That Time of the Month

A female figure sitting atop a uterus with emphasized neural networks connecting the brain and the reproductive system
A female figure sitting atop a uterus with emphasized neural networks connecting the brain and the reproductive system

You wake up one day feeling bloated and groggy. Add to that a sudden random craving for spicy cheetos or the urge to burst out in tears because someone holds open the door for you. Your phone buzzes and the little notification banner from your period tracking app reads, “Your period is tomorrow!” Ahh, it’s simply that time of the month. Once again, it’s time to undergo the monthly menstruation rituals: pads, tampons, cups, period underwear--the whole shabang. You move on with your day-to-day life while simultaneously bleeding out and following a schedule of painkillers. If your behavior seems erratic and out of the “norm,” it is dismissed because “it’s that time of the month.” Although it’s routine, we’re wrong to dismiss something that has such profound effects on roughly 50% of the population. Have we considered the menstrual cycle from a neuroscientific and neurobiological lens in order to explain these changes? In confronting the neuroscientific mystery of menstruation, it becomes evident that the menstrual cycle is a vital socio-cultural and biological component of neuroscientific research that cannot be neglected if the gender barriers in academia are to ever be dismantled.

In order to fully grasp the neurological underpinnings of the menstrual cycle, we should first understand the basics of the menstrual cycle. There are two main phases that make up the menstrual cycle: the follicular phase and the luteal phase [1]. The absence of fertilization results in menstruation, which is the shedding of the uterine lining [2]. The menstrual cycle spans from the first day of bleeding, or the day menstruation begins, to the first day of the next cycle [3]. The average menstrual cycle is approximately 28 days in young healthy people who have proven fertility and no reproductive issues. However, it should be kept in mind that menstrual cycles vary from person to person [4]. The follicular phase is a 14.6-day duration in preparation for an egg to be fertilized, which precedes the luteal phase, which is a 13.6-day duration.

The luteal phase takes place between ovulation and the first day of menstruation. There is a slow decline in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) as estrogen levels constantly increase and then decrease throughout the luteal phase. Progesterone increases after ovulation and falls rapidly before menstruation. FSH and LH will gradually increase right before menstruation. The follicular phase takes place between the first day of menstruation and ovulation. During this time, a person will experience an increase in circulating hormones. Right before ovulation LH, FSH, and estrogen peak [5]. These phases are often associated with the physical and emotional feelings that people may encounter throughout their cycle. High energy levels, better memory, and high pain tolerance are associated with the follicular phase. Sluggishness, depression, bowel problems, migraines, and abnormal glucose levels, which may result in cravings, are associated with the luteal phase [5]. Such sharp change of levels of various hormones result in the mood swings that are often associated with the menstrual cycle.

A diagram of the hormonal and physiological changes associated the menstrual cycle
A diagram of the hormonal and physiological changes associated the menstrual cycle

The influence of gonadal hormones, or sex hormones, is pivotal to understanding how the menstrual cycle affects people’s day-to-day life. Sex hormones alter the structure and function of neural systems and influence behavior [6]. Neural and behavioral functions such as mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity are all affected by hormone regulation. Gonadal hormones particularly influence the hypothalamus and the hippocampus. The hypothalamus is responsible for maintaining homeostasis of the body and releasing hormones, while the hippocampus is involved in emotional processing, perception, and memory [6]. Neuroimaging studies have revealed the relevance of hormonal fluctuations throughout the menstrual cycle on brain structures like the hippocampus that are responsible for emotion and cognition.

The main classes of sex hormones involved throughout the menstrual cycle include estrogen and progesterone. Estradiol, which is an estrogen steroid, plays a significant role in the menstrual cycle [7]. Estrogen has multiple effects on the brain: it improves learning, memory, motor skills, coordination, and reaction time; increases neuron excitability (their tendency to fire); provides neuroprotection in the hippocampus and cerebral cortex; regulates cardiovascular systems; and reduces pain sensitivity [7]. For example, higher estrogen levels have been indicative of enhanced memory recall in the hippocampus. This better memory is a key characteristic of the follicular phase where estrogen levels dramatically increase at the onset of ovulation [7]. Thus, the menstrual cycle entails a plethora of hormones with multifaceted responsibilities that demonstrate the changing neurobiology in those who menstruate.

