What causes PMS & PMDD?

Premenstrual syndrome (PMS) is a common condition that occurs in the second half of the menstrual cycle (aka, the luteal phase, which occurs after ovulation and before our period). Although numbers vary, it’s thought that around 75% of people who menstruate experience it. It involves a combination of physical, psychological, and behavioural changes (symptoms). 

Premenstrual dysphoric disorder (PMDD) is a severe form of PMS, and is classified as a type of depressive disorder. It’s thought that around 3-8% of people who menstruate experience PMDD. PMDD can impact our work, social life and relationships. In some cases, it can even lead to suicidal thoughts*.

A diagnosis of either PMS or PMDD is made by a healthcare professional. They’ll ask you to make a symptom diary over two-three cycles and ask questions about your medical history. They may also carry out a physical examination and run some blood tests, to rule out any other underlying health conditions that may be causing the symptoms. For a diagnosis of PMS, symptoms must occur during the luteal phase (and subside shortly after), be severe enough to affect everyday life, and not be due to other causes. To receive a diagnosis of PMDD, you must experience five or more symptoms, including one psychological/mood-related symptom, in the luteal phase, which are severe enough to disrupt your day-to-day functioning.

It’s not known exactly what causes PMS and PMDD, but it’s likely that there are a number of factors that contribute to our experience: 

• Our individual sensitivity to hormones and their metabolites (the substances produced when hormones are broken down) 
• Hormonal fluctuations (oestrogen and progesterone) during the luteal phase (the 2 weeks before your period)

• Neurotransmitters 
• Genetic factors 
• Inflammation and the immune system
• and more

Many media outlets point the finger at hormones. But, as with most things, it's not quite that simple. 

Most of us will experience a similar cyclic change in hormones every ~28 days (the 'standard' menstrual cycle). So, if these conditions were solely down to changing hormone levels, we'd all experience PMS and PMDD, which isn't the case. 

Similarly, studies have found that people who experience PMS or PMDD have the same concentration of hormones in their blood as people who don't get PMS or PMDD. So it can't be down to higher levels of hormones in people with PMS or PMDD, either.

In fact, the most influential factor is thought to be individuality. This tracks right back to the fact that each of us is different, very different. 

Scientists believe that people with PMS/PMDD are more sensitive to hormones and their metabolites than people without PMS/PMDD. This idea goes on to explain that, it may be that, the more sensitive someone is to hormone and metabolite levels, the more severe their PMS or PMDD symptoms. Without this increased sensitivity, fluctuating hormones experienced during the luteal phase are unlikely to affect us.

Some studies show that people who experience PMDD when they’re younger are more likely to experience depression-related symptoms at other times of significant hormonal change, such as after having a baby or during perimenopause. This correlation (between times of hormonal change and mood-related change) supports the theory that it’s our personal susceptibility to hormones that determine our symptoms, rather than the hormones themselves.

Progesterone

Because progesterone is only produced in the luteal phase of the menstrual cycle, and PMS/PMDD are only experienced during the luteal phase, many people believe progesterone plays a central role in causing PMS/PMDD. In the second half of the luteal phase, both progesterone and oestrogen levels fall. It’s this rapid drop and low level of hormones that is thought to trigger PMS/PMDD symptoms in those who are sensitive to such.

Evidence to support the role of progesterone in PMS/PMDD:

• When an egg is released during ovulation, it’s surrounded by a structure called a follicle. During the luteal phase, this develops into a structure called a corpus luteum — hence the name ‘luteal phase’. It’s the corpus luteum that produces progesterone. Some studies show that when a female experiences an anovulatory cycle (whereby there is no ovulation, therefore no progesterone produced), they don’t experience PMS symptoms.

• Some combined oral contraceptive pills (COCs) suppress ovulation and therefore prevent progesterone levels from rising. These can also prevent/reduce PMS/PMDD symptoms.

• Specific COCs contain a type of progesterone called drospirenone. Drospirenone is different to the ‘natural’ progesterone found in our bodies. These pills have been shown to help relieve some people’s PMS and PMDD symptoms and can be considered as first-line treatment for those looking to use contraceptives for PMS/PMDD relief. 

Note: not everyone finds COCs relieve PMS/PMDD symptoms. In fact, for some people, it can make them worse. This is because a handful of COCs contain a synthetic type of progesterone, which some females don’t tolerate as well as the natural form of progesterone found in our bodies.

It’s important to note that it’s not entirely clear whether the following evidence pins PMS and PMDD symptoms on progesterone per se, or its metabolite, allopregnanolone.

Oestrogen

Typically, oestrogen makes us feel good. It’s high during the follicular phase, and often helps contribute toward feelings of happiness and positivity. So, it’s not necessarily that oestrogen is involved in causing PMS or PMDD, rather, oestrogen is low during the second half of the luteal phase. When oestrogen is low, we’re less likely to feel good (aka, there’s very little positive to help balance the negative). 

