Sex hormones and mental health

Sex hormones, such as estrogen, progesterone, and testosterone, are part of the hormones called steroid hormones. The brain has receptors for these steroid hormones and therefore is an organ influenced by them, especially in emotional and cognitive regulation (1,2). During adolescence, when there is a significant rise in the levels of sexual hormones, structural changes in the brain occur, influencing not only sexual behavior but also mood and cognition (1,3).

Regarding the effect of sex hormones in the development of mental disorders, it has been suggested that estrogen and progesterone might play a role in the onset of depression. Depression is one of the most common mental disorders, and it is expected that by 2030 it will be the most socioeconomically burdened disease (2). Before puberty, girls are as propensity as boys to suffer from depression. However, after puberty women are twice more likely to suffer from this mental illness than men (2). Several factors might influence this higher risk of women being depressed, from higher rates of experienced violence, childhood sexual abuse, discrimination, lower self-esteem, and higher body shame among women, to hormonal factors (4). Moreover, more women feel depressed after menopause, which is a phase in a woman's life where the levels of estradiol and progesterone decrease significantly, and there is 50% less secretion of testosterone compared to young women (2). These low testosterone levels are also associated with low sexual motivation, which affects the life quality of the person (1). In men with depressive disorders, borderline or low total and free testosterone levels have been found (5). In the case of other mental illnesses like schizophrenia, psychotic episodes are more often when the levels of estrogen are low, for example in the menstrual phase of the cycle, post-partum, or postmenopause. On the other side, there are reduced rates of relapse during pregnancy, when the plasma levels of estrogen are high (3). This could be explained by the neuron’s protective effect of estrogens against stress and injury (3).

There are also interactions between sex hormones and other hormones, as well as with neurotransmitters. For example, estrogen plays a role in increasing the synthesis and effectiveness of serotonin, which is involved in mood (2). During chronic stress, higher levels of corticosteroids can reduce testosterone concentration, affecting not only the reproductive area of the person but also the social, emotional, and cognitive functions (1).

The influence of oral contraceptives (OCPs) on mood has been a controversial topic. A big study made with over 1 million Danish women found that the use of OPC is associated with a higher risk of depression diagnosis, suicidal acts, and antidepressant treatment, being more pronounced in adolescents. Because there are different OPCs hormone preparations and dosages, it is not surprising that other studies have found different results, for example, an increased risk of mood disorders with progestin-only OPCS but decreased when combined with estrogen-progestin OPCs (5).

Ideally, during research and psychiatric training and practice, alterations in the sex hormone levels should be taken into consideration for the treatment and study of mental illness.

References 1.Martínez-Mota, Lucía. Sexual hormones and mental health. Salud mental 2020, 43 (1): 1-2.

2.Lei, R., Sun, Y., Liao, J. et al. Sex hormone levels in females of different ages suffering from depression. BMC Women's Health 2021, 21 (215).

3.Brzezinski-Sinai, Noa A. & Brzezinski, Amnon. Schizophrenia and Sex hormones: What is the Link? Front. Psychiatry 2020, 11(693): 1-5

4.Riecher-Rössler, Anita. Sex and gender diff erences in mental disorders. The Lancet 2017, 4: 8-9.

5. Dwyer JB, Aftab A, Radhakrishnan R, Widge A, Rodriguez CI, Carpenter LL, Nemeroff CB, McDonald WM, Kalin NH; APA Council of Research Task Force on Novel Biomarkers and Treatments. Hormonal Treatments for Major Depressive Disorder: State of the Art. Am J Psychiatry 2020;177(8):686-705.