1. Introduction

Cervical intraepithelial neoplasia (CIN) and endometrial hyperplasia (EH) are two of the most clinically significant precancerous gynecological conditions encountered in women across reproductive and perimenopausal ages. Although their morphological progression and oncological outcomes have been widely studied, there is a critical research gap concerning their neurological, psychological, and psychosocial ramifications. The intersection of oncogynaecology and mental health represents a growing frontier that calls for a more integrated understanding of women’s health. CIN, arising from persistent high-risk HPV infections, is well known for its stratification into low- and high-grade lesions. These distinctions are key not only for clinical management but also for understanding the differential psychoemotional burden across the stages. As shown by Cendejas et al. (2015), treatment for cervical dysplasia significantly disrupts sexual health and self-image, underlining the persistent psychosocial consequences even after clinical resolution. This is further compounded by anxiety surrounding disease recurrence, cancer progression, and fertility, particularly among young women [1]. The psychological burden of CIN is aggravated by external factors such as interpersonal violence. In a pioneering study, Coker et al. (2000) established a strong association between intimate partner violence and incidence of cervical neoplasia, suggesting that chronic psychosocial stress and trauma may compromise immune surveillance and HPV clearance. These findings imply that CIN management must transcend cervical pathology in order to consider the broader life context of patients [11]. Parallel to CIN, endometrial hyperplasia, especially its complex and atypical forms, is a well-established precursor of endometrial carcinoma. Chen et al. (2013) and Irfan et al. (2018) both underscore the considerable coexistence of carcinoma in patients diagnosed with EH, particularly in cases involving atypia. These findings have important psychological implications. Patients diagnosed with EH often face diagnostic uncertainty and extended surveillance regimens, contributing to prolonged anxiety and emotional fatigue [2,12]. From a neuroendocrine perspective, chronic hormonal imbalances that underlie EH, such as hyperestrogenism in PCOS, are associated with psychological disturbances. Park et al. (2011) demonstrate a strong correlation between endometrial abnormalities and clinical markers of PCOS, a condition long associated with mood disorders, anxiety, and decreased quality of life [14]. Similarly, Sima (2024) explores HOMA-IR indices in perimenopausal women with abnormal uterine bleeding and shows a compelling association between metabolic dysregulation and gynecological pathology, hinting at a possible bidirectional relationship between stress and hormonal homeostasis [6]. Jónsdóttir et al. (2023) provided a valuable long-term view, showing that patients with advanced gynecological cancers continue to report diminished quality of life a full year after diagnosis. While this study focuses on invasive disease, its relevance to precancerous stages is critical. The fear of progression, especially when linked to bodily functions such as menstruation and reproduction, can deeply affect a woman’s psychological well-being, even in early disease stages [13]. Pap smear screening, though a cornerstone of CIN detection, can itself be a source of psychological strain. Parvathi et al. (2015) highlight how abnormal Pap findings, even when minimally dysplastic, necessitate follow-ups that many women find emotionally taxing. Kobelin (1999) showed that even slightly abnormal smears can predict CIN, underlining how seemingly benign clinical results can bear significant psychological consequences [3,4].

The psychosocial ramifications of histopathological uncertainty are further emphasized in the work of Çakmak et al. (2019), who reviewed a decade of EH cases and found a high frequency of concurrent carcinoma, thus validating the emotional distress patients report when faced with ambiguous or premalignant diagnoses [9]. Sangwan et al. (2020) reaffirmed the clinical necessity of robust diagnostic criteria to reduce psychological uncertainty in patients undergoing evaluation for gynecological abnormalities [5]. At the molecular level, Singh et al. (2020) provided an intriguing murine model that replicated human EH via WDR13 gene knockout. Although this study is preclinical, it gives weight to the theory that EH may involve systemic and not merely localized pathophysiology, potentially implicating pathways that also regulate neuroendocrine and behavioral states [7]. The oncological overlap with ovarian neoplasms is an emerging area of psychological relevance. Tokalıoğlu et al. (2024) explored whether granulosa cell tumors of the ovary, owing to their estrogen-secreting nature, predict concomitant endometrial pathology. While primarily gynecological, this axis reiterates the stress-inducing uncertainty that patients face when multiple organs are simultaneously involved [8]. Finally, Epplein et al. (2008) conducted a large-scale epidemiological study that demonstrated how BMI and reproductive history directly correlate with the risks of complex and atypical EH. These findings bridge the lifestyle, endocrine, and gynecological domains and highlight the cumulative psychosocial stress associated with body image, weight stigma, and reproductive planning [11]. In conclusion, the existing body of literature points to a pressing need to adopt an integrative medical-psychological framework for managing CIN and EH. This requires a multidimensional approach that includes routine psychoemotional assessments, stress hormone evaluation, counseling services, and long-term psychological follow-up. Although gynecologic oncology has made significant strides in early detection and treatment, the equally crucial psychological dimension lags behind. Bridging this gap through rigorous research and clinical practice can improve patient satisfaction and improve disease outcomes.