Allopregnanolone

When progesterone is broken down, one of the substances produced is allopregnanolone, which can bind to and activate GABA receptors in the brain. GABA receptors (which can be activated by GABA and allopregnanolone) help control emotions such as anxiety, stress, and fear, and impact our digestion, immunity, mood, sexuality, and energy storage/expenditure. 

In high concentrations, allopregnanolone has an anti-anxiety and calming effect. But in lower concentrations, allopregnanolone causes negative mood and triggers feelings of depression. During the first half of the luteal phase, progesterone and allopregnanolone are high, and once we enter the second half of the luteal phase, levels of both decrease. Therefore, it’s thought that during the week or so before our period, progesterone and allopregnanolone levels are very low, triggering symptoms of PMS and PMDD.

Evidence to support this:

Although most studies looking into this theory are based on PMDD, it might be that people with PMS experience the same differences, but to a less severe degree than those with PMDD.

Research shows that people with PMS or PMDD:

• React differently to GABA, suggesting their receptors have a different sensitivity to GABA/allopregnanolone
• Have lower levels of GABA in their blood compared to people who don’t have PMS/PMDD
• Experience a decrease in GABA between follicular and luteal phases, whereas people without PMDD experience an increase
• Experience a change in the set-up of GABA receptors during the luteal phase

There’s some research to suggest that these differences in GABA receptor activity could be the result of continued exposure to stress, which is thought to blunt the allopregnanolone-GABA response. In fact, people with high levels of continual stress could be up to 25 times more likely to experience severe PMS/PMDD symptoms than those without continuous exposure to stress. 

Considering PMS and PMDD can make us stressed, and stress can make us more likely to experience PMS/PMDD, we can end up in a very negative feedback loop of stress and PMS/PMDD making the other worse. Check out our lifestyle changes to help reduce stress levels here.

Serotonin

The neurotransmitter serotonin (also known as the happy hormone) has also been implicated in PMS/PMDD. Serotonin has several different functions in the body, including regulating mood, sleep and anxiety. 

Evidence to support this:

• Both progesterone and oestrogen influence serotonin levels.

• A study published in February 2023 suggests that people with PMDD may have up to 18% more serotonin transporters in the brain between the mid-luteal phase and menstruation. This means there are more serotonin transporters present, taking serotonin away faster than in those people without PMDD, reducing our perceived level of happiness. 

• Some people with PMDD benefit from taking SSRIs (selective serotonin reuptake inhibitors) at specific times during their cycles, which work by preventing these transporters from working. Further support for this evidence is the speed at which people taking SSRIs for PMS/PMDD can feel better. Unlike depression and anxiety, whereby it can take weeks to see an improvement in symptoms, some people with PMS/PMDD respond to SSRI treatment almost immediately.

Glutamate

Some studies also suggest that the neurotransmitter glutamate has a role to play in PMS/PMDD. Glutamate has several functions, including regulating mood. Most people will experience fluctuating levels of glutamate during the menstrual cycle, but some research suggests that people with PMS or PMDD symptoms may have an increased sensitivity to these changing glutamate levels. This, therefore, exacerbates mood-related PMS/PMDD symptoms. However, this has not yet been demonstrated conclusively in research. 

Evidence shows there's a link between the prevalence of PMS/PMDD between parents and children, and between twins. Aka, if a person experiences PMS/PMDD, their daughter is likely to experience it too. The same goes for twins. This suggests there may be certain genes that make us more susceptible to developing PMS/PMDD.

Evidence to support this idea:

• A link between specific genes and PMS/PMDD was first identified in 2007 when researchers established an association between PMS/PMDD and variants of one of the oestrogen receptors (ESR1).

• Since then, studies have found multiple differences in gene expression between people with PMDD and those without. 

• Researchers have also found that the altered stress response seen in people with PMS/PMDD (the altered GABA receptors we talked about earlier) may be caused by genetic alterations or changes in the number of copies of these genes in people with PMS/PMDD. Interestingly, whilst diet and other lifestyle factors cannot change our genetic makeup, they can influence whether or not certain genes are expressed (aka, whether or not they’re ‘switched on’). This provides a lot of support for the idea that taking a holistic approach to our health can significantly ease PMS and PMDD symptoms, by helping our bodies regulate gene expression.

PMS/PMDD symptoms may be related to the immune system. Some studies explore the relationship between PMS/PMDD and the body’s inflammatory response. Inflammation is important for our bodies to function; it enables us to respond to stressful conditions and is essential for health. However, long-term inflammation can be detrimental to physical and mental health.

Evidence to support this idea:

• The level of inflammation naturally changes during the menstrual cycle. Emerging evidence indicates that people with PMS/PMDD have higher levels of inflammatory markers in their blood than those without. 

• Studies also found that some of the most common PMS/PMDD symptoms such as low mood, cramps, appetite changes and bloating are associated with higher chronic inflammatory markers.

It’s not entirely clear whether PMS and PMDD contribute to inflammation, or inflammation contributes to PMS and PMDD, but it’s an interesting correlation nonetheless.