The female reproductive axis essentially comprises of the hypothalamic-pituitaryovarian axis and the mullerian-derived structures. The reproductive axis ages to a nonfunctional state (menopause) much earlier than the other organ systems do, at a time when a woman is otherwise healthy. The basis of reproductive senescence in women is oocyte depletion in the ovary. Perimenopause is defined by menstrual cycle and endocrine changes, such as disturbed ovarian-pituitary-hypothalamic feedback relationships, inaccurate estrogen levels, and decreased progesterone levels. Many psychopathological changes can take place, but most commonly women experience mild cognitive impairment, anxiety, irritability, mood swings, and depression. Estrogens influence depression and depressive-like behavior through interactions with neurotropic factors and through an influence on the serotonergic system.