At last, scientific proof PMT IS real

Dismissed by doctors. Patronised by partners. Now we reveal the news that vindicates millions of long-suffering women . . .

LAURA MURPHy was 17 when she first experienced disturbing premenstrual symptoms. ‘I remember crashing on the floor with such a violent panic attack I couldn’t breathe,’ recalls Laura, 37, a furniture painter from Strood in Kent. ‘It was the most terrible anxiety imaginable — it was overwhelming and exhausting.’

Her family took the view that she was just a stressed teenager ‘having a bit of a strop because my boyfriend had just gone away to university’.

For Laura, though, it was the start of years of turmoil which consumes days of her life every month. ‘When I was younger, I was only affected in the three or four days before my period started. But after hitting my 30s, it became all together more serious: with three days of slowly descending into this pit of despair and exhaustion, followed by five days which I spent crashed out in bed feeling suicidal, angry and just so tired I could barely move.

‘After my period started the fog would lift — but I’d be so exhausted I’d need another three or four days to fully recover and get back to normal life.’ Although Laura managed to graduate with a degree in design, in order to manage her need for regular time off she could only work as a temp.

Her lowest point came after her first long-term relationship ended, with her boyfriend of ten years telling her: ‘I can’t spend my life looking after you.’

‘I was heartbroken, with nothing but this endless rollercoaster ahead of me,’ says Laura. She couldn’t see a way forward: ‘I thought I was mad. I felt so alone — there was no-one who understood.’

Laura was far from mad, but suffers from one of the most well-known gynaecological disorders: premenstrual syndrome, or PMS (also called PMT).

DISMISSED AS ‘ALL IN THE MIND’

PMS is a disorder that ranges in severity, affecting an estimated three in ten women mildly to moderately, with 8 per cent of menstruating women experiencing a severe form (also known as premenstrual dysphoric disorder, PMDD). Though it’s a common problem, PMS is both poorly researched and a source of hilarity — as likely to be a punchline to a joke about female behaviour as a subject for a paper in a medical journal.

Women are seen as ‘irrational’ at ‘that time of the month’ because of their hormones. Or else the disorder is dismissed as being all in their heads — with sceptics pointing to the fact that the symptoms of PMS vary throughout the world, with women in Western cultures more likely to suffer psychologically.

Or women are simply told to get on with it. A few years ago, a female GP told Laura that yes, she did have premenstrual symptoms, but it was just part and parcel of being a woman. She said, ‘there’s nothing to be done, you’ll just have to learn to live with it’, recalls Laura. ‘She even tried to reassure me by telling me: “you’re lucky you don’t live in the Middle Ages, people would have thought you were a witch.” ’

Another doctor refused to refer her to a gynaecologist when she told him she thought she had PMDD. ‘“Where did you read about that?” he asked me. It was as though because he hadn’t heard about it, it doesn’t exist.’

These views frustrate experts such as Dr Nicholas Panay, a consultant gynaecologist at Queen Charlotte’s Hospital and Chelsea and Westminster Hospital NHS Foundation Trust and co-author of new official guidelines on treating PMS. ‘This disorder, in my view, is simply not taken seriously enough by the medical profession or the pharmaceutical industry,’ he says.

Even when women’s symptoms are taken seriously, they are often not treated correctly, he says. ‘A major problem is that many women with PMS are misdiagnosed, frequently with bipolar disorder (often referred to as manic depression).’

‘The fact that their symptoms recur every month is often missed by their GPs,’ says Dr Panay.

Indeed, though Laura has been prescribed antidepressants over the years, ‘not a single doctor suggested that hormones might be to blame.’

The worry, adds PMS expert Professor Jayashri Kulkarni, of Monash Alfred Psychiatry Research Centre in Melbourne, is that ‘opinions about the existence of PMS are fuelled by beliefs and politics, rather than by reason and good research’.

THE PROOF IT DOES ACTUALLY EXIST

BUT could all this be about to change? Last week, U.S. scientists reported the first concrete evidence that PMS is a real condition — at least at the severe end of the spectrum.

As the journal Molecular Psychiatry reported, they have identified ‘the PMDD gene complex’: a set of genes, known as ESC/E(Z), that can cause brain chemicals to behave abnormally when exposed to female hormones during the menstrual cycle, a finding hailed by Dr David Goldman, chief of human neurogenetics at the National Institute for Health in the U.S. as ‘a big moment for women’s health’.

The study, he says, ‘establishes for the first time that there are intrinsic differences in the way women respond to sex hormones at a molecular level’.

