Major depressive disorder represents one of the most common psychiatric diagnosis, and was ranked by World Health Organization as the third cause of morbidity and mortality worldwide, expecting to become the first cause by 2030. The prevalence of depression is higher in women than in men, once the puberty sets. This may be explained by the hormonal fluctuations, estrogen and progesterone, over a woman's lifespan. Some of the women may experience severe mood symptoms during the luteal phase of the menstrual cycles, known as premenstrual dysphoric disorder. In addition, it has been shown that the use of hormonal contraceptives, especially oral contraceptives (OC), may determine an induced depressive disorder. The risk of induced depressive disorder is even higher in women who start an OC treatment during adolescence, mainly because this is the period when the hormonal milieu is developing. Another important period of hormonal fluctuations is after delivery. It is described such as a hormonal ‘withdrawal state’ because in a matter of days postpartum, the hormonal levels decrease down to the levels of a non‑pregnant woman. It is worth to mention that this extreme decreasing of estrogen and progesterone is not enough in order to develop postpartum depression. It has been suggested that postpartum depression may be a consequence to differential activation of estrogen genes. Fortunately, since 2019, Food and Drug Administration approved the first specific hormonal treatment for postpartum depression, represented by brexanolone. The last period of hormonal changes is the transition to menopause, in which depressive symptoms may be determined by day‑to‑day hormonal fluctuations. There is a lot more to explore in this field for future research, regarding if there really is a direct link between the levels of estrogen and progesterone and depressive disorder, and also regarding different hormonal therapies.

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