When Charlotte was a teenager, she began suffering from bouts of severe exhaustion, anxiety and depression. Although she was quick to seek help, doctors were puzzled why an otherwise healthy young woman was suffering such debilitating symptoms. In the end, it was a therapist rather than a GP who prompted her diagnosis. Charlotte’s therapist noticed that the mysterious symptoms followed a pattern, one that a sea of other medical professionals had missed: her period.
Soon after, Charlotte was diagnosed with Premenstrual Dysphoric Disorder (PMDD). The disorder, which affects 2-10 percent of women, has physical and emotional symptoms ranging from mood swings to insomnia. What makes PMDD so distinct is that these symptoms happen during the luteal phase of a woman’s menstrual cycle – the weeks after ovulation, but before a period. PMDD is often referred to as the severest form of PMS and appears to be caused by the same reaction to hormone changes.
“It’s like your brain just doesn't work for a while,” Charlotte tells me. “You feel out of control and overwhelmed. It’s not just feeling tired but [it’s] sleeping for 14 hours, getting up, and feeling unable to even go downstairs and get yourself a drink. It’s impacted my job, it affects romantic relationships. You suddenly go from loving your partner to thinking, ‘Oh my god, I hate my boyfriend. I hate everything about him.’”
Now trials are underway of the first drug developed to specifically target the disorder. Sepranolone is currently in its second round of clinical trials and could be available between 2024 and 2025. The drug is novel because it isn’t an SSRI or hormone. Instead, it blocks the effects of allopregnanolone, a naturally produced steroid that appears to play a role in PMDD.
The researcher behind the drug, Dr.Torbjörn Bäckström, was working in a Swedish psychiatric hospital during the 1970s when he treated a female patient who’d been repeatedly sectioned for outbursts of violence. “She never understood why she had become so angry,” he tells me. “After about a year we realised this occurred once a month and was always before menstruation.”
Intrigued, Bäckström discovered a small section on PMDD in a physiology textbook that described the symptoms he’d observed in his patient. This marked the beginning of a career studying a disorder still ignored by some doctors – like Charlotte’s.
“My experience is that many patients are patted on the shoulder and told 'pull yourself together,'” Bäckström tells me, “and it's impossible. They can't pull themselves together, this is too serious a disorder. This is not caused by a factor that is easily removed or taken care of. There are psychological ways of treating this and in milder cases it helps, but in severe cases it's not enough. PMDD is mainly a gynaecological condition. Many of the symptoms are psychiatric, but the cause is the menstrual cycle.”
Marina, 35, has lived with PMDD for years and reports that the disorder often gets dismissed. She blames “the whole model” of a society that sees women as unstable. “I get totally exhausted and confused about everything,” she says. “It's very easy to go, ‘Well, this is normal, because women are hormonal and crazy.’ There's not a lot of support.”
But there are signs that the medical community is finally beginning to take the disorder more seriously. The WHO recently added PMDD to the updated version of the International Classification of Diseases – the first time it had ever been included. Dr. Tory Eisenlohr-Moul is the Chair of the Clinical Advisory Board for the International Association for Premenstrual Disorders. She describes the Sepranolone trials as “really promising”, part of a sea-change in how researchers approach premenstrual disorders.
In terms of understanding PMDD, Eisenlohr-Moul cautions against treating physical and psychological disorders as a straightforward binary. “We have evidence that there is no problem with the hormones themselves [in PMDD], the patterns and the levels are normal,” she explains. “But the emotional response implies the brain is having an abnormal reaction to normal hormone changes. And so that brain part is really key. Sepranolone is exciting because it acts in the brain to prevent these abnormal effects of hormones in PMDD.”
“I don't think that means all behavioural intervention is useless. I have women who come in suicidal every month and there are things I can teach them that help keep them alive,” she adds. “For me, mental health just refers to the emotions, thoughts, actions that are a readout of brain activity. In the case of PMDD, we just have a much clearer understanding of how the brain is affected, although we don't understand it well enough. Ninety-nine percent of things are a complicated interaction between genes and the environment.”
Women living with PMDD understand the disorder from a variety of perspectives. Amani, 32, has been struggling with the disorder since her twenties. “It's not understood at all. What I've learned is that people don’t believe you could feel so bad and still be functioning,” she tells me. “It’s one hundred percent not a mental health condition. I feel like that’s the medical profession’s way of dismissing it as a psychological issue, like it's just in your head. It makes me really angry.”
Marina takes a slightly different approach, describing the disorder as a combination of mental health and endocrine issues. “The symptoms are all mental health, but hormonal treatments, for me, work well,” she explains. “I think it’s physiological but with psychiatric facts.”
At the moment, the disorder is categorised as a disease of the genitourinary system by the WHO, with a cross-listing in a subgroup of depressive disorders. The complex role of emotional symptoms, combined with misinformation about PMDD, has made accessing treatment even harder.
“It's confusing,” says Eisenlohr-Moul, “if you go to a gynaecologist, they'll check your hormone levels. Hormone levels are perfectly normal in PMDD, so the gynaecologist says, 'you seem fine, try to sleep more, eat more vegetables, and go see a psychiatrist if you need to.’ Psychiatrists, on the other hand, will say, ‘this must be an endocrine issue because of the hormone cycling, and so I should refer you to a gynaecologist.’”
It’s clear that, even with recent advances, PMDD treatment still suffers from a perfect storm of misogyny and symptoms that don’t always fit neatly into a single box. “The number of women with it is something near the level of people that have diabetes,” Charlotte says. “It's absolutely insane we know so little about this.”
UPDATE 29/11/19: An earlier version of this article stated that Sepranolone would be available by 2022. The manufacturers clarified that the release date has changed and the piece updated as a result.