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Why don't we know more about PMS?

12 min read

What is PMS? How common is it? And what actually causes it? When it comes to premenstrual syndrome (aka PMS), even questions this simple aren’t easy to answer. Google PMS and you’ll see that the Mayo Clinic and the Office on Women's Health define PMS as a combination of premenstrual symptoms that affect 75% to over 90% of people with menstrual cycles, while the American College of Obstetricians and Gynecologists narrows down its definition to only include symptoms that significantly affect your daily life (which applies to a much smaller subset of people).

Unfortunately, these differences in definition reflect the general state of research on the topic of PMS: It’s a mess and we’re only starting to untangle things. But we are seeing PMS become less stigmatized and studied more objectively. Acceptance by the global community in recent years of premenstrual dysphoric disorder (PMDD) and its debilitating symptoms as a true gynecological disorder has opened the door to more funding and scientific legitimacy for PMS research.

As acceptance and the body of research around PMS continue to grow, we're here to explain what we know. We’ll cover some shocking PMS history, the biological theories of why we experience it, and the societal and practical reasons why we know so little about it.

Key takeaways

  • What is PMS? We lack a clearly defined definition for the condition, but PMS is typically marked by emotional, physical, and behavioral symptoms that appear after ovulation and stop or taper after menstruation starts.
  • We still don't really know what causes PMS. There are many different theories for why some of us have worse premenstrual symptoms than others, including differences in hormone sensitivity, rapid hormonal shifts, and neurochemical differences.
  • We're also still unpacking PMS risk factors. Different potential risk factors have been linked to PMS so far, including: smoking, drinking, genetics and a history of depression.
  • Why don't we know more about PMS? There are many reasons we don’t have enough quality research on premenstrual syndrome, including a complicated backstory in how society viewed the condition, historical gender bias in medical research, practical limitations to menstrual cycle research, a lack of funding from scientific bodies (like the National Institutes of Health), and the difficulties of studying a topic that's complex and poorly defined.

First things first: What is premenstrual syndrome (PMS)?

Premenstrual syndrome (PMS) is currently defined by more than 200 different emotional, physical, and behavioral symptoms that appear sometime after ovulation and stop shortly after menstruation starts.

"For some women, headaches are the worst component and for others, diarrhea and water retention — for still others, mood irritability or insomnia," OB-GYN and Modern Fertility medical advisor Dr. Jane van Dis, MD, FACOG tells us. "It's important to remember that there is no one 'way' that women experience PMS."

While the full 200-symptom list would be a lot to put into one article, emotional symptoms of PMS may include:

  • Mood swings
  • Anxiety
  • Depression
  • Irritability
  • Crying spells
  • Difficulty concentrating
  • Confusion
  • Libido changes
  • Sleep pattern disruption

Physical symptoms of PMS may include:

  • Bloating
  • Weight gain
  • Breast/chest tenderness
  • Food cravings
  • Swelling of the hands or feet
  • Headaches
  • Body aches and pain
  • Skin problems
  • Gastrointestinal upset

Where to draw the line between premenstrual symptoms and premenstrual syndrome is currently up for debate, as is an estimate for how common it is. The percentage of people with cycles who are significantly distressed by their PMS symptoms is estimated to be around 15%, with an additional 2% to 6% experiencing severe enough symptoms to qualify for a PMDD diagnosis.

What don't we know about PMS?

As we mentioned earlier, even the "what" around PMS is complicated: Medical authorities are still debating what exactly constitutes premenstrual syndrome — whether it’s defined by any monthly premenstrual symptom, or only those that interfere with your life. It's possible this question could become even more complex if more branches of PMS, like PMDD, are identified.

But the "why" of PMS is even fuzzier than the "what." This is what PMS researchers are still trying to understand.

What causes PMS? We don't know (but we have some theories)

When reading through the academic literature on PMS, all researchers agree on one thing: We know frustratingly little about what causes this condition. (We’ll dig into the reasons for this later.)

For the most part, we know that PMS is linked to the cyclical fluctuation in circulating hormones — and specifically to the luteal (post-ovulation) rise and then drop in estrogen and progesterone levels. This has been supported by the observations that PMS symptoms can reemerge in postmenopausal people when they take cyclical progestogen, and medications that suppress estrogen can relieve PMS symptoms. But as to why PMS manifests as a little weight gain for some and debilitating symptoms for others? At the moment, all we have are theories — a few of which are more fleshed out than others.

For the most part, none of the following theories rule the other ones out. In fact, considering the wide variety of ways that each of us can experience PMS, it might turn out that all of them are true to some extent.

Theory #1: Hormonal differences

Scientists originally hypothesized that people who experience stronger PMS symptoms might have higher levels of estrogen or lower levels of progesterone in the final days before menstruation. Although evidence to support this has been mixed, and most researchers have concluded that this is not the case, some researchers are still looking at hormones for an answer.