The neuroscientific approach to and research of the menstrual cycle is still in its embryonic state. Many studies have shown changes in neural activity that vary with the aforementioned phases of the menstrual cycle [1]. Hormone levels, which fluctuate throughout the menstrual cycle, change emotion and certain brain reactivity [8]. Although there is limited evidence, research suggests that emotional and cognitive processing is regulated by the menstrual cycle which may be linked with changes in the brain during specific phases of the menstrual cycle [1]. By understanding the neurological underpinnings of the menstrual cycle, menstruation will hopefully no longer be observed as a mystery of bleeding and emotional imbalances and will instead be seen through a scientific lens.

Societal stigma around women being emotional or irritable surrounds menstruation and “PMS-ing” (premenstrual syndrome). The neuroscience behind the menstrual cycle helps to understand the basis for these stereotypes of menstruation. Emotional changes during the menstrual cycle have been linked to the fluctation of various sex hormones and the phases of the cycle. During the luteal phase, premenstrual emotional disturbances are associated with exposure to progesterone [6]. Sensitivity in the amygdala, two lima-bean shaped brain structures that are responsible for fear and anger, changes with sex hormones which is evident in differiential blood flow to the amygdala [6]. Experimental data shows that the luteal phase is associated with negative emotions and slower reaction times [9]. Additionally, neuroimaging scans provide substantial insight into the physical changes in the brain that occur throughout the menstrual cycle.

Neuroimaging studies have shown neuroplastic changes in the brain throughout the menstrual cycle. Neuroplasticity is the brain’s ability to change and adapt as a result of homeostasis and reorganization in our brain as we learn and experience new things [10]. Estrogen is capable of inducing synaptogenesis, the formation of new synapses between neurons, in the hippocampus, which is another reason behind enhanced memory recall in the follicular phase [7]. However, progesterone terminates these estradiol-induced synapse formations through a rapid downregulation of synapses, making the neurons less susceptible to hormone interactions by decreasing the amount of available receptors on the neuron [7]. Progesterone levels are high throughout the luteal phase, while estrogen levels drop [6].

A study that examined differences across various brain structures showed that brain size varies according to menstrual cycle phase. During ovulation, there is an increase in gray matter and loss of cerebrospinal fluid, which can be connected to increasing progesterone levels and estradiol levels at the onset of ovulation [5]. In a volumetric MRI study, women showed an increase in volume in the right anterior hippocampus during the late follicular phase compared to the late luteal phase [5]. The hippocampus is a key brain structure for integrating emotion, cognition, and memory. Specifically in terms of memory, the hippocampus processes facial expressions and forms declarative memories (explicit things you remember like facts and events) and emotional memories (memories that evoke a significantly emotional response). The dorsal basal ganglia, a group of neural structures that is smack in the middle of the brain, also shows a size decrease during the late follicular menstrual phase [5]. The basal ganglion is responsible for voluntary motor movements and learning, especially in reward and reinforcement behavior. All of these studies reveal preliminary findings for neuroplastic changes across the phases of the menstrual cycle. Most of these changes occur in regions with critical roles in sensory perception and regulation of responses to emotional stimuli. Thus, there are clear neurophysiological changes that occur in tandem with the menstrual cycle that may also produce the psychological and behavioral changes that occur during menstruation, though further research is needed to affirm causation.

More neuroimaging scans have also detailed the influence of the menstrual cycle in reward system pathways. For example, a greater blood-oxygen-level-dependent (BOLD) response in the amygdala, orbitofrontal cortex, midbrain, and striatum was found during the follicular phase. These areas are key for autonomic control, emotional processing, and reward. Additionally, BOLD responses used to test inhibitory control (IC), which suppresses active cognitive processes in order to choose one action over another action, show that the anterior cingulate cortex (ACC) and left inferior parietal lobe have stronger network connectivity strength during the follicular phase, suggestive of higher IC during the preovulatory period [11]. The ACC is important for impulse control and decision-making, while the parietal lobe integrates sensory information into perception. Applications of these findings can explain the premenstrual increase in motivated behaviors like food cravings [12]. The data from neuroimaging and menstrual cycle studies demonstrate the necessity of further studies to elucidate neuronal activity patterns by taking into account the underlying neural components of the population at stake, including those who menstruate.

