To date, little research has been conducted to ascertain whether women’s brain activity varies during the menstrual cycle due to changes in hormone levels. Most studies on the subject have focused on its specific regions, without analysing their global functioning nor that of brain networks. Neither has the evolution of brain dynamics across its different phases been examined. To shed light on these issues, a recent study by UPF and Paris Lodron University of Salzburg has analysed the activity of women’s brains from an evolutionary and innovative perspective in the field of neuroscience.

The study concludes that the variations in the levels of hormones (progesterone and estradiol) throughout the different phases of the menstrual cycle bring about changes in various areas of the brain related to cognitive abilities, emotions and behaviour. These variations are in turn conditioned by age, according to the research recently published in an article in npj Women’s Health, a journal of the Nature group. The research is co-led by the researcher Anira Escrichs, of the Computational Neuroscience Group at the UPF Center for Brain and Cognition (CBC) and Belinda Pletzer, of the Department of Psychology and the Center for Cognitive Neuroscience at Paris Lodron University of Salzburg.

The study is based on a sample of 60 naturally-cycling women (with no hormonal treatments) aged between 18 and 35 years. To analyse the changes in brain activity during the menstrual cycle, three functional MRIs were performed on each woman (one for each phase of the menstrual cycle) in resting state, that is, without performing any specific cognitive task.

Specifically, the evolution of various brain networks in resting state was analysed related to attention, emotions, introspection, etc. When examining these networks, the researchers studied how the ability of their brain areas to propagate information to reach other parts of the brain varies. This is related to so-called metastability, or in other words, the variation in brain activity in a given region, which is conditioned by the greater or lesser speed with which it receives new information. The greater the metastability, the greater the complexity of brain dynamics and also the greater its flexibility and ability to process information.

The phases of the menstrual cycle

During the research, the variation of the complexity of brain dynamics (or metastability) was studied across the menstrual cycle. The cycle starts with the follicular phase (between the first day of menstruation and the following fourteen days), which begins when the pituitary gland of the brain releases a hormone that stimulates the production of follicles on the surface of the ovary, each of which contains an egg. Usually only one egg, which is released during menstruation will reach maturity. This usually happens about 15 days before the next menstruation and marks the onset of the ovulation phase during which this mature egg travels through one of the fallopian tubes to the uterus. After ovulation, a set of cells in the ovary, which make up the corpus luteum, release progesterone and a small amount of oestrogen. This is the luteal phase, during which a lining of the uterus is generated to prepare it for a possible pregnancy due to the effect of these hormones. If there is no pregnancy, the corpus luteum disappears and, therefore, so does the lining of the uterus due to the drop in hormone levels, and the cycle begins again.

In this study, the brain activity of women at specific times of the previous phases was examined: early follicular, pre-ovulatory, and mid-luteal phases. According to their results, the levels of metastability (brain complexity) depend on the levels of progesterone and estradiol, which vary in each of these phases. "We show that ovarian hormones modulate the dynamics of the entire brain throughout the menstrual cycle" - explains Anira Escrichs, of the Computational Neuroscience Group of the CBC at UPF.

The complexity of brain dynamics reaches its peak during pre-ovulation, starts to drop during the luteal phase, and records its minimum in the early follicular phase, that is, at the start of the menstrual cycle

During the menstrual cycle, the lowest level of metastability occurs during the early follicular phase, when the level of the two hormones is lower. The complexity of brain dynamics reaches medium levels halfway through the luteal phase, characterized by an increase in progesterone levels that peak in the middle of this period. But the maximum levels of metastability occur during the pre-ovulatory phase, when estradiol levels attain maximum concentration.

The study findings open the door to the future development of personalized treatments for women with menstrual cycle disorders. This research could be complemented in the future by other studies on the complex relationship between hormone levels and brain dynamics, also among menopausal (or pre-menopausal) women.

Image: Figure about dynamical complexity of menstrual cycle phases (Source: nature.com/articles/s44294-024-00012-4/figures/3)

Reference article: Avila-Varela, D.S., Hidalgo-Lopez, E., Dagnino, P.C. et al. Whole-brain dynamics across the menstrual cycle: the role of hormonal fluctuations and age in healthy women. npj Women’s Health 2, 8 (2024). https://doi.org/10.1038/s44294-024-00012-4

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