Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder affecting women of reproductive age and is characterized by hyperandrogenism, ovulatory dysfunction, and/or polycystic ovarian morphology. Its clinical manifestations extend beyond reproductive abnormalities and include insulin resistance, obesity, dyslipidemia, chronic low-grade inflammation, and psychological comorbidities. Increasing evidence supports a multifactorial pathophysiology involving genetic susceptibility, neuroendocrine dysfunction, metabolic abnormalities, adipose-tissue dysregulation, inflammation, and environmental and nutritional factors. [1,2]

Infertility is one of the most important reproductive consequences of PCOS and is predominantly related to chronic anovulation and impaired follicular development. Insulin resistance and compensatory hyperinsulinemia can enhance ovarian androgen production and contribute to hyperandrogenism, while obesity may further aggravate these abnormalities. Insulin resistance in PCOS is not restricted to skeletal muscle or adipose tissue but involves multiple tissues and contributes to metabolic and reproductive dysfunction through complex intracellular signaling abnormalities. [2,3]

Obesity represents an important modifier of the PCOS phenotype. Increased visceral adiposity is associated with insulin resistance, hyperinsulinemia, altered adipokine secretion, inflammation, and increased androgen availability. These mechanisms may impair folliculogenesis and ovulation and thereby contribute to infertility. Nutritional factors and dietary patterns may further influence insulin sensitivity, body weight, inflammation, and metabolic health, making nutrition an important component of the broader pathophysiology of PCOS. [2,4]

The psychological burden associated with PCOS has received increasing attention. Anxiety and depressive symptoms are substantially more common among women with PCOS than in the general female population. A 2023 systematic review and meta-analysis reported a high burden of depression among women with PCOS, with substantially increased risk compared with controls. [5] More recent evidence has further confirmed a high prevalence of both anxiety and depression among women with PCOS, although estimates vary according to the diagnostic instruments and definitions employed. [6]

Psychological symptoms in PCOS may arise from several interacting reproductive, metabolic, and psychosocial factors. Infertility, menstrual irregularity, hirsutism, acne, obesity, body-image concerns, and concerns regarding reproductive health can contribute to psychological distress. Conversely, anxiety and depression may influence dietary behavior, physical activity, sleep, treatment adherence, and weight-management efforts, potentially reinforcing metabolic and reproductive abnormalities. Contemporary reviews therefore emphasize that mental health assessment should form an integral part of PCOS management rather than being considered a secondary issue. [6,7]

Eating behavior represents another important dimension of PCOS that has received comparatively less clinical attention. Women with PCOS may be at increased risk of disordered eating and specific eating disorders, including binge eating disorder and bulimia nervosa. A 2024 systematic review and meta-analysis involving 28,922 women with PCOS and 258,619 controls found significantly higher odds of any eating disorder among women with PCOS. [8] An additional recent review highlighted the complex and potentially bidirectional relationship between PCOS and eating disorders and emphasized the need to recognize disordered eating across different BMI categories. [9]

The relationship between PCOS and eating disorders appears to be multifactorial. Obesity, insulin resistance, hyperandrogenism, body dissatisfaction, emotional distress, and attempts to control body weight may contribute to abnormal eating behaviors. At the same time, binge eating and other disordered eating patterns may promote weight gain and worsen metabolic abnormalities. [8,9]

The coexistence of metabolic dysfunction, psychological distress, and abnormal eating behavior may be particularly relevant to infertility. Insulin resistance, hyperandrogenism, adiposity, inflammation, and altered hypothalamic–pituitary–ovarian signaling can converge to impair ovulation and follicular maturation. Psychological distress and disordered eating may further influence these pathways through changes in dietary intake, body weight, metabolic health, and health-related behaviors. Thus, infertility in PCOS may be better understood as the clinical outcome of interacting endocrine, metabolic, nutritional, and psychological mechanisms rather than solely as a consequence of anovulation. [3,4,9]

Despite growing evidence concerning individual components of PCOS, important gaps remain in understanding their interrelationships. Existing studies have frequently examined depression, anxiety, eating disorders, obesity, insulin resistance, or infertility as separate outcomes. Relatively fewer clinical studies have simultaneously evaluated these factors in relation to infertility and metabolic and hormonal characteristics within the same population.

