Study Explores Promising New Approach for Treating Premenstrual Dysphoric Disorder (PMDD)
In preliminary research, Swedish scientists find that a drug blocking progesterone provides relief.
Women with premenstrual dysphoric disorder (PMDD) may eventually have a new path to treat the disorder, according to a preliminary study by Swedish researchers that found a new class of drugs helps the condition.
Billed as a “proof of concept,” the study included only 95 women, so it needs to be repeated with a larger population before the treatment can be recommended. It was published online on December 10, 2020, in the American Journal of Psychiatry.
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The drugs belong to a class known as selective progesterone receptor modulators (SPRMs), which could potentially offer a welcome option in the future for women struggling with the condition. “Given the limited options for treatment as of now, any additional option that may be effective and that doesn’t present excess risks would be promising,” says Carly Snyder, MD, a reproductive psychiatrist in private practice in New York City, who treats many women with the condition.
Premenstrual Dysphoric Disorder (PMDD) Can Be Debilitating
PMDD strikes during the luteal phase of a woman’s menstrual cycle, the time after ovulation and before menstruation. Many women experience the condition every month.
Symptoms vary, but generally include wildly shifting moods, profound irritability or anger, low energy, and poor sleep, which are severe enough to negatively impact usual life activities. “Women often say they feel as if they become different people entirely. They’re quick to anger, feel weepy and anxious, and have poor self-control during this time,” Dr. Snyder says. The disease can affects a woman’s ability to work or go to school, and relationships are often harmed by the emotional volatility.
An episode of PMDD can last a few days or the entire two weeks. Once a woman menstruates and her hormones shift, she becomes herself again.
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PMDD Is Not the Same as Premenstrual Syndrome (PMS)
Many people confuse PMDD with premenstrual syndrome (PMS), since both strike before menstruation. But PMS, which most reproductive-age women experience, generally results in uncomfortable symptoms like bloating, appetite change, and mild irritability, Snyder says. By definition, PMDD symptoms are severe enough to negatively impact a woman’s ability to function.
Current PMDD Treatments Are Not Sufficient
PMDD is officially said to affect some 5 percent of women of childbearing age, but Snyder believes the true number is higher. “Too often it is overlooked by healthcare professionals and inappropriately minimized,” she says.
Current treatment for PMDD involves serotonin reuptake inhibitors (SSRIs). “Although these drugs are effective, they are not suitable for all women,” says the study’s coauthor, Erika Comasco, PhD, assistant professor of neuroscience at Sweden’s Uppsala University and a researcher at the country’s SciLifeLab. “In addition, it would be desirable to have a treatment that more specifically addresses the mechanisms underlying this psychiatric disorder,” she says.
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Progesterone Plays a Role in PMDD
According to the Journal of Psychiatry study, fluctuations in ovarian hormones, especially progesterone, are believed to be behind the condition.
Although the exact mechanism by which progesterone might cause PMDD is not known, receptors for the hormone exist throughout the brain, including in the amygdala, hippocampus, prefrontal cortex, and other sections. Progesterone easily passes through the blood-brain barrier, the authors note.
Because of this, the notion that medicines that bind to progesterone receptors and prevent the hormone from populating the brain intrigued the researchers into conducting the study, Dr. Comasco says.
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A Drug Available in Europe Was the Specific Drug Tested
In this case, the researchers chose the medicine ulipristal acetate (UPA), a drug available in Europe under the brand name Esmya. In Europe, this medication, taken daily in a 5 milligram (mg) pill, is used to treat uterine fibroids.
The Drug Especially Helped Psychiatric Symptoms
At the start of the study, women were assessed with various mental-health tests. They also had their blood drawn to detect hormone levels. Then they were randomly assigned to take either the UPA or a placebo daily. They were followed for three months, after which they were tested again.
The results were encouraging, especially since this disease can be so difficult to treat. Some 85 percent of women taking the medicine experienced either complete (about half the women) or partial remission of symptoms. The mean improvement in symptom severity was 41 percent in the UPA group, compared with 22 percent for women taking placebos. The drug especially helped with mental health issues like depression, anger, and irritability.
The Brain Needs Better Understanding
Comasco points out that “this is the first study of this kind” using this medication.
According to the study authors, two small trials were conducted on other progesterone receptor antagonists in the 1990s, but the drugs were given too late in the menstrual cycle to be effectively evaluated.
In addition to this study, the authors are currently investigating the mechanisms by which progesterone receptor modulators impact the brain. “By neuroimaging the brain of these patients before and during treatment, using magnetic resonance imaging, we seek to define structural and functional brain signatures that can explain the relief of PMDD symptoms,” Comasco says.
Concerns and Cautions With New Treatment
In this study, side effects experienced by the women were rare and generally mild, primarily headache, nausea, and fatigue.
However, some women in Europe who have taken this medication daily to fight fibroids have experienced severe problems with their liver. This is a significant enough concern that European health regulators have recommended that women there stop taking the drug for now, while they perform a safety review, according to a March 2020 press release from the European Medicines Agency. (This issue does not affect women taking Ella for emergency contraception, the National Women’s Health Network states, because that drug is not taken continuously.)
In any event, since this was a proof-of-concept study, the researchers are not currently recommending women begin this treatment at this time.
But they note that “other selective progesterone receptor modulators with theoretically less effects on the liver are on their way into the market, potentially representing safer alternatives.”