Premenstrual Dysphoric Disorder (PMDD) is a debilitating mood disorder characterized by severe emotional, cognitive, and somatic symptoms during the luteal phase of the menstrual cycle, significantly impairing daily functioning and interpersonal relationships (1). PMDD occurs after ovulation (Day 14) and persists until the onset of menstruation (Days 24–28), aligning with cyclical hormonal fluctuations (2, 3). Unlike premenstrual syndrome (PMS), which affects up to 80% of women to varying degrees, PMDD impacts approximately 3% to 8% of women of reproductive age (4). PMDD was first recognized as a distinct clinical condition in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), where it was classified under depressive disorders (5). Despite this recognition, PMDD remains absent from the International Classification of Diseases, 10th Edition (ICD-10), which limits its diagnostic use globally and contributes to its continued marginalization in clinical practice (6). Although the recently published ICD-11 includes PMDD under gynecological disorders, this placement reflects an overly biomedical view and overlooks the neuropsychiatric complexity of the condition (7).

Initially, PMDD was conceptualized as an exaggerated response to hormonal fluctuations, with early research focusing on dysregulated estrogen and progesterone levels. However, subsequent studies have shown that women with PMDD do not exhibit abnormal hormone levels but rather heightened sensitivity to hormonal changes, particularly in the serotonergic and GABAergic systems (4, 8). Neuroimaging research consistently demonstrates cyclical changes in brain regions critical to emotion regulation and sensory integration, including the prefrontal cortex, amygdala, anterior insula, and anterior cingulate cortex (8–10). Recent studies also highlight the role of neuroinflammation and stress-induced alterations in the HPA axis as key contributors to PMDD pathophysiology (7, 8). These findings point to complex interactions between neurobiological processes and hormonal sensitivity that shape PMDD symptomatology.

Importantly, trauma and stress experiences can significantly affect these neural circuits. Research indicates that trauma exposure—whether in early life or adulthood—can disrupt key regions such as the amygdala, medial prefrontal cortex, and anterior insula, heightening emotional reactivity and impairing emotional regulation (11). Trauma's influence extends beyond emotional processes to interoception—the perception and interpretation of internal bodily states—which is increasingly recognized as a factor in PMDD (12, 13). For example, trauma-induced interoceptive dysregulation may cause heightened sensitivity or confusion about normal bodily sensations during the luteal phase, exacerbating symptoms of anxiety and distress (12–14).

PMDD's development is shaped by multiple factors, including trauma (11), stress sensitivity (2), genetic predisposition (15), and sensory processing sensitivity (10). Notably, recent studies highlight that SPS—a trait characterized by heightened sensitivity to internal and external stimuli—may play a role in PMDD by amplifying emotional reactivity and sensory overwhelm (10, 16). The dynamic interplay between trauma, SPS, and interoceptive dysfunction underscores the importance of considering these factors together in understanding PMDD's heterogeneous presentation. For example, one systematic review emphasized the link between affective switching, sleep disturbances, and stress, suggesting that remote monitoring of heart rate variability, sleep, and physical activity could help identify symptom exacerbations and guide treatment interventions (17).

Current first-line treatments include SSRIs and hormonal therapies such as oral contraceptives (7, 18). However, recent studies reveal that many women continue to experience significant somatic and sensory symptoms, highlighting the need for more comprehensive treatment approaches (10, 18). Moreover, research on PMDD's impact on daily functioning and social behavior underscores the necessity of holistic interventions that address emotional, cognitive, and sensory domains (7, 8, 16).

Despite growing recognition of PMDD's complexity, substantial gaps remain in our understanding. While earlier studies focused on mood symptoms and hormonal sensitivity, recent research has expanded the focus to include trauma, neuroinflammatory mechanisms, and sensory processing pathways (7, 8). For example, Henderson et al. identified a negative attentional bias in PMDD, suggesting that cognitive and behavioral factors may play a larger role in symptomatology than previously recognized. Likewise, Brown et al. emphasized the importance of real-time, remote monitoring of stress-related symptoms, highlighting the potential of digital health interventions for timely support. Importantly, intersectional factors such as gender identity, socioeconomic status, and cultural background have often been neglected in PMDD research, limiting the generalizability of findings and contributing to healthcare disparities.

Additionally, recent systematic reviews stress the need for research on affective switching and stress reactivity in PMDD, given their potential impact on suicide risk and overall well-being. The interplay between neuroendocrine sensitivity, trauma, interoceptive dysfunction, and sensory processing remains underexplored, with conflicting evidence on how these factors interact in PMDD pathophysiology (7, 17). These gaps underscore the need for integrated, interdisciplinary models that encompass both neurobiological and psychosocial dimensions.

This paper aims to address these gaps by developing a multidimensional framework of PMDD that integrates trauma, interoceptive awareness, sensory processing sensitivity, and hormonal sensitivity. By synthesizing recent research with existing clinical knowledge, this review seeks to provide a comprehensive understanding of PMDD and inform future research directions and treatment strategies.

Within the Predisposing Vulnerability domain, SPS has been associated with heightened amygdala activation and reduced prefrontal regulatory control—neural patterns that overlap with those identified in research on PMDD (10, 25). This trait can predispose individuals to heightened emotional and sensory reactivity during hormonally sensitive phases of the menstrual cycle, potentially setting the stage for symptom development (9, 25).

