Hormonal Contraception and Depression: Updated Evidence and Implications in Clinical Practice
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REVIEW ARTICLE
Hormonal Contraception and Depression: Updated Evidence and Implications in Clinical Practice Franca Fruzzetti1 · Tiziana Fidecicchi1
© Springer Nature Switzerland AG 2020
Abstract Hormonal contraceptives are used worldwide by more than 100 million women. Some studies have been published about the possible appearance of depressive symptoms when using hormonal contraceptives, but this link is still a matter of debate. The purpose of this review is to provide an update of the literature on this issue, and to investigate the possible explanations of this problem based on animal and human studies. The main pathway responsible for menstrual cycle-related mood changes is the γ-aminobutyric acid pathway, which is sensitive to changes in the levels of progesterone and of its metabolites, the neurosteroids. In particular, allopregnanolone is a potentiating neurosteroid with anxiolytic and anti-convulsant effects whose levels change during a normal menstrual cycle together with progesterone levels. Progestins have different effects on allopregnanolone, mainly owing to their diverse androgenicity. Moreover, they might affect brain structure and function, even though the meaning of these changes has yet to be clarified. It is important to define the groups of women in which negative mood disorders are more likely to occur. Adolescence is a critical period and this age-specific vulnerability is complex and likely bidirectional. Moreover, women with a history of mood affective disorders or premenstrual dysphoric syndrome are at a higher risk when taking contraceptives. In this review, we aim to provide clinicians with advice on how to approach these difficult situations.
Key Points
1 Introduction
The existence of a link between hormonal contraception and depression is still open for discussion.
Sex hormones are fundamental in the regulation of reproductive function of women, but their role is not limited to this aspect. Sex steroid receptors are represented in numerous regions of the central nervous system (CNS), thus indicating that estrogens, progestins, and androgens are involved in controlling vegetative, psychophysiological, and cognitive functions. They can act through genomic and non-genomic mechanisms, causing short- and long-term effects [1]. Variations in sex hormone levels are related to the appearance of specific symptoms, as a result of the CNS derangement [2]. Depression and anxiety disorder are more frequent in female individuals than in male individuals and they are the most common mental health disorders to appear during a woman’s life [3]. The relationship between sex hormones and depressive symptoms can be further and easily deduced by the appearance of these symptoms in specific periods of life (i.e., premenstrual phase, pregnancy/postpartum, and menopausal transition). Finally, some mental disorders, such as anxiety, bipolar disorder, psychotic disorders, and eating disorders, are exacerbated by the menstrual cycle [4, 5].
Hormonal contraceptives are able to modify the structure and
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