Promising treatment for premenstrual dysphoric disorder, PMDD

The mental symptoms of premenstrual dysphoric disorder improve following treatment with a progesterone receptor modulator, as demonstrated by SciLifeLab researcher Erika Comasco and Professor Inger Sundström-Poromaa, Uppsala University. The mechanism of action of the study drug provides insights into the potential molecular mechanisms underlying this psychiatric disorder and its treatment.

It has long been known that the menstrual cycle can affect women's mood and well-being. For the majority of women of reproductive age, this manifests itself in mild symptoms that do not need any treatment, but for 3-5 per cent of women, the hormonal changes during the menstrual cycle lead to disabling mental symptoms: premenstrual dysphoric disorder (PMDD).

Selective progesterone receptor modulators bind to and inhibit progesterone receptors in the brain. This is a relatively new class of drugs developed for the treatment of uterine fibroids and endometriosis. In this multicentre, double-blind, placebo-controlled clinical trial, researchers from Uppsala University, Karolinska Institutet and Umeå University have demonstrated for the first time the efficacy of a selective progesterone receptor modulator as a treatment for PMDD.

According to the study now published in the American Journal of Psychiatry, the progesterone receptor modulator primarily reduces the mental symptoms of PMDD, such as irritability and depression. Half of the women (50 per cent) receiving the treatment improved completely, while the corresponding proportion of women receiving placebo was 21 per cent.

“Side effects were mild and the ongoing development of well tolerated progesterone receptor modulators will hopefully make this a treatment option for patients with PMDD,” says Professor Inger Sundström-Poromaa of the Department of Women's and Children's Health and the Centre for Women’s Mental Health during the Reproductive Lifespan (WoMHeR) at Uppsala University.

Looking ahead, the researchers are currently investigating how progesterone receptor modulator affects the brain in women with PMDD. By neuroimaging the brain of these patients before and during treatment, using magnetic resonance imaging, the researchers aim to define structural and functional brain signatures that can explain the relief of PMDD symptoms.

The research results will be an important piece of the puzzle of improving our understanding of the mechanisms behind PMDD, the researchers say. Today, the first-line treatment for PMDD is serotonin reuptake inhibitors. Although these drugs are very effective, they are not suitable for all women and additional treatment options are of value. In addition, it would be desirable to have a treatment that more specifically addresses the mechanisms underlying this psychiatric disorder.

Comasco et al.; Ulipristal acetate for treatment of premenstrual dysphoric disorder – a proof-of-concept randomized controlled trial, American Journal of Psychiatry 2020; 0:1–10; doi: 10.1176/appi.ajp.2020.20030286, https://ajp.psychiatryonline.org/doi/abs/10.1176/appi.ajp.2020.20030286 

Further information:

Erika Comasco, Researcher at the Department of Women's and Children's Health, and Assistant Professor at the Department of Neuroscience at Uppsala University and SciLifeLab, erika.comasco@neuro.uu.se

Inger Sundström-Poromaa, Professor at the Department of Women's and Children's Health, and Centre for Women’s Mental Health during the Reproductive Lifespan (WoMHeR) at Uppsala University. inger.sundstrom@kbh.uu.se , phone: +46-70-246 51 56