Hormones play a vital role in maintaining proper bodily functions. However, these powerful chemical messengers can also profoundly impact mood and mental health, with both positive and negative consequences.
We often feel we have full control over our feelings and emotions. But how true is this perception? While scientists have long understood the significant influence of chemical messengers called neurotransmitters on the brain, an increasing body of research reveals that hormones can also shape the mind in surprisingly intricate ways.
This burgeoning knowledge is now being harnessed to develop innovative treatments for debilitating conditions such as depression and anxiety disorders.
Hormones are chemical messengers secreted by specific glands, organs, and tissues. Once released, they enter the bloodstream and traverse the entire body, eventually binding to specialized receptors at their target sites. This binding action functions as a biological “handshake,” signaling the body to perform a particular task. For instance, the hormone insulin instructs liver and muscle cells to absorb excess glucose from the blood and store it as glycogen.
The Unseen Influence of Hormones
To date, scientists have identified over 50 distinct hormones within the human body. Collectively, these numerous hormones orchestrate hundreds of physiological processes, including growth and development, sexual function, reproduction, sleep-wake cycles, and, critically, human mental well-being.
“Hormones significantly influence our mood and emotions,” states Nafissa Ismail, a professor of psychology at the University of Ottawa, Canada. “They achieve this by interacting with neurotransmitters produced and released in specific brain areas, and also by affecting fundamental processes like cell death or neurogenesis, the generation of new nerve cells.”
The susceptibility to mental health conditions such as depression, anxiety, and post-traumatic stress disorder (PTSD) tends to increase during significant hormonal transitions. This impact can be particularly pronounced in women. While depression rates remain largely similar between boys and girls during childhood, by adolescence, women become twice as likely as men to experience depression, a disparity that persists throughout their adult lives.
Could Hormones Be the Root Cause?
It is widely recognized that sex hormones exert a significant influence on women’s moods. In the days and weeks leading up to menstruation, levels of estrogen and progesterone decline. This fluctuation can lead to heightened irritability, fatigue, sadness, and anxiety for some women. A smaller, yet significant, subset of women may experience Premenstrual Dysphoric Disorder (PMDD), a severe hormone-related mood disorder characterized by extreme mood swings, intense anxiety, depression, and occasionally suicidal thoughts during the two weeks preceding menstruation.
“For many women with PMDD, this is a chronic monthly struggle that can have a profound impact on their lives,” explains Liisa Hantsoo, an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, USA.
Conversely, in women, elevated estrogen levels just before ovulation are associated with feelings of comfort and happiness. Moreover, allopregnanolone, a derivative of the hormone progesterone, is renowned for its calming effects. “If a woman is injected with allopregnanolone, she will relax,” Hantsoo confirms.
Beyond the menstrual cycle, women also navigate hormonal fluctuations during pregnancy, perimenopause, and menopause, all of which can affect mental health. Indeed, a notable 13% of women who have recently given birth experience postpartum depression.
What underlies these shifts? Shortly after childbirth, women undergo a drastic reduction in progesterone and estrogen levels. Similarly, during perimenopause, women can experience dramatic and often unpredictable fluctuations in ovarian hormones.
“It may not be about the absolute hormone levels, but more likely the transition that occurs when someone moves from low to high hormone levels, or vice versa,” notes Liisa Galea, a professor of psychiatry at the University of Toronto, Canada. “Some individuals are simply more sensitive to these kinds of fluctuations, while others may pass through menopause without experiencing any significant symptoms.”
The impact isn’t exclusive to women. Men’s testosterone levels also gradually decline with age, though these changes are typically more subtle and less distinct than those observed in women. Nevertheless, some evidence indicates that even these minor shifts can be sufficient to trigger mood changes in certain men, albeit less frequently or severely than in women.
“We observe mood changes in some men corresponding to testosterone shifts throughout their lives, and that’s definitely an understudied topic,” states Ismail.
One mechanism through which sex hormones influence mood in both women and men is by altering levels of the neurotransmitters serotonin and dopamine in the brain. Low serotonin levels have long been implicated in depression, with many modern antidepressants working by boosting this crucial brain chemical. Evidence suggests that specific estrogens can make serotonin receptors more responsive and increase the number of dopamine receptors in the brain.
Another theory proposes that estrogen provides neuroprotection, safeguarding neurons from damage, and may even stimulate the growth of new neurons in a brain region called the hippocampus. The hippocampus plays a vital role in memory and emotion. Individuals with depression and Alzheimer’s disease are known to exhibit a reduction in hippocampal neurons. Intriguingly, both antidepressants and mood-lifting psychedelic drugs like psilocybin (found in ‘magic mushrooms’) also promote the growth of new neurons in this area.
“Estrogen is neuroprotective, so it will encourage neurogenesis,” Ismail explains. “This is why, as women enter menopause, we often observe a kind of dendritic retraction [branches growing from nerve cells] from the dendrites we had previously.” This, Ismail points out, is often responsible for the ‘brain fog’ and memory issues women frequently experience during menopause.
The Body’s Stress Response
The loss of neurons in the hippocampus can, in turn, affect another critical hormonal system: the Hypothalamic-Pituitary-Adrenal (HPA) axis, which meticulously regulates the body’s response to stress. The hypothalamus, a brain region that controls the release of most hormones, sends signals to the pituitary gland when anxiety strikes. This prompts the pituitary to release adrenocorticotropic hormone (ACTH).
