Probably every woman’s been on the receiving end of a “are you moody because you’re hormonal?” joke. The stereotypes are certainly exaggerations—but did you know that your hormones do impact your brain? Estrogen helps trigger ovulation, but it has lots of other important functions, too.
What is estrogen?
You probably already know that estrogen is a female reproductive hormone produced mostly by the ovaries (though men make a small amount, too!). Importantly, estrogen triggers female sexual maturation during puberty. But its work in the female body doesn’t stop there. During each menstrual cycle, estrogen causes the endometrium (lining of the uterus) to grow back after it sheds during menstruation (your period). Estrogen is also important for pregnancy and sexual desire, and it impacts the urinary tract, the circulatory system, bones, breasts, skin, hair, mucous membranes, and pelvic muscles. It also affects the brain, which we’ll focus on in this article, drawing on research published in the journal Neuroscience and Behavioral Reviews in 2016 and a research summary from this News Medical article in 2022 [1].
How does estrogen impact brain function?
While male and female brains have a lot in common, there are also some key differences, and these differences are regulated by estrogen. One such estrogen-mediated difference is in pain perception. That’s right. Men and women actually perceive pain differently (could this have anything to do with the much-maligned ‘man cold’?) [2].
Estrogen also plays a role in fine motor control, learning, verbal memory, pain sensitivity, spatial ability, motor coordination, and mood. It can enhance learning and the formation of new memories, plus improve performance in social recognition, object recognition, and object placement tasks.
Different types of estrogen have different impacts on the brain, based on research on rodents [1]. For example, estradiol has positive effects on cognition (including working memory and spatial cognition) and neuroplasticity (the brain’s ability to adapt and change based on what you experience and on your habitual thought patterns). But estrone (the dominant form of estrogen after menopause) has negative effects on cognition due to the way it influences the hippocampus.
Estrogen’s effects depend in part on whether you’ve been pregnant before
Also, according to rodent research, the effects of estrogen in the brain are partly dependent on whether or not a female has been pregnant and given birth. For example, estrogen caused increased brain cell growth and division in the hippocampus (the brain region most responsible for memory) in middle-aged rats who had had at least four pregnancies [1]. But estrogen didn’t have the same effect in middle-aged rats who had never had babies.
How does estrogen impact brain health?
I’ve written previously about the interaction between illness and the menstrual cycle, whether that illness is temporary or chronic and physical or mental. Some women with chronic mental and physical illnesses experience worse symptoms depending on the phase of their cycle, for example. Estrogen (or, rather, the natural decrease in estrogen during certain phases) is a major reason why.
Lack of estrogen contributes to mental health struggles
For example, women with schizophrenia have more severe symptoms and more hospital admissions during their luteal phase, when their estrogen levels are lower, than during other phases of the menstrual cycle. Research is mixed on whether treating women with schizophrenia with estradiol combined with antipsychotics can help mitigate the symptoms experienced during the luteal phase.
In addition, major depressive disorder is twice as common in women as it is in men—but there is no such difference in prepubescent boys and girls. Researchers hypothesize that this difference is due to the impact of ovarian hormones, including estrogen, on the neurochemistry of major depressive disorder.
Estrogen raises other hormone levels
Estrogen can “increase cerebral blood flow, provide anti-inflammatory effects, promote neuronal synapse activity, and exert both neuroprotective and neurotrophic effects on tissue in the brain,” according to News Medical. It also increases the levels of serotonin, dopamine, and norepinephrine—and the number of receptors for them—at synapses (i.e., “the places where neurons connect and communicate with each other”). This helps protect against oxidative stress, ischemic (reduced blood flow) damage, and the damage caused by amyloid protein (involved in the progression of Alzheimer’s disease). In fact, Alzheimer’s is more common in women than in men, and is linked with a deficiency in estrogen. What’s more, estrogen may only be neuroprotective in healthy people, not people with an illness like Alzheimer’s (an idea called “healthy cell bias”).
Estrogen can protect against some medical conditions
Research suggests that estradiol might be neuroprotective in stroke, Parkinson’s disease, and multiple sclerosis (MS) because of its “anti-apoptotic and anti-inflammatory actions,” according to research published in the journal Neuroscience and Behavioral Reviews [1]. (Apoptosis is a type of cell death.) For example, women with their ovaries still intact tend to have better stroke outcomes than men, and better outcomes than women who have had their ovaries removed. Likewise, women with higher levels of estradiol tend to have better stroke outcomes than women with lower estradiol levels. Stroke damage is also worse in older women, either because they’ve gone longer with lower levels of estrogen, or because they also have lower levels of other hormones.
