Premature Ovarian Insufficiency, Early Menopause and Mild Cognitive Impairment: A Cohort Study

Background: Natural menopause (NP) typically occurs around the age of 50. In contrast, premature ovarian insufficiency (POI) and early menopause (EM) refer to the loss of normal ovarian function before the ages of 40 and 45, respectively. Surgical menopause, resulting from bilateral oophorectomy, leads to an abrupt hormonal decline. Emerging evidence suggests that early loss of ovarian function, whether natural or surgical, may impact cognitive performance. Objective: This study aimed to clarify the effect of different types of menopauses, POI and EM (spontaneous or surgical) on the risk of mild cognitive impairment (MCI). Study Design: This was an observational, cross-sectional, analytical study conducted in women’s health outpatient clinics at two university centers in Brazil. Methods: Socio-demographic factors, clinical histories, anthropometric measurements, and family histories were studied in a large population of postmenopausal women. MCI and postmenopausal symptoms were assessed using the Montreal Cognitive Assessment (MoCA) test and the Menopause Rating Scale (MRS), respectively. Data were analyzed according to the type of menopause (spontaneous or surgical) and age at menopause (POI, EM and NM) using logistic regression models. Results: A total of 519 women were studied. No significant differences were observed between the groups in the different domains and the total score, but a cognitive deficit above 85% was found in the three groups. A higher risk of MCI was observed in women with bilateral oophorectomy [adjusted odds ratio (aOR) 3.21, 95% confidence interval (CI) 1.57 to 7.19, P=0.03], use of sleep inducers (aOR 3.31, 95% CI 1.86 to 5.92, P< 0.0001), and higher body mass index (aOR 1.05, 95% CI 1.01 to 1.10, P=0.031). In contrast, more years of education were associated with a lower risk of cognitive impairment (aOR 0.93, 95% CI 0.86 to 0.99, P=0.028). Current or previous use of hormone therapy, parity, smoking, comorbidities, and use of anxiolytics or antidepressants were not significantly associated with MoCA scores. Conclusion: POI and EM are not associated with higher MCI risk. Bilateral oophorectomy, use of sleep inducers, and higher BMI are associated with an increased risk of MCI in postmenopausal women, independently of age or time since menopause. Conversely, higher educational attainment appears to be a protective factor. These results highlight the importance of identifying women at greater risk of cognitive decline based on menopausal type and modifiable factors. Longitudinal studies are needed to clarify causality and guide personalized management strategies.