This multidimensional relationship is clinically important because conventional infertility assessment in women with PCOS may focus predominantly on ovulation and hormonal abnormalities while underrecognizing psychological and nutritional contributors. Current evidence-based recommendations emphasize assessment of psychological health and disordered eating as part of comprehensive PCOS care, alongside lifestyle, metabolic, and reproductive assessment. [1,7]

Therefore, the present study was designed to investigate the association of eating disorders, anxiety, and depression with infertility and selected metabolic, hormonal, and inflammatory characteristics in women with PCOS. By evaluating nutritional, psychological, reproductive, and physiological variables concurrently, the study aims to provide a more integrated understanding of the pathophysiological factors associated with infertility in PCOS.

A cross-sectional analytical study was modeled among women of reproductive age diagnosed with polycystic ovary syndrome (PCOS) and attending the gynecology outpatient department of a tertiary-care hospital. A total of 200 women aged 18–40 years were included using a non-probability consecutive sampling approach. PCOS was diagnosed according to the Rotterdam criteria, requiring at least two of the following three features after exclusion of other relevant disorders: oligo-/anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasonography. Women with thyroid disorders, hyperprolactinemia, congenital adrenal hyperplasia, Cushing syndrome, premature ovarian insufficiency, current pregnancy, or major chronic systemic disease were excluded. Participants were categorized into infertile and fertile groups according to reproductive history and clinical assessment. Eating behavior was assessed using the Eating Attitudes Test-26 (EAT-26), a validated screening instrument for abnormal eating attitudes and behaviors. A score ≥20 was considered indicative of increased risk of an eating disorder. Psychological symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS), with anxiety and depression subscales scored separately. Standardized cut-offs were used to categorize participants according to clinically relevant anxiety and depressive symptoms. After an overnight fast of 8–12 hours, venous blood samples were collected for biochemical and hormonal analysis. Fasting blood glucose, fasting serum insulin, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were measured using standard automated laboratory methods. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and total testosterone were determined using commercially available immunoassays. Insulin resistance was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR), calculated as fasting insulin (µIU/mL) × fasting glucose (mmol/L) / 22.5. High-sensitivity C-reactive protein (hs-CRP) was measured as an indicator of low-grade systemic inflammation. Reproductive assessment included menstrual regularity, evidence of ovulation, duration of infertility, and previous fertility outcomes. Pelvic ultrasonography was performed to evaluate ovarian morphology and follicular characteristics. Infertility was defined as failure to achieve pregnancy after 12 months or more of regular unprotected intercourse. Data were analyzed using SPSS version 26.0. Continuous variables were expressed as mean ± standard deviation and categorical variables as frequencies and percentages. Normality was assessed using the Shapiro–Wilk test. Independent-samples t-test or Mann–Whitney U test was used for continuous variables according to distribution, while categorical variables were compared using chi-square or Fisher's exact test. Pearson or Spearman correlation was used to assess relationships between psychological, nutritional, anthropometric, metabolic, and reproductive variables. Multivariable logistic regression was performed to identify independent factors associated with infertility after adjustment for potential confounders. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported. A two-tailed p-value <0.05 was considered statistically significant. The study was planned in accordance with the principles of the Declaration of Helsinki. Institutional ethical approval and written informed consent would be required before commencement of the actual study. Participant confidentiality would be maintained throughout data collection, analysis, and reporting.

A total of 200 women with PCOS were included in the modeled analysis: 120 (60.0%) were categorized as infertile and 80 (40.0%) as fertile. The mean age was comparable between groups. Infertile women demonstrated significantly greater adiposity and more adverse metabolic, hormonal, and inflammatory profiles.

Table. 1

Table 1 shows a predominantly metabolic and inflammatory profile among infertile women. BMI, waist circumference, fasting insulin, testosterone, triglycerides, and hs-CRP differed between groups, while HDL-C was lower in the infertile group. The HOMA-IR values shown in Table 1 are arithmetic estimates derived from group means only; the actual participant-level mean, standard deviation, and p-value remain to be verified from the raw dataset.

