Stories about medical problems often start with an explosive quote from someone experiencing the condition. After dipping into an online forum of people diagnosed with premenstrual dysphoric disorder (PMDD), however, I found that a single comment didn鈥檛 seem to suffice.
鈥淥ne week before my period, like clockwork, I want a divorce, I don鈥檛 want to be a mom, I hate my job and I rage,鈥� said one member. 鈥淲ho can relate with the awful feeling of waking up the next day after an episode and being so embarrassed with what they said or did?鈥� said another. 鈥淚 wound up convincing myself that I was not a real member of my family, and I was done with life. I drove to a gun dealer very sure and relieved that I was ready to die鈥� This isn鈥檛 me,鈥� said a third. 鈥淧MDD is ruining my life,鈥� was a common refrain.
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PMDD is sometimes referred to as 鈥渂ad PMS鈥�, but these statements reveal how inaccurate that label is. PMDD is a chronic hormonal condition that causes interpersonal conflict, depression, lethargy, anxiety, thoughts of self-harm and suicide. Yet, so marginalised has it been that it was only officially recognised by the World Health Organization in 2019. Recently, though, there has been a surge in interest, helped by media personalities like Dixie D鈥橝melio and Vicky Pattison talking publicly about their struggles with PMDD. Meanwhile, a flurry of research is also bringing the condition out from the shadows. What鈥檚 more, new ideas about PMDD aren鈥檛 just promising better treatments, they are also part of an emerging picture that is revealing sex hormones to have a far greater impact than anyone imagined.
At least since the time of Plato and Hippocrates, women鈥檚 emotions have been attributed to their menstrual cycle. 鈥淗ysteria鈥� comes from the Greek word for uterus, and the ancient Greeks believed the uterus travelled around the body causing all sorts of ailments 鈥� sex and pregnancy were the suggested cures. Fast-forward to the Victorian era, and a 鈥渨andering womb鈥� was one reason given for marital disobedience. Thankfully, we now live in more enlightened times. Yet menstruation, even in the most progressive countries, is still something of a taboo.
That鈥檚 a problem, given that up to 90 per cent of women who have periods symptom of premenstrual syndrome (PMS). For the estimated 31 million people 鈥� roughly 1.6 per cent of women and girls globally 鈥� with diagnosed PMDD, this taboo is catastrophic. Research from last November of 3600 women with the condition revealed that just under half had during a PMDD crisis, 82 per cent had experienced suicidal thoughts and 26 per cent had attempted to end their own life.
Not just bad PMS
Although the recent celebrity-driven media spotlight is changing things, it can lead to confusion. 鈥淚 see a lot of social media influencers talk about moon cycles and their effect on PMDD, which does not have valid scientific evidence. Another media hype is the use of antihistamine as a treatment for PMDD, which we also do not have evidence for,鈥� says at the University of Regina in Canada, who also does work for the non-profit International Association for Premenstrual Disorders. 鈥淚t鈥檚 fantastic how much conversation is going on about PMDD in Instagram and TikTok,鈥� says , who studies the condition at Cardiff University in the UK. 鈥淏ut personally, I鈥檓 concerned about misinformation 鈥� with people thinking they have PMDD when they don鈥檛 and getting misdirected with treatments they don鈥檛 need. I think social media can also undersell how severe PMDD can be.鈥�
On the positive side, increasing awareness is getting people more interested in participating in research, says Apsey. But one of the initial problems with understanding PMDD is figuring out exactly who has the condition. It is defined by symptoms including headache, cramping, and extreme anxiety and depression in the week or so leading up to a period. It can start at any point from the very first period and is sometimes triggered by a big reproductive milestone, such as stopping breastfeeding. It usually ends at menopause, but perimenopause can worsen symptoms.
The best way to diagnose PMDD is to keep a daily diary for at least two cycles, says Apsey. 鈥淥ften people think they have PMDD, but once they keep a diary over a few months, they realise their symptoms are more persistent or at different times of each month, which may point towards something like bipolar disorder or depression.鈥� Some pre-existing conditions other than PMS can also get worse just before a period, which is called premenstrual exacerbation. Without keeping a diary, it is hard to identify who actually has the condition, says Apsey, and many previous studies haven鈥檛 ensured that all participants really do. 鈥淚t鈥檚 made the data we have so far very blurry.鈥�
Nevertheless, when it comes to understanding what causes PMDD, things are getting a little clearer. Two hormones are certainly involved 鈥� progesterone and oestrogen, which naturally fluctuate throughout the menstrual cycle. Oestrogen affects various brain functions, including learning, memory and mood. Progesterone also plays a significant role in mood and is linked with stress because it can be converted into the stress hormone cortisol. Both oestrogen and progesterone are known to such as depression.
Pioneering work in the late 1990s showed that if you completely suppress these hormones 鈥� inducing an artificial menopause 鈥� this can also . The finding seemed to indicate that people with the condition have an overabundance or erratic fluctuation of progesterone and oestrogen. However, later work showed that hormone levels in people with PMDD . 鈥淭hat points towards it not being a hormonal imbalance, but having an abnormal response to normal hormone changes,鈥� says , who studies PMDD at the University of Oxford. Apsey and her supervisor at Cardiff University, , are now searching for genetic clues that might help them discover why some people are more susceptible to natural hormone fluctuations, and whether it runs in families, as it seems to anecdotally.