A caveat about research on estrogen and the brain
Much of this research has been done on rats and has not been reproduced in humans because of the difficulties in conducting such research on humans. However, if the results were reproduced, researchers in Neuroscience and Behavioral Reviews wrote, “they potentially could have far-reaching implications for a number of mental health conditions” [1].
Birth control complicates research on estrogen and brain health
One of the difficulties with conducting this research is the number of women taking hormonal contraception. The Pill suppresses the menstrual cycle and the hormonal changes that go with it, and the synthetic hormones in birth control pills have their own effects on a woman. Therefore, any findings in research done with women taking hormonal contraception could not be generalized to women cycling normally.
Menstrual cycles also complicate research on estrogen and brain health
It is also challenging to conduct research that takes the natural fluctuation of hormone levels over the course of each menstrual cycle into account. This is a major reason why most medical research historically has been done on men. However, targeted timing of behavioral testing can help researchers pinpoint the impact of high versus low levels of estrogen on the brain. The same is true of testing before and after menopause.
The researchers behind the Neuroscience and Behavioral Reviews article concluded that the National Institutes of Health’s recent policy to require all research grant applicants to study the impact of sex as a variable “is welcome.” They noted that sex shouldn’t just be used to control for differences between men and women but “as an independent factor”—to answer questions such as how antidepressants may affect men and women differently.
They also recommended that research include “a thoughtful evaluation of factors such as reproductive and hormonal status,” like which cycle phase the female participants were in at the time of testing [1]. “For example, studies on oxytocin have seen an upsurge in publications recently, and many have featured only men or males. However, sex differences and estrogenic regulation of oxytocin are established,” and without including women in the research, we can’t apply any conclusions to them [1]. What’s more, even if a study were to find no significant differences between men and women, that finding would not necessarily mean that there was no significant variability within an individual woman’s cycle. The time of day of a test also matters, since hormone levels vary throughout the day (which is also true of men!).
What about synthetic estrogen, like in hormonal birth control?
The majority of women who take hormonal contraception take a combination of synthetic progesterone (progestin) with synthetic estrogen. This combination comes in pills, injections, vaginal rings, sprays, and implants. The combination is more effective at preventing pregnancy, but it can also cause more side effects. As we’ve noted before, synthetic hormones are not a replacement for the real thing. They do not provide the same benefits as natural hormones. They also come with side effects, such as an increased risk of heart disease, blood clots, and breast cancer.
One example of a commonly prescribed synthetic estrogen that isn’t birth control is Premarin. Premarin is often prescribed to women after menopause and is made from estrogen derived from pregnant horses. It is much stronger than human estrogen. Unfortunately, according to the researchers published in the journal Neuroscience and Behavioral Reviews, Premarin is associated with an increased risk of dementia and reduced cognitive functioning when combined with synthetic progestin (although the researchers noted there were some problems with the study that found this association). They also wrote that low doses of Premarin might impair reference and working memory as well as spatial reference acquisition, though medium and high doses may improve spatial working memory.
The bottom line
Since estrogen is so important for brain functioning, how can you be sure you have enough–and that it’s well-balanced by your body’s production of progesterone? Using a fertility awareness method (FAM) to chart your cycle is an indirect but effective way to keep tabs on your hormonal health. A healthcare provider trained in restorative reproductive medicine (RRM) can look at a FAM chart and observe patterns consistent with normal or abnormal hormone levels. Targeted hormone testing can provide clues as to appropriate treatment options. Particularly if you have any of the conditions or illnesses mentioned above, contact an FAM instructor and start charting. You may find that not only can you plan your family and manage your hormonal health, but you can improve your mental health as well!
References:
[1] Galea LAM, Frick KM, Hampson E, Sohrabji F, Choleris E. Why estrogens matter for behavior and brain health. Neurosci Biobehav Rev. 2017 May;76(Pt B):363-379. doi: 10.1016/j.neubiorev.2016.03.024. Epub 2016 Mar 31. PMID: 27039345; PMCID: PMC5045786. [2] Bartley EJ, Fillingim RB. Sex differences in pain: a brief review of clinical and experimental findings. Br J Anaesth. 2013 Jul;111(1):52-8. doi: 10.1093/bja/aet127. PMID: 23794645; PMCID: PMC3690315.Additional Reading:
Getting to know synthetic estrogens and progestins: What do they do to our bodies?
Reasons women need periods: The role of the menstrual cycle in brain health and development
Reasons women need periods: The role of the menstrual cycle in bone health and development