What’s more important, he adds, is: ‘we now know for certain that these are not just emotional behaviours [that] women should be able to voluntarily control’.

British experts have responded as enthusiastically. ‘It’s concrete proof that severe PMS is a genuine disease with an organic basis,’ says Dr Panay, chair of the National Association for Premenstrual Syndrome (NAPS). ‘It should hopefully convince those who viewed it as just a convenient excuse for being in a bad mood.’

The study involved 34 women with severe PMS and 33 healthy participants. Their blood cells were exposed to the female hormones oestrogen and progesterone for 24 hours. The team found that following exposure to these hormones the gene complex ESC/E(Z) was switched on — but only in women with severe PMS.

OVERSENSITIVE TO THEIR HORMONES

THE finding is being hailed as the missing link that explains why some women experience abnormal mood changes during what is, after all, a normal menstrual cycle.

‘This confirms the hypothesis that we have put forward for many years that PMS occurs not because of hormonal abnormalities per se — but that some women have a genetic vulnerability to the changes in hormone levels that occur in every woman,’ says Dr Panay.

The study may also add credence to a second theory that is attracting widespread interest: that PMS is caused by progesterone ‘withdrawal’ in the days before a period.

Levels of both progesterone and oestrogen drop at this time as the body prepares for the monthly bleed. Recent research by scientists at the University of Bristol, University College London and in Brazil has identified that in women with PMS, there is a much sharper rate of decline in progesterone — and in particular, a molecule in it known as allopregnanolone.

Allopregnanolone acts in the brain as a ‘potent sedative and tranquilising agent’, says Dr Thelma Lovick, a neuroscientist at the University of Bristol, who co-authored this research.

‘The result of an abnormal decline in levels of allopregnanolone is the anxiety and irritability that are the key characteristics of PMS,’ she says. ‘So many women have written to tell me that understanding this process makes it easier for them to manage symptoms that seem to take them over.’

PROMISE OF NEW TREATMENTS

BUT will PMS treatment improve following these findings?

To some extent treatment has already improved in recent years. New guidelines published by the Royal College of Obstetricians and Gynaecologists last month established the rule that diagnosing PMS should be less about the precise symptoms than the timing of them — ‘ideally through a symptom diary over two menstrual cycles’, says Dr Panay, who co-wrote the guidelines.

Once diagnosed, a further addition is a simple plan to help GPs treat PMS effectively — beginning with lifestyle advice, accompanied by a prescription for a combined oral contraceptive and/ or a low dose (10mg) SSRI (selective serotonin reuptake inhibitor) antidepressant, given either continuously or in the two weeks before a period.

For women whose symptoms remain, the next step is stronger prescriptions: oestrogen patches and higher doses of an SSRI — or even more powerful hormone treatments such as GnRH, a gonadotropin-releasing hormone that suppresses the menstrual cycle, causing a ‘chemical menopause’. For a handful of women who still have severe symptoms, a hysterectomy with removal of the ovaries may be the only option.

WHY DEPRESSION PILLS MAY HELP

IT’S a plan that provides a range of options which can be tried and tested — for instance SSRIs can be offered at different doses and either intermittently or permanently. Dr Lovick says her research suggests that low-dose

SSRIs may be particularly effective for PMS. ‘The odd thing is that SSRIs are supposed to interact with serotonin as their name suggests. In fact they also impact on allopregnanolone.’

One important development following the U.S. finding, according to Professor Shaugn O’Brien, a consultant gynaecologist at University Hospital of North Staffordshire, ‘could be a diagnostic blood test within the next ten years — it would be a breakthrough for PMS treatment’. Longer term, gene therapy might be an option.

For Laura and hundreds of thousands of women like her, the study is yet one more piece of the jigsaw enabling her to make sense of ‘everything I’ve been through’.

‘But I know women who will be comforted that there’s a test and cure for PMS somewhere down the line, especially as they know that the problem is genetic and they’re terrified their daughters will go through what they have suffered. It’s part of the reason I decided not to have children,’ she says.

Yet however reassuring, there are still a lot of unanswered questions about PMS. For a start, the role stress might play.

Menstrual cycle-related complaints are more likely to be reported by women who live in Europe, Australia and North America — where a Western lifestyle is thought to cause more stress, according to U.S. psychologist Joan Chrisler.

Indeed, a 2010 study of 259 women living in New York, who filled in questionnaires over two menstrual cycles, found that those who reported feeling stressed in the first month were more likely to experience severe PMS symptoms in the second month.