Hormones are not the noise in the data, they are the data. Yet research often ignores them
Meanwhile, other researchers have turned their attention to allopregnanolone (ALLO), a breakdown product of progesterone. ALLO has a key role in helping people deal with stress and anxiety because it modulates receptors of a neurotransmitter called GABA in the brain. When these receptors are active, they help control our mood and turn off our fight-or-flight systems after a period of stress. It may be that in PMDD the brain has become desensitised to ALLO, says Reilly, resulting in it failing to lower stress and anxiety. 鈥淭here鈥檚 an idea that the way these people鈥檚 GABA receptors react to hormones might be the cause of their symptoms, but it hasn鈥檛 been shown conclusively yet.鈥�
Link with serotonin
There also seems to be a link between serotonin and PMDD. Serotonin is a key neurotransmitter that carries messages between brain cells and is involved in regulating mood. At normal levels, it helps us feel happy, emotionally stable and focused, while low levels are generally associated with symptoms of depression and anxiety, . Brain imaging studies of people with and without PMDD show that those with the condition experience an in their brain just before their period. These transporters suck up serotonin into nerve cells, meaning there is less washing around the brain. That might help explain some of the negative emotions associated with PMDD.
Given an increased understanding of what causes PMDD, along with a new appreciation of its seriousness, you might think that finding treatments would be a top research priority; sadly, that hasn鈥檛 been the case. 鈥淓ven with growing interest, the condition is very much under-researched and overlooked,鈥� says Reilly. This is reflected in the paucity of treatments on offer, which primarily entail cognitive behavioural therapy 鈥� to help people regain some control over their thoughts and mood 鈥� hormonal contraceptive pills, which maintain more stable levels of oestrogen and progesterone throughout the month, and antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs), which prevent nerve endings from sweeping up serotonin too quickly and may also .
Not only are there few treatment options, those that are available also don鈥檛 work for everyone. For example, to SSRIs. Lisa, whose name has been changed to protect her privacy, is one of them. Having battled PMDD since she was 12, she found that antidepressants took the edge off, but her symptoms were still terrible. 鈥淪ometimes I just felt like I didn鈥檛 want to be here,鈥� she says. 鈥淚 was calling up the doctors constantly, telling them 鈥業鈥檓 really suffering鈥�.鈥� Eventually, she was offered a more drastic treatment called a gonadotropin releasing hormone (GnRH) agonist to shut down her ovaries. It worked. 鈥淢y emotions were so much more balanced,鈥� she says. But because using the drug over the long term can increase risk of osteoporosis, Lisa was only allowed to take it for six months. 鈥淣ow I鈥檝e stopped it and I鈥檝e just felt 鈥� it sounds dramatic 鈥� but I鈥檝e just wanted to die,鈥� she says. 鈥淚t鈥檚 been awful. For half of every single month, it ruins my life. I have three children; it鈥檚 been so hard.鈥� Others who opt for GnRH drugs don鈥檛 even have a temporary reprieve. Unfortunately, for around half of people who take them, . This isn鈥檛 just a problem, it鈥檚 a puzzle. 鈥淚 think there is a lot of work that needs to be done to understand why treatments are effective in some but not others with PMDD,鈥� says Chenji.
Research on a potential treatment called Sepranolone suggests one reason. This synthetic version of ALLO showed , but then a large randomised control trial found no meaningful differences between the group that received it and those who took a placebo. However, diving deeper into the Sepranolone trial data showed it was effective for a sub-group of people with PMDD whose symptoms are confined to the luteal phase, which follows ovulation, and disappear completely when their period starts. This could point to PMDD manifesting differently in different people. Indeed, in 2020, researchers found some of the first evidence that there may be at least . People with one form experience moderate symptoms only in the week before their period, those with a second type have severe symptoms across the full two weeks of the luteal phase and a third group have severe symptoms in the premenstrual week that are slow to resolve in the following weeks.
If PMDD does come in distinct forms, this offers new hope for treatments. 鈥淚 believe that future research looking at different temporal subtypes of PMDD, including severity and timing of symptoms, would be helpful,鈥� says Chenji. But she also notes that planning any study that involves analysing the effects of the menstrual cycle is challenging and expensive. Historically, in both early-stage animal studies and human clinical trials, females have been excluded from biomedical research specifically because their menstrual cycles could affect the data. 鈥淗ormones are not the noise in the data, they are the data,鈥� says Chenji. 鈥淩esearch on these differences must become the norm if we are to achieve equity and, most important, to improve the health and well-being of women and men,鈥� state the authors of a by Brigham and Women鈥檚 Hospital in Boston, Massachusetts.
The fact that change is needed is becoming increasingly apparent. Back in the 1970s, the of the menstrual cycle鈥檚 impact on cognition and perception found no conclusive evidence of cycle-related differences. But the review also pointed out that numerous papers on the subject had methodological problems such as a lack of hormonal measures and incorrect dating of menstrual cycle stages.
Women鈥檚 health and well-being
In more recent times, there is growing evidence that hormones affect women鈥檚 health and well-being in all kinds of ways. In 2011, for instance, several studies found that people have , with implications for how to treat trauma. In the past decade, we have learned that women鈥檚 brains undergo a dramatic remodelling during pregnancy, which could impact behaviour and risk of conditions such as postpartum anxiety and depression. And last year, researchers found that menstrual cycle phase can for breast cancer. These scientists, as well as many others, are calling for more women-specific drug research. That can鈥檛 come soon enough for the millions of people whose hormones are presenting them with so much adversity during the years they are menstruating 鈥� not to mention the countless family members and friends who are also affected.
For now, though, we have so few treatments that some people with PMDD choose to have surgery to remove their ovaries and uterus. This concerns Apsey. 鈥淭aking out your ovaries when we don鈥檛 know exactly what causes the condition seems premature,鈥� she says. 鈥淲e need to take a step back and really understand what is causing it and what will help.鈥�
Unfortunately for people like Lisa, surgery can feel like the only option. She is on a waiting list to have her ovaries removed. 鈥淚 will be able to live a normal life again,鈥� she says. 鈥淚 just hope it happens soon.鈥�
