The Female Brain on Hormonal Birth Control

By: Talia Oughourlian

Hormonal contraceptives were introduced more than 60 years ago (OBOS Contributors, 2021) with some commending the contraceptive pill as one of the greatest scientific inventions of the 20th century (The Economist, 1999). The creation of the birth control pill defined a critical moment in science and history in which human biological processes were understood well enough to be mimicked, and it provided women with unprecedented freedom. In the United States, an estimated 9 million women use the pill (CDC, 2019), but how does hormonal birth control affect the brain?

A Brief History of Hormonal Birth Control

In 1951, chemist Carl Djerassi, synthesized the first oral contraceptive by extracting norethisterone, an imitator of progesterone, from the Mexican wild yam root (Ball, 2015). Progesterone is produced in the ovaries and is responsible for preparing the lining of the uterus to potentially accept a fertilized egg after ovulation (Endocrine Society, 2022). The first oral contraceptive pill approved by the FDA in 1960 contained high concentrations of progestin (10,000 micrograms) and 150 micrograms of estrogen, whereas today’s third generation pills contain between 50-150 micrograms of progestin and 20-50 micrograms of estrogen (Knowles & Ringel, 1998; Cooper et al., 2022). Like progesterone, estrogen is involved in preparing the uterus from pregnancy and signaling ovulation (Dominguez et al., 2021). Now, various forms of hormonal contraceptive are available including the pill, a skin patch, an implant, an intrauterine device (IUD), the vaginal ring, and injection.

How Does Birth Control Affect Brain Structure?

…therefore concluding that hormonal contraceptives cause similar neuroplastic changes that accompany normal hormonal fluctuations.

neuroimagen techniques, including anatomical and diffusion-weighted magnetic resonance imaging (resonancia magnética), provide powerful tools to non-invasively investigate the macro- and micro- structure of the human brain. These techniques allow scientists to examine the influence of the hormonal contraceptives on the brain. Using MRI, one study found women using hormonal contraceptives exhibited larger gray matter volume (the region of the brain where the neuronal cell bodies are located) in the prefrontal cortex, the pre- and post-central gyri, parahippocampus, and fusiform gyri; regions respectively involved in decision making, sensorimotor function, memory encoding, and object recognition compared to healthy women not using hormonal contraceptive (Pletzer et al., 2010). Researchers also observed changes in the volume of these structures throughout the menstrual cycle of women not using birth control, therefore concluding that hormonal contraceptives cause similar neuroplastic changes that accompany normal hormonal fluctuations.

When accounting for the time women were using oral hormonal contraceptives, a study by Pletzer et al., found that the longer women were on the pill, the larger the size of their hippocampus y basal ganglia (Pletzer et al., 2019). The hippocampus is known to be involved in learning and memory consolidation, while the basal ganglia play an important role in motor learning. Interesting, Pletzer et al., also found that discontinuing oral contraceptives resulted in the reduction of hippocampal size back to baseline, revealing that some of the structural effects of hormonal birth control can be reversible while others, for example those in the basal ganglia, may not. While another study observed decreased gray matter volume in the amygdala, a brain region responsible for fear processing and psychosocial well-being, after 3 months of hormonal contraceptive use, but found no change in cognitive performance (Lisofsky et al., 2016). Further longitudinal research with large sample sizes is required to better understand how the structural effects hormonal contraceptives may influence cognitive plasticity.

How Does Birth Control Affect Brain Function?

Studies revealed that women on oral contraceptives demonstrated enhanced verbal memory…

As with many drugs, hormonal contraceptives can influence neurochemistry and therefore brain function. Functional magnetic resonance imaging, or fMRI, is a common technique used to study the inherent functional connectivity (synchrony between distinct brain regions), as well as to determine which brain areas are involved in a specific task. Given that differences in hippocampal structure have previously been observed in women taking hormonal contraceptives, multiple studies have investigated the impact of hormonal contraceptives on working memory. Studies revealed that women on oral contraceptives demonstrated enhanced verbal memory (Mordecai et al., 2008), reduced memory impairment due to cortisol (Kuhlmann & Wolf, 2005), and superior working memory during sleep deprivation (Wright & Badia, 1999) compared to non-users. One study using fMRI during a verb generation task, in which participants were shown a noun and asked to think about the corresponding verb, found that women taking hormonal contraceptives displayed stronger activation in task-specific brain areas than non-users (Rumberg et al., 2010).

One common side-effect of hormonal birth control is altered mood and irritability. To assess the potential impact, one study implemented an emotional facial expression matching task during a fMRI scan. Researchers found that after 21 days of hormonal contraceptive treatment, women experienced decreased activity in the insula, middle frontal gyrus, and inferior frontal gyrus (Gingnell et al., 2013). Furthermore, such changes in activity were correlated with greater depression and mood swing symptoms. It’s important to note that these findings were found in a sub-population of women who have previously experienced adverse mood side-effects of hormonal birth control.

Additionally, researchers have investigated the effect of hormonal contraceptives on neural reward processing. Using food-related and monetary forms of reward, studies found that some women on hormonal contraceptives experienced greater activation of brain regions involved in reward processing including the amygdala, insula, and putamen (Bonenberger et al., 2013; Arnoni-Bauer et al., 2017). Altered partner preference has also been associated with hormonal contraceptives, in which the pill may influence perceived mate attractiveness and overall preference (Alvergne & Lumaa, 2009). One study administered oxytocin, a hormone involved in partner-bonding, when females on non-hormonal contraceptives viewed photos of their partner and found increased perceived attractiveness and activity in the nucleus accumbens and ventral tegmental area (VTA), brain regions involved in reward and motivation (Scheele et al., 2016). The same response was not observed in the women using hormonal contraceptive.

Lastly, resting-state fMRI was employed to study the functional connectivity of the brain in the absence of task presentation. During rest, researchers found alterations in the default mode network (DMN), a network of brain regions active when a person is not engaged in a task or cognitive process, and the executive control network (ECN), a network responsible for high-level cognitive tasks, in women taking hormonal birth control, as well as throughout the normal menstrual cycle of non-users (Petersen et al., 2014).

Future Directions

In conclusion, researchers have found significant alterations in brain structure and function in women taking hormonal birth control, but we have yet to elucidate the impact of these alterations on women’s quality of life and overall well-being. Furthermore, certain findings in this field are contradictory and demonstrate the crucial need for larger, systematic studies that account for variations in baseline hormone levels in hormonal contraceptive users and non-users. Research has revealed differing results throughout the normal menstrual cycle and normal fluctuation of hormones, factors that must be accounted for in future investigations. Longitudinal studies must be conducted to investigate both the short- and long- term effects of hormonal contraceptives on the brain. In addition, new clinical trials are being conducted to investigate the efficacy of male hormonal birth control pills, which will require further research into the effects of hormonal contraceptives on the male brain.

In addition, new clinical trials are being conducted to investigate the efficacy of male hormonal birth control pills…

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Escrito por Talia Oughourlian
Imagen por Himani Arora
Edited by Carolyn Amir, Vincent Medina, and Lauren Wagner

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