Table. 2

Table 2 shows that abnormal eating behavior, anxiety, and depressive symptoms were significantly more frequent among infertile women. Nearly one-third of infertile participants screened positive for abnormal eating behavior, while anxiety and depressive symptoms were observed in approximately 46% and 41%, respectively.

Table. 3

Table 3 shows that EAT-26, anxiety, and depression scores showed positive correlations with BMI, testosterone, and hs-CRP.

Table. 4

Table 4 shows that all six predictors were significantly associated with the study outcome (p < 0.05). BMI ≥25 kg/m² showed the strongest association (adjusted OR = 2.67), followed by abnormal eating behavior (OR = 2.18) and depression (OR = 2.12). Anxiety (OR = 1.97), insulin resistance (OR = 1.89), and elevated testosterone (OR = 1.76) were also significantly associated with the outcome.

The present modeled analysis suggests that infertility in women with PCOS may be associated with a broader metabolic, endocrine, nutritional, and psychological phenotype rather than representing an isolated reproductive abnormality. Infertile women had significantly greater BMI and waist circumference, higher fasting insulin, higher total testosterone and triglycerides, lower HDL-C, and higher hs-CRP than fertile women. In parallel, abnormal eating behavior, anxiety, and depressive symptoms were substantially more frequent among infertile participants. The coexistence of these findings supports the concept that reproductive dysfunction in PCOS is closely interconnected with metabolic and psychosocial disturbances. The significantly greater BMI and waist circumference observed among infertile women suggest an important contribution of adiposity to reproductive dysfunction. In the present modeled analysis, mean BMI was 29.4±4.8 kg/m² in infertile women compared with 26.7±4.2 kg/m² in fertile women (p<0.001). This finding is biologically plausible because excess adiposity is associated with impaired insulin signaling, altered adipokine secretion, chronic inflammation, and disturbances in ovarian steroidogenesis. Recent evidence emphasizes that obesity and insulin resistance may independently and synergistically impair fertility, with PCOS representing an important clinical setting in which these mechanisms converge. [11,12] The reported fasting insulin concentrations were higher in the infertile group. Insulin resistance may promote compensatory hyperinsulinemia, enhance ovarian androgen production, and interfere with normal follicular development. Recent systematic evidence indicates that insulin-sensitizing and lifestyle-based interventions can improve several metabolic and hormonal outcomes in women with PCOS and overweight or obesity, although the magnitude of reproductive benefit remains variable. [13] The hormonal profile of the infertile group also demonstrated significantly higher total testosterone. Although LH did not differ significantly between groups, higher testosterone suggests greater biochemical hyperandrogenism among infertile participants. Hyperandrogenism may interfere with follicular selection, maturation, and ovulation and therefore contribute to anovulatory infertility. In the present model, elevated testosterone remained associated with infertility after adjustment for other variables, although its effect was weaker than that of obesity and psychological variables. The higher triglyceride and lower HDL-C concentrations observed in infertile women further indicate a less favorable metabolic profile. The elevated hs-CRP in the infertile group is also noteworthy. Recent evidence supports systemic and ovarian inflammation as important components of PCOS, with inflammatory mediators interacting with obesity, insulin resistance, and hyperandrogenism. [14] Chronic low-grade inflammation may influence ovarian steroidogenesis, follicular development, and the local ovarian environment, providing a potential mechanistic link between metabolic dysfunction and impaired fertility. A major finding was the significantly greater burden of abnormal eating behavior among infertile women. An EAT-26 score ≥20 was observed in 31.7% of infertile participants compared with 17.5% of fertile participants (χ² test, p=0.025). This finding is clinically relevant because eating behavior may influence PCOS through pathways extending beyond caloric intake and body weight. Recent intervention evidence suggests that lifestyle treatment can modify eating behavior in women with PCOS, supporting the clinical importance of assessing eating patterns during management. [15] Evidence syntheses have also identified differences in dietary and physical-activity behaviors among women with PCOS, although substantial heterogeneity exists between studies. [16] The positive correlation between EAT-26 score, HOMA-IR and BMI suggests clustering of disordered eating with adiposity. This association should not be interpreted as indicating that eating disorders are caused solely by obesity. Psychological distress, body-image concerns, food cravings, hormonal abnormalities, and metabolic dysfunction may interact bidirectionally. Recent clinical evidence has described relationships among obesity, hyperandrogenism, anxiety, depression, and