Knowledge of the menstrual cycle and contraceptive history is crucial when studying health, disease, and pharmacology, especially when it comes to understanding the implications of medicine on different sexes. Historically, medications have gone through clinical trials where most if not all the test participants were men [13]. Government reports from the 1980s and 90s denoted the lack of women participation and representation in federally funded studies and in areas of diseases that affected both sexes [13]. By considering the nuanced nature of the menstrual cycle and its effects throughout the body, preventative care can be more potent and effective in its treatment. Unfortunately, evidence of neurobiological and behavioral links to the menstrual cycle is currently extremely limited, which can lead to a difficulty in including those who menstruate in clinical trials for medicine and preventative treatment.

Despite the urgency to include women and those who menstruate in the world of research, findings and studies on the menstrual cycle have been difficult to replicate and the methodology has been suspect due to the meticulous and skillful handling that is required to conduct these studies [6]. For example, studies that suggest differences throughout the menstrual cycle in tasks like visuospatial ability and verbal memory only produce small differences and are difficult to replicate. Additionally, the participants in studies testing the menstrual cycle’s effect on cognition appear to be non-inclusive of all ages, with participant groups leaning toward a younger age group. This means that cognitive decline has not yet taken place and is not considered in the research [6]. Adding on to the difficulty of replication is the obstacle of genetic make-up of participants, which may interfere with certain memory tasks. Both changes in estradiol levels and the presence of a specific allele that influences decision-making together have been shown to drive the compulsivity to choose an immediate reward over delayed rewards [14]. This gene, coupled with estrogen, makes it hard to differentiate which factor is the driving force behind impulsivity in these studies regarding the effects of estrogen on impulsivity. Ovarian steroids also interact with multiple neurotransmitters like serotonin and GABA, which further nuances the bigger picture [6]. With these otherwise neglected factors eventually being taken into account, further studies may be able to provide more tangible and affirmative evidence linking neurobiological and menstrual activity together.

Despite the lack of scientific backing at the present moment, diving into further research and calling attention to a scientific and intersectional understanding of the menstrual cycle will slowly pick away at society’s prejudices and biases towards women and others who menstruate. Menstruation has been a distinguishing marker between men and women. In certain parts of the world, it is denoted as a weakness; further instilling the submissive role of women in society. The blood and fluids involved in menstruation are seen as a natural limit to the female body. As reinforced by the sexist menstrual hygiene industry, menstruation is seen as a taboo, something that must remain hidden and is shameful [15]. For example, in modern-day India there are currently hundreds of millions of girls and women who lack access to proper menstrual hygiene products, endangering their education, health, and lives [16]. Many are forced into using rags, husks, dried leaves, grass, ash, sand, or newspapers during menstruation. Inaccessibility to menstrual products is a result of a predominantly patriarchal and hierarchical society perpetuating taboos and misunderstandings regarding the menstrual cycle and menstruation [16].

From the perspective of someone who does not experience menstruation, this biological process may seem abstract and almost mythological, contriving stereotyped descriptions like PMS and moodiness, without any thought as to why this is a natural consequence of the menstrual cycle. Further research on the menstrual cycle, both on a basic scientific stance as well as through an intersectional perspective will bridge this divide and promote familiarity on this subject. Through a proper neurological understanding of the menstrual cycle, we can learn more about the implications of the menstrual cycle for those who experience menstruation.