The Secondary Vulnerability domain encompasses traumatic experiences, which exert a significant influence on both emotional regulation and interoceptive functioning. Empirical evidence indicates that trauma can alter critical neural circuits involved in emotion and bodily awareness, such as the amygdala, medial prefrontal cortex, and anterior insula, resulting in heightened emotional reactivity and impaired interoceptive accuracy (11, 22). In addition to these neural alterations, trauma has been shown to affect hormonal sensitivity through dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis, thereby increasing vulnerability to the cyclical affective disturbances characteristic of PMDD (7, 8, 20).

This dual pathway—comprising both neuroendocrine and affective mechanisms—helps explain how trauma may contribute to PMDD symptomatology even in the absence of other mediating variables. Notably, such traumatic experiences are not limited to childhood but can occur at any life stage, with enduring consequences for neurobiological systems involved in emotion regulation, stress responsivity, and hormonal integration (11). This understanding reinforces the relevance of trauma history in shaping individual differences in PMDD expression and severity.

Importantly, trauma's impact is not confined to childhood experiences; it can occur at any stage of life and still significantly shape the nervous system's responsiveness to hormonal fluctuations and stress (22, 23).

Within the Mechanism domain, emotional dysregulation and altered interoceptive awareness are conceptualized as core mediators that link vulnerability factors (such as trauma and sensory processing sensitivity) with the clinical manifestations of PMDD. Emotional dysregulation has consistently been implicated in the pathophysiology of PMDD and is considered a defining feature of the disorder's symptomatology (7, 8, 15). This dysregulation is further exacerbated by underlying neural alterations associated with trauma exposure and high sensory processing sensitivity, particularly in regions such as the amygdala, medial prefrontal cortex, and anterior insula (10, 11, 25).

Recent evidence also points to a characteristic negative attentional bias among individuals with PMDD, marked by a heightened focus on negative stimuli and increased negative appraisal, which may further intensify affective symptoms (20). In parallel, interoceptive dysfunction can amplify both emotional and physical symptoms during the luteal phase (12–14). These interoceptive alterations are not merely secondary consequences of mood disturbances but may also stem directly from neurobiological vulnerabilities shaped by trauma and high SPS (11, 21, 25). Consequently, interoception and emotional regulation are best understood as bidirectionally linked, where impaired bodily awareness contributes to emotional instability, and vice versa.

Moreover, current conceptual models suggest that trauma and SPS may exert independent effects on interoceptive functioning, over and above their influence via emotional dysregulation. This perspective highlights the need to empirically examine these potential direct pathways, particularly through neuroimaging and psychophysiological studies that assess the interplay between sensory integration, bodily awareness, and emotion regulation (11, 21, 25).

The final domain of the framework focuses on clinical outcomes, with PMDD symptomatology emerging as the result of complex, interacting mechanisms involving emotional, hormonal, and sensory processes. While the contribution of emotional dysregulation to PMDD has been well-documented and forms the basis of current diagnostic criteria (7, 8, 15), emerging models propose additional explanatory pathways that encompass sensory responsiveness and interoceptive misattunement. These processes may independently contribute to symptom severity and expression, even in the absence of overt affective disturbances (10, 20, 25).

This expanded view of PMDD emphasizes a broader symptom profile that includes not only mood-related disturbances but also somatic and sensory dimensions. For instance, individuals with elevated sensory processing sensitivity may be more reactive to hormonal shifts and environmental stimuli, which could increase vulnerability to sensory overload, fatigue, and irritability (10, 25). Similarly, interoceptive distortions may exacerbate the perception of normal luteal-phase bodily changes, reinforcing symptom severity and distress (12–14).

Hormonal sensitivity remains a central etiological factor and is understood to dynamically interact with emotional and sensory processes to modulate the onset, intensity, and variability of PMDD symptoms across cycles (7, 8). Rather than serving as an isolated driver of the disorder, hormonal fluctuations appear to act as modulators within a broader biopsychosocial network, influencing and being influenced by neurocognitive and affective mechanisms.

This reconceptualization of PMDD symptomatology supports a move away from narrowly hormone-centric models toward integrative frameworks that account for psychological and sensory vulnerabilities. It also underscores the importance of tailored clinical interventions that go beyond pharmacological symptom suppression to address trauma history, emotional processing, and interoceptive functioning.

This comprehensive framework underscores the limitations of current PMDD diagnostic criteria, which focus primarily on mood symptoms, irritability, and somatic complaints but overlook trauma, sensory processing, and interoceptive factors. By incorporating these additional dimensions, diagnostic frameworks could be refined to capture the heterogeneity of PMDD presentations better. For example, screening for SPS and interoceptive dysfunction could help identify individuals who may benefit from sensory modulation strategies or trauma-informed interventions in addition to standard treatments such as SSRIs and hormonal therapies (7, 18).

This integrated model bridges neuroendocrinology, affective neuroscience, and trauma psychology, offering a more nuanced and multidimensional perspective on PMDD. Future research should empirically test the proposed pathways using longitudinal and neuroimaging studies, focusing on how trauma, SPS, and interoception interact with hormonal fluctuations across the menstrual cycle. Additionally, research on neurodivergent populations and trauma survivors could elucidate how these factors shape individual differences in symptom expression and treatment responsiveness (20, 21). This approach will inform the development of personalized interventions that target both top-down and bottom-up processes, ultimately improving clinical outcomes for women with PMDD.