One intriguing possibility is that, even though all people with cycles might have similar levels of progesterone and estrogen during distinct phases, those who experience PMS might have a much more rapid transition in hormone levels or a larger percentage fall in hormone levels. A small study of 46 Brazilian women measured their progesterone levels three times a day and found that those without PMS had a gradual decline of progesterone over the last eight days prior to menstruation, while those with PMS had a sharp drop-off during the last three days. However, given the small study size, there is very little evidence to support this theory.

Theory #2: Hormone sensitivity

One of the most common theories in PMS research is the idea of hormone sensitivity, which suggests that some people are predisposed to have a stronger reaction to expected hormonal shifts throughout the menstrual cycle:

  • A recent review of neuroimaging findings noted that the brains of PMDD patients have increased brain metabolism (the brain breaks down substances like glucose for energy) and altered neurotransmitter activity (chemical messaging for nerve cells). Also, different regions of PMDD patients’ brains have more or less activity than expected during the luteal phase, which suggests a mixture of increased and decreased responses to fluctuating hormonal signals.
  • In one small study, researchers suppressed the ovaries of females with and without PMS, and then gave them all a standard dose of estrogen and progesterone — only those who normally experienced PMS had premenstrual symptoms when given the hormones.

Theory #3: The GABA and ALLO connection

Researchers recently started noticing that some PMS symptoms share a lot in common with insufficient activity of gamma-aminobutyric acid (GABA), a neurotransmitter that can chill out the nervous system. Here's how this connection could play out in relation to PMS:

This ALLO-progesterone link may also be another reason why SSRIs are effective treatments for PMS symptoms: SSRIs increase the conversion of progesterone to ALLO, which could help improve GABA signaling.

There's one more interesting way this ties into reproductive health: "GABA signaling has also recently been shown to be impacted in women who suffer from postpartum depression," says Dr. van Dis.

Theory #4: Serotonin dysregulation

Because selective serotonin reuptake inhibitors (SSRIs) are a first-line treatment for PMS, many researchers have focused in on the potential role of serotonin in premenstrual symptoms:

  • Neuroimaging studies have found altered serotonin activity (along with altered GABA activity) in the brains of PMDD patients.
  • Additionally, some small studies indicate that low serotonin levels might be associated with a premenstrual poor mood in healthy people.

Most likely, neither serotonin nor GABA are complete explanations for premenstrual symptoms — but they might be part of the bigger picture.

Theory #5: Brain-derived neurotrophic factor (BDNF) levels

This protein has been gaining attention in recent years because of its importance in protecting our neurons and helping them grow and form new connections. It turns out that BDNF could also be linked to premenstrual symptoms:

  • A small study found that BDNF levels in PMS patients dropped significantly during the luteal phase, whereas they actually increased in PMS-free patients.
  • Additionally, since PMS has a strong genetic component, there may be a link between premenstrual symptoms and Val66Met, which is a BDNF genetic polymorphism that is also linked to multiple mood disorders.

This relationship is also relevant for expectant parents, since low levels of BDNF might be linked to depression during pregnancy and postpartum.

Overall, it’s a good sign that there are so many different theories and insights into why some of us suffer from severe symptoms. Since PMS is experienced in countless different ways, it’s likely that many aspects of our biology contribute to how our bodies ultimately express PMS. As we learn more about the different biological reasons for our different premenstrual symptoms, this could lead to more personalized treatments — and better outcomes — for PMS.

What are the risk factors for PMS? The research here is mixed

Numerous studies have tried to piece together what exactly predisposes one to have worse premenstrual symptoms than another. It’s not uncommon to see one study identify a specific lifestyle choice as a risk factor, while another study fails to see a connection, so more research on this topic is necessary. A few of the following factors seem to have the best evidence connecting them to PMS:

  • Alcohol consumption: In a meta-analysis of 19 studies, it was determined that alcohol intake is associated with a moderate increased risk of PMS. Additionally, those who drank more than one drink per day had an even increased risk of PMS.
  • Smoking: Another meta-analysis of 13 studies also found that smoking cigarettes has a moderate association with PMS and an even higher association with PMDD. The authors suggest that nicotine might help alleviate PMS symptoms, or alternatively it might make them worse.
  • Stress: In a small study of female medical students, higher stress levels were associated with worse PMS symptoms.
  • Depression: A history of depression and several other mood disorders have been associated with a higher risk of PMS and PMDD, but much emphasis needs to be placed on the point that these are entirely different disorders that can co-occur together. (Yet another related-but-different issue is premenstrual exacerbation, where mood disorders, as well as asthma, flare up at the onset of a period.)
  • Genetics: Although we don’t know the specific genetic loci associated with PMS, a twin-based study found that PMS has a strong genetic factor. In other words, PMS might be traceable to your family history.

So… why don’t we know more about PMS?

Another writer recently pointed out that there are five times as many research articles on erectile dysfunction (ED) than there are on PMS. There are a number of different problems that may contribute to why PMS remains so under-researched in comparison to other topics.

The health of people with ovaries hasn't been a priority

First, it's important to understand that we don't know enough about women's health in general. The source of this bias has many roots. Historically, women’s bodies, their sexuality, and anything related to menstruation has been treated with everything from fear to condemnation — which still trickles down to society’s views on these topics today. Also, the healthcare system has a habit of taking complaints about pain and other medical problems less seriously when the patients are people with ovaries (especially those who are people of color). And in medical research, people who were assigned "female" at birth were systematically left out of drug and clinical trials until 1993.