ACTH then stimulates the adrenal glands to release cortisol, commonly known as the stress hormone. Cortisol, in turn, instructs the body to release sugar into the bloodstream, providing the brain and body with the immediate energy needed to respond to an emergency.
“The HPA axis is activated when someone is stressed, and in the short term, this is adaptive as it helps the body cope,” Hantsoo explains. “However, in the long term, it can be detrimental.”
Typically, the influx of cortisol into the body activates a negative feedback loop, which leads the hippocampus to signal the hypothalamus to cease its communication with the pituitary gland, thereby terminating the stress response. However, if an individual experiences chronic stress (e.g., from bullying, abuse, or violence), this crucial feedback mechanism can fail, leading to the brain being perpetually flooded with cortisol. This prolonged exposure is harmful because, over time, cortisol increases inflammation in the brain, destroys neurons in the hippocampus, and impedes its ability to provide negative feedback. Moreover, cortisol can also damage neurons in other vital brain areas, such as the amygdala and prefrontal cortex, which influence memory, concentration, and mood.
“The amygdala is the brain area that allows us to control emotions. A loss of volume in this area is associated with increased emotionality, heightened irritability, and difficulty in regulating negative emotions,” Ismail clarifies. “Atrophy in the prefrontal cortex relates to difficulties concentrating and making sound decisions at the appropriate time. Atrophy in the hippocampus is linked to problems recalling information.”
While cortisol can induce stress, oxytocin, often affectionately known as the “love hormone,” offers a contrasting, calming effect. Oxytocin helps foster feelings of warmth, comfort, and tenderness. Released during childbirth, breastfeeding, and orgasm, it appears to play a crucial role in bonding between both animals and humans.
“Oxytocin is associated with feelings of secure attachment and can help counteract the effects of stress,” Ismail notes. “When we feel safe and supported, this hormone lowers cortisol levels that might have risen due to stress.”
Research also suggests that inhaling oxytocin can make people more generous, cooperative, empathetic, and more likely to trust strangers. However, not everyone is entirely convinced, as it has not been conclusively proven that oxytocin can effectively cross the blood-brain barrier, for example.
A much more widely accepted theory posits that an imbalance of two key hormones produced by the thyroid gland (a butterfly-shaped gland in the throat) can significantly contribute to depression and anxiety. These hormones, triiodothyronine (T3) and thyroxine (T4), both help regulate heart rate and body temperature. However, when their levels are excessively high, as seen in an overactive thyroid, anxiety can readily manifest. Conversely, when levels are too low, depression frequently occurs. Fortunately, correcting these hormonal imbalances can often effectively alleviate patients’ symptoms.
“When patients visit a doctor complaining of mood changes, one of the first things a doctor will do is check their hormonal profile. Often, when we are able to correct the altered hormones, we are also able to adjust the mood,” Ismail explains.
The precise reasons why thyroid hormones impact mood remain somewhat unclear, but one prevailing theory suggests that T3 may increase serotonin and dopamine levels in the brain, or enhance the sensitivity of receptors for these vital neurotransmitters. Thyroid hormone receptors are also highly concentrated in brain areas critically involved in mood regulation.
Novel Treatments and Future Directions
This evolving understanding of hormones and their profound effects on mood is steadily paving the way for innovative new treatments. Early signs of this promise are already apparent, with a drug called Brexanolone, which artfully mimics the hormone allopregnanolone, proving remarkably effective in treating postpartum depression.
Furthermore, some evidence suggests that in cases of low testosterone, supplementing with testosterone alongside certain antidepressants can significantly enhance their efficacy. Studies also indicate that estrogen therapy, including hormone replacement therapy (HRT), can help improve the mood of some women navigating perimenopause and menopause.
Conversely, while hormonal contraception can offer remarkable relief for some women suffering from PMDD, it can paradoxically exacerbate symptoms for others. This highlights a fundamental challenge in the quest for new treatments: our incomplete understanding of why some individuals exhibit such profound sensitivity to hormonal fluctuations, while others remain largely unaffected.
“We know that hormones affect mood and mental health, but we need to understand precisely how they influence it before we can find the truly effective treatments,” Ismail emphasizes.
As we are aware, antidepressants that primarily regulate serotonin levels are not effective in all cases. Some research even indicates that these antidepressants may be particularly less effective in adolescents. Therefore, further dedicated research is urgently needed to identify the influential factors within this age group, as well as the unique aspects of their developing brains, which might render them more resistant to current therapeutic approaches.
Summary
Hormones are vital chemical messengers that regulate various bodily functions and profoundly influence mood and mental well-being. They interact with neurotransmitters and impact fundamental brain processes, affecting vulnerability to conditions like depression and anxiety. These impacts are particularly noticeable during significant hormonal transitions, such as those experienced by women throughout their reproductive lives, including pre-menstruation, pregnancy, and menopause.
Sex hormones, like estrogen and progesterone, directly influence mood by altering neurotransmitter levels and potentially offering neuroprotection in brain areas critical for emotion and memory. Additionally, the body’s stress response, regulated by the HPA axis and cortisol, can severely affect these brain regions if chronically dysregulated. Understanding these complex hormonal interactions, including thyroid hormones and oxytocin, is paving the way for targeted new treatments for mood disorders, though individual sensitivity to hormone fluctuations remains a key area for further research.