The pathophysiology of cervical intraepithelial neoplasia (CIN) and endometrial hyperplasia (EH) cannot be fully understood without a critical evaluation of the neuroendocrine and psychosocial mechanisms involved. Increasing evidence underscores that stress, inflammation, and hormonal imbalance form a bidirectional network in precancerous gynecological conditions, mediated by the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system. These systems shape not only biological susceptibility but also the emotional and cognitive landscape of affected patients. In women with CIN, persistent human papillomavirus (HPV) infection is a well-documented etiological driver. However, the variability in immune clearance suggests the role of systemic moderators, notably psychological stress and trauma. Coker et al. (2000) revealed that exposure to intimate partner violence (IPV) a chronic psychosocial stressor was significantly associated with higher rates of cervical neoplasia. The implication is that trauma-induced dysregulation of the HPA axis compromises immune defense mechanisms, facilitating viral persistence and neoplastic progression [10]. Parallel findings in EH reveal that hormonal dysregulation itself, particularly estrogen dominance unopposed by progesterone, is strongly correlated with psychoemotional symptoms. Park et al. (2011) demonstrated that women with PCOS and abnormal endometrial histology displayed significantly higher rates of depression and anxiety—further implicating hormonal neurochemistry in psychological burden. These women frequently show insulin resistance, which is not only a metabolic disturbance but also linked to neurotransmitter imbalance and poor mood regulation [14]. The study by Sima (2024) provides deeper biochemical validation, showing that perimenopausal women with abnormal uterine bleeding had elevated HOMA-IR levels, a surrogate marker of insulin resistance. This metabolic shift is often accompanied by systemic inflammation and cortisol dysregulation, which are known to affect hippocampal function and emotional processing. This strongly supports the need to consider endocrinological stress markers in psychological assessments of EH patients [6]. Animal studies further illuminate the neuroendocrine underpinnings. Singh et al. (2020) reported that mice deficient in the WDR13 gene—a regulator of endometrial growth—developed EH alongside systemic metabolic and possibly neurobehavioral changes. Although preclinical, these findings suggest that molecular changes in the endometrium may be part of a broader physiological dysregulation affecting mood and cognition [7]. From a clinical perspective, patients with high-grade CIN or atypical EH report significant health anxiety, driven by both the uncertain prognosis and the frequent follow-up procedures. Parvathi et al. (2015) emphasized that even minimally abnormal Pap smear results generate substantial emotional distress, especially in patients lacking adequate health literacy or social support. Similarly, Çakmak et al. (2019) found a high rate of coexistent carcinoma in patients with atypical EH, reinforcing the psychological burden of diagnostic ambiguity [4,9]. Notably, these psychoemotional effects are not transient. Jónsdóttir et al. (2023) conducted a longitudinal study and found that psychological impairments, including fatigue, anxiety, and body image disturbance, persist up to one year post-diagnosis in gynecological cancer patients. While their focus was invasive disease, the findings likely extrapolate to high-grade precancerous conditions given the similarity in treatment trajectories and existential concerns [13]. Adding another layer, Tokalıoğlu et al. (2024) examined granulosa cell tumors and their hormonal effect on the endometrium. These tumors produce excess estrogen, and their association with EH highlights a recurring theme: hormonal diseases often exist in tandem with significant psychological symptoms. This overlap necessitates multidisciplinary collaboration in gynecological care, incorporating endocrinologists, psychologists, and gynecologic oncologists [8]. Epplein et al. (2008) also provide a population-level view, showing that higher BMI and nulliparity are strongly associated with complex EH. These variables are also independently linked to lower self-esteem, poor body image, and increased vulnerability to mood disorders—adding a psychosocial dimension to what is traditionally considered purely biomedical risk [11]. In sum, CIN and EH are not isolated gynecological phenomena; they are embedded within a complex matrix of neuroendocrine imbalance, stress response activation, and psychoemotional vulnerability. Failure to address this matrix not only compromises holistic care but may also impair clinical outcomes. A comprehensive biopsychosocial approach—grounded in the emerging literature—is thus imperative in the prevention, diagnosis, and management of these conditions.

2. Conclusions

Neurological and psychoemotional changes are critical yet underrecognized components of uterine precancerous conditions, such as cervical intraepithelial neoplasia (CIN) and endometrial hyperplasia. The reviewed literature revealed a consistent association between these gynecological disorders and elevated psychological distress, including anxiety, depression, and impaired quality of life [1,13]. Furthermore, evidence suggests that chronic stress responses, often mediated by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, may play a significant role in modulating mood and cognitive function [2,10]. Hormonal imbalances and systemic inflammatory markers, particularly in cases overlapping PCOS and metabolic dysfunction, may further affect neuropsychological vulnerability [6,12]. Despite mounting evidence, clinical attention continues to be disproportionately focused on the histopathological and oncological endpoints. Consequently, women navigating these diagnoses often endure substantial emotional distress in silence without appropriate psychoneurological screening or interventions. Its impact on sexual health, treatment adherence, and long-term prognosis is not trivial [1]. This gap in comprehensive care highlights the urgent need for integrative, multidisciplinary approaches that incorporate psychological evaluation, counseling, and, where necessary, neurocognitive support alongside gynecological treatment. It is imperative that healthcare systems acknowledge these psychoemotional sequelae as intrinsic to the disease process rather than secondary or incidental. Early identification through validated screening tools and prompt psychotherapeutic or psychiatric referral can significantly improve patient outcomes. Moreover, understanding the biopsychosocial mechanisms underlying these changes, such as inflammation, hormonal dysregulation, trauma, and cultural stigma, can pave the way for targeted intervention. Future research should aim to quantify neurocognitive impairment, characterize stress biomarkers, and assess the efficacy of multidisciplinary care models. In sum, recognizing the interdependence of mind and body in gynecological precancerous conditions is not a luxury but a necessity. Comprehensive, patient-centered care that addresses neurological and psychoemotional domains is essential for improving both clinical outcomes and quality of life in affected women.