In regards to PMS specifically, the complex relationship between menstrual cycles and women's health wasn't historically a priority (or even on the radar) for the medical community. Hippocrates, the Greek “father of medicine,” tried to explain the physical and emotional symptoms of PMS as the result of agitated blood looking for a way to escape the uterus… and the Western medical community didn’t do much to update this theory until the 1900s.

Originally called “premenstrual tension,” the condition was renamed "premenstrual syndrome" in the 1950s to capture the wider variety of symptoms that we recognize today as PMS. But just because PMS was generally ignored by the medical literature doesn't mean it was uncommon — at the time of its naming, doctors estimated that around 40% of healthy reproductive-aged people with cycles experienced the syndrome. Despite its prevalence then and today, the complicated history of PMS has undoubtedly been a disadvantage in the research realm.

People used to view PMS as a "societal" problem

In the mid-1900s, much of the medical community’s attention to PMS was due to the fact that it was observed as a societal problem. At that time, some troubling (and possibly flawed) studies were published, linking PMS to everything from airplane crashes to violent crimes. Even the doctor who coined the term PMS, while he was musing on women’s lunar cycles in a 1954 paper, wrote: “How many of us, using the word 'lunatic,' have suspected that we were referring to the premenstrual syndrome?”

Over the following decades, PMS continued to be used as a source of mistrust toward people with cycles as rational members of society. PMS was even successfully used as a defense in the 1980s to help two women avoid prison time for murders in the UK. These and similar cases threw PMS into the spotlight — and sparked outdated arguments about how the menstrual cycle limits biological females and their ability to control themselves. But understanding and treating PMS wasn't top of mind.

Our PMS research models have flaws

Another less frequently discussed limitation of research into menstrual health is the uniqueness of the human menstrual cycle. Only a handful of primates and other animals experience menstruation — and simple animal models are usually required to speed up basic scientific research on human health topics.

Although standard lab rats don’t menstruate (they instead have what are called estrous cycles), researchers have tried to simulate PMS by giving female rats daily progesterone treatments, followed by a withdrawal period (similar to the last week of our cycles where our bodies produce less progesterone). When rats go through progesterone withdrawal, they show signs of depression, which might be useful to learn about the role of serotonin and other brain chemicals in PMS symptoms. However, since this model of PMS relies solely on a rapid drop-off of progesterone levels, it’s hard to say whether or not the results can be applied to humans.

Unexpectedly, the African spiny mouse was just discovered a few years ago to be the first example of a menstruating rodent. An observational study found that the spiny mouse eats extra food and behaves differently a few days before menstruating — which might be a natural model of PMS. We’ll see in the next few years if the spiny mouse will end up becoming the new standard for basic PMS research.

We don't have a universal definition for PMS

Although PMDD has now become a well-defined gynecological disorder with standardized diagnostic criteria, the umbrella definition of PMS is still highly variable between countries and individual medical professionals. We know of more than 200 different potential premenstrual symptoms, many of which can range from barely noticeable to debilitating. How can we choose a single cutoff point to determine whether or not someone has PMS?

Unfortunately, without a standardized diagnosis of PMS, it's incredibly difficult to make sense of conflicting results generated in different labs across the world. Most studies include a “PMS” group and a “healthy” group, but if you’ve ever sat around discussing PMS with a group of pals, you probably had a difficult time lumping everyone's experiences into just two groups. In the future, it may become necessary to group different premenstrual symptoms together and create new subcategories of PMS in order to truly research their biological origins.

The bottom line

Historically, PMS has been treated by the medical world — and society — as evidence of the emotional instability and untrustworthiness of people with cycles. How many times have you heard “that time of the month” used as a joke or an insult to discredit someone's opinion? This makes it little surprise that, although many people suffer from premenstrual symptoms, most of us don’t openly talk about them.

PMS research is lagging, and it’s time we push for change. Whether you consider your premenstrual symptoms a “syndrome” or whether you just accept them as part of your body’s biological rhythm, they still deserve to be better understood.

If you want to help in the push for better PMS research, simply speaking up about your own experience of it can help destigmatize the topic and draw awareness to its importance. Because it’s not a common topic in most people’s social circles, some of your friends might have outdated perceptions about what PMS even is.

If you want to go the extra step and contribute to emerging research on reproductive health in general, consider participating in our research.

This article was medically reviewed by Dr. Jane van Dis, MD, FACOG. Dr. van Dis is a practicing OB-GYN, volunteer clinical faculty at USC Keck School of Medicine where she serves on the Gender Equity in Medicine and Science Committee, CEO of Equity Quotient, co-founder of OB Best Practice, and co-founder of TIME'S UP Healthcare.

Did you like this article?

Dr. Adrien Burch, PhD

Dr. Adrien Burch, PhD holds a BS in molecular, cellular, and developmental biology from Yale, and a PhD in microbiology from UC Berkeley. She sifts through academic research so you don’t have to.

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