‘Simple stress reduction programmes may be an effective, nonpharmaceutical treatment for both physical and psychological symptoms of PMS,’ claimed researchers from the Department of Public Health at the University of Massachusetts, writing in the Journal of Women’s Health. It’s an approach widely supported by UK experts. ‘I certainly do not believe that PMS can be entirely explained as “First World problems”,’ says Dr Panay. ‘But I also think that stress can exacerbate symptoms in women susceptible to PMS.’

Dr Carrie Sadler, Derbyshire GP and PMS expert, agrees. ‘The disorder is caused by a combination of factors but the symptoms will be more severe in a woman who has tendency to PMS and who is working in a stressful job than a woman with the same tendency to the disorder who has a happier, less stressful life,’ she says.

SYMPTOMS VARY WORLDWIDE

THEN there is the question of the differences in PMS around the world — taken by some to suggest that the disorder is actually all in the mind. They point to evidence, for instance, that U.S. women are more likely to complain of negative emotions, whereas Chinese women say they are more sensitive to the cold at this time.

Yet such discrepancies can be better explained by different cultural values, according to Professor Kulkarni.

Dismissing PMS because only Western women complain of psychological problems, she says, ‘fails to take into account the fact that mental health disorders are not given a priority in cultures where there are many other battles to contend with — and where the non-life-threatening conditions such as PMS are given little consideration’.

Further, there may be a physical explanation for geographical variations in the experience of PMS.

‘It may seem that Western women are more likely to complain about negative emotional symptoms,’ says Dr Kate Clancy, a professor of anthropology at the University of Illinois in the U.S. ‘But the important factor could be that we eat more and are less active than women in less affluent countries and as a result we have the highest levels of progesterone — the hormone responsible for PMS — of all women globally.’

Western women therefore feel the drop in progesterone before their period more keenly, she says.

But Dr Lovick isn’t convinced: ‘we simply don’t have the evidence that Western women have higher levels of progesterone.’ She agrees that Western women may be more vulnerable to PMS simply because they have fewer pregnancies and therefore more menstrual cycles.

A further concern is that ‘the

puzzlingly widespread belief in PMs’ has led to all manner of grievances and hardships suffered by women being wrongly ascribed to hormonal disruption. ‘if a woman is distressed, anxious or depressed, the tendency is to automatically think there’s a hormonal explanation for it — rather than thinking it could be something happening in her work or home life,’ says Dr sarah romans, of the Department of Psychological Medicine at the University of Otago in New Zealand.

she reviewed 47 studies all claiming to show an association between low mood and the premenstrual phase and found only seven of them showed that women experienced the symptoms in the run-up to their period.

RIGHT TREATMENT CAN BE LIFE-CHANGING

iNDEED, over-medicalisation of women’s ‘normal’ symptoms has been a hot issue, particularly in the U.s. the American Psychiatric Association was accused of ‘medicalising’ PMs by ‘creating’ a new disease, PMDD, which was added to its latest edition of the Diagnostic and statistical Manual of Mental Disorders, the psychiatrists’ bible, in 2012.

Yet for Laura, the ‘discovery’ of PMDD was a lifeline. Just over a year ago, she was finally referred to a hospital specialist.

‘i came out of that appointment and cried in the street with relief. it was the first time a doctor had got it, had understood what i was going through and had talked about hormones causing the problems.’

since then, Laura has been using oestrogen patches and testosterone gel along with a progesterone pessary, to smooth out the cyclical changes in her hormone levels.

‘i still notice my cycle, though it’s nowhere near so pronounced. i’m a bit grumpy, or tend to want crisp sandwiches. And i’m still more tired than i should be for two weeks of the month — though i need less recovery time.’ she is due to have a Gnrh injection imminently. if she feels better on the treatment, she could have a hysterectomy within a year. ‘i want that surgery,’ she says.

Laura has now started a support group that has 650 members. ‘i get emails every day from women thankful to be in touch with a group instead of managing all alone for years, often decades,’ she says.

‘the most pitiful are those who have spent years fearing that their children would be taken away from them because they feel that they are such bad mothers for part of every month.

‘i often think of the GP who dismissed my symptoms and refused to refer me to a specialist because he’d never heard of PMDD, condemning me to several years of unnecessary suffering — and i fear that this is still happening today.’

NATIoNAl Association for Premenstrual Syndrome: pms.org.uk UK PMDD Support facebook.com/groups. ukpmddsupport/