A panel of assorted faces representing the diversity among those who may experience menstruation
A panel of assorted faces representing the diversity among those who may experience menstruation

In addition to the societal abstraction of the menstrual cycle coupled with developing scientific understandings of menstruation, common associations with the menstrual cycle stereotypically stir up images of cramps, cravings, and sanitary products, along with connotations of irritability. These aforementioned depictions of menstruation are all a product of PMS, a physiological and psychological phenomena that occurs before the onset of menstruation. About 95% of women of reproductive age experience premenstrual symptoms, while 5% of those women experience severe forms of premenstrual symptoms [17]. The physiological characteristics feature breast tenderness, bloating, headaches, food cravings, and constipation, while the psychological characteristics involve mood swings, irritability, and tiredness [17]. Premenstrual dysphoric disorder (PMDD) is a more severe case of PMS where symptoms of PMS become disruptive of day-to-day activities and relationships.

A more thorough understanding of the triggers of PMS and PMDD through neurobiological research can allow medical professionals to identify this condition earlier and intervene rapidly. New neurological and biological theories have led to a better understanding and approach for developing therapeutics and treatment for PMS and PMDD. For instance, the varying levels of gonadal hormones throughout the menstrual cycle is a sign of changes in neurotransmitter activity, including neurotransmitters like serotonin. These varying levels may result in provisional changes in mood and behavior, which are signature features of PMS and PMDD. Surprisingly, serotonin reuptake inhibitors (SSRIs), which are antidepressants that allow more serotonin to interact with postsynaptic neurons and further prolong serotonin’s effect on the body, can alleviate not only psychological complaints associated with PMS but also physical complaints [18]. Serotonin is a key player in regulating mood. Estrogen has been linked with serotonin activity, so decreased serotonin leads to decreased levels of estrogen. Thus, mood disturbances during PMS can be explained by decreased estrogen exposure, which is ultimately driven by low serotonin [1]. SSRIs have been increasingly used as the first line of defense for PMS, and can be taken at any point of the menstrual cycle [19]. SSRIs have been found to be effective in alleviating symptoms of PMS, but side effects such as nausea and extreme fatigue are relatively frequent [19].

The concerning lack of scientific knowledge on women’s health and the menstrual cycle is inevitably dangerous for future scientific research and medical treatment. To avoid further disparity in representation, a better understanding of female physiology and the effects of cyclical hormonal changes can help. This bias is inherent in medical research. Medical research is fundamentally flawed due to the lack of incorporating sex differences in study designs, tools, and analysis [20]. An improper understanding of diseases and drug effects on women results from a lack of inclusion of women in medicinal research. The apprehension to include women in research has stemmed from the stigma of “hormonal” nature of women [20].

Unfortunately, medical research often views the menstrual cycle as an obstacle instead of accepting the menstrual cycle as an integral part of medical research. As a result, women are all too often relegated to the sidelines. For example, in studies on sports and exercise medicine research, women are disproportionately underrepresented [21]. Thus, exclusion of women in research studies is a direct result of a lack of understanding the nature of the menstrual cycle since it is deemed a “major barrier” in clinical trials because of the varying hormone levels that must be kept track of during studies. [21]. Exercise research on women participants is often done during the early follicular phase of the menstrual cycle, which is when hormone levels are at the lowest [21]. Therefore, this avoids consideration of hormonal influence on many physiological processes in those who menstruate.

Future emphasis and work on menstruation in neurobiological research will open up pathways for inclusivity in scientific and medicinal literature. For now, there is limited research that introduces the connection between hormonal changes throughout the menstrual cycle with that of behavioral, emotional, and cognitive changes in the day-to-day lives of those who experience the menstrual cycle. Although this article places an emphasis on presumed understanding of menstrual cycles as a natural process in female bodies, we must also recognize that transgender and non‐binary people face this biological function as well. The social gatekeeping and gendering of menstruation present in society is a crucial societal component that researchers should take note of in studies and future scientific research in order to fully understand the depths of what the menstrual cycle is and who experiences it [22]. Further research in the area of the basic neurobiology behind the menstrual cycle can allow for future research done on the effects of the menstrual cycle during menopause and postmenopause, use of contraceptives, and hormonal disorders like polycystic ovarian syndrome. Therefore, there should also be emphasis on a more inclusive sample in future studies that will accurately represent the population that experience the menstrual cycle and further our understanding of its neurological effects.

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