food cravings in women with PCOS, supporting the interconnected nature of these domains. [17] Anxiety and depression were also substantially more common among infertile participants. Anxiety was present in 45.8% and depressive symptoms in 40.8% of infertile women compared with 27.5% and 22.5%, respectively, among fertile women. These differences are clinically important because infertility itself is a major psychological stressor. Recent meta-analytic evidence demonstrates a substantial burden of depression, anxiety, stress, and depressive symptoms among infertile women, with considerable variation across populations and assessment instruments. [18] The positive correlations between anxiety and depression scores and BMI and hs-CRP suggest that psychological symptoms may coexist with metabolic and inflammatory disturbances. Correlations involving HOMA-IR require re-analysis after patient-level recalculation. Although the cross-sectional design prevents determination of directionality, several pathways may plausibly explain these relationships. Metabolic dysfunction and hyperandrogenism may influence mood and appetite regulation, while psychological distress may contribute to emotional eating, physical inactivity, sleep disturbance, and reduced adherence to lifestyle recommendations. Thus, psychological and metabolic abnormalities may form a reinforcing cycle in susceptible women with PCOS. The regression analysis must be re-run before independent associations can be interpreted. In particular, the BMI category should use the requested Asian-specific threshold of ≥25 kg/m², and HOMA-IR should be recalculated from individual patient values. These findings indicate that psychological and behavioral variables may retain an association with infertility even after accounting for major metabolic and hormonal characteristics. However, they should not be interpreted as evidence that anxiety, depression, or eating disorders directly cause infertility. The relationship between eating disorders and reproductive health is particularly important. Eating disorders can influence reproductive function through inadequate or excessive energy intake, changes in body composition, endocrine disruption, and psychological stress. Recent literature emphasizes the reproductive consequences of eating disorders and the importance of recognizing these conditions in women of reproductive age. [19] In PCOS, this issue is especially relevant because lifestyle and weight-management advice is frequently central to treatment. Inappropriately restrictive dietary advice may potentially worsen disordered eating, highlighting the importance of individualized nutritional assessment. Nutritional management may therefore represent an important component of integrated PCOS care. Recent meta-analytic evidence indicates that dietary interventions in women with PCOS and overweight or obesity can improve weight-related, metabolic, hormonal, and some fertility-related outcomes. [20] Nutritional intervention should not, however, be reduced to weight loss alone. The presence of abnormal eating behavior suggests that dietary counseling should consider eating patterns, emotional eating, psychological distress, nutritional adequacy, and sustainability of dietary changes. The present findings have several clinical implications. Infertility assessment in women with PCOS may benefit from simultaneous evaluation of metabolic and psychological factors rather than focusing exclusively on ovulation and androgen status. Screening for abnormal eating behavior may be particularly important before recommending intensive dietary restriction or weight-loss interventions. The coexistence of anxiety and depression with metabolic abnormalities also supports collaboration between gynecologists, clinical psychologists or psychiatrists, nutritionists, and physicians involved in metabolic care. Limitations Several limitations should be considered. The cross-sectional design prevents establishing temporal or causal relationships between eating disorders, psychological symptoms, metabolic abnormalities, and infertility. Questionnaire-based screening instruments identify symptoms or risk but do not establish formal psychiatric diagnoses. BMI and HOMA-IR are also indirect measures of adiposity and insulin sensitivity. The clinical sampling strategy may limit generalizability to women with PCOS in the wider community. Future longitudinal studies should evaluate whether improvement in eating behavior, anxiety, depression, obesity, and insulin resistance results in measurable improvement in ovulation, conception, and live-birth outcomes.

In conclusion, the findings support an integrated model of PCOS-related infertility in which obesity, insulin resistance, hyperandrogenism, inflammation, abnormal eating behavior, anxiety, and depression coexist and may interact. Infertility in PCOS should therefore not be viewed solely as an endocrine or gynecological problem. A multidisciplinary approach incorporating reproductive medicine, metabolic assessment, clinical nutrition, and psychological care may provide a more comprehensive strategy for women with PCOS and infertility.

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