Exacerbations of menstrual cycle-related symptoms have also been observed for mental health conditions characterized by psychosis, mania, depression and substance use 10 . Notably, the incidence of many mental health disorders , such as depression, increases during puberty 11 — a developmental period that also marks the onset of menarche, which is often followed by up to 2 years of irregular menstrual cycles — suggestive of a potential link between early hormonal instability and emerging psychiatric vulnerability. Furthermore, higher rates of psychiatric comorbidities have been reported in women with menstrual disorders. The reason for such associations remains unknown. Symptoms of prevalent neurological conditions, including epilepsy, movement disorders, migraine, stroke and multiple sclerosis, are all influenced by menstrual cycle phases (or their elimination by hormonal contraceptives). Individuals with these listed conditions report menstrual disorders more commonly compared with individuals without these conditions 12 .