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Despite the fact that irritability is frequently the main presenting complaint of perimenopausal and postmenopausal women, studies specifically researching irritability in this population are scant. One hundred sixty three (163) peri- and postmenopausal women non-HT users, attending a menopause clinic, were included in this cross-sectional study. The investigation focused on whether the occurrence of inward and outward irritability in menopause is associated with various menopausal parameters, such as vasomotor symptoms, insomnia, menopausal status, hormone levels, and with the presence of chronic disease. Furthermore, we examined the possible association of inward and outward irritability with measures of anxiety and depression. Outward and inward irritability of peri- and postmenopausal women seem to be related to chronic disease, a factor that may be partially influenced by the older age of menopausal women. Outwardly directed irritability is found to be related to FSH and LH levels, independently of specific menopausal symptoms, such as vasomotor symptoms or insomnia. Outward irritability was found to be positively correlated with depressive symptomatology, whereas inward irritability correlated with both anxiety and higher depressive symptomatology.